C HA P T E R 19
Disorders of the Reproductive Tract
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Maria R. Schnobrich*
This chapter will review the normal anatomy and physiol-
ogy of the mare and stallion with a discussion of pathology
and common clinical presentation of reproductive disorders.
There will also be a discussion of breeding management and
advanced reproductive techniques for fertility enhancement
and diagnosis of reproductive dysfunction.
Reproductive Anatomy and Physiology
of the Nonpregnant Mare
Maria R. Schnobrich
Y INTRODUCTION
Equine reproductive anatomy and physiology deviate from
those of other domestic animals in several notable ways,
requiring an in-depth understanding for appropriate repro-
ductive management and treatment. This section will serve as
a review of reproductive anatomy and physiology of the non-
pregnant mare, focusing on the clinically important features
and highlighting where the mare differs from other species.
Y REPRODUCTIVE ANATOMY
The reproductive anatomy of the mare includes structures intrin-
sic to the reproductive tract (tubular tract and ovaries) and struc-
tures that are remote from the reproductive tract that play a role
in regulating reproductive function (hypothalamus, anterior pitu-
itary, retina, and the pineal gland) or are linked to reproductive
function (mammary gland). This section will review the embry-
onic origin and key features of the relevant anatomic structures.
Internal Reproductive Tract
The mare’s reproductive tract includes the ovaries (gonads),
the tubular tract (oviducts, uterus, cervix, vagina, and vesti-
bule), and the external genitalia (vulva and clitoris).
* The editors and authors acknowledge and appreciate the contributions of
Daniel C. Sharp, Michael B. Porter, Nigel R. Perkins, John B. Chopin, Carlos
R. F. Pinto, Dale L. Paccamonti, Elizabeth Metcalf, Grant S. Frazer, Michelle
M. LeBlanc, Elaine M. Carnevale, Marco A. Coutinho da Silva, and Juan C.
Samper as previous contributors to this chapter. Some of their original work
has been incorporated into this edition.
Ovaries
The paired ovaries are composed of tissue derived from meso-
derm (ovarian parenchyma and vasculature) and the primor-
dial germ cells (oocytes).1 The ovaries are shaped like kidney
beans and are approximately 2 to 4 cm in height and 8 to 10 cm
in length.2 They are usually located at the most cranial aspect
of the reproductive tract, approximately 15 cm caudal to the
corresponding kidney, suspended in the mesovarium.3,4 The
ovaries are generally positioned with the long axis of the ovary
parallel to the mare’s spine, and the ovulation fossa (the con-
cave portion of the ovary) directed ventrally.4
Resting on the abdominal viscera, the position of the ovaries
is somewhat variable within the sublumbar region between the
10 and 2 o’clock position, ventral to the fourth or fifth lumbar
vertebrae, approximately 4 to 8 cm craniolateral from the tip
of the uterine horn.5 Ovarian size varies with hormonal envi-
ronment and follicular activity. The ovaries are usually small
and inactive during anestrus (3–4 cm in length) or can be quite
large (10–12 cm in length) when multiple follicles are present in
estrus, in vernal or autumnal transition, or under the influence
of gestational hormones. The preovulatory follicle of the mare is
usually larger (≥35 mm) than that in most other domestic spe-
cies and can be appreciated on transrectal palpation as a toned,
fluid-filled vesicle that has a characteristic difference in consis-
tency compared with the surrounding ovarian tissue.3-6
The mare’s ovary is unique compared with other domestic
species in two ways: (1) the cortex (containing the follicles and
oocytes) is internal to the ovarian medulla (ovarian vasculature),
which lies on the exterior of the ovary, and (2) ovulation occurs
internally, releasing the oocyte through the ovulation fossa,
whereas ovulation occurs over the entire exterior surface of the
ovary in other species.4,6 This unique anatomy of the mare’s ovary
makes transrectal palpation and identification of corpora lutea
not practical or accurate.4,6 In addition, pathology of the ovula-
tion fossa can result in infertility, because the ovulated oocytes
may be prevented from reaching the oviduct for fertilization.
Oviduct
The oviducts (uterine tubes) originate from the most ante-
rior segment of the paramesonephric or müllerian ducts.1
The concentric tissue layers of the oviduct from the exter-
nal surface to the oviductal lumen consist of serosal surface,
muscularis (longitudinal and circular muscular layers), sub-
mucosa, and mucosa. In the 500-kg mare they are approxi-
mately 20 to 30 cm in length and travel a tortuous path in the
mesosalpinx from the ovary to the tip of the uterine horn.4
1217
 1218 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
The oviduct is divided anatomically into three sections: the
infundibulum, the ampulla, and the isthmus.1-4 The infun-
dibulum is a funnel-shaped dilation covering the ovulation
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fossa that transports the oocyte from the ovary to the ampul-
lary region of the oviduct where fertilization occurs.1 Follow-
ing fertilization, the conceptus passes through the isthmus
(the narrowest portion of the oviduct that enters the uterus at
the uterotubal junction) to the uterine lumen. The uterotubal
junction has a muscular sphincter that selectively allows
embryos (which produce prostaglandin E2 [PGE2]), but not
unfertilized oocytes, to pass into the uterus at approximately
5.6 to 6 days post ovulation (Fig. 19.1).7,8 In addition, the
unique anatomy and physiology of the uterotubal junction
make salpingitis rare in the mare compared with other spe-
cies such as cattle and swine.6,9
Uterus
The mare’s uterus consists of two uterine horns and a uterine
body that are derived from the partial fusion of the parame-
sonephric ducts.1,3,5 The mare’s uterine tissue layers are as fol-
lows from external to internal lumen: serosa (perimetrium),
the myometrium (outer longitudinal smooth muscle fibers
and inner circular fibers separated by a vascular layer), and the
endometrium. The endometrium is divided histologically into
three layers from deep to superficial lumen: (1) the stratum
spongiosum (loose connective tissue, submucosa, and glands),
(2) the stratum compactum (1-mm region beneath luminal
epithelium with a high density of stellate stromal cells), and
(3) the luminal epithelium (consisting of simple columnar epi-
thelium).4,5 The uterus, ovaries, and oviducts are suspended in
the abdomen by the broad ligament in a T-shape or Y-shape
when viewed from above.3,4 The broad ligament originates
from the sublumbar region, and the fibers converge over the
uterine body and cervix, causing the mare’s uterus to have a
less distinct tubular feel when palpated transrectally compared
with cattle.6 The endometrium of the mare’s uterus has 5 to
10 longitudinal folds that extend from the tips of the uterine
horns through the uterine body and are continued through the
cervix where they become the cervical folds seen on vaginos-
copy (Fig. 19.2).4,10 The function of the endometrial folds has
been theorized to aid in sperm transport to the oviduct and
to provide channels for removal of fluid and debris following
breeding.4
The uterus is the site of semen deposition during breeding
and where the developing fetus is nurtured during pregnancy.
It is a dynamic and changing environment influenced by cir-
culating and local hormones that dramatically alter uterine
size, contractility, tone, secretory activity of glands, immune
competence, and overall character and function.
FIG. 19.1 Oviductal papilla or uterotubal junction as viewed from hys­
teroscopic evaluation of the uterine lumen.
Cervix
The mare has a muscular cervix (approximately 6–7 cm in
length) derived from ectodermal tissue and the fusion of the
paramesonephric ducts.1,4 The cervix of the mare differs from
some other farm species in that it lacks prominent cervical
rings and can easily be dilated by digital manipulation.6 The
luminal epithelium is a secretory, stratified squamous epithe-
lium, surrounded by an internal circular and longitudinal outer
muscular layer. The longitudinal folds of the uterus are contin-
uous with the cervical folds and give the scalloped appearance
of the external cervical os during estrus.4 The external cervical
os is located in the vaginal fornix (anterior vagina) and has
two bands of tissue that extend from the dorsal and ventral
margins to the vaginal wall (dorsal and ventral frenulum) that
are often confused with adhesions (Fig. 19.3).2,4,9
The cervix can be appreciated with transrectal palpation as
a tubular structure with variable tone, located in the anterior
pelvic inlet in the region of the bladder. The cervix of the mare
differs from the cow in that it is less prominent and tubular on
palpation due to a more dorsal insertion of the broad ligaments
and the lack of fibrocartilaginous rings. The mare’s cervix can-
not be grasped and used to retract the reproductive tract as in
a cow.6 The cervical length of most mares is approximately 5 to
7 cm, and the width increases during estrus to approximately
2 to 4 cm. Cervical size, tone, and character will vary with
breed, age, prior trauma, and reproductive status.2,4 The cervix
is a versatile structure that in estrus provides lubrication and
accommodates the stallion’s penis during intromission. It then
maintains tone and serves as a protective barrier to the uter-
ine environment in diestrus and pregnancy, and finally dur-
ing parturition it dilates to allow expulsion of the fetus. These
dynamic changes are under the control of reproductive hor-
mones, allowing veterinarians to use the cervix clinically as a
barometer of the mare’s hormonal milieu (Fig. 19.4).
Vagina
The vagina originates from the fusion of the paramesonephric
ducts cranially (mesodermal origin) and the urogenital sinus
FIG. 19.2 Excised uterus postmortem with the uterine lumen exposed
to show endometrial folds.
 CHAPTER 19
caudally (ectodermal origin).1 It consists of a collapsed poten-
tial space extending from the cranial vaginal fornix caudally
to the transverse fold.1,11 Some authors consider the vestibule
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as part of the vagina, and others define the caudal border at
the transverse fold.4,11,12 The vaginal epithelium is aglandular,
stratified squamous tissue and is surrounded by a thin wall of
fibroelastic tissue and scant smooth muscle.11 The cranial por-
tion of the vagina lies in the peritoneal cavity and is covered by
serosa, without a distinguishable muscular layer. The caudal
vagina lies in the retroperitoneal space and is not covered with
serosa. This has clinical implications, because cranial vaginal
lacerations can result in peritonitis. The lumen of the vagina is
normally collapsed, and the vestibulovaginal fold (or hymen)
in normal mares prevents aspiration of air and fecal material
into the vagina. The mucosa of the vagina should be pale pink,
and fluid should only be present at certain times (lochia post
foaling or small amounts of translucent fluid during estrus).
Otherwise, pathology should be suspected.
The vestibulovaginal fold (transverse fold or “hymen”) is a
fold of tissue derived from the fusion of the paramesoneph-
ric ducts cranially and the urogenital sinus caudally.1 This fold
of tissue provides a barrier against external contamination of
the cranial vagina and uterus. It is easily visualized as a sheet
of pink tissue at the cranial aspect of the vestibule when one
parts the vulvar lips (Fig. 19.5).13 When a vaginal or specu-
lum examination is performed on a maiden mare this tissue
FIG. 19.3 Cranial vaginal fornix demonstrating the dorsal and ventral
frenulum of the cervix.
FIG. 19.4 Change in appearance of the external cervical os as viewed through vaginal speculum examina­
tion, during different hormonal environments in the mare.
Disorders of the Reproductive Tract 12191219
may need to be broken down manually (causing minimal dis-
comfort). It is usually thin, occasionally fenestrated, and easily
torn. The function of this tissue as a barrier can be assessed by
parting the labia, and if air is aspirated into the vagina (as diag-
nosed by an audible noise or on visual evidence of pneumo-
vagina on transrectal ultrasound) then it is determined that
the vestibulovaginal seal is incompetent.13 Clinically, failure of
this seal may be less of a concern if the mare has an adequate
vulvar seal.
Vestibule
The vestibule, originating from the caudal urogenital sinus
(ectoderm), is the region of the reproductive tract that
extends from the vestibulovaginal fold to the vulvar lips.1 The
vestibule of the mare is lined by stratified squamous epithe-
lium, and a series of branched vestibular glands are present with
openings visible in the ventral and lateral vestibular walls.11 The
lateral walls of the vestibule contain erectile tissue that form the
left and right vestibular bulbs, which associate abaxially with the
constrictor vestibuli muscle.4 The external urethral orifice lies
beneath the vestibulovaginal fold, and the position of the ure-
thral opening relative to the pelvis and this fold may predispose
the mare to urovagina or urometra (Figs. 19.6 and 19.7).4
Vulva
The paired vulvar labia arise from the ectodermal tissue of the
urogenital sinus and provide the first and arguably the most
important external barrier to the internal reproductive tract.1,4
The vulvar labia of normal mares appose completely, with no
mucosal surface visible. The ventral commissure is rounded
and houses a prominent clitoris (approximately 2 cm in diam-
eter), lying in the clitoral fossa, which can be seen rhythmically
everted during estrus (“winking”). The dorsal commissure of
the vulva is pointed, and its location and degree of cranial
inclination are often critically evaluated during a reproduc-
tive examination, because poor vulvar conformation has been
associated with contamination and pathology (Fig. 19.8).12,13
Mares with an increased cranial angle to the vulva, sunken
anus, or poor labial apposition are predisposed to fecal con-
tamination of the reproductive tract and may require cor-
rective surgery (Caslick or episioplasty and Gadd or perineal
body reconstruction).5,13
Clitoris
The mare’s clitoris arises from ectodermal tissue and consists of
a body and glans clitoris.1,12 The clitoral body (5 cm in length)
is formed from the crura of the ischium.12 The mare’s glans cli-
toris is more prominent than in most domestic species (2–3 cm
in diameter), and, similar to the male homolog, the glans penis
contains erectile tissue.1,12 The clitoris lies within the clitoral
 1220 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
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FIG. 19.5 Appearance of vestibulovaginal fold (hymen) in a mare fol­
lowing urethral extension surgery. (Courtesy Dr. Rolf Embertson.)
FIG. 19.6 Opening of the dilated urethral sphincter under the vestibu­
lovaginal fold. (Courtesy Dr. Rolf Embertson).
fossa (fossa clitoridis) and has three sinuses present in the
skin overlying the clitoris (Fig. 19.9).2,3 There are two smaller
lateral sinuses and a larger median sinus that can accumulate
debris and provide an environment that promotes growth of
certain pathogenic bacteria (Taylorella equigenitalis).4,12,14
Nonreproductive Tract Anatomy
Mammary Gland
The mammary glands are derived from ectodermal tissue and
lie in the inguinal region, often inconspicuous even during
lactation.1 The mare’s udder consists of left and right laterally
compressed halves with its respective teat.2 Each teat has two
(sometimes three) separate lactiferous duct systems that empty
into a single ostium.2 There may be two or three ostia per teat,
with each opening representing a separate duct system. Dur-
ing lactation the glands are soft and should not be firm and
distended if the foal is nursing adequately. When not lactating,
the glands involute and become soft and flaccid.
Hypothalamus and Pituitary Gland
The hypothalamus (part of the diencephalon) is located below
the thalamus in the rostral aspect of the brainstem.2,3 The
hypothalamic nerve cell bodies (hypothalamic nuclei) that
influence reproductive function are grouped into “tonic” and
“surge” centers.1 Neurons in these regions have axons that
either terminate into a capillary system that perfuses the ante-
rior pituitary or that terminate in the posterior pituitary to
release hormones into systemic circulation.1,2 The hypothal-
amohypophyseal portal system carries gonadotropin-releas-
ing hormone (GnRH) from hypothalamic nerve endings in
undiluted small concentrations to target cells in the anterior
pituitary.1,2,4
The pituitary is divided into the posterior lobe (neurohy-
pophysis) and the anterior lobe (adenohypophysis), which is
further divided into anterior and intermediate lobes.3,12 The
anterior pituitary cells under stimulation from GnRH release
their hormones into the systemic circulation. The primary
hormones released from the anterior pituitary’s gonadotroph
cells include follicle-stimulating hormone (FSH), luteinizing
hormone (LH), and prolactin (PRL). Neurons from hypo-
thalamic nuclei such as the paraventricular nuclei (PVN) in
the hypothalamus extend directly into the posterior pituitary,
where upon stimulation of the cell body, hormones (oxytocin
and vasopressin) are directly released into circulation.1,2,4
Y REPRODUCTIVE PHYSIOLOGY OF THE
NONPREGNANT MARE
Reproductive Hormones
Environmental factors (daylight length, pheromones, and
nutrition) transmit information through neural signaling and
the pineal gland to the hypothalamus to regulate the release of
GnRH.1,4-6 The pulse frequency of release is regulated by posi-
tive and negative feedback from other reproductive hormones
(inhibin, estrogens, and progestogens) secreted by the repro-
ductive tract. The reproductive tract undergoes changes as a
result of this hormonal milieu, which is dictated by the inter-
play of the hypothalamic-pituitary-gonadal (HPG) axis. Table
19.1 summarizes the major reproductive hormones and their
primary targets and effects. Fig. 19.10 is a simplified summary
of this hormonal axis and the reproductive tract illustrating
the hormones, their targets, and effects.
Reproductive Phases of the Nonpregnant Mare
The mare is a seasonally polyestrous, long-day breeder with
regular estrous cycles repeated when daylight is long and
resources for the dam and foal are optimal.4-6 The mare’s
annual reproductive rhythm (in the Northern Hemisphere)
can be divided into four phases: (1) winter anestrus, (2) vernal
transition, (3) ovulatory/breeding season, and (4) autumnal
transition. The transition into these different phases is medi-
ated through environmental clues, most notably length of
exposure to light or photoperiod.4,5,15
 CHAPTER 19
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FIG. 19.7 (A) Urovagina as viewed on vaginoscopy with hyperemic vaginal mucosa and (B) as viewed on
transrectal ultrasound with hypoechoic fluid present in the vagina. (Courtesy Dr. Patricia Sertich).
It is believed that this change in photoperiod is con-
veyed by the retina through a multineuronal pathway that
modulates melatonin secretion, which then regulates hypo-
thalamic secretion of GnRH.4,5 Under increasing daylight,
melatonin secretion is reduced (the majority of melatonin is
secreted during night/dark), and melatonin’s inhibitory influ-
ence on GnRH synthesis and secretion is removed, resulting
in increased GnRH secretion. Increasing concentrations of
GnRH stimulate follicular development and the start of the
vernal transition.4
Winter Anestrous/Anovulatory Season
Generally the incidence of mares undergoing a period of repro-
ductive quiescence or anestrus varies in relation to increasing
distance from the equator. The incidence of anestrus at lati-
tudes between 30° and 50° is approximately 70%, whereas at
latitudes between 10° and 30°, less than 50% of mares experi-
enced anestrus.15-18 During anestrus the mare’s production of
GnRH is reduced, resulting in a decrease in pituitary secretion
Disorders of the Reproductive Tract 12211221
of FSH and LH. Consequently there is little follicular develop­
ment and no corpora lutea formation, and thus circulating
concentrations of estradiol and progesterone are low.
Palpation and ultrasonography of the reproductive tract
during anestrous reveal small inactive ovaries (largest follicle
<10 mm), a flaccid uterus, and a cervix that may have tone
but will relax and give way to digital pressure or dilation. No
uterine edema or intraluminal uterine fluid should be pres-
ent, and the cervix is often pale pink and appears closed on
vaginoscopy. Reproductive behavior is considered ambivalent,
with neither strong aversion to the stallion nor demonstrative
teasing. Occasionally breeding will be permitted by the anes-
trous mare and can be mistaken as a sign of true fertile estrus
and follicular development. This is confusing because the term
anestrus means lack of estrus or receptivity to the stallion,
and as previously mentioned mares in this period have been
known to allow breeding and even demonstrate receptive sex-
ual behavior. This highlights another difference in mare repro-
ductive physiology compared with most domestic species.
 1222 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS

Vernal Transition/Anovulatory Receptivity

As the length of daylight increases, hypothalamic GnRH pro-
duction and secretion increases, resulting in an increase in
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circulating FSH and eventually LH concentrations.4,19 Sev-

FIG. 19.8 Poor perineal conformation in a mare with episioplasty
(Caslick type) in place. Note the sunken anus and cranial tilt of the dorsal
vulva. (Courtesy Dr. Rolf Embertson).
eral waves (average of 3.7) of follicular growth and regression
occur without ovulation before the first ovulation of the sea-
son.20,21 The first ovulation marks the end of vernal transition
and the beginning of regular interovulatory intervals or the
“breeding season.” FSH levels are variable during transition,
whereas LH concentrations remain low, resulting in prolonged
periods of estrus for approximately 1 to 2 months before ovu-
lation.22 Early follicular waves have decreased steroidogenesis,
so estradiol elevates only in the later follicular waves that result
in ovulation.23 These transient infertile estrus periods may
cause the inexperienced owner or practitioner to waste time
inappropriately breeding a mare that will not ovulate, generat-
ing unnecessary costs and possibly contaminating the mare. It
should be noted that not all mares have a defined transitional
phase, and some remain in deep anestrus and only develop
one follicular wave prior to ovulation.24
Reproductive evaluation of the mare during this time usu-
ally reveals large ovaries with multiple medium (>20 mm) to
large follicles and no corpora lutea. Endometrial edema may
vary from nonexistent to prominent, and there is a palpable
increase in uterine thickness and tone. Small amounts of intra-
uterine fluid may be present coinciding with increased uter-
ine edema. The mare’s cervix relaxes under an environment
of increasing estradiol and minimal to no progesterone. The
mare’s behavior is often characterized as persistent, inter-
mittent, or irregular intervals of estrus in which the mare is
receptive to mating but because of lack of ovulation will not
conceive.5,6,15 This can be a very frustrating time for owners
with horses in training because they often complain of persis-
tent estrus, which some feel interferes with performance.

Ovulatory Receptivity/Breeding Season

FIG. 19.9 Clitoris with smegma in the clitoral fossa.
Following the first ovulation of transition, the mare begins to
have regular interovulatory intervals (estrous cycles). The time
the first ovulation occurs may vary based on individual, lati-
tude, management, and breed. In the Northern Hemisphere,
the first ovulation of the year usually occurs naturally around
late April to May.4 The average estrous cycle duration in the
mare is 21 days (range 18–24), with estrus (follicular growth
with sexual receptivity) lasting 4 to 7 days on average, and
diestrus (active corpus luteum [CL] and nonreceptivity) last-
ing 14 to 15 days.4-6
Estrus. Estrus is defined as the behavior of sexual receptiv-
ity to the stallion but also refers to the phase in the estrous
cycle when the mare is approaching ovulation and is sexu-
ally receptive.21,22,25 Estrus in the mare, as stated previously,
is typically around 7 days, lasting longer at the beginning of
the breeding season and growing shorter toward the end.4,5
During early estrus, follicles are recruited to grow under in-
creasing FSH and LH secretion, and progesterone is low (<1
ng/mL).1,4,5 As the cohort of follicles grow (3–5 mm/day) they
secrete estradiol, which has a positive feedback on the ante-
rior pituitary, inducing an increase in LH secretion and thus
follicular maturation.1,4,22 Inhibin, produced from the grow-
ing dominant follicles, inhibits FSH secretion, and one or
two dominant follicles continue to develop (>30 mm) under
stimulation from LH alone. This single follicle or occasionally
two or more dominant follicles continue to grow, and when
preovulatory estradiol levels are reached, an increased LH (an
 CHAPTER 19 Disorders of the Reproductive Tract 12231223

TABLE 19.1 Summary of Reproductive Hormones*

Name of Biochemical
Hormone Classification Source Target Tissue Main Action
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GnRH Neuropeptide Hypothalamic surge and Anterior lobe of the pitu- Release of FSH and LH from
(decapeptide) tonic centers itary (gonadotroph cells) the anterior pituitary
FSH Glycoprotein Anterior lobe of the pituitary Ovary (granulosa cells) Stimulates follicular
(gonadotroph cells) development
LH Glycoprotein Anterior lobe of the pituitary Ovary (cells of theca in- Induction of ovulation,
(gonadotroph cells) terna and luteal cells) follicular maturation
Luteal tissue support
Prolactin Protein Anterior lobe of the pituitary Mammary cells Induces maternal behavior,
(lactotroph cells) induction of lactation
Oxytocin Neuropeptide Synthesized in the hypothala- Myometrium and endome- Induces uterine contractions
(octapeptide) mus, stored and released trium, myoepithelial cells and milk ejection, induces
from the posterior pituitary in the mammary gland prostaglandin release
Evidence of production in the and promotes maternal
endometrium behavior
E2 Steroid Granulosa cells of the follicle, Hypothalamus, entire Facilitates receptive sexual
placenta reproductive tract behavior, regulates GnRH
secretion, enhances
secretory activity of the
reproductive tract, and
enhances uterine motility
P4 Steroid Corpus luteum and placenta Uterine endometrium, Inhibits sexual receptivity,
myometrium, mammary alters endometrial gland
gland, and hypothalamus secretion, promotes main-
tenance of pregnancy, and
inhibits GnRH release
Testosterone Steroid Cells of the theca interna of Brain, skeletal muscle, and Substrate for E2 synthesis,
the follicle granulosa cells abnormal masculinization
Inhibin Glycoprotein Granulosa cells of the follicle Gonadotrophs of the ante- Inhibits FSH secretion
rior pituitary
Prostaglandin Prostaglandin Endometrium and follicle Corpus luteum, uterine Luteolysis, promotes uterine
F2α (PGF2α) (C-20 chain fatty myometrium, and ovula- contraction, role in ovula-
acid) tory follicles tion induction
Melatonin Neuropeptide Pineal gland Hypothalamus Inhibits GnRH secretion
  

E2, Estradiol; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; P4, progesterone; PGF2α, prostaglandin F2α.
Adapted from Blanchard TL, Varner DD, Schumacher J, et al. Manual of Equine Reproduction. 2nd ed. St. Louis, MO: Mosby; 2003, and information from
other sources.

LH surge) is induced, causing ovulation.24,26,27 The process of
ovulation is thought to take approximately 2 to 7 minutes and
results in the oocyte being released from the follicle through
the ovulation fossa. Ovulation generally occurs 1 to 2 days
after the initial rise in LH, with LH concentrations reaching
peak levels usually 1 day after ovulation has occurred.1,4,26 Re-
markable tissue remodeling occurs so that the oocyte can be
released, and it is suggested that this process is mediated by
prostaglandins (PGE2 and PGF2α) and tissue-remodeling en-
zymes (MMP-1 and MMP-2).1,23,28
During estrus, the reproductive tract prepares for mat-
ing. There is increased lubrication of the tract as uterine
and cervical glands increase mucus and glandular secre-
tion. Ultrasonography of the ovaries reveals multiple follicles
(>20 mm) that grow 3 to 5 mm/day, often with one or two
dominant preovulatory follicles reaching preovulatory sizes
of 35 to 50 mm.4,5 Immediately before ovulation the follicu-
lar wall may thicken, the follicle softens, and often the mare
is sensitive to palpation in the periovulatory window.4,5,25
Endometrial edema is maximal 3 to 4 days before ovulation
and then decreases approximately 1 to 2 days before ovu-
lation.3,26 The mare’s uterus becomes more edematous and
“doughy” on transrectal palpation, with the cervix relaxing
significantly as ovulation approaches.1,5,26 During estrus,
scant hypoechoic intraluminal fluid can often be visualized
on transrectal ultrasound in the normal mare, but it is widely
believed that greater than 2 cm of fluid—or echogenic fluid at
any time—is associated with decreased pregnancy rates and
possible pathogy.30,31 The cervix relaxes as ovulation nears,
becoming edematous, pliable, and well lubricated. These
changes serve as a tool for the clinician to evaluate the mare’s
hormonal environment and thus accurately time breeding
(see Fig. 19.4). The behavioral signs observed during estrus
include elevation of the tail in the presence of the stallion;
eversion of the vulvar lips to expose the clitoris or “winking”;
squatting with rotation of the pelvis, urination, and leaning
toward the stallion; turning the head back toward the stal-
lion; and moving toward the stallion.32 Monitoring sexual
 1224 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
ESTRUS
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hypothalamus
anterior pituitary
,L
H
FS
inhibin
dominant
estrogen follicle
ovary
uterus
+ uterine ed
ema
+ cervical
relaxation
FIG. 19.10 Illustration of major reproductive hormones, their site of production, and the main targets in
the nonpregnant mare. llustration courtesy of Stephanie Gayer.
behavior of the mare is an essential part of good broodmare
management because it helps to identify the current stage of
the cycle and to determine the optimal time to breed or when
a mare is returning to estrus.
Diestrus. Diestrus is characterized by the elevation in
circulating progesterone from the CL that rises shortly after
ovulation.1,4 Progesterone levels in the blood rise from <1 ng/
mL during estrus to peak levels (8–16 ng/mL) at approxi-
mately 6 days post ovulation, and progesterone levels above 4
ng/mL persist until luteolysis occurs.4,5 Clinically this is use-
ful if one is unsure of the mare’s current stage of the estrous
cycle, because a serum progesterone can determine whether
there is active luteal tissue present (>1 ng/mL). FSH levels
rise and fall during diestrus, inducing follicular development
and estradiol secretion, but because of the inhibitory action
of progesterone on LH secretion, these diestrus follicles rarely
ovulate.33 Luteolysis occurs when episodic bursts of PGF2α
from the mare’s endometrium are released at 13 to 16 days
post ovulation in the absence of maternal recognition of
pregnancy. Luteolysis is rapid, and progesterone concentra-
tions plummet to <1 ng/mL within 2 days of initial prosta-
glandin release.4
During diestrus, the reproductive tract functions to sup-
port an early pregnancy. The uterus becomes toned, and
uterine contractions change to facilitate establishment of
pregnancy.34,35 The cervix elongates and closes, protecting
the uterine environment from caudal reproductive tract con-
tamination.4,5 The signature feature of ovarian morphology in
diestrus is the presence of an active CL, and it is important to
note that follicles can be any size during diestrus (from 10–50
mm in normal mares). Because of the inside-out structure
of the ovary and the restriction of ovulation to the ovulation
fossa, the CL remains almost entirely within the ovary, making
identification by transrectal palpation difficult. The advent of
DIESTRUS
GnRH
LH
progesterone
PGF 2α indu corpus
ced
luteo
lysis
luteum
ovary
e
ne ton
+ uteri
ne
ical to
cervix + cerv
transrectal ultrasound imaging has improved diagnostic capa-
bilities by enabling practitioners to visualize the corpora lutea,
and with increasing resolution, often aged inactive corpora
lutea can be visualized as well. During mid to late diestrus
there is normally no uterine edema or intraluminal fluid pres-
ent. The mare is categorically nonreceptive to the stallion and
may kick out, strike, and demonstrate avoidance to precopula-
tory interactions of a stallion.32
Autumnal Transition. During the “autumnal transition”
the mare progresses from regular interovulatory intervals to
ceasing ovulation and finally into anestrus. Often changes as-
sociated with this transition begin to occur shortly after the
summer solstice in the Northern Hemisphere. The beginning
of this period is marked as following the last ovulation of the
season.36 The transition is characterized by irregular estrous
intervals, failure of ovulation, and a prolonged or shortened
luteal period. Photoperiod and environmental stressors (nu-
trition, temperature, and stress) are all believed to have some
role in the decrease in gonadotropins during this period.4,36
During this approximately 60-day window, GnRH, FSH, and
LH production and secretion decrease, and consequently, sys-
temic estradiol and progesterone concentrations eventually
wane to basal levels.4,36
Reproductive tract examination at this time often reveals
multiple large anovulatory follicles in early transition to mini-
mal ovarian activity late in transition, with occasionally the
last CL still visible with transrectal ultrasound. The uterus
under the decreasing estradiol and progesterone becomes
increasingly flaccid with minimal to no edema. The cervix
often remains toned and closed because of the dwindling pro-
gesterone from the last ovulation. Mares often demonstrate
erratic estrus duration and frequency, similar to the vernal
transition, again making their behavior a source of frustration
for owners.
 CHAPTER 19
Postpartum Period
Immediately after expulsion of the fetus, the equine uterus
begins the rapid process of involution. The mare’s placentation
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(diffuse and epitheliochorial) requires less endometrial repair
following parturition compared with other domestic species
(bovine, caprine, and ovine), enabling a mare to conceive
and carry another pregnancy again shortly after foaling.1,4,5
Histologic return of the endometrium to the pregravid size
is reported to occur by 10 to 14 days, and the uterine size is
reported to return to the pregravid state over a period of 23 to
32 days.4,37,38 “Foal heat” is defined as the first period of sexual
receptivity and ability to conceive after parturition and usually
begins 7 to 9 days after foaling.4 The first ovulation post foal-
ing occurs on average at 9 days post parturition.4 Depending
on the efficiency of uterine involution, the fertility of this foal
heat varies. There are many different opinions on the fertility
of “foal heat” breeding, and it is likely that breed and man-
agement may have an influence. If significant fluid (>3) cm is
present within the uterus at foal heat, then breeding the mare
is not recommended.38 In addition, studies regarding the effect
of season on first postpartum ovulation suggest that mares that
foal in January and February tend to have longer intervals from
foaling to the first fertile ovulation than mares that foal in late
spring. After the foal heat most mares have a second 30-day
heat that occurs approximately 14 days after the end of the foal
heat and may represent a more reasonable time to breed. It has
been suggested based on several studies that increased preg-
nancy rates and decreased embryonic loss occurs when mares
are bred at least 10 to 20 days postpartum. Some authors sug-
gest an even longer period is needed following parturition to
return to prepartum per cycle pregnancy rates.38-40
During the postpartum window in hospitalized patients,
it is important to monitor daily rectal temperatures, uterine
fluid accumulation, and the attitude of the mare, because sig-
nificant endometritis can develop into metritis in mares not
given the opportunity to ambulate and expel lochia. Although
fluid within the uterine lumen by ultrasound is not abnormal,
lavage and ecbolic agents may be helpful to assist with invo-
lution. In healthy mares the uterine fluid (lochia) and debris
usually dissipate 7 to 10 days after parturition.4,30,31
Lactational Anestrus
Lactational anestrus, or inhibition of follicular development
because of nursing, is not as well defined in the mare as it is
in other species.6 Because of the prevalence of foal heat and
normal cyclicity in the majority of mares nursing foals, most
believe it does not exist at all but is a consequence of stress
from the puerperal period and perhaps increased metabolic
demands. Limited studies have been performed in which foals
were removed from mares at varying time points after partu-
rition. One study indicated that removal of the foal hastens
the onset of estrus.41 Foal removal has been associated with
elevated LH concentrations and increased ovarian follicle
diameter in some studies and conflicting results in others.40,41
Mare Breeding Soundness Examination
Maria R. Schnobrich
This section will describe the reproductive evaluation of
the mare (also known as a breeding soundness examination
[BSE]), the procedures involved, and the common pathologies
identified. A BSE of the mare may be performed for a variety
Disorders of the Reproductive Tract 12251225
TABLE 19.2 Details of Information to Be Gathered During
History Taking
History Comments
General health Vaccination, deworming, foot care, den-
tal care, nutritional history, systemic
diseases, and management
Athletic Level of activity, age at which athletic
career ended, any known drug usage
Cycling Length of estrus, expression of estrus,
interovulatory interval
Breeding Number of cycles bred, breeds per
cycle, natural or artificial insemination,
fertility of stallion, age at which the
mare was last bred
Pregnancies Number of diagnosed pregnancies and
outcomes
Foaling Any history of dystocia, type of man-
agement
Prior reproductive Diagnoses, treatment, management
examinations
Prior reproductive Nature of surgery, date performed, and
surgeries outcome
Drug use during Ovulation induction, estrous cycle
breeding season manipulation
  
of reasons including prepurchase or prebreeding examination
to confirm normal reproductive tract findings, the evaluation
of subfertile mares, or identification and treatment of repro­
ductive tract pathology. Procedures that should be performed
in all BSEs include proper identification of the individual,
review of signalment and pertinent medical and reproductive
history, general physical examination, perineal examination,
transrectal palpation and ultrasonography of the reproductive
tract, vaginoscopy, and digital cervical and vaginal examina-
tion. Additional procedures that may be considered depending
on the purpose of the BSE and preliminary findings include
uterine culture and cytology, uterine biopsy, and hysteroscopy.
Next is a stepwise description of the procedures performed
when conducting a thorough BSE.
Y IDENTIFICATION
Detailed identification of the mare is of utmost importance for
legal and ethical reasons. The recording of acquired brands,
tattoos, and detection of a microchip should all be considered
to supplement the physical description or photographs. In
the worst-case scenario, improper identification can lead to
erroneous conclusions and recommendations being made or
to procedures being performed on the incorrect mare, which
could compromise a pregnancy.
Y SIGNALMENT AND HISTORY
History and signalment may suggest possible problems and
guide the diagnostic approach (Table 19.2). The administra-
tion of certain medications (anabolic steroids, progestogens,
and GnRH vaccine) during an athletic career can affect the
horse’s future fertility, and the possibility of previous admin-
istration should be investigated. The use of anabolic steroids
can cause masculine behavior and changes to the external
 1226 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
genitalia. There might also be a downregulating effect on the
HPG axis, causing reproductive senescence that has to reverse
over time. The use of an anti-GnRH vaccine (Equity; Pfizer
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Animal Health, West Ryde, Australia) is used as a reportedly
effective way to inhibit estrus in fillies. Unfortunately, a num-
ber of fillies have had prolonged ovarian inactivity in their
breeding career caused by this vaccination.42- 44 Several cases
have been described of cytogenetically normal mares that
have prolonged (four seasons or more) ovarian inactivity after
the use of the GnRH vaccine. The age when the vaccine was
administered may also have an effect because peripubertal fil-
lies receiving the vaccine appear to have more prolonged peri-
ods of ovarian inactivity.
Breeding history should include detailed information from
the immediate past, including information on the standard
of current or previous breeding management and facilities. It
is also valuable, although more difficult, to obtain historical
information on the mare’s entire breeding career. Particular
attention should be paid to the specific details of the time and
cause of any pregnancy loss; any dystocia and follow-up repro-
ductive function; or known trauma, hemorrhage, or pathology
associated with breeding, pregnancy, or foaling, because these
may highlight particular regions that should be evaluated
more critically during examination. Often a detailed breeding
history of an infertile mare will help direct the evaluation and
diagnostics used, because a mare that has never had an early
pregnancy diagnosed has a different differential list compared
with a mare with repeated early pregnancy loss.
In addition to breeding history, the mare’s medical his-
tory and current management should be evaluated to identify
areas (nutrition, hoof care, pain management, deworming and
vaccination) that may need to be addressed to optimize the
chances of conceiving and carrying a pregnancy to term. Any
previous or current medical issue should be evaluated to deter-
mine whether it is still having any adverse effects on the mare’s
systemic health, and appropriate management and treatment
should be initiated to optimize the overall health of the animal.
Y BEHAVIOR
The season of the year should be considered when assess-
ing reproductive behavior in the mare, because transitional
anestrous mares and mares in estrus can demonstrate simi-
lar behavior despite being at different reproductive phases.45
The behavior expected for each phase of the reproductive
cycle is described in the previous section. Assessing the mare’s
response to a stallion while in estrus is important and can help
time appropriate breeding and determine whether additional
steps must be taken to safely achieve live cover. If a foal is pres-
ent with the mare, then estrus may not be demonstrated as
readily to the stallion until the foal is taken away. In addition,
shy or aggressive behavior toward the teaser by the mare while
in true physiologic estrus might require additional training
and management in a live-cover breeding situation. Overly
aggressive, stallion-like behavior when presented with a teaser
may also help confirm the presence of a hormone imbalance
or reproductive pathology.
Y GENERAL PHYSICAL EXAMINATION
General observation of the mare while loose and being led
to the stocks will allow assessment of behavior and prelimi-
nary assessment of comfort, condition, and conformation and
may highlight musculoskeletal issues. A brief general physical
examination should be performed to ensure that the mare has
no detectable condition that could interfere with the ability
to conceive or carry a foal to term. The practitioner should
inspect the mammary glands visually and with palpation for
evidence of abnormalities such as spurious lactation, mas-
titis, fibrosis, and neoplasia. Excessive body condition and
abnormal fat deposits (cresty neck) or hair coat may suggest
endocrine disorders such as metabolic syndrome or pituitary
pars intermedia dysfunction (PPID), which may have nega-
tive effects on the mare’s fertility.45-48 Poor body condition has
been associated with decreased fertility, and an underlying
cause should be identified and addressed. The mare’s hair coat
should also be evaluated, as a poor hair coat may suggest sys-
temic health concerns.
Y RESTRAINT
The mare must be adequately restrained before further exami-
nation. What constitutes adequate restraint will depend on the
mare’s disposition, the skill and experience of the handler and
veterinarian, the procedures being performed, and the facilities
available. Particular care must be exercised when performing
a BSE on mares with little prior exposure to transrectal palpa-
tion or vaginal speculum placement. Stocks are generally rec-
ommended for a BSE, although adequate restraint (chemical
and/or twitch or lip chain) with the mare backed out of a stall
door will suffice for practitioners comfortable working under
these conditions. If hysteroscopy is to be performed, then it
is recommended that the mare be sedated and restrained in
stocks. The stocks minimize the mare’s movement during the
examination and protect the veterinarian and equipment.
Chemical restraint facilitates a safe and efficient examina-
tion for certain BSE procedures that are less well tolerated or
more prolonged. Chemical restraint may cause some degree of
relaxation of the perineum, and therefore it is recommended to
assess perineal conformation prior to sedation. In addition α2-
agonists cause increased uterine tone. The dose of sedation is
based on the behavior and excitability of the mare. In general
detomidine HCl (0.01–0.02 mg/kg) and butorphanol tartrate
(0.01–0.02 mg/kg) administered intravenously (IV) often pro-
vide adequate sedation for most procedures. Xylazine (0.2–1.0
mg/kg) or detomidine HCl (0.006–0.01 mg/kg) is admin-
istered again if sedation is not adequate or if the procedure
length dictates additional redosing.
Y EXAMINATION OF EXTERNAL
GENITALIA
The perineal region is inspected for indications of vulvar dis-
charge and gross abnormalities of the anogenital region. Vul-
var discharge or urine scalding of the inner thighs may suggest
infection, urine pooling, or urinary incontinence. Fluid and
dried secretions in the tail may give evidence of vulvar dis-
charge as well. Clitoral enlargement or abnormal anogenital
distance may indicate prior exposure to androgens or proges-
togens or an intersex condition (Fig. 19.11). Normal vulvar
lips are vertical, have good tone, and are in close apposition.
Vulvar integrity is important in forming an effective seal
against contamination of the genital tract with air, urine, feces,
and potential pathogens.13,49 Vulvar conformation is assessed
by digital palpation adjacent to the vulvar lips to locate the
 CHAPTER 19
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FIG. 19.11 Abnormal anogenital distance in a Friesian male pseudo­
hermaphrodite.
position of the caudal bony pelvic brim (tuber ischii) relative
to the dorsal commissure of the vulva. Pascoe’s description of
Caslick index has been modified to produce a simple assess-
ment technique for vulvar conformation.49 Generally the dor-
sal commissure should be level to less than 4 cm above the
brim of the pelvis with well-apposed labia and minimal cranial
tilt of the vulva, and the anus should be in the same vertical
plane as the vulvar lips. Sunken anus, thin vulvar lips, poor
labial apposition, and cranial tilt to the vulva all predispose to
fecal contamination and have been associated with decreased
pregnancy rates.13,49 To determine the competency of the vul-
var seal and the vestibulovaginal fold, transrectal ultrasound
can be performed, and the vagina and vestibule can be evalu-
ated for air contamination. Traditionally this evaluation has
been performed by gently parting the vulvar lips to determine
whether air is readily aspirated into the vagina.13 If there is
poor labial apposition or aspiration of air, then the mare may
be prone to pneumovagina and at increased risk of ascending
vaginitis and subsequently endometritis.13
• Vulvar conformation (VC) good: No Caslick is required.
Dorsal commissure of the vulva is less than 4 cm above the
bony pelvic brim, and vulvar lips are within 10 degrees of
vertical and form an effective seal.
• VC marginal: Caslick may be required. Dorsal commissure
of the vulva is 4 to 7 cm above the bony pelvic brim, vulvar
lips are within 10 to 20 degrees of vertical, and vulvar lips
still form an effective seal.
• VC poor: Caslick or some other corrective procedure is
definitely required. Dorsal commissure of the vulva is 5 to
9 cm or more above the bony pelvic brim, vulvar lips are 30
degrees or more in front of vertical, and the vulvar seal is
not effective.
Disorders of the Reproductive Tract 12271227
• I t should be noted that in certain breeds (Thoroughbreds)
the Caslick’s is recommended in almost every mare, as even
those mares that appear to have normal vulvar conforma-
tion are predisposed to contamination, and ascending pla-
centitis is a more common occurrence.
Y TRANSRECTAL PALPATION AND
ULTRASOUND EXAMINATION OF
THE REPRODUCTIVE TRACT
It is essential that the nonpregnant status of the mare is con-
firmed before any procedure is performed that could compro-
mise a pregnancy. Transrectal palpation of the genital tract is
generally considered safe and appropriate but does carry some
risk of rectal mucosal trauma and potentially laceration. The
risk increases if excessive force is used, if palpation contin-
ues in the presence of pneumorectum, and if the mare strains
excessively. Mild sedation to minimize anxiety and reactivity
may be accomplished with an α2-agonist as described previ-
ously, with or without an opioid (e.g., butorphanol). Admin-
istration of N-butylscopolamine (0.3 mg/kg) by IV injection
several minutes before the examination may also help pre-
vent straining and relax the rectum, but it may interfere with
accurate assessment of uterine tone.50 As noted previously, α2-
agonists increase uterine tone, and N-butylscopolamine will
decrease uterine tone.
Transrectal palpation of the reproductive tract should pro-
ceed with an organized, methodical approach. For example,
one author, after removing all fecal material, palpates the
left ovary, left uterine horn, right uterine horn, right ovary,
right uterine horn, uterine body, and finally the cervix. It is
important to note the ovarian position, follicular activity, size,
texture, and presence of the ovulation fossa. The loss of a pal-
pable ovulation fossa can be an early indicator of distortion
of the normal ovarian shape secondary to neoplasia or other
pathology.51,52 The position of the uterus relative to the brim
of the pelvis; the size, tone, sacculations, or differences in tex-
ture of the horns; and the presence and character of endome-
trial folds should be assessed. The general tone of the uterus
should be evaluated and compared with the stage of the cycle;
for example, one would expect a toned uterus in diestrus, and
conflicting findings may suggest pathology. The cervical size
(approximate length and width), tone, and consistency are
assessed by pressing the cervix down against the pelvic floor.
Cervical relaxation can most effectively be measured on a slid-
ing scale that spans from the closed toned cervix, 0% relaxed
(i.e., tightly closed, tubular cervix) to 100% relaxed (i.e., indis-
tinguishable from adjacent uterus), and should be critically
evaluated if appropriate tone is present for the stage of estrous
cycle.
It is important to purposefully assess anatomic structures
other than the reproductive tract as part of the palpation
examination, including the pelvic inlet, caudal aorta, broad
ligaments, bladder, intestines, and lymph nodes. Note the
presence of soft tissue or bony changes that may narrow the
diameter of the pelvic inlet, suggest pathology (aortic aneu-
rysm, neoplasia), or potentially interfere with foaling. For
example, firm swellings in the broad ligaments may suggest
previous hemorrhage, neoplasia, or an abscess. Structures that
may narrow the pelvic inlet and cause a potential problem for
foaling include abscesses, lacerations, hematomas, neoplasia,
vascular aneurysms, bladder stones, and pelvic fracture.
 1228 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS

TABLE 19.3 Application of Transrectal Palpation and Ultrasound of the Genital Tract for Assessing Various Parameters
Organ Structure Detail of Assessment Technique
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Ovary Ovary Size, shape, presence of ovulation fossa P, US

Echotexture of contents US
Consistency of tissue P
Corpus hemorrhagicum Presence P, US
Corpus luteum Presence or absence, size, shape, echotexture US
Follicles Size P, US
Shape, wall thickness and echotexture, echotexture US
of contents
Turgidity P
Uterus Diameter, shape, tone, wall thickness, endometrial P, US
folds, luminal fluid (larger amounts)
Wall echotexture, endometrial folds, luminal fluid US
volume and echotexture
Cervix Length, width, depth P, US
Echotexture US
Relaxation P
Vagina and vestibule Fluid accumulation, gas (air) accumulation P, US
  

P, Transrectal palpation; US, ultrasound.

Transrectal ultrasound examination should be considered
a routine part of a reproductive tract examination. It allows
the use of electronic calipers for measuring structures and
facilitates the assessment of tissue and fluid characteristics as
well as subtle pathology that may not be detected by palpation.
Table 19.3 presents comparative information on the applica-
tion of palpation and ultrasound for assessing various genital
tract structures.
The basic approach as described previously for rectal exam-
ination is used for transrectal ultrasound examination. Most
practitioners use a 5- to 10-MHz linear rectal probe, and focal
distance is set at a depth of 5 to 10 cm for initial evaluation.
While holding a linear transducer, the practitioner extends the
fingers beyond the end of the probe to assist in locating genital
tract structures and prevent the probe from penetrating the
rectal wall. The uterine body is initially identified as a land-
mark by sweeping the probe from side to side in the anterior
pelvis. The uterine body is then followed cranially to the bifur-
cation, and the probe is swept out toward one uterine horn and
ovary. Structures are examined in the same order as for palpa-
tion alone: left ovary, left horn, right horn, right ovary, uterine
body, cervix, bladder, and finally vagina and vestibule. The
orientation of the probe is adjusted to attempt to get a clear
cross-sectional image of the uterine horns, and in the longitu-
dinal plane the uterine body, cervix, and vagina are visualized
by moving side to side while moving the transducer caudally
(Figs. 19.12 and 19.13).
A simple recording system should be used with defined
abbreviations. This ensures that records can be understood at
a later date and facilitates an efficient communication between
multiple attending veterinarians. Ovarian size, follicles, and
the presence of any corpora lutea should be recorded along
with any suspected cysts or abnormal structures. Uterine horn
diameter should be measured about one third of the distance
from the bifurcation, and the presence of endometrial edema
and depth and character of any intraluminal fluid (in the dor-
soventral plane) should be recorded. Uterine and cervical
tone as assessed by palpation should be recorded. All follicles
larger than 15 mm in diameter are recorded individually, and
smaller follicles are recorded as multiple small follicles or may
be measured and recorded in some cases. The tone of the fol-
licles present should also be recorded, because often there is a
loss of turgidity in preovulatory follicles.
Y DIAGNOSIS OF OVARIAN PATHOLOGY
Abnormal ovarian enlargement should be suspected if an ovary
is greater than 10 cm in diameter and the increased size cannot
be attributed to recent ovulation or a follicle and persists for
more than a month.51-53 Large ovaries may be associated with
physiologic causes (e.g., persistent follicles, hematoma, mul-
tiple corpora lutea in midgestation) or pathologic processes
(e.g., neoplasia, hematoma, abscess).
Neoplasia more commonly affects one ovary, although it
can affect both, and typically results in an alteration in ovarian
size, shape, and consistency. There appears to be no consis-
tent pattern in the change affecting a neoplastic ovary with the
exception of teratomas in which the diagnosis may be based
on the detection of germ tissues, including cartilage, hair, and
bone. Other neoplasias may present as single large cystic or
multicystic structures or even solid tissue, and in rare cases
no ultrasonographic evidence of ovarian abnormality is pres-
ent. In many cases the diagnosis of ovarian neoplasia is based
on persistent unilateral ovarian enlargement with obliteration
of the ovulation fossa and an inactive or normally function-
ing contralateral ovary.54,55 There might be a history of aber-
rant ovarian activity before the development of the tumor.54 A
granulosa cell tumor (GCT), the most common ovarian neo-
plasia, may produce varying levels of testosterone, estrogen,
inhibin, and anti-müllerian hormone (AMH) but rarely pro-
duce progesterone.56-58
Functional ovarian tumors, such as the granulosa-theca
cell tumor (GTCT) or granulosa cell tumor (GCT), may
manifest as masculinization of appearance. Increased plasma
 CHAPTER 19 Disorders of the Reproductive Tract 12291229
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FIG. 19.12 Longitudinal image of the cervix with air in the vagina. Orientation in this image is cranial to
the right and caudal to the left. This image was made by combining two images taken as the probe was
positioned caudally.

FIG. 19.13 Longitudinal image of the bladder, pelvic urethra, and opening of the ureter in the dorsal
bladder wall. This image was made by combining serial images of the tract obtained with a standard linear
rectal probe.

concentration of AMH, inhibin, or testosterone in conjunc-
tion with clinical signs (abnormal ovarian parenchyma or
abnormal behavior) is considered diagnostic of GTCT.57,59 The
ultrasonographic appearance of most GTCT is characteristic,
varying from uniformly dense multiloculated to cystic (Fig.
19.14), although it should be noted that some GTCT tumors
present with no detectable abnormalities on transrectal pal-
pation or ultrasound and are confirmed at the time of histo-
logic tissue analysis with the only presenting complaint being
abnormal behavior.59,60
Anovulatory follicles often grow to an unusually large size
(50 mm or greater) and fill with blood, organizing into a struc-
ture with the ultrasonographic appearance of a hematoma
that gradually recedes over time. Some of these structures
appear to develop a thick rim of tissue resembling luteal tis-
sue, with the mare entering a diestrus state, with progester-
one concentrations greater than 4 ng/mL. Other mares do not
develop a thick rim of tissue, and the structure may appear to
be inert. There is a lack of consensus regarding terminology,
with some authors distinguishing anovulatory hemorrhagic
follicles (AHFs; no luteinization) from luteinized unruptured
follicles (development of luteal rim). Others suggest that the
two structures are variations of the same condition.61,62 The
condition appears to be more common in mares approaching
winter anestrus and in pregnant mares under the influence
of equine chorionic gonadotropin (eCG), and there is some
 1230 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
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FIG. 19.14 Transrectal image of a granulosa-theca cell tumor with mul­
tiloculated “honeycomb” appearance.
evidence to suggest an increased incidence in mares adminis-
tered a luteolytic agent.61 Anovulatory follicles occur in 8% of
all estrous cycles63 but in 5% of estrous cycles in the early ovu-
latory season and 20% of estrous cycles in the late ovulatory
season.63 The ultrasonographic appearances of ovulatory and
anovulatory follicles are largely the same. Rarely is the ovula-
tion process normal in these structures, so mares that develop
these processes may have a history of infertility and irregular
estrous cycles.
Failure of the normal process of luteolysis may result in
prolonged luteal maintenance. Diagnosis depends on confir-
mation of nonpregnant status and the presence of a CL for a
period longer than the normal diestrus length (approximately
14 days)64. This condition, termed pseudopregnancy, must be
differentiated from cases in which a mare is ovulating between
examinations and exhibiting an apparently persistent CL. Lute-
olysis depends on PGF2α release from the uterus,65-67 which
relies on the timely (approximately 12-14 days after ovulation)
mechanism for endometrial PGF2α release to be functional.
An ovulation during diestrus will prolong diestrus, and the
resultant CL can last for more than 2 months.65,67 Other rea-
sons for failure of luteolysis include the release of PGF2α when
the CL is still immature and unable to optimally respond to
PGF2α (traditionally thought to be 5 days post ovulation), the
failure of PGF2α to be released at the proper time, and low-
level chronic release PGF2α from the endometrium (which has
been described in mares with endometritis).68
Small cystic structures may be palpated or visualized with
transrectal ultrasound adjacent to the ovary. These structures
often have an ovoid or serpentine shape, contain anechoic
fluid, are outside the ovarian parenchyma, and are usually
less than 2 cm in diameter. The structures (paraovarian cyst
or epoöphoron) are typically incidental findings assumed to
be cystic remnants of the mesonephric tubules and ducts.1
It is possible that these structures could interfere with gam-
ete transport if they obstruct normal function of the ovarian
bursa and infundibulum but are almost always functionally
insignificant.
Very small and inactive ovaries may be secondary to sea-
sonal anestrus, reproductive senescence in old mares, pitu-
itary gland dysfunction, severe malnutrition, administration
of anabolic steroids, administration of anti-GnRH vaccine, or
congenital infertility resulting from sex chromosome abnor-
malities.45,69-71 Sex chromosome abnormalities are often asso-
ciated with hypoplasia or segmental aplasia of the tubular
tract. Karyotyping may be used to further investigate such
mares. Chromosomal abnormalities have also been reported
from subfertile mares that have foaled previously and have no
detectable abnormalities of the genital tract. In light of this
fact, karyotyping may be considered in mares in which routine
diagnostic procedures fail to explain subfertility.72-77
Individuals with 63,X0 karyotype tend to be small in
stature and phenotypically female, with a small uterus and
ovaries.71,74,78 These mares demonstrate irregular estrus or
ambivalence in the presence of a stallion, and the uterus palpa-
bly and histologically can be within normal limits.71,74 Plasma
estrogen levels are low, and plasma LH levels are normal to
high.71 Sex reversal is a disorder that occurs in horses and
most commonly results in an infertile animal.72,76,77 The two
most common forms of sex reversals are a female phenotype
with male karyotype 64,XY, and a male phenotype with female
karyotype 64,XX. There can be a wide phenotype variation
with both conditions.72,79
The X trisomy is relatively rare in the horse. The XXX
mare is infertile, often demonstrates erratic estrus, has normal
external genitalia, and is phenotypically female with a small,
thin-walled uterus and small hypoplastic ovaries. Some of
these mares have been known to develop follicles and undergo
what appears to be ovulation.79-82
Mosaics and chimeras occur when the individual has
more than one cell line with different chromosomal make-
ups. 63,X/64,XX mosaics are phenotypically female; the
uterus varies in development, but ovaries may be small and
nonfunctional. These horses may show estrus and have an
enlarged clitoris. Endometrial biopsy often reveals glandular
hypoplasia.70,72,73
Y DIAGNOSIS OF UTERINE PATHOLOGY
Endometritis
Endometritis refers to infectious or noninfectious inflamma-
tion of the endometrium, which is a major cause of infertil-
ity in the mare. It is critical to differentiate this from metritis,
in which inflammation extends to the myometrium and can
cause life-threatening sequelae such as sepsis or laminitis.
While endometritis compromises a mare’s fertility, the mare
with endometritis is generally not systemically compromised
from the condition and can live a normal life if untreated. A
later section in this chapter discusses diagnosis and treatment
of endometritis in detail because of its importance in success-
ful mare breeding management. This section of the text will
review diagnosis of endometritis for the purpose of the BSE.
Transrectal ultrasonography is very useful for evaluating
presence, quantity, and echotexture of uterine luminal fluid.
Increased echogenicity of uterine fluid is positively correlated
with the amount of debris or white blood cell infiltration into
the fluid and is more common in older mares.83,84 Table 19.4
presents a grading system for recording uterine fluid echotex-
ture.85 The presence of grade I, II, or III fluid during any stage
of the cycle likely indicates endometritis. The presence of
fluid in diestrus has been associated with a lower pregnancy
rate and a higher embryo loss rate,86 presumably caused by
high levels of PGF2α in the fluid from the neutrophils.87 The
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TABLE 19.4 Classification System for Recording Uterine Fluid
Echotexture
Grade Ultrasound Appearance Gross Appearance
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I White (hyperechoic) Thick and creamy
II Light gray Milky
III Black with white specks Obvious sediment in fluid
IV Black (anechoic) Clear fluid
TABLE 19.5 Grading System for Recording Volume of
Intrauterine Fluid
Maximum Fluid
Classification Depth (mm) Gross Description
VS 1–2 Barely detectable
S 1–5 Often focal
M 5–20 Obvious fluid
L >20 Immediately apparent
  
L, Large; M, moderate; S, small; VS, very small.
presence of more than 2 cm of intraluminal fluid in the dorso-
ventral plane during estrus, the presence of fluid during dies-
trus, and fluid present 72 hours after insemination are strong
indicators of mares’ increased susceptibility to endometritis.31
Table 19.5 presents a grading system for recording the volume
of intrauterine fluid.
Complete absence of detectable intraluminal fluid during
estrus is associated with the absence of cytologic inflamma-
tion in most cases.31,88 The significance of anechoic (grade IV)
luminal fluid is less clear. Small or very small volumes of clear
fluid during estrus are likely to be normal, particularly if pres-
ent during early estrus before complete cervical relaxation and
maximal uterine drainage. Large volumes of clear fluid during
estrus, fluid that persists into late estrus, or smaller volumes
during early diestrus suggest an increased predisposition to
endometritis and reduced pregnancy rates compared with
mares without fluid.88-90 Luminal fluid visible more than 12
to 20 hours after breeding indicates mating-induced endome-
tritis.31,90,91 This condition has been reported in 10% to 15% of
mares being bred by live cover on a commercial Thoroughbred
stud farm.91 A more thorough discussion of endometritis and
the significance and character of intraluminal fluid is included
later in this chapter.
Discrete hyperechoic reflections present in the uterine
lumen on ultrasonographic examination may indicate air,
urine crystals, mucoid debris, and foreign material. Pneu-
mouterus may be seen in normal mares soon after uterine
culture, intrauterine treatment, artificial insemination (AI), or
natural breeding but should not be seen more than 24 hours
after breeding or treatment. The presence of pneumouterus at
times other than after breeding or uterine therapy indicates
loss of integrity of physical barriers to contamination (vulva,
vestibulovaginal sphincter, and cervix), and the cause of this
should be identified.
Endometrial Cysts
Circumscribed, discrete collections of fluid within the uter-
ine lumen may indicate endometrial cysts, intraluminal fluid
accumulation, or a conceptus. Endometrial cysts are usu-
ally classified as lymphatic or glandular. Lymphatic cysts
Disorders of the Reproductive Tract 12311231
are generally larger, anechoic, intraluminal cysts visualized
by transrectal ultrasonography, whereas the glandular cysts
remain small and surrounded by fibrocytes and are not easily
identified with transrectal ultrasound. Cysts may protrude into
the uterine lumen or remain intramural. Cysts may be single,
discrete structures closely resembling a conceptus or complex,
compartmentalized structures with irregular borders. Cysts
that protrude into or occlude the uterine lumen may reduce
fertility by interfering with embryo mobility and maternal rec-
ognition of pregnancy.92,93 Cysts within the endometrium may
interfere with gland function, and an increased number of
cysts is likely an indication of a compromised endometrium.94
Properties of an early conceptus that can be used to distin-
guish it from an endometrial cyst include movement through
the uterine lumen between days 10 and 16 post ovulation;
spherical, symmetric appearance with specular reflection vis-
ible on ultrasound; rate of growth (cysts are assumed to grow
little if at all); and appearance of the embryo proper after
about day 20, or presence of heartbeat after day 25. In addi-
tion, there are palpable changes in the tract that are consistent
with early pregnancy (e.g., increased uterine tone and closed,
elongated cervix persisting after day 14 post ovulation), and
general failure to return to estrus that would not be expected
in the nonpregnant mare. The association between cysts and
reduced fertility is debated, and the incidence of endometrial
cysts increases with age and parity.94,95 Large cysts or large
numbers of cysts may interfere with uterine clearance, embry-
onic movement, maternal recognition of pregnancy, and early
placentation. Extensive glandular cystic change may also
adversely affect uterine gland function and compromise estab-
lishment or normal development of pregnancy. To determine
whether a cyst is intraluminal and assess its location better, the
uterus can be distended with sterile saline or lactated Ringer’s
solution (LRS), and the outline of the cyst relative to the lumen
can be evaluated with transrectal ultrasound. Hysteroscopy is
also helpful for identifying the degree of interference a cyst
has with the uterine lumen (Fig. 19.15). Biopsy of cysts and
removal by laser or manual rupture have been described. To
minimize inflammation and prevent recurrence, cyst removal
with a diode laser has been reported to be very effective and
safe and to have improved the fertility of previously barren
mares.95
Pyometra
Pyometra is a chronic condition with accumulation of mucoid
or mucopurulent material within the uterine lumen with or
without cervical occlusion. The condition may occur in the
presence or absence of a CL and usually does not result in
systemic signs of illness. Pyometra may be mistaken for preg-
nancy on palpation as a result of fluid distention of the uterus
but can be diagnosed effectively with transrectal ultrasound.96
Treatment of pyometra usually involves dilation of the cervix
to allow drainage and uterine lavage with or without antibiotic
use.
Adhesions
Adhesions and scarring of the endometrium may result from
infusion of irritating solutions into the uterus, cesarean section,
and trauma associated with foaling or dystocia. Occasionally,
redundant tissue from failure of normal uterine development
or the absence of one uterine horn can be seen.97 Adhesions
involving the cervix have similar initiating causes and can
impair cervical function. The role of chronic endometritis or
 1232 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
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FIG. 19.15 Hysteroscopic image of a cluster of intraluminal lymphatic
cysts in the uterine horn.
FIG. 19.16 Luminal adhesions diagnosed on hysteroscopic evaluation
of a mare with chronic endometritis.
iatrogenic causes such as mechanical curettage in uterine or
cervical adhesions is less clear. Adhesions may reduce fertility
by interfering with function of the uterotubal junction, uterine
clearance, embryo movement, maternal recognition of preg-
nancy, and normal placentation.98,99
Occlusive adhesions may result in the accumulation of fluid
in the proximal portions of the tubular tract, and this may be
detected on palpation or ultrasound examination of the tract.
More commonly, adhesions are detected during hysteroscopy
(Fig. 19.16). Occasionally these adhesions can cause a pyome-
tra that can progress to systemic illness if infection is estab-
lished without drainage.
Focal uterine lesions may respond well to surgical removal
using a biopsy instrument or laser surgical equipment guided
by hysteroscopy.98 If the lesions are extensive or affecting the
deeper layers of the endometrium, then the prognosis may
be poor and treatment not warranted. Cervical adhesions are
commonly managed by manual disruption and then repeated
application of topical ointment containing an antimicrobial
and steroid in an attempt to prevent recurrence. In many
horses, cervical adhesions tend to recur once treatment stops.
Ventral Uterine Sacculation
Ventral sacculation is associated with a loss of normal muscle
contractility in the uterine wall, with the uterine sacculations
occurring most often at the ventral base of one or both uter-
ine horns. The condition is more common in older, multipa-
rous mares and may result in an increased risk of endometritis
due to loss of the normal contractile mechanisms responsible
for expelling uterine luminal fluid. This may also be linked to
mares that have a more pendulous uterus. When the uterocer-
vical angle is more ventral than horizontal, the mare is more
prone to fluid accumulation because of a reduced mechanical
ability to expel fluid.99
Vaginal and Cervical Examination
Good hygienic practice is essential in performing any vaginal
procedure, particularly those that involve penetration of the
cervix, to avoid inoculating the uterus. Cleanliness is perhaps
the simplest and most fundamental principle of good repro-
ductive practice. The practitioner should wrap the proximal
portion of the tail at a minimum, or enclose the tail in a plastic
sleeve and tie it to the mare’s neck with a quick-release knot.
Alternatively, an assistant may hold it out of the way. The peri-
neal region should then be washed with water and mild deter-
gent or povidone–iodine scrub and rinsed thoroughly. The
practitioner should then wipe just inside the vulvar lips with
damp cotton and clean smegma from the clitoral fossa and
sinuses. This is particularly important for mares with sloping
vulvar lips or if a rectal examination has just been performed.
The presence of fecal matter in the vestibule without a history
of any invasive procedure indicates a failure of the vulvoves-
tibular seal.
Use of sterile, plastic sleeves for vaginal procedures is ideal.
A practical alternative used by one author is to keep in a dust-
free area a zipper storage bag (e.g., Ziploc) containing clean
plastic sleeves to be used for vaginal procedures only. A new
sleeve is taken out carefully by grasping it only at the open end,
or each sleeve is turned inside out immediately before putting
it on to minimize the risk of contamination. Tearing off the
fingers from a plastic sleeve and putting on a sterile, surgical
glove can increase sensitivity and also facilitate cleanliness.
Sterile lubricant and equipment should be used. The practitio-
ner should be meticulous to prevent contamination of either
equipment or sleeves and gloves during any procedure.
Vaginal Speculum Examination
A sterile, lubricated speculum is inserted into the vestibule in
a slightly dorsal direction to avoid the urethral opening and
pushed through the vulvovestibular sphincter, with sphincter
integrity assessed as the speculum is inserted. Because they
reduce the risk of iatrogenic infection, single-use, sterile, dis-
posable specula are preferred over metal Caslick specula for
routine examinations. In some cases, a self-retaining metal
Caslick speculum may provide better visualization of the
vagina and vestibule.
Vaginoscopy is useful for the detection of vaginal hyper-
emia, fecal contamination, suppurative exudate, persistent
hymen, urine pooling, varicose veins, vaginal trauma, recto-
vaginal defects, and cervical defects. Although examination
with a vaginal speculum may be performed at any stage of
the cycle, evaluation of mares suspected of urovagina is best
performed during estrus, because estrogenic relaxation of the
genital tract and perineal region is maximal at this time.100
Vaginal speculum examination is an important component of
 CHAPTER 19
the BSE and often highlights abnormalities not identified by
transrectal palpation and ultrasonography.
The timing of the vaginal examination in relation to the
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rectal examination is also important. If the rectal examination
is performed first, then fecal contamination of the perineum
and vulva is often increased. This slight disadvantage is offset
by the advantage of doing the rectal ultrasound examination
first to assess pneumovagina and pneumouterus. The presence
of air in the vagina and uterus is difficult to interpret after a
vaginal examination. However, if air is present before a vaginal
examination, then it may indicate dysfunction of the vulvoves-
tibular fold. Repeated vaginoscopy may be associated with an
increased risk of iatrogenic vaginitis and persistent infection.
As a result, one author prefers to perform routine assessment
of cervical relaxation by transrectal palpation.
The vestibule and vestibular mucosa are evaluated by part-
ing the vulvar lips and by continuing to look in the speculum
as it is withdrawn following vaginoscopy. Varicosities of the
vestibulovaginal fold are best recognized and evaluated in this
manner.
Manual Examination of the Vagina
and Cervix
Examination of the genital tract is incomplete without manual
exploration of the vagina and cervix. The major benefit in this
procedure is the detection of cervical defects. Once the hand is
inserted into the anterior vagina, the forefinger is placed into
the cervical lumen and the thumb in the vaginal fornix. The
hand is then rotated and the entire circumference of the cervix
is palpated between finger and thumb to feel for disruption in
the cervical musculature. Abnormalities in the musculature or
damage to submucosal layers might interfere with the ability of
the cervix to close effectively. The cervical canal should be eval-
uated for any defects, tortuosity, or diverticula in which debris
can accumulate. Cervical abnormalities (adhesions, muscular
defects, and diverticula) are considered significant if they pre-
vent the cervix from relaxing during estrus to facilitate uterine
clearance, disrupt the ability to form an effective seal during
diestrus and pregnancy, or serve as a nidus of infection. The
examiner should also consider the length and diameter of the
cervical canal in relation to the estrous stage of the mare. A par-
tial tear involving the external os of the cervix may not require
TABLE 19.6 Clinicopathologic Techniques Available for Diagnosing Endometritis in Broodmares
Relative Sensitivities
(Number of Disease-Positive Animals That
Methodology Test Test Positive)
Kalayjian swab Culture Low
Cytology Moderate
Double-guarded swab Culture Low
Cytology Not performed
Low-volume lavage Culture Moderate
Cytology High
Biopsy Culture Moderate
Cytology Moderate
Cytology brush Culture Low
Cytology High
Adapted from LeBlanc MM, Causey RC. Clinical and subclinical endometritis: both threats to fertility. Reprod Domest Anim. 2009;44:10; Nielsen JM. Endometritis
in the mare: a diagnostic study comparing cultures from swab and biopsy. Theriogenology. 2005;64:510; and Overbeck W, Witte TS, Heuwieser W. Comparison
of three diagnostic methods to identify subclinical endometritis in mares. Theriogenology. 2011;75:1311.
Disorders of the Reproductive Tract 12331233
treatment if the cervix can still maintain an effective seal during
diestrus. For this reason, assessment of the severity of cervical
disruption should be performed when the mare is in diestrus.
Alternatively, the diestrus tone can be replicated by the admin-
istration of progesterone for a few days to close the cervix.
Care should be taken while performing a manual examina-
tion of the vagina and cervix to take time to palpate the vagi-
nal surface for pathology such as rectovaginal fistulas, vaginal
lacerations and scar tissue, varicosities, urine crystals, perivag-
inal hematoma or abscesses, and any abnormal mass or struc-
ture that may suggest pathology. In cases in which the mare is
suspected of urovagina, the integrity of the urethral sphincter
should also be assessed.
Endometrial Culture and Cytology
Endometrial culture and cytology are performed as diagnostic
tools for identification of endometritis, assessment of its sever-
ity, and determination of etiology. A variety of instruments and
techniques have been described for sampling the mare’s endo-
metrium for cytologic analysis, microbial culture, and DNA
isolation, and there is much debate regarding the methodol-
ogy and interpretation of these diagnostics. At this time the
gold standard based on sensitivity and specificity of correctly
identifying a bacterial or fungal infection is believed to be
culture of a biopsy sample obtained with a guarded technique
and histologic evaluation of the sample. This is not always
practical, so at a minimum a culture (double-guarded swab or
guarded small-volume lavage) and cytology (double-guarded
swab, swab cap, small-volume lavage, or guarded brush tech-
nique) should be performed.101-104 Table 19.6 summarizes
the sensitivity and specificity of each method for diagnosing
endometritis. Generally, it is believed that a negative aerobic
culture with no inflammation on cytology is reflective of no or
subclinical endometritis; a negative culture with inflammation
on cytology (>2 neutrophils per 400–1000× field) is a false-
negative and the offending agent has likely not been identified;
and a positive culture with inflammatory cytology is consid-
ered positive for endometritis.105,106 There is debate regarding
what constitutes inflammation as well as what is truly a uterine
pathogen, but the reader is referred to the section on endo-
metritis later in this chapter for a more in-depth discussion of
this topic.
Relative Specificities
(Number of Disease-Negative Animals That
Test Negative)
High
High
High
Not performed
High
Moderate
High
High
High
High
 1234 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
If endometritis persists despite appropriate treatment, cul-
tures are often obtained from multiple sites in the genital tract,
including endometrium, cervix, vagina, clitoral fossa, and
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clitoral sinuses. For the majority of mares a double-guarded
endometrial swab or fluid sample is often the only sample
submitted for aerobic culture, although anaerobic and fungal
cultures may be useful in some cases. There is an increasing
body of evidence to suggest the presence of commensal bac-
terial in the mare’s vaginal and caudal reproductive tract, as
well as possibly dormant bacteria in the endometrium, which
may confuse the results of culture.107-109 Endometrial culture
should be performed before any other invasive procedure in
a BSE to reduce the risk of inadvertent contamination of the
uterine lumen before culture samples are obtained.
A guarded culture rod or small-volume lavage set should
be used to minimize the risk of contamination with material
from sites other than the uterine lumen. There is a lack of con-
sensus on the optimal time of the cycle for obtaining endome-
trial culture and cytology samples. Some experts recommend
performing endometrial cultures on the first or second day of
estrus, when uterine secretions are increasing and the flush-
ing action of the uterus is just beginning.110-112 Mares with
endometritis have been reported to accumulate free luminal
fluid in late diestrus, and this represents an alternative time for
endometrial culture, although it can result in contamination.86
Often culture and cytology samples are obtained regardless of
where the mare is in her cycle, because there is a limited period
available for evaluation. If the mare’s endometrium is cultured,
biopsied, or the cervical barrier breached in diestrus, then it
is recommended to induce luteolysis (PGF2α administration)
after the evaluation to help the mare resolve any contamina-
tion or iatrogenic inflammation.
To perform a double-guarded swab culture of the endome-
trium, the practitioner should carry the guarded culture rod
into the vagina and through the cervix which can be accom-
plished through a speculum or manually. The capped rod is
then passed through the cervix and the culture tip pushed
through the guard and rolled against the endometrial surface
for 30 to 60 seconds. The culture tip is withdrawn into the rod,
and the outer sheath is rotated three times to collect endo-
metrial cells in the cap for cytologic analysis. The guard and
swab are removed gently, avoiding contamination of the cap
with vaginal or vestibular secretions. The rod is then extracted
without contacting the sheath and placed into a transport cul-
ture medium (Amies medium is an example). The cap’s con-
tents are tapped onto a glass slide for cytologic evaluation.106
The sample should ideally be transferred onto the final
growing medium (e.g., trypticase soy agar (TSA), 5% sheep
blood and eosin methylene blue (EMB), and a thioglycolate
broth) as quickly as possible after the sample is obtained to
allow quantification of colony numbers as an indication of
severity of infection. When possible, quantification of colony
growth should be performed, because heavy growth after 24 to
48 hours’ incubation is more meaningful than a few scattered
colonies. If immediate plating is not possible, then transfer
the culture tip in a sterile manner into appropriate transport
medium. Use of transport medium allows proliferation of
some species and possibly reduced growth of others, so colony
counts are not interpretable.
A wide range of organisms have been isolated from horses
with acute endometritis. A combination of positive culture
and evidence of inflammation on endometrial cytology is suf-
ficient to diagnose endometritis and identify major pathogens.
A positive bacterial culture in the absence of any cytologic
evidence of inflammation or clinical signs is considered likely
to be caused by contamination during the culture procedure
and does not indicate endometritis, although Escherichia coli
has been an agent associated with minimal inflammation and
should considered if heavy growth is identified.105,106
In the absence of cytologic evidence, it is particularly dif-
ficult to interpret culture results. Recovery of relatively pure
or heavy cultures of the following organisms may be consid-
ered indicative of endometritis: β-hemolytic streptococci, E.
coli, Pseudomonas spp., Klebsiella spp., and Candida spp.113-116
Recovery of other organisms without concurrent cytologic
information should be viewed with more suspicion.
Endometrial cytology is used by some practitioners as
a rapid screening test for detection of endometrial inflam-
mation in mares at the beginning of the breeding season or
before they are bred. When it was first described in the mare,
the detection of neutrophils was correlated with positive bac-
teriologic findings. When no or low numbers of neutrophils
were detected, bacteriologic findings were more often nega-
tive.117 Mares with cytologic evidence of inflammation had
lower 28-day pregnancy rates than mares with normal cyto-
logic results, irrespective of culture results. Day 28 pregnancy
rates were also lower in mares that had bacteria isolated from
their uterus, even if cytologic results were normal.118
Numerous techniques have been described for collecting
cytologic samples.117-119 The approach used by the author is
simple, rapid, and feasible in busy clinical practice. As pre­
viously described, a guarded culture rod (Kalayjian Industries
Inc., Long Beach, CA) can be used to obtain both endometrial
culture and cytology samples. The swab tip is withdrawn back
into the sheath and the rod rolled against the endometrium
to collect fluid and cells in the cap. After the rod is withdrawn
from the mare, the cap can be cut off and tapped against a slide
to make the smear from the small drop of fluid. The smear
is dried and stained using any commercial Romanowsky-type
staining kit (e.g., Diff-Quik; American Scientific Products,
McGaw Park, IL). If no endometrial cells are seen on an initial
inspection of the slide, then the sample may not have been col-
lected from the uterus, and another sample should be taken.
The presence of polymorphonucleocytes (PMNs) is gener-
ally believed to indicate infectious endometritis, but the most
appropriate methodology for quantifying PMNs remains sub-
ject to debate.120- 122 Suggestions for criteria to diagnose endo-
metrial inflammation include observation of more than two
PMNs in five high-power microscope fields (400×–1000×) or
more than one PMN per 10 endometrial cells in more than
one area of the slide.121,122 In most mares with clinical endome-
tritis, there are large numbers of PMNs evident on cytologic
evaluation, and occasionally intracellular phagocytized bacte-
ria may be seen.
Endometrial Biopsy
Preparation for endometrial biopsy is the same as for cul-
ture or cytology. There is debate as to the best time in the
cycle to obtain an endometrial biopsy. Diestral samples have
been recommended over estral samples because physiologic
changes in the endometrium during estrus make the slides
more difficult to interpret.119,122,123 However, samples may be
taken at any stage of the cycle as long as the information on
the stage of cycle is provided and the person reading the slide
has experience in evaluating equine endometrial biopsies. In
the absence of clinically detectable pathology involving the
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FIG. 19.17 Rigid endometrial biopsy rod with alligator forceps.
uterus, a single endometrial biopsy sample is representative of
the entire endometrium.124,125 However, another study found
that even in clinically normal mares endometrial biopsy scores
varied with the site selected; thus it may be prudent to collect
more than one sample.124,126-128
The sterile biopsy instrument is used to recover a sample
containing at least 2.5 cm of luminal epithelium. The most
commonly used instrument is a rigid alligator forceps (Fig.
19.17). The hand covers the basket as the instrument is guided
(with jaws closed) through the cervix and into the uter-
ine lumen. The tip of the biopsy forceps is guided manually
through the cervix. Once the instrument’s tip has been passed
into the uterine lumen, the guiding hand is withdrawn and
inserted into the rectum to guide the closed tip to the site
desired for sampling (most commonly the base of a uterine
horn). The instrument is then turned on its side and the jaws
gently opened. A portion of endometrium is pressed between
the jaws using the index finger within the rectum, and the
jaws are closed and the instrument retracted in a quick tug to
remove the tissue sample.
A simpler vaginal technique is useful for collecting biopsy
samples when there is no need to sample from a specific site.
The instrument is introduced into the uterine lumen, and the
hand is left in the vagina with the index finger in the cervi-
cal lumen. The tip of the instrument is advanced about 2 to 3
cm into the uterine lumen with the jaws closed. The jaws are
opened and the instrument advanced an additional 1 to 2 cm.
The instrument can then be deviated slightly to one side and
the jaws closed to collect a sample. The sample is taken from
the cranial uterine body close to the bifurcation. This approach
has the advantage of being quick and simple. It allows the
operator to return for a second sample immediately if the first
sample is too small, whereas the rectovaginal technique often
results in gross contamination of the instrument and vulva
during the procedure, making a second sample impossible
unless the mare is cleaned again and a second sterile instru-
ment is available.
The specimen is removed from the biopsy basket using a
small-gauge needle and transferred to fixative solution, prefer-
ably Bouin fixative or 10% buffered formalin. Samples placed
into Bouin fixative should be transferred to 10% formalin or
80% ethanol after 12 to 24 hours for optimal retention of cell
detail and tissue integrity.119,123
There is a strong case to be made for clinicians to read slides
from their own cases or to involve a reproductive specialist
familiar with biopsy interpretation. Although expert assess-
ment by a trained pathologist may better reflect histologic tis-
sue changes, it is vital to interpret histologic change in light
of clinical and historical information about the mare. Training
Disorders of the Reproductive Tract 12351235
and practice will allow the clinician to detect most of the com-
mon pathologic changes seen in biopsy samples. An endome-
trial biopsy report should include the histologic evaluation and
an epicrisis, which provides a biopsy grade (I, IIA, IIB, or III);
prognosis for carrying a foal to term and treatment/manage-
ment recommendations based on the histologic character of
the endometrium; and the results of reproductive examination,
endometrial culture and cytology results, and patient history.
The method of biopsy evaluation differs but should be a
repeatable sequence that allows one to determine the pathol-
ogy present in the endometrium. The clinician must first
ensure that cellular characteristics are consistent with the
stage of estrous cycle. Pathologic changes include inflam-
mation, fibrosis, cystic glandular distention, and lymphatic
stasis.10,119,122,123,127 Generally, inflammation is evaluated by
characterizing the cell type frequency, distribution, and
character. The uterine luminal contents, the epithelium, the
superficial endometrium (stratum compactum), and the
deeper endometrium (stratus spongiosum) are all described
based on the cellular infiltrate present (neutrophils, eosino-
phils, lymphocytes, plasma cells, and hemosiderophages), the
frequency (mild, moderate, or severe), and for the endome-
trium, the distribution (diffuse, multifocal, perivascular, or
periglandular). Acute inflammation is associated with PMNs
and an increased likelihood of positive endometrial culture.119
Increasing numbers of PMNs and their presence in deeper lay-
ers of the lamina propria indicate more severe inflammation.
Chronic inflammatory change includes lymphocytes, plasma
cells, eosinophils, and mast cells. Eosinophils have been asso-
ciated with urometra, pneumouterus or pneumovagina, and
yeast. Hemosiderophages are often associated with parturition
or abortion.119,122-126,128
Endometrial fibrosis is believed to be a permanent degen-
erative change seen as increased fibrocytes surrounding the
endometrial glands; when this is severe it causes the clustering
of glands (fibrotic nests) or gland branches. Fibrosis can also
be seen adjacent to the basement membrane of the luminal
epithelium. Fibrosis often forms in concentric layers around
gland branches or glands, and the number of layers of fibro-
sis is related to the severity of the degenerative change.127,128
Fibrosis may be localized or diffuse, and the more widespread
or severe the change, the more adverse the effect on gland
function and fertility. These degenerative changes appear to be
closely associated with age rather than parity.10,127,129-132 Severe
degenerative endometrial fibrosis can occur in the older
maiden mare that has not had the challenges of pregnancy and
exposure to semen.127,131,132
Cystic glandular distention may be seen in normal mares
during anestrus. When diagnosed in mares during the breed-
ing season, it is considered a pathologic change and is asso-
ciated with reduced fertility. Glandular fibrosis may also be
associated with cystic distention of the affected glands. Exten-
sive fibrosis interferes with uterine gland function and may
result in early embryonic death.10,128
Persistent endometrial atrophy is associated with an
extremely poor breeding prognosis.10,123,126,128 Large empty
spaces on the biopsy slide must be interpreted with caution,
because they may be artifacts associated with sample process-
ing. If the spaces appear to be lined with an endothelial cell
layer, then it indicates lymphatic stasis. Widespread lymphatic
stasis may be associated with reduced contractile capability
within the uterus, a doughy feel to the uterus on transrectal
palpation, and reduced fertility.119
 1236 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
Assessment of severity and distribution of pathologic
changes allows the sample to be classified into one of four
diagnostic and prognostic levels based on a modified version
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of the original three-level system proposed by Kenney.10,119,128
  
Category I: No significant changes in the endometrium and
no treatment required; predicted foaling rate following
conception is 80% to 90%.
Category IIA: Slight to moderate inflammatory change. Scat-
tered fibrotic change may consist of either fibrosis around
individual gland branches or fewer than two fibrotic nests
per high-power field. There is moderate cystic glandular
distention or extensive lymphatic stasis. If two or more
of these changes are present in the same sample, then the
sample is classified as IIB. Expected foaling rate following
conception ranges from 50% to 80%.
Category IIB: Inflammatory change is widespread and mod-
erately severe. There is widespread fibrotic change or up to
four fibrotic nests per high-power microscope field. Wide-
spread, severe cystic glandular distention or lymphatic sta-
sis is evident. If two or more of these changes are present,
then the sample is classified as III. Expected foaling rates
following conception are 10% to 50%.
Category III: The mare exhibits widespread severe changes
that may include fibrosis or severe inflammation or both.
The expected foaling rate following conception is less than
10%.
Use of paired biopsy samples taken at the initial diagnos-
tic workup and again 4 weeks after completion of treatment
appears to improve the usefulness of the biopsy as a prog-
nostic indicator of a mare’s fertility.129 Mares that were clas-
sified as grade III pretreatment and that improved to grade II
after treatment achieved a foaling rate of 40%, whereas mares
that were still grade III after treatment had a 0% foaling rate.
This is likely a result of improvement in reversible pathologic
changes.129,130,132 This approach allows effective use of the
grade III categorization on the follow-up biopsy to justify rec-
ommending that such mares be culled from the breeding pro-
gram or consider other alternatives (embryo transfer, oocyte
transfer, or intracytoplasmic sperm injection [ICSI]).
The epicrisis of the biopsy report summarizes the histologic
findings and interprets the significance of these changes in
light of culture and cytology results, reproductive examination
findings, and patient history. Ideally the epicrisis identifies
the significant pathology and severity and guides appropriate
treatment and future reproductive management.
Uterine Endoscopic Examination: Hysteroscopy
Hysteroscopy allows direct visual inspection of the uterine
lumen through a flexible fiberoptic endoscope. It is indicated
when other diagnostic procedures do not detect a cause for
subfertility, a mare has persistent endometritis despite appro-
priate treatment, or to further examine a mare with suspected
uterine pathology.4-6
Hysteroscopy is most commonly performed when the mare
is in diestrus, or the cervix can remain closed enough to allow
insufflations/dilation of the uterus for evaluation.133-135 Seda-
tion is usually required because the procedure is associated
with mild discomfort. The perineum is aseptically prepared
as for other vaginal or uterine procedures, and a sterilized
endoscope is inserted in the vagina and guided digitally
through the cervix and into the uterus. The cervical lumen is
then occluded, either by insertion of one or two fingers into
the cervix alongside the endoscope or by gently holding the
external os of the cervix around the endoscope. The uterine
lumen is distended with saline or water infused through a
flexible catheter held adjacent to the endoscope or with air
delivered through the endoscope. Endometrial folds should
be assessed while the uterus is being distended, because they
flatten out and become difficult to distinguish in the fully dis-
tended uterus. The endoscope is then manipulated through
the uterine lumen, allowing visualization of the entire endo-
metrial surface, including the tips of the uterine horns and the
two oviductal papillae. Hysteroscopy allows direct visualiza-
tion of a variety of abnormal changes, including inflamma-
tion, polyps or neoplasia, cysts, retained endometrial cups,
bacterial or fungal plaques, adhesions, and severe scarring or
fibrotic change. It can also aid in various procedures, including
guided retrieval of foreign bodies, laser surgical management
of conditions such as endometrial cysts or adhesions, biopsy of
pathologic sections of endometrium, or hysteroscopic hydro-
tubation of the oviducts.
Excessive distention (>100 mm Hg) of the uterus may
cause discomfort and an elevated heart rate and should be
avoided.133 Mares subjected to hysteroscopy appear to be at
risk of developing subsequent endometritis caused by the
inflammation associated with the procedure. It is often help-
ful to administer an antiinflammatory agent before the pro-
cedure (flunixin meglumine 1.1 mg/kg IV or dexamethasone
0.04 mg/kg IV) and perform a uterine lavage (1–5 L sterile
saline or LRS) with oxytocin (10–20 IU intramuscularly [IM])
following the procedure. If hysteroscopy was performed when
the mare was in diestrus, then administering a luteolytic agent
is recommended to return the mare to estrus and facilitate
recovery from the procedure. In addition, evaluating and cul-
turing the mare’s endometrium on the subsequent estrus is
recommended to address any residual inflammation or infec-
tion associated with the procedure.
Y HORMONAL ASSAYS
In the nonpregnant mare, serum or plasma samples may be
collected for measurement of a variety of reproductive hor-
mone concentrations, including progesterone, estrogens, tes-
tosterone, inhibin, AMH, and gonadotropins. Other systemic
conditions that may have effects on cyclicity and fertility
include equine metabolic syndrome, PPID, and general sys-
temic illness. The reader is referred to Chapter 16 for a discus-
sion on appropriate testing for endocrine disorders.
Progesterone is produced by ovarian luteal tissue. Serum
progesterone concentrations are low during estrus and begin
to rise 12 to 24 hours after ovulation, peaking between days
5 and 10 after ovulation.4,5,136,137 Progesterone assays in non-
pregnant mares can be used to assist in determining the stage
of the cycle and to confirm that ovulation has occurred. They
are also used as an indirect method of pregnancy diagnosis,
but false-positive results are common.1,6
Progesterone is necessary for early pregnancy maintenance,
and primary luteal insufficiency has been linked to pregnancy
loss.138,139 Low levels of progesterone are associated with
increased early pregnancy loss, and higher levels of progester-
one are associated with double ovulations.140-142 Older mares
appear to require a higher level of progesterone to maintain
pregnancy.138,139 Progesterone levels on day 7 were signifi-
cantly lower in mares with periovulatory intrauterine fluid
 CHAPTER 19
accumulation and significantly lower in mares that underwent
embryonic loss.88,139 The presence of luminal fluid in diestrus
was associated with a lower progesterone level and increased
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embryonic loss, indicating endometritis as a cause for lower
progesterone levels.31,86,138,139
Some researchers recommend that progesterone concen-
tration in the peripheral blood of pregnant mares should be
above 2.5 to 4 ng/mL for normal pregnancy maintenance;
this will be discussed in more detail later.142 Single samples
of peripheral blood concentrations are difficult to interpret
because repeated sampling of normal pregnant mares has
shown that blood levels vary widely over short periods.137,138
It is clear that in the mare the serum progesterone taken at
a single time point must be critically compared with normal
values for stage of cycle and pregnancy, because these change
significantly as a part of normal physiology.
Thyroid gland dysfunction has been discussed as a cause
of subfertility in mares with recommendations to measure
total serum thyroxine (T4) or thyroxine response to admin-
istration of thyroid-stimulating hormone (TSH). Endogenous
thyroxine is significantly affected by season and reproductive
status.16,143 Thyroxine is seasonally regulated when mares are
kept on a constant energy balance out of the breeding sea-
son.143,144 Although thyroidectomy of pony mares did not have
any adverse effect on reproductive performance,144 mares that
continued to cycle out of season had higher levels of thyrox-
ine than anestrous mares, which has led some clinicians to
supplement subfertile mares with thyroxine.16,143,145,146 Mares
with low thyroxine levels were more likely to enter anestrus
after parturition.16 Research has demonstrated that the horse is
rarely truly hypothyroid as is seen with other domestic species,
and a study evaluating the effect of thyroxine supplementation
of mares with low T4 (<16 μg/dL) found no benefit of supple-
mentation on early pregnancy rates.146 Several other studies
have shown there was no association between thyroxine level
and pregnancy rate 15 to 16 days after ovulation.144,146
Ovarian neoplasia, particularly GCTs, may be associated
with increased production of testosterone, inhibin, and AMH
by the affected ovary. Serum inhibin concentration is elevated
in approximately 80% of mares with a GCT, and testosterone is
elevated in about 50% to 60% of cases.147-149 Recent work sug-
gests that an increase in AMH, a hormone expressed in granu-
losa cells of preantral and small antral follicles, is elevated in
mares with GCT tumors. It is believed that an elevated con-
centration of serum AMH is the most sensitive test for GCT at
this time, with a sensitivity of 98%.148-150 A study in 2013 dem-
onstrated that the sensitivity of elevated blood AMH (95%)
for the detection of histologically confirmed GCTs was signifi-
cantly greater than that of either an elevation in inhibin (85%)
or testosterone (55%) alone or the combination of inhibin and
testosterone (89%).149,150 Generally normal concentrations in
nonpregnant mares for inhibin, testosterone, and AMH are
less than 0.7 ng/mL, less than 45 pg/mL, and less than 4 ng/
mL, respectively, but these values should be compared with the
laboratory normal in which samples are being processed.149,150
Horses with PPID often exhibit variable degrees of hirsut-
ism with a range of other systemic signs. The direct effect on
the reproductive tract and fertility is currently a subject of
much debate. Anecdotally, mares with PPID can have repro-
ductive changes such as increased incidence of anovulatory
follicles, loss of uterine tone, increased fluid accumulation,
decreased cervical relaxation, and decreased resistance to bac-
terial or fungal endometritis. Diagnosis and treatment of this
Disorders of the Reproductive Tract 12371237
disorder are discussed in the later section Endometritis and
Uterine Therapy.
The measurement of estrogen concentration in blood,
urine, feces, milk, and saliva has been used for monitoring the
estrous cycle, determining pregnancy status,92-94 and monitor-
ing fetal-placental viability. Peripheral blood estrogens may be
either unconjugated or conjugated (bound to sulfates), and
different forms of estrogens are found in the mare, particularly
during pregnancy. Estrogen production in the pregnant mare
will be reviewed more thoroughly later, but generally conju-
gated estrogens exist in the circulation at much higher concen-
trations than the unconjugated forms, and measuring either
estrone sulfate or total conjugated estrogens has historically
been used to assess pregnancy status and viability. Often a
dramatic increase in peripheral blood estrone sulfate concen-
trations occurs in pregnant mares after day 60 of pregnancy,
whereas in fecal assays this increase may take up to 150 days
to occur.153,156,157 A rapid decline of estrone sulfate concentra-
tion in a pregnant mare may indicate loss of fetal viability.155-158
One of the difficulties of measuring specific estrogens is the
cross-reactivity on most commercially available immunoas-
says and interpreting findings relative to normal changes in
concentration.
Equine chorionic gonadotropin (eCG, formerly known as
pregnant mare serum gonadotropin [PMSG]) is a hormone
produced from the trophoblast cells derived from the chorionic
girdle that invade the endometrium, forming “endometrial
cups” at around day 35 of gestation.1,4,6,158,159 This hormone has
both FSH and LH effects on the ovary, inducing the formation
of accessory CLs to help maintain pregnancy until the placenta
develops and produces hormones that support the pregnancy
in later gestation. The accessory or secondary CLs form from
follicles that often luteinize without ovulating.159 Pregnancy
loss after day 35 can sometimes be associated with undetect-
able eCG concentrations in blood and the failure of endome-
trial cup formation, which is presumed to play an essential role
in pregnancy maintenance. Pregnancy loss after day 35 may be
associated with a positive or elevated eCG blood concentra-
tion following pregnancy loss, and affected mares often do not
cycle properly because follicles fail to ovulate normally and
luteinize. When ovulation does occur, the pregnancy rate is
low, presumably because of a low-grade endometritis resulting
from the presence of endometrial cups,160-162 which have a life
span of about 100 days and are therefore nonfunctional after
about 150 days’ gestation.160 However, there have been reports
of the prolonged survival of endometrial cups after abortion
and even normal foaling.161,162 The abnormal persistence of
endometrial cups lasts an average of 18 months but could last
up to 30 months. This has implications into the next breeding
season, and mares showing aberrant ovarian activity should be
investigated for the possibility of persistent endometrial cups
(Fig. 19.18). Peak elevation of eCG occurs naturally between
days 50 and 85 of gestation (15–125 IU/mL) and should be
gone from the serum after 150 days’ gestation.162 Mares have
been observed clinically to have abnormal, accessory CLs,
retained endometrial cup tissue, and erratic cycles with eCG
levels of 2 IU/mL, highlighting the importance of testing eCG
in appropriate cases.
The measurement of serum or plasma concentrations of
GnRH, gonadotropins (FSH and LH), and steroids appears
to offer promise in the diagnostic assessment of the hypo-
thalamic-pituitary-ovarian axis. The anterior pituitary gland
produces FSH in response to GnRH release.1,4,163,164 FSH is
 1238 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
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FIG. 19.18 Hysteroscopic image of retained endometrial cups present
in the base of what was the pregnant horn.
released in a bimodal pattern with peaks (35 ng/mL) in early
and late diestrus. There are two major waves of follicular
growth coincident with the two surges of FSH.4,164-166 FSH
starts to rise 4 to 5 days before an ovarian follicular wave. The
peak of FSH is 3 days before the emergence of the wave, which
then plateaus for 5 days. Sampling of circulating blood FSH
would be performed in mares with inactive ovaries or erratic
follicular waves to determine the cause.
GnRH release from the hypothalamus stimulates LH release
from the anterior pituitary gland,4,166 although there is an asso-
ciation between releases of oxytocin in estrous mares and LH
release, which suggests that repeated sexual stimulation might
also increase LH and advance ovulation.167 LH concentrations
are low during the midluteal phase (5 ng/mL) but rise a few
days before estrus after progesterone decreases (<1 ng/mL)
because of luteolysis. LH peaks (45 ng/mL) during estrus after
ovulation and returns to midluteal levels over a few days.166
Little information is available regarding the existence of
abnormalities in the hypothalamic-pituitary-ovarian axis and
either their relationship with subfertility or their detection
by measurement of hormone concentrations. Assessment of
the production and release of either GnRH or FSH and LH
presents practical difficulties, because this may require can-
nulation of the pituitary venous sinuses.168 In addition, these
hormones are released in a pulsatile manner, with pulse fre-
quency and amplitude influencing function.4,169 Finally, there
are varying isoforms with differing bioactivity that may be dif-
ficult to distinguish on enzyme-linked immunosorbent assay
(ELISA) or radioimmunoassay (RIA).169,170
Leptin is a protein synthesized by adipose (fat) tissue.171,172
It acts as negative feedback to brain centers to control obe-
sity (satiety centers) in times of nutritional abundance.171-176
During starvation, reduced leptin levels cause changes in
reproductive endocrinology that limit reproductive activ-
ity.173 Short-term feed restriction (for 24 hours) significantly
decreases leptin levels in mares but does not affect reproduc-
tive hormones.176 There might be a seasonal influence on
leptin levels because mares in good body condition experience
a general decline in leptin concentrations during winter. The
decline is not as great as that observed in mares in poor body
condition, and the mares in good body condition continue to
have estrous cycles through winter.177
Currently, the measurement of these and other hormones of
the central nervous system appears to be restricted to research
applications. Measuring these products may offer considerable
benefits in the future, but additional research and develop-
ment are required before it can be of use to field practitioners.
Y CONCLUSION
Following evaluation, interpretation of test results, and a review
of the mare’s history, a summary of the BSE findings should be
made with the goal of identifying any abnormalities, provid-
ing a possible treatment plan, and discussing with the owner/
client the prognosis for future reproductive health. There are
conditions that may not have a treatment option (karyotype
abnormalities, severe adhesions, and chronic incurable endo-
metritis), but for all mares, regardless of the pathology, several
options such as specific treatment plans, surgical correction
(cervix, urethra, perineal body, and vulva), and advanced
reproductive options (embryo transfer and ICSI) should be
discussed. For some clients the BSE serves to ensure that an
investment in the mare’s prospective breeding career is not
in vain, and a BSE with no abnormalities can provide useful
information. It should be emphasized, based on the findings
from that one examination, that a mare’s prospective breeding
status cannot definitively be labeled as fertile or infertile but
that the mare meets or does not meet the normal parameters
that one would expect for a satisfactory potential breeding ani-
mal. It is also important to recognize the legal implications of
a BSE, and if the examiner is not comfortable or experienced
enough to make a conclusion, then it is best to consult with
an experienced practitioner or trained reproductive specialist.
Mare Reproductive Pathology
Maria R. Schnobrich
This section is a review of specific reproductive pathology in
the nonpregnant mare. Some of this has been discussed as part
of the findings of a BSE in the previous section, but this section
will provide more details regarding pathogenesis, diagnosis,
and treatment options.
Y VULVAR PATHOLOGY
The integrity of the vulvar lips and their anatomic relation-
ship to the perineal area and anus are essential components
of a mare’s reproductive health, because they are the first bar-
rier against uterine contamination from the external environ-
ment. The endocrine patterns associated with each stage of the
estrous cycle and pregnancy can influence the disposition of
the vulva, with increased estrogen relaxing vulvar tone and
increasing vulvar length. Generally the vulva should have at
least two thirds of its length below the pelvic brim, the slope of
the vulva in relation to the vertical axis should not be greater
than 10 degrees, and the vulvar lips should have an even and
firm apposition. Absence (natural or acquired) of a normal
perineal conformation can facilitate the entry of air (pneumo-
vagina), feces, and potential pathogens into the reproductive
tract, which jeopardizes the fertility of the mare as mentioned
previously.4,6,13
Body Weight
Severe loss of body condition, as experienced by some preg-
nant mares not adequately supplemented during the winter or
 CHAPTER 19
during lactation, results in a sunken anus, an increased slope
of the vulva, and loss of fat that maintains adequate conforma-
tion. An apparently normal perineal conformation noted in
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mares in good body condition may become less than adequate
if loss of body weight is extreme. With weight loss the cau-
dal barriers to the reproductive tract become less efficient and
pneumovagina and contamination of the reproductive tract
can occur. Contamination of the vagina with feces during mid
to late gestation may lead to ascending bacterial placentitis,
which is one of the leading causes of abortion and neonatal
septicemia in the United States.178
Parity and Age
Aging of the mare associated with repeated foaling can cause
stretching and loss of tone of the perineal muscles that allow
the vulva to form an effective barrier. Injury to the mare during
foaling aggravates this condition, resulting in loss of vulvar tone
and apposition of the labia. Mares undergoing repeated episi-
otomies also may have permanent damage to vulvar structures.
Caslick Vulvoplasty
Surgical closure of the dorsal part of the vulvar labia is
intended to correct poor perineal conformation. The Caslick
procedure removes the vulvar mucosal surface at the muco-
cutaneous junction of the labia from the dorsal commissure
to a level approximately level or below the brim of the pelvis.
The vulvar opening is reduced significantly, and the opposing
debrided labia are sutured together. Decreasing the length of
the vulvar cleft, one decreases entry of air and potential patho-
gens into the vestibule and vagina in a mare otherwise suscep-
tible to pneumovagina, fecal contamination, and associated
complications. It has been reported that Caslick-operated
mares with poor perineal conformation that successfully foal
should be resutured immediately after parturition to minimize
the chances of uterine contamination and consequent endo-
metritis. This preventive measure is believed to contribute to
adequate pregnancy rates and maintenance of pregnancy until
term.4,49,178-181
This procedure, however, is overused in mares in which such
intervention is not warranted. Paradoxically, a mare with suc-
cessive Caslick surgeries may experience considerable loss of
vulvar tissue, generating an abnormal perineal conformation.
Another indirect complication associated with the Caslick vul-
voplasty is the increased incidence of vulvar lacerations and
dystocias in mares in which the vulva was not opened before
foaling. Regardless of the originating cause, the Caslick opera-
tion is used to correct first-degree perineal laceration affect-
ing only the perineal skin and vulvar mucosa. Second-degree
(laceration of deeper tissues of the perineal body) and third-
degree (a defect resulting in communication of the ventral rec-
tum with the dorsal vagina) lacerations require more elaborate
reconstructive surgery to correct.180 As a rule, any corrective
surgery of the perineal body and vulva should be delayed until
inflammation and edema of the involved tissues have resolved.
Mares with third-degree rectovestibular laceration invari-
ably develop endometritis, but endometrial biopsy of mares
affected with third-degree laceration have shown a rapid endo-
metrial response to surgical repair of the laceration. Mares can
be artificially inseminated by 2 weeks after surgery.181
Equine Coital Exanthema
Equine coital exanthema is a venereal disease caused by
equine herpesvirus type 3 (EHV-3). Mares infected with
Disorders of the Reproductive Tract 12391239
equine coital exanthema develop pustules and ulcers in the
vulvar mucosa and perineal area. Once the lesions start to heal
(usually by 14 days after the onset of clinical signs), character-
istic depigmented small circular areas (usually <1 cm) in the
vulvar labia and perineal skin are visible.182 Similarly to other
herpesvirus-induced diseases, lifelong infection is the rule.
Recrudescence may occur after stimuli such as stress, systemic
disease, or trauma to the genital area. No specific treatment is
recommended other than disinfection of pustules and ulcers
to prevent secondary bacterial infections during the acute
phase. Natural service should be avoided while active lesions
are present to prevent transmission of the disease. One can
artificially inseminate affected mares during the symptomatic
stage of the disease or wait until 6 weeks after complete healing
of equine coital exanthema–associated lesions before natural
service.
Neoplasia
Melanoma is the most common disease of the vulva and
perineum, affecting 80% to 100% of adult gray horses and,
less frequently, aging horses of other colors. Common sites for
melanoma include the anus, perineum, and vulva. No effective
treatment is available for melanomas, but oral treatment with
cimetidine (a histamine H2 antagonist) has been reported with
variable success, resulting in partial or complete regression of
melanocytic nodules.183 In addition, recent research has sug-
gested autologous vaccination or other types of vaccines for
melanomas may be effective.184 Squamous cell carcinomas are
less common than melanomas, and hemangiosarcomas have
been reported.185
Y CLITORIS
The clitoris in the mare is an important reservoir for the bac-
terium Taylorella equigenitalis, which is the causative agent in
mares affected with contagious equine metritis (CEM). The
disease is highly contagious, and the organism can be har-
bored in the clitoral fossa and sinuses (especially the median
sinuses) for prolonged periods. To test a mare for CEM, the
practitioner should swab the median clitoral sinuses and then
seed an Amies charcoal medium to be transported (preferably
kept at 4°C) to a diagnostic laboratory.
Even in CEM-free areas, it is important to remember that
the clitoral sinuses may function as nidi for uterine infection,
especially infection that was iatrogenically induced during
diagnostic procedures of the reproductive tract or AI. Careful
asepsis of the perineal and vulvar area (including the clitoral
fossa) with a mild disinfectant before any invasive procedures
are performed minimizes the risk of introducing potential
pathogens into the uterus. In rare cases, clitorectomy may be
performed to eliminate this nidus of infection.
Congenital anomalies of the external genitalia occur in
intersex animals that may have underdeveloped vulvar labia
associated with an abnormally enlarged clitoris. Treating pre-
pubertal mares or pregnant mares with anabolic steroids may
lead to enlargement of the clitoris in the mare or foal exposed
to androgens in utero, resulting in a partially and permanently
exteriorized clitoris.
Y VAGINA
The vestibule is the area that separates the vulva and clitoris
from the vagina proper. At the cranial border of the vestibule,
 1240 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
where it meets the vagina, lies the vaginovestibular fold. This
folded mucous membrane acts as the second physical barrier
between the uterus and the external environment. In young
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horses the hymen is usually a weak membranous extension
of the vaginovestibular fold. Occasionally, a persistent hymen
may be present in a maiden mare. A manual examination of
the vagina is usually sufficient to rupture the persistent hymen.
Some mares with a persistent hymen may accumulate fluid in
the vagina proper and uterus (mucometra). Once the persis-
tent hymen is disrupted, evacuation of the fluid is uneventful.
Pneumovagina
Listening for an inrush of air into the vagina when one gen-
tly parts the vulvar labia, or evidence of air in the vagina on
transrectal ultrasound, can test the adequacy of the vaginoves-
tibular fold as a physical barrier to external contaminants. A
positive test (noticeable sound of air rushing in to the vagina,
or air visualized in the vagina on transrectal ultrasound) indi-
cates that the vestibular fold is not properly restricting the
vagina proper from the outside environment.
Improper functioning of the first barrier (vulva) and sec-
ond barrier (vaginovestibular fold) may lead to the constant
or frequent entry of air into the vagina. The condition may
be exacerbated during estrus, when the perineal body is more
relaxed than in other stages of the estrous cycle. Accumula-
tion of small amounts of a frothy fluid in the cranial vagina
may indicate pneumovagina. Fecal staining and debris may
also suggest this condition as well as the presence of air in the
vagina and occasionally the uterus (pneumouterus), which
is visible as hyperechoic particles seen in these areas during
transrectal ultrasonographic examination.
In mares with severe alteration of the perineal conforma-
tion, vulvar closure using Caslick vulvoplasty may not correct
the problem, and surgical reconstruction of the perineal body
(perineoplasty) is recommended. In addition, in mares with
poor body condition, weight gain may also be beneficial.
Urovagina
Urovagina, also known as vesicovaginal reflux or urine pool-
ing, refers to the presence of urine in the cranial vagina and
possibly in the uterus. As with pneumovagina, mares with
marginal perineal conformation may be predisposed to accu-
mulate urine in the vagina during estrus, when reproductive
organs and the perineal body are relaxed. In older mares with
splanchnoptosis, the reflux of urine into the genital tract may
be permanent. Urovagina can cause vaginitis, cervicitis, endo-
metritis, and placentitis, which ultimately result in infertility.
Perineoplasty and urethral extension are common surgical
procedures to correct this condition. In some cases fluid may
only be appreciated in the uterus, and the fluid can be sam-
pled and a creatinine concentration evaluated to determine
whether urine is present. Generally values >2 mg/dL are con-
sidered consistent with urine contamination.
Varicose Veins
During estrus and especially during pregnancy, varicose veins
may develop in older mares. Varicose veins can be present in
any part of the vagina; however, they often are found in the
vaginovestibular area. Bleeding may occur after natural service
or spontaneously during mid to late gestation. Occasionally,
persistent hemorrhage results in considerable blood loss, but
the condition usually subsides with the end of pregnancy. Cau-
tery or ligation of varicose veins is warranted if hemorrhage is
persistent or frequent. There is anecdotal evidence of success
with topical application of commercially available hemorrhoid
creams containing phenylephrine HCl 0.25% for less severe
cases.
Neoplasia
Vaginal neoplasms are not common in mares, but leiomyo-
mas, squamous cell carcinoma, and melanomas have been
reported.
Vaginitis
Minor tears, lacerations, and hematomas are common findings
in the vaginas of mares after foaling. Medical treatment gener-
ally is not needed, and most mares do not show complications
in the postpartum period. If more serious trauma occurs, then
the mare may develop vaginitis. Mares with extensive vagini-
tis or a large hematoma may show signs of pain and refuse to
stand quietly to nurse the foal. Vaginal abscesses can develop
when a vaginal laceration becomes infected with local flora or
fecal contamination.108 Clinical signs caused by swelling from
a hematoma or abscess include vulvar discharge, stranguria,
and straining to defecate. Treatment with antibiotics and
antiinflammatory drugs is warranted when extensive vaginitis
or abscesses are found in the vagina. An abscess impinging on
the urethra or interfering with defecation may require drain-
age. Occasionally, vaginal trauma may result in adhesions that
can interfere with uterine drainage.
Rectovaginal Fistulas
During parturition the foot of the foal may be directed toward
the dorsal vagina or ventral rectum and if unattended may
cause a third-degree perineal laceration. However, if the dys-
tocia is corrected in time, then the damage may be limited to
a first- or second-degree rectovaginal tear or rectovaginal fis-
tula. Surgical correction of the anatomic defect is necessary
to restore fertility if the defect allows vaginal contamination
to occur. Generally in the case of the complete loss of barrier
between the rectum and vagina, the mare is evaluated 3 to 4
weeks after injury to allow the tissue to heal before surgical
repair to prevent failure of corrective surgery.
Breeding Trauma
Vaginal lacerations may occur during natural service when
the stallion’s penis is disproportionately large compared with
the mare’s reproductive tract, or restraint of the mare prohibits
appropriate coupling during mating. Depending on the loca-
tion of the tear in relationship to the peritoneal reflection, a
vaginal tear may communicate with the peritoneal cavity,
likely resulting in peritonitis, or may be retroperitoneal. Treat-
ment includes broad-spectrum antibiotics, antiinflammatory
drugs, and tetanus prophylaxis. Peritoneal lavage may be ben-
eficial if the tear communicates with the peritoneal cavity. A
breeding roll positioned under the tail of the mare and dorsal
to the penis of the stallion prevents the stallion from insert-
ing the full length of its penis into the vagina and may help
prevent mating-induced trauma. Some tears are large enough
to require surgical correction, and any mare with excessive
bleeding or discomfort after live cover should be evaluated.
Y CERVIX
The cervix is the last of the three physical barriers protecting
the uterus from the external environment. Cyclic hormonal
 CHAPTER 19
changes dictate the tone of the cervix. During estrus the cer-
vix is relaxed and open. High concentrations of progesterone
during diestrus or pregnancy cause the cervix to be elongated,
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tubular, firm, and tightly closed. These changes are readily
appreciated with transrectal palpation. Moreover, a vaginal
examination during estrus reveals the cervix positioned low
in the cranial vagina and relaxed, well lubricated, and easily
dilated, allowing access to the uterus. During diestrus or preg-
nancy, a vaginal examination reveals a tightly closed cervical
os that is pale and positioned high off the floor of the vagina.
Cervicitis
Inflammation of the cervix often accompanies vaginitis or
endometritis. Cervicitis usually occurs in the postpartum
period, especially after a dystocia. Severe cervicitis associated
with metritis also may occur in mares infected with organ-
isms, such as T. equigenitalis, that cause copious purulent dis-
charge.186 Infusion of certain chemicals (e.g., chlorhexidine,
strong iodine solutions) into the uterus to treat endometritis
may irritate not only the endometrium but also the cervix and
vaginal mucosa. If the practitioner intends to use such solu-
tions, care must be taken so that adhesions and fibrosis do not
result as a sequela.
Trauma
Although cervical lacerations can occur during natural ser-
vice, these lesions are usually small and resolve without major
consequences. Occasionally, maiden mares are found in estrus
with a tightly closed cervix that might suffer laceration during
natural service, especially if the stallion is much larger than
the mare. However, these tears are usually small and heal with-
out further treatment. Most serious lacerations occur during
parturition. They may result from normal parturition, or they
may be iatrogenic, occurring during intervention to correct a
dystocia by mutation or fetotomy.
Although one should examine the cervix digitally after a
difficult foaling or dystocia (especially if a fetotomy is per-
formed), the extent and severity of a cervical laceration are
best evaluated once the cervical lesion has healed. The com-
petency of the cervix should be evaluated during diestrus or
when the mare is under the influence of exogenous proges-
togens so that the competency of the cervical canal can be
accurately assessed. Diagnosis of cervical transluminal adhe-
sions and anatomic defects is best performed by digital exami-
nation of the cervix rather than by vaginoscopy. Transrectal
ultrasound and hysteroscopy can also be useful in detecting
cervical defects. Because surgical correction is difficult and
not always rewarding, the practitioner should take a biopsy
sample of the uterus to assess the mare’s ability to maintain a
pregnancy before attempting surgical correction of a cervical
laceration.
Generally any cervical defect that impairs cervical function
should be addressed. In a retrospective study evaluating mares
that had surgical repair of a cervical defect within 24 months,
the postoperative pregnancy rate (67.24%) was greater than
mares that did not undergo repair or waited longer than 24
months for repair (41.78%).187
Polyps or Cysts
Occasionally, pedunculated cystic structures are apparent on
transrectal ultrasound, vaginoscopic, or digital examination
of the cervix. These structures are often attached to the cervi-
cal os or emanate from the cervical lumen and protrude into
Disorders of the Reproductive Tract 12411241
the vagina or uterine body. Although their cause is unknown,
they do appear to be associated with infertility, and removal by
laser or ligation is recommended.
Y UTERUS
Ventral Sacculations
Aside from changes associated with pregnancy, other patho-
logic conditions cause focal enlargements in the ventral por-
tion of the uterus. These uterine changes usually are associated
with increased age and parity and invariably are found at the
base of one or both of the uterine horns. Inexperienced vet-
erinarians may mistake these enlargements for a pregnancy,
especially if they do not use ultrasonography to confirm their
palpation findings. Mechanisms contributing to formation of
ventral uterine enlargements have been identified, including
but not limited to endometrial atrophy, focal myometrial ato-
nia, and lymphatic lacunae.92 Furthermore, in older and mul-
tiparous mares the uterus may tilt ventrally in relation to the
pelvic brim (uterine splanchnoptosis). Mares with ventral sac-
culations and uterine splanchnoptosis have a higher incidence
of delayed uterine clearance than normal mares.99
Endometriosis
Endometriosis was once known as chronic infiltrative endo-
metritis and currently refers to the presence of fibrosis in
the stromal and periglandular compartments. The degree of
endometriosis is associated closely with the ability of a mare to
establish and maintain a healthy pregnancy until term. Parity
and age contribute to degenerative changes occurring in the
endometria of mares.10,130
Fibrotic changes may occur around the endometrial glands
and in association with the basement membrane in the stra-
tum compactum. The amount and pattern of distribution of
the fibrotic tissue has been classified descriptively as slight (one
to three layers of periglandular fibrosis), moderate (4 to 10 lay-
ers), and severe (more than 10 layers).10 Cystic glandular dila-
tion is another manifestation of endometriosis. Periglandular
fibrosis, glandular epithelial hypertrophy, or inadequate lym-
phatic drainage may lead to dilation of the endometrial glands.
Other degenerative alterations in the endometrium that
lead to endometriosis include lymphatic lacunae and angio-
sis.130,188 Lymphatic lacunae are histopathologic indications of
lymphangiectasia. Angiosis (a vascular pathologic condition)
is associated with aging and parity, especially in uteri with
ventral sacculations and associated venous congestion, which
are pathogenic factors for angiosis.188 No treatments exist
for these anatomic and vascular degenerative changes in the
uterus. Mares with lymphatic lacunae and disseminated uter-
ine angiosis are at risk for infertility caused by delayed uterine
clearance and persistent mating-induced endometritis.130,188
Pregnancy loss attributed to endometrial fibrosis more
commonly manifests during the embryonic period. The secre-
tion of histotroph by the endometrium is critical for proper
embryonic development. The area of the endometrium in
immediate contact with the conceptus has been shown to
undergo specific changes in glandular density on days 16
through 30 of gestation; this is a period during which embry-
onic loss is commonly diagnosed in mares with endometro-
sis.189 If pregnancy continues to progress beyond the initial 30
days of gestation, then abortion during the early fetal period
may still occur if uterine fibrosis interferes with implantation of
 1242 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
the placenta. Microcotyledonary attachments begin to develop
by 80 to 120 days’ gestation.190 Ultrastructural evaluation of
the placenta in mares with chronic degenerative endometritis
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(CDE; endometriosis) has shown a delay in microcotyledon
development and a reduction in the number of microcotyle-
dons and villi per surface area. Endometrial atrophy may not
result in abortion but can influence fetal growth. Fetal weights
in mares with degenerative endometritis were lower than in
normal mares.191 Endometrial atrophy may be evident on
inspection of the placenta after delivery.192
Endometritis
Whereas endometriosis reflects chronic structural changes
associated with age and parity, endometritis encompasses
endometrial changes associated with acute or chronic inflam-
mation. The changes associated with endometritis are modu-
lated by the action of a local immune system and influenced
by the hormonal milieu. A transient endometritis nor-
mally occurs in all mares that were mated naturally or arti-
ficially inseminated. Mares mount an inflammatory reaction
in response to the presence of semen in the uterus, but this
apparently normal inflammatory response subsides (histologi-
cally) within 2 to 3 days.193,194 Detection of intrauterine fluid
by ultrasonography per rectum 24 hours after mating suggests
delayed clearance. Persistent mating-induced endometritis is
a clinical entity that has been recognized as a major cause of
infertility in mares. A more detailed discussion on endometri-
tis is found in later sections of this chapter.
Endometrial Biopsy
An endometrial biopsy, as covered in the section on BSE, is
often considered a routine part of a complete BSE. Because an
endometrial biopsy can aid in predicting the chances of a mare
carrying a foal to term, one should consider the information
provided by a biopsy before purchasing the horse or under-
taking reproductive surgery such as repair of a cervical tear.
Biopsies sometimes provide information that is useful in the
diagnosis of infertility and may provide a basis for treatment.
One must realize, however, that an endometrial biopsy alone
is often not the most significant part of a BSE but must be con-
sidered in light of other information obtained from the history
and reproductive examination.
Generally a biopsy specimen is taken from a site at the base
of one of the uterine horns. When procuring a biopsy, the
practitioner should take care not to obtain tissue from a site
near the internal cervical os. Glands are less dense near the
cervix, making a biopsy obtained from that area less represen-
tative of the uterus and more difficult to interpret. Moreover,
accidentally taking a biopsy sample from the cervix can result
in adhesions.
A single biopsy has been considered to be representative of
the entire uterus, but studies have shown that variation by as
much as an entire category may exist among sites.125 Therefore
one first should perform a thorough examination by palpation
and ultrasonography to determine whether any areas of the
uterus appear to be abnormal and also to rule out pregnancy
before taking a biopsy. If one detects an abnormal area, then
biopsy samples should be obtained from the abnormal and the
normal areas. Repeated or multiple biopsies do not signifi-
cantly affect fertility. A mare may become pregnant when bred
just a few days after a biopsy specimen is taken.195
One must relay all pertinent history, including the estrous
stage during which the biopsy sample was obtained, to the
pathologist reading the sample. Periglandular fibrosis may
appear worse in biopsy samples taken during anestrus because
of the sparseness of glands. In addition, biopsy samples taken
during anestrus or transition may have evidence of increased
inflammation because the cervix has been in a relaxed state for
a prolonged period as a result of the absence of progesterone.
Endometrial biopsies are classified into four categories as
previously described (I, IIA, IIB, and III). A mare with a cat-
egory I biopsy has an essentially normal endometrium. The
likelihood of the mare becoming pregnant and carrying a foal
to term, estimated at 80% to 90%, depends more on broodmare
management than on the inherent fertility of the mare. Mares
with a category III biopsy have severe pathologic changes in
the endometrium and an estimated 10% chance of carrying
a foal to term, even with good breeding management. Most
mares are classified as a category IIA or IIB with an estimated
50% to 80% and 10% to 50% chance, respectively, of carrying
a foal to term, reflecting a combination of management prac-
tices and the inherent fertility of the mare.
The clinician’s primary concerns are the severity and dis-
tribution of inflammation and the presence of degenerative
changes such as periglandular fibrosis, angiosis, and lymphatic
lacunae (enlarged and dilated lymphatics). Degenerative
changes carry a worse prognosis than inflammatory changes
because they are considered permanent and progressive. No
effective treatment for these conditions has been identified. The
origin of such degenerative conditions is not known but widely
presumed to be caused by repeated insults to the uterus. These
conditions are more common in older mares.130 Dilated lym-
phatics often indicate a uterine clearance problem. However,
the practitioner can diagnose delayed clearance more reliably
by ultrasonographic examination in the post-breeding period.
Although biopsy can reveal the presence of an inflamma-
tory condition, other methods (e.g., examination of perineal
conformation) are necessary to reveal the reason that the con-
dition is present, and an endometrial culture is needed to iden-
tify the particular pathogen. A repeat biopsy after appropriate
therapy may provide insight regarding the extent to which
treatment was successful and aid in determining a prognosis
for future fertility.129
Endometrial Cysts
Endometrial cysts often are cited as a cause of infertility, but
a clear cause-and-effect relationship has not been established.
The proportion of mares with endometrial cysts increases
with age. Mares older than 11 years of age are more than four
times as likely to have endometrial cysts compared to younger
mares, and most mares older than 17 years of age have endo-
metrial cysts. Reports that associate endometrial cysts with a
lower pregnancy rate or increased embryonic loss often fail
to account for the effect of advancing age. When one controls
for confounding effects, such as parity and age, the assump-
tion that cysts are causing infertility is not supportable. When
confounding factors were accounted for in the analysis of
nearly 300 mares, endometrial cysts did not have a statisti-
cally significant effect on establishing or maintaining preg-
nancy, although the time of initial pregnancy diagnosis was
not controlled strictly.94 Another report by a different group of
researchers who did control the time of pregnancy diagnosis
similarly found no difference in pregnancy loss between mares
with cysts and those without, although mares with endome-
trial cysts tended to have a lower day-40 pregnancy rate. The
effect of cysts on fertility appeared to be quantitative because
 CHAPTER 19
an effect was not evident until a mare had numerous cysts or
the cysts were large. However, even then the effect of endo-
metrial cysts on fertility was much less than that with delayed
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uterine clearance or intrauterine fluid accumulation. A quan-
titative effect of endometrial cysts could be caused by interfer-
ence with embryonic mobility. It is well known that the equine
embryo undergoes a period of mobility after entering the
uterus and finally becoming fixed in place at approximately
16 or 17 days of gestation. If mobility is restricted during this
period and the embryo is not permitted to come in contact
with a sufficient portion of the endometrium, then maternal
recognition of pregnancy may not occur, resulting in luteolysis
and embryonic loss.
Rather than viewing endometrial cysts as a cause of infer-
tility, one should consider them as an indication of underlying
pathologic changes in the uterus. Large endometrial cysts are
usually of lymphatic origin, and their occurrence may be asso-
ciated with a disruption of lymphatic function.
Endometrial cysts are best diagnosed with ultrasonography.
Cysts are identified as hypoechoic, immoveable structures,
with a clear border, as opposed to intraluminal fluid, which is
movable and has a less distinct shape or border. Endometrial
cysts are usually multiple and most commonly found at the
base of the uterine horns. Cysts may change in size and num-
ber between estrus, diestrus, and pregnancy.
Endometrial cysts can complicate a diagnosis of early preg-
nancy. They are often similar in size and appearance to an
early conceptus. Cysts that appear spherical often are shown
to have a more irregular shape if the ultrasound probe can
be reoriented in relation to the cyst. To make the diagnosis
of early pregnancy easier and more reliable, the practitioner
should record the size and location of endometrial cysts using
a diagram or by storing ultrasonographic images during a pre-
breeding examination. Even so, it may be necessary to repeat
the pregnancy examination or delay confirmation in some
mares with endometrial cysts. In most cases of endometrial
cysts, no treatment is necessary other than recording their size
and location for future reference during pregnancy exami-
nation. However, if the cysts are sufficient in size or number
such that they pose a potential threat to embryonic migration,
treatment can be aimed at facilitating the establishment of
pregnancy by providing exogenous progestogen.
Progestogens, usually in the form of altrenogest (0.044 mg/
kg/day, administered orally), can maintain pregnancy even
when the signal for maternal recognition of pregnancy is lack-
ing. Numerous studies have shown the ability of altrenogest
to maintain pregnancy after luteolysis or in ovariectomized
mares. It is important to note that if progestogen therapy is
deemed necessary, then the correct dose and frequency of
administration are required or the effort is wasted. For exam-
ple, once-a-month administration of medroxyprogesterone is
insufficient to maintain pregnancy. Therefore it would not be
beneficial in mares with large or numerous endometrial cysts.
Alternatively, endometrial cysts may be removed surgically.
Laser surgery is an ideal method if the equipment is available.
Ligation and transection of the stalk of pedunculated cysts
is an alternative. Merely puncturing and draining the cyst or
incising its wall does not usually provide long-term remission.
Transluminal Adhesions
Trauma or severe infectious or chemically induced (e.g., after
intrauterine infusion of irritating chemicals) endometritis may
induce the formation of transluminal adhesions in the uterus.
Disorders of the Reproductive Tract 12431243
These lesions are usually asymptomatic and found during hys-
teroscopy. Uterine adhesions may cause the retention of endo-
metrial secretions, resulting in mucometra or pyometra. Early
embryonic motility, a phenomenon paramount for maternal
recognition in horses, may be impaired by intraluminal adhe-
sions. Treatment modalities include manual disruption of
intraluminal adhesions or ablation by way of laser surgery.
Pyometra
Pyometra is an accumulation of purulent exudate in the
uterus. Unlike cows, mares with pyometra do not neces-
sarily have a persistent CL, and many may cycle normally.
A cervical anatomic defect or persistent “hymen” that pre-
vents the clearance of fluid from the uterus may predispose
mares to pyometra. However, this condition also can affect
mares without an apparent anatomic defect in the reproduc-
tive tract. One can diagnose pyometra readily by transrec-
tal ultrasonography when intraluminal fluid with moderate
echogenicity is visible in the uterus. Because most mares
with pyometra are brought to the veterinarian’s attention at
an advanced stage, degenerative changes such as endometrial
atrophy may preclude mares from returning to normal fertil-
ity after treatment. A biopsy sample of the uterus should be
examined before treatment to determine the prognosis for
potential fertility. Although medical evacuation of the uterus
may be attempted, hysterectomy is an option for mares
refractory to treatment or with advanced degeneration of the
endometrium (severe endometriosis).
Neoplasia
Uterine neoplasms are uncommon in mares. Leiomyomas,
often referred to as fibroids, are benign mesenchymal neo-
plasms derived from smooth muscle and often are associated
with the presence of fibrous tissue. Leiomyoma is the most
common neoplasm affecting the uteri of mares; small neo-
plasms do not necessarily result in reproductive failure. Leio-
myosarcoma, lymphosarcoma, and adenocarcinoma are rare
malignant neoplasms affecting mares.
Neoplasms affecting the equine uterus are usually discov-
ered during rectal palpation and transrectal ultrasonogra-
phy in broodmares during the breeding season. If a uterine
neoplasm is suspected, then the clinician should perform
uterine endoscopy and take a biopsy sample of the tissue for
final diagnosis. Surgical excision of neoplasms is indicated
when extensive hemorrhage and endometritis are present or
when the presence of the neoplasia would be incompatible
with establishing a pregnancy. Prognosis for future fertility is
reduced, but pregnancy has been reported in mares with par-
tial hysterectomy.196
Uterine Lacerations
Uterine lacerations can occur during unattended or assisted
parturition. Rectal and vaginal palpation and abdominocen-
tesis aid in diagnosis.197 Uterine lacerations historically have
been thought to occur most frequently in the dorsal wall
of the uterine body, but more recent work has suggested an
increased frequency in the uterine horn with the right side
affected (73%) more often than the left.198,199 Uterine lacera-
tions, once confirmed, are surgically repaired because they
can cause life-threatening peritonitis or persistent infertility.
Adhesions involving the serosal surface of the uterus may
occur after cesarean section or uterine tears. No effective treat-
ment, other than attempted surgical excision, exists once the
 1244 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
adhesions form. Therefore some recommend daily palpation
of the uterus to avoid adhesion formation following cesarean
section.
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Uterine Artery Rupture
There is conflicting evidence about what the predisposing fac-
tors are for uterine artery rupture. Age (>15 years) and parity
have been shown to be contributing factors for mares at risk
for uterine artery rupture.5,200-202 Periparturient artery rup-
ture can occur before foaling but most often occurs during or
immediately after parturition. The mare may appear to have
colic post foaling, or the hemorrhage may occur after uter-
ine lavage or transrectal palpation several days later. In one
study, mares with periparturient arterial rupture represented
1.5% of the total equine necropsy cases; there was no predilec-
tion for the left or right sides, and the uterine artery was the
most commonly ruptured vessel.201 Uterine vessels undergo
extensive dynamic remodeling during pregnancy and the
postpartum period, and this is thought to contribute to pro-
gressive degenerative vascular changes. If a mare is believed
to be hemorrhaging, then the most common treatment regi-
men includes sedation and hemostatic support (aminocaproic
acid and Yunnan Baiyao). Although many different treatments
have proven to be effective, the most important goal is keep-
ing the mare quiet and comfortable.202,203 If a mare survives
an acute episode of rupture of the uterine artery, then anti-
microbial therapy is indicated to prevent the hematoma from
becoming an abscess. Monitoring the mucous membranes and
pulse for 30 minutes after foaling is indicated if the parturition
was induced or assisted by a veterinarian and especially when
an intervention to correct a dystocia is performed.204 In mares
that survive a ruptured uterine artery, fertility is usually not
altered, but mares may be at increased risk for repeated fatal
hemorrhage during the subsequent parturition. Further dis-
cussion of this condition can be found in the pregnant mare
section.
Y UTERINE TUBES
As mentioned previously, mares are unique in that unfertil-
ized oocytes are retained in the uterine tubes or oviducts and
are not transported to the uterus. The mechanism accounting
for this phenomenon (selective transport of fertilized ver-
sus unfertilized oocytes) has been demonstrated to involve
embryo secretion of PGE2.8 A healthy oviduct responds to
embryonic signals, resulting in proper timing of tubal trans-
port. Diagnosis of pathologic conditions in the uterine tubes
is difficult, but laparoscopic evaluation and patency tests have
been described.
Postmortem examination of reproductive tracts revealed
that salpingitis was common in mares: 37% had infundibulitis,
21% had ampullitis, and 9% had isthmitis. In that study 50%
of mares were more than 15 years old, and 85% were older
than 11 years of age. The infundibulum generally was found
adhered to the uterus, mesovarium, or ovary. The incidence of
adhesions on the right side was significantly higher than that
on the left side.205
Postmortem analysis of uterine tubes has suggested that
tubal patency is not a major problem in mares. Oviductal
obstructions are less common in the mare than in the cow,
although masses of collagen have been found in the ovi-
ducts of young maiden mares and pregnant mares and were
observed more often in mares that are more than 7 years
old.206 An examination of 700 postmortem specimens, pri-
marily from mares older than 11 years of age, found that
almost all oviducts were patent, although more than 40%
had adhesions involving the infundibula.205 Only one uter-
ine tube was found to be occluded among 1248 pairs of uter-
ine tubes that were flushed postmortem.205,206 Despite this
research, there is evidence that oviductal treatment with
PGE2 topically through a laparoscopic approach and oviduc-
tal flushing have increased fertility in a certain population of
mares that have unexplained infertility that includes a his-
tory of no early pregnancy seen despite what appears to be a
normal reproductive tract.207-211
Y OVARY
The presence of an enlarged ovary in a mare may be normal
or an indication of a pathologic ovarian condition. Consider-
ation of the various possibilities and careful diagnostic proce-
dures are necessary so that normal ovaries are not surgically
removed. A thorough history review, including changes in
behavior, estrous cycle characteristics, sexual behavior, and
the last observed estrus, is important. Ultrasonography, palpa-
tion, and hormonal assays are helpful in reaching an accurate
diagnosis. In some mares, sequential examinations are benefi-
cial in determining changes in the size of ovaries or various
structures on an ovary.
Discovery of an enlarged ovary may be an incidental find-
ing during a normal reproductive examination or may be stim-
ulated by specific clinical signs. Behavioral changes or signs of
colic in a mare warrant examination of the reproductive tract,
with special attention to the ovaries. Mares with a history of
infertility often are suspected of having abnormalities of the
ovaries and deserve a thorough examination before surgical
removal of an enlarged ovary. The clinician must consider var-
ious factors, such as season and pregnancy status, when inter-
preting a finding of ovarian enlargement. Large ovaries may be
normal during the transitional periods in the spring and fall
and are expected during certain stages of gestation.
Neoplasia
Granulosa cell tumors (GCTs) or granulosa-theca cell tumors
(GCTCs) are the most common tumors of the reproductive
tract in mares. They are benign sex cord tumors that can occur
in mares of any age; they also have been reported in foals and
pregnant mares. Although the granulosa and the theca interna
cell layers may be involved, the granulosa cell layer most com-
monly is affected.
Behavioral changes are common in mares with GCTs that
secrete steroid hormones. Behavior may be stallion-like, or
persistent estrus or anestrus may occur, depending on the
steroid production of the tumor. In other cases of GCTs,
behavior may be unchanged yet the mare may be showing
signs of abdominal discomfort, lameness, anemia, or other
signs seemingly unrelated to the reproductive system. Stal-
lion-like behavior is the most commonly reported behav-
ioral change observed. This is possibly because the change
from previous behavior is obvious to the owner and causes an
increased challenge in handling the mare. In one report of 63
mares diagnosed with GCTs, 20 exhibited anestrus, 14 were in
persistent estrus, and 29 showed stallion-like behavior, which
is usually associated with elevated serum testosterone (>45 pg/
mL). However, persistent estrus has not been correlated with
elevated estrogen.147,212-214
 CHAPTER 19
On rectal palpation the affected ovary is often enlarged,
whereas the contralateral ovary is typically small and inactive.
Atrophy of the contralateral ovary can be misleading during
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winter anestrus, when ovaries are small and minimal follicular
growth occurs. Atrophy of the contralateral ovary is not abso-
lute. Although unusual, GCTs have been reported in preg-
nant mares and in cyclic mares with a functional contralateral
ovary and even in both ovaries.212,213 The enlarged ovary may
be smooth or knobby, hard or soft, and may feel as if multiple
follicles are present as described previously. Typically, one can-
not palpate the ovulation fossa on the affected ovary, although
with any greatly enlarged ovary the fossa may be difficult or
impossible to palpate. In one report a mare developed a GCT
in the contralateral ovary 4.5 years after the initially affected
ovary was surgically removed.213 Ultrasonographic evaluation
often shows the classic multiloculated appearance, with cystic
structures having sharp rather than rounded borders. How-
ever, sometimes the tumor may appear solid or with a single
larger cystlike hypoechoic area.147,214 Although ultrasonogra-
phy is a useful adjunct, it may not yield a definitive diagnosis
as mentioned previously. The ultrasonographic image of GCTs
can be similar to that of other ovarian abnormalities, espe-
cially ovarian hematomas. A variety of reported appearances
makes diagnosis based solely on ultrasonography impossible
in many instances.
Mares with GCTs have changes in the circulating hormone
concentrations as previously described. Although testosterone
often is elevated in mares with GCTs exhibiting stallion-like
behavior, testosterone is within normal limits in 10% to 50%
of cases. Testosterone in normal cycling mares is less than
approximately 45 pg/mL and often is greater than 100 pg/mL
in mares with stallion-like behavior. McCue reported that only
54% of mares with GCTs had elevated testosterone, yet 87%
had elevated inhibin, leading to the conclusion that inhibin
is a better indicator of the disease.147,214 Inhibin suppresses
FSH, leading to a decline in follicular growth, which explains
the profound negative feedback effect on the contralateral
ovary. Recent work, as mentioned in the previous section,
has highlighted the increased sensitivity (98%) of an elevated
AMH concentration for detecting the presence of a GCT.149
At this time most practitioners will have the hormones AMH,
inhibin, and testosterone tested, and an abnormal elevation
in these concentrations, in conjunction with behavioral signs
and abnormal ovarian architecture that persists >30 days, is
considered sufficient evidence for the presence of a GCT and
the recommendation for unilateral ovariectomy.149,215
Overall, the prognosis for life and reproductive function in a
mare with a GCT is good. Depending on the time of year when
the ovary is removed, the individual mare, and the length of
time the tumor has been present, resumption of ovarian activ-
ity usually occurs 83 to 392 days after surgery, with a mean of
209 days. If the intended use of the mare is solely as a brood-
mare, then a reproductive examination, including a uterine
biopsy, is recommended before surgery.
Teratomas, although uncommon, are the second most com-
mon ovarian tumors. They contain at least two, if not all three,
germinal layers. Most teratomas found in mares are benign.
They usually contain hair and also may contain bone, teeth,
and neural tissue. Teratomas are usually an incidental finding
because most are small and do not often cause significant ovar-
ian enlargement. However, on occasion, large teratomas develop
that result in ovarian enlargement. Teratomas do not affect the
estrous cycle and, therefore, lack obvious outward clinical signs.
Disorders of the Reproductive Tract 12451245
Serous cystadenomas are neoplasms of epithelial origin
usually found in older mares. These tumors do not metas-
tasize. Although they have been found in mares with high
plasma testosterone,216 behavioral changes are not charac-
teristic. The contralateral ovary is not affected, continues to
have normal activity, and does not atrophy; and affected mares
usually continue to cycle. On the affected ovary the ovulation
fossa is not obliterated and is palpable.
Dysgerminomas are highly malignant tumors that are also
of germ cell origin. They metastasize rapidly to the abdominal
and thoracic cavities and are considered the counterpart of the
testicular seminoma. Because of their nature, dysgerminomas
can affect other organ systems, and cases have been reported
of associated hypertrophic pulmonary osteoarthropathy.217
Clinical signs on presentation, therefore, often are unrelated to
the reproductive system. These tumors carry a poor prognosis.
Ovarian Abscess
Ovarian abscesses often are attributed to procedures involving
puncture of the ovary, such as biopsy or follicle aspiration. As
assisted reproductive techniques became more successful and
therefore more popular, the incidence of ovarian abscesses was
thought likely to increase. However, this has not proved to be the
case. Moreover, not all ovarian abscesses can be attributed to iat-
rogenic causes. Ovarian abscesses have been reported in mares
that have had no such procedures performed on them. In these
cases, abscesses are likely caused by the hematogenous spread of
bacteria or may be associated with strongyle migration.
Affected mares may be febrile and anorectic with an ele-
vated white blood cell count. On ultrasonographic examina-
tion the enlarged ovary typically has a thick-walled, fluid-filled
structure. The fluid is usually heterogeneous and hyperechoic.
Medical management with long-term antibiotic therapy has
been successful in treating these cases. Surgical removal of the
affected ovary is an alternative treatment, but one must take
care that the abscess does not rupture in the abdominal cavity.
Ovarian Torsion
Ovarian torsion, a condition not uncommon in women, has
been reported in a mare with a large GTCT that was show-
ing signs of abdominal discomfort.218 It might be suspected
in mares with known ovarian enlargement if sudden signs of
abdominal pain develop.
Non-neoplastic Ovarian Enlargement
An ovarian hematoma can form after follicular aspiration or
as hemorrhage occurs into the follicular lumen after ovula-
tion. On occasion this hemorrhage can be excessive, possibly
because of an anticoagulant present in follicular fluid. Hema-
tomas can be large, up to 20 cm in diameter or more. Although
the ovulation fossa is still present, palpating it can be diffi-
cult if the hematoma is large. The ultrasonographic appear-
ance varies, causing confusion with a GCT. Large fluid-filled
cavities may be observed, or the hematoma may have a more
solid appearance, sometimes with fibrin strands. A trait that is
sometimes useful in differentiating a hematoma from a GCT
is the responsiveness to administration of PGF2α. Hemato-
mas that are at least 5 or 6 days old often respond to PGF2α by
decreasing in size because of the luteolytic effect. GCTs do not
respond to PGF2α treatment with any change in size, shape,
or ultrasonographic appearance. Because the follicle wall still
undergoes luteinization despite the presence of the hematoma,
progesterone concentrations in blood may rise, and cyclicity
 1246 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
usually remains unaltered. Unless the hematoma obstructs the
ovulation fossa, fertility is usually not compromised. However,
because of the presence of a hematoma, the enlargement of the
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ovary may persist for several estrous cycles even though the
life span of the luteal tissue is normal. Because this structure
is a postovulatory phenomenon, the oocyte has been released
and the mare may become pregnant if she is mated.
Anovulatory follicles are most common in mares near the
end of the breeding season as they go through the autumn
transition. These follicles grow to an unusually large size (70–
100 mm) yet fail to ovulate. Instead, they fill with blood and
develop a gelatinous consistency. A thick (compared with a
normal follicle) wall commonly forms. The follicles become
firmer and then regress over time, usually disappearing within
a month. Free-floating echogenic spots are evident in the
antrum of the follicle on ultrasonography, and these increase
in number as the follicle grows. When the follicle stops grow-
ing, the contents become organized with an echogenic appear-
ance and fibrin strands. Formation of luteal tissue around the
periphery of the anovulatory follicle is usually minimal in a
true autumnal follicle that occurs at the end of the season.
The cause of anovulatory follicles is unknown, although they
have been hypothesized to be caused by changes in the hor-
monal status of the mare that occur with autumn transition.
This hypothesis does not explain the occasional occurrence
of anovulatory follicles during the breeding season, however.
Luteinized anovulatory follicles, although unusual during the
ovulatory season, most often occur in older mares, mares with
endometritis and mares administered luteolytic agents. Their
response to induced luteolysis varies.
During gestation, ovarian enlargement is normal and
should be expected when eCG levels are elevated and acces-
sory CLs are present. Ovarian enlargement is associated with
increased follicular activity and subsequent ovulation (sec-
ondary CLs) or anovulatory luteinization (accessory CLs). An
increase in follicular growth begins before day 20 of gestation.
New CLs form at approximately day 40 of gestation. Corpora
hemorrhagica and hemorrhagic follicles are most common
from day 40 to 60. Mares bred early in the season have greater
follicular activity during the first 4 months of gestation than
mares bred after July.
As described previously, mares undergo transition from
winter anestrus to the normal ovulatory season during the
spring. The spring transition is characterized by the develop-
ment and regression of several follicular waves without ovula-
tion, and the ovaries can be quite large, with multiple follicles
on each ovary. This transitional period until ovulation occurs
lasts for a variable time depending on the mare, photoperiod,
and other undetermined factors. The ovaries can be large dur-
ing the spring transition and may be mistakenly called cystic.
No treatment is necessary, although a combination of proges-
terone and estrogen often is used to suppress follicular activ-
ity in an attempt to hasten the onset of ovulation and normal
cyclicity.
Small and inactive ovaries normally are found in mares
in deep anestrus, prepubertal mares, and pregnant mares in
the last third of gestation when, curiously, the fetal gonads
are larger than the ovaries of the dam. Mares subject to severe
malnutrition, of advanced age, treated with anabolic steroids,
and with chromosomal alterations leading to gonadal dysgen-
esis may have abnormally small and inactive ovaries. Mares
administered GnRH vaccines have also been demonstrated to
have prolonged periods of ovarian inactivity.42,44
This section has provided the basic approach to the most
common pathologies associated with the reproductive tract
of the nonpregnant mare. The following section serves as an
in-depth discussion of endometritis, which is arguably one of
the most important topics in reproductive management of the
horse because it is the most common problem associated with
establishing pregnancy in the mare.
Endometritis and Uterine Therapy
Charles F. Scoggin, Kirsten E. Scoggin
Endometritis is the leading cause of subfertility in broodmares.
Identification of the cause(s), targeted therapy, and periodic
monitoring are important components of successful manage-
ment. In addition, some causes (e.g., sexually transmitted dis-
eases [STDs]) have important regulatory considerations and
can affect international trade and transport. This section will
provide an overview of the pathophysiology, methods of diag-
nosis, and treatment strategies for endometritis.
Y INTRODUCTION
Inflammation of the uterus following breeding is considered
a normal yet transient physiologic response in mares.219 Most
mares (∼90%) are capable of managing this inflammation
with little to no intervention; these individuals are considered
reproductively normal or resistant mares. The other 10% either
have or are prone to endometritis and are considered suscep-
tible mares.220,221 Causes of susceptibility include infiltration of
pathogenic organisms, anatomic and functional defects, aber-
rant local immune response, and method of breeding.
Y PATHOPHYSIOLOGY OF
ENDOMETRITIS
In clinical broodmare practice, the most important causes of
endometritis are (1) infectious endometritis (IE), (2) post-
mating-induced endometritis, (3) CDE, and (4) STDs. These
diseases are not mutually exclusive and can occur in tandem.
Infectious Endometritis
Infectious endometritis occurs following colonization of
the uterus with opportunistic bacteria. The most frequently
encountered pathogens in mares are β-hemolytic strepto-
cocci (Streptococcus equi ssp. zooepidemicus; β-strep) and E.
coli.222,223 Less common but no less pathogenic are the bacteria
Pseudomonas aeruginosa and Klebsiella spp. and the yeast Can-
dida spp. and Aspergillus spp. As will be discussed later, these
microbes are identified by microbiologic techniques, cytologic
evaluations, and histologic studies of the endometrium.
Persistent Mating–Induced Endometritis
Equally as significant as IE is persistent mating–induced
endometritis (PMIE). This condition occurs when mares have
anatomic or physiologic abnormalities that lead to excessive
intraluminal fluid accumulation and/or impairment of the
uterine clearance mechanisms. Normal or resistant mares
should typically have only a trace amount (e.g., <1 cm in
depth) of anechoic fluid seen on transrectal ultrasound 24 to
36 hours after breeding.224 In contrast, susceptible mares will
 CHAPTER 19 Disorders of the Reproductive Tract 12471247
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FIG. 19.19 Light micrograph of an endometrial cytology from a mare

with persistent mating–induced endometritis (PMIE). Numerous neutro­ FIG. 19.20 Cross-sectional transrectal ultrasonographic image of the
phils and eosinophils are present in this sample. Bacterial colonies are uterus from a mare with persistent mating–induced endometritis (PMIE).
also evident. Note the edema pattern present within the endometrium that is associ­
ated with the echogenic intraluminal fluid. (Courtesy P.M. McCue).
have a significant amount of echogenic fluid measuring sev-
eral centimeters within the uterine lumen. This fluid is usu-
ally an accumulation of inflammatory cells, uterine secretions,
and semen (Fig. 19.19). Endometrial edema is often present
and excessive, indicating an exaggerated local inflammatory
response (Fig. 19.20).
Chronic Degenerative Endometritis
Chronic degenerative endometritis is typically considered an
age-related phenomenon.225 Changes within the reproductive
tract associated with CDE occur regardless of parity or past
reproductive history. A recent review on this subject evalu-
ated data from three different regions of the world with large
Thoroughbred breeding programs.226 On average, reproduc-
tive efficiency in broodmares increased steadily until ∼10
years of age and remained relatively steady until ∼14 years of
age. Reproductive performance slowly but steadily declines FIG. 19.21 Light micrograph of an endometrial biopsy showing age-
thereafter and goes into a downward spiral by the late teens. related changes in the stratum compactum consistent with chronic
Mares with CDE are readily diagnosed by endometrial biopsy. degenerative endometritis (CDE). Note denuded epithelium, sparsity of
Common findings include increased fibrosis, cystic glandu- glands, and foci of inflammatory cells. (Courtesy C.F. Scoggin).
lar distention, and lymphangiectasia (Figs. 19.21 and 19.22).
Clinically, these changes put mares at risk for either IE or
PMIE. In addition, age-related changes occur to other impor- have focused on characterizing this cytokine signaling path-
tant parts of the reproductive system, such as the cervix and way in the mare reproductive tract in response to bacterial
perineum.227,228 The clinician is thus reminded to evaluate all or breeding-induced endometritis (reviewed in Woodward
structures of the reproductive tract when managing endome- and Troedsson230). Current experimental models use either
tritis or other causes of subfertility. bacteria (such as β-strep or E. coli) or spermatozoa to induce
an inflammatory response. In these models, upregulation of
Molecular and Gene Expression Studies proinflammatory cytokines—such as tumor necrosis factor-α
Recent studies have shown there are multiple and complex (TNF-α), IL-1β, and IL-8 (a neutrophil chemoattractant), as
signaling pathways involved in both experimental and clini- well as the antiinflammatory cytokine IL-10—was observed
cal cases of endometritis. Included in these events is release of within 3 hours after challenge.231 This same group also found a
proinflammatory and antiinflammatory cytokines. The inter- systemic increase in serum amyloid A (SAA) expression up to
leukin (IL)-1 cytokine family (IL-1α, IL-1β, and IL-receptor 12 hours after inoculation. A follow-up study comparing mares
antagonist [IL-1Ra]) plays an important role in immune regu- classified as resistant or susceptible to persistent endometritis
lation and inflammatory processes.229 Several recent studies found that both groups exhibited an immune response after
 1248 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
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FIG. 19.22 Light micrograph of an endometrial biopsy of the stratum
spongiosum. Age-related changes are evident and consistent with chronic
degenerative endometritis. (Courtesy C.F. Scoggin).
E. coli infusion, but the susceptible mares showed a sustained
cellular immune response (up to 72 hours).232 The susceptible
mares showed an increase in IL-1β and IL-8 expression at 24
hours, and IL-1β at 72 hours compared with resistant ones. In
addition, susceptible mares had a decrease in IL-6 and TNF-
α expression compared with resistant mares at 3 hours post
infusion. In this study, there was no upregulation or downreg-
ulation observed for the inflammatory-modulating cytokine
IL-10, but this may be caused by a lower dose of E. coli used for
the bacterial challenge.
Endometrial cytokine gene expression was also analyzed
in mares resistant and susceptible to persistent post-breeding
endometritis. Fumuso et al.233 examined the expression of
IL-1β, IL-6, and TNF-α in resistant and susceptible mares 24
hours after AI and found that both groups detected an increase
in these proinflammatory cytokines, but the susceptible mares
had overall higher basal levels of these cytokines. The same
research group subsequently found that susceptible mares had
an increased expression of IL-8 (which mediates recruitment
and leukocyte activation at sites of inflammation) and lower
expression of the antiinflammatory mediator IL-10 com-
pared with resistant mares 24 hours after insemination.233,234
The cytokine response to killed spermatozoa was also com-
pared between resistant and susceptible mares at multiple
time points after insemination (0, 2, 6, 12, and 24 hours).235
Both groups exhibited changes in cytokine expression, but
significant differences between groups were only observed
at the 6-hour time point. Six hours after insemination, sus-
ceptible mares had a lower expression of the antiinflamma-
tory cytokines IL-1Ra and IL-10 and the proinflammatory
cytokine IL-6 (which can stimulate the immune response and
also has antiinflammatory properties236 compared with resis-
tant mares). Thus the inflammatory gene response may dif-
fer in mares with persistent breeding-induced endometritis.
A better understanding of the molecular causes and pathways
involved in the disease could lead to new treatments aimed at
targeting these particular pathways. These include treatment
with immune-modulating substances either locally or sys-
temically and will be discussed in a later section pertaining to
therapeutic options for endometritis.
Biofilm Infections
Over the past decade biofilm infections have received a great
deal of attention as a cause of mare subfertility. Bacteria can
exist in one of two states: The first is the free-floating or plank-
tonic state, and the second is the biofilm state. This biofilm
state contains a community of bacteria, and together they cre-
ate an added barrier of protection against the host’s immune
system and antibiotic agents above and beyond the capability
of planktonic bacteria. These biofilms are proposed as a cause
for persistent and chronic endometrial infection, and research
is actively being pursued on this topic.
Biofilm is made up of an exopolysaccharide matrix (EPS)
that is produced by the bacterial community within the bio-
film.237 This EPS contains plasmids that can be shared among
this community to confer resistance to outside stresses or an
adverse environment. The EPS also allows for chemical signal
transduction, allowing bacteria to coordinate their activities to
increase efficiency and resiliency of the biofilm. The presence of
biofilm has been found in various areas, including the bladder
and skin wounds, and can lead to persistent infections, making
treatment and resolution difficult. The actual presence of biofilm
within the mare’s uterus has not been confirmed, but research
appears to be on the precipice of answering that question.238,239
Pathogenic bacteria implicated in biofilm formation in the
mare are E. coli, K. pneumoniae, P. aeruginosa, and β-strep.
A presumptive diagnosis of uterine biofilm infection can be
made in mares that fail to respond to conventional treatments
as determined by repeated “dirty” cultures and inflammatory
cytologies. Current therapies are aimed at disrupting biofilm
formation and will be discussed in a subsequent section.
Sexually Transmitted Diseases
There are several equine STDs that are of relevance from
both clinical and regulatory standpoints. Readers are
strongly encouraged to contact their local U.S. Department
of Agriculture-Animal and Plant Health Inspection Service
(USDA-APHIS) official for updated information or whenever
a reportable or foreign animal disease (FAD) is suspected.
Questions pertaining to the handling of potentially infected
gametes (e.g., spermatozoa and embryos) should be directed
to these and other regulatory officials.
Contagious Equine Metritis
As the name implies, CEM is a contagious disease affecting
the uterus of the mare. It is of increased significance because
of its impacts on international transport of livestock. A true
venereal disease, CEM is caused by the bacterium Taylorella
equigenitalis, a gram-negative coccobacillus that is considered
highly contagious.240 Transmission via fomites also appears
to be likely and was implicated as a cause for an outbreak in
the United States from 2008 to 2009. Clinical signs vary from
relatively unapparent to copious vulvar discharge originat-
ing from the uterus.241 The majority of CEM-affected mares
are otherwise clinically normal and will resolve the infec-
tion within 2 to 4 weeks. Unfortunately, by the time clinical
signs are observed, at least one cycle is lost to endometritis,
and spread of the disease is rapid to other mares and stallions.
Inapparent or “silent” carrier stallions are the most common
 CHAPTER 19
source for disease transmission among horses. What ensues
is a significant drop in productivity (as measured by per cycle
pregnancy rates) and increased costs associated with manage-
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ment and veterinary care. As will be described later, treat-
ment for T. equigenitalis is fairly straightforward and consists
of careful cleansing of the internal and external genitalia and
application of local antiinfective agents. Systemic antibiotics
may be needed in severe cases. To the authors’ knowledge,
no vaccine exists for this disease. Because of the fairly recent
outbreak of CEM, the United States has undergone a reclas-
sification in its status as a CEM-free country. As this chapter
goes to press, international transport of horses to and from
the United States is permissible by most agricultural ministries
provided proper screening and required treatments are per-
formed prior to introduction of the animal into the country’s
breeding population.
Equine Viral Arteritis
Equine viral arteritis (EVA) is another disease that has impor-
tant regulatory implications. It occurs following infection with
equine arteritis virus (EAV), an enveloped, single-stranded
virus. 242 Clinical signs vary in degree and intensity and include
vasculitis, distal limb edema, pyrexia, rhinitis, conjunctivitis,
and anorexia. Most important, it can cause abortion outbreaks
and severe neonatal pneumonia in naive herds, causing sig-
nificant economic damage and lost productivity. Modes of
transmission include respiratory secretions and other body
secretions, including semen, fetal fluids/tissues, and fomites.
Most mares mount a significant immune response to the dis-
ease and are generally considered immune for several years
following clinical infection. Current estimates suggest that
30% to 70% of exposed stallions will become persistently
infected with the virus and are referred to as “shedder” stal-
lions.243 For a more complete review of EVA in stallions, the
reader is referred to Chapter 8 and the section of this chapter
related to diseases of the stallion. In mares, disease is usually
self-limiting, and treatment consists primarily of supportive
care and isolation strategies. A modified live virus vaccine is
commercially available in the United States (Arvac; Zoetis,
Inc., Parsippany-Troy Hills, NJ 07054) and has been approved
for use in nonpregnant breeding stock. The authors have used
it safely in mares at various stages of gestation. Control of dis-
ease is best accomplished by screening, isolation, and vaccina-
tion. Breeding with EAV-infected semen is permissible with
proper documentation of the mare’s vaccination status. Cer-
tain breed registries and state agricultural departments have
restrictions regarding vaccination of breeding stock and use of
EAV-infected semen. The reader is encouraged to compile and
organize this information before vaccination or use of semen
from a shedder stallion.
Equine Herpesvirus Type 3
EHV-3 is the causative agent of equine coital exanthema. It
is not currently considered a reportable disease in the United
States. This virus is transmitted primarily via coitus, but trans-
mission can also occur via fomites, including shared examina-
tion gloves and vaginal specula. Clinical disease is primarily
manifested as vesicular and painful lesions on the external
genitalia of both mares and stallions. These lesions cause
discomfort during reproductive evaluations and during live-
cover matings, but aside from transient and often self-limiting
pyrexia, infection typically has no lasting or impressionable
effects on fertility.244 Lesions will take 4 to 6 weeks to heal and
Disorders of the Reproductive Tract 12491249
are characterized by focal areas of depigmentation. Gentle
cleansing of active lesions may soothe and reduce inflamma-
tion. Reports of antiviral treatments are sparse, and treatment
is usually tincture of time. Mares can resume breeding once
the lesions have healed. Recrudescence of this particular her-
pesvirus is unknown.245 Control is aimed at early detection
and temporarily removing infected animals from breeding
until lesions have subsided. There is no commercially available
vaccine against EHV-3 in the United States.
Dourine
Dourine is a serious STD of equids because of its high mor-
bidity and mortality. The etiologic agent is the protozoa Try-
panosoma equiperdum. Infection affects several body systems,
and clinical signs include intermittent fever, swelling of and
discharge from the genitalia, cutaneous plaques, and neuro-
logic signs.246 It is generally considered a chronic and pro-
gressive disease; the onset of recumbency usually indicates
terminal disease. This disease has been eradicated in several
developed countries, including the United States. It is still seen
in Africa, the Middle East, South America, and Central Amer-
ica, but sporadic outbreaks have been reported in Asia and
Germany.240 Diagnosis is made via compatible clinical signs
and a complement fixation (CF) test, which is prone to false-
positives from other species of Trypanosoma. Newer methods
of diagnostics, including ELISA and polymerase chain reac-
tion (PCR) technologies, are currently being explored for both
testing and screening purposes. If found in a particular area,
then infected animals should be identified, and breeding activ-
ity should cease until positive animals have been removed,
usually via culling. Treatment with antiprotozoal drugs has
been performed in some endemic areas, but they are unproven
and even discouraged because of the concern of generating
inapparent shedding animals.
Piroplasmosis
Piroplasmosis is a disease that became prevalent in the United
States earlier this decade after a fairly long period of absence.
It is considered an FAD in the United States, but it is endemic
in many other parts of the world. This disease is caused by
the protozoa Babesia caballi and Theileria equi (formerly Babe-
sia equi). Transmission occurs either via a vector (e.g., ticks)
or mechanically (e.g., improperly sanitized instruments). It
also has the potential to be transmitted venereally in cases of
hemospermia. Piroplasmosis creates disturbances to the cir-
culatory, musculoskeletal, abdominal, and nervous systems.
Clinical signs can be nonspecific and may vary based on the
severity of disease and degree of chronicity. Horses surviving
the acute phase of the disease can become carriers. Diagnosis
can be made based on observation of the organism on blood
smears and serologic testing. Treatment with antiprotozoan
medications is unproven, and recrudescence is a concern.240
Similar to other reportable diseases, concerns about a poten-
tial FAD should be directed to the local USDA-APHIS official.
Y DIAGNOSTICS
History
Evaluation of past reproductive, medical, and manage-
ment issues is tantamount to an effective workup of suscep-
tible mares. Calculation of per cycle pregnancy, embryonic
loss, and live foal rates are useful measures of reproductive
 1250 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
efficiency. Disturbances to other body organs may also factor
into susceptibility. Chronic injuries to the musculoskeletal
system can be particularly problematic because they can be
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a source of steady pain and ill-thrift. Metabolic disease can
also affect fertility (e.g., PPID). This disease is covered more
thoroughly in Chapter 16, but it can affect the reproductive
system by leading to chronic infections and erratic cyclic-
ity. Finally, consideration should be given to stallion fertility.
Chances of conception are improved by selecting a stallion
of known fertility. With respect to the phenomenon of mare-
stallion incompatibility, it has never been proven in horses;
nevertheless, the potential exists as suggested by numer-
ous anecdotal reports of switching stallions and improving
fertility rates in problem mares.
Reproductive Evaluations
The importance of a thorough physical examination cannot be
overstated. As mentioned previously, abnormalities in other
body systems can adversely affect reproductive efficiency in
broodmares. These should be noted and incorporated into the
future plan. Screening for infectious and metabolic disease
should also be performed when indicated.
Reproductive evaluations consist of inspection of both
the external and internal genitalia, including the mammary
glands. Perineal conformation is judged by evaluating the dec-
lination and location of the vulva with respect to the anus and
ischium. A more objective measure is calculating the Caslick
index described by Pascoe.49 In normal mares, the anus, vulva,
and ischium lie in a relatively similar vertical plane, with about
two thirds of the vulva lying dorsal to the ischium. The vulvar
lips should form a tight seal enclosing the vestibule, urethral
orifice, and clitoris. Abnormal findings include a forward-tilt-
ing pelvis, sunken-in anus, and more of the vulva lying dorsal
to the ischium than ventral. Clinically, these abnormalities can
lead to pneumovagina and urovagina, as well as fecal contami-
nation of the vestibule and vagina.
Palpation per rectum should reveal two ovaries that are
kidney-bean shaped with readily distinguishable ovulation
fossae. The uterine horns, uterine body, and cervix should also
be identified and felt for tone, relative turgidity, and location
of the uterus relative to the pelvis. Sweeping these structures
in a continuous motion can help identify adhesions and/or
intramural masses. Susceptible mares often have a pendulous
uterus, which can restrict uterine clearance. Rectal ultraso-
nography is a key component of mare reproductive examina-
tions and allows for further characterization of the ovaries,
uterus, cervix, and vagina. Archetypal findings of endometri-
tis are echogenic, intraluminal uterine fluid exceeding 2 cm
high by 2 cm wide, exaggerated endometrial edema using a
subjective scoring system, and pneumovagina as evidenced by
hyperechoic flecks within the vaginal vault.
Moving caudal to cranial, the three important barriers to
the uterus are the vulva, the vestibulovaginal fold, and the
cervix. Breakdowns in any of these barriers can lead to acute
or chronic inflammation and/or contamination with patho-
genic organisms. A vaginal examination can identify sources
of vulvar discharge, the relative seal of the vestibulovaginal
fold, character of the vagina, and integrity of the cervix. Most
theriogenologists prefer to do both speculum and manual
examinations because some abnormalities are best visualized,
whereas other abnormalities are best palpated.
Finally, evaluation of the udder is recommended. Abnor-
malities are rare but can affect rearing and mothering ability,
and they suggest endocrine disorders. Congenital defects, pre-
vious trauma, and infections can occur within the mammae.
Admittedly, it is unusual for abnormalities of the mammae to
be associated with endometritis. However, it is worthy to men-
tion that milk production can be adversely affected in severe
cases of endometritis that progress to metritis.
Assessment of the Endometrium
The past two decades have brought forth significant advance-
ments in diagnostics used for identifying endometritis. This
particular section will include both time-honored techniques
(e.g., culture, cytology, and biopsy) that comprise a minimum
database expected for evaluating mares with endometritis as
well as discussion of new techniques that may aid in the diag-
nosis and management of endometritis. Table 19.6 provides a
list of various clinicopathologic techniques available and their
relative merit for diagnosing endometritis in the mare.
When samples are procured from the internal reproductive
tract, the mare should be adequately restrained with her tail
held or tied out of the way. Her rectum should be evacuated and
her perineum thoroughly cleansed to remove feces, smegma,
and other debris. The clinician should use sterile gloves, rods,
sleeves, speculums, and swabs to maintain cleanliness.
Endometrial Culture
With respect to endometrial cultures, several means are avail-
able for acquiring samples. The most common method con-
sists of using either a Kalayjian or double-guarded swab. The
penetrating portion of the swab is protected within the palm
or fingers of the clinician before entering the vaginal vault. The
external os of the cervix is located, and the swab is fed through
the cervix and into the lumen of the uterus. After contacting
the endometrium, the swab is popped through the protective
cap or sheath and gently rolled along the endometrium. Care
must be taken to turn the swab in the same direction to pre-
vent it from snapping off within the endometrium. The swab
is then retracted back into its sheath(s) and placed in hold-
ing media, properly labeled, and submitted to the laboratory
for culture and sensitivity. Aerobic cultures are most com-
monly submitted. In cases of suspected anaerobic or fungal
infections, the clinician should communicate directly with
the laboratory when preparing these cultures and attempting
to identify the agent(s) involved. The major advantage of the
swabbing technique is the relative ease by which it can be col-
lected. Some clinicians prefer this method when using a spec-
ulum for accessing the vaginal cavity. The major downside of
this method is that it involves sampling only a small portion of
the endometrium. Focal infections can thus be missed, leading
to a false-negative result.
Other means of obtaining uterine cultures are low-volume
lavage (LVL), direct aspiration of intraluminal fluid, and biopsy
specimens. The LVL is a popular method for evaluating cases
of acute and chronic endometritis, especially in susceptible
mares. It consists of feeding a Bivona catheter into the uterus
and instilling a predetermined amount of physiologic saline or
LRS. The uterus is gently massaged per rectum, and the efflu-
ent is collected via gravity. The retrieved fluid is first evaluated
for its relative clarity and amount of mucus. Although sub-
jective, visual assessment appears important because a cloudy
efflux is highly correlated with the presence of bacteria.247 This
fluid is then transferred into sterile 50-mL conical vials and
subsequently centrifuged at 400g for 10 minutes. The super-
natant is poured off, and two sterile cotton swabs are placed
 CHAPTER 19
in the pellet: one for culture and one for cytology (see later).
The primary advantage of the LVL is that it provides a more
representative sample of the entire endometrium. The main
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disadvantage is that it is prone to false-positive bacteriologic
results caused by potential contamination from the vagina.
Direct aspiration of intraluminal fluid entails collection of
fluid already present (as diagnosed by ultrasound) within the
lumen of the uterus. It can be accomplished by feeding a flex-
ible insemination pipette into the uterus, attaching a syringe to
the other end of the pipette, and under ultrasound guidance,
gently aspirating fluid from the uterus. This fluid is submit-
ted to the laboratory for both culture and cytology. Advan-
tages to this method are that it does not require the addition of
fluid into the uterus, and the recovered fluid has a high prob-
ability of containing inflammatory debris and/or pathogenic
microbes. Disadvantages include the need for increased tech-
nical expertise and, in cases in which mares do not have a great
deal of intraluminal fluid, unsuccessful retrieval.
A final means of obtaining an endometrial culture is the
collection of an endometrial biopsy. A more thorough discus-
sion of the technique and histologic evaluation was provided
in an earlier section. Biopsy samples can also be used to obtain
both microbiologic and cytologic samples. For bacteriology,
the sample itself can be smeared on a blood agar plate, or a Cul-
turette can be run over the specimen and placed into transport
media before immersion into a fixative. Impression smears
can also be made and evaluated with common staining tech-
niques. The major benefits of this technique are improved sen-
sitivity of bacteriology findings relative to the guarded swabs
and cytologic evaluation, a high positive predictive value, and
the potential to identify infectious organisms deeper within
the stratum compactum.222 Drawbacks of this method include
an increased technical skill in obtaining the sample and rela-
tively low negative predictive value.
Endometrial Cytology
As alluded to earlier, endometrial cytology is often per-
formed in tandem with endometrial cultures. They are col-
lected in the same manner as endometrial cultures, with
clinician preference representing the deciding factor as to
what method to use. When Kalayjian swabs are used, a cytol-
ogy specimen can be obtained by gently rolling the outer
sheath of the rod within the endometrium to allow the cap
to collect a sample. It is important that the culture swab has
been retracted back into the sheath before the rod is rolled to
collect the cytologic specimen. Once collected, the rod can
be withdrawn from the mare, the swab placed in transport
media, and the cap gently “flicked” onto two separate slides,
one for an eosin-nigrosin stain and one for a Gram stain.
The specimen is then evaluated for the presence of inflam-
matory cells using bright-field microscopy. Other examples
include the previously described LVL technique, mare cytol-
ogy brushes, and impression smears from biopsy specimens.
Mare cytology brushes are similar to those used in women
for Papanicolaou (Pap) smears and attached to a plastic rod
in a fashion similar to those of double-guarded swabs, and
the procedure is identical. Biopsy specimens collected for
histology can be used to make impression smears onto slides
before immersion in fixative.
In addition to advancements in sample collection, our
understanding and interpretation of results have also evolved.
No technique is perfect, and each is prone to both false posi-
tives and false negatives, which influences the sensitivity
Disorders of the Reproductive Tract 12511251
(percent of disease-positive subjects that test positive) and
specificity (percent of disease-negative subjects that are nega-
tive) of each test. Table 19.6 lists probability measures for each
previously described technique used to diagnose endometri-
tis. Uterine biopsy samples are the most consistent and serve
as the “gold standard” in comparing the worthiness of other
diagnostics for detecting endometritis. At least two studies
have shown that bacteriology results obtained from endo-
metrial biopsy samples are superior to guarded-swab tech-
niques for positive identification of bacterial pathogens.222,248
Additionally, these studies and another106 demonstrated the
importance of collecting both a culture and cytology. Indeed,
cytology was at least twice as sensitive as culture in predicting
the presence of endometritis.106 The LVL technique has dem-
onstrated improved sensitivity for detecting bacterial growth
relative to the guarded swab but had lower specificities for
culture and cytology than the swab method.220 Consequently,
it appears that LVL underestimates inflammation, which may
be caused by dilution of retrieval fluid. However, it should be
noted that when researchers factored in the character of the
efflux, the specificity substantially improved.
Endometrial Biopsy and Histology
Histologic evaluation of biopsies is an invaluable tool and
widely agreed to be the gold standard when measuring a mare’s
future reproductive capacity.10 The procedure as described
previously involves aseptic preparation of the perineum, and
60-cm uterine biopsy forceps are used to obtain the sample.
Aside from proper restraint, mares generally do not react to
the biopsy, and minimal aftercare is warranted. The instru-
ment is then removed from the vagina, and the sample is
immersed in a suitable fixative. The authors prefer Bouin
solution over 10% neutral-buffered formalin as histologic
architecture and luminal contents are better preserved, but
samples must be transferred from Bouin solution into another
fixative (e.g., water and alcohol) within 24 hours to avoid tis-
sue disruption. Formalin is a suitable alternative and should
be used if samples are not going to be processed immediately.
If the sample is intended to be used for concurrent culture
and cytology, then these samples should be obtained from
the biopsy before immersion into a fixative. Multiple biopsies
can be collected from different areas of the uterus, and focal
abnormalities detected within the endometrium can be biop-
sied via ultrasound guidance or hysteroscopy. Samples can be
submitted for processing and preparation. Each grade is asso-
ciated with the likelihood of the mare carrying a pregnancy
to term (expressed as a percentage) and has been previously
described 249:
Grade I: Normal endometrium or mild, focal inflammation or
fibrosis; >80% of maintaining a pregnancy until term.
Grade IIA: Mild to moderate inflammation and/or multifocal
fibrosis with one to three layers of fibroblasts surrounding
glands or less than two fibrotic nests per 5-mm linear field;
50% to 80% chance of maintaining a pregnancy to term.
Grade IIB: Moderate inflammation and/or multifocal to dif-
fuse fibrosis with four or more layers of fibroblasts sur-
rounding glands or two to four fibrotic nests per 5-mm
linear field; 10% to 50% chance of maintaining a pregnancy
to term.
Grade III: Severe inflammation and/or diffuse fibrosis with
five or more nests per 5-mm linear field; <10% chance of
maintaining
a pregnancy to term.
 1252 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
Review and interpretation of the sample by a theriogenolo-
gist are recommended to ascribe a grade and offer a treatment
plan (i.e., epicrisis).
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The above techniques represent a minimum database for
evaluation of a subfertile mare. As a summary, these include
a thorough history; physical examination; reproductive evalu-
ation; and culture, cytology, and biopsy of the endometrium.
Theriogenologists have gained an appreciation of the relative
benefits and limitations of each test and how using them in
tandem improves the reliability of the results and the incit-
ing cause. However, there are some instances in which either
routine diagnostics fail to identify the problem or prescribed
treatment fails. The next section discusses advancements in
diagnostics that are improving both the accuracy of results
and response to therapy.
Y ADJUNCTIVE TECHNIQUES
Hysteroscopy
Hysteroscopy allows for complete visual assessment of the
lumen of the uterus via video endoscopy. This imaging tech-
nique can identify transluminal adhesions, congenital abnor-
malities, persistent endometrial cups, uterine tears, foreign
bodies, and focal areas of inflammation/infection. Ideally, this
procedure should be performed while the mare is in diestrus
so that the cervix is closed, allowing for proper insufflation.
Priming with progesterone is an option when preparing a
mare for hysteroscopy. The endoscope should be cold steril-
ized with an appropriate disinfectant and then rinsed thor-
oughly with sterile saline or LRS. The procedure is usually
performed under standing sedation. The perineum is cleansed
appropriately, and the distal end of the scope is guided into the
vagina. Evaluation of the vaginal vault can be useful for detect-
ing sources of persistent or periodic hemorrhagic discharge
(e.g., varicose veins) or cervical abnormalities. The end is then
passed through the cervix and into the uterus. Insufflation
with air or a balanced polyionic fluid allows for visualization
of the entire lumen as the uterus expands. The scope is then
maneuvered for a complete evaluation of the body and both
horns. Each horn should be examined along its entire length
to visualize the papilla representing the uterotubal junction.
A normal endometrium is pale pink in color with a mostly
homogeneous smoothness. If the examination is performed
during estrus, then endometrial edema will be grossly evident,
characterized by folds and a glistening surface.250 Video 19.1
provides an example of a normal endoscopic examination of
the mare’s reproductive tract. The endoscope was advanced
through the cervix, and rapid insufflation distended both
horns, allowing for complete visualization of the body and
both horns of the uterus.
A hallmark sign of acute endometritis is cloudy, neutro-
phil-laden fluid. Video 19.2 is an example of an abnormal
endoscopic examination with mucopurulent exudate diffusely
throughout the endometrium. Subsequent biopsy specimens
yielded a heavy growth of β-strep. Signs of chronic endome-
tritis are more variable, but they would include focal changes
in texture or color, erosions or ulcerations, and plaques or
mucoid debris.250 After hysteroscopy is completed, the uterus
should be lavaged, and a luteolytic dose of PGF2α is recom-
mended to contract the uterus and open the cervix for proper
drainage.
Hysteroscopy can also assist with treatment. When used in
conjunction with an Nd:YAG laser system, it can be used to
remove endometrial cysts, adhesions, and retained endome-
trial cups.160 Additionally, it can facilitate ligation of vessels
and removal of masses within the uterus or vagina. Other uses
for endoscopy of the reproductive tract include low-volume
insemination, fetal mummification or membrane extraction,
hydrotubation of the oviducts, and foreign body removal.
Serum Amyloid A
Acute phase proteins (APPs), such as haptoglobin and SAA,
are produced in the liver and stimulate the innate immune
response and assist in the elimination of infection.251 Their
production is stimulated by proinflammatory cytokines,
including IL-1, IL-6, and TNF-α, which help to modulate the
local and systemic immune response. Studies in horses have
measured SAA in monitoring the inflammatory response to
various clinical conditions, such as castration,252 endome-
tritis and placentitis,253,254 induced arthritis,255 and neonatal
illness.256
These proteins are also thought to play a role in the inflam-
matory cascade of the mare’s reproductive tract. Studies in
cattle have shown elevations in APPs associated with other
clinical and diagnostic signs of endometritis257,258 and could
potentially be useful biomarkers in broodmares. SAA is a
major protein that normally has low or undetectable levels in
a healthy horse; however, plasma concentrations can increase
more than 10-fold in response to injury or trauma.259 SAA
concentrations remain stable at baseline levels during the 4
months before parturition260 and significantly increase within
36 hours postpartum.261 Studies of mares experiencing early
embryonic loss showed increased levels in peripheral SAA 72
hours after insemination and ovulation,262 but a field study
comparing SAA concentrations at days 0 and 15 between
mares with early embryonic loss to matched mares that main-
tained pregnancy found no correlation between elevated SAA
levels and pregnancy loss.263 A study by Nash et al.264 found
that peripheral SAA levels did not increase at 24 hours post­
insemination with frozen/thawed semen, but a local response
within the uterine was not tested. Recent studies have focused
on the SAA response in equine endometritis using the bacte-
rial-induced model to monitor changes in peripheral concen-
trations of SAA, as well as local changes, by measuring gene
expression within in the endometrium. Uterine infusion of
high doses of E. coli yielded a measurable increase in SAA,
which significantly correlated with upregulation of SAA in
endometrial biopsies at 3 and 12 hours post infusion.231 Thus,
selected markers of the systemic acute phase reaction were
altered in the circulation in response to experimental IE. A
subsequent study by the same group evaluated the effect of
glucocorticoid therapy on SAA endometrial gene expression
in susceptible mares after E. coli infusion. Researchers found
a decrease in SAA concentrations in treated mares,265 sup-
porting previous clinical studies demonstrating the efficacy of
preemptive steroid treatment in mares prone to PMIE.266,267
More studies are necessary to further characterize the correla-
tion and clinical usefulness of measuring SAA concentrations
in cases of endometritis.
Y TREATMENT STRATEGIES
Antibiotics
The use of antibiotics in broodmare reproduction has a
lengthy history. Local intrauterine infusions have been used
for decades to treat or act as a prophylactic measure against
 CHAPTER 19
endometritis. Systemic antibiotics have gained popularity
over the past few years for use either in conjunction with or
as an alternative to intrauterine infusions. Doses, routes, and
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frequency for systemic antibiotics almost always follow pub-
lished guidelines for administration of these drugs in horses
(please see Chapter 2 for a detailed discussion). However,
when choosing a systemic antibiotic, it is important to base the
choice on sensitivity results and whether it can attain effective
concentrations in the endometrium and other tissues of the
urogenital system. These and other indications and options for
antibiotic use in broodmares will be discussed next.
Intrauterine Antibiotics
In 1992, Pycock and Newcombe published a report in which
they showed a significant association between postmating
intrauterine antibiotics and improved pregnancy rates.268 The
authors hypothesized that these results were related to reduc-
ing or eliminating bacteria tracked into the uterus following
breeding. In other words, because the act of mating, especially
live cover, was viewed as an inherently dirty process, the use
of intrauterine antibiotics assisted local immune defenses in
treating opportunistic bacteria. Interestingly, intrauterine anti-
biotics used alone yielded pregnancy rates similar to those in
mares treated solely with a single dose of oxytocin. However,
when these two treatments were combined, pregnancy rates
were significantly higher than in other treatment groups.
This study gave credence to prophylactic intrauterine anti-
biotic infusions and popularized their use sufficiently where
they have become a routine part of a postmating examination
in live-cover operations regardless of other findings (or lack
thereof). With concerns over antimicrobial resistance reach-
ing near pandemic levels, this practice is no longer condoned.
A more prudent and scrupulous course of action is to use
antimicrobial agents when there is clinical and/or diagnos-
tic evidence for treatment. Indeed, a recent review regarding
the prophylactic use of intrauterine antibiotics concluded that
despite justifiable pressures, use of antimicrobials in this man-
ner was questionable, and the use of alternative treatments such
as ecbolics and uterine irrigation may be more beneficial.269
When selecting an antimicrobial for intrauterine delivery,
factors to consider include:
• Appropriate sensitivity pattern
• Stage of estrous cycle
• If it is relatively nonirritating to the endometrium and geni-
talia
• Compatibility of different agents if two different drugs are
mixed
Although some clinicians discourage empiric therapy,
there are instances in which delaying treatment or ignoring
one’s clinical intuition and other findings may have negative
consequences. As such, broad-spectrum antibiotics can be
chosen that meet the other requirements given earlier. With
respect to the stage of the estrous cycle, past studies suggest
that intrauterine treatment should only be performed while
the mare is in estrus. Treatment during diestrus may have
unintended consequences—namely, iatrogenic contamination
and increased risk of fungal endometritis.270 Selection should
also depend on the chemical properties of the antibiotic and
its respective diluent. Ideal solutions should be nonirritat-
ing, attain proper minimum inhibitory concentration (MIC)
concentrations for the targeted microbe, and leave minimal
residues. Other characteristics, such as -cidal or -static effects
and concentration-dependent or time-dependent doses, can
also be factored in. However, most doses are empiric. Dosages
Disorders of the Reproductive Tract 12531253
for various antibiotics for intrauterine delivery are listed in
Table 19.7.
In a recent survey involving more than 200 equine practi-
tioners, Dascanio et al.271 reported that ceftiofur was the most
commonly used antibiotic by a narrow margin over gentami-
cin (21% vs. 19%, respectively). These two were followed by
ticarcillin and clavulanic acid (13%), ampicillin (12%), other
(12%), amikacin (5%), procaine penicillin (3%), potassium
penicillin (3%), and ticarcillin (3%). It was not specified if
these selections were made based on culture and sensitivity.
Regarding empiric therapy, one study showed that 100% of
clinical isolates of β-strep were susceptible to both ampicil-
lin and penicillin G, whereas 100% of E. coli were sensitive to
gentamicin.272
Frequency and length of treatment are other important
considerations. As shown in Table 19.7, most uterine infusions
are performed once daily. The exception is ticarcillin and cla-
vulanic acid, which, based on previous studies, indicates that
multiple daily infusions may be more appropriate to achieve
therapeutic concentrations than the standard once-daily dos-
ing.273 On the other hand, ceftiofur has been found to reach
effective concentrations when delivered either intrauterine or
IM.274,275 A recent report demonstrated the potential benefit of
a water-soluble solution of enrofloxacin for treating resistant
infections.276 Therapeutic concentrations were above MICs in
half of the test mares, and no long-lasting effects on the endo-
metrium were noted, indicating its relative safety. Studies of
other antibacterial agents in the uterus are in need of evalua-
tion to combat recurring infections and address antimicrobial
resistance.
Systemic Antibiotics
The use of systemic antimicrobial agents to treat endometri-
tis has gained significant momentum over the past decade.
Dosages are listed in Table 19.7. The benefits of systemic anti-
biotics compared with those given via the intrauterine route
are the ability to treat regardless of stage of the estrous cycle
and the ability to maintain effective and steady therapeutic
concentrations for a prolonged period. Additionally, they are
not subject to the adverse environment of the uterine lumen
and will not iatrogenically inoculate the reproductive tract,
as would occur with repeated vaginal treatments.220 Disad-
vantages are increased costs associated with higher volumes
used and daily treatments. Less common but no less important
risks are antibiotic-induced diarrhea, injection site reactions,
thrombophlebitis, and anaphylaxis.
Systemic treatment should either be preceded by or per-
formed concurrently with uterine irrigation to remove lumi-
nal inflammatory debris. Irrigation should be performed
judiciously to reduce the risk of tracking bacteria into the
reproductive tract. Systemic antimicrobials can also be used
in conjunction with ecbolics, which are discussed in the fol-
lowing section. To the authors’ knowledge, studies comparing
the effects of systemic versus intrauterine or other therapies
are lacking.
Ecbolics
Ecbolics are used to induce contractions of the uterus to pro-
mote uterine drainage. Oxytocin is a neuropeptide produced
in the hypothalamus and released by the posterior pituitary.
It is frequently given exogenously for its ecbolic effect, and
its usefulness for uterine clearance has been previously doc-
umented.268,277 Exogenous treatment is somewhat empiric,
but consideration should be given to the stage of estrous
 1254 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS

TABLE 19.7 Antibiotic Drugs, Systemic and Intrauterine Doses, and Clinical Considerations for Treatments of Endometritis in the
Marea
Drug Systemic Dose Intrauterine Dose Anticipated Spectrum of Activity Comments
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Amikacin sulfate 10–15 mg/kg, IV, 1–2 g, q 24 h Gram (−) Buffer with bicarbonate for
q 24 h intrauterine use
Ampicillin 29 mg/kg, IV, 1–3 g, q 24 h Gram (+) and Escherichia coli Dilute in high volumes (∼200 mL)
q 12 h to prevent precipitation when
using intrauterine dose
Ceftiofur 2 mg/kg, IV or 1–2 g, q 24 h Gram (+) and (−) Dilute with sterile water only for
sodium IM, q 12–24 h intrauterine use (inactivated in
saline)
Ceftiofur crystal- 6.6 mg/kg, IM, Not approved or Gram (+) and (−) Can be given q 7 days for two
line-free acid two doses 4 studied for more doses and maintain effec-
days apart intrauterine use tive endometrial tissue concen-
trationsb
Enrofloxacin 5–7.5 mg/kg, IV, 50 mL of water- Gram (−) Only compounded formulations
q 24 h; 7.5 mg/ based 2.5% available for PO and intrauterine
kg, PO, q 12 h suspension, use
q 24 hc
Gentamicin 6.6 mg/kg, IV or 1–2 g, q 24 h Gram (+) and (−) Buffer with equal volume
IM, q 24 h bicarbonate solution and dilute
further in sterile water or saline
for intrauterine use
Neomycin 5–15 mg/kg, PO, 4 g, q 24 h Gram (−) Infrequently used
q 24 h
Polymyxin B 5000 U/kg, IV, 100,000 IU, q 24 h Gram (−) Dilute in 1 L fluids when admin-
q 8–12 h istering systemically; dilute in
100–200 mL for intrauterine use
Potassium 20,000–40,000 5 million units, Streptococcus equi subsp. Synergistic with aminoglycosides
penicillin G U/kg, IV, q 6 h q 24 h zooepidemicus when given IV; adverse interac-
tion when administered concur-
rently for intrauterine used
Procaine 20,000–40,000 5 million units, S. equi subsp. zooepi- Possible intraluminal residues for
penicillin G U/kg, IM, q 24 h demicus intrauterine use
q 12 h
Sulfadiazine and 24 mg/kg, Not approved or Gram (+) and Nocardioform Emerging resistance of S. equi
trimethoprim PO, q 12 h available in the species subsp. zooepidemicus
United States
Ticarcillin and 50 mg/kg, IV or 3–6 g, q 12–24 h Gram (+) and (−) Dilute in 60–120 mL sterile water
clavulanic acid IM, q 6–8 h for intrauterine use
  

IM, Intramuscular; IV, intravenous; PO, orally.

aAdapted from LeBlanc MM. The chronically infertile mare. Proc Ann Conv Am Assoc Equine Pract. 2008; 54:391-407.
bFrom Scofield D, Black J, Wittenburg L, et al. Endometrial tissue and blood plasma concentration of ceftiofur and metabolites following intramuscular admin-

istration of ceftiofur crystalline free acid to mares. Equine Vet J. 2014; 46:606-610.
cFrom Schnobrich MR, Pearson LK, Barber BK, et al. Effects of intrauterine infusion of a water-based suspension of enrofloxacin on mare endometrium. J

Equine Vet Sci. 2015; 35:662-667.

dFrom Wallace SM, Chan LY. In vitro interaction of aminoglycosides with beta-lactam penicillins. Antimicrob Agents Chemother. 1985; 28:274-281.

cycle when implementing a dosing strategy. For example, IV
administration of 30 units to estrous mares was shown to
reduce uterine contractions compared with lower doses of 5
to 10 units.278 Interestingly, the density of oxytocin receptors
is highest in late diestrus and decreases during estrus and early
diestrus,279 and the uterine response to oxytocin is inversely
related to progesterone concentrations.280 It thus seems pru-
dent to adjust doses with respect to the stage of the estrous
cycle. Current recommended doses are 10 to 20 units during
estrus and 25 to 40 units after ovulation.220 Routes of admin-
istration include IV, IM, and intrauterine. Oxytocin is not a
“silver bullet,” and its effects can be limited by anatomic (e.g.,
closed cervix, pendulous uterus) and mechanical (e.g., fibro-
sis aberrant contractions) deficits concurrently involving the
reproductive tract. Carbetocin, a synthetic analog, has been
available in countries outside the United States. Its plasma
half-life is over two times that of oxytocin and may be useful
in mares that do not respond to oxytocin.281
Oxytocin is directly responsible for the release of PGF2α
from the endometrium, as evidenced by a spike in its metab-
olite (PGFM) in the serum shortly after oxytocin adminis-
tration.279 Exogenous administration of PGF2α can thus be
used clinically as an ecbolic, and research suggests that the
synthetic analog, cloprostenol, produces the best response
 CHAPTER 19
TABLE 19.8 Intrauterine Therapies and Lavage Fluid Additives
Agent Intrauterine Dose
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NAC, 20% 30 mL in 150–250 mL saline, q 24 h
Antimicrobial peptides 60 mL
(Ceragyn)
Dimethyl sulfoxide (90%) 50 mL in 1 L saline, q 24 h
Hydrogen peroxide (3% USP) 20 mL qs to 60 mL with saline
Kerosene 250–500 mL, once
Lactated Ringer’s solution 1–6 L, q 12–24 h
10% povidone–iodine solution 5–15 mL in 1 L saline, q 24 h
Saline (0.9%) 1–6 L, q 12–24 h
Tricide (EDTA-tris) 250–500 mL, q 24 h
Vinegar (5%) 100 mL in 1 L saline, q 24 h
CDE, Chronic degenerative endometritis; EDTA, ethylenediaminetetraacetic acid; IE, infectious endometritis; NAC, N-acetylcysteine; qs, as much as needed.
among the PGF2α preparations studied.282 The primary differ-
ence between oxytocin and PGF2α is that the former produces
strong and rapid uterine contractions over a relatively short
period (∼0 minutes). The latter produces lower amplitude
contractions over a longer period (4–6 hours). These varying
effects should be considered when implementing treatment. It
is relatively unknown how much oxytocin and how many con-
tractions are needed to obtain the ideal clinical effect. Dosing
of oxytocin usually involves multiple daily dosing, but PGF2α
typically involves a single daily dose. There is some evidence
that cloprostenol can interfere with early luteal development,
but the clinical significance is unknown because fertility is not
compromised in mares treated through the second day after
ovulation.283
Other drugs potentially affecting uterine contractility are
the α2-agonist sedatives and nonsteroidal antiinflammatory
drugs (NSAIDs). Detomidine causes contractions in normal
non-pregnant mares, whereas NSAIDs, because of their inhib-
itory action on inducible prostaglandin release, may inhibit
uterine clearance.
Lavage and Nonantibiotic Therapies
Uterine lavage or irrigation is an important component in the
treatment and management of endometritis. In mares suscep-
tible to PMIE, lavage can be performed before or after breed-
ing. No detrimental effects on pregnancy rates were seen in
mares lavaged with LRS before mating.284 However, it appears
that lavage should be withheld for a minimum of 4 hours after
mating.285 In mares with endometritis secondary to other dis-
ease processes (e.g., retained fetal membranes [RFMs], metri-
tis, pyometra), lavage can be performed multiple times a day to
evacuate septic uterine contents. Isotonic fluids, such as LRS,
are preferred when performing uterine lavage because of the
more physiologic pH, but saline can be substituted if needed.
Additives are frequently combined with lavage fluids.
Examples are listed in Table 19.8. Both betadine and hydro-
gen peroxide have antiseptic properties, whereas dimethyl
sulfoxide (DMSO) and N-acetylcysteine (NAC) are used for
their mucolytic and antiinflammatory activities. Vinegar is
Disorders of the Reproductive Tract 12551255
Indications/Comments
Mucolytic
Potential biofilm disruptor
Mucolytic
100 mL in 1 L Potential biofilm disruptor, antiseptic,
lavage fluids counterirritant
Counterirritant; used for cases of CDE
Used for lavage to assist with uterine
drainage and clearance of debris
Disinfectant
Lavage and diluent fluid
Synergistic effect with aminoglycosides and
clotrimazole, used in cases of chronic IE
and suspect biofilm production
Yeast infections
added to fluids to increase acidity, which is commonly done
for treatment of yeast infections. These treatments are fol-
lowed by regular fluids or fluids without additives. Uterine
lavage should be repeated daily until the effluent is clear. One
common veterinary disinfectant that has been shown to cause
substantial irritation to the uterus and should be avoided is
a 2% chlorhexidine gluconate (CHG) solution.286 Dilution to
0.25% CHG has been shown to be less irritating, but sanitizing
properties were not evaluated.
NAC is a mucolytic agent that is useful when treating cases
of endometritis. Treatment involves diluting a 20% (200 mg/
mL) solution in 150 to 250 mL of saline to achieve a 3.3% solu-
tion and instilling it into the uterus.287 This can be done 24 to
48 hours before or 6 to 24 hours after breeding. Serial uter-
ine lavages are often performed 12 to 24 hours after infusion
and repeated until the efflux is clear. In a clinical study, mares
treated with NAC before breeding had higher fertility rates
than those that were not, and treatment had no adverse effects
on the endometrium as judged by uterine biopsy.288
Kerosene is a clear liquid formed by fractional distillation of
petroleum. Primarily used as a fuel, it can also be used as a sol-
vent for removing grease and tenacious mucilage, as well as a
pesticide for killing lice and bed bugs. Intrauterine infusion of
kerosene in subfertile mares was first reported by Bracher et al.289
They reported relatively high early pregnancy (87.5%) and live
foal (62.5%) rates in subfertile mares treated with kerosene on
the cycle before mating. Despite inducing intense inflammation,
no long-term side effects, such as cervical or uterine adhesions,
were observed in mares treated with kerosene. Kerosene can be
used at any stage of the estrous cycle, including diestrus and up
to 48 hours before breeding. The only adverse effect observed
was mild scalding on the gaskins of a small proportion (<5%)
of mares. Mares who have gone more than 1 year barren, who
have not responded favorably during multiple cycles of other
intrauterine therapies, or who have severe intrauterine fluid
accumulation are candidates for uterine infusion of kerosene.
Treatment is thought to perform a chemical curettage of the
endometrial epithelium, effectively stripping the epithelium of
debris, inspissated material, and microorganisms.290
 1256 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
Recommendations for the volume of kerosene to be infused
varies among theriogenologists. Some use moderate volumes
(e.g., 90 mL), whereas others use much larger volumes (500
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mL). Because of this rather wide variation in volume, some
postulate that contact time with the endometrium may be
just as important as (if not more than) the volume of the
infusate. Unfortunately, this observation is purely subjective,
because no studies exist comparing these variables. Approxi-
mately 12 to 16 hours post infusion, uterine lavage with LRS
is performed. Lavage should be repeated daily until the efflu-
ent is clear. Effluent character can vary from mostly clear
(yet strongly odorous of kerosene) to hemorrhagic with the
consistency of curdled milk. Caution should be taken when
handling and using kerosene because it is flammable, and it
is recommended to turn mares out in the paddock overnight
after infusion. The authors have found kerosene to be a reliable
and successful treatment option in the management of CDE.
Other fluid additives include those targeting potential bio-
film infections. Based on the current understanding of biofilm
infections, treatment should target both the EPS and the bac-
teria within the biofilm community. Purported biofilm dis-
ruptors include the previously mentioned hydrogen peroxide,
DMSO, chelating agents containing tris-EDTA, and Ceragyn
(Purishield Life Sciences, LLC, Walnut Creek, CA 94597),
which is a proprietary and commercially available antimicro-
bial peptide mimic. All of these agents have shown varying
results in vitro for reducing biofilm mass and/or killing organ-
isms within a biofilm.239
Long used as an antiseptic, hydrogen peroxide (H2O2) has
shown a broad spectrum of activity against various microbes,
including bacteria, virus, fungi, yeast, and spores. In mares, the
recommended dose is 20 mL of a 3% H2O2 solution diluted to
60 mL in LRS.287 An in vitro study demonstrated that 1% H2O2
was effective against most pathogens in both their planktonic
and biofilm state, except for P. aeruginosa, which was capable
of inactivating H2O2.239 Bacterial resistance to H2O2 has been
documented in human cases, but research is lacking in horses.
Buffered chelator solutions have proven useful in cases of
refractory bacterial and fungal infections.291 Tris-EDTA has
been shown to potentiate the effects of certain antimicrobial
agents, presumably by altering cell-wall permeability.292 Ami-
noglycosides are one such example, and the two can be mixed
together. β-lactam antimicrobials may precipitate in the pres-
ence of Tricide, which is thought to inactivate this class of anti-
biotics. In vitro studies evaluating the use of a similar buffered
chelator solution, tris-EDTA, showed it to be highly effective
on free-floating bacteria.239 However, tris-EDTA was incon-
sistent in disrupting biofilm production from clinical isolates
of P. aeruginosa239; thus it is by no means a silver bullet for
suspected biofilm infections.
Naturally occurring antimicrobial peptides (AMPs) are pro-
duced and used by neutrophils to degrade bacteria. Ceragyn
(Purishield Life Sciences, LLC, Walnut Creek, CA) is a com-
mercially available wound-healing medical device that is mar-
keted as an AMP mimic. Anecdotally, AMPs need only come
in contact with the cell membrane to exert a bactericidal effect.
Other attributes of AMPs include a broad spectrum of activity,
less risk of developing resistance to microbial defense mecha-
nisms, and direct activity against biofilm. Ceragyn is also being
distributed as a uterine lavage device labeled for use either 4
hours before or 6 to 48 hours after breeding. Preliminary stud-
ies evaluating its activity against certain biofilm-producing
bacteria have been promising. Ferris239 showed that Ceragyn
was effective in degrading biofilm biomass produced in vitro
by E. coli, K. pneumoniae, P. aeruginosa, and β-strep, and it was
also capable of killing β-strep within a biofilm. More research
is necessary on this and other products to further evaluate their
clinical efficacy. One thing for certain is that none appears to
be a panacea for treating chronically dirty mares.
Adjunctive Therapies
Several other therapies exist for the treatment of endometritis.
Most can be used quite effectively in conjunction with other
therapies. As will be discussed next, some of these therapies
are thought to assist with uterine drainage, whereas others act
on the immune system to modulate the response to breeding.
Acupuncture
Acupuncture has its origin in Eastern medicine and has
been used for a wide range of conditions affecting the mare’s
reproductive tract. For endometritis, acupuncture is thought
to induce uterine contractions to help with the expulsion of
intraluminal fluid. A retrospective study involving 44 brood-
mares showed a reduction in postmating fluid and improved
pregnancy rates in mares with a history of susceptibility.293
Controlled studies are necessary to compare this modality
to more traditional treatments such as oxytocin and uterine
lavage. Moreover, current protocols and methods used (e.g.,
“wet versus dry” needling, electrostimulation) are subject to
individual practitioner preferences, and measuring response
can be confounded by a lack of control subjects. As stated in
a review on the use of acupuncture in equine reproduction:
“Although acupuncture physiology and efficacy have yet to be
thoroughly defined in a traditional Western medicine sense,
current research demonstrates a case for continued use as well
as further investigation.”294
Immunomodulators
Influencing either systemic or local immune defense systems
has been investigated in broodmares. Corticosteroids have
been used to modulate the immune response of susceptible
mares, with the primary benefits thought to be reduction in
neutrophil margination into the uterus and countering lym-
phangiectasia. The clinical benefit of dexamethasone was
described in a report by Bucca et al.267 in which they reported
improved pregnancy rates in susceptible mares treated with 50
mg (IM) of dexamethasone before breeding. Prednisolone (0.1
mg/kg, PO, b.i.d.) beginning 2 days before breeding has also
been used to manage acute inflammation when breeding with
frozen semen.266 Attention should be paid to patient selection
and length of dosing schedule because of potential untoward
side effects of steroid administration in equids.
Modulation of local defense mechanisms has been explored
as a means to improve fertility rates in susceptible mares. More
specifically, improving the phagocytic activity of mononuclear
cells and reducing the production of proinflammatory cyto-
kines are possible benefits of altering uterine immune systems.
Mares treated with a commercially available Mycobacterium
cell-wall extract showed a quicker reduction in inflammation
compared with controls.295 A similar product containing Pro-
pionibacterium acnes was shown to increase pregnancy and
live foal rates in barren mares treated with this product when
combined with conventional management strategies.296 Use
of these agents for endometritis thus appears to warrant more
consideration in the management of endometritis, especially
PMIE.
 CHAPTER 19 Disorders of the Reproductive Tract 12571257

Although commonly used to treat orthopedic conditions, freezing, compared with control stallions.301 Although not
regenerative therapies have been explored for their efficacy in yet fully evaluated, the use of OM3FAs may help decrease
the management of endometritis. Foaling mares treated with inflammation and improve the chance of maintaining a viable
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a combination intrauterine infusion of autologous plasma and pregnancy.

antibiotics had higher pregnancy rates than control mares.297
The purported benefit was thought to be improved opsoniza-
tion of bacteria, but this treatment has not garnered wide-scale
use. More recently, the use of platelet-rich plasma (PRP) was
explored. Preliminary studies showed intrauterine infusion
of PRP caused downregulation of inflammatory cytokines
and improved pregnancy rates in susceptible mares.298,299
Researchers at Colorado State University evaluated the use of
autologous conditioned serum (ACS) and mesenchymal allo-
geneic stem cells (MSCs) in reproductively normal mares.238
Mares treated with ACS 24 hours before a dead-sperm chal-
lenge had significantly lower neutrophil counts 6 and 24
hours after this challenge compared with control mares. Those
treated with MSCs had significantly lower neutrophil counts 6
hours after sperm challenge relative to controls. More research
and clinical studies are necessary to explore further the effi-
cacy and indications for these treatments. Given the current
costs, resources necessary, and foresight required to imple-
ment these therapies, they currently seem more of a novel or
stopgap therapy in cases in which conventional therapies have
repeatedly failed.
Exercise
The authors are advocates of providing breeding animals with
as much exercise as possible. Farm and ranch management,
climate, and overall health of the mare are factors dictating the
type and amount of exercise. Farm practices in central Ken-
tucky are such that horses are turned out in large multiacre
fields with other broodmares for significant portions of the
day. Turnout during inclement weather is at the discretion of
the farm, but most horses are much more resilient to adverse
environmental conditions than thought. Potential benefits of
exercise include toning of the hindquarters to improve peri-
neal conformation and improved uterine clearance associ-
ated with locomotion. In addition, exercise and socialization
engage horses both mentally and physically. In humans, physi-
cal fitness has proven health benefits in staving off the ill effects
of advancing age, which is the most significant factor affecting
reproductive efficiency in broodmares.226
Other supplements include antioxidants and hormone
mimics. Antioxidant therapy may be beneficial in staving
off sperm membrane damage from free radicals in the semi-
nal plasma or uterus. Hormone-mimicking agents are pur-
ported to enhance breeding performance by improving libido,
increasing sexual arousal, or removing inhibitions. Peer-
reviewed and independent studies supporting the use of many
of these products are lacking, so further research is necessary
to determine the precise value of these products. Furthermore,
caution should be exercised in using or mixing supplements
because of potential adverse interactions.
Y FUNGAL ENDOMETRITIS
Endometritis secondary to colonization of the uterus with
fungi is an uncommon (1%–5% of cases) but highly frustrating
clinical condition in mares.302,303 Fungal pathogens most com-
monly identified from uterine cultures are Candida spp. and
Aspergillus spp. However, other organisms have been reported.
For example, Cladophialophora bantiana was identified in one
case report of a 15-year-old Standardbred mare that was sub-
sequently euthanized because of the zoonotic potential of the
pathogen.304 Skin and feces are the most common sources of
fungi, but fungal elements have also been found in the urethral
fossa and penis of stallions, leading to potential (although
unlikely) venereal transmission.270,305 Factors predisposing
mares to fungal endometritis include prolonged intrauterine
antibiotic therapy, immunosuppressive therapy, endocrine
disease, or foaling trauma.270 The diagnosis of fungal endo-
metritis is made based on a combination of aerobic culture
and cytology, as described in a previous section. The pres-
ence of budding yeasts (Fig. 19.23) and/or branching hyphae

Supplements
A number of nutritional supplements are available to be fed to
horses, some of which have either documented or anecdotal
evidence supporting their use. Supplementation with omega-3
fatty acids (OM3FAs) has become popular, and a small body of
research supports their use. Supplementing the diets of mares
and stallions with OM3FAs has improved certain measures of
reproductive performance. For example, mares fed a commer-
cially available supplement containing docosahexaenoic acid
(DHA)/OM3FA (Releira, Arenus, Fort Collins, CO 80524) was
associated with a reduction in endometrial cytokine expres-
sion in mares bred with frozen semen as compared to con-
trol mares.300 Supplementation with OM3FAs has also been
postulated to improve follicular and luteal health to support a
healthy pregnancy, but these assertions are in need of further
study. With respect to stallions, those fed a DHA-enriched
nutraceutical showed improved seminal quality judged by FIG. 19.23 Uterine cytology demonstrating the presence of budding
higher progressive motility after 24 and 48 hours of test cool- yeast organisms using a modified Wright-Giemsa stain. (Courtesy C.F.
ing as well as significantly higher postthaw motility following Scoggin).
 1258 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
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FIG. 19.24 Endometrial cytology from a mare demonstrating numer­
ous and prolific branching fungal hyphae using a modified Wright-Giemsa
stain. (Courtesy C.F. Scoggin).
(Fig. 19.24) is diagnostic for fungal endometritis. Endome-
trial biopsies have also been used to diagnose and/or confirm
more invasive forms of fungal endometritis when cytology is
inconclusive. Other methods, such as quantitative PCR, have
been developed to detect and identify fungal DNA in equine
endometrial samples. These can be used in conjunction with
cytologic and/or histologic samples to confirm a diagnosis and
further quantify the organism(s) present.306
Treatment for fungal endometritis has historically been
based on individual case studies using empiric dosing sched-
ules. Myriad treatments are available, but none of them appear
to be particularly effective or carry a broad spectrum of activ-
ity. Various antifungal agents and their dosing regimens are
provided in Table 19.9. Antifungal drugs are typically divided
into two main categories: polyenes and imidazoles. Polyene
antibiotics include amphotericin B, natamycin, and nystatin.
The imidazole drugs include clotrimazole, ketoconazole, and
miconazole.307 Triazoles (fluconazole and itraconazole) are
another group of synthetic antifungals used to treat yeast
infections. Based on a retrospective study by Beltaire et al.,308
polyenes are the best first choice for treatment of yeast infec-
tions (100% in vitro susceptibility), but care must be taken
when using these antifungals because of their potential cyto-
toxicity. Consequently, these drugs are typically used locally
as intrauterine infusions. Polyenes were also effective against
most molds (69%–100%), whereas the imidazole drugs were
only marginally effective (38%–46%) against molds and sep-
tated hyphae. All mold isolates were resistant to fluconazole.
Reports such as these are beneficial for improving the effi-
ciency and, potentially, the success of treatment. Moreover,
although fungal endometritis is an uncommon problem, it is
an area of research that could benefit from prospective studies
that correlate clinical outcomes with fungal culture and treat-
ment approach.
Another treatment for fungal infections often used in con-
junction with antifungal agent(s) is uterine lavage with white
wine vinegar. The acetic acid component can decrease the pH
of the uterine environment, inhibiting growth of planktonic
fungi. Typically used in an in-and-out fashion, regular fluids
(e.g., LRS) are used for irrigation until the effluent is clear. The
chitin inhibitor, lufenuron, has also been used to treat fungal
infections.309 Instillation of 540 mg of this drug diluted in 60
mL of physiologic saline has been used to resolve coloniza-
tion of the uterus by both Candida spp. and Aspergillus spp.
Despite these promising results, however, this treatment failed
to develop steam as a viable treatment. Currently, treatment
of fungal infections is deemed difficult, and resolution usu-
ally involves both a lengthy treatment schedule and tincture
of time.
Y CONCLUSION
Endometritis is an important and ongoing issue in brood-
mare management. Numerous causes of endometritis have
been identified, and the disease may manifest itself in many
ways. No matter how innovative or novel a treatment is, it
cannot replace the importance of first performing a thorough
physical and reproductive examination. Careful evaluation of
history, stallion fertility, perineal conformation, and repro-
ductive organs will help identify problem areas that may need
to be addressed before endometrial treatment. Goals of man-
agement include assisting with uterine drainage/clearance,
addressing anatomic defects, implementing appropriate anti-
microbial therapy, modulating the inflammatory response,
and using other means to create a hospitable environment for
sperm transport and a developing conceptus.
Hormonal Manipulation of the Mare
Carleigh E. Fedorka, Maria R. Schnobrich
This section will describe how hormonally based therapeutics
are used to optimize reproductive efficiency in the mare. The
background physiology and underlying targeted response or
goal of each treatment will be described. The reader is referred
to previous sections in this chapter for a review of the natu-
ral hormonal targets and physiology of the nonpregnant and
pregnant mare.
Y VERNAL TRANSITION
Mares are seasonally polyestrous breeders, and during winter
or shortened periods of daylight increased melatonin secre-
tion from the pineal gland inhibits the release of GnRH.
Because of this, the majority of mares experience a period of
reproductive senescence when daylight is abbreviated. As day
length increases in the early spring in the Northern Hemi-
sphere, the suppression of the HPG axis is downregulated. The
mare then enters the “vernal transition,” which is character-
ized by a marked increase in FSH with low levels of luteinizing
hormone (LH) and, therefore, a lack of ovulation as described
previously.
Many hormonal regimens have targeted this transitional
phase and are aimed at shortening the anovulatory period and
hastening the onset of normal cyclicity. Increasing the exposure
to light (to 14.5 hours a day, equivalent to a 100-W bulb in a
stall, or “enough light to read a newspaper”) beginning approx-
imately 60 days before the start of the targeted first ovulation
has proven to be the most widely used and effective means of
shortening the time to the first ovulation of the season.310 This
 CHAPTER 19
TABLE 19.9 Antimycotic Drugs, Doses, and Clinical Considerations for Treatment of Endometritis in the Mare
Drugs Systemic Dose Intrauterine Dose
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Amphotericin B 0.3–0.9 mg/kg, IV, 100–200 mg, q 24 h
q 24–48 h
Clotrimazole Not reported 500–700 mg, q 24 h
Fluconazole Loading dose of 14 mg/ 100 mg
kg then 5 mg/kg, PO
or IV, q 24 h
Itraconazole 5 mg/kg, PO or IV, Not reported
q 12–24 h
Ketoconazole 20 mg/kg (in 0.2 N HCl), Not reported
NGT, q 12 h
Lufenuron Not reported 540 mg qs 60 mL
with saline
Miconazole Not reported 500–700 mg, q 24 h
Nystatin Not reported 0.5–2.5 million units,
q 24 h
HCl, Hydrochloric acid; IV, intravenous; NGT, nasogastric tube; PO, orally; qs, as much as needed.
is achieved through the use of outdoor paddock lighting, the
stabling of horses for increased periods under lights, or the
addition of lighted masks.311 Along with the use of lights to
effect the photoperiod, hormonal manipulations are often used
in conjunction to hasten the onset of normal cyclicity.
Dopamine is secreted in synapses between dopaminer-
gic neurons in the median eminence of the hypothalamus
and hypothalamic GnRH neurons. Research has shown that
inhibition of dopamine (D2 dopamine receptors) increases
LH secretion, although the exact mechanism is unclear. It is
believed to act by removing the inhibition on PRL secretion
and possibly through the reduction on the negative feedback of
estradiol on GnRH.312 Many dopamine antagonists including
sulpiride, domperidone, and perphenazine have been tested,
but inconsistencies in dosage, treatment onset, and duration
of studies have caused high variability in the outcomes of these
studies, making comparisons difficult.
Domperidone significantly hastens the time to first ovu-
lation (51 days vs. 129 days for controls).313 When begun on
January 15, and without the addition of a lighting program,
treatment with domperidone results in increased LH, estra-
diol, and PRL concentrations, and six of eight treated mares
resumed normal cyclicity after treatment. Perphenazine,
another dopamine antagonist, is also able to shorten the
anovulatory period by approximately 30 days when adminis-
tered at a dosage of 0.08 mg/kg daily when used without the
addition of a lighting program.314
Sulpiride is another commonly used dopamine antagonist.
In a study by Mari et al. its effectiveness was compared with
that of domperidone.315 Mares were treated with 1 mg/kg sul-
piride (Championyl), 1 mg/kg domperidone (Motilium), or
a control daily for 25 days without the addition of a lighting
program. Sulpiride significantly decreases the length of time
to the first ovulation (36.9 days) compared with both dom-
peridone (74.7 days) and control (81.4 days), and it hastens the
establishment of pregnancy by an average of 20 days.315 In a
second study, mares were treated with sulpiride once the pres-
ence of a 25-mm follicle was noted. Daily treatment of 1 mg/kg
sulpiride results in a hastened follicular development.316
Disorders of the Reproductive Tract 12591259
Anticipated Spectrum of Activity Comments
Broad spectrum Dilute to 1 mg/mL in 5%
dextrose and administer
over 1–2 h
Broad spectrum —
Yeast —
Yeast, Aspergillus spp., and —
dimorphic fungi
Candida spp. Must be given via NGT to
avoid irritation from acid
Candida spp. Chitin inhibitor
Broad spectrum —
Yeast Dilute in sterile water to
avoid precipitation
Another strategy for manipulating the vernal transition
is through the supplemental use of progestogens, in particu-
lar altrenogest. The mechanism of action is believed to be
caused by negative feedback on the hypothalamic-pituitary
axis, which when removed, results in an increase in LH. Daily
administration of 27 mg of altrenogest (Regu-Mate) when a
20-mm follicle is present significantly decreases the length of
time to ovulation compared with controls.317
Additionally, first ovulation can be hastened by use of
GnRH analogs. Equine follicle-stimulating hormone (eFSH)
at a dose of 12.5 mg IM (Bioniche) twice daily has been shown
to hasten the time to first ovulation when administered to
transitional mares once the presence of a 25-mm follicle is
noted.318 In addition, recombinant eFSH (reFSH) has been
developed, and when it is administered at a dosage of 0.65
mg twice daily, it is able to stimulate follicular development
in anestrous mares under lights. Unfortunately, these mares
did return to anestrus after treatment and ovulated naturally
at a similar time as control mares.319 It can be difficult to reli-
ably obtain eFSH; therefore this protocol, while effective, is not
frequently used. Another protocol using a GnRH agonist con-
sists of administration of 25 μg of buserelin twice daily (SQ)
once the mare has developed a 20-mm follicle until ovulation
occurs.320 Ovulation induction is achieved in most GnRH
analog protocols with the administration of human chorionic
gonadotropin (hCG) at varying dosages of 1500 to 3000 IU,
either IV or IM, once a follicle has reached the size of 35 mm
or greater.321
Y SYNCHRONIZING THE
ESTROUS CYCLE
To optimize breeding efficiency, the ability to predict estrus
and ovulation becomes an important tool to successful repro-
ductive management. Although mares show variability in
their response to hormonal treatment, the concept of fixed-
timed insemination, or “appointment breeding,” has been suc-
cessful in equine reproduction. Common reasons for estrous
 1260 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
synchronization include synchronization of a group of mares
(e.g., in an embryo transfer program), manipulation of ovula-
tion timing to best fit a popular stallion, limited show schedule
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for breeding, and strategic management of insemination with
shipped or frozen semen.
To manipulate the estrous cycle of the mare with some
precision, one must understand the basic endocrine events
of the normal 21- to 22-day cycle of the mare as previously
reviewed.4 The day of ovulation is considered to be day 0 and
is preceded by a period of estrus of variable length (5–7 days).
Most hormone regimens used to synchronize estrus are
aimed at manipulating and shortening the luteal phase (dies-
trus) of the cycle. Perhaps the simplest method of synchro-
nizing the cycle of a mare is through the use of synthetic
preparations of PGF2α, which effectively and reliably shorten
diestrus through inducing luteolysis and removal of the source
of progesterone production. There was previously a belief that
one had to wait until day 5 post ovulation to reliably induce
luteolysis with a single dose of PGF2α.322,323 Research has dem-
onstrated that repeated doses of PGF2α administered after
ovulation prevented CL formation, and breeding on the subse-
quent estrus was not associated with a decrease in pregnancy
rates.324 The size of the follicle at the time of prostaglandin
administration often dictates the duration to ovulation, with
larger follicles ovulating sooner.
It is critical to evaluate the follicles present at the time of
PGF2α administration for two reasons: (1) to note if the mare
has a large follicle, and therefore reexamination and breed-
ing can be scheduled appropriately, and (2) because inducing
estrus and breeding on a large diestral follicle is not optimal
and waiting until the follicle regresses may be more ideal.
Mares that were administered prostaglandin when follicles
were larger than 30 mm had an approximately 20% lower per
cycle pregnancy rate than mares bred on a natural estrus.325
It has also been demonstrated that treatment of mares with
a PGF2α analog on day 0 (ovulation) or day 1 has a negative
effect on the developing CL. Not only are the size and echo-
genicity of the CL reduced, but also a transient and significant
suppression in progesterone levels occurs. Most important,
pregnancy rates may be lower in treated mares.326-328 Treat-
ment with PGF2α analogs increases the risk of AHFs, and
this risk should be taken into consideration, most critically in
mares that may be predisposed to developing AHF.329
A number of PGF2α preparations have been used success-
fully for luteolysis in the mare. Side effects associated with
PGF2α administration include sweating, anxiety, diarrhea,
and signs of colic. The severity of the side effects depends on
the dose and preparation of PGF2α. A two-dose regimen at a
much lower dose (0.5 mg PGF2α) is equally effective in induc-
ing luteolysis as a higher single dose (50 mg PGF2α) but devoid
of adverse effects.330 Similarly, a single dose of 25-μg clopros-
tenol (Estrumate; Bayer Corp., Shawnee, KS), that is one tenth
of the previously recommended dose, is effective in inducing
luteolysis and does not cause adverse side effects.331 Generally
most practitioners use 10 mg of dinoprost (Lutalyse) or 250 μg
of cloprostenol 5 days post ovulation. Cloprostenol is associ-
ated with fewer side effects and has also been shown to be as
effective at inducing luteolysis as dinoprost, although cost may
factor into the decision of which drug is used.
Treatment with progestogens with or without estrogens
represents one of the oldest and most reliable means of syn-
chronizing estrus in the mare, especially when coupled
with appropriate light exposure and PGF2α administration.
Exogenous administration of progesterone simulates the
diestrus period of the estrous cycle. Repositol progesterone,
progesterone in oil (Sigma Chemical Co., St. Louis, MO), or
oral progestin compounds (altrenogest [Regu-Mate], Intervet
Inc., Millsboro, DE) are effective in suppressing estrus but not
necessarily effective for inhibiting follicular development or
ovulation.
When synchronizing mares, one protocol that is used com-
monly is to administer progesterone for a minimum of 10 days
in cycling mares and 14 days in transitional mares. On the last
day of progesterone treatment, a PGF2α injection is adminis-
tered to induce luteolysis of any remaining CL. As in treatment
with prostaglandins alone, the mare should be evaluated at the
time of prostaglandin administration because follicle growth
may still occur with progestogen administration. Scheduling
for breeding and predicting ovulation can be made based on
the follicle size at the time of induced luteolysis. Generally it
is believed that most mares come into heat 3 to 5 days after
the last treatment of progesterone and ovulate an average of
7 days after treatment, but this depends on the size of the fol-
licles present on the ovary at the time of luteolysis.
Addition of estradiol to a synchronization protocol inhibits
follicular growth and allows better synchrony of ovarian struc-
tures at the time of luteolysis. Often referred to as “P and E” or
“programming,” this is done by administering daily injections
(IM) of 10 mg of estradiol-17β and 150 mg of progesterone
once the presence of a 20-mm follicle is noted. On the tenth
day, the mare is administered PGF2α and is evaluated at this
time with transrectal ultrasound. Breeding is recommended
once a dominant follicle is greater than 35 mm, and this tends
to coincide with day 19 from the start of treatment. This pro-
tocol is considered superior by some because the addition of
estradiol inhibits follicular activity; thus, at the time of pros-
taglandin administration all mares on this protocol should
have minimal follicular activity and ovulate in a similar time
period.
The oral progestogen preparation altrenogest is perhaps
still the most popular progestin compound for use in mares.
Altrenogest is easy to administer, not painful, and has few
adverse effects. Although most commonly used for estrus sup-
pression, it does not inhibit follicular development; therefore,
it is rarely used when attempting to synchronize a mare’s fol-
licular growth. Injectable preparations of repositol altreno-
gest may be effective in suppressing estrus from a behavior
standpoint, but they have not been thoroughly investigated for
their ability to effectively synchronize follicular growth and
ovulation.
For several reasons, all progestogen preparations should
be used with caution in mares that are susceptible to delayed
uterine clearance or uterine infections. Progesterone increases
the tone of the cervix, and its use may inhibit the physical
clearance of fluid. Progesterone has also been associated with
lower immunoglobulin levels (especially IgG) in the uterus.332
Thus the combination of adverse effects of most progestogens
can lead to delayed uterine clearance, endometritis, pyometra,
and other undesirable reproductive conditions.
Y SUPPRESSION OF ESTRUS
Although most hormonal regimens act to hasten the interval
to estrus and ovulation, there are commonly requested behav-
ioral and managerial reasons to suppress estrus. Altrenogest
was designed to prevent show mares from exhibiting unwanted
 CHAPTER 19
estrus during performance, and it has proved to be effective in
this regard, suppressing signs of estrus in 95% of mares that
were given a daily dose of 0.044 mg/kg for 3 days. In an attempt
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to find a more economic and less time-consuming means of
suppressing estrus in mares, progestin-estradiol implants
(Synovex; Syntex Animal Health, Des Moines, IA) licensed for
food animals have been investigated in mares. Although some
mare owners report an improvement in the behavior of the
mare, scientific reports have been less supportive of their use.
McCue et al. found that mares treated with these implants did
not show suppression of estrous behavior and cyclicity, even at
20 times the usual dose.333 Vanderwall et al. have examined the
effect of oxytocin administration during diestrus on prolong-
ing time to luteolysis.334 Mares that received oxytocin (60 IU
twice daily IM) on days 7 through 14 after ovulation demon-
strated prolonged luteal function up to 30 days after ovulation,
suggesting that oxytocin administration may offer a means of
long-term suppression of estrus. Medroxyprogesterone has
also been suggested anecdotally to suppress estrus, but this has
not been substantiated by any research. It was found to have
no suppressive effects on follicular activity, although anecdot-
ally many trainers claim benefits.335
Immunization against GnRH is another effective means
of suppression of follicular development in the mare. When
considering this treatment, it should be noted that a subset
of mares may show estrus or sexual receptivity despite the
absence of follicular activity. Mares vaccinated twice, 4 weeks
apart, with a GnRH vaccine (Equity; Pfizer Animal Health,
Sydney, Australia) did not return to follicular estrus during
that breeding season but returned to cyclicity the next year.
Foaling rates were not significantly different from control
mares.336 The vaccine is not commercially available world-
wide, and there are reports of long-term infertility following
vaccination.337 Another form of immunization as a means
for inhibiting fertile estrus is through immunocontraception.
Joone et al. demonstrated that vaccinating pony mares with
porcine zone pellucida (pZP) causes an extended anestrus
in 86% (six out of seven) of mares and inhibited pregnancy
in all vaccinated animals.338 In addition to its suppression of
follicular development, it was determined that this treatment
was reversible, because all mares returned to normal cyclicity
within 10 months post treatment. Unfortunately, the pZP vac-
cine is not available commercially, and these results should be
critically reviewed due to small study size.
Another option for suppression of estrus is the BioRelease
formulated progesterone or altrenogest (BET Pharm, Lex-
ington, KY). These injectable drugs have been effective for
estrus suppression using either a vehicle with a delayed release
of hormone or microparticle formulation (used in absorb-
able sutures). A study by Storer et al. showed that altrenogest
suspended in either the sustained-release vehicle at a dosage
of 225 mg or 500 mg altrenogest suspended in the lactide-
glycolide microparticle significantly increases the interovula-
tory interval (3.9 days from Lutalyse to ovulation compared
with 33.5 days when the microparticle formulation was
administered).339
Theoretically, if the LH surge has not yet occurred, then oral
progestogen treatment should inhibit LH release and delay
ovulation. Altrenogest at label dose or double the label dose
is effective in delaying ovulation compared with control mares
if an ovulation induction agent has not been administered.340
Intraluminal fluid retention, possibly caused by decreased
uterine contractility, has been observed in some treated mares.
Disorders of the Reproductive Tract 12611261
Delaying the interval to first ovulation of postfoaling
mares results in higher pregnancy rates for the first heat cycle.
Although some breed on this “foal heat,” it has been consis-
tently demonstrated that delaying breeding until the second
estrus, or “30-day heat,” post foaling is associated with higher
pregnancy rates and decreased pregnancy loss.39 Breeding on
foal heat or before 10 days post foaling is associated with an
increase in pregnancy loss, which is likely because of a more
hostile uterine environment, though this may be breed depen-
dent.39,341,342 To optimize the maintenance of those early preg-
nancies yet still increase the reproductive efficiency of the
mare by breeding her back as soon as possible, delay of the
first postpartum interval to ovulation has been attempted.
Due to some of the adverse effects of progestogen adminis-
tration this can be accomplished by delaying administration
of an ovulation-inducing agent. The combination of 150 mg
of progesterone and 10 mg of estradiol-17β (E2-17β; Sigma)
has been suggested to prolong ovulation until at least day 10
post foaling.343 Most experienced practitioners will evaluate
the mare critically post foaling to determine whether a foal
heat breeding is appropriate (additional time needed for invo-
lution, breed practice, availability of stud, pregnancy to carry,
or embryo transfer), and this protocol is rarely used.
Y INDUCING OVULATION
Induction of ovulation is useful for assuring timely ovulation
relative to insemination, to synchronize mares, and to shorten
estrus length. Limitations of semen availability and longevity
include stallions that are available only one day for live cover,
semen being limited to a strict shipment schedule for cooled
shipped semen, and the small time window of semen viabil-
ity when using a single dose of frozen semen. A number of
ovulation-inducing agents have been investigated and are used
in practice. The most effective agents possess LH activity with
varying degrees of FSH activity. The hCG (Chorulon; Intervet,
Millsboro, DE), with its potent LH-like activity, is currently the
least expensive and perhaps the most popular agent used for
the induction of ovulation. Given IM, IV, or subcutaneously,
hCG reliably induces ovulation within 48 hours in mares with
a 35-mm or larger follicle, and it is effective at doses ranging
between 1000 and 5000 IU.
Use of hCG in the mare has some limitations. First, with its
repeated use, antibody development may occur.344,345 Second,
mare owners often complain about the apparent pain associ-
ated with administration of some hCG products, although this
is a rare occurrence. Finally, the reliability of hCG in its abil-
ity to hasten the interval to ovulation, especially in the older
or compromised mare, has been questioned. Regardless of its
potential disadvantages, hCG remains a popular, inexpensive,
and effective means of inducing ovulation in most mares.
Synthetic GnRH analogs also have proven to be effective
in inducing ovulation because they cause endogenous release
of LH, prompting ovulation.346 Examples of synthetic GnRH
analogs are deslorelin acetate (Ovuplant; Fort Dodge, Can-
ada), buserelin (Intervet; Millsboro, DE), and Cystorelin (BET
Pharm, Lexington, KY).327-348 The use of Ovuplant, when left
in place, has been associated with delayed return to estrus and
in some cases may inhibit follicular activity for prolonged peri-
ods (anecdotally up to 3 months), but removal of the implant
a few days after insertion can ameliorate this delay. Injectable
deslorelin is available through compounding companies in the
United States. One option that is approved in the United States
 1262 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
by the Food and Drug Administration is the injectable Sucro-
Mate, which contains 1.8 mg/mL deslorelin acetate. Sucro-
Mate has been shown to effectively induce ovulation within 48
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hours when 1 mL is injected IM once the mare has developed
a follicle larger than 30 mm. In a large clinical study done by
Ferris et al., a higher number of mares ovulated when treated
with SucroMate compared with hCG, and there was no differ-
ence in the interval of time between injection and ovulation
for either treatment.349 The general impression of practitioners
is that the GnRH analogs are more reliable in inducing ovu-
lation, especially in mares that are prone to ovulation failure
(e.g., older mares, mares in vernal transition, mares concomi-
tantly treated with prostaglandin-inhibiting agents such as
many antiinflammatory drugs).
Ovulation-induction agents are reliable and effective only
if given at the appropriate time during estrus. If endometrial
edema and a large dominant softening follicle (>35 mm in
diameter) are present, then hCG, deslorelin acetate, and buse-
relin are expected to induce ovulation in an average of 36, 41
to 48 hours,344 and 24 to 48348 hours, respectively, after admin-
istration. Samper reported that 98% of mares with maximal
endometrial edema given hCG or deslorelin consistently ovu-
lated within 48 hours of administration.350 Most remarkably,
most mares to which Ovuplant had been administered at the
proper time ovulate 36 to 40 hours later, facilitating timely
ovulation relative to a scheduled breeding.351
Y SUPEROVULATION
In an effort to increase the number of offspring produced in
the lifetime of an animal or in any given season, research-
ers have investigated numerous means of superovulating to
enhance the number of oocytes available for fertilization.
Overall, attempts at reliable superovulation in mares have not
been as successful as those in the food animal industry, and
increasing the number of ovulations and the gain regarding
embryos recovered have been minimal. Unlike the swine and
bovine models, the administration of porcine FSH prepara-
tions is ineffective in mares.352 Stimulation of endogenous FSH
secretion by indirect and direct immunization against inhibin
has not resulted in a superovulatory response in mares.353
The administration of equine pituitary extract preparations
in research trials increases the number of embryos recovered
from 0.5 per cycle to 2.2 per cycle but with high variability
among mares.354,355
Promising results have been achieved with the use of
eFSH (Box 19.1). Treatment of cycling mares with eFSH in
early diestrus (12.5 mg, administered twice daily) increased
the pregnancy rate compared with untreated control mares
(1.8 vs. 0.6, respectively).356 In another study, in which
Welsh et al. incorporated a “coast” period into the previously
described experimental design, the ovulation and embryo
recovery rate were 3.8 ± 1.2 ovulations and 1.7 ± 1.4 embryos,
respectively.357
Because of the inability to obtain eFSH on the commer-
cial market, investigators began examining recombinant
proteins. The combination of recombinant LH (reLH) and
reFSH proved efficient at stimulating numerous ovulations.358
Although the protocol is intensive, it appears to be the most
efficient in stimulating numerous ovulations. Treatment com-
mences when a 22- to 25-mm follicle is noted, with IM injec-
tions occurring twice daily (1.3 mg reLH/0.65 mg reFSH).
Luteal regression is stimulated by PGF2α administration on
BOX 19.1  
Recommended Protocol for Superovulation in
Mares Using Equine Follicle-Stimulating Hormone
1. Determine the day of ovulation.
2. Monitor follicular development in early diestrus.
3. Begin eFSH therapy (12.5 mg IM twice daily) when the
largest follicle is 22 to 25 mm in diameter.
4. Administer cloprostenol (259 μg IM) on the second day
of eFSH therapy.
5. Discontinue eFSH treatment when follicle(s) are greater
than 32 to 35 mm in diameter.
6. Administer hCG (2500 IU) to induce ovulation.
7. Breed or inseminate according to standard procedure.
eFSH, Equine follicle-stimulating hormone; hCG, human chorionic gonado-
tropin; IM, intramuscular.
Adapted from McCue PM, LeBlanc MM, Squires EL. eFSH in clinical equine
practice. Theriogenology. 2007; 68:429-433.
the second day of reFSH treatment. Three days after the onset
of treatment, reFSH dosage was reduced to once daily injec-
tions until a follicle of greater than 29 mm was present. This
was followed by 1.3 mg reLH being administered three times
daily until the majority of the follicles reached 35 to 38 mm,
at which time hCG was administered to induce ovulation.
Compared with only reFSH treatment, this dual treatment
of reFSH/reLH significantly increased the number of ovula-
tions and number of embryos retrieved but did not increase
the number of anovulatory follicles observed.358 The incidence
of anovulatory follicles has been a concern in the majority of
other superovulation protocols. Unfortunately, neither of the
recombinant proteins is available commercially.
Y CERVICAL DILATION
One of the more challenging conditions encountered when
breeding mares is failure of the cervix to relax during estrus.
Although not objectively studied, this condition is more com-
mon in older maiden mares and certain breeds. However, even
normal maiden mares may not have the same degree of cervical
relaxation during estrus that is typical of multiparous mares.
This condition is also seen in mares with cervical trauma,
adhesions, and fibrosis, which prevent normal relaxation. On
transrectal palpation, the cervix may feel toned instead of soft
in estrus, and transrectal ultrasound of the cervix may show
increased echogenicity of the cervix, which can be evidence of
fibrosis. Often it is not clear until the periovulatory period that
this pathology exists, and it frequently results in fluid accumu-
lation and increased incidence of PMIE.
Although this condition does not prevent breeding, it can
prevent dilation of the cervix by the penis of the stallion in
natural cover and the normal evacuation of fluid in the hours
after breeding, setting the stage for delayed uterine clearance
and persistent endometritis. A synthetic PGE1 analog, miso-
prostol (Cytotec; Searle Corp., Chicago, IL), has been used
successfully in women for cervical dilation. For years, clini-
cians have used this therapeutic to stimulate cervical relaxation
in the horse and gotten promising results, but a controlled
study by McNaughten et al. demonstrated that the applica-
tion of misoprostol directly to the external cervical os had no
effect on the tone, length, height, or degree of relaxation.359
This treatment is still being used clinically, both to stimulate
 CHAPTER 19
cervical relaxation for breeding and during the induction of
parturition, with successful anecdotal results. In addition,
N-butylscopolammonium bromide combined with sterile gel
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and applied to the cervix has anecdotally resulted in cervical
relaxation. In addition to relaxing the cervix around the time
of breeding, these agents have also been used to soften the cer-
vices of pregnant mares in preparation for induced parturition
at various stages and may help prevent cervical trauma.360
Y OVIDUCTAL CONTRACTION
The early embryo secretes PGE2, which is believed to play
a role in the contractility of smooth muscle of the oviduct
and allow selective transport of the embryo into the uter-
ine lumen.8 PGE2 is also secreted during the high-mobility
phase of the embryo within the uterus and is suspected to
stimulate uterine contraction and enhance uterine tone.361
Laparoscopic application of PGE2 along the serosal surface of
the oviduct can modify embryo transport. Interestingly, not
only is embryo transport hastened, but also the unfertilized
oocytes that are rarely recovered in the mare are released.
Laparoscopic-guided PGE2 application on the mare’s oviduct
has been reported to assist in clearing oviductal debris and
improve the fertility in a small subset of mares suspected of
having oviductal pathology.362
Y UTERINE CONTRACTILITY
One of the most common hormones used to induce uterine
contractility is oxytocin. Naturally produced by the hypothala-
mus and stored in the posterior pituitary, it induces uterine
contractions after sexual intercourse and during labor, aids
in involution of the uterus, and promotes social bonding.
Synthetic oxytocin increases intrauterine pressure in a dose-
dependent manner from 2.5 to 10 IU in reproductively normal
mares and mares suffering from delayed uterine clearance.194
This is affected by the day of the cycle in which oxytocin is
administered, with the periovulatory phase being more influ-
enced by exogenous oxytocin than the postovulation phase.280
This appears to be affected by season, because anestrous mares
that have been primed with progesterone show minimal con-
tractile response when oxytocin is administered, although
uterine tone increases. Clinically, oxytocin is used to facilitate
uterine clearance in mares suspected of experiencing abnor-
mal fluid accumulation. When administered at a dosage of 10
to 20 IU IM two to four times daily in the periovulatory period,
it is shown to be effective in promoting uterine clearance. It is
recommended that exogenous oxytocin not be administered
before 4 hours after breeding—and not immediately before
breeding—to avoid any negative effect it may have on sperm
transport to the oviduct.
The combination of PGE2 and oxytocin is also used to
induce parturition in the late-gestation mare. Mares pretreated
with 2.0 mg of intracervical PGE2 6 hours before IV admin-
istration of 15 IU oxytocin have increased cervical diameter,
a decreased necessity for repeated oxytocin injections, and a
hastened time to parturition compared with mares lacking
PGE2.360 Mares pretreated with PGE2 before oxytocin injec-
tion also produce foals that stand and nurse more swiftly than
mares that are induced solely by oxytocin. Clinically, the addi-
tion of PGE2 to the protocol has shown anecdotal evidence of
hastening parturition as well as reducing the necessary dosage
of oxytocin required to stimulate parturition.363
Disorders of the Reproductive Tract 12631263
Prostaglandins have also been shown to induce uterine
contractions, and the administration of the synthetic PGF2α
analog cloprostenol at a dosage of 250 μg has been shown to
be effective at inducing more coordinated, longer effects than
oxytocin (>6 hours compared with 20 minutes, respectively).
The use of cloprostenol was also shown to be more effective at
improving uterine clearance in a subset of mares.282
Y HORMONAL SUPPORT OF
PREGNANCY
The equine pregnancy differs from other species in that proges-
terone is almost undetectable in the serum of pregnant mares
in the latter half of pregnancy. Instead, in the second and third
trimesters, the fetal-placental unit produces high concentra-
tions of metabolites of progesterone, deemed progestogens,
which inhibit uterine contractions and maintain cervical clo-
sure, promoting the optimum uterine environment for preg-
nancy. Despite conflicting evidence regarding the benefits of
progestogen supplementation, progestogen supplementation
throughout gestation is common. Recent studies have fur-
ther elucidated the hormonal regulation of pregnancy and the
proper supplementation protocols and should be reviewed by
practitioners and breeders alike. This will also be discussed in
more detail in the following sections describing management
of the pregnant mare.
In the horse, the initial source of hormonal support for
pregnancy is the progesterone derived from luteal cells of the
primary CL. Progesterone secretion is sustained for nearly 30
days post ovulation because of the poorly understood mecha-
nism of maternal recognition of pregnancy and subsequent
suppression of luteolysis. A secondary surge of progesterone
occurs roughly 35 days into gestation in response to the for-
mation of endometrial cups, which actively synthesize eCG.
Because of its dual LH and FSH functionality, it stimulates fol-
licular growth and development in addition to ovulation and/
or luteinization.364 It is because of this dual functionality that
accessory CLs are able to form and continue the luteal synthe-
sis and secretion of progesterone. This increase in progester-
one lasts until approximately 120 days of gestation, when the
endometrial cups are destroyed by an endometrial lympho-
cytic immune response.
At approximately 120 days of gestation, the steroidal regu-
lation of pregnancy transfers from ovarian to fetoplacental.
At this time, uterine quiescence is thought to be maintained
by metabolites of progesterone and pregnenolone, commonly
referred to as the progestogens, and specifically 5α-pregnane-
3,20-dione (5α-DHP) and 20α-hydroxy-5α-pregnane-3-one
(20α-5P).365-368 This hormonal support of pregnancy is made
possible through synchrony of the fetal gonads, fetal adrenals,
and the placenta functioning as complementary endocrine
organs. Although these progestogens increase in concentra-
tion in maternal serum later in gestation, progesterone rapidly
declines and remains at basal concentrations until the abrupt
rise immediately before parturition.
In addition, the fetoplacental unit produces large quantities
of dehydroepiandrosterone (DHEA) in late gestation, which
rapidly are aromatized within the placenta into estrogens. In
addition to estrone sulfate and estradiol, the equine-unique
estrogens equilin and equilenin are also produced in high
concentrations throughout late gestation.368 Total estrogen
concentrations rapidly rise starting at approximately 100 days’
 1264 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
gestation into thousands of nanograms per milliliters, peak
roughly 2 weeks before parturition, and then promptly decline.
Estrone sulfate has been used as a marker of fetal well-being
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in early pregnancy, because it represents the effective process
of a conversion of the fetal gonadal production of estrogen.155
Fetal estrogens are enzymatically converted to soluble estrone
sulfate by the placenta. When estrone sulfate declines, it sug-
gests that this conversion process has been disrupted, either
from fetal demise or placental dysfunction.155 Some have
argued that estrogen supplementation in mares with low total
estrogens during gestation may help, and there is a growing
body of knowledge suggesting beneficial effects.369 In contrast
to other species, the horse has a rapid decline in total estro-
gen concentration before parturition, the exact reasoning for
which has not been clearly determined. Esteller-Vico et al. did
a study in which Letrozole, a potent aromatase inhibitor, was
used to significantly suppress estrone sulfate in circulation in
late-gestation mares.369 Although estrone sulfate concentra-
tions were suppressed to basal levels, gestational length was
not affected, further indicating the lack of sufficient data and
indicating the necessity for further work exploring estrogen
supplementation in late gestation.
Poor uterine tone, the presence of abnormal uterine edema,
low serum progesterone, and a small-for-age embryo are all
indicators of a compromised pregnancy, which often lead to
hormonal supplementation. Unfortunately, none of these con-
ditions is well characterized, and their diagnosis and interpre-
tation vary considerably among practitioners. In addition, low
serum progesterone concentrations have been shown to cor-
relate poorly with early embryonic loss.370 Still, many practi-
tioners supplement with progestogens throughout pregnancy.
The two most common types of exogenous progestogens are
oral altrenogest (Regu-Mate) or daily IM injections of proges-
terone in oil. In a study done by McKinnon et al., five differ-
ent synthetic progestogens were evaluated for maintenance
of pregnancy.371 Only altrenogest, administered at the rec-
ommended dosage of 0.044 mg/kg daily, provided sufficient
support for maintenance of pregnancy after luteolysis was
induced using PGF2α. In addition to Regu-Mate, a long-acting
progesterone formulation is currently available on the market
(BioRelease P4 LA 150) that has been shown to be effective
when administered once every 7 days (BioPharm). In addi-
tion, BioRelease also produces sufficient levels of progesterone
for pregnancy maintenance in the absence of luteal tissue.372
Although both provide adequate embryonic support in the
absence of luteal functionality, the BioRelease formulation
is less labor intensive, requiring weekly injections instead of
daily.
Although it has been well documented that progesterone
concentrations in serum are negligible in late gestation, sup-
plemental progestogens are routinely administered. In cases
of suspected placentitis, placental separation, placental insuf-
ficiency, inflammatory conditions, and supplemental proges-
togens are used to promote uterine quiescence and for their
antiinflammatory properties. Altrenogest is recommended
for the treatment of placentitis in addition to antimicrobi-
als and antiinflammatories, which when combined signifi-
cantly decrease the risk of abortion caused by experimentally
induced placentitis.373 Routine supplementation with altreno-
gest in late gestation is associated with clitoral enlargement in
female offspring and an increase in serum LH in prepubertal
fillies produced by mares that underwent treatment.374 Foals
born to mares that have received altrenogest in late gestation
have been found to be immunocompromised, with a lower
neutrophil/lymphocyte ratio than normal foals.375 Although
this may be caused by dysmaturity at birth, these results were
contradicted by a second study, which found that supple-
mental altrenogest in late gestation has no antiinflammatory
effects on the endometrium of mares post parturition.376 A
more comprehensive discussion of this topic will be covered
in a later section.
Y INDUCTION OF LACTATION IN THE
BARREN MARE
When the foal’s dam has died, cannot lactate appropriately, or
a suitable nurse mare or foster dam is unavailable, lactation-
induction protocols are used to provide a lactating mare for
the foal. Lactation can be induced in the barren mare, which
can alleviate the need for producing an orphan foal from a
nurse mare. Chavatte-Palmer et al. demonstrated that a hor-
monal manipulation of the mare, beginning at any time in her
cycle, could induce lactation within days of treatment.377 This
protocol involves placement of an intravaginal sponge con-
taining 500 mg altrenogest and 50 mg estradiol benzoate, and
it has proved effective. A week after the onset of treatment, a
second sponge is placed, containing 100 mg estradiol benzoate
in addition to 50 mg/100 kg body weight sulpiride. In a second
study, domperidone (1.1 mg/kg) was evaluated in replacement
of sulpiride. Both treatments induce lactation within 7 to 12
days after the beginning of treatment, including the produc-
tion of colostrum.
A second study found that routine IM injections of sul-
piride (twice a day at a dose of 0.5 mg/kg) beginning during
diestrus and continuing for 9 to 14 days effectively induced lac-
tation.378 Large mare-to-mare variability was seen when con-
sidering daily milk output. It has been noted that mares were
only responsive to sulpiride when the ovaries were function-
ally performing steroidogenesis and producing estrogen and
progesterone. Neither anestrous nor ovariectomized mares
responded to treatment. Clinically, induction of lactation is
assisted by daily milking and repeated oxytocin injections.
A follow-up study done by Korosue et al. demonstrated that
foal size is not affected by the use of a lactationally induced
surrogate mare.379 Hormonal stimulation of lactation had no
effect on subsequent reproductive performance, indicating
that these foster mares may still achieve pregnancy.
Breeding Management to Optimize
Pregnancy Rates
E. Bradecamp
There are several components of breeding management that
can be manipulated and controlled in an attempt to optimize
pregnancy rates. Fertility can be measured by per cycle preg-
nancy rate, which is the number of estrous cycles required to
establish a pregnancy. The more concise the breeding manage-
ment is, the more likely pregnancy rates will be maximized
and the more efficient, both economically and timely, the
breeding program will be.
It is imperative to recognize that breeding management
can be divided into two categories, the mare factors and the
 CHAPTER 19
stallion factors. Additionally the human factor—the manage-
ment of the mare and stallion that is directly affected by human
decisions—cannot be overlooked as an important element in
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the success of a breeding program. Regardless of how fertile a
mare or stallion may be, human factors that result in less than
optimal management may yield decreased pregnancy rates.
Y STALLION MANAGEMENT TO
OPTIMIZE PREGNANCY RATES
The gold standard for the measurement of stallion fertility is
per cycle pregnancy rate. Semen analysis can provide a pleth-
ora of information and values regarding the quality of sper-
matozoa in an ejaculate. While a single in vitro test cannot
reliably predict fertility, ejaculates with higher percentages
of morphologically normal, progressively motile sperm yield
higher pregnancy rates than ejaculates that exhibit poorer
quality morphology and motility. Second, even if a stallion has
excellent fertility, poor management of that stallion can result
in poor pregnancy rates; therefore proper management is
essential to optimize fertility. Depending on the breeding pro-
gram and the method by which the mares are bred (live cover
or AI with fresh, cooled shipped semen or frozen semen),
there are important conditions that must be met to maximize
pregnancy rates.
Y OPTIMIZING PREGNANCY RATES
WITH FIELD BREEDING
Although less reported in scientific research and literature,
field breeding remains the primary method of breeding for
many stud farm operations around the world. In North Amer-
ica, many large ranches and pregnant mare urine (PMU) farms
(farms that establish pregnancy in mares to recover estrogens
from urine for commercial use) continue to rely on pasture
breeding to achieve pregnancy or “settle” mares. It is important
to realize that even with the many management techniques
used in programs that utilize hand breeding or AI, higher
pregnancy rates are not guaranteed and often are not achieved
above those yielded by pasture breeding. At the same time,
pasture breeding does have its limitations; mature stallions are
often restricted to 20 to 35 mares with which they can breed
live cover in a pasture setting. Placing a stallion with a herd of
mares that is too large may have a negative effect on his ability
to achieve optimal pregnancy rates, and it may be detrimental
to the stallion’s health. In breeding programs in which stallions
are booked to greater than 100 mares per season, other meth-
ods of breeding must be used to optimize pregnancy rates.
When using field breeding, it is ideal to have a closed herd
of mares that has had time to establish its order of dominance
before introducing the stallion. The stallions are typically left
with the mares for a period of time that allows every mare to
pass through two consecutive heat cycles (45–60 days). The
stallion is then removed from the herd, and pregnancy exami-
nations are performed 21 or more days later. If a mare is bred
on the day that the stallion is removed and does not ovulate
for several days, this allows for every mare to be a minimum
of 14 days pregnant at the time the pregnancy examinations
are performed.
Ideally, once the herd is established and the stallion has
been added, more mares should not be added to the herd
Disorders of the Reproductive Tract 12651265
because a new hierarchy will need to be established, and the
stallion may not accept the new mare, even if she is in estrus.
Injuries are more likely to occur when new horses are added
to the herd. If a new mare must be added, then the stallion
should be removed for a couple of days to allow the mares to
reestablish their hierarchy, and then the stallion can be added
back in the herd. If the mare is an outside mare (not native to
the farm), then it is imperative that she has been appropriately
quarantined before being added to the herd to prevent disease
transmission that would negatively affect the herd health and
fertility.
Pastures need to be maintained with safe fencing and ide-
ally without direct contact with other horses across fence lines.
The fields need to be large enough to allow horses to get away
from more aggressive pasture mates. All horses should be
unshod and have their feet trimmed to minimize injuries and
lameness.
BSEs should be performed on both the mares and the stal-
lion before the beginning of the breeding season to identify
any need for treatment or management changes. An entire
breeding season can be lost when mares that have been housed
with a stallion for 45 to 60 days are not checked for pregnancy
until several weeks after the stallion has been removed, and
then reproductive pathology is discovered.
Several factors aid in maximization of pregnancy rates
when using field breeding, including:
• For fertile stallions, a BSE should be performed before the
breeding season, and ideally the stallion has a history of
successful field breeding.
• Εach fertile mare should have a BSE performed before the
breeding season.
• Do not overextend a stallion and house him with more
mares than he can breed successfully. A young, inexperi-
enced stallion may not be able to breed as many mares as
an older, more mature stallion.
• Maintain a closed herd to reduce the possibility of stress
and introduction of diseases that could negatively impact
pregnancy rates.
• Maintain good herd health practices, such as vaccination,
deworming, hoof care, dental treatments, and an adequate
plan of nutrition. These should all be addressed, in place,
and up-to-date before the breeding window to minimize
stress during this period.
Y OPTIMIZING PREGNANCY RATES
WITH LIVE COVER IN
HAND BREEDING
Many small stud farms rely on breeding mares live cover,
and all Thoroughbreds bred to be registered with the Jockey
Club are required to be bred live cover. The key factors affect-
ing pregnancy rates in live-cover situations are ensuring that
the stallion’s book size is appropriate, based on the stallion’s
history and daily sperm production, and that the mares bred
are suitable for mating and ovulate in a timely manner after
breeding. Ovulation should occur within 48 hours of breeding
or the mare should be bred again. Ideally the mare should be
administered an ovulation-inducing agent to ensure ovulation
occurs within 24 hours following breeding.
A more thorough discussion of how to calculate an appro-
priate book size based on the stallion’s testes size and seminal
parameters can be found in later sections. Briefly, Love et al.
 1266 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
described how to estimate a stallion’s book size based on testes
size and predicted or known daily sperm output (DSO).380 If
a stallion is booked to more mares than is appropriate for his
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DSO, then he may fail to meet an acceptable per cycle preg-
nancy rate, resulting in more mares needing to be rebred on
subsequent cycles and compounding an already overestimated
book size. Monitoring a stallion’s ongoing per cycle pregnancy
rate as the breeding season progresses aids in identification
of any pathology and mismanagement or fertility issues and
allows for necessary evaluations and adjustments to stallion
management to be made to optimize fertility.
Research has also shown that for approximately 60% of
stallions “reinforcement breeding” after the stallion has cov-
ered the mare results in improved pregnancy rates by approxi-
mately 10%.381 Reinforcement breeding involves collecting
the postejaculate semen that drips from the urethra follow-
ing dismount, which is combined with an appropriate semen
extender to be inseminated into the mare’s uterus. Reinforce-
ment breeding has been most beneficial to stallions that rou-
tinely dismount before completing ejaculation. One stallion
the author worked with had a 30% increase in per cycle preg-
nancy rates when reinforced breeding was added to stallion
management.
Y OPTIMIZING PREGNANCY RATES
WITH ARTIFICIAL INSEMINATION
WITH FRESH SEMEN
If the stallion and mare reside on the same farm, then instead
of breeding via live cover, the stallion’s semen may be collected
and the mare bred with the fresh semen by AI. As with live
cover, the mare should be programmed to ovulate within 24 to
48 hours post breeding. To optimize pregnancy rates, when the
ejaculate is going to be used to breed more than one mare on a
given day, each mare should be inseminated with a minimum
of 500 million progressively motile sperm or 250 million pro-
gressively motile, morphologically normal sperm. Although
some stallions can achieve acceptable per cycle pregnancy
rates with fewer sperm per insemination dose, until a stallion’s
minimum sperm/dose threshold is determined, 500 million
progressively motile sperm are considered an appropriate dose
for fresh semen. To improve pregnancy rates with a subfer-
tile stallion, one can increase the number of sperm per dose
or perform deep-uterine-horn or hysteroscopic insemination
techniques to deposit the semen closer to or on the oviductal
papilla ipsilateral to the dominant follicle.
Y OPTIMIZING PREGNANCY RATES
WITH ARTIFICIAL INSEMINATION
WITH COOLED SHIPPED SEMEN
When one is breeding with cooled shipped semen, proper
preparation of the semen is paramount to obtaining maximum
pregnancy rates. In this program the semen is collected from
the stallion, processed according to known standards of semen
preparation, and placed in a cooling device (Equitainer or dis-
posable shipper) to be maintained at 5°C until it arrives at the
location for insemination. Generally most semen is shipped in
this program overnight for arrival the next day, although this
may vary depending on shipping options available. Once the
semen arrives, the mare is artificially inseminated and ideally
will ovulate within 24 hours post insemination. Human error
in the preparation of the semen for shipment and delayed
time from insemination to ovulation or missed ovulation
are the most common detriments to establishing successful
pregnancies.
Before the start of the breeding season a BSE should be
performed on every stallion and mare considered for use in
this program to identify pathology, establish ideal semen-
processing techniques to optimize pregnancy rates, and mini-
mize costs associated with multiple breedings. Regarding the
stallion, a longevity analysis of sperm motility using differ-
ent semen extenders and different conditions should be con-
ducted to identify processing and packaging that optimally
maintains sperm motility for 24 to 48 hours under cooled con-
ditions. Generally semen processing for cooled shipped semen
involves the following:
1. Immediately after the semen is collected it is extended to a
minimum of 1:3 ratio of semen to extender (ideally 1:4 or
greater), and kept at room temperature out of direct light
until analysis and packaging are complete. The extender
should be warmed to 37°C before collection and then al-
lowed to passively cool to room temperature at the same
rate as the semen to prevent any temperature shock of the
semen when the two are combined.
2. The final concentration of the extended semen should be
between 25 and 50 million spermatozoa per milliliter.
3. Industry standards have established that a minimum of 1
billion progressively motile sperm should be included in
each dose of cooled shipped semen to optimize pregnancy
rates.
The mare that is to be bred should be administered an
ovulation-inducing agent 24 hours before breeding to ensure
that she ovulates within 24 hours after breeding. When two
doses of semen are available, reports conflict as to whether
better pregnancy rates are achieved if both doses are insemi-
nated at the same time or if the mare should be bred twice
approximately 24 hours apart.382,383 Unfortunately, both stud-
ies contained a limited number of stallions, and more research
needs to be conducted in this area to answer this question. The
fertility of the stallion and reproductive health of the mare and
how well an individual stallion’s spermatozoa tolerate cooling
also factor into what management options are best.
Y OPTIMIZING PREGNANCY RATES
WITH ARTIFICIAL INSEMINATION
OF FROZEN SEMEN
When frozen semen is used for breeding, accurate timing of
breeding in relationship to ovulation is imperative to achieve
maximum pregnancy rates. Frozen-thawed semen does not
remain viable in the mare (estimated 12 hours on average)
as long as fresh or cooled semen (approximately 48 hours),
potentially because of capacitation-like changes that occur
during the cryopreservation process.384 Recent studies have
shown that similar pregnancy rates can be obtained with fro-
zen and cooled shipped semen, and Loomis et al. reported first
cycle pregnancy rates of 60% and 63%, respectively, in a study
of three farms with a combined total of 36 stallions shipping
either cooled or frozen semen to a total of 648 mares.385 The
number of doses available for insemination on a given cycle
dictates whether the mare can be bred with two doses using
a timed insemination protocol or if the mare is bred with one
 CHAPTER 19
dose once ovulation is detected. Similar pregnancy rates can
be achieved with either method as long as insemination occurs
no more than 12 hours before and 6 hours after ovulation. If
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two doses of semen are available, then the mare is adminis-
tered an ovulation-inducing agent once a 35-mm follicle and
maximal uterine edema are observed. Insemination occurs at
24 and 41 hours later, with ovulation being confirmed within
12 hours of the second ovulation. If only one dose of semen is
available, then the ovulation-inducing agent is administered as
described earlier, and starting 24 hours later transrectal ultra-
sonography is performed approximately every 6 hours until
ovulation is detected, at which time the mare is bred. Frozen
semen causes a more severe inflammatory reaction in the
endometrium than fresh or cooled shipped semen because of
the removal of seminal plasma and its antiinflammatory prop-
erties. Because of this, the decision to breed with one dose ver-
sus two is made based on the mare’s reproductive health and
history.
Proper handling of frozen semen is also important to
ensure that maximal pregnancy rates are achieved. Frozen
semen must be maintained in appropriate liquid nitrogen
storage units until immediately before thawing and should not
be exposed to ambient temperature air at any time for more
than a couple of seconds. Exposure to ambient air will result in
thawing and then refreezing when returned to the liquid nitro-
gen, resulting in damage to the spermatozoa. Frozen semen
should be thawed according to instructions that are included
with the semen when it is shipped to ensure that maximum
viability is maintained. If no instructions are included then it
is safest to thaw at 37°C for 30 seconds for 0.5-mL straws, with
larger straws requiring a longer thawing time. Once thawed,
the semen should be inseminated into the mare immediately.
Although there is no set industry standard for the number of
total or progressively motile sperm required for a dose of fro-
zen semen, there are some guidelines. In a study of more than
30,000 mare inseminations in the French National Stud, it
was concluded that when mares were inseminated with doses
containing less than 750 × 106 total frozen-thawed sperm, the
resulting per cycle pregnancy rates were lower.386 Based on
these results, the World Breeding Federation of Sport Horses
currently recommends this as the accepted minimum number
of sperm per dose of frozen semen. Additionally, Volkmann
and van Zyl showed that per cycle pregnancy rates were signif-
icantly higher when the insemination dose of frozen-thawed
semen was increased from 137 to 210 × 106 to 222 to 333 ×
106 progressively motile sperm (44% vs. 73%, respectively).387
Based on these studies, it has become industry standard that a
commercial dose of frozen semen should contain 200 million
progressively motile sperm and possess greater than 30% pro-
gressive motility on thawing. It should be remembered that,
unlike in the bull, fertility varies greatly from stallion to stal-
lion and may not always be highly correlated to motility.
Y OTHER FACTORS AFFECTING
PREGNANCY RATES
In addition to proper management of the stallion and mare,
there are other variables that affect pregnancy rates. Under-
standing, controlling, or adjusting management of the mare to
address these variables when possible will ensure that optimal
pregnancy rates will be achieved. In addition, it is important to
understand how these factors, listed below, will affect expected
Disorders of the Reproductive Tract 12671267
pregnancy rates and allow the clinician to provide the owner
with a realistic prognosis for reproductive success:
• Reproductive status of the mare (barren, foaling, or maiden)
• Age of the mare or stallion
• Time of year of breeding
• Presence of endometritis
• The effects of inflammatory cytology and positive culture
on pregnancy rates
• Uterine and systemic treatments that can aid in improving
pregnancy rates in mares with endometritis
• Corticosteroids
• Ecbolics
• Uterine lavage
• Intrauterine and systemic antibiotics
• Antiinflammatories and mucolytics
Although these factors will not be discussed in this section,
they are covered in detail in other sections. It is important
to remember that appropriate management of these vari-
ables can aid in obtaining optimal pregnancy rates. Regard-
ing the reproductive status of the mare, the highest per cycle
pregnancy rates of age-matched mares under 9 years of age
is in the maiden > foaling > barren mares, although excep-
tions can occur. Generally the highest pregnancy rates are
achieved with young fertile animals using fresh or cooled
semen. Per cycle pregnancy rates decrease, and increases in
pregnancy loss occur when mares age.388,389 Breeding outside
of the natural breeding season, when daylight is short, can be
associated with a decrease in fertility in both mares and stal-
lions, with animals farther from the equator demonstrating
a more dramatic, longer period of reproductive quiescence.
Although it has been shown that endometritis, associated
with the presence of fluid in the uterus, inflammatory cytol-
ogy, and positive cultures all result in decreased pregnancy
rates, it has also been shown that appropriate treatment of
these pathologies can result in improvement in pregnancy
rates.390
There exists a population of mares for which these tradi-
tional breeding programs do not meet acceptable expecta-
tions because of poor uterine health, repeated pregnancy loss,
or inability to deliver a viable foal at term or the desire for
more than one offspring per season. For these mares, assisted
reproductive techniques such as embryo transfer and oocyte
aspiration for ICSI are options that should be considered when
consulting with the client.
Equine Embryo Transfer
E. Bradecamp
Embryo transfer as a means to produce offspring is used for
several different reasons in the equine industry. As mentioned
previously, it is the next option for mares that cannot generate
viable offspring because of reproductive tract limitations (cer-
vical damage, persistent endometritis, fibrosis, and repeated
pregnancy loss), systemic issues (laminitis, pelvic fracture,
and lameness), when the client would like to have multiple
offspring in one season, or in a healthy performance mare
that cannot carry a pregnancy because of competition. Briefly,
equine embryo transfer involves breeding a “donor” mare with
the desired genetics, monitoring ovulation, and recovering the
embryo through a uterine flush 7 to 8 days post ovulation. The
embryo is then transferred into a synchronized “recipient”
 1268 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
mare that will carry the pregnancy to term and raise the foal.
A multitude of factors play a role in the success of an embryo
transfer program, and a comprehensive understanding of
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the effects of donor mare fertility, recipient mare manage-
ment, and embryo procurement and processing techniques is
imperative to maximize the chances of obtaining a pregnancy.
This section will provide an overview of the factors involved in
managing donor and recipient mares and the techniques for
flushing, transporting, and transferring equine embryos.
The first live foal produced by embryo transfer was reported
by Oguri and Tsutsumi in Japan in 1974.391 Initially, embryo
transfers were performed surgically by using a standing flank
laparotomy, by which the embryo was deposited into the uter-
ine lumen through a small incision in an exteriorized uterine
horn. The incision was then closed, the uterine horn returned
to the abdomen, and the flank laparotomy site closed. By the
late 1990s, with advancements in the technique of transcer-
vical transfer, Foss et al. reported that pregnancy rates from
nonsurgical embryo transfer could be achieved that were
comparable or superior to surgical transfer.392 Since that time,
nonsurgical embryo transfer has become the industry stan-
dard of care.
Initially, it was hoped that embryo transfer would provide
a modality by which to obtain foals from mares with vari-
ous causes of infertility. Although successful in some of these
cases, embryo transfer success depends on the cause of infer-
tility and may not improve pregnancy rates for some infertile
mares. The procedure has proven to be more successful in
mares that become pregnant but fail to maintain their preg-
nancies than in mares in which no pregnancy has ever been
diagnosed. Embryo transfer allows foals to be produced from
show or race mares that the owner desires to keep in competi-
tion; mares that cannot carry a pregnancy because of systemic,
musculoskeletal, or reproductive disease; 2-year-old mares;
and mares that have foaled late in the breeding season. This
allows them to remain open so that they can be bred back early
the following year. Embryo transfer also allows embryos to be
cryopreserved and stored for later use.
The success of an embryo transfer program is dependent
on multiple factors, including donor mare fertility, recipient
fertility and synchrony, semen quality, and expertise of the
veterinarians managing the mares and performing the pro-
cedures. An extensive review of the factors affecting embryo
transfer rates will be provided later in this section. The major-
ity of embryos are shipped to recipient herds with proper
synchronization and selection, but owner-provided recipient
mares may also be used. Although a majority of breed regis-
tries (with the Jockey Club being one exception) now permit
registration of foals produced by embryo transfer, mare own-
ers need to check with their specific breed registry to familiar-
ize themselves with the regulations of that organization. Some
registries allow an unlimited number of foals to be produced
from a mare in a given year, whereas some registries, such as
the United States Trotting Association, only permit one foal
per mare per year to be registered.
Y DONOR MARE
Factors Affecting Fertility
The fertility and age of the donor mare has a significant effect
on the success of an embryo transfer program. The chances of
obtaining an embryo is highest in young (less than 10 years of
age), fertile mares, with Foss et al. reporting embryo recovery
rates as high as 84.2% in show mares; 59.7% in multiparous,
nonbarren mares; and as low as 30% in mares with a history of
infertility.392 McCue et al. reported that one or more embryos
were recovered from 144 of 252 flushes (57.1%) from mares
15 years of age and younger and 93 of 236 flushes (39.4%)
from mares older than age 15.393 Marione et al. also showed
that mare age had a significant effect on embryo recovery rate.
When mares were divided into three age groups—fillies (3 and
4 years old), middle-aged mares (aged 5–10 years), and old
mares (aged 13–25 years)—the embryo recovery rates were
171/244 (70.1%), 774/1081 (71.6%), and 385/701 (54.9%),
respectively, with significantly fewer embryos recovered from
the old mares.394
The type of semen used to breed the donor mare also has
an effect on pregnancy rates and embryo recovery rate. Squires
et al. reported that pregnancy rates were highest when fresh
semen was used (60%–77%) and were significantly lower
when chilled (44%) or frozen semen (46%) was used.389 The
quality of the sire’s semen should be taken into careful consid-
eration in an embryo transfer program. Stallions with poor per
cycle pregnancy rates will subsequently yield poorer embryo
recovery rates.
Both exercise and heat have the potential to negatively
affect embryo recovery rates. This should be taken into consid-
eration when attempts are being made to obtain embryos from
mares that are concurrently in active training and/or compe-
tition. A study performed by Kelley et al. demonstrated that
exercised mares had lower peak LH concentrations, higher
cortisol levels, and altered follicular dynamics compared with
nonexercised mares.395 The exercised mares had longer inter-
ovulatory intervals, fewer 6- to 10-mm follicles, and more
follicles 20 mm or greater on the day of deviation, suggesting
delayed deviation. Additionally, when embryo transfer was
performed on the exercised and control mares, significantly
fewer embryos were recovered from the exercised mares.
Mares were divided into three groups: nonexercised controls,
mares that were exercised moderately for 30 minutes a day
during the periovulatory period but rested after ovulation for 7
days, and mares that were exercised for 30 minutes daily from
the periovulatory period until day 7 post ovulation. Embryo
recovery rates were significantly higher in the controls (67%)
than the partially exercised (44%) or fully exercised (43%)
groups. Vascular perfusion of the periovulatory follicular wall
was significantly decreased on the day before ovulation in
both groups of exercised mares, and vascular perfusion of the
follicular wall was correlated with the likelihood of recovering
an embryo.395 Mortensen et al. also demonstrated that when
mares were exercised for 30 minutes daily under ambient con-
ditions of over 30°C and over 50% humidity, an increase in
rectal temperatures from 38°C to 39.9°C occurred. Embryo
recovery rates in the exercised mares decreased by 50% com-
pared with the control mares, and 50% fewer grade I embryos
were recovered from the exercised mares.396 Conversely, there
have been studies that did not show any effect from exercise
in hot, humid conditions on embryo recovery rates, but the
mares in these studies experienced less elevation in rectal tem-
peratures and may have been at a higher fitness level than the
mares in other studies.
Managing the Donor Mare for Embryo Transfer
Management of the donor mare for embryo transfer is very
similar to managing any mare that is being bred. The mare
 CHAPTER 19
should be in good body condition and health, and any health-
related problems should be addressed and every attempt made
to keep the mare pain and stress free. Mares should be bred to
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minimize and modulate the inflammatory process that natu-
rally occurs in the reproductive tract with breeding, and the
treatments required to do this may vary greatly from mare to
mare. Young, healthy mares usually require minimal treatment,
whereas older, subfertile mares may require more aggressive
treatment modalities that aid in the evacuation of fluid from
the uterus and minimize the development of postbreeding
endometritis. It is imperative that the exact day of ovulation is
documented to ensure that the embryo flush is performed on
the correct day post ovulation. Embryo flushes are performed
7 to 8 days post ovulation. If the mare is less than 10 years of
age and was bred with fresh or cooled shipped semen, then the
flush may be performed on day 7 or day 8, depending on the
clinician’s preference. Embryo flushes are typically performed
on day 8 in older mares and mares bred with frozen semen.
The embryo appears to be slightly delayed in its early develop-
ment and transport in older mares and when frozen semen is
used, so recovery 1 day later allows an increased likelihood of
recovering an optimally developed embryo.355
When multiple embryo flushes are going to be performed
on a donor mare within one breeding season, it is impera-
tive to be cognizant of the inflammation that is incited with
each breeding and flush cycle. Research has shown that these
inflammatory episodes are additive, and mares that have had
multiple embryo flushes performed during a season have
higher levels of inflammation and fibrosis observed on uter-
ine biopsies compared with control mares. Carnevale et al.
showed a positive correlation between repeated embryo
recovery attempts and chronic inflammatory changes in the
uterus.397 Additionally, although there is anecdotal evidence
that repeated embryo flushes over several years have a nega-
tive effect on the fertility of some mares, there are studies that
do not show an alteration in embryo recovery rates with an
increasing number of successive embryo collections.
Y RECIPIENT MARE
The ideal recipient mare should be 3 to 10 years of age, of
good body size (15.2–16.2 hands) or as close to the same size
of the donor mare as possible, systemically healthy, easy to
handle, and reproductively sound. Standardbred and Quarter
Horse–type mares have historically shown to be well suited
as recipient mares, but the predominant type of mare within
any individual recipient herd is often dictated by the types of
mares available as recipients within that geographic region,
and potentially the predominant types of donor mares are
flushed. Although it has been well demonstrated that the size
of the mare’s uterus controls the size of the fetus, allowing the
transfer of draft horse embryos into ponies to produce live
foals without resulting in severe dystocia, it has been demon-
strated that when there is a gross disparity (draft to pony) the
fetus may not reach its full potential size as its siblings that
are transferred into recipients of similar size to the donor. It
should be noted that these studies examined the extremes of
embryo transfer, and it is because of the mares’ ability to con-
trol fetal size that embryo transfer can be performed so readily
in mares and the offspring produced are able to mature to their
genetic potential when light horse breeds are transferred into
light horse breeds. Intrauterine growth restriction (IUGR), a
potential for increased incidence of osteochondritis dessicans
Disorders of the Reproductive Tract 12691269
lesions, and changes in conformation have been attributed to
large differences in the recipient and donor mares, and every
effort should be made to best match the recipient to the size of
the donor mare.
Detailed descriptions of the specific surgical and nonsurgi-
cal procedures involved in the collection, shipping, and trans-
fer of equine embryos is beyond the scope of this text, and
the reader is referred to other recent texts and publications for
such information.
The Pregnant Mare
Igor F. Canisso, Maria R. Schnobrich
This section will review the physiology and relevant anatomic
considerations for clinical management of the pregnant mare.
In addition, management, treatment, and pathology associ-
ated with the pregnant mare and periparturient period will be
discussed.
Y PHYSIOLOGY OF GESTATION
Maternal Recognition of Pregnancy
Once the oocyte is fertilized, the zygote begins its journey down
the oviduct, reaching the uterine horn by days 6 to 7.398-401
Older mares and mares bred post ovulation or with frozen
semen are thought to have delayed embryonic vesicle trans-
port through the uterine tubes by 1 or 2 days. It has been sug-
gested that the early equine embryonic vesicle must be viable
and signal its presence in the uterotubal junction to allow its
passage into the uterine lumen.4,402 This mechanism is thought
to be mediated by embryonic production of PGE2,401 which
is supported because PGE2 administered in the oviduct has-
tens embryonic transport through the uterine tube.8 Nonfer-
tilized oocytes are thus retained in the mare’s uterine tubes
until complete degeneration occurs.4 Detailed descriptions of
the early development of the equine embryo are outside the
scope of this text, and the reader is referred to elegant reviews
published elsewhere.4,401-403 Early embryonic development in
the horse is characterized by the formation of a tough, elastic,
unusual acellular mucin-like glycoprotein “capsule” covering
the trophectoderm and the overlying zona pellucida.400,403 This
structure is first detected by day 7 post ovulation and com-
pletely envelops the spherical conceptus until as late as days 23
to 25 of gestation.400,403 Although the term embryo is used rou-
tinely to describe the early conceptus, it is important to under-
stand that what is generally being discussed is the embryonic
vesicle as well as the embryo proper. These two structures will
ultimately develop into the fetal membranes and fetus, respec-
tively. Embryonic development has progressed sufficiently by
day 40 of gestation, and the term fetus is used thereafter.4
The longitudinal arrangement of the endometrial folds is
suggested to favor mobility of the spherical equine embryo.4
After entering the tip of the uterine horn by days 6 to 7, the
embryo moves down toward the uterine body by day 8.404,405
The intrauterine mobility phase continues until days 15 to 17
post ovulation, and during this period the embryo may move
between the horns 10 to 20 times each day.399,401,404-406 An
embryo-derived factor is suspected to signal the suppression
of the uterine luteolysin (PGF2α) release, which interrupts
the oxytocin-PGF2α interaction in mares and allows early
 1270 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
pregnancy maintenance.279,407-409 The mobility of the spheri-
cal equine conceptus is critical for this proposed blockage of
luteolysis,398,399,401 which is why large uterine cysts are thought
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to cause pregnancy loss.135,410,411 If the enlarging vesicle cannot
pass by a large lymphatic uterine cyst, then it may be unable
to come into contact with all endometrial surfaces and inhibit
PGF2α production.93 Historically, it has been suggested that
maternal recognition of pregnancy starts by 10 days post
ovulation in mares,412 but a recent study reported success-
ful establishment of pregnancies when day 10 embryos were
transferred to recipient mares ovulating within 2 to 6 days of
the donor mare.413 This suggests that the luteolytic cascade
does not begin until day 12 and that the critical window for
maternal recognition of pregnancy in mares likely occurs
between days 12 and 14 post ovulation.
If maternal recognition of pregnancy does not occur or the
mare is not pregnant, luteolysis begins with release of PGF2α
by endometrial cells into the systemic circulation. This is in
contrast to ruminants, in which PGF2α is delivered directly
to the ovary via the countercurrent exchange between the
ovarian artery and uteroovarian vein.414,415 If the mare is not
pregnant or embryonic migration is impaired by day 15 of the
cycle, then there is increased expression of cyclooxygenase-2
(COX-2) by endometrial epithelial cells compared with preg-
nant mares.416,417 Therefore inhibition of the COX-2 enzyme is
considered a key factor for maternal recognition of pregnancy
in mares.412,417 Interestingly, although this release of PGF2α is
stimulated by oxytocin produced by luteal cells in ruminants,
there is no such luteal production of oxytocin in the mare,
with the endometrium being its primary source.4,418
The embryonic vesicle typically becomes fixed at the base of
one of the uterine horns with the embryonic pole of the vesicle
opposite to the mesometrial attachment (antimesometrial).419
This fixation is a result of the increasing embryonic vesicle
diameter, uterine tone, and its arrival at the uterine bifurca-
tion, which presumably has the smallest lumen diameter. An
early vascular indicator of the future position of the embryo
proper consists of a colored spot seen on Doppler imaging
of the endometrium close to the wall of the embryonic pole.
This finding may prove useful when differentiating between
a cyst and a vesicle before the embryo proper becomes vis-
ible on the ultrasound image.420,421 In postpartum mares, the
embryo usually becomes fixed in the more involuted horn,421-
424 with higher pregnancy losses being associated with those
embryonic vesicles that fix in the previously gravid horn by an
unknown mechanism.424
Placentation
The trophoblast cells of the early embryo are programmed to
form the absorptive placental contact with the endometrium.4
The mare has a nondeciduate, epitheliochorial, diffuse, micro-
cotyledonary placenta.4,402,403,425-430 The entire maternal sur-
face of the fetal membranes becomes covered with delicate,
diffuse microvilli that interdigitate with the proliferating lumi-
nal epithelial cells to form intricately branched microcotyle-
dons.425-430 The interdigitation tends to be deeper at the tip
of the nongravid horn, which may help explain the higher
incidence of fetal membrane retention in that horn.431-433 In
a normal pregnancy the noninvasive allantochorion extends
slowly to fill the uterus by days 80 to 85 of gestation, and its
microcotyledonary architecture, which provides both hemo­
trophic and histotrophic nutrition for the growing fetus, is not
fully established until days 120 to 140 of gestation.4,161 During
the second half of gestation, most of the mitotic activity is con-
fined to the periphery of the microcotyledons, which are still
growing.434,435
Vascular endothelial growth factor, a potent vasculogenic
and angiogenic factor, and its two main receptors, Flt-l and
KDR, are expressed on both the endometrium (i.e., mater-
nal) and chorioallantois (i.e., fetal) throughout gestation in
the mare.436 These molecules are presumed to facilitate the
continuing development of the prominent fetal and maternal
capillary networks within the microplacentomes of the equine
placenta.436-438
Degenerative changes (endometriosis) in the endometrium
can adversely affect the ability of the microcotyledonary pla-
centa to facilitate optimal hemotrophic nutrition and exchange
of waste products.437 If the pregnancy is maintained, dysfunc-
tional placental attachment can lead to the birth of dysmature,
weak foals through intrauterine growth restriction (IUGR),
which may have detrimental consequences on the health and
athletic performance of the mature horse.437,439,440
Failure of microcotyledon development results in the char-
acteristic white, avillous portions on the maternal surface of
aborted twin fetal membranes.441,442 Although histotrophic
nutrition (i.e., through secretions from endometrial glands
and absorption by the chorionic cells) is likely to remain
important throughout gestation, adequate hemotrophic nutri-
tion is essential to support the rapid fetal growth that occurs
during the latter part of gestation.4 The morphology of endo-
metrial blood vessels observed on uterine biopsy can vary con-
siderably, depending on the age and reproductive status of the
mare.443 Mild to severe degenerative lesions may be observed
in smaller and larger arterial and venous vessels in as many as
20.5% of the endometrial specimens examined.188 Unaltered
vessels were detected only in maiden mares.188
The incidence and severity of angiopathy increase with the
number of previous pregnancies and with advancing age.188,443
Changes in the endometrial vasculature of multiparous mares
have been compared with the so-called pregnancy sclerosis of
other species, with fraying and disruption of the elastic inter-
nal membrane, medial and adventitial elastosis and fibrosis,
and calcification processes within the media.188,443
In multiparous mares, cycles of vascular growth during
pregnancy and subsequent involution postpartum are thought
to result in progressive degenerative vascular changes in the
endometrium. Aging processes, chronic inflammation, and
short foaling intervals have been implicated as additional det-
rimental factors.188,437,438,443 Severe angiopathy is frequently
combined with phlebectasia and lymphangiectasia, possibly
indicating a reduced ability of the vessels to adapt to the vary-
ing demands of uterine circulation, with a decrease of uterine
perfusion and lymph drainage.188,443 In addition, mares with
a grade III biopsy score, consistent with severe endometrial
degenerative changes (Kenney and Doig classification249) had
lower vascular perfusion during early pregnancy than mares
with grades I and II (no or minimal endometrial fibrosis).444
Angiosis in older, multiparous mares might therefore be inti-
mately related to infertility, possibly because of detrimental
effects on early embryo nourishment and subsequent pla-
centation. Controlled studies have demonstrated the impact
that uterine capacity and placental area can have on the size
and birth weight of the foal and postnatal development.445-448
In one study, pony embryos were transferred into draft mare
recipients, and then the genetic dams were bred and allowed
to carry a full sibling to term.445 The embryo-transfer foals
 CHAPTER 19
were all larger than their siblings at birth, presumably due
to the larger uterus in the draft mare recipients.445 Although
the increased milk production of the draft mares may have
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explained the subsequent faster growth rates, it was noted
that all three draft-gestated foals were still heavier at 4 years
of age.445
Recently a similar study demonstrated that pony foals born
from draft recipient mares (i.e., a model for enhanced uterine
environment) had insulin resistance postnatally, whereas Sad-
dlebred foals born from pony mares (i.e., model for restricted
uterine environment) had increased sensitivity to insulin
and were considerably lighter.447 A similar embryo transfer
experiment used a Thoroughbred-in-Pony (Tb-P) and Pony-
in-Thoroughbred (P-Tb) comparison, with Thoroughbred-
Thoroughbred and Pony-Pony transfers acting as controls.449
The Tb-P foals were lighter than the P-Tb foals and had lower
placental weight, volume, and surface area and reduced post-
natal adaptive responsive and hypercortisolemia.448,449 Alto-
gether, these studies were consistent with an earlier study
in which a Shetland pony mare was inseminated with Shire
semen and a Shire mare was bred with Shetland pony semen.
The foal out of the pony mare was 50% of the weight of the half-
sibling that was gestated in the Shire mare, with the marked
size discrepancy remaining after maturity.448 On the practical
side, as mentioned in the discussion on embryo transfer, these
studies demonstrated the importance in embryo transfer pro-
grams of having embryo recipients compatible with the body
frame of the embryo donor to avoid effects of an enhanced
or restricted uterine environment. It is worth noting that sud-
den weight loss may mimic the situation of a restricted uterine
environment, which may result in deficient fetal growth and a
weak newborn foal. This has been observed in clinical practice
and demonstrated experimentally in Thoroughbred primipa-
rous mares using a Streptococcus equi subsp. equi infection-
mediating nutritional insults.450
Endocrinology of Pregnancy
Endocrinology of equine pregnancy has been elegantly
reviewed elsewhere, and the reader is referred to those pub-
lications for more detailed description of all endocrinologic
events that occur during pregnancy.4,451 Regardless of whether
the mare is pregnant or not, there is a rapid organization and
vascularization of the corpus hemorrhagicum, which culmi-
nates in the formation of a CL and increased progesterone
production.4 There is controversy as to whether large (i.e.,
granulosa cells origin) and small luteal cells (i.e., internal
theca origin) are steroidogenically active as in other domestic
mammals. The lack of progesterone receptors and steroido-
genic enzymes in small luteal cells substantiates the hypoth-
esis that small luteal cells do not secrete progesterone.452 It
is interesting to note that after undergoing artificial insemi-
nation, mares that became pregnant had significantly higher
progesterone concentrations as early as 5 days post ovulation
when compared with mares that did not become pregnant.453
Additionally mares experiencing pregnancy loss or premature
luteolysis may have decreased progesterone concentrations by
10 to 15 days post ovulation.454,455 This finding highlights the
importance of checking progesterone concentrations in mares
with recurrent embryonic death by 10 days post ovulation and
at pregnancy diagnosis on day 15 for mares exhibiting signs of
premature luteal regression (e.g., poor uterine/cervical tone,
endometrial edema, absent/small CL, presence of a smaller
than expected embryonic vesicle).455
Disorders of the Reproductive Tract 12711271
After day 15 post ovulation, nonpregnant mares normally
start undergoing luteolysis and return to estrus and ovulate
at 20 to 22 days on average from the previous primary ovula-
tion.4 However, some normal mares (bred and nonbred) may
experience prolonged luteal function caused by diestrual ovu-
lation, endometrial lesions, or for unknown reasons.4,66
In pregnant mares, the chorionic girdle is a distinct and
specialized structure that can be seen surrounding the top
third of the embryonic vesicle by day 25 post ovulation.398,399
At around 35 days post ovulation, invasive trophoblast cells
originating from the chorionic girdle detach from the embry-
onic vesicle and successfully invade the endometrium.4,456-460
The invasive cells aggregate to form the endometrial cups,
which are endocrinologically active tissue that secrete large
quantities of eCG.456-460
Endometrial cups become visible by day 38 to 40 as a ring
of small, pale plaques in the endometrium that surround the
developing conceptus.4,401-403 Because fetal cells are provided
by the sire and thus differ genotypically from the mater-
nal cells, the fetal antigens invoke a cell-mediated immune
response.461,462 This influx of lymphocytes creates a pro-
nounced, localized immunologic reaction, and by day 120 of
gestation, the endometrial cups are sloughed.461-463 The subse-
quent necrotic tissue and inspissated secretions form invagi-
nations into the chorioallantois and may still be seen on the
allantoic surface at delivery as allantoic pouches.464
Equine chorionic gonadotropin, a large-molecular-weight
glycoprotein, has both FSH-like and LH-like activity, as pre-
viously described.465 During early pregnancy, periodic surges
(10–12 days apart) of pituitary FSH trigger the waves of ovar-
ian follicular development.466 The eCG also promotes lutein-
ization and ovulation of ovarian follicles, forming accessory
(secondary) CLs that augment the progesterone production
from the primary CLs that developed at the time of concep-
tion.4,401,402 This process is critical to ensuring pregnancy
maintenance before the placenta is fully capable of supporting
pregnancy at ∼100 days’ gestation.4,401,402
High concentrations of eCG may be detected in the blood
of pregnant mares from 40 to 120 days' gestation.4,401 Interest-
ingly, mares losing pregnancies during this interval of gesta-
tion may have a prolonged and persistent presence of active
endometrial cups that secrete eCG, causing erratic estrous
behavior, unreliable follicular development, luteinization of
immature follicles, and unpredictable ovulation. Anecdotally,
the treatment of persistent endometrial cups can be attained
through laser therapy, intrauterine infusion of kerosene, lavage
of the uterus with hypertonic saline, and endoscopic removal
of cysts, but these have not been critically evaluated.
The equine embryonic vesicle is capable of producing large
quantities of estrogen.451 Estrogen concentrations increase sig-
nificantly in the yolk sac and uterine lumen by day 12 post
ovulation, with estradiol becoming the predominant estrogen
in the yolk sac by 18 to 20 days post ovulation.467 Another
unique feature of early gestation in the mare is that the cor-
pora lutea produce increasing concentrations of conjugated
estrogen (e.g., estrone sulfate) and testosterone in response to
eCG.468-471 Starting by 70 days post ovulation, there is a pro-
gressive increase in estrogen concentration (presumably of
fetoplacental origin), peaking by 210 to 240 days post ovula-
tion and progressively declining toward parturition.451
Fetoplacental estrogens are synthesized from androgens
produced by the enlarged fetal gonads.472 Bilateral fetal gonad-
ectomy performed between days 197 and 253 of gestation
 1272 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
causes a precipitous drop in plasma estrogen levels that then
remains basal until small foals are spontaneously delivered
in 70 to 97 days.473 After day 220 the enlarged gonads gradu-
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ally shrink into an insignificant size by birth.471 Two groups
of estrogens can be found in pregnant mares: classic phenolic
estrogens (estradiol, estrone, and their conjugated forms) and
equine-specific steroid ring B unsaturated estrogens (equilin
and equilenin).472 DHEA and 7-dehydro DHEA serve as pre-
cursors for classic estrogens and for ring B unsaturated estro-
gens (equilin and equilenin), respectively.
Four separate components combine to produce the proges-
terone and biologically active 5α-reduced pregnanes needed
to maintain pregnancy in the mare.4,451,474 The primary CL is
prolonged beyond its cyclical life span by the downregulation
of endometrial oxytocin receptors to prevent activation of the
luteolytic pathway. Its waning progesterone production is sup-
plemented from day 40 of gestation by the formation of acces-
sory CLs that develop in the maternal ovaries as a result of the
gonadotropic actions of pituitary FSH and endometrial eCG.4
The equine fetoplacental unit produces significant quanti-
ties of progesterone and C-21 progestogens.4,474 The placenta
(chorioallantois and endometrium) initially uses maternally
derived cholesterol to metabolize into pregnenolone and then
progesterone. A significant amount of progesterone origi-
nates from this source, starting from approximately day 70 of
gestation.4,474
In normal pregnant mares, peripheral progesterone con-
centration starts to decline by 4 months of gestation, reaching
baseline levels by days 150 to 180.473-475 Progesterone may be
undetectable in the serum by this time (<1 ng/mL), depending
on the type of assay used, and is no longer indicative of what
is happening at the uterine level, because the placenta secretes
progesterone and progestogens directly to the endometrium
and underlying myometrium. In the second half of gestation,
most of the placental-derived progesterone is further metabo-
lized into 5α-reduced pregnanes (5α-dihydroprogesterone
or 5α-pregnane-3,20-dione, and 20α-5P or 20α-hydroxy-5α-
pregnane-3-one, together with other 5α-reduced metabo-
lites of progesterone and pregnenolone).4,367,474 Even later in
gestation, it has been suggested that another steroid, perhaps
5α-pregnane-3,20-dione (5α-DHP) and not progesterone, is an
important precursor for the other progestin metabolites found
in circulating plasma.4,367,474 A recent study demonstrated that
5α-DHP binds to the progesterone receptor with at least the
same affinity to progesterone and is thought to be responsible
for pregnancy maintenance in the mare for the second and
third trimester of pregnancy.451,474 In the final months of ges-
tation, the enlarging fetal adrenal gland secretes appreciable
quantities of pregnenolone, which is then used by the placenta
to synthesize progestogens.4 Even at this late stage in equine
gestation, there is insufficient adrenal 17α-hydroxylase activ-
ity to convert the pregnenolone into fetal cortisol, so it passes
out in the umbilical vessels and is converted to 5α-reduced
pregnanes in the placenta. Thus, unlike with ruminants, there
is a significant increase in the mare’s plasma progestogen con-
centrations during the last 4 to 6 weeks of gestation followed
by a precipitous drop in concentrations at the time of partu-
rition.4,473 A premature rise in progestins has been observed
in mares with chronic placentitis, and this phenomenon is
thought to be associated with fetal stress and premature matu-
ration of the pituitary adrenocortical axis and more progester-
one escaping placental metabolization.476 When pony mares
were subjected to intrafetal injections of adrenocorticotropic
hormone (ACTH) at day 300 of gestation, maternal plasma
progestogen concentrations increased significantly.477
Physiology of parturition in the mare is not as well docu-
mented as in ruminants. The precise mechanism that couples
the fetal hypothalamic-pituitary-adrenal axis in the foal that
is carried to term remains to be determined.451,478 Across spe-
cies, under normal conditions parturition is triggered when
the fetus becomes fully mature.478-481 In the mare, the fetal
cortisol concentrations remain basal until the last 2 days' ges-
tation, when a marked rise culminates in parturition,4,481 and
enhanced adrenocortical activity in the fetus is also associated
with onset of parturition in many species.479,482 Final matura-
tion of the fetus results in increased ACTH release from the
pituitary and subsequent stimulation of the fetal adrenal cor-
tex. However, it is not until the maturing adrenal gland attains
17α-hydroxylase capacity that the high levels of pregnenolone
are metabolized into fetal cortisol.4,483,484 Disruptions of these
fetal maturational processes, with suppression of fetal adreno-
cortical activity, have been suggested to be key events in the
pathophysiology of fescue toxicosis.485 The normal fetal matu-
rational change (pregnenolone conversion into fetal cortisol)
causes the maternal progestogen levels to plummet, result-
ing in a rising estrogen-to-progestogen ratio, and in the final
hours, estrogen ultimately becomes dominant in the prepartu-
rient mare.4,451,486
Intrafetal injections of ACTH result in precocious matu-
ration of the equine fetus and reduction in gestational length
mediated through adrenal regulation of fetal maturation
and production of maternal progestogens.481 Further work is
required to establish the optimal gestational age and dosage
for maternal ACTH administration before clinical recommen-
dations can be given for this therapy.485
Previously it was thought that transplacental transfer
of cortisol was very minimal because of the presence of the
enzyme 11α-hydroxysteroid dehydrogenase, which inacti-
vates cortisol, converting it into cortisone.487 However, work
out of the United Kingdom demonstrated that healthy Thor-
oughbred mares receiving 100 mg of dexamethasone at days
315, 316, and 317 of gestation could deliver live foals.488 This
demonstrated that practitioners managing high-risk pregnan-
cies may be able to rescue the foal or improve the likelihood
of a viable foal being delivered alive if the above protocol is
applied.
Relaxin is produced by the placental trophoblast cells and
is speculated to be involved in softening the pelvic ligaments
to facilitate fetal passage and to promote uterine quiescence
until parturition is imminent.4 The myometrium becomes
more responsive to oxytocin and PG, and eventually the high
concentrations of oxytocin and PGs may overcome the inhibi-
tory effects of relaxin.4,483,489 The sudden dominance of estro-
gen is thought to promote cervical production of PGE2. PGF2α
promotes myometrial contractility by acting on intracellular
calcium, but PGE2 promotes cervical relaxation.486
Endocrinology of Parturition
The third trimester of pregnancy is characterized by increasing
concentrations in PGF2α, promoted by estrogen.490 Estrogen
also increases expression of oxytocin receptors and myo-
metrial gap junctions, facilitating the ability of the uterus to
have coordinated contractions. Interestingly, pregnant mares
experience an increase in estrogen and PGF2α concentrations
during the night,473,491 which may explain the phenomenon
of the majority of foalings occurring at night.492 Together this
 CHAPTER 19
results in increased myometrial contractility, which facilitates
normal parturition.493 During stage I of parturition, the con-
tracting myometrium forces positional changes in the fetus to
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prepare for expulsion, and the chorioallantoic sac begins to
be pushed against the softening cervix, eventually resulting in
rupture of the chorioallantois, which defines the onset of stage
II of parturition. Once the foal is engaged in the birth canal,
expulsive efforts during vaginal passage of the foal are driven
by rising oxytocin and prostaglandin concentrations, which
will reach peak concentrations during stage II of parturition.
Contraction of the abdominal muscles (maternal straining) is
almost always associated with large sustained uterine contrac-
tions. Mares with severe debilitating conditions (e.g., chronic
diarrhea, neoplasia), advanced age with poor body condition
score, and mares with abdominal bandage (e.g., following
colic surgery, body wall rupture, hydrops) may be unable to
have adequate abdominal contractions, resulting in a delayed
second stage of parturition and dystocia. Such mares need
assistance delivering their foals and may progress to a dystocia
due to uterine inertia if not assisted.
Concentration of PRL increases in the last week before par-
turition; this increase is responsible for mammary develop-
ment and the initiation of lactation.4 Prolactin release from
lactotrophs in the anterior pituitary is regulated by hypotha-
lamic secretion of PRL-releasing factor. The PRL-inhibiting
factor is thought to be dopamine.4 Oxytocin is synthesized in
the supraoptic and paraventricular nuclei of the hypothalamus.
Milk is produced in the alveoli and expelled into the lactifer-
ous ducts and teat cisterns when oxytocin causes contraction
of the myoepithelial cells. It is assumed that nursing by the foal
stimulates the release of oxytocin from the neurohypophysis.
Myometrial Activity
The myometrium of the uterus is composed of an inner cir-
cular and an outer longitudinal smooth muscle layer. This
arrangement of muscle fibers permits regulation of luminal
size (circular) and uterine length (longitudinal).4 The uterus
is palpably flaccid during and immediately after estrus and
then increases in tone and becomes turgid if the mare is preg-
nant.4,494 Myometrial activity is vitally important to uterine
clearance following breeding.494-496 Uterine contractions also
play an integral role during the embryo mobility phase of early
gestation.496 Between at least days 9 and 16 post ovulation, the
spherical equine conceptus migrates continuously throughout
the uterine lumen, propelled by peristaltic myometrial contrac-
tions.4,402 This unusually long period of intrauterine movement
ensures that the conceptus delivers its antiluteolytic signal to
the entire endometrium. Conceptus mobility is high between
days 10 and 14 after ovulation but can be reduced immediately
and markedly by an IV injection of flunixin meglumine.
This suggests that prostaglandins are the primary stimulus
for the myometrial contractions that drive migration of the
conceptus.407 The embryo produces prostaglandins that act as
myometrial stimulants, and then subsequent uterine contrac-
tions result in embryo mobility.404 The conceptus produces
estrogens by day 12, and these, along with embryonic produc-
tion of PGE2, are thought to play a role in stimulating uterine
contractions and increasing uterine tone during the mobility
phase.4 Progesterone is vital for embryonic development, and
it plays a role in the mobility, fixation, orientation, and main-
tenance of the equine conceptus.497
Because there is little, if any, progesterone in the maternal
circulation during late gestation, the quiescence of the uterus
Disorders of the Reproductive Tract 12731273
is thought to be maintained by progestogens, which are utero-
placental metabolites of pregnenolone and progesterone.367,498
These hormones are thought to play a significant role through
a paracrine action within the fetus and uteroplacental tis-
sues.498 Administration of a progestogen (altrenogest) will
prevent PG-induced abortion in the first trimester of preg-
nancy.115 There is considerable controversy and confusion sur-
rounding the use of progestogen supplementation in the later
trimesters, which will be discussed later.
The cellular mechanisms involved in myometrial contrac-
tility have not been well characterized in the pregnant mare,
and it may not be appropriate to extrapolate from studies in
nonpregnant mares. The classic theory in many species is that
myometrial excitation and uterine contractility are suppressed
by the so-called progesterone block.499 Progesterone and pro-
gestogens were once assumed to be necessary for myometrial
quiescence in the pregnant mare, and it was also thought that
binding of 5α-dihydroprogesterone to endometrial proges-
terone receptors controlled uterine prostaglandin production
and inhibited myometrial activity.500 It is now known that
5α-dihydroprogesterone binds to the progesterone receptor
with equal affinity.474 The oxytocin-neurophysin I gene is tran-
scribed into mRNA in the endometrium of mares, and mRNA
levels are negatively correlated with serum progesterone con-
centrations.501 However, progestogens were ineffective at con-
trolling myometrial contractility in vitro and did not inhibit
the effects of oxytocin, raising questions about the accuracy of
the progesterone block theory in the mare.502
A reduction in circulating progestogen levels by experimen-
tal blockade with the 3β-hydroxysteroid dehydrogenase inhib-
itor (epostane) did not increase myometrial activity (labor) in
late-gestation pony mares as it does in other species of domes-
tic animals.368,503 However, despite a paucity of evidence that a
deficiency of fetoplacental progestogen production is a cause
of pregnancy loss in the mare, exogenous progestogen therapy
is widely used as a form of preventive insurance in pregnant
mares, in the belief that it will promote uterine quiescence and
guard against the possibility of pregnancy failure. The proges-
togens may enhance the activity of the endometrial enzyme
15-hydroxyprostaglandin dehydrogenase, promoting rapid
metabolism of prostaglandins into inactive metabolites.368
Early cases of premature luteal regression can only survive if
the mare is treated with progestogens, and this has been used
as a reason to justify progestogen supplementation.455
Electromyographic activity in the uterus of pregnant mares
increases during the last week before foaling, even though the
circulating progestogen levels are still quite high.451,493,504 There
is a progressive, reversible rise in myoelectrical activity at night
in the last 6 days preceding parturition.505 The endocrine pro-
file of the periparturient mare is characterized by increasing
concentrations of progestogens and decreasing estrogens.369
Despite this decline, estrogens are essential for normal partu-
rition in the mare. Recent work suggests that nightly elevations
in estradiol-17β levels may bring about changes in the utero-
placental tissues, which facilitate the PG and oxytocin release
that promotes the onset of myometrial contractions.369 Pashen
and Allen demonstrated that if the fetal gonads are removed,
then the pregnancy would continue, but there were weak inef-
fective myometrial contractions and significantly reduced
prostaglandin production during labor.490 However, a recent
study failed to demonstrate the importance of estrogen in
late-term pregnant mares; peripheral estrogen concentrations
were reduced by 90% with letrozole (aromatase inhibitor), and
 1274 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
mares still delivered foals normally and no changes in vascular
perfusion were observed.369
The high levels of relaxin in the preparturient mare may
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act by inhibiting myometrial contractions until rising oxy-
tocin and PG concentrations become overwhelming.479 The
number of oxytocin receptors and myometrial gap junctions
may not increase until just before parturition in the mare.493
At that time the myometrium becomes remarkably sensitive
to even low doses of oxytocin.369 A rapid membrane depolar-
ization will result in the onset of strong, coordinated uterine
contractions that characterize the first stage of labor. In the
last 6 hours before rupture of the chorioallantois, a signifi-
cant increase in PGF2α concentrations occurs before there is
a significant increase in oxytocin concentration.506 Even if the
PGF2α concentrations are reduced by the COX inhibitor flu-
nixin meglumine (1.1 mg/kg), oxytocin administration can
still facilitate an expedient delivery.506,507
Teratogenesis
Little is known about the embryotoxic, and possible tera-
togenic, effects of chemicals, drugs, and other agents that
may be administered to pregnant mares. Goiters have been
reported in two newborn Arabian foals after the mares had
been supplemented with excess iodine during the final 24
weeks of pregnancy.508 Phenothiazines, thiabendazole, and
organophosphate anthelmintics have been reported to cause
pregnancy loss.6 Likewise, Sudan grass or sorghum pastures
have been reported to be toxic to the fetus.6,509 In recent years
more definitive documentation has become available with
respect to the toxic effects of some medications. When griseo-
fulvin was used to treat dermatomycosis in a mare during the
second month of pregnancy, the mare carried a male foal to
331 days' gestation.510 The foal showed bilateral microphthal-
mia, severe brachygnathia superior, and palatocheiloschisis.
The lesions were incompatible with life, and the animal was
euthanized. Griseofulvin administration during pregnancy
has been associated with similar lesions in other species.
Given that the development of the eyes and facial bones in the
horse occurs in the second month of pregnancy, the lesions
described in this case most likely can be attributed to griseo-
fulvin administration.
Three weak, recumbent neonatal foals with skin lesions,
including a thin, wooly coat, were born to mares being treated
for equine protozoal myeloencephalitis.511 The foals were anemic,
leukopenic, azotemic, hyponatremic, and hyperkalemic. The
pregnant mares had received sulfadiazine or sulfamethoxazole-
trimethoprim, pyrimethamine, folic acid, and vitamin E orally.
Serum folate concentrations in the three foals and two mares
were lower than those reported in the literature for clinically nor-
mal broodmares. At necropsy each foal had lobulated kidneys
with thin cortices and a pale medulla. The spleen and thymus
were small. Histologic examination revealed marked epidermal
necrosis without inflammatory cells, thin renal cortices, renal
tubular nephrosis, lymphoid aplasia, and bone marrow aplasia
and hypoplasia. These observations indicated that oral admin-
istration of 2,4-diaminopyrimidines (pyrimethamine with or
without trimethoprim), sulfonamides, and folic acid to mares
during pregnancy is related to congenital defects in newborn
foals. Further investigations are warranted to ascertain the toxic
agent and to determine at what stage of gestation the fetus is most
vulnerable. In general there is a paucity of research on known
teratogens in the pregnant mare, but research into the known
effects in the mare and effects in other species and the potential
risk and necessity of the given treatment should always be con-
sidered prior to administration of any medication to a pregnant
mare.
Y PREGNANCY DIAGNOSIS
Standard transrectal imaging technique will permit an expe-
rienced practitioner (using a 5-MHz ultrasound transducer
under optimal lighting conditions) to detect up to 98% of
embryos as early as day 11 after confirmation of ovulation.512
However, the first pregnancy check is not usually performed
prior to 14 days post ovulation, as asynchronous twins are more
likely to be diagnosed and the increased vesicle size makes
pregnancy confirmation easier. The black (anechoic) spherical
vesicle is characteristic of the ultrasonographic appearance of
the equine pregnancy at this stage. Novices should realize that
bright white (echoic) lines at the upper and lower margins of
the vesicle are the normal ultrasound artifact (referred to as
“specular reflection”) generated by the ultrasound waves pen-
etrating and reflecting through a perfectly round fluid struc-
ture.513 It also must be appreciated that the equine embryonic
vesicle can be anywhere in the uterine lumen before fixation
on day 16.
Diagnostic errors can easily be made unless the entire
length of both horns and the uterine body down to the cervix
are meticulously searched during an ultrasonographic exami-
nation. Confirmation of mobility, as well as the presence of
the specular reflection, is useful in differentiating an embry-
onic vesicle from a cyst. At the time of fixation at the base of
a uterine horn, the yolk sac has three germ layers (ectoderm,
mesoderm, and endoderm) near the embryonic pole, and only
two layers (ectoderm and endoderm) at the opposite pole.4
The difference in rigidity between the three-layered ventral
wall and the two-layered dorsal wall explains the character-
istic guitar pick–shaped image on ultrasound by day 18. The
thickest portion of the yolk sac wall (embryonic pole) rotates
to a ventral position. The change from the previous spheri-
cal shape is caused by uterine turgidity and thickening of the
dorsal uterine wall. The increased uterine tone is responsible
for the failure of the embryonic vesicle’s diameter to enlarge
between days 18 and 26, thus creating the classic growth pro-
file that plateaus during this period.4
By day 21 post ovulation, the amniotic cavity has com-
pletely formed, and the embryo can often be detected by ultra-
sound. As the allantoic sac enlarges, the embryo proper can be
seen to be raised off the ventral floor by day 24. The embryo
can be seen suspended on a thin echoic line that delineates
the apposition of allantois and yolk sac.513 This separating
membrane tends to be horizontal, and thus it is a useful means
for differentiating a singleton from twin embryonic vesicles.
In the latter case the adjacent walls of the two vesicles tend
to form a vertical separation. The primitive heartbeat can be
detected between 22 and 25 days and is a useful indicator of
embryonic viability. By day 40 the embryo (now called a fetus)
has been elevated to the dorsal pole because the allantoic cav-
ity has almost completely displaced the vestigial yolk sac. The
membranes and blood vessels that separate the allantois and
yolk sac give rise to the umbilical cord. The increasing size
of the fetus causes the fetus and amniotic sac to gradually
descend back to the floor of the chorioallantoic vesicle by day
48. The remnant of the yolk sac is incorporated into the umbil-
ical cord. The site in which the umbilical cord attaches to the
chorioallantois identifies the horn and site in which embryo
 CHAPTER 19
fixation originally occurred. The dorsal attachment ensures
that the developing fetus will not compress this vital area.402
These gestational developments can be used by the prac-
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titioner to determine whether the pregnancy is developing
normally. Generally each practitioner will have set gestational
ages that pregnancy evaluations are performed to ensure nor-
mal development of the pregnancy. Most practitioners will
perform ultrasound evaluations at the following times: 14 to
16 days to ensure normal size and identify the presence of
twins, 28 to 30 days to confirm normal development, heart-
beat and no twin before the formation of endometrial cups, 42
to 60 days to assess development and potential sex of the fetus,
and later checks vary more after this period with either one or
monthly evaluations thereafter. Generally mares with a history
of pregnancy loss or abnormal ultrasound findings are evalu-
ated and monitored more frequently to determine appropriate
management and treatment.
Although ultrasonographic examinations have become
standard practice for confirmation of pregnancy in mares, it
is still essential that the veterinarian be competent at manual
diagnosis. By 18 days after breeding, an experienced clinician
may be able to perceive changes in uterine tone and consis-
tency that, coupled with palpation of a narrow elongated cer-
vix, are consistent with early pregnancy. However, it should
be remembered that it is not uncommon for a persistent CL
to provide a prolonged progesterone environment in a non-
pregnant mare. It is important not to mistake the curvature
at the base of the uterine horn for an embryonic vesicle.4
An ultrasound image of the embryonic vesicle is required to
definitively confirm pregnancy at this early stage. However,
the gradually enlarging embryonic vesicle will eventually cre-
ate a discernible ventral bulge that has been described as being
the size of a hen’s egg (day 30), goose’s egg (day 35), and orange
(days 40–45). Because there is minimal dorsal distention at
this stage of pregnancy, it is essential that the ventral aspect
of each uterine horn be examined. Errors can be made if the
fingers are not passed far enough around the cranial aspect
of the uterine horn to reach well under the uterine body and
horns. A ventral bulge that is consistent with a 35- to 45-day
pregnancy can be identified by the distinct margins that are
palpable when the fingers are moved along the ventral aspect
of the uterus. The conceptus becomes more oval as it expands
during the third month of pregnancy. At 90 days, the chori-
onic vesicle is comparable in size and shape to a football. The
mare’s age and the number of previous foals will affect the rate
of descent of the gravid uterus over the pelvic brim. Positive
pregnancy diagnosis becomes progressively more difficult as
the large, heavy uterus descends into the abdominal cavity.
Normal pregnant mares should have a thin, pliable uterine
wall, whereas pyometra cases have a thickened uterine wall
and viscous purulent fluid in the uterus. The fetus itself is not
always palpable before day 120 of gestation, but gentle bal-
lottement will usually reveal the fetus after that time. Palpation
of some part of the fetus should be able to confirm pregnancy
status between 5 months and term.
Blood tests for pregnancy are sometimes indicated, espe-
cially in Miniature breeds.514 Measurement of eCG levels veri-
fies that the mare has endometrial cups but does not guarantee
that a viable fetus is still present.4 With this caveat in mind,
eCG is suitable for determining pregnancy status in Minia-
ture mares between 40 and 100 days after mating.515 However,
mares that have been diagnosed as pregnant should undergo
a blood estrone sulfate test 100 or more days after mating to
Disorders of the Reproductive Tract 12751275
eliminate the possibility of a false-positive diagnosis. Deter-
mination of eCG concentration is used to confirm suspicious
retention of endometrial cups in mares with history of losing a
pregnancy in the first 100 days.
The fetoplacental unit secretes large quantities of estro-
gen.4,451 Measuring blood estrone sulfate levels is recom-
mended as the method of choice for determining pregnancy
status in Miniature mares 100 or more days after mating.515
Fecal estrone sulfate measurements provide a noninvasive
alternative to blood testing from 150 days after mating. How-
ever, the discrimination between pregnant and nonpregnant
estrone sulfate concentration is not as great in feces as it is in
blood.515 Determination of estrone sulfate and eCG concentra-
tions can be used in some cases as confirmatory pregnancy
diagnosis tests. For example, Miniature mares presented for
pregnancy diagnosis are initially screened with an abdominal
ultrasound. If signs of pregnancy are detected (fetal fluids,
fetal heartbeat, and movements) then the mare is confirmed
pregnant, but if one fails to identify these findings with ultra-
sound, then blood can be collected for eCG and/or estrone
sulfate determination. Nonpregnant mares will have baseline
concentrations for both hormones.
Y MANAGEMENT OF TWINS
In the mare it is assumed that most twin pregnancies arise
from double ovulations, but occurrence of monozygotic
and triplet pregnancies has been reported.516-519 Presumably,
monozygotic twin pregnancies may occur more often in mares
following the transfer of a single embryo for unknown rea-
sons.516 There is a higher incidence of double ovulations in
Thoroughbred and Warmblood mares, but mares of any breed
may consistently double ovulate.520-524
In a large retrospective study involving more than 3000
cycles in 1581 Thoroughbred mares, multiple ovulation
occurred in 29.3% of cycles.523 Incidence of multiple ovula-
tion increased with age (20.7% in 2- to 4-year-olds; 35.6% in
17- to 19-year-olds). Multiple ovulations may occur synchro-
nously (same day or <2 days apart) or asynchronously (>2
days apart).4,523 Asynchronous ovulation is termed diestrous
ovulation because more than 2 days after the first ovulation
the concentrations of progesterone will rise and the mare is
in diestrus. Both synchronous and asynchronous ovulation
may result in twin pregnancies, particularly if semen from
a fertile stallion was used for breeding. This emphasizes the
importance of counting the number of CLs present at the first
(13–16 days) and second (23–28 days) pregnancy diagnosis,
as well as meticulous ultrasound evaluation looking for the
presence of a second embryonic vesicle, even if only one ovu-
lation was detected. Epidemiologically, mares ovulating from
different ovaries are more likely to have twin pregnancies than
mares ovulating in the same ovaries. In addition, asynchro-
nous ovulations within the same ovary are less likely to result
in twin pregnancies compared with synchronous ovulations in
the same ovary.4,525 In a large study with Thoroughbred mares
in the United Kingdom, 25.2% of multiple ovulations were
apparent as multiple pregnancies and 37.8% as single preg-
nancies at 13 to 14 days post ovulation.523 In a previous study
of Thoroughbred mares in the United Kingdom, the rate of
twin vesicles present at days 13 through 16 after ovulation was
reported to be between 10.3% and 13.1%.526 This was similar
to a Swedish study (n = 430) in which the frequency of twin
vesicles at days 14 through 15 was 10.5%.527
 1276 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
In the past, veterinarians often discouraged breeding of a
mare when two large (>30 mm) follicles were palpated or to
recheck the second follicle 10 to 12 hours after the first detected
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ovulation.528 Because an ovulated oocyte is less likely to result
in a viable embryo after this time, a delayed breeding could
be performed in anticipation of the second ovulation. Today
it is recommended to breed all eligible mares irrespective of
the number of preovulatory follicles and perform a thorough
pregnancy diagnosis between 13 and 16 days. The widespread
adoption of early ultrasonographic pregnancy examinations
has permitted the focus to be placed on embryonic vesicle
reduction after the presence of a twin pregnancy is confirmed.
Manual Reduction
The increasing size of the embryonic vesicle, coupled with the
increasing tone of the early pregnant uterus, will lead to the
fixation of the conceptus at the base of one uterine horn by day
16.4 When performing pregnancy diagnosis in mares, particu-
larly during the first 100 days of pregnancy, it is essential that
the ultrasonographic examination of the uterus is thorough,
ensuring a complete evaluation of both uterine horns and the
uterine body extending back to the cervix. This is especially
important before day 16, because the vesicle moves freely
within the lumen of both horns and the uterine body.525 If twin
vesicles are detected, then manually separating them before
day 16 will be easier. Successful elimination of one vesicle is
more likely at that time because the uterine walls are thin and
minimal pressure is required to crush a vesicle.529 A definite
pop can often be felt when the vesicle ruptures, but success
always should be confirmed by ultrasound. This sensation is
attributable to the rupture of the embryonic capsule.4,530
The downside to this approach is that an early embryonic
vesicle can easily be confused with an endometrial cyst. The
embryo itself does not become readily identifiable until the
fourth week of pregnancy (i.e., embryo proper and beating
heart). Thus it is good practice to note the size and location of
any cysts at the time the mare is being examined for breeding.
Uterine cyst mapping is more easily performed post ovulation
when the uterine horn becomes more toned because of the
increasing progesterone concentrations. Interestingly, some
cysts change shape according to the uterine tone. The print-
ing of high quality pictures of the cysts or the ability to record
them in a flash drive connected with the ultrasound machine
has proven particularly useful in mares with excessive lym-
phatic cysts. If there is no record of cyst size and location, then
it is virtually impossible to distinguish early twin vesicles from
a singleton and a cyst with a single examination. This is espe-
cially true because asynchronous ovulations are likely to result
in considerable size discrepancy between the two vesicles.4
If the clinician evaluates a mare at first pregnancy diagno-
sis and there is a suspicion of twins but no lymphatic uterine
cysts mapped, it is recommended that the clinician record the
size and location of each structure and reevaluate the mare in
1 or 2 days. In the next reproductive ultrasound, there will be
little change in format of lymphatic uterine cysts, but embry-
onic vesicles should grow approximately 4 mm per day and
are likely to move.530 Early diagnosis of twin pregnancies is
paramount for the best odds to successfully reduce one of the
embryonic vesicles before fixation because delays may make
separation of unilaterally fixed vesicles more difficult because
of their ongoing growth and the increased uterine tone.
Manual reduction of bilaterally fixed vesicles requires less
manipulation than with unilateral twins. It is a relatively easy
procedure, and success rates exceeding 90% are not uncom-
mon if the vesicle is crushed before day 16.529,531 After fixa-
tion a success rate of 75% is still possible if the bilateral twin is
crushed before day 30.529 If the vesicles are unilaterally fixed,
then the clinician should attempt to move the more proxi-
mal vesicle toward the tip of the uterine horn. At this loca-
tion the manual reduction procedure is less likely to disrupt
the remaining vesicle. The vesicle can be crushed by pinching
it between the thumb and fingers. Alternatively, the vesicle is
squeezed against the mare’s pelvis using the ultrasound probe
or fingers until it ruptures. If the twins can be separated before
crushing, then the success rate may be similar to that for
reduction of bilateral twins. If the unilateral twins cannot be
separated or are greater than 20 days' gestation, then the suc-
cess rate is lower.532 After fixation and with unilaterally fixed
vesicles (<20 days), it is the authors’ preference to reduce twin
pregnancies using the “snowflake” method, which consists of
applying pressure with the transducer until hyperechoic spots
(resembling snowflakes) are observed within the embryonic
vesicle. A perceived advantage of this method is that there is
less manipulation of the uterus and therefore less possibility
of trauma to the other vesicle. Potentially the damaged vesicle
that presented the snowflake appearance will release the fluid
from the yolk sac slowly, which will be less likely to dislodge
the viable vesicle and cause the loss of both embryonic vesicles.
Because squeezing an embryonic vesicle results in
increased concentrations of 15-ketodihydro-PGF(2α) and cor-
tisol,533 most clinicians commonly administer a combination
of antiinflammatories (flunixin meglumine 1.1 mg/kg q 24
for 3 days) and progesterone (150–300 mg/day per mare) or
altrenogest (0.044 mg/kg) until pregnancy diagnosis at 25 days
post ovulation.
Transrectal ultrasound should be used to identify twin
pregnancies and to maneuver the embryonic vesicle toward
the tip of the uterine horn or against the cervix in exceptional
cases. For a large majority of twin reductions, the authors rec-
ommend using the transducer of the ultrasound to identify,
manipulate, and squeeze the embryonic vesicle to be reduced.
In certain mares, one of the authors (IC) recommends mov-
ing the embryonic vesicle toward the tip of the uterine horn
with ultrasound and then squeeze one vesicle with the hand
without the transducer. This seems to be particularly useful for
small embryonic vesicles (∼10–12 mm). If the practitioner is
not able to comfortably separate vesicles that are next to each
other, then it is recommended to recheck the mare within 1
hour or during the next day if the embryonic vesicles are not
likely to be fixed the next day. Rechecking the mare the next
day may enable the practitioner to reduce one pregnancy man-
ually because the embryonic vesicles have grown in diameter
and might be located in an easier location to perform manipu-
lation and manual reduction.
The likelihood of success improves with experience.529,530 If
the unilateral vesicles are not detected until after day 20, then
manipulations can easily result in the disruption of both vesi-
cles. If the practitioner is not experienced in performing man-
ual twin reduction, then the unilaterally fixed vesicles should
not be the ones used to gain experience. The best option in
these cases may be to wait and see whether natural reduction
occurs or refer to a more experienced colleague.
Natural Reduction
There is negligible natural reduction of twins before day 15,
when the vesicles are close to the end of their mobility phase.4
 CHAPTER 19
Thus manual reduction is the treatment of choice if twins are
diagnosed before fixation. Almost three quarters (70%) of
twin embryonic vesicles become fixed unilaterally, with only
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30% of twin vesicles becoming fixed bilaterally.534,535 When
twin vesicles are dissimilar in size, there appears to be a much
higher incidence of unilateral fixation. The larger vesicle is
thought to serve as an impediment to the continued mobil-
ity of the smaller vesicle.402 Fortunately, natural reduction to
a singleton is far more likely with unilaterally fixed vesicles.
More than 80% of unilaterally fixed twins are likely to natu-
rally reduce to a singleton, with over half of these occurring
between days 16 and 20.6,158,159 On the other hand, the major-
ity of bilaterally fixed vesicles will continue to develop. The
proposed mechanism for reduction has to do with loss of
apposition between the embryo’s trophoblastic surface and the
endometrium, especially if the embryo proper is adjacent to
another vesicle.402,534-537
Pregnancy Termination with Prostaglandin
The probability of natural reduction occurring decreases sig-
nificantly by day 40.534,536 If natural reduction does not occur,
termination of the early pregnancy with a PG injection may
be considered. This should lyse the CLs that resulted from
the double ovulation, and the precipitous decline in proges-
terone will bring the mare back into estrus. However, treat-
ment failures have been reported, and successful termination
of the pregnancy should be confirmed by ultrasound.538 This
treatment must be given before day 35 because once the endo-
metrial cups begin to form, repeated PG injections may be
necessary to terminate the pregnancy.498 Owners should be
aware that the mare is unlikely to return to normal ovulatory
cycles until the cups are sloughed. In the interim, they secrete
eCG, a hormone that causes the development of accessory
CLs. As mentioned previously, mares with elevated eCG dem-
onstrate erratic estrous behavior, unreliable follicular develop-
ment, and unpredictable ovulation.
If a mare carries twins into the latter half of gestation,
then it is quite likely that abortion will occur between 7 and
9 months. Induced abortion is not without risk, and own-
ers should be aware of the potential for dystocia, cervical
lacerations, and fetal membrane retention.529 Although sev-
eral researchers have investigated induction of parturition
at term, few protocols for early termination of an advanced
pregnancy have been published. The natural PG analog clo-
prostenol has been used at various doses and frequencies, but
results are inconsistent with respect to efficacy and duration
to fetal expulsion. Daels et al. administered cloprostenol (250
μg) daily until fetal expulsion or for up to 5 days in mares that
were 98 to 153 days pregnant. Fetal expulsion occurred after
two to three cloprostenol administrations.498 The addition of
intracervical PGE1 on the second day may help dilate the cer-
vix and hasten delivery.
In Argentina, polo pony breeders do not want male colts;
thus a large number of embryo-recipient mares undergo
induced abortion to terminate pregnancies of male fetuses
following fetal gender determination by 60 days post ovula-
tion. Recently, a new technique was introduced that consists
of administering one dose of 500 μg of cloprostenol diluted
in 10 mL of saline intracervically; this technique resulted in
100% of the 104 mares aborted within 48 hours. A follow-up
study reported that 84.4% (27 of 32) of mares aborted in 48
hours following a single uterine infusion with cloprostenol.539
The same study reported that most mares underwent 1 to 2
Disorders of the Reproductive Tract 12771277
anovulatory cycles (57.2%), whereas about 37.5% apparently
ovulated normally and 6.2% progressed to anestrus. Follow-
ing abortion, 18 mares were reused as an embryo recipient
and became pregnant after embryo transfer (mean 58 ± 4.4
days).539
Transvaginal Ultrasound-Guided
Twin Reduction
Even though the advent of transrectal ultrasonography has
dramatically improved the ability of veterinarians to make
an early diagnosis of twin pregnancies, diagnostic errors still
occur. This could be caused by an early pregnancy diagnosis
when the second vesicle was too small to detect, incomplete
examination of the entire uterus, poor image quality, or an
inability of the clinician to differentiate two embryonic vesi-
cles that are closely apposed to each other. If natural reduction
does not occur or the diagnosis of twins is not confirmed until
after 30 days, then transvaginal aspiration of one vesicle is an
option.529,532,540 The results are best if the procedure is per-
formed before day 35 and preferably before day 25. Although
spontaneous reduction of twin pregnancies can occur even
after day 40, the probability of this occurring is low. Natural
twin reduction is more likely to occur if an obvious size dis-
crepancy between the two vesicles is present at this time.
If a transvaginal reduction is to be attempted, the mare
should be treated with flunixin meglumine. Many clinicians
will also administer oral altrenogest. Because sedation causes
significant uterine relaxation, most clinicians use a lidocaine
enema to reduce straining.541 The transvaginal aspiration
technique uses a 5.0-MHz or 7.5-MHz endovaginal curvilin-
ear transducer. The transducer and casing should be cold dis-
infected or sterilized before use. The assembled unit is then
placed in a sterile transducer cover that has been filled with
sterile lubricating gel. The transducer is advanced aseptically
until its footplate contacts the cranial vaginal wall, lateral to
the cervix. The clinician grasps the pregnancy rectally and
advances a sterile, 60-cm, 18-gauge spinal needle with an
echogenic tip along the needle guide in the transducer casing.
A dotted line on the ultrasound screen can be used to select a
path for the needle entry into the embryonic vesicle. A sharp
jab of the needle penetrates the vaginal wall, peritoneal lin-
ing, uterus, and ultimately the allantoic or yolk sac. A 60-mL
syringe is attached to the needle, and the embryonic fluid is
aspirated. Aspiration should be stopped when there is a danger
of damaging the adjacent vesicle of unilateral adjacent twins.
If a bilateral twin is being eliminated, then the needle can be
moved within the vesicle until all detectable fluid has been
aspirated. The success rate is better for bicornuate twin reduc-
tions.529 Death of the remaining twin is most likely to occur
within 2 weeks of the procedure. A recent retrospective study
compared two techniques for reducing twin pregnancies by
35 to 45 days post ovulation. Both techniques used the trans-
vaginal ultrasound-guided approach to either stab one of the
embryos/fetuses or to aspirate the yolk sac or allantoic sac, and
no difference in the results was found between the two tech-
niques.541 Experienced operators may achieve a live singleton
birth in about one third of cases.
Craniocervical Dislocation
Results of postfixation twin reduction techniques have been
inconsistent regarding the production of a single healthy foal.
A craniocervical dislocation method entails dislocating the first
cervical vertebra from the cranium, disrupting the ligamentous
 1278 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
attachments, and severing the spinal cord either through a
flank incision or transrectally.529 A transrectal approach may
be performed on a sedated mare between 60 and 90 days, but
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the mare’s body frame and operator’s arm length may limit
the ability to perform the procedure safely. For the transrectal
approach, propantheline bromide (30 mg IV) is recommended
to relax the smooth muscles of the uterus and rectum, and flu-
nixin meglumine (1.1 mg/kg) is administered to inhibit PG
release. Daily altrenogest (0.044–0.088 mg/kg) is recommended
for 3 to 4 weeks following the procedure or until the beating
heart from only one fetus is present. A surgical procedure has
been used most frequently on twin pregnancies of between
2 to 4 months’ duration, and the twin closest to the tip of the
horn is selected for elimination. This technique is performed
with uterine and fetal manipulation through a flank incision,
which enables one twin to be reduced before complete placenta
formation has occurred. This allows the remaining fetus to use
the entire endometrial surface and to grow to its full potential.
Interestingly, a fetus was reported as having a beating heart for
as long as 7 weeks following craniocervical dislocation.529
Transcutaneous (Abdominal)
Ultrasound-Guided Fetal Puncture
In advanced twin pregnancies (up to approximately 5.5
months), it is possible to attempt reduction by a transab-
dominal approach.532 Fetal intracardiac injection of potassium
chloride (KCl) is effective but requires accurate placement of
the KCl into the fetal heart. Best results are obtained when the
pregnancy is between 115 and 130 days. At this stage experi-
enced operators can achieve a 50% success rate.532 Procaine
penicillin G can cause fetal death when injected into either the
fetal thorax or abdomen, but the effect is not instantaneous.
The advantage of the latter treatment is that it does not require
precise placement of the injection into the fetal heart. Procaine
penicillin G also reduces the likelihood of bacterial infection,
and the injection can be visualized on the ultrasound screen.
Mares should be started on oral altrenogest, systemic antibiot-
ics, and flunixin meglumine on the day of the procedure. The
antibiotic coverage and antiinflammatory medication should
be continued for 3 days in uncomplicated cases.
A 3.0-mHz transducer can be used to image the 90- to 130-
day fetus in the caudal abdomen, just cranial to the udder, and
best results may be obtained after day 115.532,542 Once the mare
has been sedated, the uterus will relax, and the location of the
fetuses will shift cranially. A sedative–analgesic combination
that works well for this procedure is acepromazine (10 mg),
xylazine (100 mg), and butorphanol (10 mg). The smallest or
most easily accessible fetus is selected for reduction. The ven-
tral abdomen should be surgically prepared and local anes-
thetic infiltrated at the puncture site. An 18-gauge, 8-inch
spinal needle with stylet can be used for most fetal injections,
but the length of the needle is determined by the depth of
the fetus from the abdominal wall. Specialized needles with
echogenic tips are available to provide better visualization via
ultrasound.529 Once the location of the selected twin’s thorax
is confirmed, the needle is introduced through the aseptically
prepared skin, abdominal wall, and uterus. If procaine penicil-
lin G is to be injected, then the needle may puncture either the
fetal thorax or abdomen. Up to 20 mL is typically injected into
the fetus. Fetal death should be confirmed the next day.529,532
Although the benefits of supplemental progestin ther-
apy are debatable, many clinicians suggest that the mare be
medicated for at least 2 weeks if the initial twin reduction has
been successful. It is essential that fetal viability is checked
regularly because supplemental progestogen therapy may
interfere with normal pathways that facilitate elimination of
the dead fetuses if both die. Most abortions occur within 1 to
2 months after the reduction procedure.532 If the operator is
experienced in the technique, between 40% and 60% of cases
reported have resulted in delivery of a live foal, although it
should be noted that conservative estimates in clinical prac-
tice are more likely and often the remaining twin experiences
some degree of IUGR.529,532 The eliminated twin in these cases
can be seen as a mummified remnant contained within an
invaginated pouch that protrudes into the allantoic space of
the viable foal’s fetal membranes. One theory for the loss of
both twins after an intrafetal injection has to do with the pres-
ence of vascular anastomoses between the two fetoplacental
units.532 It has been suggested that circulation of either the
injected solution or other tissue degradation products could
result in the death of the adjoining twin fetus. Small anasto-
mosing vessels are present between twin vesicles as early as 40
to 60 days' gestation.
Y EARLY PREGNANCY LOSS
AND ABORTION
Embryonic Loss
Pregnancy losses occurring prior to day 40 of gestation are
defined as embryonic losses, whereas losses beyond this point
are considered fetal losses or abortions (Table 19.10).4 Accord-
ing to the stage of occurrence, pregnancy wastage may also
be classified as stillbirth (delivery of a dead foal ≥300 days of
gestation), abortions (losses from 40 to 300 days of gestation),
and neonatal losses (deaths during the first week or 60 days
of life).
Between 10% and 15% of mares undergo embryonic loss
or abortion at some time in gestation, and most of these losses
occur during the first 40 days' gestation, when the primary
CL is the sole source of progesterone.526,543 However, cur-
rent evidence suggests that untoward luteolysis is not com-
mon in this period as suspected, and the losses that do occur
have other underlying causes. Luteal insufficiency/premature
luteal regression has been documented, however, in mares as
described above.453,454
In a study of 376 Thoroughbred pregnancies, 12.2% expe-
rienced embryonic loss within 45 days after ovulation,544
whereas a much larger study (n = 3373 mares) reported a loss
of 7.2% to 8.0% by day 42.526 Three quarters of the losses in
the smaller study occurred between 16 and 25 days, and the
loss was highest in previously barren mares, followed by aged
mares (>15 years) and mares of more than 10 parities. These
results were similar to those reported by Swedish investiga-
tors.527 Increasing mare age was the single biggest limiting fac-
tor to an otherwise high rate of fertility in the larger study of
well-managed Thoroughbreds in the UK.526 Higher embry-
onic losses may be expected in mares that are bred during the
first postpartum estrus and in those with cysts in the uterus.
It is not easy to differentiate between fertilization failure
and embryonic loss before day 10 because this is the earliest
stage of development in which ultrasonographic detection is
possible under ideal research conditions. Fertilization failure
rates and embryonic losses are higher in aged mares.545-549 Fer-
tilization rates in young, well-managed mares may exceed 90%
 CHAPTER 19 Disorders of the Reproductive Tract 12791279

TABLE 19.10 Causes of Embryonic Losses in Mares

Intrinsic Endometrial disease Endometritis will have deleterious effects on the embryo, which may result in
prostaglandin production and early return to estrus
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Endometrial fibrosis causes improper embryonic nutrition because the horse is highly
dependent on uterine milk secretions for survival during the embryonary period
Large lymphatic uterine cysts in the uterine lumen may result in improper endometrial
signaling resulting in failure of maternal recognition of pregnancy
Large cysts present at the base of the uterine horn may result in embryonary death
caused by improper embryo nutrition from endometrial glands
Progesterone insufficiency Premature luteal regression or improper CL formation is thought to cause early return
to estrus, and low progesterone concentrations in plasma affect secretions of pro-
teins in the uterine milk and, consequently, embryonic growth
Maternal age Older mares have defective oocytes, advanced stage of endometrial fibrosis, more
lymphatic and endometrial gland uterine cysts, and endometrial fibrosis, which are
associated with higher pregnancy losses
Lactation Lactating mares experience higher rates of pregnancy loss, particularly if under poor
nutrition
Foal-heat breeding Mares bred in the foal heat have higher rates of embryonic losses, particularly if the
mare ovulates before day 9 postpartum, resulting in arrival of the embryo in utero
while the endometrium has not been completely regenerated
Postovulation breeding Breeding post ovulation results in higher pregnancy losses, probably related to oocyte
aging
Site of intrauterine fixation Embryonic vesicles fixed at the uterine body, particularly the caudal body, present
of the embryonic vesicle higher incidence of pregnancy loss; this condition is known as “body pregnancy”
Maternal chromosomal Mares carrying chromosome abnormalities are prone to producing defective
abnormality embryos, which result in embryonic or early fetal loss
Embryonic defects Embryos presenting with morphologic abnormalities and underdeveloped for the
stage of development result in higher embryonic losses
Extrinsic Stress Stress will result in an increase in cortisol concentration and potentially reduction of
LH and luteal function, or it may result in ovulation failure
Nutrition Poor nutrition is associated with reduced progesterone and higher rates of embryonic
losses
Season/climate Anecdotally severe weather (heat/cold) is thought to result in higher pregnancy loss
Under experimental conditions mares exercised under intensive Texas weather had
a reduced embryo recovery rate compared with mares without exercise, and they
tended to present more grade II embryos
Embryo manipulation Embryo transfer, in vitro–produced embryos, or embryos resulting from ICSI are
thought to result in higher pregnancy rates
  

CL, Corpus luteum; ICSI, intracytoplasmic sperm injection; LH, luteinizing hormone.

and appear to be over 80% in aged mares.547,550 Oocytes from
aged mares may be more likely to result in nonviable embryos
because of inherent morphologic defects.547,551 Carnevale
transferred oocytes from young and aged mares into young
recipients so that fertilization and early embryonic develop-
ment occurred in an optimal oviductal environment. The day-
12 pregnancy rate in the recipients that received the oocytes
from aged mares was significantly less than that achieved
with the younger mares’ oocytes.552 Research has shown that
embryo recovery rates are considerably lower in aged mares
and that there are significant losses occurring before day 14 of
pregnancy.545,553-555
The uterine environment may not be the only reason for
subfertility in some mares. Embryos collected from normal
mares resulted in similar pregnancy rates in both fertile and
subfertile recipients (advanced stages of endometrial pathol-
ogy) at day 28.556 In a reversal of study design, embryos were
collected from the oviducts of normal and subfertile mares
4 days after ovulation and then transferred into normal recipi-
ents. Pregnancy rates were lower in those normal mares that
received embryos from the subfertile donors.553 Thus, although
the uterine environment may have a delayed effect on embry-
onic and fetal loss, it appears that oocyte quality and oviductal
influences play a significant role in the problem of subfertility
and early embryonic loss in mares.557 In practice, embryonic
losses that may be detected between days 14 and 40 can range
between 8% and 15% in young, well-managed mares to 25%
or 30% in aged mares.526,550,558 The presence of endometrial
inflammation and uterine fluid accumulation will have a det-
rimental effect on early embryo survival and can markedly
increase the likelihood of early pregnancy loss.83,85,544
Early Fetal Loss
In one study of Thoroughbred mares, only 4% to 6% of preg-
nancy losses occurred between day 40 and day 150 gesta-
tion, and only a further 2% to 3% occurred before term.526
 1280 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
Formation of the endometrial cups is a defining moment
related to early pregnancy loss in mares. If the embryo dies
before day 35, the chorionic girdle cells do not invade the
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endometrium, and the endometrial cups do not form. These
mares should return to normal estrous cycle activity and may
be successfully bred again during the same breeding season.
However, if the fetus is lost after day 40, the endometrial cups
are irreversibly established.4 Thus, mares that lose the preg-
nancy after day 40 following endometrial cup formation will
have elevated eCG concentrations until those endometrial cups
slough between days 120 and 140 of gestation. This will result
in a false-positive blood test for pregnancy using an assay for
eCG. Retention of the endometrial cups after fetal loss results
in erratic estrous behavior, unreliable follicular development,
and unpredictable ovulation.161 Thus this unique physiologic
mechanism typically prevents mares suffering fetal loss after
endometrial cup formation from being bred back during the
current breeding season.160
Pregnancy losses in mares may be multifactorial and dif-
ficult to determine. Beyond day 40 of gestation the second-
ary corpora lutea receive powerful luteotropic support from
eCG, which results in increased progesterone concentrations.
This makes the corpora lutea resistant to luteolysis as multiple
exogenous doses of prostaglandin may be required to induce
abortion. From day 80 to 100 until term the supply organ (pla-
centa) and target tissues (endometrium and myometrium) are
in direct contact with one another over their entire surfaces.
Little evidence suggests that a deficiency of progesterone pro-
duction is a cause of pregnancy loss in the mare.543 Certainly,
fetal death may follow uteroplacental insufficiency or an over-
whelming sepsis.559 In recent years there has been a general
consensus that the inflammatory mediator PGF2α may play an
integral role in many cases of pregnancy loss. It is well known
that PGs are luteolytic and increase uterine contractility. Thus,
in the first 70 to 80 days, when the pregnancy depends on pro-
gesterone production by the corpora lutea (primary and acces-
sory), the mare is especially susceptible to the luteolytic effects
of PGs. It is important to remember, however, that repeated
exogenous PG injections may be required to electively ter-
minate a pregnancy once the endometrial cups have formed.
This is because some of the immature accessory CLs may not
be sufficiently developed to respond to the first PG injection.
Another probable abortigenic feature of PGs may be myo-
metrial hypermotility. This may be associated with placental
inflammation or high systemic levels of PG.
An early pregnancy may be lost subsequent to PG-induced
luteal deficiency associated with endotoxemia.560,561 The det-
rimental effect of the endotoxin could be prevented only if a
COX inhibitor (flunixin meglumine) was administered before
clinical signs of endotoxemia were evident.498,562,563 Thus,
although gram-negative septicemia and endotoxemia asso-
ciated with many gastrointestinal crises are known to result
in elevated levels of inflammatory mediators, any pregnancy-
sparing effect of PG inhibitors is likely to be effective only
if antiinflammatory agents such as flunixin meglumine are
administered in the acute phase of the disease.559 Because a
healthy fetoplacental unit can produce enough progesterone
to sustain the pregnancy after 80 days' gestation, the con-
cept of prophylactic altrenogest past 3 months of gestation is
controversial.371,498,543,563
Although recent in vitro studies suggest that progesterone
may not be the primary regulator of myometrial quiescence, in
situations in which elevated PG levels are likely, there appears
to be adequate clinical justification at present to provide exog-
enous progestogen support for high-risk pregnant mares.502,564
Based on current knowledge, the administration of a double
dose (0.088 mg/kg/day) of altrenogest is suggested during the
acute phase of a medical or surgical condition when PG levels
are likely to be elevated.565 If oral medication is not possible,
then short-term use of progesterone in oil (300 mg/day IV)
is warranted. An IM injection of a compounded long-acting
progesterone formulation (BioRelease P4 LA 150 mg/mL)
every 7 days may also be an efficacious and suitable alternative
to currently available progesterone formulations that require
daily administration.372 In the author’s practice, LA P4 is used
in situations where daily dosing is not possible or not reliable.
Mares at high risk for imminent abortion should preferably
receive short-acting progestogens.
Administration of supplemental progesterone is based
on further work by Daels et al. demonstrating that proges-
tin treatment could prevent PG-induced abortion at 3 to 5
months of gestation if a higher dose of progestin (0.088 mg/kg
altrenogest) was administered.498,563 Abortion did not occur
in five of eight progesterone-treated mares and eight of eight
altrenogest-treated mares, and endogenous PGF2α secretion
was inhibited, compared with values in aborting mares. It was
concluded that circulating progestogen concentrations may
play a role in the outcome of pregnancy during PG-induced
abortion, which may occur after exposure to endotoxin.
It seems logical that separation of the chorioallantois from
the endometrium will disrupt local endocrine function. The
fetoplacental unit does attempt to compensate for this placen-
tal dysfunction by increasing progesterone production.564,566
However, endotoxemia may harm placental circulation and
disrupt vital steroid metabolism within the fetoplacental unit.
Thus administration of flunixin meglumine to pregnant mares
is indicated early in the course of any condition in which
endotoxemia is possible.567-569 If a mare develops a surgical
colic condition during late pregnancy, then the fetus is at risk
not only from the maternal endotoxemia that can be associ-
ated with gastrointestinal crises but also from any maternal
hypoxic episodes that may occur during anesthesia.568,570-572
Acute enteritis or colitis in a pregnant mare can also result in
abortion caused by the effects of endotoxemia.570,572 Because
maternal hypoxia is a risk factor for abortion, intraoperative
hypoxia must be avoided if a pregnant mare requires surgery.
Approximately 16% to 20% of mares can be expected to abort
after colic surgery, but superior intraoperative ventilation and
oxygenation techniques may reduce this risk.570,572 Stage of
gestation and duration of anesthesia are less critical factors if
maternal oxygenation is adequate. Apparently, aberrations in
the cardiovascular and metabolic status of the mare and fetus
are more detrimental to pregnancy maintenance than the
actual medical or surgical condition.
Mare Reproductive Loss Syndrome
In the spring of 2001, an epidemic reproductive crisis affected
the equine breeding industry in central Kentucky, southern
Ohio, West Virginia, and Tennessee and ultimately cost hun-
dreds of millions of dollars. Mares foaled prematurely with
premature separation of the chorioallantois (late-term “red
bag” abortions). Many mares that were approximately 45 to
80 days pregnant suffered acute fetal loss, and most affected
mares failed to resume normal cyclic activity until after the
official breeding season had closed because endometrial cups
had been formed before the occurrence of mare reproductive
 CHAPTER 19
loss syndrome (MRLS).573 The Appalachian region to the
north also reported a high number of similar cases. Reports
of weather patterns and an unusually high emergence of east-
ern tent caterpillars (ETCs; Malacosoma americanum) were
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identical in both the central Kentucky and southeast Ohio
regions.574 The epidemic that affected the horse industry in
the Ohio Valley in late April and early May of 2001 and 2002
became known as MRLS.
During the initial outbreak, the state diagnostic laboratory
was inundated with late-term aborted fetuses, and practitio-
ners identified approximately 2000 early fetal losses.575 Many
of these were detected during what should have been a routine
fetal gender determination. Fortunately no contagious infec-
tious cause was identified, and this newly recognized disease
became self-limiting as the breeding season progressed. Vet-
erinarians and scientists involved in the epidemic considered
the possibility of mycotoxins, ergot alkaloids, phytoestrogens,
and even cyanide from wild cherry tree foliage.576-578 A tem-
poral correlation was established between MRLS and the pres-
ence of ETCs.573,576,579-590 Mares inadvertently ingest ETCs
when large numbers are present on pasture, hay, or in the
water supply. Abortions consistent with MRLS can be induced
by oral administration of whole ETCs or their exoskeletons,
which contain hairs (setae). Ingested setae embed into the
submucosa of the gastrointestinal tract. Fetal loss occurs when
bacteria from the alimentary tract (Streptococci, Actinoba-
cilli) establish infection in which the local immune system
is compromised (the fetoplacental unit). Management strat-
egies for controlling ETC have been proposed to reduce the
risk of MRLS.575,583 A similar abortion syndrome in Australia
is associated with ingestion of hairy processionary caterpillars
(Ochrogaster lunifer).590
Placentitis
Placentitis is a major cause of pregnancy loss in late-term
pregnant mares.178,591,592 Inflammation of the placenta can
affect the interchange of gases, nutrients, and waste products
along with disruption of both fetal metabolic and endocri-
nologic pathways.593 In recent years, controlled studies and
clinical observations from various laboratories and practices
across the world have contributed to major advancements in
the recognition and treatment of equine placentitis. The reader
is referred to recent comprehensive reviews for additional,
more detailed, information.594,595 Four types of placentitis
are described based on macroscopic lesions: ascending (focal
extensive), nocardioform (focal mucoid), diffuse (hematog-
enous), and multifocal.594
The disease tends to be a sporadic, individual mare problem
that seldom has any lasting effect on mare fertility. Both bacte-
rial (Streptococcus zooepidemicus, S. equisimilis, E. coli, Entero-
bacter agglomerans, P. aeruginosa, and K. pneumoniae) and
fungal (Aspergillus spp.) organisms may be the cause. Over-
all, ascending placentitis is the most common type observed
worldwide. 594 Ascending infection results in necrotizing and
suppurative inflammation of the chorioallantois that may
lead to detachment of the placenta in the area surrounding
the cervical star and ventrally toward the uterine body. 594 At
the time of diagnosis, the cervix is usually soft, and purulent
exudate may be found draining into the vagina. Because the
cervical star is the most common site of placentitis in mares,
this part of the fetal membranes should be thoroughly and
closely examined after abortion and at any foaling. The ves-
tibular sphincter, cervix, and vulvar lips are important barriers
Disorders of the Reproductive Tract 12811281
to prevent ascending infections. Many aged mares require a
Caslick procedure and cervical reconstruction to prevent the
likelihood of ascending infection. Young mares, however, with
apparently appropriate vulvar conformation and intact cervix
may also develop ascending placentitis. The most commonly
isolated bacteria are beta hemolytic streptococci (Streptococ-
cus equi subsp. zooepidemicus or equi), E. coli, and Enterococ-
cus spp., although a broad range of other bacteria have also
been isolated from affected mares. In some horses, mixed bac-
terial and fungal infections occur; it has been suggested that
the fungal infection occurs secondary to a primary bacterial
infection.594
Focal mucoid placentitis is characterized by lesions located
in the base of the uterine horns and uterine body.596 It is com-
monly associated with nocardioform placentitis in which
the fetal lungs are also affected with suppurative lesions, but
other microorganisms (e.g., Cellulosimicrobium cellulans) can
cause similar lesions.597 Nocardioform placentitis was first
diagnosed in mares in central Kentucky in 1986 as a sporadic
cause of abortion and weak foals. Since that time, it has been
described in mares in Florida, Italy, South Africa, and Aus-
tralia.594,596 The number of confirmed cases of nocardioform
placentitis has varied widely from year to year, with more than
400 cases in central Kentucky in 2011.
Nocardioform placentitis is associated with gram-positive
branching actinomycetes including Crossiella equi and Amyco-
latopsis spp. It has been suggested that these microorganisms
may gain access to the uterus at breeding, but this unusual
form of equine placentitis does not become apparent until
the latter part of gestation.598 The initial lesion is localized on
the most dependent aspect of the chorion in the cranioventral
aspect of the uterine body and subsequently extends cranially
into the base of the horns and circumferentially around the
placenta.596 Outcomes vary from abortion to birth of a nor-
mal foal. Some foals are born prematurely, whereas others are
delivered at term but may be stillborn or weak with an emaci-
ated appearance.594,596, 598 Vaginal discharge is not a feature of
this condition because the region of the placenta including the
cervical star is not involved. After the fetus has been expelled,
affected mares rapidly clear the infection and usually experi-
ence no adverse effects on subsequent fertility.594,596,598 When
the fetal membranes are examined, there is an obvious line of
demarcation between pathologic and normal tissue, with the
affected area being covered by a characteristic thick, brownish,
mucoid, viscous material.594,596,598 The underlying chorionic
villi are reduced in size, and in the central portion of the lesion,
the chorionic surface may be completely denuded.594,596,598
Leptospira spp., the most common cause of hematogenous
placentitis,594 causes diffuse lesions with large numbers of spi-
rochetes in the affected placental tissues.596 Its occurrence is
rather sporadic, but outbreaks have been described.594,596 Late-
term mares may abort with no premonitory clinical signs, and
occasionally an infected premature or full-term weak, icteric
foal may be delivered. The placenta is edematous, with a
necrotic chorion covered with a mucoid exudate.178,596,599 The
gross placental lesions are associated with thrombosis, vascu-
litis, and inflammatory cell infiltrates. The spirochetes tend
to be numerous and are readily demonstrated in the stroma
and villi of the placenta.596,599 A microscopic agglutination
test (MAT) on fetal fluids (heart and body cavities) or mater-
nal serum is likely to reveal a high titer (1:6400-1:819,200 or
greater).600 Leptospires may be detected in the fetus by the
fluorescent antibody test (FAT), silver staining, or darkfield
 1282 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
microscopy.600 Immunohistochemistry is more sensitive than
silver staining and more specific than serology (MAT).601,602
The fetal kidney should be submitted for a FAT because this
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tissue yields the highest percentage of positive results and is
also the best tissue for culture.596,603 If urine is to be submitted
from an infected mare (FAT or darkfield analysis), it is impor-
tant to obtain collection instructions and an appropriate trans-
port medium from the diagnostic laboratory. The specimen
must be obtained before any antimicrobial therapy has been
administered. A recent retrospective study demonstrated that
PCR is the most sensitive method in diagnosing Leptospira
spp. in abortion cases.600
In the genus Leptospira, the species L. interrogans con-
tains several pathogenic serogroups (common antigens) and
serovars (specific strain). Serogroups consist of closely related
serovars. The predominant serovar affecting horses varies with
country and region. The Bratislava serovar is most commonly
isolated from aborted fetuses in Northern Ireland, but in cen-
tral Kentucky most leptospiral abortions have been associated
with the Pomona serogroup, occasionally the Grippotyphosa
serogroup, and rarely the Hardjo serogroup.600,604 Equine lep-
tospiral infections previously reported as being L. pomona are
now thought to be more correctly identified as L. interrogans
serogroup Pomona serovar Kennewicki and L. kirschneri sero-
group Grippotyphosa serovar Grippotyphosa.600,604 In North
America pregnant mares are considered to be incidental hosts
that become infected after exposure from maintenance hosts
(i.e., wildlife such as skunks and raccoons for Kennewicki and
Grippotyphosa and cattle for Hardjo).600,604 Infected mares
may shed leptospires in the urine for up to 14 weeks.604 Thus
therapy is aimed at prevention of urinary shedding and pos-
sibly prophylactic treatment of pregnant in-contact mares that
have high titers. A combination of penicillin (10,000 to 15,000
IU/kg, administered intramuscularly) and streptomycin (10
mg/kg administered intramuscularly) every 12 hours for a
period of 1 week has been recommended, but streptomycin is
no longer widely used in equine practice. High doses of potas-
sium penicillin G (20 million units IV every 12 hours) may
be effective in preventing infection of a fetus if the mare has
a high titer, but this recommendation has not been validated
in controlled studies. The dosage and duration of treatment
appear to be important. Oxytetracycline (5 to 10 mg/kg) has
also been suggested, but it was less effective at preventing uri-
nary shedding of leptospires in all cases tested (5 of 7 infected
mares).605 Anecdotally, doxycycline and enrofloxacin have
been used in clinical practice as tools to prevent abortion in
mares exposed to other mares aborting with leptospiral infec-
tions, but it is important to note that to date neither drug has
been proven to be safe to the fetus or efficacious at treating and
preventing placentitis in mares.
An approved vaccine for leptospirosis recently became
available for horses in the United States, but its efficacy for
prevention of abortion has not been assessed. Attempts
should be made to prevent direct contact between mainte-
nance hosts and pregnant mares and also to prevent expo-
sure to urine infected by these species (e.g., contaminated
water and feed).594 It may be prudent to vaccinate mares
with the equine vaccine if they reside on the same property
as pregnant mares with confirmed leptospiral abortion and
to isolate aborting mares.594,596
Rhodococcus equi has been incriminated as the cause of
placentitis and abortion in mares.606 Mycoplasma spp. have
been associated with infertility, endometritis, vulvitis, and
abortion in mares.607 Nocardia spp. have been described as
a cause of placentitis in two mares in Florida. Lesions were
similar to nocardioform placentitis, but foals were born with
suppurative lung lesions.608 Cases of mycobacterial abortion
and placentitis were confirmed by microbiologic techniques,
PCR, and immunohistochemistry.609 The atypical mycobac-
teria were within the nontuberculous group and classified as
saprophytic and opportunistic microorganisms acquired from
the environment (soil, water, and decaying vegetation).609,610
Gross lesions observed within the submitted cases varied from
none to those of a “nocardioform-like” placentitis. Affected
fetuses exhibited varying degrees of malnourishment and
chronic placentitis. Several fetuses had granulomatous to pyo-
granulomatous pneumonia, and one fetus without pneumonia
contained disseminated granulomas in various organs.609,610
Cellulosimicrobium cellulans is a gram-positive branch-
ing bacillus that is an opportunistic microorganism found in
the soil.597 The nine described cases of equine abortion and
placentitis resulting from C. cellulans had nocardioform-
like placentitis lesions as well as granulomatous pneumonia.
Because atypical Mycobacteria and C. cellulans organisms can
cause similar gross and histologic lesions within the fetus and
placenta, they should be considered as differential diagnoses
when gross placental lesions suggestive of nocardioform pla-
centitis are encountered.597,609,610
Protozoal Abortion
There is limited information available on the association
between equine Neospora infections and abortions.611-616 How-
ever, the apicomplexan protozoan parasite Neospora caninum
has been recognized as a major cause of abortion in cattle.616
Antibodies against Neospora spp. have been described in
mares that recently aborted.614 Using an agglutination test,
researchers found that the number of animals with elevated
(>80) anti-Neospora spp. antibody titer was higher in a group
of 54 aborted mares than in a randomly chosen group of 121
mares (P < 0.001). N. caninum DNA was found in 3 of 91 fetal
brains, 2 of 77 fetal hearts, and 1 of 1 placenta and was present
in both brains and hearts of two fetuses. The mere presence of
the organism in an aborted fetus does not necessarily implicate
it as being the cause of the abortion.616 Antibodies to Neospora
spp. were detected in the sera from 11.9% of 800 asymptom-
atic horses in Israel and from 37.5% of mares that aborted.617
Antibodies to Neospora spp. have also been detected in mares
in Brazil.612 Further investigations will be needed to determine
whether there is an association between equine reproductive
failure and Neospora spp. infection.612,615
Viral Abortion
Equine arteritis virus (EAV) and equine herpesvirus 1 (EHV-
1) are the most important causes of viral abortion in horses in
the world. Both viruses are associated with acute respiratory
tract infection and are discussed in detail in Chapter 8.
EAV is transmitted through inhalation or venereally in the
semen of asymptomatic (shedder) stallions.618-623 Abortion
may occur if pregnant mares become infected in the later stage
of gestation (5–10 months).619,622,624,625 Clinical signs are vari-
able but may include fever, conjunctivitis, nasal discharge, and
dependent edema that is associated with vasculitis.618,620,626
Clinical signs are mild or subclinical in many horses and
may be clinically indistinguishable from other respiratory
infections. Viral myometritis with degeneration of myocytes
and infiltration of mononuclear cells leads to transplacental
 CHAPTER 19
infection of the fetus.627 Affected placentae are edematous,
and degenerated fibroblasts may be observed in the subvil-
lous layers. Lesions in the fetal tissue include an atrophy of
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the lymphoid follicles in the spleen and lymph nodes with
degenerated lymphocytes. Immunofluorescence can detect
EAV antigen in the myometrium and the endometrial glands
in the dams, in the subvillous layer of the placentae, and in the
aborted fetuses. The virus may be recovered from the uterus
and fetus, but the placenta is likely to yield the greatest amount
of the virus. The disease may be controlled by an effective vac-
cination program and screening tests.618
Most abortions associated with herpesvirus are caused by
EHV-1, but occasional abortions are associated with other
equine herpesviruses.592,628 The number of abortions result-
ing from EHV-1 infection has declined over the past 20 years,
and isolated abortions, rather than abortion storms, are now
a more common feature of this disease.629 This is due to the
widespread adoption of stringent vaccination programs in
combination with improved management practices on brood-
mare farms.630,631 Pregnant mares should be vaccinated with
an approved vaccine at 5, 7, and 9 months of gestation. Many
farms also vaccinate at 3 months. New arrivals should be iso-
lated for 3 weeks, and groups of pregnant mares should be
isolated by stage of gestation. It is especially important to seg-
regate pregnant mares from weanlings and other horses.632
EHV-1 can infect the fetus if a mare is viremic during
pregnancy. The virus causes abortion as a result of the rapid
detachment of the placenta.633,634 Endothelial cells in the
endometrium and allantochorion are often infected by the
virus, with accompanying vascular lesions. The fetus can be
infected by way of the chorionic vasculature or by inhalation
of infected amniotic fluid.635-637 Abortion may occur soon after
the mare is infected or several weeks have elapsed. Therefore
maternal serology is of little diagnostic value.638 The aborted
fetus will be fresh, with copious amounts of pleural and perito-
neal fluid. The trachea may contain a fibrin clot. Small necrotic
foci may be discernible on the swollen liver. A hyperplastic,
necrotizing bronchiolitis may be seen in lung sections, and
large intranuclear eosinophilic inclusion bodies are a char-
acteristic histologic lesion. Although vaccination is widely
practiced, owners should be aware that the protection is not
absolute. If a pregnant mare is exposed to infected animals
that have recently been to a show or that are returning from a
training facility, then it is possible that any protective immu-
nity conferred by the vaccine will be overwhelmed. Abortions
have been associated with reactivation of latent virus that was
induced by transport stress.639 Therefore a history of regular
vaccination of an aborting mare does not eliminate the pos-
sibility of a herpesvirus-related abortion. Neutralization and
indirect immunofluorescence tests, as well as PCR and virus
isolation, are used for EHV-1 diagnostics. Antigen detection,
in combination with virus isolation and PCR from fetal lungs,
gives reliable results. More detailed reviews have been pub-
lished, and the reader is referred to these for a more in-depth
discussion.640,641
A number of other acute viral infections have been asso-
ciated with abortion in horses, especially if the horse suffers
severe systemic illness at the time of initial infection. For
example, mares may abort as a result of the systemic effects of
acute infection with equine infectious anemia virus (EIAV),
although it is not generally considered an abortigenic virus.642
When widespread vaccination against West Nile virus was
adopted in the United States, some suggested that the killed
Disorders of the Reproductive Tract 12831283
virus vaccine that was used might result in abortions, still-
births, and deformities in foals. However, subsequent criti-
cal review clearly demonstrates that vaccination of pregnant
mares during any period of gestation is not associated with an
increased incidence of pregnancy loss.643
Treatment of Placentitis
Under field conditions, placentitis is diagnosed in mares pre-
senting with compatible clinical signs of premature mammary
gland development and vulvar discharge (with ascending pla-
centitis). These clinical signs should prompt the practitioner to
perform a transrectal palpation and ultrasonographic exami-
nation. Typically mares presenting with signs of placentitis
will have demonstrable placental thickening and separation of
the placenta from the endometrium.594
Placentitis is detrimental to the pregnancy not only because
it disrupts nutrient exchange but also because of the inflam-
matory mediators (proinflammatory cytokines) that are
released. The exact cause of fetal expulsion is not known, but
ensuring myometrial quiescence is central to most therapeutic
regimens.505,644 Placentitis cases have substantially increased
concentrations of PGF2α and PGE2 in the fetal fluids.645,646
Thus antiinflammatory medication (flunixin meglumine at
1.1 mg/kg; phenylbutazone at 4 mg/kg, every 12 hours) is
generally recommended,647 although there are no controlled
studies to specifically demonstrate their efficacy. 594 Placenti-
tis associated with early abortions tends to be acute, with the
fetus succumbing to bacteremia with no to minimal placental
lesions.648
Broad-spectrum antibiotics that have been recommended
for treatment of equine placentitis include trimethoprim-­
sulfadiazine (15–30 mg/kg PO every 12 hours), procaine peni-
cillin (30,000 IU/kg/day) and gentamicin (6 mg/kg/day), and
ceftiofur (1–5 mg/kg, every 12 hours).647,649-651 Ceftiofur has
been used for treatment of placentitis, but a recent study dem-
onstrated that this drug does not cross the placenta and was
ineffective for treatment of experimentally induced placenti-
tis. 652 Gentamicin was undetectable in the plasma of newborn
foals after mares were treated with the antibiotic (6.6 mg/kg)
an hour before parturition, and it was initially believed that
gentamicin does not cross the placenta of mares at term.653
Murchie et al. monitored drug concentrations in the allantoic
fluid of pregnant pony mares using in vivo microdialysis to
determine whether this method could detect allantoic concen-
trations of drugs in normal mares and those with placentitis.654
Pharmacokinetic comparisons indicated that potassium peni-
cillin G (22,000 IU/kg q.i.d.) persists much longer in allantoic
fluid than blood, whereas gentamicin (6.6 mg/kg/day) exhib-
ited similar profiles in the two compartments. Flunixin meglu-
mine (1 mg/kg b.i.d.) was not detected in allantoic fluid. In
infected mares penicillin G achieved a similar peak concen-
tration in allantoic fluid, whereas peak gentamicin concentra-
tion appeared to be reduced relative to drug concentrations in
noninfected mares. Thus penicillin G and gentamicin appear
to undergo effective placental transfer in pregnant mares, but
transplacental drug transfer may be altered selectively if active
placental infection is present.
If the localized production of high concentrations of pros-
taglandins stimulates the formation of gap junctions, then
the subsequent myometrial hypermotility may impede pla-
cental blood flow as the uterus contracts.505,644,655 This will
reduce fetal oxygenation and increase fetal stress. Because it
is known that progesterone inhibits gap junction formation,
 1284 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
it has been suggested that progestin supplementation may be
beneficial when uteroplacental inflammation is suspected.594
This is the rationale behind the current recommendation to
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treat suspected placentitis cases with a double dose of altreno-
gest (0.088 mg/kg/day).594,647 Delaying premature labor long
enough to allow accelerated fetal maturation may improve foal
survival rates.656
A primary goal in the treatment of placentitis is to delay
premature labor long enough to allow accelerated fetal mat-
uration to occur, with the goal of improving foal survival
rates.594 The progestogens may enhance the activity of the
endometrial enzyme 15-hydroxyprostaglandin dehydroge-
nase and thus promote rapid metabolism of PGs into inactive
metabolites.368,564 Although altrenogest is not metabolized
to 5α-pregnanes, both 5α-DHP and 3β-5P levels may be
increased as a result of supplementation.657 However, Ousey
and others have suggested that progesterone supplementation
may be contraindicated because high levels could inhibit the
placental enzyme 3β-hydroxysteroid dehydrogenase.368,564,658
This enzyme produces progesterone from pregnenolone;
thus inhibition could interfere with the normal fetoplacen-
tal steroidogenic pathway. At present this widely used ther-
apy remains controversial, and even if it does no harm, the
expense of long-term progestin supplementation may not be
warranted in many cases. Essentially, the use of hormone ther-
apies is subjective and to a large extent reflects lack of under-
standing about the endocrine relationships among the mare,
placenta, and fetus.
The rationale for other treatment regimens is based on
extrapolations from the human medical literature and appli-
cation of sound reasoning for the potential efficacy of a par-
ticular drug. Scientific investigation in this area is crucial.
Previously, an oral β2-sympathomimetic drug (clenbuterol)
has been suggested to suppress uterine motility in mares with
placentitis.647,659 In the United States the product is marketed
as an oral formulation to treat chronic reactive airway obstruc-
tion. Research is needed to determine what oral dose of this
bronchodilatory compound, if any, is actually effective on the
gravid uterus. In countries in which an intravenous formula-
tion is available, a 300-μg IV dose of clenbuterol will reduce
uterine tone for approximately 2 hours.660,661 However, daily
IV administration of clenbuterol to mares showing maximal
milk calcium levels was not effective in preventing the onset of
myometrial contractions and delivery in normal foaling mares
at term.662
The administration of pentoxifylline (8.5 mg/kg PO b.i.d.)
is questionable. While it does not seem to improve perfusion
in the mare reproductive tract,663,664 some clinicians advocate
it because it is used in humans to treat tissue ischemia, because
of its ability to modulate the inflammatory process by down-
regulating proinflammatory cytokines, and because of its
possible effect on erythrocyte deformability.647,649,656 Pentoxi-
fylline appears to have good uterine penetration and has been
detected in the allantoic fluid of mares.650,651 Despite these
conflicting studies, a multipronged approach (i.e., antibiotics,
antiinflammatory agents, altrenogest) to long-term therapy
for placentitis may improve fetal survival and foal viability.
Noninfectious Causes of Abortion
Twins
In North America the incidence of twin abortions has
decreased significantly because of early intervention after
ultrasonographic diagnosis of a multiple pregnancy.178,529,532
Before the widespread adoption of this technology, twin
abortions were a major cause of fetal loss.441,442 A large Euro-
pean study (n = 12,648 pregnancies) of Thoroughbred mares
revealed a twinning rate of 3.5%, with 443 twins and only two
triplets.665 The type of placentation in the mare (diffuse, micro-
cotyledonary) makes it highly unlikely that a twin pregnancy
will be carried to term. Obviously there is a finite endometrial
surface area available for allantochorion attachment. The more
common unicornuate twin vesicles are a problem, because
one conceptus is inevitably restricted to the proximal aspect
of the gravid horn.421 Thus the two conceptuses are literally
in a deadly competition for adequate nourishment and subse-
quent placentation. If the twin pregnancy is maintained until
the latter part of gestation, the nutrient demands of the rap-
idly growing fetuses outstrip the placental attachments. Fetal
growth is such that nutrient demands may be met until the lat-
ter half of gestation, when the marked fetal development in the
last trimester usually requires more exchange capability than
the smaller placenta provides. The fetus becomes stressed as
it becomes progressively emaciated and ultimately dies.529,666
Death of one fetus or both fetuses is followed by abortion, with
the characteristic avillous areas on the fetal membranes con-
firming the amount of placental disruption.178,442,522 Affected
mares develop premature mammary enlargement and may
“run” milk before aborting. Transabdominal ultrasonographic
evaluation may be useful to confirm the diagnosis at this late
stage. Although the area of apposition of the two chorioallan-
toic membranes (twin membrane) may be seen, measurement
of fetal thoracic diameters and heart rates can confirm the
diagnosis of twins.666 Twin abortions in the last few months
of gestation are likely to cause a dystocia. Bicornuate twins are
more likely to survive, because each membrane can attach to
an entire horn and one side of the uterine body, but the result-
ing foals are likely to be stunted as a result of IUGR.402,442,529
The live birth of twin foals is extremely uncommon, and many
of these neonates do not survive, with as few as 14% of surviv-
ing foals reaching the second week of neonatal life.442,531 The
mares are prone to fetal membrane retention and may be diffi-
cult to rebreed. Thus it is not surprising that the equine breed-
ing industry has always tried to prevent twin pregnancies.
After such a diagnosis the owner is faced with three choices:
attempt elimination of one fetus in utero, manage the preg-
nancy to term in the remote hope of two viable foals, or induce
abortion. Management of a twin pregnancy was discussed in
more detail in a previous section.
Umbilical Cord Compromise
On rare occasions, a large ossified remnant of the yolk sac
may compromise blood flow through the umbilical cord and
result in abortion.667 The pathologic condition referred to as
umbilical cord torsion may be defined as excessive twisting of
the cord such that there is complete or partial occlusion of
the umbilical vessels or urachus.668 The two umbilical veins
that return oxygenated blood from the placenta fuse within
the distal aspect of the amniotic portion of the cord, and a
single vein enters the fetal abdomen.669 Strangulation may
occur if the cord becomes tightly wrapped around a portion
of the fetus. Pressure sites on or around fetal parts may be
caused by the effects of constriction by prolonged tension on
a strangulated umbilical cord.670 Affected fetuses are not usu-
ally expelled immediately after death, so some degree of tissue
autolysis should be expected.671
 CHAPTER 19
The length of the equine umbilical cord in normal gestation
can be quite variable, and factors that affect cord length and the
number of twists present are unknown. Lethal umbilical torsion
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appears to be a sporadic condition with no apparent increased
risk for future problems in mares that abort as a result of fetal
complications.672 Whitwell has shown that some mares have
three or more foals with abnormally long cords.441 A study of
93 Standardbreds did not demonstrate an effect of sire on cord
length, and much larger studies will be required to ascertain
whether genetics are involved.429 Although the possibility of a
heritable component for cord length cannot be discounted, a
more plausible explanation may be that abnormally long cords
are associated with the amount of fetal movement.669
Ultrasonographic studies of fetal mobility have helped
explain the characteristic twisting feature of the normal
equine umbilical cord.402,673-675 Differing from ruminants, the
equine amnion floats freely within the allantoic fluid. Fetal
rotation within the amniotic cavity and amniotic sac rotation
within the allantoic cavity result in the characteristic twisting
of the equine umbilical cord.676,677 The lumen of both uterine
horns becomes constricted (presumably by localized circular
muscle contractions) between 5 and 7 months, and the allan-
toic fluid along with the fetus is contained within the confines
of the uterine body.402,673-676 Ginther has described that as the
noncord horn remains closed, the cord horn gradually per-
mits the entry of the hindlimbs between 7 and 9 months.675
The limbs can enter the horn only when the fetus is in dorsal
recumbency because the angle between the horn and body is
so acute by this stage of gestation. Thereafter, the hindlimbs
remain enclosed within the cord horn, and the hooves extend
to the horn tip by the tenth month. It is interesting that the
peak incidence of abortions due to umbilical torsions occurs
when the hindlimbs can become permanently enclosed in the
uterine horn. In some instances this may prevent the unravel-
ing of those critical few rotations that can lead to circulatory
compromise. There is no doubt that a longer umbilical cord
predisposes the fetus to this condition.
Reports from the United Kingdom suggest that with the
decline in twin abortions, excessive twisting of the umbilical
cord has become the most frequently made diagnosis in some
laboratories. These abortions were associated with excessively
long cords, with many over 80 cm in length.592,678 Because spi-
raling of the equine cord (four to five times over its length)
is a normal feature, it is important to ensure that the fetal
demise was caused by vascular compromise.669,677 Evidence
of pathologic twisting with tension and compressive forces on
the affected portion of the cord may include aneurysms, tear-
ing of the intima of vessels, hemorrhage, thrombosis of vessels,
blanched constricted areas, local edema, and urachal dilations
of varying sizes. Inadequate perfusion can cause intravascular
thrombosis in the peripheral tissues of the chorioallantois and
possible necrosis of the aspect of the placenta that is most dis-
tant from the attachment of the cord (the cervical pole of the
body segment).669,671 These findings are by no means defini-
tive, and there may be variability in interpretation among lab-
oratories. Other considerations should include general agonal
changes and the potential effects of cord tension when a live
fetus is expelled. Whitwell’s morphologic studies have estab-
lished normal metrics for equine fetal membranes. The aver-
age length of the umbilical cord in a Thoroughbred is 55 cm
(95% confidence interval; 36–83 cm; n = 143).679
Williams reviewed 168 cases of umbilical cord torsion
from the University of Kentucky Veterinary Diagnostic
Disorders of the Reproductive Tract 12851285
Laboratory, representing 6% of equine fetus submissions over
a 5-year period.672 The gestational age ranged between 5 and
10 months, with a mean of 7.5 months. Umbilical cord length
varied between 62 and 125 cm, with an average length of 96
cm. The cords tended to be highly twisted, with areas of con-
striction, edema, hemorrhage, and fluid-filled sacculations.
The fetuses were slightly to moderately autolyzed in a man-
ner consistent with fetal death before abortion. Urinary blad-
der dilation was observed in some cases. The most consistent
histopathologic finding was evidence of necrotic changes with
secondary deposition of calcified material in the blood vessels
of the chorioallantois.591,672 A less common cause of abortion
resulting from cord obstruction is when an excessively long
amniotic portion of the cord becomes tightly wrapped around
a portion of the fetus.670,679,680 Although it may be more com-
mon for a fetal extremity to be involved, the author managed
a case in a pony mare in which the tightly wrapped cord left a
deep groove around the lumbar region, with evidence of local
edema.670
Y GENDER DETERMINATION
(FETAL SEXING)
The advent of fetal sexing has permitted early gender determi-
nation to influence the value of the pregnant mare. Factors that
may vary depending on the predicted sex of the foal include
choice of state for foaling, appraisals and insurance coverage,
sales reserves, bookings for stallion service the next season,
and retention or sale of the mare.681 Accurate determination of
the sex of the equine fetus can be made using either transrec-
tal or transabdominal ultrasonography.78,681-683 Fetal gender
should be certified only when the identifying structures have
been clearly delineated and the accuracy of the determination
is guaranteed. Accurate determination of fetal sex may be dif-
ficult or impossible in some cases because of excessive mare
or fetal movement or because the fetus is located too ventrally
to permit adequate imaging. Although tranquilization (e.g.,
xylazine and butorphanol tartrate) is sometimes used, it may
cause the uterus to relax and drop away from the examiner.681
A 5.0-MHz linear array transducer is adequate for transrectal
gender determination, but a 3.5-MHz transducer will ensure
the depth of penetration that is required to obtain transab-
dominal images.
Gender determination is based on ultrasonographic assess-
ment of the relative location of the genital tubercle, an embry-
ologic structure that is initially located between the rear limbs
in both sexes. The genital tubercle differentiates into either a
clitoris or a penis and has an ultrasonographically distinctive,
hyperechoic, bilobulated appearance in both sexes. Curran
reported that the optimal time for gender determination is
between days 59 and 68, and Holder concurs that a window
between days 60 and 70 is ideal.681,682 A second ideal period
for gender determination may be between days 110 and 120,
because the genitalia are now well developed and the fetus
tends to be more accessible again. After this time the increas-
ing depth of the uterus means that a diagnosis may not be pos-
sible if the fetus is in an anterior (cranial) presentation at the
time of the examination.681 If the transabdominal approach
is used, then the optimal window of time in both sexes is
between 100 and 220 days' gestation.78,681,682 Thereafter, it may
become increasingly difficult to identify the anatomic struc-
tures required to make an accurate gender determination.
 1286 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
Detailed instructions for fetal sexing by ultrasonography have
been described.78,681,682 Transabdominal gender identifica-
tions based on the presence of the penis or prepuce (or both)
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in males and mammary glands and teats or fetal gonads in
females can be quite accurate.78
Y MONITORING PREGNANT MARES
Placentitis should be suspected in mares that develop pre-
mature mammary enlargement (with or without vulvar dis-
charge). Varying blood markers have been recommended
to monitor late-term pregnant mares.594 Relaxin is a protein
hormone produced by the placenta. Low concentration of
peripheral relaxin has been associated with various causes
of placental dysfunction including fescue toxicosis, oligohy-
dramnios, and placentitis.684,685 Currently, however, there is
not a commercially available assay, and normal concentrations
of relaxin are highly variable among mares.
Serum amyloid A and haptoglobin have been suggested
to be useful diagnostic and prognostic markers for ascend-
ing placentitis.253,261 Similarly, alpha-fetoprotein and estradiol
17β472 have been shown to be useful markers for experimen-
tally induced ascending placentitis. It remains to be deter-
mined, however, if these molecules are useful for diagnosis of
naturally occurring placentitis.
Measurement of an equine fetal protein and estrone sul-
fate levels in maternal plasma has not proved useful for early
detection of fetal stress associated with medical and surgical
colics.514,686 In central Kentucky, a commercial laboratory
offers a test to measure “total estrogens” that purportedly
measures different fractions of nonconjugated classic pheno-
lic estrogens present in late-term pregnant mares. Mares with
lower concentrations of total estrogen are supposedly prone to
abortion.687 Before day 310 of gestation, total estrogen levels
of less than 1000 ng/mL may be indicative of fetal stress, and
mares with levels of less than 500 ng/mL are likely to have a
severely compromised or dead fetus. This assay has not been
tested under controlled conditions.
It is important to remember that the circulating concen-
trations of hormones in maternal plasma represent a small
percentage of the levels that are being metabolized by the
fetoplacental unit.368,564,688 The definitive studies on mare
progestogens (progestins) were performed using gas chro-
matography-mass spectrometry (GC-MS) or liquid chroma-
tography.368,475,688 It is imperative that clinicians understand
that common commercially available assays (e.g., RIA, ELISA)
using an antibody raised against progesterone or estrogen usu-
ally cross-react with several other steroids present in plasma of
pregnant mares. Thus the results typically reported by the lab-
oratories as being progesterone, estradiol, or estrone represent
a mix of different progestogens and estrogens, respectively. In
clinical practice this might be of particular relevance when the
practitioner tries to compare results from an assay presented
by one laboratory to the results obtained from another labora-
tory. Assay results may not be readily comparable.
Although placental pathology has been associated with
increased plasma progestin concentrations in some reports,
others failed to detect differences in plasma progestin con-
centrations in mares with impending abortion and mares
with normal pregnancies when monthly blood sampling was
performed.368,439,475,476,688 Therefore it is recommended that
whenever possible, serial samples (e.g., daily for 3 days, then
weekly) be obtained from a mare in which the condition is
suspected; doing so may help the clinician identify a clinically
useful trend in progestogen concentrations.688 Unfortunately,
in practical settings this might not be feasible, making proges-
terone measurement not applicable to all situations.
Plasma progestogen concentrations increase in normal
mares as gestation progresses, and concentrations in the
maternal plasma may range between 5 and 50 ng/mL or even
higher as mares approach term. It is thought that chronic fetal
stress may cause the increased progesterone and pregnenolone
concentrations (as well as those of several metabolites) that
have been observed in mares with placentitis.688,689
Ousey has described three abnormal progestogen patterns
that may be clinically useful: a rapid decline, precocious ele-
vation, and failure to increase at term.368,688 A rapid decline
is consistent with fetal death or imminent fetal expulsion
and may be seen after a uterine torsion or colic.367,688 Preg-
nant mares that have experienced colic or uterine torsion and
have plasma progestogen concentrations below 2 ng/mL are
at high risk for fetal loss.686 Prolonged increase of progesto-
gens for several weeks before delivery (especially if earlier than
305 days' gestation) is consistent with metabolic activity in the
fetus and uteroplacental tissues despite the presence of pla-
cental pathology.476,646,688-692 Although typically small with
poor skeletal development, foals born after being exposed to
chronic fetal stress (placentitis) tend to exhibit precocious
maturation, even when delivered several weeks early.693
Transrectal ultrasonography provides an excellent assess-
ment of the current status of the caudal allantochorion, and
as such it is an invaluable aid when examining a mare in late
pregnancy that exhibits signs of placentitis.694,695 An image of
the ventral placental tissues in the area adjacent to the cervical
star provides the ability to accurately diagnose the early stages
of ascending placentitis.694,695 Experienced clinicians are able
to observe abnormal tissue thickness and even evidence of
placental separation with an associated pocket of inflamma-
tory exudate. Early therapeutic intervention may provide the
best chance for a successful outcome. In a normal placenta the
chorioallantoic membrane and endometrium are intimately
connected, making them ultrasonographically indistinguish-
able from each other. Thus a combined tissue measurement
is used, and normal values for the combined thickness of the
uterus and placenta (CTUP) have been established.696 The
amniotic membrane should not be included, and this should
be remembered if the fetal limbs are active at the time of the
examination. The area 1 to 2 inches cranial and ventral to the
cervix provides the most consistent CTUP measurement in
normal mares, and this is the recommended site for any mea-
surements. The ultrasound image should be frozen once the
landmark vessel (a branch of the uterine artery) in the ventral
uterine wall is located, and caliper measurements are taken
from the inner dorsal surface of the ventral uterine vessel to
the edge of the allantoic fluid.694 It is recommended that three
individual measurements be recorded.
An increased CTUP at any point from midgestation until
term may indicate placental disruption and pending abor-
tion.697 Transrectal CTUP measurements that are considered
abnormal would be greater than 8 mm (between days 271 and
300), greater than 10 mm (between days 301 and 330), and
greater than 12 mm after day 330.694,696,698
An increased CTUP measurement in the absence of other
clinical signs constitutes only weak evidence of placentitis.
While examining a mare suspected to have placentitis, the
practitioner must be looking for further signs of placentitis,
 CHAPTER 19
such as placental separation, intracervical fluid accumulation,
vulvar discharge, or premature mammary gland develop-
ment.594 Placental folds, amnion, and at times individual mare
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variation may be responsible for apparent increased CTUP in
the absence of placentitis.
Most practitioners do not recommend vaginal examina-
tion of pregnant mares unless the mare is presenting with
purulent vulvar discharge or has other clinical indications for
performing the exam. If such an examination is warranted,
however, it is important to employ strict hygienic procedures
when performing a vaginal speculum examination on a mare
with a high-risk pregnancy, because the first two barriers to
the pregnant uterus will be breached (i.e., vulvar lips, vestibu-
lar sphincter). Mares at risk for abortion often have a moist,
hyperemic, relaxed cervix. Even if vaginal discharge has not
been reported, many of these cases have a purulent cervical
discharge if placentitis is present. Whereas cervical soften-
ing and vaginal discharge may be present if the infection is
localized around the cervical star, in the case of nocardioform
placentitis, the lesion does not involve the cervical star, and
vaginal discharge is conspicuously absent.596,699,700 Although
transrectal ultrasound is an extremely useful aid in diagnosing
ascending placentitis, the site of the nocardioform lesion makes
it of limited diagnostic value in these cases.659 Transabdominal
examination of the ventral uterus may reveal separation of the
chorioallantoic membrane from the endometrium, often with
evidence of hyperechoic fluid accumulation between the two
surfaces. Placentitis and associated placental edema will result
in a thickened uteroplacental image. The CTUP on a transab-
dominal ultrasound image should be between 7 and 12 mm.
Transabdominal ultrasonography has become a rou-
tine diagnostic aid for evaluating mid- to late-term mares.
Although the 5.0-MHz linear array transducer is ideal for
transrectal reproductive ultrasonography, some probes have
shallow depth of penetration (approximately 10 cm) that lim-
its their usefulness for transabdominal examinations in mares
in late pregnancy. The author recommends use of a transducer
that achieves 15- to 20-cm depth for optimal transabdominal
examination. If the mare does not have a pronounced plaque
of ventral edema, most modern ultrasound units with a 5.0-
MHz transducer will be sufficient to image the uteroplacental
unit and some of the fetal fluids and allow assessment of the
fetal heart rate.
Either a 3.5- or 2.5-MHz curved linear array or sector
scanner transducer is best for transabdominal examinations
because these can penetrate to a depth of 20 or 30 cm, respec-
tively. Although the 70- to 90-day fetus may be imaged from
the ventral abdomen, just cranial to the mammary gland, the
late-gestation gravid uterus extends along the ventral abdo-
men to the xiphoid.694,701-704 By the ninth month of gestation,
the fetus should be in anterior (cranial) presentation and dor-
sopubic or dorsolateral position402,675,702; thus in late gestation
the fetal head should be positioned near the mare’s pelvis. An
abnormal presentation or the presence of twins is possible
if a fetal head is detected along the ventral abdomen dur-
ing late gestation. A more detailed examination is indicated
in such cases. The posture of the extremities varies with fetal
movement.702
A standardized methodology must be followed when scan-
ning the uterus from the ventral abdomen, starting just cranial
to the mare’s mammary gland and moving cranially to locate
the fetal thorax. The ribs cause multiple acoustic shadows that
delineate the thoracic cavity. A complete examination of the
Disorders of the Reproductive Tract 12871287
fetus and uterus involves scanning cranially to the xiphoid in
multiple parasagittal planes and then scanning from the left
to right sides of the abdomen in multiple transverse planes.704
Transabdominal ultrasound examination is an important
diagnostic tool when attempting to identify the presence of
twin fetuses during late gestation. Identification of the non-
gravid horn can be useful to help rule out the possibility of
twins. Obvious size discrepancy often serves as confirmation
that twins are present. In other cases one thoracic cavity does
not contain a beating heart, confirming that one of the twins
has already died.
In a normal pregnancy the majority of the fetal fluids are
within the allantoic cavity. The amnion is imaged as a thin
membrane that surrounds the fetus and lies in close contact
with the fetus over much of its body. The amniotic mem-
brane divides the imaged fetal fluid into two distinct cavities.
It is most easily seen around the fetal neck, shoulder, tho-
rax, and foreleg. The largest pocket of amniotic fluid is usu-
ally imaged at the point where the forelimb and neck meet
the thorax.704 The maximum vertical depth of amniotic and
allantoic fluid and the echogenicity and character of amniotic
and allantoic fluid are useful guides to fetal well-being. Any
measurements of fluid depth should be made as perpendic-
ular to the uteroplacental surface as possible. In the normal
equine pregnancy, the maximum ventral fetal fluid pocket
depth for amniotic fluid is 8 cm, and it is 13 cm for allantoic
fluid.694,703,704 Extremes in either direction are not normal.
Obviously deficient amounts of fetal fluid indicate placental
dysfunction, and excessive amounts suggest a hydrops condi-
tion. Fetal fluid quantities should be considered excessive if
the maximal vertical amniotic fluid depth exceeds 14.9 cm or
the maximum vertical allantoic fluid depth exceeds 22.1 cm.
The quality of the fetal fluid is scored from 0 (clear) to 3 (echo-
genic fluid with numerous particles).702 It is not unusual for
echogenic particles to be noted in the fetal fluids, especially
during periods of fetal activity. These represent sloughed cells
and proteinaceous debris. The fetal skin releases vernix as
the pregnancy advances, and these free-floating particles can
increase the cloudiness of the amniotic fluid. Thus an increase
in the number of echogenic particles in late gestation may not
be abnormal.702 However, if a high-risk pregnancy is being
regularly monitored and a sudden increase in fluid turbidity
(grade 3) is observed, the prognosis is not good.702 The clini-
cian should consider the possibility of inflammatory exudates,
meconium passage by a compromised fetus, or even hemor-
rhage. It should be remembered that hippomanes (allantoic
calculi) are a normal feature of the equine pregnancy. These
structures may often be observed as free-floating echogenic
accumulations on the ventral aspect of the allantoic cavity.704
An equine biophysical profile has been proposed as a guide
to assessing fetal well-being and predicting perinatal morbid-
ity and mortality.694,702,705 Although a low score is definitely
indicative of a negative outcome, higher scores do not guar-
antee the birth of a viable neonate. While establishing the bio-
physical profile of fetuses during pregnancy is an interesting
concept, some clinicians question its validity for clinical prac-
tice as it is a time-consuming technique, and results are not
necessarily useful in determining interventions. Fetal breath-
ing, heart rate and rhythm, fetal tone, and general activity are
useful guides when evaluating fetal health and well-being.
Therefore chemical sedation of the mare is not recommended
because commonly used drugs are likely to induce fetal bra-
dycardia and suppress normal fetal activity.706 Fetal breathing
 1288 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
is characterized by movement of the diaphragm between the
thorax and abdomen in conjunction with rib cage expansion
without any other movement by the fetus. Fetal breathing pat-
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terns should be monitored for at least 30 seconds.694,704
When fetal heart rate and rhythm are monitored, it is not
appropriate to scan for only 10 to 15 seconds and then mul-
tiply by a correction factor to obtain the number of beats per
minute. Beat-to-beat variations and observation of periodic
accelerations are important. It is normal for the heart rate
accelerations to occur in association with fetal activity. Mul-
tiple measurements of fetal heart rate and assessments of
fetal heart rhythm should be made over a 30-minute period
while evaluating the fetus, fetal fluids, and placenta. Ide-
ally, three measurements should be obtained with the fetus
at rest and another three after periods of activity. It is diffi-
cult to accurately monitor the heart rate during periods of
fetal activity, unless M-mode echocardiography equipment
is available. Fetal heart rates vary with the stage of gestation
and the amount of fetal activity at the time of the examina-
tion.694,707-709 The fetal heartbeat is normally regular and will
decrease from greater than 120 beats/min in midgestation to
between 60 and 90 beats/min in late gestation. Cardiac accel-
erations (20–40 beats/min above baseline) are normal if they
are associated with fetal movement, but persistent tachycardia
in the absence of fetal activity indicates fetal stress. A resting
heart rate in excess of 104 beats/min indicates fetal stress in
a late-gestation fetus.702,704 A heart rate of less than 57 beats/
min in a fetus that is less than 330 days' gestation and a rate
of less than 50 beats/min in a fetus older than 329 days' gesta-
tion should be considered abnormal. A fetus suffering from
hypoxia will have a slow heart rate, with minimal limb activity
or fetal breathing, indicative of central nervous system depres-
sion. However, if the condition is chronic and ischemic condi-
tions are developing, then the fetus will become tachycardic
despite a lack of fetal activity. This is a prelude to fetal demise.
In terminal cases extreme bradycardia ensues just before fetal
death. Although failure to observe fetal activity may be caused
by the stage of the normal rest-activity cycle, confirmation of
a regularly beating heart at least verifies that the fetus is alive.
This is a major advantage over transrectal fetal ballottement, in
which failure to detect movement can raise unnecessary con-
cerns about fetal health.
If Doppler ultrasound equipment is available, then the
Doppler transducer is placed directly over the site in which
the best image was detected by the ultrasound scan. Tracings
of fetal heart rate and rhythm can be recorded over time (usu-
ally at intervals of 5 to 10 minutes). This makes analysis easier
and serves as a permanent record of the fetal status at the time
of the recording. If there is some question about the presence
of twins after a transabdominal ultrasound examination, then
fetal electrocardiogram (ECG) tracings may show two distinct
fetal patterns.708,709 Features of the ECG tracing that should
be noted include fetal heart rate and rhythm, accelerations
and decelerations, complex polarity changes, and beat-to-
beat variation. In the last weeks of pregnancy fetal foals usu-
ally have a baseline heart rate in the range of 60 to 75 beats/
min. Transient low heart rates of less than 60 beats/min are
not uncommon. These troughs warrant concern only if they
are not interspersed with accelerations. Likewise, transiently
elevated rates in the order of 120 beats/min (occasionally >200
beats/min) are not abnormal, provided they return to baseline.
If the fetal heart rate is found to be less than 60 beats/min or
greater than 120 beats/min during an observation period, then
more frequent monitoring is justified to determine whether
the fetus is distressed. Beat-to-beat variations are normal, and
a finding of no variability is an ominous sign. Maternal medi-
cations such as alpha-2 agonists (e.g., detomidine, xylazine)
or opioids (e.g., butorphanol) will reduce fetal heart rate vari-
ability transiently.
The fetus is noted to have tone if it is observed to flex and
extend the limbs, torso, or neck. Tone is poor or absent if the
fetus appears flaccid. Fetal movements include partial to full
rotation around the long axis of the fetus as well as less marked
activity such as extension and flexion of the extremities. Fetal
activity is rated on a scale from 0 to 3, with 3 being a very active
fetus. A score of 0 indicates that no fetal movement was noted
during the examination period. Long periods without notice-
able fetal activity are cause for concern and should be evalu-
ated in conjunction with information about the fetal heart
rate and rhythm. The fetus may be distressed, suffering from
advanced hypoxia and central nervous system depression.
Fetal aortic diameter is correlated with the weight of the
pregnant mare and the final neonatal foal weight.694,702,703
Thus the pregnant mare’s weight can be used to estimate
what the fetal aortic diameter should be, using the regression
equation (Y = 0.00912 × pregnant mare’s weight in pounds +
12.46), where Y is the predicted fetal aortic diameter (in mil-
limeters).702,703 The actual diameter of the fetal aorta should
then be measured in the thoracic cavity as close to the fetal
heart as possible. A smaller-than-predicted aortic diameter
may indicate a dysmature or growth-retarded fetus (IUGR) or
twins. The maximal thoracic diameter is measured from the
spine to the sternum over the caudal part of the thorax, and
in a late-gestation fetus it should be 18.4 ± 1.2 cm. It has been
correlated with fetal aortic diameter and neonatal foal weight
in high-risk pregnancies.702, 703 Foal girth measurements and
hip height are also correlated with fetal aortic diameter mea-
surements.704,710 Fetal biparietal measurements and orbital
diameters have also been used to estimate fetal size.694,710 Eye
length (sclera to sclera) is a useful predictor of days before
parturition in small ponies.711 Decreased blood flow to the
placental unit inhibits fetal growth, and some form of chronic
placental insufficiency should be suspected when small fetal
size is detected.
It is important to monitor fetal viability if a high-risk preg-
nancy is being maintained on altrenogest supplementation.
Although most nonviable fetuses will be aborted, there is a
report of a mummified fetus being retained when the mare
was receiving long-term progestogen supplementation.712
Y COMPLICATIONS IN LATE GESTATION
Once confirmed to be at least 45 to 60 days pregnant, most
mares can be expected to carry the fetus to term. The inci-
dence of fetal loss after 100 to 120 days' gestation is low and
accounts for only a small percentage of total pregnancy wast-
age. Fetal death and maceration are very uncommon in the
mare. A set of macerated twins were seen by one of the authors
(GF) in a draft breed mare that suffered no ill effects systemi-
cally. The mare was evaluated only after the owner noticed a
foul-smelling vaginal discharge.713
Ventral body wall ruptures and uterine torsions are
uncommon, and hydrops of the fetal membranes is an espe-
cially rare condition. Accurate diagnosis and appropriate
management of these clinical cases can prevent the devel-
opment of a life-threatening condition. If a ventral body
 CHAPTER 19
wall rupture or uterine torsion is present, then the birth of
a viable foal may still be possible provided that the case is
properly managed.714 In referral hospitals, mares with body
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wall defects tend to be presented in advanced stage, mak-
ing management more challenging. Outcomes for several
diseases of the late-term pregnant mare can be improved by
training farm personnel and horse owners to identify clini-
cal problems. Owners should be trained to check late-term
pregnant mares daily or weekly for signs of placentitis (e.g.,
vulvar discharge, premature mammary gland development)
and areas of focal ventral edema. As described elsewhere in
this text, ventral edema may be observed in some normal
periparturient mares. Mares with expanding areas of edema
in the ventral abdomen should be examined immediately by
palpation and ultrasonography of the area and surrounding
body wall. Muscle failure can frequently be felt and observed,
and medical treatment, rather than surgical, may provide a
better outcome for dam and fetus.715
Hydrops of the Fetal Membranes
Hydrops is a condition of the last trimester, with the preg-
nancy developing normally until somewhere between 7.5
months and term. Hydrallantois and hydramnios are rare
conditions of pluriparous mares that involve a pathologic
accumulation of fluid within the allantoic and amniotic com-
partments, respectively. Normal volumes of allantoic fluid in
mares vary from 8 to 18 L at term. In documented cases of
hydrops, the allantoic fluid volume ranged from 110 to 230 L.
Just as with cows, hydrallantois accounts for most dropsical
conditions in the mare.716-719 The pathophysiology of hydral-
lantois in the cow has been related to a placental abnormality,
whereas hydrops amnion has been associated with a fetal head
anomaly that precludes swallowing.200 Dysfunctional placen-
tation may cause an increased production of transudate or
disruption of transplacental fluid absorption. There does not
appear to be any consistent abnormality of the fetus or fetal
membranes that is characteristic of the condition in the mare.
A mare with confirmed hydramnion delivered a viable foal.720
A mild diffuse placentitis or endometrial vasculitis has been
incriminated in some cases. A potential correlation between
hydrallantois and Leptospira infection has been suggested, but
causation has not been established.720
Generally there is a sudden onset of abdominal distention,
and walking becomes difficult. The mare may exhibit variable
degrees of colic. There is a progressive loss of appetite, and
the mare may experience some difficulty in defecation. The
increasing pressure on the diaphragm causes dyspnea, and
the mucous membranes may appear cyanotic, especially when
the mare is recumbent. On physical examination the rectal
temperature is normal, but the heart rate will be increased.
Transrectal palpation reveals characteristic findings. Copious
lubrication and extreme caution should be used because pas-
sage of the forearm will be impeded by pressure from the large
fluid-filled uterus. In advanced stages, the feces tend to be cov-
ered with mucus as a result of the prolonged passage through
the lower gastrointestinal tract. The gross distention of the
uterus means that the fetus is usually not palpable. Failure
to detect the fetus by external ballottement further supports
the diagnosis, but some mares may not tolerate ballottement.
Transabdominal ultrasound may confirm the presence of
excessive amounts of hyperechoic fluid. A thorough examina-
tion from both sides of the abdomen should be performed to
rule out the possibility of twins.
Disorders of the Reproductive Tract 12891289
Owners should be advised that this is a progressive condi-
tion, and it is extremely unlikely that the mare will be able to
sustain the pregnancy and deliver a viable foal. Despite this, a
recent report documented a case that was successfully man-
aged until a viable foal was delivered at 321 days' gestation.720
In that case the mare was provided with close monitoring
of maternal and fetal health, in combination with care that
included a supportive belly wrap, antiinflammatory medica-
tion, and altrenogest. A partial drainage technique is some-
times used in an attempt to manage cases that were diagnosed
within 2 to 4 weeks of term. Affected mares receive abdomi-
nal support (belly band), IV fluids, broad-spectrum antibiot-
ics, and antiinflammatory medication. The technique of slow,
repeated drainage requires a major time commitment and
would not be cost effective in many cases. Fetal death may
occur as a result of placental separation. There also appears
to be a considerable risk for iatrogenic fetal infection after
contamination of the fetal fluids, despite attempts to perform
the drainage technique in an aseptic manner. Despite heroic
attempts in valuable mares, the fetus is likely to be lost in cases
of hydrallantois. The prognosis for mare and foal survival may
not be favorable, particularly when the mare is <300 days' ges-
tation. Owners may opt to euthanize a mare without further
effort, for economic reasons, if the foal has little chance of
survival.
In most cases induction of parturition may be advisable
before the mare’s condition deteriorates further. Continued
abdominal enlargement will predispose the mare to body wall
tears or prepubic tendon rupture, and uterine rupture has
also been reported.721 Induction of parturition is not without
risk (shock and dystocia), but the prognosis for survival of
the mare is good provided appropriate supportive therapy is
instituted, particularly at an early stage of disease. The progno-
sis for the mare’s reproductive future may also be favorable if
there are no untoward sequelae (cervical lacerations, retained
fetal membranes, and metritis) or severe dystocia.
Application of PGE1 to the cervix before induction may
facilitate atraumatic fetal extraction.360 Six of eight mares that
had previously developed a hydrops pregnancy subsequently
became pregnant and delivered normal healthy foals at term.
Before a therapeutic induction of parturition, the tail
should be wrapped, the perineal area cleansed, and an indwell-
ing IV catheter inserted. Large-volume IV fluid therapy may
become necessary if hypovolemic shock develops as the allan-
toic fluid is discharged.714 In some cases controlled drainage
may be beneficial before inducing delivery. An added compli-
cation in hydrops cases is that the thickened, edematous cho-
rioallantoic membrane may be difficult to rupture.716 If digital
pressure alone is unsuccessful, then an endometrial biopsy
forceps can be used to create an opening in the chorioallantois.
Some authors report that the lack of pressure from the atonic
uterine wall will result in minimal release of fetal fluid from
the punctured chorioallantoic sac, but in most cases there is a
massive release of fluid once the chorioallantoic membrane is
ruptured. If insufficient fluid release occurs, a sterile nasogas-
tric tube can be introduced into the uterus to begin controlled
siphoning of fluid. The authors recommend detaching the cau-
dal pole of the chorioallantois and introducing a nasogastric
tube through the cervix and the chorioallantois. An alternative
technique is to introduce a thoracic trocar catheter through
the cervix and employ a sharp puncture of the chorioallan-
tois. This approach permits the excess fluid to be removed by
controlled drainage. Administration of IV fluids with gradual
 1290 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
removal of the excess allantoic fluid will permit the mare’s car-
diovascular system to adapt.
Oxytocin and PGF2α injections have been used in an
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attempt to abort these cases.716-718 Although oxytocin is
widely considered to be the most efficacious method for rou-
tine induction of parturition, in mares with hydrops condi-
tions the distended uterine musculature may not contract
effectively.716,722 This primary uterine inertia is common, and
gentle manual dilation of the cervix, or perhaps prior topical
application of PGE1, may be warranted.360 A smooth induc-
tion and manual extraction of the foal was reported for one
mare after two doses of cloprostenol administered 30 minutes
apart.723 Efficacy of ecbolics is likely more favorable in mares
with mild to moderate distention of the uterus.
The abdominal musculature may be weakened by stretch-
ing, and thus the typical stage II abdominal contractions may
be compromised. If an abdominal bandage is in place, many
mares will not have abdominal contractions, and classic stage
II of labor will not occur without intervention to manually
extract the foal. Malpositioning and malpostures are not
uncommon. The fetus may need to be extracted by assisted
vaginal delivery, but care should be taken not to traumatize the
cervix by overzealous traction. The expelled fetus will gener-
ally be alive, and humane euthanasia is usually warranted.
After delivery of the foal, oxytocin administered as a con-
tinuous rate infusion at 1.0 IU/min or as an intermittent intra-
muscular bolus at 5 to 10 units q 30 min should be included in
the treatment plan to promote uterine involution and facilitate
fetal membrane expulsion. Retention of the fetal membranes
should be expected, and appropriate treatment for removal
of these membranes and prevention of the metritis-laminitis
complex is indicated. Uterine involution should be monitored
by transrectal palpation and ultrasonography.
Ventral Body Wall Hernias and Prepubic
Tendon Rupture
Apart from those with pathologic pregnancies, mares with
ventral body wall defects are generally close to term.715,724,725
Damage to the abdominal sling of the pregnant mare may
involve rupture of the transverse abdominis and oblique mus-
cles, the rectus abdominis muscles, and the prepubic tendon.
In extreme cases the rupture may lead to hemorrhage, shock,
and death. The prepubic tendon attaches to the cranial bor-
der of the pubis, and lordosis occurs if the tendon is ruptured.
Although breed (draft breed and Standardbred mares) and
age (older mares) may predispose a mare to development of
the condition, in most cases there is no apparent predisposing
cause. The extreme abdominal distention associated with the
hydrops condition may cause rupture of the ventral muscu-
lotendinous support. Defects in the ventrolateral abdominal
wall are more common than complete prepubic tendon rup-
ture, and bilateral involvement of the abdominal wall seems
to be most common.9 In a retrospective study of 13 cases, only
three were categorized as being caudal midline (prepubic ten-
don lesions), and all three had additional involvement of the
body wall musculature.715
The most obvious clinical sign of an impending ventral
body wall rupture is a thick plaque of ventral edema extend-
ing a variable distance cranial to the udder. However, ventral
edema may be a normal consequence of late pregnancy, and
it can indicate external trauma. A large ventral swelling may
also occur with hematomas from external trauma and should
be considered as a differential diagnosis. Mares in late preg-
nancy often develop a thick plaque of ventral edema that can
extend from the udder to between the forelimbs. This is asso-
ciated with the compressive weight of the gravid uterus on the
venous and lymphatic drainage of the ventral abdomen. The
presence of a hemorrhagic secretion in the mammary gland
supports a diagnosis of tissue trauma rather than pregnancy
edema. Unilateral edema is more indicative of damage to the
ventrolateral body wall, but it may be associated with partial
rupture of the prepubic tendon. The extreme pain associated
with progressive enlargement of a ventral body wall rupture
causes a marked tachycardia that may not be responsive to
analgesics.
Pregnant mares with a ruptured prepubic tendon or abdom-
inal wall may show signs of colic and generally are reluctant to
move. If the prepubic tendon is completely ruptured, then the
pelvis will be tilted such that the tailhead and tuber ischii are
elevated and a lordosis will be present.714,715,724,725 The mam-
mary gland is often displaced cranially and ventrally because
of the loss of the caudal attachment to the pelvis, and bloody
secretion is usually present. A rent in the abdominal muscula-
ture may be complicated by bowel incarceration.
Confirmation of the tentative diagnosis is sometimes dif-
ficult. Because it is not always possible to be certain that a rup-
ture has already occurred, mares with severe ventral edema
should be confined to a stall with exercise restricted to hand
walking. Rectal palpation of the defect is usually not possible
because of the advanced stage of the pregnancy. External pal-
pation is generally unrewarding because of the thickness of the
edema, although some crepitation of the ventral abdominal
wall may be noted. The mare is generally extremely sensitive
and resists palpation of the area. Ultrasonographic examina-
tion of the posterior aspect of the ventral abdomen may be
useful in some cases and can detect the presence of a bowel
segment.204,704,714,715 Rupture of the prepubic tendon can be
identified as disruption of the tendon fibers immediately cra-
nial to the pubis, whereas abdominal wall muscle tears are seen
to be discrete tears within muscle fibers, often associated with
hematomas.715 An accurate assessment of the dimensions of
the defect often cannot be made until the fetus and fetal fluids
are expelled and the ventral edema has subsided. Often body
wall tears can be found in the flank as well, and transcutaneous
ultrasound in the flank region may be beneficial.
Depending on the degree of discomfort and stage of preg-
nancy, termination of the pregnancy may be the most humane
treatment for the mare, given that further tissue damage is
likely to occur to some degree until parturition. The possi-
bility of a segment of intestine becoming incarcerated in the
defect also should be considered. In extreme cases the mare
may eventually become recumbent, especially if there is a rap-
idly expanding body wall defect. Owners should be aware that
unless parturition is imminent, the prognosis for the foal is
not good because fetal readiness for birth is difficult to pre-
dict. If it is determined that the goal for the owner is to save
the fetus, the management plan should focus on supportive
care to facilitate maintenance of the pregnancy to term. In
these mares the treatment is essentially supportive, and the
prognosis for the foal is good. Antiinflammatory drugs will
help alleviate the mare’s discomfort. An abdominal sling (belly
band) made of canvas or padded leather or a snug abdominal
bandage help provide support for the ventral abdominal wall.
If a sling is used, the area over the back must be well padded to
prevent pressure necrosis because the purpose of this support
 CHAPTER 19
is to transfer the weight of the gravid uterus to the vertebral
column. Reducing the bulk of the ration and feeding a mild
laxative may help reduce the degree of abdominal exertion
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associated with defecation.
Assistance with parturition should be available because the
mare may experience difficulty in mounting sufficient abdom-
inal pressure to expel the fetus, especially if the mare has an
abdominal bandage.715,725 However, one report suggests that
some mares can position the foal and complete delivery unas-
sisted.715,724 Arrangements for an alternate source of colostrum
should be made because ventral edema may prevent the foal
from suckling. The owner should be informed that although
in some cases surgical repair of the defect may be possible by
mesh herniorrhaphy, rebreeding the mare with an expecta-
tion of carrying the foal to term is usually not advisable. Some
mares with small, unrepaired defects may subsequently foal
without assistance, but the possibility that future pregnancies
may exacerbate the condition should be considered. Embryo
transfer offers a viable alternative if this procedure is con-
doned by the relevant breed society.
Uterine Torsion
Uterine torsion accounts for 5% to 10% of all complicated
obstetric conditions in the mare.726,727 Neither mare age nor
parity appears to be a significant risk factor.728,729 The causes of
uterine torsion in the mare are not well defined. The condition
is much more common in cattle, and in that species a large
term fetus has been implicated as a major risk factor. Most
uterine torsions in cows occur at term and are thought to be a
direct result of fetal positional changes during late first-stage
and early second-stage labor. A striking difference between
the mare and the cow is that more than 50% of uterine tor-
sions in mares occur before the end of gestation.730 It seems
that most equine uterine torsions occur before term, and cases
may be seen as early as 8 months of gestation.714 One report
documented a mare affected as early as 126 days' gestation.731
A multicenter retrospective study of 63 cases reported that
59% of the mares were at less than 320 days of gestation.728
Although Ginther et al. have shown that the fetus is locked
in a dorsopubic position during the final months of gestation,
it is still possible for the entire pregnancy (uterus and fetus)
to rotate approximately 90 degrees on the lower maternal
abdominal wall.402 This occurs because any rotational move-
ment of the caudal half of the fetus (pelvis and hindlimbs) by
necessity will involve the close-fitting uterus. It seems likely
that in extreme cases this rotating action can lead to a clini-
cal uterine torsion. Owners who work closely with their mares
may observe excessive fetal movements in the flank area 1 or
2 days before. In a recent study, 80% of term fetuses were in a
dorsosacral position when the uterine torsion was corrected.
This suggests that fetal righting reflexes may have played a role
in creating the torsion.726 Vigorous fetal movements during
the latter stages of gestation are likely to be a significant factor
in the etiology of this condition in the mare.
The clinical signs that attract the owner’s attention are the
result of abdominal pain and may include restlessness, sweat-
ing, anorexia, frequent urination, sawhorse stance, looking at
flanks, and kicking at the abdomen. When the veterinarian is
first contacted, the signs may have been present for a period
ranging between 2 hours and 3 days or more, especially if signs
are intermittent and moderate. In mares that are close to term,
the owner may assume that the signs indicate impending par-
turition. In more extreme cases the signs are more severe and
Disorders of the Reproductive Tract 12911291
may be associated with concurrent involvement of the small
or large colon. Veterinarians should always consider the pos-
sibility of uterine torsion when a mare in the last trimester of
gestation exhibits a mild, persistent colic. Delay in making a
definitive diagnosis increases the likelihood of fetal compro-
mise. In one study of 63 cases, the mean time to admission
was more than 20 hours.728 Occasionally the condition may
remain undiagnosed for several weeks.732 In these instances
an owner may have attempted treatment with analgesics that
were prescribed for previous mild colic episodes.
Transrectal palpation is essential to determine whether a
uterine torsion is present. All late-pregnant mares that display
signs of mild to moderate colic warrant a thorough transrec-
tal examination to rule out the possibility of uterine torsion.
Although vaginal involvement in torsion is very common in
the cow, uterine torsions in the mare seldom cause detectable
changes in the vagina.714,733,734 Thus vaginal examination is
generally not diagnostically useful in mares.
On transrectal palpation the clinician should aim to care-
fully advance the forearm while palpating for a taut band on
either side of the rectum. The broad ligament on the side of the
torsion tends to be more caudal and is palpable as a tight verti-
cal band. As the arm is advanced further, the opposite ligament
will be palpable because it is pulled horizontally across the top
of the uterus before being displaced ventrally. An accurate
examination of the broad ligaments will confirm the diagno-
sis, determine the direction of the torsion, and give some idea
of the severity of the torsion. One retrospective of 54 mares
reported that 79% of referred cases were rotated no more than
180 degrees, and 59% of cases involved clockwise torsion.728
A transrectal ultrasound examination is useful to evalu-
ate the condition of the fetal fluids and to note whether any
placental detachment has occurred. The degree of uterine
compromise can be gauged by noting the thickened uterine
wall and distended vasculature. Compression of the veins and
lymphatics occurs before occlusion of the arterial blood sup-
ply; thus the initial changes will be associated with pooling
of fluid within the uterine wall. The compressive forces of the
displaced broad ligaments may cause variable amounts of con-
striction of the small colon.734,735
Transabdominal ultrasonographic imaging may be used
to assess fetal viability (heart rate and rhythm) and to evalu-
ate the character of the fetal fluid. Compression of the uter-
ine blood supply can cause fetal hypoxia and a fetal stress
response, especially in more advanced pregnancies. Abdomi-
nocentesis may provide prognostic information and guide the
clinician in choosing a mode of correction.197 Because it may
be difficult to obtain peritoneal fluid from a mare in late gesta-
tion, transabdominal ultrasonography is sometimes useful in
locating a pocket of fluid.
Uterine rupture can be a complication of uterine torsion in
the mare.734,736 Mild uterine torsions, or those of short dura-
tion, do not alter the color, cellularity, or total protein content
of the peritoneal fluid.197 Mares with severe or chronic uter-
ine torsion may develop significant uterine compromise that
results in changes in the composition of the peritoneal fluid.
Any alterations in the composition of the peritoneal fluid may
indicate the presence of a compromised or ruptured uterine
wall or concurrent gastrointestinal involvement.3 A flank lapa-
roscopic examination can confirm the condition of the uterine
wall.737 This information will facilitate an informed choice of
surgical approach or perhaps support a decision for euthana-
sia if economic considerations preclude surgical intervention.
 1292 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
The stage of gestation and the mare’s heart rate are impor-
tant prognostic indicators for mare survival. A recent study
reported that mares that died had significantly higher heart
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rates (mean 74 beats/min) at admission than survivors (mean
59 beats/min).728 Increased fetal size and the weight of the
gravid uterus make correction closer to term (>320 days)
more difficult, and this may explain the poor mare survival
rate (65%) compared with cases in less advanced pregnancies
(<320 days), in which survival rates are excellent (97%). Own-
ers should be advised that fetal survival rates are not as good,
but a similar effect of stage of gestation applies. The chances
of the foal surviving exceed 70% if the mare is at less than 320
days' gestation, but only about 30% survive when mares are
closer to term.
If the mare is presented in stage I of labor and the cervix
is sufficiently dilated to permit passage of a well-lubricated
arm into the uterine body, then it may be possible to reach
the fetus. It should be grasped ventrolaterally and then rocked
back and forth until sufficient momentum is achieved to con-
tinue up in an arc. This reproductive maneuver may not be
possible in mares with reproductive tract swelling because of
a chronic, undiagnosed torsion. This manipulation should roll
both fetus and uterus back into a normal position. More than
80% of term torsions may be corrected in this manner.716,727
Options for management of a preterm uterine torsion are roll-
ing the mare, flank laparotomy, or a ventral midline celiotomy.
In the controlled referral hospital environment, the method
of correction is not associated with mare survival, but both
rolling and midline celiotomy require general anesthesia and
thus entail those additional risks.728 There is a significant effect
on foal survival if the mare is at less than 320 days’ gestation,
and using the standing laparotomy approach should provide a
significantly better prognosis compared with the ventral mid-
line approach. However, the final decision must be based on
several factors, including the severity of pain being exhibited
by the mare, client financial constraints, and surgeon prefer-
ence. It should also be noted that a ventral midline celiotomy
permits better assessment of uterine viability and evaluation of
the gastrointestinal tract compared to a flank incision.
The anesthetized mare may be rolled in an attempt to rotate
the mare’s body around the stationary gravid uterus.738 It is
essential that the mare be positioned in lateral recumbency
and rolled in the direction of the torsion. The aim of the pro-
cedure is to roll the mare such that the pelvis “catches up” with
the displaced uterus. Correction by rolling the mare is contro-
versial. Citations in the literature report on a limited number
of cases.730,738,739 Concerns with this approach include the fol-
lowing: Unsuccessful attempts to correct the torsion will pro-
long its adverse effects, misdiagnosis of the direction of the
torsion means that rolling the mare may make the condition
worse, the condition of the uterus cannot be evaluated, and
displacement of the colon may result.714 In addition, a higher
risk of placental detachment and uterine rupture has been
reported.204,739,740 Another concern is that if general anes-
thesia is induced under less than ideal conditions, maternal
hypoxia may cause fatal complications in the already compro-
mised fetus.
In the standing flank approach, a grid incision is made on
the same side as the direction of the torsion.734 The torsion is
corrected by placing the forearm under the uterus. The uterus
and contents are rocked back and forth to gain momentum.
A combination of lifting and rotating movements generally
results in easy correction of the torsion. The presence of a live
fetus greatly facilitates the detorsion manipulations. More dif-
ficulty may be experienced in mares that are close to term,
and this may justify the more expensive ventral midline celi-
otomy approach. If the standing procedure is attempted, then
an incision in the opposite flank will permit a second surgeon
to assist by gently pulling across the top of the uterus as it is
elevated from below. If the fetus is dead, then the mare should
abort naturally once the uterine torsion has been corrected,
removing the need for hysterotomy and any associated com-
plications.571,714 However, the mare should be closely moni-
tored, and obstetric assistance must be available to correct any
malposition or malposture. Mares experiencing intractable
pain should receive general anesthesia during the operation.
A ventral midline celiotomy is also indicated when significant
uterine compromise is a concern or another problem coexist-
ing in the abdomen is suspected.
The prognosis for mares with uterine torsion depends on
the degree of vascular compromise. The severity and duration
of the condition affect placental circulation and subsequent
fetal viability.714 In chronic cases in which there is significant
uterine compromise, it is feasible to perform an ovariohyster-
ectomy to salvage the mare for nonbreeding purposes.732,741 If
the fetus is alive and the uterine wall is not severely congested
and edematous, then the prognosis for both the mare’s sur-
vival and for the birth of a live foal at term is good. Progesto-
gen supplementation for 3 to 5 days after the manipulations
involved in correcting a uterine torsion may be indicated to
promote myometrial quiescence and maintenance of the pla-
cental attachment. Although supplementation after a uterine
torsion would be in the last 2 to 3 months of gestation, there
are reports of mares retaining a nonviable fetus (one that died
at 3–5 months’ gestation) while receiving progestins.712 Thus
if progestin supplementation is administered to a mare after
correction of a uterine torsion, then it is prudent to monitor
fetal viability at regular intervals. There is probably little merit
in continuing the supplementation once the mare has been
discharged from the hospital. In one study 28 of 30 mares that
were pregnant at the time of discharge subsequently delivered
a live foal, and future fertility was good (24 of 29 were success-
fully rebred).728
Vaginal Hemorrhage
Visible blood on the tail hairs or hindlimbs of a pregnant mare
warrants careful examination.742 The integrity of placental
attachment immediately cranial to the cervix should be evalu-
ated using transrectal ultrasonography. A pocket of fluid may
be evident if placental separation has occurred, and measure-
ments of the CTUP should be made.697 An increased CTUP
measurement is indicative of placentitis.594 Because two of
the three barriers protecting the fetus (vulvar lips, vestibular
sphincter, and cervix) will be entered when performing a vagi-
nal speculum examination, it is essential to ensure stringent
hygiene. Often, blood clots can be seen in the vestibule when
the vulvar lips are parted. A sterile speculum should be cov-
ered with sterile lubricant and then gently inserted into the
vagina. Some mares with bloody vulvar discharge may have
experienced trauma inflicted by herdmates.743
In some mares there may be evidence of a serosanguineous
discharge from the cervical os. Mares that are aborting a twin
pregnancy may also develop a bloody vaginal discharge. How-
ever, the practitioner should be aware that the most common
source of vaginal hemorrhage in pregnant mares is from vari-
cose veins in the vestibulovaginal fold (hymen), not from an
 CHAPTER 19
impending abortion. In many cases no blood is visible in the
cranial vagina. If the cervix is closed, pale, and covered with
tenacious mucus, then it is unlikely that the blood is associated
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with the fetoplacental unit. Although the blood could be asso-
ciated with cystitis or urolithiasis, the source of the hemor-
rhage usually is varicose vessels in the remnants of the hymen
at the level of the vestibular sphincter or cranial vagina. It is
not unusual to miss these as the speculum is inserted; thus
particular attention should be paid to this area as the specu-
lum is withdrawn.742
Vaginal varicosities are most likely to occur in older, mul-
tiparous mares during the latter months of gestation.742,744
A large plexus of dilated veins can develop in the peduncu-
lated mucosa at the level of the vestibulovaginal junction or
less commonly in the cranial vagina. The veins can become
engorged from 1 to 2 cm during late gestation. If the vessels are
ulcerated, there may be intermittent, mild episodes of bleed-
ing from the ventral commissure of the vulva. An owner may
report seeing large blood clots in the bedding when the mare
is fed in the morning. Although this quantity may be alarm-
ing to an owner, it can be explained as merely representing
the discharge of pooled blood while the mare was recumbent
during the night. Another explanation is that the pull of the
rectal attachments when standing creates sufficient tension
in the vaginal wall to control hemorrhage, whereas blood
loss can occur when the mare is recumbent. In more severe
cases there may be dried blood on the perineum, tail hairs,
and hindlimbs. Overt vaginal hemorrhage may be sufficient to
cause anemia.744
The etiology of vaginal varicosities in mares is unknown.
The condition is not an uncommon complication of preg-
nancy in pluriparous women, and it has been proposed that
a similar obstruction of venous return is responsible for the
development of vaginal varicosities in the mare. Poor vulvar
conformation with cranial displacement of the perineum may
be involved in some cases.49,742,744 It is possible that repeated
stretching of the vestibulovaginal tissues and changes in the
vulvar conformation of pluriparous mares create a physical
impairment of venous return from the vestibular and vaginal
components of the internal pudendal vein. The dilated veins
are generally located on the cranial aspect of the vestibular
fold and on the dorsal aspect of the caudal vaginal wall. Thus
vaginal varicosities can be easily missed when a tubular specu-
lum is introduced, and they may not be evident during with-
drawal. In some cases a tri-valve metal Caslick speculum may
provide better exposure so that the tissues of the vestibulo-
vaginal fold can be everted and fully explored. If the diagnosis
is still inconclusive, then the next logical step in the physical
examination is ultrasound and endoscopic visualization of the
vagina and cranial vestibulovaginal fold. The clinician should
first advance the flexible scope toward the cervix and then
angle the lens back to better evaluate the cranial aspect of the
vestibulovaginal fold. If vaginal varicosities are present, usu-
ally no treatment is necessary, because the vessels will regress
spontaneously after foaling (benign neglect).742 However, if
there is persistent or excessive hemorrhage or the owner is
distressed, then the offending vessels can be cauterized (dia-
thermy) or ligated.742,745 Locating the source of the bleeding
can be difficult. Traction on the adjacent vaginal mucosa may
arrest the bleeding and help identify the site in such cases. Sub-
mucosal resection of a pedunculated plexus of varicose veins
has been reported to be successful.742,744 Some authors have
had success with topical application of a human hemorrhoid
Disorders of the Reproductive Tract 12931293
cream to prominent or suspected vessels. Treatment is gener-
ally successful, and no recurrence has been reported.
It is important to consider bleeding from the urinary tract
when vaginal hemorrhage is the presenting complaint. If an
owner reports having seen bloody urine on the stall floor, then
it should be remembered that normal equine urine contains
pyrocatechin. This oxidizing agent can cause urine to turn
red-brown after exposure to air.742 Hematuria can result from
several disorders of the urinary tract.746 If blood is present
throughout urination, then the lesion is likely to be in the kid-
neys, ureters, or bladder. If the endoscopic examination has not
identified vaginal varicosities as the source of the hemorrhage,
then the endoscope should be advanced down the urethra to
visualize the bladder lumen (cystoscopy). Although uroliths
are more common in geldings and stallions than in mares, a
urolith may cause mucosal irritation and hemorrhage, result-
ing in hematuria.747,748 Rectal palpation may reveal a firm
mass in the bladder that can be imaged by ultrasonography.
The pelvic portion of the urethra should also be palpated.742
Although neoplasia of the urinary bladder is rare, mares are
reported to be twice as likely as male horses to develop pri-
mary bladder tumors.746 Squamous cell carcinoma is the most
commonly reported bladder tumor, but transitional cell car-
cinomas can also occur. The condition has been reported as a
cause of hematuria, often with blood clots.749 A more detailed
discussion of hematuria may be found in Chapter 14.
Fescue Toxicity and Agalactia
A wide range of reproductive problems (e.g., thickened pla-
centa, abortion, prolonged gestation, dystocia, dead or weak
foals, agalactia) have been attributed to the effects of the fun-
gal endophyte (Acremonium coenophialum, now known as
Neotyphodium coenophialum).750-752 The endophyte produces
a dopaminergic, vasoactive ergopeptine alkaloid (ergovaline).
This alkaloid disrupts the fetoplacental production of progesto-
gens, but the precise mechanism has not been established.753, 754
Umbilical vein progestogen levels suggest that the disruption is
not at the level of placental steroidogenesis, which is a remark-
able observation when the fetal membranes are so edematous.
Premature chorioallantoic separation and the failure of the
membrane to rupture (red bag) are attributable to the edema-
tous splanchnic mesoderm.750 ACTH, T4, triiodothyronine,
progestogen, and cortisol concentrations are lower in foals
born to endophyte-exposed mares, suggesting that the effects
are actually at the level of the fetal hypothalamic-pituitary axis,
thyroid, and adrenal cortex.753 This is likely to be the basis for the
prolonged gestation and fetal dysmaturity that are associated
with fescue toxicosis.
Ergovaline also inhibits prolactin secretion in affected
mares by acting as a dopamine agonist at the maternal pituitary
level.754 Prolactin secretion can be inhibited experimentally by
administering dopamine agonists such as bromocriptine.755
Such prolactin-inhibiting treatment of pregnant mares results
in agalactia and also mimics the other symptoms of fescue
toxicosis (thickened placenta, prolonged gestation, and dysto-
cia). An effect of fescue toxicosis in pregnant mares is a low-
ering of the circulating relaxin levels.756 Clinical observations
suggest that a one-time injection with fluphenazine improved
pregnancy outcome by reducing the adverse effects of fescue
toxicosis concomitant with a stabilization of plasma relaxin
concentrations. (Caution should be exercised with the admin-
istration of fluphenazine to horses because this drug may cause
severe extrapyramidal neurologic signs.) These data support
 1294 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
the hypothesis that systemic relaxin may be a useful biochemi-
cal means of monitoring placental function and treatment effi-
cacy in the mare.756
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Because mares in late pregnancy are so susceptible to the
toxic effects of ergopeptine alkaloids, they should not be per-
mitted to graze in endophyte-infected tall fescue pastures or
ingest hay derived from such pastures. Short-term exposure
by mares at 300 days’ gestation results in a significant decline
in both PRL and total progestogen concentrations within 48
hours. Fortunately, removal of pregnant mares (300 days' ges-
tation) from infected pasture results in a significant increase in
prolactin and progestogen levels within 3 days. This will pre-
vent the development of the typical symptoms associated with
fescue toxicosis.753 Even when alternate feed sources are lim-
ited, every attempt should be made to remove pregnant mares
from endophyte-infected fescue by 30 to 60 days before the
expected foaling date. When this is not possible, prophylactic
administration of the dopamine receptor antagonist domperi-
done (Equidone) at 1.1 mg/kg or sulpiride administered orally
in the last month of gestation can prevent the negative effects
of fescue toxicosis.314,751,757-759
Y FOALING MANAGEMENT
Gestation length is notoriously unpredictable in mares, and
the greatest predictor of gestation length may be the mare her-
self.760,761 Although the frequently recommended minimum
gestation length for successful induction is 330 days, it must
be remembered that many mares will carry a foal past 340
days and occasionally to 360 days and beyond. Some mares
may carry and deliver a normal foal by 320 days of gestation.
Light exposure affects gestation length in mares, particularly
early in the foaling season when mares tend to have longer
gestation lengths.762 Mares foaling early in the season should
be kept under lights for normal cyclicity postpartum and for
normal gestation length. Mares bred in the fall will foal during
the summer and will tend to have shorter gestation periods.
There also appears to be some breed variability in gestation
length, with the mean for Friesians reported at 332 days, Lipiz-
zaners reported at 334 days, Andalusians reported at 337 days,
and Arabians reported at 340 days.761,763,764 In a retrospective
study of Standardbred mares, the mean duration of gestation was
343.3 days, and it was significantly greater for colt fetuses (344.4
days) than for filly fetuses (342.2 days).765 An average gestation
length of 344.1 ± 0.49 days was reported in a recent Thorough-
bred study (n = 344 mares). Colt foal pregnancies were signifi-
cantly longer (346.2 ± 0.72) than fillies (342.4 ± 0.65).766 Colts
were carried 1.5 days longer in a study of 495 Friesian mares.763
The sire has been associated with duration of gestation, and ges-
tation after mating with certain sires was consistently less than
340 days in duration, whereas duration after mating with other
sires was consistently more than 350 days.763,765 In Andalusians
and Arabians, a delay of 1 month in breeding corresponded to a
decrease of 3 days in the gestation length.761
Because gestation length is highly unpredictable in mares,
several other methods have been recommended for use in rou-
tine foaling management. Every periparturient mare should
be watched closely so that assistance is available at parturition
to maximize chances of mare and foal survival. Assisted par-
turition allows early intervention and correction of simple to
more complicated dystocias, allows the clinician to determine
if the foal requires immediate veterinary attention, and allows
intervention in cases of a “red bag” delivery (i.e., premature
placental separation).
Although mammary development is a somewhat useful
sign of approaching parturition in normal mares, monitor-
ing changes in mammary secretion electrolyte concentrations
and pH are useful tools to monitor time of imminent partu-
rition.767-769 An inversion in the sodium:potassium ratio fol-
lowed by a rapid rise in calcium (Ca) concentrations in the last
24 to 48 hours has been correlated with fetal maturity in both
mares and jennies.767 Exact values may vary with the type of
chemistry analyzer used by the diagnostic laboratory.
In a normal term pregnancy, the combined mammary secre-
tion levels of Ca (>40 mg/dL), potassium (>30 mEq/mL), and
sodium (<30 mEq/mL) are indicative of fetal maturity.767 Serial
assessment of these concentrations is most useful because of
daily fluctuations that may occur. Calcium concentration of 10
mmol/L (40 mg/dL, 400 ppm) in mammary secretions is a reli-
able indicator of fetal “readiness for birth.”760,767,768
Several stallside tests can measure the Ca ion (Ca2+) con-
centration in mammary secretions based on a colorimetric
change of pads on a test strip. Water hardness kits are also
useful for determining the concentration of Ca in mammary
secretions.770-774 These involve titration of a diluted sample
until an indicator dye changes color, and although they are
more labor intensive than the test strips, they are reported to
provide a more reliable guide for predicting the onset of par-
turition within the next 24 hours. However, it is important to
ensure that the water hardness kit is measuring only Ca con-
centrations if it is being used to determine the safest time to
induce parturition.760 Many kits merely test for divalent cat-
ions, which include magnesium as well as Ca. Because mag-
nesium levels peak earlier than Ca concentrations, misleading
information about fetal maturity may be obtained.768,771 If the
intent is merely to predict the onset of spontaneous parturi-
tion, the type of test is not as critical.
A study has questioned the interpretation of calcium car-
bonate (CaCO3) test kit data that has formed the basis of rec-
ommendations that 200 ppm or 250 ppm CaCO3 should be
used as the benchmark for readiness for birth. Paccamonti con-
tends that because Ca in milk is not in the form of CaCO3, any
test that measures CaCO3 levels in solution must be adjusted
to account for this fact.760 Because the molecular weight of
CaCO3 is 100 and that of Ca is only 40, the conversion factor is
2.5 (i.e., divide the CaCO3 ppm by 2.5 to obtain the Ca ppm).
Furthermore, because mammary secretions usually must be
diluted before a water hardness test can be used to measure
Ca, Paccamonti recommends that 1 mL of secretion be diluted
in 4 mL of distilled water. Thus the final reading should be cor-
rected by a factor of 5.760 The division by 2.5 to convert CaCO3
to Ca and the multiplication by 5 to correct for the dilution
mean need only be doubled to provide an accurate level of Ca
ppm. Using this logic, Paccamonti contends that the reports
using 200 to 250 ppm CaCO3 as an indication of readiness for
birth are actually using Ca values of only 80 to 100 ppm. How-
ever, if these values are corrected for the reported test dilution
(1:6) factor, then the CaCO3 level being reported would have
been 1400 to 1750 ppm (560–700 ppm Ca; 14–17.5 mmol/L).
These corrected values are thus in excess of the 400 ppm (10
mmol/L) Ca concentrations reported by other researchers.
It is obviously important to keep these calculations in mind
because water hardness kits may vary and technicians may
use different dilutions. Inappropriate application of the math
could lead to an erroneous conclusion about fetal maturity
and subsequent induction of a premature foal.760
Generally mammary secretion Ca concentrations are
more reliable for predicting when a mare is unlikely to
 CHAPTER 19
spontaneously foal rather than for determining when she is
likely to foal. Ley used a water hardness kit and reported that
CaCO3 levels greater than 200 ppm (see preceding discussion)
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indicated a 54% probability of spontaneous foaling within 24
hours, 84% probability of spontaneous foaling within 2 days,
and 97% probability of spontaneous foaling within 3 days. A
small percentage of mares foaled within 24 hours despite a
CaCO3 level below 200 ppm.769 However, using Paccamonti’s
logic, this equates to a corrected value of less than 560 ppm
Ca2+. Because a value of 400 ppm Ca2+ indicates readiness for
birth, it is not surprising that some of these mares foaled.
Although the fetus initiates parturition, the mare appears
to be able to regulate the actual timing of delivery775; thus any
untoward changes in the mare’s environment may cause her
to postpone the delivery and create discrepancies with predic-
tions based on mammary secretion electrolyte concentrations.
Calcium and other electrolyte concentrations can change rap-
idly during a single day, so testing secretions in the morning
and evening may be useful. If a single test is to be performed,
it is preferable to check the Ca levels late in the day. Generally
the more rapid the rise in milk Ca levels, the more imminent
is parturition. Primiparous mares can be especially difficult to
monitor because no change in mammary secretion electro-
lyte composition may be detected until immediately before
foaling.770
Serial assessment of pH from the mammary gland secre-
tions in periparturient mares may also be useful in prediction
of foaling.776- 778 A positive predictive value for foaling within
72 hours and a negative predictive value for foaling within 24
hours were 97.9% and 99.4%, respectively, using a pH strip
test.778 The pH of mammary gland secretions is highly and sig-
nificantly correlated with electrolyte concentrations (Ca, Na,
K) in those secretions. Mares that present a rapid reduction
(0.5 to 0.8 pH units) from alkaline (e.g., 7.8) to slightly acidic
pH (6.8 to 6.4) over 24 hours will typically foal within the next
24 hours.777 Mares that present with a slow reduction in pH
tend to foal when the pH reaches 6.4 to 6.2 and will have an
acidic pH for several days prior to foaling. A subset of mares
will have only a mild reduction in pH and may foal with an
alkaline pH (7.4 to 7.8). These mares will not have a sodium/
potassium inversion and will foal with low calcium concentra-
tions in their mammary secretions.777
There are several methods to measure the pH of mare
mammary secretions. While pH test strips are cheap and read-
ily available, they may not be sufficiently sensitive to detect
clinically relevant changes in pH. A hand-held pH meter that
allows more accurate determination may be preferred.
Placentitis and other placental pathology are often asso-
ciated with precocious mammary gland development and
premature changes in mammary secretion electrolyte concen-
trations. Milk electrolyte changes are unreliable for assessing
fetal readiness for birth in abnormal pregnancies (e.g., pla-
centitis, impending twin abortion) or when domperidone for
milk production has been administered. In cases of abnormal
pregnancies there may be elevated mammary secretion cal-
cium concentrations (>10 mmol/L; >400 ppm; >40 mg/dL)
before day 310 of gestation.476
Y INDUCTION OF PARTURITION
Induction of parturition may be indicated as a clinical man-
agement procedure for some high-risk pregnancies, including
mares with hydrops, ruptured prepubic tendon, and ventral
herniation. These mares often require assistance with delivery
Disorders of the Reproductive Tract 12951295
because the stage II abdominal contractions may be compro-
mised.714 Induction of parturition should not be practiced for
convenience alone but should only occur for reasons associ-
ated with the clinical well-being of the mare or foal. Owners
should be advised that complications such as dystocia, prema-
ture placental separation, fetal hypoxia, and dysmaturity are
not uncommon sequelae of the induction procedure.770,779-781
The aim of a controlled foaling is not only to deliver a viable
foal but also to prevent any injury to the mare that may com-
promise future fertility.
Induced foalings are sometimes indicated to ensure that
optimal veterinary assistance is available when complications
are expected and to optimize resuscitation attempts when a
compromised fetus has been monitored in utero. When fetal
stress is detected in a high-risk pregnancy, the clinician is
faced with the dilemma of inducing delivery and attempt-
ing supportive care in a neonatal intensive unit or leaving the
compromised fetus in utero. Owners should be informed that
delivery is indicated only if the probability of extrauterine sur-
vival exceeds that for continued maternal support.
Experience suggests that an abnormal uterine environment
is often more conducive to maintaining a fetal foal’s life than a
neonatal intensive care unit. A fetus that has been exposed to
an adverse uterine environment for some time may be more
tolerant of premature delivery.565 Many clinicians administer
a dose of corticosteroids to the mare if premature delivery
appears inevitable. This may stimulate surfactant production
and promote accelerated maturation of the fetal lung.
The normal physiologic processes in the prepartum mare
and fetus were discussed in a previous section. There is clear
evidence that the fetal hypothalamic-pituitary-adrenal axis
initiates the final stages of fetal maturation, which initiates
the hormonal cascade that culminates in parturition.564 Final
maturation of the fetus results in increased ACTH release from
the pituitary and subsequent stimulation of the fetal adre-
nal cortex. It is not until the maturing adrenal gland attains
17α-hydroxylase capacity that the high levels of pregnenolone
are metabolized into fetal cortisol. These vital changes lead to
a fetal cortisol rise in the last 2 or 3 days before birth; thus
the equine fetus is at a substantially increased risk of dysmatu-
rity or prematurity if the induction is not carefully planned.770
This planning has traditionally involved confirmation of gesta-
tion length, monitoring mammary development and milk or
colostrum production, and ultimately evaluating the amount
of cervical softening.782 The fetus will usually be in the dorso-
pubic position, with neck and limbs flexed before induction.
The incidence of posterior and transverse presentations is rare,
but detection of these abnormalities by rectal palpation before
induction would be reason to reevaluate the induction plans.
Delivery by cesarean section may be a more prudent course of
action, especially with transverse presentations.
The presence of cervical softening has traditionally been
suggested as a prerequisite for optimal induction of parturition
in the mare, and in a recent study mares with a relaxed cervix
before induction had a more rapid delivery.722 The same study
found that foals delivered from mares with a preinduction
relaxed cervix stood and nursed sooner and had fewer signs of
intrapartum asphyxia (hypercapnia and maladjustment) than
foals delivered from mares with a nondilated cervix. Mares
that developed parturient complications (premature placental
separation and dystocia) all had a closed cervix before induc-
tion. The status of the cervix is controversial because earlier
reports suggest that inductions may proceed successfully even
though the cervix is tightly closed and covered with mucus.781
 1296 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
Administration of intracervical PGE2 (2.5 mg) before
induction of parturition may aid in cervical relaxation and
inducing parturition, though no difference was apparent in
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the mean interval from initial oxytocin treatment to rupture of
the chorioallantois or to the delivery of the foal in mares pre-
treated with PGE2 compared to mares administered oxytocin
alone.360 However, the impact on foal viability was positive in
that foals delivered from PGE2-treated mares suckled sooner.
The application of intracervical PGE2 may have some merit
in termination of a pathologic pregnancy (e.g., hydrops) in
which the induction is known to be premature and is aimed at
salvaging the breeding prospects of the mare. Although there
is no correlation between myometrial strip (in vitro) response
to oxytocin treatment and gestational age, premature induc-
tion with oxytocin can take much longer (1–2 hours) than an
induction in mares at term. This is consistent with the belief
that a critical sequence of hormonal changes are required
before fetal expulsion can occur. Because the aborted fetus
will generally be alive and gasping for air, it is advisable to
have ready some euthanasia solution to euthanize the non-
viable neonate. After delivery, not all fetuses will have easily
accessible blood vessels; intracardiac injection of euthanasia
solution may be considered if immediate humane euthanasia
is required.
Several experimental protocols have been reported for
induction of parturition in the term mare, including glu­
cocorticoids,779,781,783-785 prostaglandins,779,781,786,787 and oxy-
tocin.360,507,722,780-782 High (100 mg/day) and repeated doses
(administered IM daily for 4 days) are required for glucocor-
ticoid induction because this regimen has limited efficacy in
the mare (which is not the case with ruminants).781 However,
a more recent study suggests that multiple injections of dexa-
methasone given to healthy mares at days 315 through 317 of
gestation can induce precocious fetal maturation and delivery
of viable foals within 5 to 7 days. The mares remained healthy
with no evidence of laminitis.783 Further studies are needed
to determine whether dexamethasone treatment can be used
safely in mares with compromised pregnancies. Prostaglan-
din induction is not very efficient in the mare. The synthetic
products (e.g., cloprostenol) are more effective than natural
prostaglandin, but results can be quite variable. Oxytocin is
the preferred drug for induction of parturition in the mare.
A wide range of protocols have been suggested over the years,
including a bolus dose (20–75 units), low doses (2.5–20 units)
repeated every 15 minutes to effect, and as a slow IV drip of 60
to 120 units total (1–2 units/min).
The choice of oxytocin regimen is less important for foal
viability than appropriate case selection and adherence to cri-
teria for induction.722,770 A low-dose protocol has been recom-
mended because it appears to work only in those mares that
have a mature fetus.507 Mares were diagnosed as being ready
for birth by mammary secretion Ca strip test measurements.
A single injection of 2.5 IU oxytocin (administered IV) was
given between 1700 and 1900 hours and resulted in the deliv-
ery of a normal foal within 120 minutes in 95% of mares. In
response to the first oxytocin injection, 24 of 38 (63%) treated
mares foaled. Another 9 of 38 (24%) foaled the next evening
in response to the second injection, and 3 of 38 (8%) foaled
in response to the third treatment. It was concluded that the
major advantage of injecting a daily low dose of oxytocin
appears to be that such a low dose induces delivery in only
those mares that are carrying a mature fetus and are ready to
foal. It has been proposed that this low-dose, early-evening
oxytocin protocol could be used as a reliable method to induce
parturition or to predict that the mare would not foal that
night, if parturition did not occur within 2 hours of treatment.
However, even this promising protocol has limitations because
it is still possible to occasionally induce a mare to deliver a
premature foal.
Villani and Romano studied the effects of a daily oxyto-
cin treatment (3.5 IU) on 174 full-term Standardbred mares
that had mammary secretion Ca levels of ≥200 ppm.788 In this
study 69% of the mares foaled within 2 hours of treatment
(51.3% responded to the first oxytocin administration, 14.2%
to the second, and 3.4% to the third). No significant differ-
ence between treated and control mares was observed in the
gestational length (340 ± 8 days vs. 337 ± 7 days), duration of
foaling (10 ± 5.6 minutes vs. 11 ± 4.9 minutes), incidence of
dystocia (1.4% vs. 1.7%), or failure of rupture of the allanto-
chorion (0% vs. 0.6%). No significant difference was observed
in the incidence of placental retention between treated and
control groups (8.1% vs. 6.3%). Physical and behavioral char-
acteristics were normal in foals of both groups. The authors
concluded that daily injections of low doses of oxytocin in at-
term mares showed only moderate efficacy for inducing par-
turition. However, the easy applicability and safety—for both
mare and foal—of this method of foaling induction make it a
useful tool to simplify the management of mares in commer-
cial stud farms.
Because most inductions will be performed because com-
plications are expected, the clinician should be well prepared
before administration of the induction agent (low-dose oxy-
tocin). Even if the induction is not being performed by an
IV drip, it is recommended that an IV catheter be inserted.
This will facilitate rapid induction of general anesthesia if
obstetric difficulties ensue. A fully stocked obstetric kit and
ample volumes of lubricant should be placed outside the
stall. Neonatal resuscitation efforts should be anticipated, and
appropriate supplies (e.g., oxygen delivery system) should be
readily available. Premature separation of the placenta is not
an uncommon complication of induced births. The clinician
should immediately rupture the exposed chorioallantois and
then assist with fetal delivery in conjunction with the mare’s
expulsive efforts. Overzealous traction at this time may cause a
laceration of the cervix if it is not yet fully dilated. If necessary,
an oxygen tube can be placed in the foal’s nostril during the
minute or two that may be required to complete the assisted
delivery. Additional discussion of neonatal resuscitation and
critical care is included in Chapter 20.
Y MANAGEMENT OF THE PREGNANT
MARE
A series of manuscripts addressing the effects of nutrition on
various aspects of equine reproduction have recently been
published.789-792 Copper is an overemphasized factor in the
etiopathogenesis of osteochondrosis lesions. Supplementa-
tion of pregnant mares with copper had no significant effect
on the concentration of copper in the liver of foals at birth or
on the frequency or severity of lesions in articular cartilage at
160 days of age.793 Regular exercise and routine hoof mainte-
nance are important for broodmares. A regular anthelmintic
program is essential to ensure the mare’s well-being. It will also
reduce the exposure of the foal to parasite eggs in the mare’s
feces and the transmammary transfer of Strongyloides westeri
 CHAPTER 19
larvae. Pregnant mares should be current for all vaccinations
that are recommended for their particular geographic loca-
tions. In North America it is especially important to advise
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owners about the importance of a regular vaccination pro-
gram for EHV. Owners and farm managers should be aware
of the need to isolate pregnant mares from transient horses
to reduce the risk of infectious disease, especially respiratory
viral infections. A tetanus booster may be indicated 1 month
before foaling. The American Association of Equine Practi-
tioners has published a general guideline for vaccination of
horses, including pregnant mares. The reader is referred to
that publication for current best practices related to vaccina-
tion of horses.794
Ideally the mare should be transferred to the final foal-
ing environment at least 1 month before the due date. Foals
are born essentially agammaglobulinemic, and the neonate
depends on passive transfer of colostral immunoglobulins
to provide initial protection from environmental pathogens.
If a vulvoplasty (Caslick surgery) has been performed, plans
should be made to open this approximately 1 week earlier than
the expected foaling date. If the mare has a history of a pre-
vious hemolytic foal (neonatal isoerythrolysis), plans should
be made to prevent the neonate from suckling the mare until
all the colostrum has been removed or plans for compatibility
testing of the milk and foal blood should be made. The mare
may be screened for the presence of antibodies to common
equine blood antigens 2 weeks prior to the anticipated foal-
ing date to identify mares at risk for producing incompatible
colostrum. At-risk mares should be milked immediately post-
partum and the foal not allowed to suckle its dam for 24 hours.
Some practitioners recommend administering sulpiride or
domperidone for early milk production and milking the mare
prepartum to avoid colostrum formation. An alternate source
of colostrum from an appropriate donor should be available
for the foal and plasma supplementation considered.
Those responsible for monitoring the foaling process
should understand that mammary development, followed by
distention and waxing of the teats and then relaxation of the
perineal area, indicates approaching parturition in the mare.
The use of mammary secretion electrolyte concentrations
and pH to predict foaling was discussed in a previous section.
Although it is accepted that the fetus signals its readiness for
birth, the mare can regulate the final timing of delivery. Elec-
tronic monitoring systems that can be used to signal the start
of parturition are also available.
Inexperienced personnel should be counseled about nor-
mal foaling events and instructed in how to recognize when
professional assistance is required. Inappropriate interven-
tion by ill-informed individuals can jeopardize the foal’s life
and potentially cause life-threatening complications in the
mare. Separation of the fetal membranes will deprive the fetus
of oxygen, and this is the critical factor that must be consid-
ered when assessing an obstetric case that involves a live foal.
Although most references suggest that fetal survival rates are
very low if the foal is not delivered within 30 to 40 minutes
of chorioallantoic rupture, one author reports having deliv-
ered live foals by cesarean section up to 90 minutes later.795
Another study reports high foal survival rates in mares
referred with dystocia for as long as 1.5 hours post rupture of
the chorioallantois. These authors suggest that, because trans-
verse presentation appears to be more common in draft mares,
parturition does not progress as expected, mares stop having
uterine contractions, and, as a consequence, there is minimal
Disorders of the Reproductive Tract 12971297
placental detachment. These are cases that were promptly
presented to the veterinary hospital and that had minimal, if
any, vaginal intervention at the farm. It is likely that limited
vaginal intervention is less disruptive to the placental attach-
ment, and these foals are not deprived of their oxygen sup-
ply. Keeping the mare on her feet, and walking if necessary,
may help to reduce straining while professional assistance is
sought. If a mare is located a great distance from a referral
facility equipped to provide appropriate care, the mare should
be sedated with detomidine, and oral clenbuterol should be
administered prior to transport.
Normal Parturition
Terminology
The terms presentation, position, and posture are used to
describe the orientation of the fetus as it enters the vaginal
canal. Often a fetus is described as having been malpresented
or malpositioned when the only anomaly present is postural,
the most common cause of dystocia in the mare.796 To prevent
confusion, the all-encompassing term fetal maldisposition may
be used to describe the combination of presentational, posi-
tional, and postural abnormalities that can contribute to a dys-
tocia. Presentation describes the aspect of the fetus that enters
the vaginal canal first and the orientation of the fetal spinal
axis to that of the mare (anterior or posterior longitudinal;
ventral or dorsal transverse). More recently, use of the terms
cranial and caudal presentation has become more common.
Position describes the relationship of the fetal dorsum (lon-
gitudinal) or head (transverse) to the quadrants of the mare’s
pelvis. The normal position for delivery is dorsosacral. A fetus
that is still on its side would be right or left dorsoilial, and a
fetus that is upside down would be dorsopubic. The terms right
and left cephaloilial refer to the position of the fetal head rela-
tive to the mare’s pelvic walls, and they imply that a transverse
presentation was present. Posture is purely fetal and describes
the relationship of the extremities (head, neck, and limbs) to
the foal’s body (flexed or extended).200,796
Fetal Kinetics
Fetal mobility has been discussed with respect to umbilical
cord torsion and abortion. Fetal rotation within the amniotic
cavity and amniotic sac rotation within the allantoic cavity
result in the characteristic twisting of the umbilical cord.676,677
A highly efficient mechanism ultimately guides most equine
fetuses into a cranial, longitudinal presentation. Ultrasono-
graphic studies have noted the percentage of anterior, poste-
rior, and transverse presentations at 5 to 6 months to be 52%,
29%, and 19%, respectively, but the fetal presentation becomes
predominantly anterior between 7 and 11 months.673,675-677,682
Vandeplassche reported the incidence of anterior, posterior,
and transverse presentations in the normal parturient mare
population to be 98.9%, 1.0%, and 0.1%, respectively.797 Gin-
ther observed that muscular contractions close the lumen of
both uterine horns between 5 and 7 months; thus the allantoic
fluid (with the fetus) is confined to the uterine body.673,674,676
During this time the fetus positions itself so that its head end
points toward the mare’s cervix (cranial presentation). It has
been proposed that neurologic signals within the fetal inner ear
may respond to the slope of the ventral uterine wall and guide
the fetus to lie with its head elevated toward the cervix.673 In
most cases the noncord horn remains closed, whereas the cord
horn gradually permits the entry of the hindlimbs between 7
 1298 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
and 9 months. The limbs can enter the horn only when the
fetus is in dorsal recumbency because the angle between the
horn and body is so acute by this stage of gestation. There-
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after the hindlimbs remain enclosed within the cord horn,
and the hooves extend to the horn tip by the tenth month.
Thus the selective closing and opening of the uterine horns,
with subsequent trapping of the hindlimbs, is believed to be
a key feature of the mechanism that ultimately directs fetal
orientation into cranial presentation.673,675 Entrapment of the
hindlimbs within the uterine horn generally means that the
caudal portion of the anteriorly presented fetus will be lying
in a dorsopubic, and occasionally dorsoilial, position.675 Gin-
ther’s ultrasonographic investigations substantiated the classic
radiographic study demonstrating that the full-term equine
fetus is initially lying in a dorsopubic position with the head,
neck, and forelimbs flexed.675,798
In early pregnancy the mesometrial attachments suspend
the uterine horns so that they point cranially and dorsally, but
by late gestation the horn containing the hindlimbs comes to
rest on the dorsal surface of the uterine body with the tip of the
horn directed back toward the cervix.402,675 The hooves and
horn tip may be pushed so far caudally that they actually come
to lie over the fetal head, meaning that when a rectal evalua-
tion of a mare that is in late gestation is performed, the fetal
hooves that are palpable may be attached to the hindlimbs. In
some mares the vigorous, piston-like thrusts of the hindlimbs
in association with elevation of the fetal rump may push the
hooves past the cervix into the rectogenital pouch. This obser-
vation may explain the acute colic episodes that have been
previously attributed to uterine dorsoretroflexion. Although
the caudal aspect of the fetus is intimately associated with the
uterine wall, the cranial portion has room to rotate within the
uterine body itself. Ultrasonographic studies on mares close to
term (>330 days' gestation) have shown that the cranial half
of the fetus was in dorsopubic position approximately 60%
of the time and in dorsoilial position about 40% of the time.
The forelimbs and head were usually flexed (about 80%), but
the remainder of the head or limbs was extended.673 Postural
changes are common; thus rectal palpation before the onset of
first-stage labor is not a good predictor of impending dystocia.
However, detection of a posterior or transverse presentation
at this late stage is cause for concern, and appropriate plans
should be made to manage the impending delivery.
Stages of Parturition
Behavioral changes that characterize the first stage of partu-
rition include the mare looking at her flank, frequently lying
down and getting up, stretching as if to urinate, and passing
small amounts of feces. Patchy sweating may develop, and
some mares will leak colostrum.200,796 The restless behavior is
similar to that of mild colic and is associated with the develop-
ment of coordinated uterine contractions that increase uterine
pressure and push the chorioallantoic sac (in the region of the
cervical star) into the gradually dilating cervix. The increas-
ing uterine tone during stage I of parturition may stimulate
the fetus to extend its head and forelimbs up into the dilat-
ing pelvic canal.402 Once the head and forelimbs are fully
extended, they are unlikely to return to a flexed posture unless
the foal reacts to manual intervention on the part of a foaling
attendant. However, it is possible for the neck or a forelimb
to develop a malposture if it is not correctly aligned when
the mare begins an expulsive effort. Passage of the urine-like
allantoic fluid (“water breaking”) concludes the first stage of
labor. Rupture of the chorioallantois and passage of the allan-
toic fluid does not occur until the fetlocks, or sometimes the
knees, are at the level of the external cervical opening. If the
chorioallantois does not rupture, then further separation from
the endometrium can result in a red bag delivery, with the vel-
vety red membrane appearing at the vulvar lips. In a normal
delivery the chorioallantois is thought to remain attached to
the endometrium until after the foal is delivered.796
Failure of the chorioallantois to rupture is a common com-
plication of induced parturition.722 If this happens, then con-
tinued separation from the endometrium will compromise
transplacental oxygen exchange, and fetal hypoxia is likely.796
Premature separation of the placenta, or red bag, is an emer-
gency situation, and foaling attendants should be instructed
to break the membrane and provide gentle traction in unison
with the mare’s expulsive efforts. Although the foal should be
delivered as quickly as possible, injudicious traction at this
time may cause a laceration in an incompletely dilated cer-
vix.796 Applying traction only in conjunction with the mare’s
expulsive efforts will reduce the likelihood of creating cervical
trauma.
As parturition progresses, passage of the fetus into the pel-
vic inlet initiates a reflex release of oxytocin from the posterior
pituitary (Ferguson reflex), enhancing uterine contractility.200
Stage II is characterized by strong abdominal contractions that
provide the expulsive force necessary to expel the fetus. Most
mares will assume lateral recumbency once active straining
commences. Many get up once or twice during stage II labor
in what is believed to be a further attempt to correctly position
the fetus.796 Appearance of the translucent fluid-filled amnion
at the vulvar lips can be expected to occur within 5 minutes
of rupture of the chorioallantois.799 Any delay in the stage II
expulsion process increases the likelihood of fetal asphyxia or
neonatal problems associated with hypoxia caused by placen-
tal separation. At least one hoof should be visible within the
amniotic sac, and the other should be located approximately
2 inches behind it. If everything is progressing normally, then
the soles of the hooves should face down toward the mare’s
hocks, and the foal’s head should be resting between the carpi.
By the time the nose has reached the vulva, the cranial half
of the torso should have rotated from a dorsopubic to a dor-
soilial position. The mare probably assists the fetus to reposi-
tion itself by the characteristic side-to-side rolling each time
she becomes recumbent. It is likely that some dystocias involv-
ing fetal malposition and malposture are caused by the failure
of a compromised fetus to actively participate in the foaling
process. Less vigorous or absent fetal righting reflexes early in
the parturient process have been suggested by many authors
as a cause of fetal maldisposition.200,726,798 The observation
that ventral deviation of the head and neck is more likely to
be present if the fetus is in a dorsoilial position than in a dor-
sosacral position further substantiates the hypothesis that the
fetal righting reflexes are compromised early in these cases.726
The second stage of labor in the mare is rapid, with the most
forceful contractions occurring as the chest passes through the
pelvic cavity. Most foals are delivered within 20 to 30 minutes
after the chorioallantoic membrane ruptures. Primiparous
dams generally require more time to expel the fetus than do
multiparous dams.200,799 The amniotic sac usually ruptures
during these expulsive efforts. However, the equine amniotic
sac is not attached to the chorioallantois, as is the case with a
ruminant placenta, and the foal sometimes may be delivered
with a portion of the sac wrapped around its head. Foaling
 CHAPTER 19
attendants should be instructed to promptly free the foal’s
head from the amniotic sac to prevent suffocation. Active
straining ceases once the foal’s hips are delivered, and the mare
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will rest in lateral recumbency. An active foal will extract the
hindlimbs from the vagina as it struggles to stand. Stage III of
parturition involves expulsion of the fetal membranes, which
typically takes between 30 minutes and 3 hours.200 Owners
should be advised to seek veterinary assistance if passage of
the membranes is delayed beyond 4 to 6 hours because life-
threatening toxic metritis and laminitis are common sequelae
of fetal membrane retention.
Etiology of Dystocia
The incidence of dystocia in the general horse population var-
ies among breeds (Thoroughbreds 4%, Shetland ponies 8%,
draft breeds 10%).800 Dystocia is one of the few true emer-
gencies in equine practice. Literally a matter of minutes can
determine a successful outcome (i.e., the birth of a live foal).
Perinatal asphyxia associated with dystocia is a major cause
of equine reproductive loss.591,592 The long fetal extremities
(limbs and neck) predispose the mare to foaling problems.
Alert, informed foaling attendants are essential to ensure that
abnormalities are recognized early. Attendants should suspect
that the mare is experiencing obstetric problems if either the
first or the second stage of parturition is prolonged or not
progressive.
Signs that a mare may be in dystocia include the failure of
any fetal parts or of the amniotic membrane to appear at the
vulvar lips for a prolonged period after rupture of the chorio-
allantois, appearance of only one hoof at the vulva, hooves
upside down at the vulva, hooves and nose in an abnormal
relationship, and nose but not hooves at the vulva. The most
common impediments to delivery are malpostures of the fetal
extremities (head and neck and limbs).726 An experienced
foaling attendant may be able to correct minor problems and
facilitate a successful delivery, but inappropriate intervention
can have potentially fatal consequences for the mare. Further-
more, obstetric manipulations can easily damage the uterus
and cervix to the extent that the mare’s reproductive future is
jeopardized.
Management of Dystocia
When attending to a mare in dystocia, the veterinarian should
make a rapid assessment of the mare’s general physical condi-
tion, noting in particular mucous membrane color and refill
time (hemorrhage, dehydration, and shock). A mare that is
aborting in late gestation may experience a dystocia because
the dead fetus cannot participate in the delivery process. A
malodorous discharge and fetal hair in the hands of the clini-
cian strongly suggest the presence of an emphysematous fetus.
The perineal area should be inspected to determine the pres-
ence and nature of any vulvar discharge and the presence of
fetal membranes and to identify any fetal extremities. Exces-
sive hemorrhage or vulvar swelling may indicate that inter-
vention by inexperienced individuals has caused trauma to the
reproductive tract. Occasionally, a foaling mare will present
with rectal prolapse, an everted bladder, or intestinal loops
protruding from the vulvar lips. The intestines may be of fetal
origin if there is incomplete closure of the ventral abdomen,
but a ruptured vagina is more likely. In the later scenario the
foal’s foot may have ruptured the floor of the cranial vagina,
but injudicious manipulations by an inexperienced attendant
should not be discounted. If a rectal prolapse or the urinary
Disorders of the Reproductive Tract 12991299
bladder is evident, then an epidural anesthetic should be
administered to prevent further straining. Alternately, the
mare may be anesthetized to facilitate hoisting the hindquar-
ters. The advantage of this approach is that the straining can
be stopped immediately. This is especially important if the
prolapse involves an intussuscepted colon (type IV). In these
cases a palpable defect may extend several feet into the rectum,
and avulsion of the mesentery can be a fatal complication that
is not readily amenable to surgical correction.
Due to the unpredictable and potentially violent nature
of mares in stage II of labor, the use of stocks for restraint is
contraindicated. The initial examination can be performed
on a standing mare with no more restraint than a twitch or
lip chain if her demeanor permits this to be performed safely.
It is important to ensure that the examination area is clean,
with good footing. There should be ample space for the mare
handler, obstetrician, and assistants to move to safety if neces-
sary. Although most veterinary tranquilizers readily cross the
placenta and can compromise the fetus, adequate restraint is
essential for the safety of all involved.801 Sedation with tran-
quilizers may be necessary for some uncooperative mares, and
in extremely intractable cases it may be preferable to anesthe-
tize the mare with a short-acting combination. In these cases
a hoist should be available to elevate the hindquarters because
manipulating the foal is sometimes difficult when the mare is
in lateral recumbency. Although not essential, an initial rec-
tal examination may help the practitioner rule out the pres-
ence of a term uterine torsion and determine the condition of
the uterine wall (tears and spasm). It also may provide useful
information regarding the disposition of the fetus. Before any
vaginal examination the mare’s tail should be wrapped and the
perineal area thoroughly cleansed. The clinician’s arms and
hands should be scrubbed, and the clinician should wear ster-
ile obstetric sleeves. Cleanliness and lubrication are the cor-
nerstones of obstetrics.
The mare’s vagina and cervix are easily traumatized by
the friction associated with vaginal manipulations. Once the
mucous membranes have been abraded, it is likely that adhe-
sions and fibrosis will follow. Thus copious amounts of lubri-
cant are vital to ensure that the soft tissues of the genital tract
are not traumatized to preserve the mare’s future fertility.802
Lubricants include methyl cellulose, polyethylene polymer,
white petrolatum combined with 10% boric acid, and mineral
oil. Water-soluble lubricants are generally not as desirable,
because they rapidly lose their lubricating abilities in the pres-
ence of fluids. If a large volume of lubricant is to be pumped
around the fetus, then investigating the possibility of a uterine
laceration is essential. In a referral situation, abdominocentesis
should be performed. Serosanguineous to sanguineous fluid
that contains elevated total protein levels and an increased
white blood cell count is highly suggestive of a uterine rup-
ture.197 If a uterine tear is unlikely, obstetric lubricant may be
gently instilled into the uterine lumen using a clean stomach
tube and pump.802 This is repeated as often as necessary during
the procedure to keep the fetus and reproductive tract coated
with lubricant.
The vagina, cervix, and accessible parts of the uterus should
be carefully explored to ascertain the source of any hemor-
rhage. Lacerations should be noted and their presence dis-
cussed with owners or the attending personnel before any
veterinary manipulations are attempted. Occasionally, the
cause of the dystocia is a pelvic deformity (e.g., callus, neo-
plasia). It is important to determine the degree of cervical
 1300 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
dilation. If the mare has been in labor for some time, then it is
possible that the uterus is relatively dry and tightly contracted
around the fetus. This will make intrauterine manipulations
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much more difficult, especially because it becomes difficult to
repel the fetus back into the uterus without risking rupture.
When the uterus is contracted, warm lubricant tends to induce
some uterine relaxation, and the volume expansion creates
additional space in which to perform manipulations.204,802
Myometrial contractions (uterine spasm) can be controlled
by tocolytic drugs (isoxsuprine and clenbuterol) if they are
available for veterinary use.800 Some mares never stop hav-
ing strong uterine contractions; general anesthesia is highly
beneficial for these mares and allows the clinician to perform
appropriate obstetric interventions.
Although fetopelvic disproportion is less common in the
mare than the cow, it can be a factor in some equine dysto-
cias.445,796,803 The disposition of the fetus should be noted and
fetal viability determined. Care should be exercised because
active fetal response to manipulations can easily complicate
an initially simple dystocia. Placement of a rope snare behind
the ears and into the foal’s mouth ensures that the clinician
always has control of the head. This will facilitate correction
of a potentially life-threatening development such as lateral
deviation of the head and neck if the fetus pulls away from
the clinician’s manipulations. If the snare is placed around
the mandible, then it is essential that only gentle traction be
applied to guide the fetal head through the vaginal canal.
Excessive force may cause a fracture of the mandible. When
obvious fetal movement is absent, digital withdrawal may be
initiated in response to pinching of the coronary band. Slight
digital pressure over the eyelid onto the eyeball may arouse
a response, as may stimulation of the tongue (swallowing). If
the thorax can be reached, then the fetal heartbeat is definitive.
In posteriorly presented cases the digital and anal reflexes are
useful as indicators of fetal viability. Occasionally, it may be
possible to reach the umbilical cord.
The clinician should inform the owner of the various
options, costs, and prognosis once the current status of the foal
is known and the cause of the dystocia has been determined.
Ensuring that the owner is aware of the potential complica-
tions that may arise is especially important because postpar-
tum medical care can become quite expensive. If delivery of a
live foal is anticipated, then the clinician should consider the
potential for fetal cardiovascular compromise before adminis-
tering any tranquilizers to the mare. Light sedation of the mare
with acetylpromazine (2–3 mg/100 kg IV) has minimal effect
on the foal and may be useful in some cases.801 Xylazine is pref-
erable to detomidine if the fetus is viable because its depres-
sant effects are of much shorter duration. However, neither
xylazine nor detomidine should be used alone to sedate a dys-
tocia case because some apparently sedated mares can become
hypersensitive over the hindquarters.706,801 The combination
of xylazine and acetylpromazine provides good sedation in
a quiet mare.198 The author routinely uses a combination of
xylazine (0.3–0.5 mg/kg IV) and butorphanol (0.01–0.02 mg/
kg IV) for standing obstetric procedures if more sedation is
required (e.g., fetotomy procedure). This provides good seda-
tion and analgesia, and additional doses may be administered
as necessary. Attendants are instructed to keep the lip chain
loose and to tighten it only when instructed to do so. This will
ensure that it retains its effectiveness when required to divert
the mare’s attention. LeBlanc suggested a xylazine (1.1 mg/
kg) and morphine (0.1–0.2 mg/kg) combination for sedation
of fetotomy cases but cautions that gastrointestinal stasis is a
frequent complication.801
Although most dystocias can be resolved at the farm fairly
quickly by brief manipulation and assisted vaginal delivery,
the practitioner should consider the alternatives if resolution
is likely to take more than 10 to 15 minutes. Prolonged, unpro-
ductive vaginal manipulations are contraindicated in equine
obstetrics. Decisions on the next course of action should be
based on the viability of the foal, the clinician’s obstetric skills,
the availability of equipment and facilities, and the financial
constraints imposed by the owner.
An epidural does not prevent the mare’s myometrial con-
tractions or the abdominal press, and the time involved in
administering an effective epidural anesthetic may make this
form of restraint impractical when a live foal is present.796,801
However, if the foal is dead, epidural anesthesia does reduce
vaginal sensitivity and thus the mare’s perception of vaginal
manipulations (Ferguson reflex). Caudal epidural anesthesia
should be used at the clinician’s discretion, especially if general
anesthesia or referral may become necessary. When an epi-
dural is indicated, the author uses a combination of xylazine
(0.17 mg/kg) and lidocaine (2–3 mL) diluted in saline, such
that the final volume does not exceed 8 to 10 mL to reduce
the likelihood of hindlimb weakness.801,804 Excess volume can
cause the mare to become ataxic. Short-term general anesthe-
sia may be indicated when minor postural abnormalities are
present and maternal expulsive efforts make correction diffi-
cult. Xylazine (1.1 mg/kg IV) followed by ketamine (2.2 mg/
kg IV) provides a general anesthetic with a smooth, short (10–
15 minutes) duration. Addition of the central-acting muscle
relaxant guaifenesin (1 L of a solution of 5% guaifenesin in 5%
dextrose) can provide an additional 10 to 20 minutes for fetal
manipulation.801
In referral equine hospitals that are located close to well-
managed broodmare farms, the fetus is often still alive when
the mare arrives. A well-coordinated dystocia team that uses
a defined protocol can minimize time spent nonproduc-
tively. Intrapartum intratracheal intubation and positive pres-
sure ventilation of the fetus (ex utero intrapartum treatment
[EXIT]) during resolution of the dystocia has been shown to
improve survival rates. It should be remembered that positive
pressure ventilation must be continued once begun because
it promotes the conversion from fetal circulatory patterns
to neonatal patterns, essentially eliminating the role of the
umbilicus.805 In referral hospitals it is common practice to
anesthetize the mare after a brief vaginal intervention and
then maintain the mare on halothane-oxygen with controlled
ventilation. Because halothane anesthesia has been shown to
compromise umbilical circulation, the concentration should
be kept to a minimum if the foal is still alive.806
Total intravenous anesthesia (the so-called triple drip of
ketamine, xylazine, and guaifenesin) may be preferable until
the foal has been delivered.801 The mare should be venti-
lated with oxygen, and IV fluids should be administered as
required. If the hind-end elevation technique is used, almost
three quarters of such cases can be resolved by controlled vagi-
nal delivery. However, if the fetus is still alive and has not been
delivered within 15 minutes, an immediate cesarean section
is performed, with a 30% foal survival rate possible, provided
the time from rupture of the chorioallantois to presentation at
the veterinary hospital is minimal.795,807 Fertility after cesar-
ean section is quite good, and adverse reports probably pertain
more to the extent of vaginal manipulation after surgery.808,809
 CHAPTER 19
If a hoist is available in the field, then hobbles can be placed
on the hind pasterns and the hindquarters briefly elevated 1
to 2 feet. The combination of a relaxed uterus and the effects
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of gravity can facilitate fetal repulsion and manipulation. If
attempts at mutation are successful, then the mare should be
lowered into lateral recumbency to permit extraction of the
foal. Prolonged dorsal recumbency results in compression
of the aorta and vena cava and reduction in venous return,
cardiac output, and blood pressure.801 Hindlimb paresis may
develop after prolonged hindquarter suspension and can com-
plicate the recovery process. The use of pads to support the
hindquarters will help take some weight off the limbs while
the mare is suspended.
Mutation is an obstetric term that is used to describe
manipulation of the fetal extremities, with correction of any
positional abnormalities, so that assisted vaginal delivery can
proceed.200 Although extra space is available for manipula-
tions when the fetus has been repelled into the uterus, the
clinician should remain cognizant at all times that overzeal-
ous obstetric manipulations are a major cause of uterine
rupture.197,198,200,204,735,810-812 Repulsion of the fetus from the
maternal pelvis is contraindicated if the uterus is contracted
down around the fetus. In countries where they are legal, toco-
lytic agents are effective in relaxing a contracted uterus. If the
fetus is dead, many cases may be amenable to correction by
fetotomy provided that the clinician has the appropriate skills
and equipment.813-817 Although poor technique and inappro-
priate fetotomy cuts often lead to infertility, experienced clini-
cians can rapidly resolve a dystocia while preserving the mare’s
future breeding potential. The alternative is cesarean section.
Traction must be applied with careful regard for both
maternal and fetal well-being. Often traction applied entirely
by hand is all that is necessary. Obstetric straps or chains may
provide a better grip, with one loop above the fetlock and a
second loop encircling the pastern. In assisted vaginal deliver-
ies, traction should be applied as an adjunct when the mare is
exerting expulsive force and should be released when the dam
stops straining, permitting rest and recovery. This approach is
critical to permit adequate dilation of the caudal reproductive
tract. Copious lubrication and slow traction with continuous
monitoring of cervical dilation are especially important when
a controlled vaginal delivery is performed on an anesthetized
mare. Excessive use of force may be associated with fetal frac-
tures (ribs, vertebrae, and limbs), maternal soft tissue trauma,
and uterine prolapse.818 No more than two or three people
(depending on size and strength) should apply traction to the
fetus.
Cranial (Anterior) Presentation
An anteriorly presented fetus that is in the dorsosacral posi-
tion with head and forelimbs extended should require minimal
traction to complete the delivery, assuming that the vaginal
canal is well lubricated. By ensuring that slightly more traction
is applied to one limb than the other, the practitioner reduces
the width of the fetus across the shoulders and can successfully
deliver most cases. If progress is not being made, then all trac-
tion should stop and the vaginal canal must be fully explored.
There are three likely possibilities: elbow lock (incomplete
extension of the forelimb), dog-sitting or hurdling posture,
and occasionally a fetus that is too large.
Absolute or relative fetopelvic disproportion is uncommon
in the mare even when the foal has been carried several weeks
past the expected due date. In fact, some cases of prolonged
Disorders of the Reproductive Tract 13011301
gestation may involve a smaller than normal, dysmature fetus.
In a referral hospital study, fewer than 2% of dystocias were
attributed to this condition.726 It is significant, however, that
approximately 30% of referral hospital dystocia cases are in
primiparous mares.726,799 Primiparous mares were dispro-
portionately represented in a report on dystocia and neonatal
asphyxia from the central Kentucky area.178 Although fetopel-
vic disproportion is not common in the mare, obstetric assis-
tance (traction) is required much more often in primiparous
mares.200,730 Dystocia in these mares is further complicated by
a tight vaginovestibular sphincter, which may predispose pri-
miparous mares to lacerations and rectovaginal tears. If copi-
ous lubrication and gentle traction do not help, then cesarean
section or partial fetotomy are the only alternatives.
Incomplete elbow extension may be unilateral or bilateral
and should be suspected if the fetal muzzle lies at the same
level as the hooves. In this posture the fetal elbows will be
tucked back under the shoulder joint, causing increased depth
and width of the fetus within the maternal pelvic inlet. Cor-
rection involves repelling the fetal trunk so that the forelimbs
can be extended, raising the elbows up over the floor of the
pelvic inlet.
In a dog-sitting or hurdling posture, there is either bilateral
(dog-sitting posture) or unilateral (hurdling posture) hip flex-
ion. This causes the fetal hooves (or hoof) to push against the
pelvic brim during attempts at fetal extraction. The unilateral
posture is more common.726 Severe trauma can be inflicted on
the mare if this malposture is not recognized and inappropri-
ate amounts of traction are applied. Thus it is important to
stop all traction and repel the fetus enough to sweep the floor
of the pelvic inlet. In extreme cases the hindlimb may actu-
ally extend under the fetus and up into the vagina.726 Although
the hindlimb may be successfully repelled if the fetus is alive,
it is a difficult procedure and is associated with some risk of
uterine laceration. Judicious use of a snare or fetotome may
facilitate safe repulsion of the hindlimb by looping the pas-
tern and using the instrument to repel the hoof away from the
pelvic brim. Repulsion should not be attempted on a stand-
ing mare if the fetus is dead, because the hindlimb may not
return to its normal position. In such cases the hoof of the
flexed hindlimb can puncture the ventral uterine wall as the
foal is being extracted. If a dog-sitting or hurdling foal is dead,
it is then recommended that general anesthesia and hoist-
ing of the hindquarters be used to reduce the risk of ventral
uterine rupture.819 In experienced hands, partial fetotomy
is a viable alternative to cesarean section.813,814,817 A surgical
alternative to a cesarean section involves manipulation of the
hindlimb through a ventral midline celiotomy incision. An
assistant may be able to extract the fetus through the vagina
once the hindlimb has been grasped through the ventral inci-
sion. If successful, this technique will reduce the potential for
contamination that may be associated with cesarean section.
If a cesarean section is performed, some surgeons prefer to
remove that portion of the foal that is protruding through the
vulvar lips before withdrawing the hind end out through the
surgical site.
In a foot-nape posture one or both of the forelimbs is dis-
placed over the foal’s head and pushed against the roof of
the vagina.802 To correct this malposture the fetus must be
repelled into the uterus by applying pressure to the head. Once
the forelimbs have been replaced under the head, fetal extrac-
tion can proceed quite uneventfully. If not corrected imme-
diately, then the mare’s straining can cause the fetal hoof to
 1302 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
lacerate the vaginal roof, and in extreme cases it can result in a
rectovaginal fistula. A fistula is all that occurs if the foal with-
draws its hoof from the rectum before delivery. A third-degree
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perineal laceration occurs if the strong expulsive efforts of the
mare cause the limb that has penetrated the rectum to dissect
through the caudal rectovaginal shelf and rupture through the
anal sphincter, creating a cloaca.820,821
Carpal flexion is a common cause of dystocia. It may be
unilateral or bilateral, and typically the affected carpus is
located at the pelvic inlet.802 To safely correct this malpos-
ture, the fetal body must first be repelled into the uterus. If the
dystocia is prolonged, then the amount of uterine contraction
may preclude meaningful repulsion of the fetus back into the
uterus. Because the fetus is likely to be dead in these cases, a
relatively simple fetotomy cut can be made at the level of the
distal row of carpal bones. This permits safe delivery of the foal
without the need to traumatize the reproductive tract and gen-
erally facilitates extraction within minutes.813,815,817 If the foal is
alive, then repulsion into the uterus will permit the flexed limb
to be grasped at the level of the fetlock and pastern. By rotat-
ing the wrist, the obstetrician can rotate the carpus laterally
while bringing the flexed fetlock medially and caudally into
the birth canal. This maneuver allows maximal use of available
space by obliquing the extremity through the pelvic inlet. The
obstetrician should be aware that flexural deformities are con-
sidered to be the most common congenital anomaly of foals
and that the rigid deformity often means that a cesarean sec-
tion or fetotomy must be performed.178,591,797,813,814 Limb con-
tractures are generally bilateral. Contracture is more common
in the forelimbs than the hindlimbs but can involve all four
limbs.797,802 Severely affected limbs cannot be straightened,
and needless trauma can be inflicted on the genital tract by
unrewarding attempts to manually correct the malposture. It
is important that the clinician cup the hand over the bottom
of the fetal hoof at all times while attempting to straighten the
limb. Failure to do so may result in injury to the reproductive
tract. Application of an obstetric chain or rope to the distal
limb can be a useful aid. This permits traction to be applied
to the distal limb while the hand covers and guides the hoof.
The single most common abnormality in referral hospi-
tal dystocia populations is a reflected head and neck.726,797,816
Unfortunately, these malpostures are often iatrogenic in that a
viable fetus has pulled back from the initial vaginal interven-
tion that aimed to correct a minor postural problem. If the
mare strains while the foal’s head is pulled back, it is then pos-
sible for the muzzle to engage the wall or floor of the pelvic
inlet. The mare’s forceful expulsive efforts may then drive the
head and neck ventrally or laterally along the thorax while the
forelimbs are pushed farther into the vaginal canal. Ventral or
lateral displacements of the head and neck can be very difficult
to correct. The length of the foal’s neck often makes it impos-
sible to reach the head. Inexperienced clinicians should con-
sider referral as soon as the condition is diagnosed, because
prolonged unrewarding manipulations can easily jeopardize
the mare’s future fertility. A relatively simple fetotomy cut can
resolve these cases quite atraumatically if the fetus is dead when
the veterinarian arrives. The author believes that this approach
is preferable to prolonged and often unsuccessful attempts at
manual correction of this extremely difficult malposture.
If the fetus is alive, then an attempt can be made to place
eye hooks or to loop a snare around the mandible. Some obste-
tricians even suggest applying a clamp on an ear to pull the
head back enough to place a snare. The author prefers to use a
snare whenever possible. If traction can be applied to the head,
then the foal’s body must be carefully repelled while attempts
are made to bring the head and neck around into a normal
posture for delivery. Factors influencing the successful out-
come include uterine tonicity, clinician arm length and skill,
and the presence or absence of torticollis and facial scoliosis.
As with contracted tendons, it is essential that the practitioner
consider the possibility of a wry neck. This condition is not
amenable to correction by mutation, and needless trauma can
be inflicted on the genital tract by unrewarding attempts at
correction. Ventral deviation of the head is relatively easy to
correct if the fetal nose is just below the brim of the pelvis
(poll posture). It is generally easier to rotate the head laterally
before attempting to bring the muzzle up over the pelvic brim.
In more severe cases the neck is tucked down between the
forelimbs and the head is often beyond reach (nape posture).
If attempts to reposition the head and neck are unsuccessful,
then cesarean section or fetotomy are indicated.
Shoulder flexion posture may be unilateral (“swimming”
posture) or bilateral (“diving” posture). To gain access to the
retained limb, it is usually necessary to repel the head and neck
into the uterus. An immediate cesarean section may be prefer-
able if the foal is alive, because correction of this malposture
can be difficult and time consuming. If this is not an option, it
is then recommended that a soft rope snare be placed on the
fetal head (behind ears and into mouth) so that the head can be
readily retrieved once the shoulder flexion has been corrected.
If the limb can be reached, then correction of this malposture
is performed in two stages. Initially, the shoulder flexion is
converted to a carpal flexion when the limb is grasped in the
area of the humerus working down to the distal radius. The
limb is then pulled caudally and medially as the fetal body is
repelled. The carpus is then hooked over the brim of the pelvis
to create a carpal flexion, which is then corrected as previously
described. It must be remembered that it is not always pos-
sible to repel the head sufficiently to gain access to the retained
forelimb. In these cases cesarean section is the only option for
delivery of a live foal. If the fetus is dead, then a fetotomy cut
to remove the head and neck may provide sufficient room to
correct the malposture.
Caudal (Posterior) Presentation
A foal in posterior presentation will have the soles of the
hooves facing up. Although the author has seen dystocias in
which an anteriorly presented foal was in a dorsopubic posi-
tion with both forelimbs extended, this is a very unusual com-
plication. Foaling attendants should be instructed to wash the
mare’s perineum and then to use a clean arm to check for the
hocks somewhere in the vaginal canal. Gentle traction on the
hindlimbs in conjunction with the mare’s expulsive efforts
may facilitate delivery of a live foal. However, approximately
half of the fetuses may be malpositioned as well, and they often
require veterinary assistance to permit an atraumatic delivery.
Foals in a caudal (posterior) presentation are more likely to be
in a dorsoilial position than foals in a cranial (anterior) pre-
sentation.726 Although a normally positioned fetus in a cau-
dal presentation may not be particularly difficult to deliver,
it is more likely to suffer hypoxia because of compression of
the umbilical cord under the fetal thorax or because of pre-
mature rupture of the umbilical cord.802 Although only about
1% of foals are presented posteriorly, this malpresentation
accounts for between 14% and 16% of referral hospital dys-
tocia cases because any postural abnormalities create a major
 CHAPTER 19
complication.726,797,800 Typically both hindlimbs are involved,
and these types of dystocia cases (hock flexion and hip flexion)
are extremely difficult to correct under field conditions. Hock
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flexion malposture accounts for about one quarter of referred
posterior cases.726,797,800 Correction of a hock flexion is dan-
gerous because of the risk of perforation of the dorsal aspect of
the uterus. The fetus must be repelled into the uterus while one
hock is pushed dorsolaterally and the distal limb is directed
medially. The procedure for obliquing the extremity into the
birth canal is similar to that previously described for correc-
tion of a carpal flexion. An obstetric chain or strap can be used
to apply traction to the limb while the hoof is cupped in the
hand. Straightening a flexed hock entails considerable risk
because the hock is invariably forced against the dorsal uterine
wall. When the uterus is contracted, there is a real possibility
of causing a laceration or perforation. Cesarean section may
be preferable for delivery of a live fetus. The author strongly
believes that fetotomy is a safer procedure than attempts at
mutation if the fetus is dead. Approximately half of referred
posterior presentation cases are breech (bilateral hip flexion
posture).726,797 A cesarean section is indicated if the fetus is
alive because the manipulations involved in correcting this
malposture are time consuming and extremely difficult. The
comments for managing a hock flexion apply because if muta-
tion is attempted, the hip flexion must first be converted into
a flexed hock posture. A key point is to remember to flex both
hocks before attempting to straighten a limb. If one limb is
extended into the vaginal canal while the other hip remains
flexed, then the fetal body will move back into the pelvic canal,
and this will make it extremely difficult to access the retained
limb. If the fetus is dead, the author recommends attempting
to convert the bilateral hip flexion into a hock flexion posture,
followed by correction with two fetotomy cuts through the
distal row of tarsal bones. This may be safer and less traumatic
than attempting to straighten the limbs, provided that the
clinician is experienced in the use of a fetotome. Attempts to
correct a bilateral hip flexion by fetotomy, without first creat-
ing a bilateral hock flexion, are often unrewarding because of
the difficulty in correctly placing the fetotomy wire. Referral
for cesarean section will often provide the best prognosis for
future fertility in these cases.
Transverse Presentation
Only about 1 in 1000 foals is presented transversely. Success-
ful resolution of these dystocia cases requires a significant
amount of obstetric experience, which explains why these rare
presentations account for between 10% and 20% of referral
hospital dystocia cases.726,797,809 Most transverse presentations
are ventral transverse, with the abdomen and limbs of the fetus
presented toward the birth canal. Although the widespread
adoption of ultrasonography has markedly reduced the likeli-
hood of a twin birth, this possibility must always be explored
when more than two limbs are present in the birth canal.178,591
In some instances it may be possible to repel the head and
forequarters of the fetus while extending the two hindlimbs
into the pelvic canal. If the manipulations are successful, the
transverse presentation is thus converted into a posterior pre-
sentation for vaginal delivery. The likelihood of successfully
resolving one of these cases is improved if the mare has been
anesthetized and the hindquarters elevated.802 Transverse pre-
sentations may be associated with flexural limb deformities,
angular limb deformity, and spinal deformity. If the fetus is
alive, then the delivery method of choice is cesarean section.
Disorders of the Reproductive Tract 13031303
Dorsal transverse presentations, with the spinal column of the
fetus presented toward the birth canal, are very rare. These
cases warrant an immediate referral for cesarean section even
if the foal is dead. Although an experienced obstetrician may
be able to deliver a transversely presented fetus by fetotomy,
the owner should be advised that this will be a difficult and
time-consuming procedure, with a high risk of trauma that
will likely impede the mare’s future fertility.802,813,814
Fetal Anomalies
Hydrocephalus is not uncommon in equine fetuses, especially
in pony breeds.726,797,822 The condition occurs when increased
intracranial pressure causes the bones of the skull to enlarge,
sometimes almost doubling the size of the head. The skull is
often very thin, and many affected foals can be delivered after
incising the soft portion of the skull with a finger knife, allow-
ing the skull to collapse. The trunk of the hydrocephalic fetus
is generally smaller than normal and seldom interferes with
delivery. If the enlarged cranium is bony, then a fetotomy cut
may be necessary to reduce the size of the head.
Y CARE OF THE POSTPARTUM MARE
The fetal membranes should be examined after every delivery
to ensure that they have been passed intact and to check for
any placental anomalies that may indicate impending prob-
lems in the neonate. The chorioallantois often has tears that
can be misleading, especially if the mare has trod on the mem-
branes repeatedly. Examining the allantoic side of the mem-
brane may be helpful in that the blood vessels can be pieced
together and will give some idea as to whether a portion is
actually missing.431 Ideally, all foaling mares should receive a
brief physical examination within 24 hours of parturition. If
the mare’s attitude is normal and she displays typical maternal
behavior toward the foal, then the udder should be checked
and the perineal area inspected for evidence of trauma.
A detailed reproductive examination is usually unwar-
ranted because it may unnecessarily disrupt the normal
mare-foal bond that is developing at this time.823 Routine
postpartum use of oxytocin or prostaglandin (cloprostenol)
therapy is not warranted because there is no apparent benefit
for uterine involution in normally foaling mares.824 If the mare
has a foal that is unable to suckle from the mare, or the mare
and foal must be housed in stalls with limited exercise, treat-
ment with oxytocin (10–20 IU IM) every 6 hours should be
considered. All mares should receive a thorough reproductive
examination at the foal heat.
Occasionally an enlarged ovary is detected. This may be
a GTCT that has enlarged during the course of the previous
pregnancy or an ovarian hematoma due to intrapartum bleed-
ing. Prompt diagnosis and surgical intervention may permit
the mare to resume normal cyclicity and conceive during the
current breeding season.
Abdominal discomfort in the peripartum mare may be
due to uterine contractions, especially if the mare has been
treated with oxytocin to promote passage of the fetal mem-
branes. However, other causes of abdominal pain should not
be discounted.736,825-827 When a postpartum mare displays
abdominal discomfort, transabdominal ultrasound and/or
abdominocentesis may be indicated, especially if the mare
does not respond to an analgesic dose of flunixin meglumine.
The normal foaling process does not alter the composition
of the peritoneal fluid from within the normal range. Even
 1304 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
a dystocia does not necessarily cause significant changes in
the peritoneal fluid. If an experienced obstetrician performs
the vaginal manipulations or fetotomy, then the fluid should
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remain normal.197 If the peritoneal fluid is normal, then the
mare should be monitored closely for signs of clinical dete-
rioration. Repeated abdominocentesis or ultrasound may be
indicated when clinical signs suggest that a parturient-related
abdominal lesion may be present because the peritoneal fluid
constituents can change within hours.197 A single elevated peri-
toneal fluid value (total protein, white cell count, or percent
neutrophils) may be an incidental finding. Elevation of two or
more values often signals the onset of clinical abnormalities. If
a postpartum peritoneal fluid sample has a total protein value
above 3.0 g/dL in conjunction with a white blood cell count
greater than 15,000 cells/μL and a white blood cell differen-
tial count greater than 80% neutrophils (especially if degen-
erative changes are present), then the presence of a potentially
life-threatening lesion is likely.197 The peritoneal fluid analysis
should not be viewed in isolation and must be considered in
conjunction with the history and clinical signs being exhib-
ited by the mare. Detection of changes in the peritoneal fluid
almost invariably indicates the presence of foaling-related
trauma in either the reproductive or the gastrointestinal tract.
An early diagnosis followed by appropriate medical or surgi-
cal intervention (or both) will often result in a favorable out-
come. If treatment is not implemented until the affected mare
has become depressed and febrile, with accompanying signs of
shock and toxemia, then the prognosis may be more guarded.
Periparturient Hemorrhage
The arterial supply to the uterus is supported by the mesome-
trium (broad ligament). The major blood supply to the uterus
is from the uterine artery, a branch of the external iliac artery.
It forms a cranial branch that supplies the proximal uterine
horn and a caudal branch that supplies the distal uterine horn
and uterine body. The smaller ovarian artery gives off a uter-
ine branch that anastomoses in the proximal horn with the
cranial vessels from the uterine artery. The urogenital artery
is a branch off the internal pudendal artery, and it gives rise
to the caudal uterine artery along with vessels to the rectum,
ureter, bladder, urethra, and vagina. The caudal uterine artery
supplies the lateral side of the cranial vagina and continues
past the cervix to ramify on the uterine body, in which it anas-
tomoses with the caudal branch of the uterine artery.4,828,829
Hemorrhage from these vessels, especially the large-diameter
uterine artery, is a significant cause of periparturient colic
signs and death in older multiparous mares.811,826,829-831 How-
ever, a retrospective study of 73 cases suggests that peripar-
turient hemorrhage can occur in mares of any age or parity,
and the condition may occasionally occur before foaling.832 In
a study of 98 postpartum deaths, almost 40% were caused by
uterine artery rupture.826 The rupture may be anywhere along
the vessel and is typically 2 cm or 3 cm in length and oriented
parallel to the long axis of the vessel. Generally, there is no evi-
dence of a predisposing aneurysm.826 An association with low
serum copper levels has been proposed as a reason for vessel
fragility in aged mares.833
There appears to be a predilection for right-sided uterine
vessel rupture. It has been suggested that the extent of cecal
displacement of the gravid uterus to the left may be sufficient
to place increased tension on the vessels in the right broad
ligament.826,830 Although the added stress of dystocia may
increase the chances of arterial rupture, many cases occur in
mares that appeared to have an uneventful delivery. Hemor-
rhage from the hypertrophied vessels that supply the gravid
uterus may be rapidly fatal, especially if the artery ruptures
directly into the peritoneal cavity. The mare may be found
dead or moribund with pale mucous membranes, tachycar-
dia (up to 140 beats/min), and tachypnea. Heroic attempts to
administer blood transfusions, plasma expanders, and associ-
ated fluid therapy may save the life of some valuable mares, but
costs may be prohibitive.204
If the bleeding is contained within the broad ligament, then
the mare may be trembling and will exhibit signs of extreme
pain (anxiety, sweating, and colic), presumably as a result of
the stretching of the broad ligament as the hematoma devel-
ops.204,811,826 The color of the mucous membranes may not
change initially because of vascular compensation, and often
these initial colic signs are mistaken for the typical discom-
fort experienced by postpartum mares as the uterus contracts.
However, if significant hemorrhage is present, the color of the
mucous membranes will eventually become pale, and capillary
refill will be delayed. These mares must be monitored closely
because the hematoma can subsequently rupture out of the
mesometrium and lead to rapid exsanguination.830
If a ruptured artery is suspected, then the mare should not
be disturbed any more than is necessary to perform an exami-
nation. In many cases, postponing, or even forgoing, rectal
palpation may be prudent. Although an internal examination
will reveal valuable diagnostic information, transabdominal
ultrasound, abdominocentesis, and assessment of packed cell
volume may be all that is necessary to confirm that an acute
hemorrhagic episode has occurred. Transabdominal ultraso-
nographic evaluation will reveal free blood in the abdominal
cavity if the hematoma has torn the broad ligament. If the broad
ligament tears after a uterine artery rupture, then a bloody tap
invariably results, with an elevated red blood cell count in the
peritoneal fluid.197 The centrifuged sample will have a pink or
hemolyzed appearance if hemoperitoneum is present. A smear
that reveals phagocytosed erythrocytes indicates hemorrhage
rather than contamination during sampling. Even if a clot has
contained most of the hemorrhage within the broad ligament,
there is often considerable blood loss into the peritoneal cavity.
The initial hemogram during an acute hemorrhagic episode
can be confusing because the relative loss of erythrocytes and
plasma may not alter the hematocrit immediately. Splenic con-
traction will also temporarily increase the hematocrit.
Ideally, mares suspected to have acute hemorrhage should
not be transported because movement could destabilize the
clot and prove fatal. Any supportive therapy should be admin-
istered at the stall until the mare has stabilized. The foal should
be kept safely nearby so that the mare does not become unduly
distressed.
Most recommendations for the management of postpar-
tum hemorrhage in mares are based on the collective wisdom
of experienced clinicians and from methodologies that have
been extrapolated from the human trauma literature. The
approach taken will be governed by the facilities and exper-
tise available and financial constraints. In some instances an
extreme hypotensive state may actually offer the best chance
for survival (conservative approach), whereas in other cases
an attempt to restore intravascular pressures and circulatory
volume could be indicated. The conservative approach is to
confine the hypotensive mare to a dark, quiet stall with mini-
mal disturbances. In some cases a platelet–fibrin plug allows
the rent in the vessel to be sealed once the arterial pressure
 CHAPTER 19
falls. Tranquilizers (especially acetylpromazine) should be
used with caution, because any induced drop in blood pres-
sure may exacerbate the hypovolemic shock. Some clinicians
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use hypotensive resuscitation by administering a vasodilating
agent in conjunction with IV fluid therapy. The idea in this
instance is to provide lifesaving volume replacement while
maintaining a low mean arterial pressure. In life-threatening
situations anything that may stabilize the mare is worthwhile,
but the clinician should consider the possibility of imped-
ing resolution of the hematoma by rapid expansion of blood
volume and elevation of blood pressure. The need to support
cardiac output and ensure oxygen delivery must be balanced
against the prospect of the increased arterial pressure promot-
ing further hemorrhage.
Although costly, an aggressive therapeutic approach can
occasionally save the life of a valuable mare. If the mare pre­
sents in shock and appears to be deteriorating rapidly, then
a large IV catheter should be inserted and substantial fluid
therapy begun. Whole-blood transfusions must be given
slowly and thus are of little benefit for resuscitative purposes
when rapid volume expansion is required. One option is rapid
administration of 2 to 3 L of hypertonic saline followed with
10 to 20 L of LRS over a period of 2 to 4 hours. An alternative
to the hypertonic saline is the high oncotic pressure exerted
by colloids (e.g., 3 L hydroxyethyl starch). Synthetic oxygen-
carrying fluids are commercially available but extremely
expensive. Supplemental oxygen can be provided by nasal
insufflation at a flow rate of 5 to 10 L/min. If the hematocrit
continues to drop to under 15%, then whole-blood transfu-
sions (6–8 L over several hours) may be warranted. Benefits
include provision of oxygen-carrying cells, clotting factors,
and oncotic pressure (albumin).
A shock dose of corticosteroid is indicated. Because hem-
orrhagic shock can cause ischemic-reperfusion damage to the
gut and lungs (multiple organ failure), broad-spectrum anti-
biotics, antioxidant drugs, and antiinflammatory medication
may be warranted if the mare survives the initial hemorrhagic
crisis. Flunixin meglumine (1.1 mg/kg) is administered to
reduce the inflammatory cascades activated by ischemia and
may help to alleviate the mare’s discomfort. Low-dose (10–20
IU) oxytocin therapy is controversial, and some feel it aids
uterine involution, reducing the weight supported by the liga-
ments. Higher doses should be avoided because an induced
colic episode may precipitate a fatal hemorrhage. Antifibri-
nolytic drugs (aminocaproic acid and tranexamic acid) may
assist with clot stabilization. Pentoxifylline increases erythro-
cyte flexibility and may increase oxygen delivery to ischemic
tissues. It should be remembered that there is little refereed
veterinary literature to validate the use of some of these medi-
cations in the horse. For instance, a conjugated estrogen prod-
uct has been proposed on the basis of its ability to shorten
prolonged bleeding times in humans. However, the benefit, if
any, would not be realized until several days after the crisis has
passed. Likewise, anecdotal reports suggest that naloxone (8
mg) may be efficacious, but the concept has been extrapolated
from small animals, and controlled equine studies are lack-
ing. A controversial historical therapy to promote hemosta-
sis in the horse is the use of IV buffered 10% formalin, which
is thought to enhance the activation of the clotting cascade.
However, controlled studies were not able to demonstrate an
effect on coagulation parameters or template bleeding times
in normal horses.203 Broad-spectrum antibiotics should be
administered to prevent infection of the hematoma. Yunnan
Disorders of the Reproductive Tract 13051305
Baiyao, an herbal supplement, has been used by some practi-
tioners to facilitate hemostasis.
If hemorrhage is contained within the wall of the uterus,
then the intramural hematoma may be an incidental finding at
the foal heat examination. However, some mares may exhibit
variable signs of abdominal discomfort, even to the extent of
warranting an exploratory celiotomy.834-836 If an endometrial
laceration severs an artery in the uterine wall, then substantial
hemorrhage may ensue, often with blood escaping from the
vagina. The mare should be confined to a stall and low-dose
oxytocin therapy instituted. Uterine irrigation is contraindi-
cated because it will disrupt clot formation and prolong the
hemorrhagic episode. The internal pudendal artery, one of
the terminal branches of the internal iliac artery, gives rise to the
umbilical artery and the urogenital artery before terminating
in branches to the perineal area and the vestibular bulb. The
small cranial vesicular artery supplies the apex of the bladder
before the remainder of the umbilical artery terminates into
the cordlike round ligament of the bladder. The urogenital
artery gives rise to a caudal uterine branch that runs crani-
ally on the side of the vagina and ramifies with the caudal
branch of the uterine artery on the body of the uterus. The
urogenital artery also supplies branches to the rectum, ure-
ter, caudal bladder, and urethra and continues as the vaginal
artery to the caudal portion of the reproductive tract.4,828,829
A hematoma arising from these vessels may dissect along the
fascial plane within the pelvic cavity and present as a large uni-
lateral vulvar swelling.811 Affected mares typically will experi-
ence violent colic. Abscessation of a retroperitoneal hematoma
can become a life-threatening complication after a dystocia;
thus prophylactic broad-spectrum antibiotic coverage is war-
ranted.826 Mares with an infected retroperitoneal hematoma
often develop signs of toxemia. In these cases the peritoneal
fluid has an increased total protein content (3.0–5.0 g/dL) with
a massive increase in the white blood cell count (often exceed-
ing 100,000 cells/μL).197
Uterine Prolapse (Eversion)
Uterine prolapse, or eversion, is an uncommon complication
of equine parturition that may occur up to several hours (and
occasionally several days) after fetal delivery.837 The condition
may be complicated by bladder eversion (or prolapse), uter-
ine rupture, or intestinal herniation and may be rapidly fatal if
the uterine artery is ruptured.200,800,812,826 If the mare is stand-
ing and personnel are available, then instructions should be
given to place the uterus in a large plastic bag and elevate it
to the level of the vulva. This may prevent further damage to
the endometrium and, more important, will relieve the ten-
sion on the uterine vessels.837 Fluid therapy may be indicated,
and any calcium deficit must be corrected. Epidural anesthesia
may reduce the amount of reflex straining provoked by vagi-
nal manipulations, but it will not eliminate the mare’s strong
abdominal press.801 General anesthesia may be necessary if
the mare exhibits violent discomfort or if straining is exces-
sive. Any uterine lacerations should be closed with absorb-
able sutures. The well-lubricated uterus is then pushed back
through the vagina with a kneading motion. The fingertips
can easily damage the edematous tissue, and manipulating
the uterus through a plastic bag will reduce the likelihood of
a finger rupturing the wall.204 Ultrasonography is useful to
evaluate any suspicious contents. A trapped bladder may be
aspirated through a large-diameter needle, but a loop of bowel
may require a ventral midline celiotomy.
 1306 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
The replaced uterus should be distended with sterile
saline to ensure that the tips of both horns are fully extended.
Repeated low doses (10–20 IU every 2 hours) of oxytocin
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should be administered to promote uterine involution. Failure
to ensure complete extension of the uterine horns into a nor-
mal position within the abdomen may result in discomfort,
straining, and recurrence of the prolapse.204 Vulvar retention
sutures should not be necessary provided that the uterus has
been completely returned to its normal position, the calcium
deficit has been corrected, and low-dose oxytocin therapy has
been administered. Broad-spectrum antibiotics, NSAIDs, and
tetanus prophylaxis are indicated. The mare should be closely
monitored for evidence of internal hemorrhage. Affected
mares may exsanguinate after the uterus has been replaced.
Ischemic damage to trapped bowel is a potential compli­
cation. The clinician should be cognizant of the potential
risks of endometritis-metritis, septicemia, endotoxemia, and
laminitis. Between 2 and 3 days of intrauterine therapy may
be warranted, depending on the condition of the exposed
endometrium.
Partial Inversion (Intussusception) of the
Uterine Horn
Injudicious traction on a retained fetal membrane remnant
may invert the tip of the uterine horn, and this may progress to
complete uterine prolapse.204 If only the horn is affected, then
compromised circulation and pressure on nerve endings may
produce signs of abdominal discomfort; thus the tips of both
uterine horns should be rectally palpated when a postpartum
colic case is evaluated. The affected horn will be shorter than
normal and extremely thickened.800,812 Manual reduction by
pressure from within the uterine lumen may be possible in
some cases, and infusion of several liters of saline solution
will usually ensure extension of the affected horn.800 Oxytocin
(10–20 IU) should then be administered and the fluid drained
from the uterus as it contracts. Resolution of the problem
should be confirmed by rectal palpation.
Uterine Rupture
In any dystocia case there is a risk for iatrogenic tears, and the
uterus should always be checked for any obvious lacerations
immediately after extraction of the fetus. Early recognition
is important because the prognosis is worse once peritoni-
tis develops.197,810,811,826,838 However, obstetric intervention is
not always the cause of uterine tears. Occasionally, the foal’s
hoof may be forced through the dorsal uterine wall during the
mare’s expulsive efforts, and the mare may be found with a
loop of bowel protruding through the vulvar lips. The exposed
bowel should be rinsed with sterile saline and replaced, but a
ventral midline celiotomy may be warranted to fully evaluate
intestinal damage and to repair the uterine laceration. A more
common lesion in unassisted deliveries is a tear toward the
tip of the gravid uterine horn.199,838 Although the fetal hooves
are covered with hard gel-like pads that presumably protect
the placenta and uterine wall, the vigorous piston-like thrusts
of the hindlimbs may occasionally cause a rupture.402,675,839
Affected mares generally experience bouts of colic and
become depressed, febrile, and anorectic as peritonitis devel-
ops. The interval from occurrence of the tear to diagnosis and
initiation of therapy has a marked impact on the prognosis
for survival.197,199,204,811,826,838 It may not be possible to ascer-
tain uterine integrity by vaginal palpation alone. The tips of
the horns may be especially difficult to palpate from within
the postpartum uterus. The changes in the peritoneal cavity
depend on the duration of the condition, but generally one can
expect to see serosanguineous to sanguineous fluid containing
elevated total protein, increased white blood cell counts, and
often extracellular and intracellular bacteria.197,198,838,840
Laparoscopic evaluation of the uterus may confirm the
diagnosis and provide useful information when determining
the need for surgery.841 Complete perforation of the uterine
wall is not necessary for peritonitis to develop if traumatic
obstetric manipulations have damaged the uterine wall.842
However, a fetotomy procedure does not alter the composi-
tion of the postpartum peritoneal fluid if it is performed
correctly.197
If a uterine laceration is suspected (partial or full), then
the mare should receive systemic broad-spectrum antibiotic
coverage along with nonsteroidal antiinflammatory medica-
tions in an effort to prevent development of endotoxemia or
other systemic infections. Oxytocin therapy (10–20 IU every
2 hours) will promote uterine involution. The dose can be
increased if the mare does not become uncomfortable. Fluid
therapy should be administered as necessary, ensuring that
calcium levels are within the normal range. Intensive medi-
cal management may suffice for small dorsal uterine tears, but
most warrant suturing if costs are not a limitation.199,838,840,841
Opinions vary on the need for—and usefulness of—peritoneal
lavage.838,841 Large full-thickness tears warrant surgical inter-
vention. In some instances a laceration in the uterine body can
be sutured blindly in situ, but often a ventral midline celiot-
omy is the preferred approach.204,736,810,840
Retained Fetal Membranes and Toxic Metritis
Once the umbilical cord ruptures, there is a sudden cessation
in blood flow through the capillary network in the placenta.200
This causes a reduction in the tissue volume of the micro-
cotyledons, and the rhythmic tubocervical contraction waves
cause the membrane tips to separate and invaginate into the
horn. The ongoing tubocervical detachment process causes the
membranes to be passed inside out with the allantoic surface
exposed. The membranes should be expelled within 3 hours
after parturition, and the incidence of retention has been
reported to range between 2% and 10% of foalings.727,843,844
Membrane retention tends to be most commonly associated
with the tip of the nongravid horn and appears to be associ-
ated with dysfunction of the initial separation process.432
In circumstances in which tissue inflammation is common
(e.g., abortion, dystocia, cesarean section), it is more likely that
membrane retention will occur. In these cases the endometrial
edema may trap the microcotyledons within the endometrial
crypts. Mares with membrane retention may have a signifi-
cantly lower serum calcium level.845 The number of endo-
metrial mast cells observed during the puerperal period is
significantly lower in the endometrium of mares with retained
fetal membranes.846 It is likely that some dysfunction of the
normal endocrine-related maturational processes within the
microcotyledons is involved. There may be an association
between inbreeding and the high incidence of fetal membrane
retention in Friesian mares.763,847
Appropriate management of a mare with fetal membrane
retention varies depending on the time since foaling.848
Although some mares, especially those foaling in a natural
environment, may not experience any complications, prophy-
lactic medication is recommended under intensive husbandry
 CHAPTER 19
conditions.844,849 Bacterial contamination in this environment
is highly likely. If a severe metritis develops, then inflamma-
tion of the uterine wall permits bacteria and toxins to enter
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the systemic circulation, producing septicemia and endotox-
emia.842,850 Laminitis is a frequent sequela.204
The approach to treating RFMs varies considerably,
depending on the duration of membrane retention and the
presence or absence of metritis with septicemia. In normal,
unassisted foalings, one or two treatments with oxytocin may
be all that is required to facilitate passage of the RFMs. The
protruding placental remnants should be tied in a knot above
the mare’s hocks. An initial low dose (10–20 IU) of oxytocin is
recommended because some postpartum mares are especially
sensitive to this hormone and may experience a severe bout
of colic within minutes of treatment. Higher doses are likely
to be counterproductive because myometrial spasm will occur
instead of the desired rhythmic tubocervical contractions. If
colic does occur, then the mare should be sedated so that she
does not roll and possibly injure the neonate. In these cases
the next dosage of oxytocin should be reduced. Each mare’s
response to the initial treatment governs the subsequent dose
recommendations of 10- to 20-IU incremental increases every
30 minutes to 2 hours.
Distention of the chorioallantoic sac with fluid, known as
the Burns technique,851 promotes membrane expulsion (5–30
minutes) in most postdystocia mares. A major advantage is
that expulsion of the intact fetal membranes will remove any
contaminants that may have been introduced by the obstet-
ric procedures.851 The technique works only if a sterile naso-
gastric tube can be passed beyond the torn distal fragments
and is best performed while the membranes are still fresh.
In more protracted cases the rapidly autolyzing chorioallan-
tois becomes friable and generally tears once the fluid pres-
sure increases. When the procedure is performed the exposed
fetal membranes are held tightly around the tube while 12 to
15 L of solution are infused. The opening is then tied off with
umbilical tape. The exact mechanism is unknown, but expan-
sion of the uterine lumen may dilate the endometrial crypts
such that the weight of the membranes can atraumatically pull
the microcotyledons free. Endogenous oxytocin release can be
supplemented to enhance uterine contractions.
Because the uterine response to oxytocin wanes during the
postpartum period, the dose may be increased in small incre-
ments every 2 hours in mares that retain their fetal membranes
despite the initial therapy. If a hospitalized mare is receiving
IV fluids, then each oxytocin treatment can be added to the
fluid line. Another option is to add oxytocin to the fluid bag
at a dose that is calculated on the basis of the flow rate (1 IU/
min).204 However, a disadvantage of this approach is that these
fluids must be discarded if the mare becomes uncomfortable
yet still requires rehydration. The calcium ion plays a vital role
in myometrial contractility, and it is important to ensure that
calcium levels are within the normal range.768,852 Supplemen-
tal calcium can markedly expedite the rate of passage, which
suggests that uterine hypomotility is a component in some of
these cases.844 Controlled exercise is often beneficial in pro-
moting uterine involution but is not always feasible if the mare
is hospitalized or is being kept in a stall while a compromised
neonate is being medicated.
It is widely accepted that excessive traction on the fetal
membranes is contraindicated, but a recent study suggests that
cautious manual removal of the membranes may not be as del-
eterious as previously thought.853 When the membranes are
Disorders of the Reproductive Tract 13071307
extracted by force there is inevitably disruption of the epithelial
barrier, making the traumatized uterine lining more suscep-
tible to bacterial invasion and the development of metritis.850
Endometrial trauma is also likely to contribute to the devel-
opment of periglandular fibrosis. It is not uncommon for the
membrane tip to tear off and remain firmly attached within
the nongravid horn.432 Injudicious traction on the membranes
can also cause an inversion of the tip of the uterine horn, and
this can progress to a complete uterine prolapse.
If the fetal membranes have not been expelled after 2 days
of supportive therapy, then the autolytic tissue becomes less
firmly embedded. A gentle twisting technique, with minimal
traction, applied within the attached horn will often result in
successful removal of the entire chorioallantois. This proce-
dure works best while the uterus is being distended during a
uterine lavage. A potentially effective treatment for RFMs in
mares may be intraplacental injections of collagenase.854,855
If the membranes have been retained for 6 to 8 hours when
the mare is first examined, then systemic antibiotic therapy is
indicated.204 Drugs that have been recommended for systemic
administration include ampicillin, gentamicin, kanamycin,
penicillin, ticarcillin, and trimethoprim-sulfamethoxazole. If
a remnant is missing when the membranes are examined, then
the approach to therapy should proceed as if the entire mem-
brane were still present. Characteristic signs of toxic metri-
tis are fever, depression, anorexia, tachycardia, and injected
mucous membranes. The foal will not be receiving adequate
milk intake, and many of these mares will have bounding digi-
tal pulses and evidence of laminitis.
Transrectal palpation will reveal a large, thin-walled, atonic
uterus that contains moderate to large amounts of fetid fluid.
A large volume of toxic, red-brown, watery fluid can accumu-
late within the pendulous postpartum uterus before any obvi-
ous vaginal discharge becomes evident. Often the history will
reveal that the fetal membranes were discarded without being
checked to ensure that they were passed intact.
Because the endometrium is likely to be necrotic, therapy
should include broad-spectrum antibiotics, antiinflamma-
tory drugs, and IV fluids if indicated. Tetanus prophylaxis
is advisable. A combination of penicillin and gentamicin is
widely used to provide broad-spectrum systemic coverage,
especially against the coliforms that frequently contribute to
endotoxemia and laminitis.856 Flunixin meglumine should
be administered to ameliorate the effects of endotoxemia. It
is commonly administered IV at a reduced dose (0.25 mg/kg,
t.i.d.).204 Phenylbutazone (2–4 mg/kg) and provision of deep,
soft bedding and padded shoe support are useful to alleviate
pain when laminitis appears to be imminent. Radiographs
can be useful to monitor changes in the position of the pedal
bone. Vasodilators such as acetylpromazine maleate may be
administered by IM injection (0.02–0.04 mg/kg every 4–6
hours).856 Further discussion of the diagnosis and treatment
of endotoxemia and laminitis are found in Chapters 10 and 12,
respectively.
The uterus should be lavaged with sterile saline or very
dilute (“weak tea”) povidone-iodine solution. If povidone-
iodine is used, then the final concentration should not exceed
0.1%; this is equivalent to 10 mL of 10% povidone-iodine
solution (e.g., Betadine) in 1 L of saline. If costs are a con-
cern, then 90 mL in a 9-L bucket of clean water may suffice.
Extreme caution should be exercised to keep from puncturing
the inflamed uterine wall with the tube. The lavage should be
repeated until the returning fluid is relatively clear. The goal of
 1308 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
therapy is to eliminate toxins and to prevent the rapid prolifer-
ation of bacteria, especially coliforms and possibly anaerobes.
The administration of intrauterine antibiotics in the postpar-
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tum mare is controversial because little scientific validation
has been performed. Intrauterine administration of antibiot-
ics and antiseptics may depress the phagocytic activity of uter-
ine neutrophils, and many chemicals are known to irritate the
endometrium in mares being infused for endometritis.
The pharmacokinetic properties of each drug will influ-
ence its efficacy in the postpartum uterus. Most of the studies
of intrauterine therapy in mares have addressed therapy for
endometritis in nonparturient animals. The efficacy of anti-
biotic formulations in the presence of the mixed bacterial
population and tissue debris associated with fetal membrane
retention in the mare remains to be established. The antibiotic
of choice should be added to a large infusion volume (2–3 L) to
ensure uniform distribution across the inflamed endometrial
surface once a lavage has removed the toxic fluid and necrotic
debris. Infusion of 2 g of amikacin after a uterine lavage is
often clinically effective. Polymyxin B may have some merit
because of its endotoxin-binding ability. Powdered and pro-
pylene glycol–based oxytetracycline formulations are known
to be irritating when infused into the involuted uterus and
should be avoided.6,857 Other antibiotics that have been sug-
gested for postpartum intrauterine therapy include ampicillin
(3 g), ticarcillin and clavulanic acid (1–3 g), and gentamicin
(2–3 g). Fewer than 60% of isolates from metritis fluid appear
to be sensitive to ampicillin. The authors do not support intra-
uterine antimicrobial therapy in the postpartum mare.
Recently a technique has been described that is believed to
cause immediate placental release. This technique consists of
cannulating the umbilical cord vessels and using an adaptor to
connect the catheter to a garden hose. Water is pumped into
the mare uterus until the chorioallantois is detached from the
endometrium.858 A success rate of 93% for immediate release
of the placenta is reported.
Gastrointestinal Complications
Prolonged straining during dystocia can lead to variable
amounts of rectal mucosa being forced out through the anal
sphincter (type I rectal prolapse). The tissue then becomes
subject to trauma, contamination, and vascular compromise.
If not promptly corrected, then pressure from the anal sphinc-
ter will cause venous congestion and swelling. This promotes
more straining, and the condition can deteriorate rapidly. A
type II prolapse involves all or part of the ampulla recti. An
epidural anesthetic may help decrease straining. Topical glyc-
erin or dextrose may be applied to the prolapsed tissue to
reduce edema.204 A purse-string suture can cause additional
straining and will impede defecation.859 Fecal softeners should
be administered and the diet modified (e.g., pellets, pasture) to
help produce soft feces.569
Chronic prolapses may warrant surgical resection of the
devitalized mucosal mass. In a type III prolapse, there is a
full-thickness rectal prolapse and an intussusception of the
peritoneal rectum or small colon. In a type IV prolapse the
intussuscepted bowel protrudes through the anus such that
there is a palpable trench that may extend several meters
into the rectum, depending on the length of the intussus-
ception.859-861 Midventral celiotomy is usually necessary to
reduce the intussusception, although some smaller prolapses
will reduce after an attendant has extracted the foal. The short
mesentery that supports this section of bowel is often torn
from the colon. These cases have a guarded prognosis, depen-
dent on the vascular integrity of the affected small colon. This
condition can develop when as little as 6 to 10 inches of bowel
appear to be prolapsed. The avulsion most likely occurs when
the mare’s intermittent straining forces an extra 4 to 6 inches
of bowel in and out of the rectum. Thus it is imperative to pre-
vent straining as soon as possible. If the foal has not yet been
extracted, it may be best to immediately anesthetize the mare
and then elevate the hindquarters before attempting to correct
the cause of the dystocia.
In rectal prolapse cases that have been managed conser-
vatively, one of the first postpartum clinical signs may be
discomfort attributable to impaction colic. If avulsion of
the mesocolon has occurred, then ischemic necrosis of the
affected bowel will cause a delayed peritonitis. Because early
intervention is essential, sequential abdominocentesis is indi-
cated when a type III or IV rectal prolapse is being conser-
vatively managed. Initially, there may be negligible changes
in the composition of the peritoneal fluid. However, if an
avulsion has occurred, the compromised segment of bowel
will soon lose its integrity, and a massively increased white
blood cell count can occur within 24 to 48 hours as peritonitis
ensues.197 Laparoscopic evaluation of the abdomen can pro-
vide an immediate assessment of bowel integrity and permit
an accurate prognosis to be given to the owner. The affected
colon is not readily accessible for resection and anastomosis,
so the prognosis in most cases is guarded.
Variable degrees of uncomplicated impaction are not
uncommon in the postparturient mare, possibly as a result
of localized perineal pain causing reluctance to defecate.204
Astute managers will note an absence of fecal matter in the
stall. Treatment with fecal softeners (e.g., mineral oil) and
analgesics generally corrects the problem. Laxative feeds (e.g.,
bran mash) are effective in reducing the incidence of con-
stipation in foaling mares.800 Postpartum mares appear to
be at an increased risk for development of a large colon tor-
sion.570,826,862 This condition presents as an especially violent
colic with readily discernible abdominal distention. Exten-
sive ischemic damage affects the prognosis, but early surgical
intervention can increase the survival rate.863 Bruising of the
abdominal viscera can occur during foaling, with subsequent
development of moderate to severe signs of impaction colic
and peritonitis. Occasionally, the mesentery may be torn from
a segment of intestine, leading to ischemic necrosis and perito-
nitis. An early diagnosis and prompt surgical intervention may
save the mare’s life.197,737,825-827,864 A rent in the mesentery or
broad ligament at the time of foaling may permit a segment of
bowel to become incarcerated even weeks later.568,820,826,827,865
Owners should be advised that surgical correction is feasible
only if the segment of devitalized bowel is accessible.
Although mares tend to reduce their feed intake in the days
leading up to foaling, ensuring a reduction in the amount of
available roughage may help reduce the incidence of bowel
rupture.800 The tip of the cecum is the most likely site of a foal-
ing-related rupture in the alimentary tract. On rectal palpa-
tion the inflamed serosal surfaces will feel roughened, with a
discernible crepitus. Abdominocentesis will reveal dark green-
brown gastrointestinal fluid that contains plant material and
massively increased neutrophil numbers. Humane euthanasia
is indicated because the leaking ingesta incites a severe peri-
tonitis with accompanying septic shock, and the condition is
likely to be rapidly fatal.826,866-869 Diaphragmatic herniation
has been reported as a rare parturient complication in heavily
 CHAPTER 19
pregnant mares.735,870-872 Colic symptoms are attributable to
strangulating obstruction or tension on the mesentery. Some
mares may exhibit respiratory distress. Transthoracic ultraso-
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nography can help confirm the presence of bowel within the
thorax.873 Surgical repair of the defect may not be possible,
and assisted ventilation will be required.871,872
Vaginal Lacerations and Bladder Prolapse
Primiparous mares are especially susceptible to vaginal
trauma. Vaginal lacerations are most likely to occur during
injudicious attempts to relieve dystocia. Although most lac-
erations are retroperitoneal, they still may contribute to severe
vaginitis, fibrosis, and possibly abscessation. If ventral trauma
is present, then a urinary catheter should be passed to check
for urethral integrity. In some instances ligation of a severed
artery will be necessary. Emollient creams, tetanus prophy-
laxis, broad-spectrum antibiotics, and antiinflammatory drugs
are indicated. A major concern is the possibility of herniation
of intestine into the vagina if the tear is located just caudal
to the cervix in the vicinity of the urogenital pouch.826,874 If
eventration has occurred, the bowel should be cleansed and
examined for evidence of vascular compromise. If the involved
intestine appears to be grossly normal, it should be rinsed with
sterile saline and returned to the abdominal cavity. If vascular
compromise is detected at the time of the initial examination,
then the prognosis is guarded and a ventral midline celiotomy
to facilitate resection is warranted. A bladder prolapse occurs
when the bladder is forced up through a vaginal laceration. The
viscus rapidly becomes distended as a result of the continued
accumulation of urine from the ureters and an inability to void
urine because of kinking of the urethra. The edematous serosal
surface of the bladder may protrude through the vulvar lips.
The exposed organ should be thoroughly cleansed and gen-
tly returned to the abdominal cavity. It may be necessary to
administer an epidural and aspirate urine to facilitate replace-
ment. If possible, the vaginal laceration should be sutured once
any viscera have been returned to the abdominal cavity. In
some cases the severity of the trauma precludes successful clo-
sure, and the wound must heal by second intention.874 Place-
ment of a Caslick suture reduces the possibility of bacterial
aspiration. Mares may be cross-tied for several days to decrease
the risk of eventration brought about by elevation of intraab-
dominal pressure as the mare lies down.204 The mare should be
treated for impending peritonitis (e.g., broad-spectrum antibi-
otics, NSAIDs). Tetanus prophylaxis is indicated. If severe colic
symptoms develop, bowel compromise should be suspected.
Eversion of the Urinary Bladder
The mare’s urethra has a large diameter, and occasionally the
bladder may be everted up into the vagina after severe strain-
ing.875 If the everted bladder protrudes through the vulvar
lips, then the exposed mucosal surface will rapidly become
edematous, and urine may be seen to drip from the ventral
surface. Closer inspection will reveal that the urine is drib-
bling from the exposed papilliform openings of the ureters
on the dorsal surface of the neck of the bladder.876 A lip
chain and epidural may provide adequate restraint to facili-
tate replacement. The mucosal surface should be thoroughly
cleansed and any defects repaired. Sterile lubricant should be
applied and the friable organ gently massaged back through
the urethra. In some instances it may be necessary to incise
the urethral sphincter if the bladder mucosa is especially
thickened.876 This incision should be closed once the bladder
Disorders of the Reproductive Tract 13091309
has been replaced. A Foley catheter can be inserted to lavage
the bladder lumen and ensure complete repositioning. Broad-
spectrum antibiotic coverage, NSAIDs, and tetanus prophy-
laxis are indicated.
Rupture of the Urinary Bladder
Occasionally, the bladder may rupture as a consequence of
increased intraabdominal pressure in the foaling mare or
because of direct trauma during parturition.877-879 Clinical
signs are delayed and are associated with electrolyte imbal-
ances. Affected mares may be depressed and inappetent,
with failure to void urine. Clinical examination will reveal
tachycardia, tachypnea, and decreased gastrointestinal activ-
ity. Blood chemistry will reveal elevated serum levels of cre-
atinine, blood urea nitrogen, and potassium in addition to
decreased sodium and chloride levels. Evaluation of a perito-
neal fluid sample helps confirm the diagnosis. The fluid will
contain elevated urea and creatinine levels and calcium car-
bonate crystals. Cystoscopy is useful to evaluate the size and
extent of the bladder injury. Once the mare’s medical condi-
tion has been stabilized, surgical repair is indicated.820,877-879
A standing vaginal approach eliminates the need for general
anesthesia and allows excellent observation and repair of blad-
der tears in adult mares.879
Rectovaginal Fistulas and Perineal Lacerations
A first-degree perineal laceration involves the mucous mem-
brane of the vestibule and the skin of the vulvar lips. In second-
degree perineal lacerations, the deeper tissues of the perineal
body are involved. Both of these conditions may be associated
with unassisted delivery of a large foal or may be a sequela of
dystocia. The laceration may be amenable to immediate repair
and placement of a Caslick suture, or the clinician may elect
to wait until the wound has granulated. The mare should be
treated with broad-spectrum antibiotics, antiinflammatory
medication, and tetanus prophylaxis. Provision of a bran mash
diet and administration of mineral oil or stool softeners may
facilitate defecation during the initial inflammatory period.
Third-degree perineal lacerations generally occur during
unassisted foalings when the fetal hoof catches on the vaginal
roof at the vestibulovaginal junction. Forceful straining by the
mare can drive the hoof through the rectovaginal shelf such
that the fetal hoof comes to lie within the rectum. If the fetus
is viable, it may remove the affected limb and delivery will
proceed unimpeded, but a rectovaginal fistula results. If the
limb remains within the rectum, then continued passage of the
fetus causes the trapped limb to tear out the perineal body and
anal sphincter. The resulting defect is called a third-degree peri-
neal laceration. These injuries do not respond well to imme-
diate surgical intervention, and the general recommendation
is to wait 4 to 6 weeks before attempting reconstructive sur-
gery.820,875,880 In the interim the mare should be treated with
broad-spectrum antibiotics, antiinflammatory medication,
tetanus prophylaxis, and fecal softeners.
Grade IV (full-thickness) rectal tears that communicate
directly with the peritoneal cavity have a poor prognosis and
can occur as a result of parturition.881,882 Tears tend to occur
just cranial to the caudal peritoneal reflection. Such cases
warrant immediate intervention, and the rectum should be
packed to prevent abdominal contamination during trans-
port to a referral hospital. A standing technique that permits
an easy and effective stapled primary closure repair has been
described.881
 1310 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
Perineal Bruising and Vulvar Hematomas
Much of the swelling after prolonged obstetric manipulations
is edematous. Fecal softeners such as oral mineral oil and bran
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mash are recommended to ease the passage of feces through
the swollen and bruised perineal area.735,806 Hematomas in the
vaginal wall and vulvar lips are not uncommon, especially in
primiparous mares and mares that have delivered an extremely
large foal. It is important to differentiate a bulging vestibular
hematoma from an everted or prolapsed bladder.800,829 Needle
aspiration of vulvar hematomas is not recommended because
of the risk of abscessation. Broad-spectrum antibiotics and tet-
anus prophylaxis are indicated. Most hematomas will resolve
uneventfully, but some vulvar, vaginal, or pelvic hematomas
may warrant drainage in 7 to 10 days.735
Postpartum Eclampsia (Lactation Tetany)
Postpartum eclampsia, or lactation tetany, is extremely rare in
mares but may occur in animals that are lactating heavily. The
highest incidence is reported in draft breeds, but the author
has encountered a case in a pony mare. Equine eclampsia is
generally associated with some type of stress (e.g., change in
surroundings). Early signs include restlessness, tachypnea,
staring eyes, twitching, trembling, and clonic spasms (espe-
cially diaphragmatic). The clonic spasms gradually become
more tonic, and eventually the mare may be unable to stand.
The differential diagnosis is tetanus, but the nictitating mem-
brane is not prolapsed. The condition responds well to intrave-
nous calcium gluconate administration.200
Assisted Reproductive Techniques for
the Mare
E.A. Bradecamp
The development of new assisted reproductive techniques for the
mare has allowed production of offspring from mares that are
infertile using standard breeding techniques or embryo transfer.
Y INTRACYTOPLASMIC SPERM
INJECTION
Currently, intracytoplasmic sperm injection (ICSI) has
become the most common assisted reproductive technique
used to obtain pregnancies from mares that have failed to pro-
duce pregnancies themselves or via embryo transfer. ICSI is
also used to obtain pregnancies from stallions that have very
poor fertility or from which there is a limited amount of semen
available. During ICSI a single sperm is selected, aspirated
into a fine-bore needle, and injected into a mature oocyte. The
injected oocyte can be transferred into a recipient’s oviduct or
cultured to allow embryo development883 and then transferred
into a recipient once it reaches blastocyst stage. Cochran et al.
reported the first successful ICSI of an equine oocyte that was
matured in vitro. Foals have been produced by ICSI using
oocytes matured in vivo or in vitro.884,885
Currently, there are several commercial ICSI labs to which
mares can be shipped for management for oocyte aspiration
and ICSI, or oocytes can be collected at a remote location and
shipped for ICSI. Subsequently, the fertilized oocytes are cul-
tured until the blastocyst stage is reached. The embryos can
then be transferred into on-site recipients, if available, or
shipped to an off-site recipient herd.
Oocytes can be collected from preovulatory dominant or
nondominant follicles. Oocytes from preovulatory follicles
are collected between 24 and 36 hours after the administra-
tion of hCG (1500–2500 IU, IV) or deslorelin (1.5 mg, IM) to
the donor, with the oocytes collected between 18 and 20 hours
before anticipated ovulation. Therefore oocytes are probably at
metaphase I or II. Criteria for hCG administration are as fol-
lows: (1) a follicle greater than 35 mm in diameter, (2) relaxed
cervical and uterine tone, and (3) uterine edema or estrous
behavior for a minimum of 2 days. Some mares, especially old
mares, do not consistently respond to hCG. In these cases the
authors use a combination of deslorelin acetate (1.5 mg, IM)
and hCG (2000 IU, IV), with hCG administered between 4 and
5 hours after deslorelin. Oocytes have been collected from the
follicles of mares by laparotomy,886 colpotomy,887 flank punc-
ture,888,889 and ultrasound-guided follicular aspiration.890,891
Currently, most laboratories collect oocytes through the flank
or with transvaginal ultrasound-guided punctures.
For the collection of oocytes using flank puncture, the tro-
car is placed through the flank ipsilateral to the preovulatory
follicle at approximately the position of the ovary. The ovary is
manipulated per rectum to position the preovulatory follicle
against the end of the cannula. While stabilizing the ovary per
rectum, the clinician places a needle (12–17 gauge) through
the cannula and into the follicular antrum and removes the
follicular fluid and oocyte by gentle suction and lavage of the
follicle. Transvaginal ultrasound-guided follicular aspiration
requires use of an ultrasound machine and a probe fitted to a
special needle case. Linear, curvilinear, and sector transducers
have been used. The transducer is placed in a casing contain-
ing a needle guide. Rectal contractions may be minimized by
administration of propantheline bromide (0.04 mg/kg, IV)892
or N-butylscopolamine or intrarectal use of lidocaine before
the procedure. The clinician applies a nontoxic lubricant to the
transducer and positions it against the anterior vaginal wall,
lateral and dorsal to the external cervical os and ipsilateral to
the follicle to be aspirated. The follicle must be carefully posi-
tioned through transrectal manipulations with the follicular
apex juxtaposed to the needle guide. The needle is advanced
through the needle guide to puncture the vaginal and follicu-
lar walls. In the authors’ laboratory, a 12-gauge double-lumen
needle is used. The follicular fluid is aspirated from the follicle
using a pump set at approximately 150 mm Hg or with suc-
tion from a large syringe. After removing the follicular fluid,
the clinician lavages the lumen with between 50 and 100 mL
of flushing liquid. Typically, modified Dulbecco’s phosphate-
buffered solution or a sterile commercial embryo flush solu-
tion is used. Heparin (10 IU/mL) is added to the flush solution
to prevent coagulation of blood in the aspirate. By use of this
technique, oocytes were typically collected successfully from
between 70% and 80% of the follicles in client donors.892
The major clinical advantage of ICSI is that limited sperm
numbers or poor-quality sperm can be used to produce off-
spring, and pregnancies can be obtained from infertile mares
that failed to produce embryos and pregnancies through
embryo transfer.
Y OOCYTE TRANSFER
Although the first successful oocyte transfer was performed
in 1988, the technique was not used for commercial transfers
 CHAPTER 19
until the late 1990s.892-894 Oocyte transfer involves the trans-
fer of an oocyte from a donor into the oviduct of a recipient,
and the recipient is inseminated within the uterus. Fertilization,
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embryo development, and fetal development occur within the
recipient, preventing problems associated with ovulation or the
tubular genitalia of donors. The incidence of ovulatory failure
increases with age and during the autumn months.704,895 Pro-
longed exposure to an abnormal follicular environment results
in aging and death of the oocyte. Some types of ovulatory fail-
ures can be detected with ultrasound as an atypical morphology
of the follicle or ovulatory site. Mares that repeatedly fail to ovu-
late can provide oocytes for transfer successfully if oocytes are
collected before deleterious changes occur within the follicle.892
Historically, the uterus has been considered the primary
cause of reduced fertility in the mare. Mares with pyometra or
persistent endometritis are expensive to treat and frequently
do not provide embryos. Mares with cervical lacerations,
cervical or uterine adhesions, or urine pooling often fail as
embryo donors. Oviduct dysfunction is a rare impediment to
fertility and can occur in young or aged mares. When the ovi-
ducts of old mares (>20 years) and young mares (2–9 years)
were flushed between 1 and 4 days after ovulation, collection
rates of recently ovulated oocytes or oviductal embryos were
significantly higher in the young mares than in the old ones
(26 of 27 [96%] vs. 17 of 29 [59%], respectively).547 In sub-
fertile mares pathologic changes of the oviducts were imaged
using scanning electron microscopy, and significantly fewer
sperm were detected in the caudal isthmus in subfertile mares
than in fertile mares. Few sperm found in the oviducts of
subfertile mares were motile, whereas oviducts of the normal
mares contained highly motile sperm.896 Obstructions of the
oviductal lumen are postulated to be the cause of subfertility
in some mares. Globular masses composed of type I collagen
were found more frequently in older than in younger mares.206
Oviductal masses were found in the oviducts in 73% (16 of 22)
of mares between 2 and 22 years of age; in a small number of
mares (3 of 43), the masses occupied and distended the ovi-
ductal lumen and could have resulted in infertility. The equine
embryo remains in the oviduct for 5 or 6 days before entering
the uterus; therefore oviductal problems such as inflammation
could affect embryo viability.897
Oocyte Donors
Requirements for oocyte donors are minimal. Uterine infec-
tions in donor mares should be treated to prevent introduction
of a pathogen into the abdominal cavity during transvaginal
oocyte collections. Donors should have regular estrous cycles
with growth of a preovulatory follicle. The age of the donor
affects success rates. When oocytes were collected from the
follicles of young donors (6–10 years) and old donors (20–26
years) and transferred into the oviducts of young recipients
(3–7 years), significantly more oocytes from young than old
donors developed into embryonic vesicles (11 of 12 [92%] vs.
8 of 26 [31%], respectively).552 A higher incidence of morpho-
logic anomalies was observed in oocytes from older than from
younger mares.551 Although younger mares are better candi-
dates for oocyte donors, older (≥20 years) mares frequently are
presented to commercial oocyte transfer programs, and preg-
nancies are obtainable through repeated transfers.884
Oocyte Culture and Transfer
Oocytes are sensitive to temperature changes; therefore the
clinician should warm media and equipment for handling
Disorders of the Reproductive Tract 13111311
the oocyte to 38.5°C. On collection the flushing solution is
poured into large search dishes and examined under a dis-
secting microscope to locate the oocyte. One can transfer
oocytes collected at least 30 hours after hCG administration
to the donor immediately into a recipient’s oviduct. Oocytes
are usually collected 24 hours after administration to the
donor and between 12 and 16 hours before transfer. Most
oocytes are cultured in medium similar to that first described
by Carnevale and Ginther.552 The timing of oocyte collection
(24 vs. 36 hours after administration of hCG to donors) did
not affect pregnancy rates.898 A modification of these pro-
cedures was to collect oocytes 24 hours after hCG admin-
istration and immediately transfer them into the recipient’s
oviduct. Oocyte maturation was completed within the ovi-
duct, and recipients were inseminated after oocyte matura-
tion should have been completed (at 16 hours after transfer).
Pregnancy rates were not statistically different for oocytes
matured within the oviduct or within an incubator (43% vs.
57%).899
Because the reproductive tract of the recipient provides the
environment for sperm transport, fertilization, and embryo
development, recipient mares should be young (optimally
4–10 years) and have normal reproductive tracts. Cyclic and
noncyclic hormone-treated mares have been used as oocyte
recipients. When cyclic mares are used, recipients are syn-
chronized with the donor, and the recipient’s own oocyte is
removed by transvaginal or flank aspiration before transfer of
the donor’s oocytes.900 Anestrous and early transitional mares
are used as recipients during the nonovulatory season.892,901
During the breeding season a high dose of a GnRH agonist
(4.2 mg deslorelin acetate)902 or injections of progesterone
and estrogen (150 mg progesterone and 10 mg estradiol)894
have been administered to reduce follicular development in
potential recipients. The endocrine environment of the cyclic
mare is imitated in the noncyclic recipient with administra-
tion of estradiol (1.5–5 mg daily for 3–7 days) before transfer.
Estradiol often is given to obtain a recipient with a relaxed,
open cervix and moderate endometrial edema. Progesterone
(150–200 mg daily) or a progestin is administered after trans-
fer. Pregnancies are maintained through the administration of
exogenous progesterone or progestins.892
Because oocytes are transferred surgically, adequate expo-
sure of the oviduct is essential, and mares with short, thick
flanks or short, broad ligaments are not good candidates for
recipients. Most oocyte transfers are performed through a
standing flank laparotomy. Tranquilization, preparation,
closure, and aftercare of recipients are similar to previously
described methods for embryo transfer.903 The authors gener-
ally use a fire-polished glass pipette to transfer oocytes. The
oviductal os is located by following the outline of the oviduct
along the external surface of the infundibulum. The end of the
structure is identified and the pipette containing the oocyte
is inserted into the os, and the pipette is carefully advanced 2
to 3 cm. The oocyte and a minimal amount of medium (<0.1
mL) are deposited into the ampullary region of the oviduct,
the ovary is gently returned to the abdominal cavity, and the
surgical site is closed.
Insemination of Recipients
In a commercial oocyte transfer program, use of stallions with
good fertility is essential for success, but cooled, transported
semen frequently is provided from stallions of variable fertil-
ity.892,904 The equine oocyte remains viable for approximately
 1312 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
12 hours after a natural ovulation.4 Because of this limited life
span, recipients must be inseminated before or directly after
oocyte transfer or both. Pregnancies have occurred when
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recipients were inseminated only before905,906 or after899 the
transfer of oocytes. However, for most experimental transfers,
recipients were inseminated before transfer (approximately 12
hours) and after transfer (approximately 2 hours), with a total
of 2 × 109 motile sperm. In a commercial program using older
donors and cooled semen from numerous stallions of variable
fertility, pregnancy rates when recipients were inseminated
before or before and after oocyte transfer were significantly
higher than when recipients were inseminated only after trans-
fer (18 of 45 [40%], 27 of 53 [51%], and 0 of 10 [0%], respec-
tively).904 The results suggest that insemination of a recipient
once before transfer with at least 1 × 109 progressively motile
sperm from a fertile stallion is sufficient. However, if fertility
of the stallion is not optimal, then insemination of the recipi-
ent before and after transfer could be beneficial.
After insemination and transfer, the uterus of the recipi-
ent should be examined with ultrasound to detect intrauterine
fluid collections. Recipients with intrauterine fluid collections
are treated like an ovulating mare, with oxytocin or PGs to
stimulate uterine contractions or with uterine lavage and anti-
microbial infusion.
Success of Oocyte Transfer
Pregnancy rates for commercial transfers using older donors
and semen of variable quality ranged between 27% and 40%
per transfer.892,904 In contrast, experimental transfers under
similar conditions using oocytes from young mares and fertile
stallions resulted in pregnancy rates between 54% and 83% per
transfer.27 However, one or more pregnancies were obtained
for more than 80% of donors during the breeding season in
a commercial oocyte transfer program.892 All mares in the
program had histories of reproductive failure in breeding and
embryo transfer programs, with a mean of 7 years (range of
3–15 years) from the last successful pregnancy or embryo
collection.892
In Vitro Maturation and Fertilization of Oocytes
In vitro fertilization is not as repeatedly successful in the mare
as it is in many other species, with only two foals born after
in vitro fertilization.907,908 One problem in trying to study
procedures such as in vitro fertilization in the horse is the
paucity of equine oocytes. Oocytes often are collected from
the preovulatory follicles of live mares. Collection of oocytes
from small follicles during diestrus results in reduced collec-
tion rates compared with collection of oocytes from preovula-
tory follicles.909 In one study,908 oocytes were collected from
small follicles and preovulatory follicles. Oocytes collected
from small follicles were matured in vitro for 36 to 38 hours
before transfer, whereas oocytes collected from preovulatory
follicles were transferred immediately into a recipient’s ovi-
duct. Embryo development rates after transfers were 9% for
in vitro maturation and 82% for in vivo. In contrast, some lab-
oratories have been very successful in developing methods to
collect and mature oocytes from small follicles. Colleoni et al.
reported an oocyte recovery rate of 58%, or 11 oocytes per
ovum pick-up session.910 At this time, in vitro embryo produc-
tion is best achieved with oocyte aspiration, followed by ICSI
to achieve fertilization, then embryo maturation in vitro, and
transfer at the blastocyst stage into a recipient.
Research involving oocytes from excised ovaries is aimed
at developing a method for salvaging gametes from the ovaries
of valuable mares that have died or been euthanized. One can
collect ovaries from mares immediately after death and ship
them to a facility for oocyte recovery, maturation, and trans-
fer. This technique was first attempted in 1999,892 and a preg-
nancy was established that later underwent embryonic death.
However, more recent attempts have resulted in pregnancies
and healthy foals after shipment of ovaries from mares that
were euthanized for various medical reasons.911,912 Currently
obtaining a late-term pregnancy or pregnancies from about
one of four sets of ovaries that are shipped to a laboratory for
oocyte recovery is anticipated.
Cryopreservation of Oocytes and Embryos
Cryopreservation of the equine oocyte results in the preser-
vation of female genetics, whereas cryopreservation of the
embryo results in the preservation of the female and male
genome. The first foal was produced from a cryopreserved
embryo in 1982.913 Procedures for embryo cryopreservation
have been reviewed.914 Cryopreservation of small embryos
(morulae or early blastocysts <300 μm) has consistently
resulted in acceptable pregnancy rates close to 50%.915,916
Cryopreservation of larger embryos (≥300 μm) is usually
unsuccessful. Embryo collection is recommended on day 6
or 6.5 after ovulation.914 Embryo donors are examined twice
daily for ovulation, or embryo collections are timed from
administration of an ovulation-inducing agent.917 In recent
years vitrification procedures have been used to successfully
cryopreserve small equine embryos.917-919 The advantage of
vitrification over traditional slow-cooling methods include
cryopreservation, which is a rapid procedure (<15 minutes)
that requires minimal equipment and results in better preg-
nancy rates post thaw. Recently a technique that involves
aspiration of fluid from the blastocele cavity before vitrifica-
tion in larger embryos has been reported to have reasonable
success rates.920
Although cryopreservation of the oocyte is difficult, suc-
cessful fertilization of cryopreserved oocytes has been
described.921, 922 In 2001, the first foals were born after cryo-
preservation of oocytes.906 Clinical use of oocyte cryopreser-
vation has not been reported and is currently not used in a
clinical setting.
Y ASSISTED REPRODUCTIVE
TECHNIQUES FOR THE STALLION
Maximum fertility was obtained when fertile mares were
inseminated every other day during estrus with 500 × 106
progressively motile sperm.923 Insemination of low numbers
of sperm would be beneficial for frozen semen that is of lim-
ited supply, semen from subfertile stallions with low sperm
numbers, and insemination of sex-sorted sperm. The follow-
ing discussion summarizes techniques for low-dose or assisted
inseminations. A more complete discussion on stallion semen
processing will be found in a later section.
Deep Intrauterine Insemination
Uterine contractions move sperm into the tips of the uterine
horns within 20 minutes of routine AI.924 The aim of deep uter-
ine insemination (also known as “deep-horn insemination”)
 CHAPTER 19
is to increase the number of sperm entering the oviduct ipsi-
lateral to ovulation.925-927 A flexible insemination pipette is
passed through the cervix and into the uterine horn ipsilat-
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eral to the preovulatory follicle. Then rectal manipulation is
used to advance and position the catheter at the tip of the
uterine horn in which the sperm are then deposited. Fresh,
cooled, and sex-sorted sperm in volumes ranging from 0.2
to 1.0 mL of commercial semen extender have been used for
deep intrauterine inseminations. Pregnancy rates after deep
intrauterine inseminations with 5 × 106 progressively motile
sperm were between 30% and 50%,923,928 and inseminations
with 25 × 106 progressively motile sperm ranged between
57% and 63%.929,930 However, in a study by Woods et al.,930
control mares were inseminated with 25 × 106 progressively
motile sperm in the uterine body, and pregnancy rates were
not significantly different between standard and deep uterine
inseminations. Because control inseminations were not done
in many studies, the true benefit of deep uterine insemination
has not been determined.
Hysteroscopic Insemination
Hysteroscopic insemination involves deposition of sperm
directly onto the papilla of the uterotubal junction. A minute
volume of extended sperm (approximately 0.05–0.25 mL) is
desired for hysteroscopic insemination. Sperm are centrifuged
through a density gradient to select a sperm population with a
high percentage of motility. Numbers of fresh sperm insemi-
nated ranged between 1 and 10 × 106 progressively motile
sperm, with pregnancy rates between 40% and 75%.928,931-933
Studies have been conducted using higher volumes931 or lower
sperm numbers,931 but fertility was reduced.
With hysteroscopic insemination, semen is aspirated into
an equine gamete intrafallopian transfer (GIFT) catheter
(Cook Animal Health, Bloomington, IN) protected by an outer
polypropylene cannula and loaded into the working channel
of the videoendoscope. With a sterile gloved arm in the vagina
of the mare, the operator guides the flexible endoscope (1.6
m in length) through the cervix and uterine lumen; directs
the endoscope along the uterine horn ipsilateral to the pre-
ovulatory follicle; and on imaging the papilla of the uterotubal
junction, extrudes the outer cannula and then the inner GIFT
catheter containing the sperm suspension from the working
channel of the endoscope. When the tip of the GIFT catheter
touches the papilla, the operator bubbles the inseminate onto
the surface of the papilla.931
Low-dose insemination with frozen-thawed sperm maxi-
mizes the use of a conventional dose of frozen sperm (800–
1000 × 106 progressively motile sperm) by reducing the
number of sperm needed for insemination. Using 5 or 10 × 106
frozen-thawed progressively motile sperm, different investiga-
tors obtained pregnancy rates between 33% and 47%.932,934,935
Alvarenga et al.936 inseminated client mares with 100 to 150 ×
106 frozen-thawed sperm from 15 Warmblood stallions and
obtained an overall pregnancy rate of 57%, demonstrating
that hysteroscopic insemination can be applied immediately
in the horse industry. Current rates for sorting sperm into X
chromosome–bearing or Y chromosome–bearing populations
are approximately 10 million sperm per hour, meaning that
low-dose inseminations are necessary for sex-sorted sperm.
Several studies have been conducted using hysteroscopic
insemination of sex-sorted sperm, resulting in pregnancy
rates between 25% and 44%.932,934
Disorders of the Reproductive Tract 13131313
Gamete Intrafallopian Transfer
GIFT involves transfer of oocytes and sperm into the recipi-
ent’s oviduct. Compared with oocyte transfer, GIFT requires
low numbers of sperm. The first successful GIFT in the
horse was reported in 1998.901 GIFT sperm are often selected
through a density gradient to select a population with a high
percentage of morphologically normal, motile sperm, free of
debris and seminal plasma, with 1 to 5 × 105 progressively
motile sperm transferred with an oocyte into the recipient’s
oviduct. Optimal procedures for GIFT have probably not been
established, although pregnancy rates between 27% and 82%
have been reported.899,937 GIFT is a potentially valuable tech-
nique to produce pregnancies from subfertile stallions, frozen
semen, and sex-sorted sperm. However, the type of sperm
and even extenders may have an effect on the success of GIFT.
Pregnancy rates with GIFT were lower when cooled or frozen
semen was used for GIFT (pregnancy rates of 25% and 8%,
respectively) compared with pregnancy rates with fresh semen
(82%).938
Y CONCLUSION
New assisted reproductive techniques have been developed
that allow for the production of offspring from mares and
stallions that would be considered subfertile or infertile when
more standard breeding procedures are used. Although cost,
expertise, and availability of these procedures may be limit-
ing factors in their widespread use at this time, their clini-
cal potential for preservation of valuable equine genetics is
important to recognize.
The Stallion
Charles F. Scoggin
This section will describe the relevant anatomy, physiology,
and management of the stallion and discuss pathology associ-
ated with the reproductive tract of male horses.
Medical conditions affecting stallions are generally no
different from what we see in other horses, with the obvious
exception being those pertaining to the reproductive organs.
The incidence of problems associated with the genitalia or
gonads is inherently low because there are proportionally
fewer intact male horses compared with female horses and
geldings. Nonetheless, on the vast majority of farms and
ranches, stallions are one of—if not the—most valuable assets
of the breeding operation and represent a very large financial
investment. Time off in the breeding shed because of illness
or injury can have significant and negative effects on both the
stud farm and the stallion. Problems must thus be addressed
efficiently and appropriately to minimize financial losses and
maximize fertility. Understanding the relationship between
the reproductive system and other organs in the stallion allows
for a thorough evaluation with the intent of achieving a timely
diagnosis and therapeutic plan.
Stallions are considered by some to be the most coveted and
financially relevant assets of a breeding farm. Consequently,
the importance of keeping them happy and healthy cannot
be overemphasized. Understanding the various anatomic and
physiologic attributes of breeding stallions allows for proper
reproductive management and health care.
 1314 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
Y REPRODUCTIVE ANATOMY
Internal Genitalia
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Testicles
Reproductively normal stallions should have paired testes that
are readily palpable within the scrotum. Normal equine testes
are relatively ovoid in shape. Each is oriented mostly in the
horizontal plane, with the head (caput) and tail (cauda) of the
epididymis located on the cranial and caudal poles, respec-
tively, of the testis. The body (corpus) of the epididymis runs
along the dorsal aspect of each testis. Occasionally, the testes
may rotate up to 180 degrees without any apparent signs of
discomfort or swelling. Such rotation is usually temporary but
may occasionally become permanent. It should also be distin-
guished from spermatic cord rotation, which is a pathologic
condition described later. This condition strays from normal
and may adversely affect perfusion to the testis. As such, this
finding should be taken into consideration when performing a
reproductive evaluation on a breeding stallion and duly noted
within the records. An important landmark is the proper liga-
ment of the tail of the epididymis, which is a remnant of the
fetal gubernaculum. The proper ligament attaches the tail of
the epididymis to the caudal pole of the testis. Clinically, this
ligament is palpable as a fibrous nodule that can be large in
newborn colts and mistaken for the testis, and it may also be
a useful reference in determining the relative orientation of
the testis. The ligament of the tail of the epididymis is another
gubernacular remnant that attaches the tail of the epididymis
to the parietal vaginal tunic of the scrotum and anchors the
testis and epididymis to the scrotum.
Each testicle is encapsulated by the tunica albuginea. This
tough collagenous membrane contains smooth muscle that
sends supporting trabeculae into the testicular parenchyma,
dividing the testis in adjoining lobules. Functionally, this mus-
cular investment is thought to assist with sperm transport
and determine the relative tone and turgidity of the testicle.939
Normal testes should be firm but resilient on palpation. Soft or
hard testes are abnormal and may be associated with myriad
conditions, including neoplasia, degeneration, infection, and
trauma.
Each testis is composed of several different cell types. Some
of these have endocrine functions, whereas others have exo-
crine or homeostatic functions. The parenchyma of the testis
accounts for 85% to 90% of the testicular volume. It is com-
posed of the seminiferous tubules and the interstitial tissue.
These work in tandem to manufacture, mature, and deliver
spermatozoa for fertilization of female gametes.
The seminiferous tubules are lined with an epithelial layer
(seminiferous epithelium) composed of germ cells and Ser-
toli cells. Germ cells will be present at various stages of devel-
opment, from early spermatogonia to mature spermatids,
and are the most prominent cell types. The interstitium is
formed by Leydig and myoid cells and comprises ∼15% of the
parenchyma.940
Because of the complexities of the spermatogenic process,
it and the various stages of germ cells involved in spermato-
genesis will be covered in a separate section. What follows
immediately is a brief description of the other cells involved
in testicular function.
Sertoli Cells. Sertoli cells are pivotal for germ cell matura-
tion, serving as nurse cells and forming the blood-testis bor-
der. These cells help nurture and support developing germ
cells through their exocrine secretions that bathe the devel-
oping germ cells. These cells also have important endocrine
functions, and by secreting androgen binding protein (ABP),
activin, and inhibin, they can affect the hormonal milieu of the
testis. The former’s role is to bind dihydrotestosterone (DHT;
the bioactive form of testosterone) to maintain proper concen-
trations of DHT in the seminiferous tubules and epididymis,
whereas the latter two are responsible for stimulating or sup-
pressing FSH, respectively. Sertoli cells also produce other
proteins that are necessary to support and regulate sperma­
togenesis. Examples include ceruloplasmin and transferrin,
which act as carrier proteins for copper and iron, respectively,
and are necessary for proper testis function.
The blood-testis barrier divides the seminiferous epithe-
lium into basal and adluminal compartments via tight gap
junctions formed between Sertoli cells. This barrier func-
tions primarily to protect the haploid spermatozoa found in
the seminiferous tubules from the host immune system that
would recognize them as foreign; thus its primary function is
one of providing immune privilege to the adluminal compart-
ment of the seminiferous tubules.
The number of spermatogenic cells and ultimately the total
sperm production of a given stallion are determined by the
number of cells that can be accommodated between the tight
gap junctions between two Sertoli cells. Sertoli cell numbers
increase steadily during puberty and continue to rise with
maturity. The number of Sertoli cells within the adult stallion’s
testes was once thought to be finite. However, recent research
suggests that Sertoli cells are not stable; instead, their numbers
fluctuate with season.941
Leydig Cells. Leydig, or interstitial, cells are the main
source of testosterone production. Androgen production is
mediated primarily via pituitary secretion of LH, and Leydig
cells contain an abundance of LH receptors. Through steroid
production, Leydig cells provide the feedback mechanisms on
the pituitary necessary to maintain spermatogenesis, second-
ary sex characteristics, and libido. Testosterone concentration
in the testicular microcirculation is at least 10 times higher
than that in the systemic circulation. Season and not age ap-
pear to affect the testosterone production in adult stallions,
which is mediated through a change in total number of Leydig
cells rather than total volume of cells per testis. In contrast to
Sertoli cells, Leydig cell numbers do not increase dramatically
with age, but both number and size of these cells can vary with
season.942
Myoid Cells. Myoid cells appear essential for proper tes-
ticular function. They provide architectural support to the
seminiferous tubules and likely play an important role in in-
tratesticular movement of sperm. In addition, myoid cells also
modulate Sertoli and Leydig cell function via paracrine fac-
tors. One example is production of the mesenchymal factor
PmodS, which has been shown in vitro to stimulate release of
transferrin from Sertoli cells.943
Germ Cells. In contrast to mares, normal stallions con-
tinually produce germ cells. This process of development of
a diploid germ cell to a haploid spermatozoa capable of fer-
tilization requires approximately 57 days, and the number of
germ cells produced is directly correlated with the total vol-
ume of the testes.944 Germ cells line the seminiferous tubules
and can be found in different stages of maturation from early
diploid stem cell spermatogonia to almost fully mature hap-
loid spermatids. The process by which these primordial cells
transform into spermatozoa is referred to as spermatogenesis.
 CHAPTER 19
Spermatogenesis follows a chronologic order in the develop-
ment of germ cells yet is also a highly complex process. The
spermatogenic process will be reviewed later in the discussion
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of stallion physiology.
Testis Cell Interactions. The importance of the relationship
between the individual cells within the testes cannot be over-
stated. For example, Sertoli, or “nurse,” cells have a direct in-
teraction with germ cells, and Leydig cells interact with Sertoli
and germinal cells through hormonal signals. The myoid cell
produces at least one paracrine factor that interacts directly
with the Sertoli cell. Paracrine and autocrine modulating fac-
tors, products of the peritubular cell, appear to have an effect
on ABP function. In turn, the myoid cell is under the regula-
tory influence of transforming growth factors α (stimulatory)
and β (inhibitory). Other factors involved in cell-to-cell com-
munication of the cells of the testis include collagen, plasmi-
nogen activator, vitamin A, pyruvate, and carbohydrates.945
Most of these products and mechanisms have not been inves-
tigated extensively in the stallion.
Epididymides
The specific absorptive and secretory functions of each seg-
ment of the stallion epididymis remain the subject of consid-
erable debate and investigation. The histologic structure of
the epididymis changes as it continues through its different
regions, with epithelial height being greatest proximally and
smooth muscle components greatest distally.946 As spermato-
zoa are transported from the excurrent ducts into the head,
along the body, and into the tail, they undergo a number of
morphologic and physiologic changes that ultimately render
them motile and fertile. Specific maturational changes that
occur include (1) acquiring the capacity for progressive motil-
ity, (2) shedding of the cytoplasmic droplet, (3) plasma and
acrosomal membrane alterations, (4) DNA stabilization, and
(5) metabolic changes.947 All these changes occur primarily at
the level of the mid to distal corpus.947,948 The tail of the epi-
didymis serves primarily as a storage site for nearly competent
spermatozoa that are ready for ejaculation.
Fluid resorption occurs throughout the epididymis and at
a steady rate, which results in a significant increase in sperm
concentration. Stallions with high-volume ejaculates with rel-
atively low sperm concentration and poor sperm morphology
may have epididymal dysfunction. However, the association
has yet to be clearly defined.
Spermatic Cord
The spermatic cord supplying each testis is enveloped in the
parietal layer of the vaginal tunic, which extends distally from
the internal inguinal ring. Within each cord are the corre-
sponding deferent duct, testicular artery, testicular veins, lym-
phatic vessels, and nerves. The cremaster muscle is situated in
the caudolateral borders of each spermatic cord. The testicu-
lar artery, a branch of the abdominal aorta, descends through
the inguinal ring into the cranial border of the spermatic cord
in a tortuous manner and divides near the testis into several
branches to supply the testis and epididymis. These small
branches, embedded in the tunica albuginea, enter the paren-
chyma by way of the trabeculae and septae of the testis. A cor-
responding network of veins leaves the testis and surrounds
the testicular artery in a tortuous manner, forming the pampi-
niform plexus. This arrangement of artery and veins serves a
critical role in thermoregulation of the testis in the stallion.
The pampiniform plexus allows for heat exchange from the
Disorders of the Reproductive Tract 13151315
testicular artery to the venous side, resulting in testicular arte-
rial blood being several degrees cooler than systemic blood
temperature. Abnormal distention of the veins of the pampi-
niform plexus is termed a varicocele and is an uncommon
condition in stallions. Palpation of the spermatic cord of an
affected stallion reveals the dilated and often tortuous vessels.
Varicoceles are usually not painful but can result in fluid accu-
mulation around the vaginal tunics, most often involve only
one side of the spermatic cord, and usually are diagnosed by
the observation of the dilation of the vessels from the pampi-
niform plexus with ultrasonography. The condition has been
identified in stallions with normal semen parameters.949
Accessory Sex Glands
In the stallion, the accessory sex glands are composed of the
bulbourethral glands, prostate gland, seminal vesicles, and
ampullae. Their secretions produce the seminal plasma that
makes up most of the ejaculate volume. The ampullae, which
are dilations of the vas deferens before opening in the collicu-
lus seminalis, are also considered a storage site for sperm.
Short exposure to seminal plasma appears to be important
for sperm function, but long-term exposure to seminal plasma
components may be detrimental to spermatozoa survival for
some stallions. Often termed “toxic” seminal plasma, sperma-
tozoa exposed to certain stallions’ seminal plasma quickly lose
their viability, leading to subfertility. AI programs deal with
this potential detrimental effect by dilution of semen with
semen extenders in fresh or fresh-chilled programs and by
centrifugation to remove seminal plasma in frozen semen pro-
grams and some chilled-shipped programs. Live-cover opera-
tions may counter toxic seminal plasma by infusing semen
extender into the mare’s uterus before or after mating.
Seminal plasma appears to suppress the inflammatory
response of the endometrium of the mare to sperm after
insemination or natural mating. Although the functions
of the specific components of the seminal plasma remain
rather obscure, the fluid suspends the ejaculated sperm
and also is thought to be a source of energy, protein, and
other macromolecules required for sperm functions and
metabolism.950-952
Next is a brief discussion on the anatomy and functionality
of the stallion’s accessory sex glands.
Bulbourethral Glands. Multiple ductules from the bul-
bourethral glands enter the dorsomedial wall of the pelvic
urethra caudal to the prostatic ductules. Bulbourethral gland
secretions compose most of the presperm or first fraction of
the ejaculate and serve as a cleanser and pH stabilizer in the
urethra before ejaculation.
Prostate Gland. In the stallion the prostate is formed by a
central isthmus and two lateral lobes located on the caudola-
teral borders of each vesicular gland. Multiple ductules from
the prostate enter the lumen of the pelvic urethra in the dorsal
urethral wall lateral to the colliculus seminalis. The watery se-
cretions of the prostate contribute to the presperm fraction of
the ejaculate.
Ampullae. The ampullae are the enlarged distal portions
of the deferent ducts. They converge caudad and pass beneath
the prostate gland but lie dorsal to the pelvic urethra. At their
distal ends they continue through the dorsal wall of the ure-
thra, opening into the colliculus seminalis alongside the excre-
tory ducts of the seminal vesicles. The ampullae, in addition to
serving as a sperm storage area, have many branched tubular
glands located within the thickened wall.953
 1316 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
The ampullae are a common site for blockage caused by sta-
sis of sperm (as would be seen in a sexually inactive stallion)
or an inability to effectively void spermatozoa. This condition
is referred to as spermiostasis or plugged ampullae and can
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cause subfertility if not properly managed. This condition will
be discussed later.
Seminal Vesicles. The seminal vesicles or vesicular glands
are paired, pyriform, and thin-walled structures lying lateral
to the ampullae. On occasion they may extend far cranially
to hang over the brim of the pelvis. The caudal ends of the
glands converge, passing under the prostate as they lie parallel
to the ampullae, terminating in the seminal colliculus in the
dorsal wall of the urethra. The excurrent ducts of the vesicular
glands open lateral to the excurrent ducts of the ampullae at
the colliculus seminalis of the urethra. Secretions of the vesic-
ular glands compose the gel fraction of the ejaculate. Higher
gel volumes can be collected with increased sexual stimula-
tion and season. The specific function of the gel fraction is
unclear, and it should be removed when processing semen for
evaluation or AI. The seminal vesicles are the glands that are
most prone to bacterial infections. Diagnosis is based on the
cytologic evaluation of the semen with the presence of white
blood cells. Treatment and management typically involve both
local and systemic antibiotics based on culture and sensitivity
results.
External Genitalia
The penis and scrotum comprise the extent of a normal stal-
lion’s external genitalia. The penis is comprised of smooth
muscle and encased in a sheath of tissue, often referred to as
the prepuce. The penis of the stallion is composed of a root, a
body, and a glans penis and is musculocavernous. The penile
base arises at the ischial arch in the form of two crura that fuse
distally to form the single dorsal corpus cavernosum penis
(CCP) enclosed by a thick tunica albuginea. The corpus cav-
ernosum, corpus spongiosum, and corpus spongiosum glandis
are the three spaces that make up the erectile tissue of the penis.
Engorgement of these spaces with blood from branches of the
internal and external pudendal arteries and obturator arteries
is responsible for an erection. The cavernous spaces within the
penis are continuous with the veins responsible for drainage.
The corpus spongiosum originates in the pelvic area and sur-
rounds the penile urethra within a groove on the ventral side of
the penis and forms the corpus spongiosum glandis at the dis-
tal end of the penis.954 The corpus spongiosum glandis creates
the distinct bell shape of the stallion penis after ejaculation.
The distal end of the urethra contains a distinct urethral
process, which is visible within the center of the glans penis
and surrounded by an invagination known as the fossa glan-
dis. Within the fossa glandis are diverticulae and a urethral
sinus. Accumulation of secretions in these areas can occur to
form “smegma,” and further coalescence can form semifirm
concretions (“beans”) within one or all of these sites. There-
fore careful examination and cleansing of this area are impera-
tive during the reproductive evaluation of a stallion or before
breeding.
The bulbospongiosus muscle and two retractor penis
muscles are located ventrad on the stallion penis and run the
length of the organ. The former is responsible for providing
rhythmic contractions or pulsations to assist in moving the
penile urethral contents (semen and urine) distally during
ejaculation; the latter are responsible for returning the penis to
the sheath after detumescence.
The prepuce is formed by a double fold of skin that is hair-
less and well supplied with sebaceous and sweat glands. The
primary preputial function is to contain and protect the non-
erect penis. The external part of the prepuce, or sheath, begins
at the scrotum and is continuous with the scrotal raphae. The
internal layer of the prepuce extends caudally from the orifice
to line the internal side of the sheath and then reflects crani-
ally toward the orifice again before reflecting caudally to form
the internal preputial fold and preputial ring. This additional
internal fold allows the considerable lengthening (approxi-
mately 50%) of the penis during erection. During erection the
preputial orifice is visible at the base of the penis just in front
of the scrotum, and the preputial ring is visible at approxi-
mately the midshaft of the penis.
The penis and prepuce of a breeding stallion can best be
examined after teasing with an estrous mare, when one can
observe the stallion drop the penis and attain a full erection.
The prepuce and penis should be free of vesicular, prolifera-
tive, or inflammatory lesions such as those found in horses
with coital exanthema, squamous cell carcinoma, or cutane-
ous habronemiasis. Removal of smegma accumulations is nec-
essary for a complete examination of the skin surfaces.
Y REPRODUCTIVE PHYSIOLOGY
OF THE STALLION
Sexual Differentiation
Mammalian sexual differentiation is a complex process. Tim-
ing is crucial, and an intricate series of intracellular and extra-
cellular signaling events during specific periods of embryonic
and fetal development must occur for sexual differentiation to
proceed normally. Sexual differentiation is established by the
chromosomal sex at fertilization when oocytes comprising the
X chromosome encounter the X-bearing or Y-bearing sperm.
Ovarian or testicular development pathways are initiated by
the bipotential embryonic gland, which is a diverse popula-
tion of somatic cells and germ cells. The testis-determining
factor, located on the Y-region, is known as the sex-deter-
mining region (SRY in humans, and Sry in horses and other
mammals). The presence of SRY activates the testis-specific
pathway and suppresses the ovary-specific genetic develop-
ment pathway in most mammals, and the reader is referred
to more comprehensive reviews on this topic.955-959 The pro-
tein product SRY is expressed in XY somatic cell precursors
and in conjunction with steroidogenic factor 1 (SF1) acts as a
molecular switch specifically to upregulate expression of SOX9
in the SOX (SRY-related high-mobility group box) gene fam-
ily.957 Initially, SOX9 is expressed in the bipotential gonad of
both sexes, whereas SOX9 expression in XX gonads is down-
regulated, and expression of SOX9 in XY gonads is signifi-
cantly upregulated. On reaching a certain threshold, somatic
cell precursors differentiate into testis-specific Sertoli cells.957
Upregulation of SOX9 protein expression also leads to a series
of molecular events to advance testis differentiation by pro-
moting cellular and structural organization. Protein expres-
sion of SOX9 is also responsible for a negative-feedback loop
to repress SRY expression. Despite cessation of SRY expres-
sion, expression of the SOX9 and SF1 proteins continues and
is maintained at high levels in Sertoli cells to further promote
Sertoli cell development. Factors and signaling pathways that
also play an important role in Sertoli cell differentiation include
the signaling molecule FGF9 (fibroblast growth factor) and its
 CHAPTER 19
receptor FGFR2, as well as prostaglandin D2 (PGD2). Expres-
sion of FGF9 is activated downstream of SOX9 and SRY. Both
FGF9 and SOX9 work together in a positive feedforward loop
in which SOX9 protein is required to upregulate FGF9 expres-
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sion. This then maintains SOX9 expression to further promote
differentiation into Sertoli cells.960 In the absence of FGF9 or
FGFR2 expression in XY mice, SOX9 expression was lost and
Sertoli cells did not develop, resulting in sex reversal.961,962
Upregulation of FGF9 during testis development also actively
represses the female gene wingless-related MMTV integration
site 4 (WNT4), which is required for ovarian development.963
Thus FGF9 expression is critical for testis development.
Another autoregulatory loop that works independently
from FGF9 and promotes Sertoli cell development is the
PGD2-mediated signaling pathway. Sertoli cells secrete
PGD2, causing neighboring somatic cell precursors to express
and accumulate SOX9, spawning more Sertoli cells,964 but
this particular signaling pathway is not essential for testis
development.
Testicular Descent
Normal descent of the testes into the scrotum is somewhat
variable and typically occurs between the last 30 days' gesta-
tion and the first 10 days of birth. In some colts the testes may
descend into the inguinal region and remain there for some
time before fully descending. Both endocrine and anatomic
events must occur for proper migration of the testes into the
scrotum. Androgens and AMH are involved in the signaling
for testicular descent.965-968 Traction of the gubernaculum,
which attaches the caudal pole of the testis to the parietal vagi-
nal tunic of the scrotum, is believed to draw the developing
testis and epididymis into and through the inguinal ring.2
Cryptorchidism is the condition in which one or both testes
fail to descend into the scrotum by 2 years of age. It is one of
the most common congenital defects occurring in colts, yet
the causes remain obscure and are presumably multifactorial.
A true genetic link has not been found, but anecdotal evidence
abounds about certain family lines in particular breeds whose
males are prone to the condition. Diagnosis and management
of this condition will be discussed later.
Puberty
This period is defined as the age at which a colt is able to
mount, copulate, and successfully impregnate a mare and gen-
erally occurs during the second spring after the year of birth
in the Northern Hemisphere. It should be noted that in some
cases colts as young as 8 months have been able to achieve
pregnancies. In some large breed horses (e.g., draft breeds)
there may be a delay in puberty. Puberty should not be con-
fused with sexual maturity. Whereas puberty signifies the time
in which a male can successfully impregnate a female, sexual
maturity indicates the time period after which a stallion has
fully developed secondary sexual characteristics and fully
developed genitalia. Puberty occurs earlier (e.g., ∼2 years of
age), whereas sexual maturity is reached at approximately 5
years of age.
The hypothalamic pulse generator is a group of cells located
in the arcuate nucleus of the hypothalamus.965 Neuroen-
docrine activity from this generator stimulates the onset of
puberty via pulsatile secretion of GnRH from the hypothala-
mus, which stimulates the secretion of LH and FSH from the
anterior pituitary. Season, age, breed, nutritional status, and
external hormones affect puberty. In horses, onset of puberty
Disorders of the Reproductive Tract 13171317
occurs around 12 to 18 months and is complete by 18 to 24
months, as previously mentioned.969
Endocrinology
The pineal gland plays a significant role in the seasonality of
the horse. Specifically, the retina captures photoperiod infor-
mation and transports it by way of nerve fibers to the pineal
gland. In horses, photoperiod stimulation (i.e., long days)
inhibits the production of melatonin. Because melatonin
inhibits GnRH release in horses, suppression of melatonin
leads to increased pulses of GnRH from the hypothalamus.
Unlike mares, stallions do not undergo a complete reproduc-
tive quiescence during short days and will continue to produce
sperm year round. The cause for this partial refractoriness of
the stallion to changes in photoperiod is not well understood
but likely clinically insignificant in normal fertile stallions.
The hypothalamus, pituitary, and testes (HPG axis) must
work in synchrony for a stallion to be able to start and sustain
sperm production. The primary role of the hypothalamus is
the production of the 10-amino-acid peptide GnRH, which is
secreted in multiple daily pulses and then transported via the
hypothalamic-pituitary portal system to the anterior pituitary.
In addition to melatonin-mediated stimuli, the hypothalamus
responds to tactile, olfactory, and visual stimuli.970
The pituitary, which is connected to the hypothalamus
by neural fibers, has two lobes. The anterior lobe possesses
GnRH receptors. Binding of GnRH activates these receptors
and induces secretion of FSH or LH. FSH and LH act on the
Sertoli and Leydig cells, respectively, stimulating production
of steroids and other protein hormones. The peptide hor-
mones inhibin and activin regulate FSH secretion at the level
of the pituitary. Steroid hormones produced in the testis (e.g.,
estradiol, testosterone) feed back at the level of the pituitary to
inhibit FSH and LH secretion and to regulate GnRH secretion
from the hypothalamus.
Because of the complexity of interactions among hormones,
their target tissues and other important physiologic events,
current methods do not exist to accurately predict infertility
in stallions. As will be discussed later, pharmaceutical therapy,
particularly supplementation with exogenous hormones, is
empiric, somewhat unreliable, and only of benefit in certain
instances.
Spermatogenesis
Spermatogenesis describes a series of chronologic changes
occurring within the seminiferous tubule that transforms
a large, round diploid spermatogonium into a haploid sper-
matozoon capable of fertilization. This process takes approxi-
mately 57 days in stallions and is not affected by frequency of
ejaculation or sexual stimulation. Next will be a brief review
of the spermatogenic process. However, many of the com-
plexities are beyond the scope of this chapter, so the reader
is directed to reviews on this subject for more in-depth
information.939,949,971
The process starts when an A1 stem cell spermatogonia
undergoes mitosis, giving rise to (1) a second A1 spermato-
gonia to maintain a constant population of stem cells and (2)
an A2 spermatogonia. In turn, the A2 spermatogonia gives rise
to A3, A3 to B1, and B1 to B2. Spermatogenesis can be divided
into three phases of similar length: spermatocytogenesis, mei-
otic divisions, and spermiogenesis.
Spermatocytogenesis is characterized by the mitotic divi-
sions of A and B spermatogonia. Meiotic divisions result in the
 1318 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
formation of primary spermatocytes from B2 spermatogonia,
followed by formation of secondary spermatids. Leptotene
spermatocytes that form immediately after the first meiotic
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division are shielded from the host’s immune system by the
blood-testis barrier. Spermiogenesis is characterized by the
transformation of round spermatogonia to elongated sperma-
tids and, ultimately, spermatozoa. During spermiogenesis, the
acrosome arises from the Golgi complex, and compaction of
DNA occurs because of expression of protamine genes at the
spermatid stage. The end of spermatogenesis is characterized
by spermiation, which is the release of elongated spermatids
into the lumen of the seminiferous tubule and represents the
transition to a spermatozoa.972
Seasonality
Stallions are subject to seasonal influences. For example,
concentrations of LH and testosterone, DSO, and libido all
increase during times of the year that coincide with periods
of longer exposure to light, or “long days.”973-975 However, stal-
lion reproduction does not appear to be as tightly regulated by
season as that of mares. When given the opportunity, stallions
will breed year round and are capable of ejaculating normal
sperm and achieving adequate pregnancy rates.973
Because stallions are seasonal long-day breeders, exposure
to artificial lighting programs has been used in the manage-
ment of commercial breeding stallions. It is thought that it can
hasten the onset of improved breeding behavior and sperm
production. Such strategies are used on several commercial
stud farms in the United States. Two studies reported no det-
rimental effect on photostimulated stallions.975 Another study
demonstrated that light therapy increased testicular size and
sperm production, but changes were transient.976,977 In addi-
tion, some stallions experienced a reduction in testis size and
circulating testosterone concentrations by June, which could
potentially have a negative effect on reproductive efficiency,
especially in stallions of already questionable fertility.
Sexual Behavior
Stallions will demonstrate sexual behavior in many ways.
Vocalization, snorting, bowing of the neck, biting/nipping,
striking, and the flehmen response are all typical signs associ-
ated with normal breeding behavior. Depending on the indi-
vidual stallion, these precopulatory signs will be expressed
with various frequencies and intensities. Libido or “sex drive”
is the vigor with which stallions display breeding behavior.
Strength of libido is dependent on numerous factors such as
genetics, farm and breeding management, season, and exter-
nal stimuli (olfactory, visual, and auditory) and is highly vari-
able among individual stallions. When exposed to an estrous
mare, stallions should drop their penis within 2 minutes,
which is referred to as the “latency to erection” period, and
attempt to mount the mare or phantom mount in 3 to 5 min-
utes. Once intromission occurs, stallions give several (five to
eight) vigorous pelvic thrusts, followed by three to five short
thrusts immediately before ejaculation. External signs of ejac-
ulation that are used to determine whether ejaculation has
occurred are rhythmic and frequent urethral pulsations in the
penis (fremitus), flagging of the tail, and head relaxation. A
single stallion tends to be consistent in his breeding behavior,
provided that the conditions under which he usually mates are
the same.978 Exceptions to these rules are stallions that have
never bred before (i.e., novice stallions). Their behavior can
be somewhat erratic because of inexperience but will evolve
and stabilize with increased breeding frequency. Management
of the abnormal behavior and the novice stallion will be dis-
cussed later.
Y CLINICAL EVALUATION OF
THE STALLION
Assessments of stallions for their suitability as breeding ani-
mals are called breeding soundness evaluations (BSEs).
However, the author prefers the term stallion reproductive
evaluations (SREs) because BSE is commonly associated with
examination of bulls for their relative virility. The criteria used
to determine the value of and measure the reproductive per-
formance of males are vastly different between the two spe-
cies. Thus it seems reasonable to use a separate term to avoid
confusion.
Many SREs are performed as either part of a prepurchase
examination or as annual evaluations (typically performed
before the breeding season) to monitor reproductive capac-
ity. Other indications for SREs would be a precipitous drop in
fertility or as partial fulfillment of an insurance examination.
An example of a typical form to record findings from an SRE
is shown in Fig. 19.25.
Recommendations for determining whether a stallion met
the criteria to be considered satisfactory for breeding were out-
lined in the (no longer available) Manual for Clinical Fertil-
ity Evaluation published by the Society for Theriogenology in
1983.
Standards by which a stallion is judged to be a satisfactory
breeder include the ability to
1. Render 75% of 40 mares pregnant via live cover (or 120
mares by AI) in one breeding season;
2. Produce ≥1 billion progressively motile, morphologically
normal sperm in the second of two ejaculates collected an
hour apart;
3. Have a total scrotal width of 8 cm; and
4. Be free of undesirable/hereditable defects.
Stallions failing to meet these requirements are given either
differed or unsatisfactory status based on findings from the
evaluation. Much advancement in our knowledge of repro-
ductive physiology and breeding management has been made
since this manual’s publication, and some theriogenologists
have acknowledged the need for updating the requirements.979
Moreover, problems often arise when trying to quantify bio-
logic systems, especially when there is more “skin in the game”
than just finances. For example, there are certain intangibles
a stallion may represent that prove nearly impossible to cal-
culate. Farm management practices, whether knowingly
or unknowingly, can also influence reproductive efficiency.
Therefore data obtained from the SRE should always be inter-
preted with respect to individual farms and stakeholders.
Breeding Records
The importance of maintaining accurate and current breeding
records cannot be overstated. Both computer-generated and
manual records can be used to evaluate and track a stallion’s
reproductive efficiency. In addition, these records are invalu-
able to clinicians when asked to assess a stallion for his repro-
ductive performance.
In central Kentucky, “Horse Farm Management,” provided
by the Jockey Club Information Systems (Jockey Club Infor-
mation Systems, Lexington, KY) is an example of a digital
 CHAPTER 19 Disorders of the Reproductive Tract 13191319

program that can track and compile data about past and cur- baseline radiographs of the distal limbs can prove useful for
rent reproductive parameters. For example, this program can screening, monitoring, and treating orthopedic issues.
generate reports on the numbers of mares bred, mare informa- Careful attention should be paid to the external genitalia.
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tion, and seasonal summary reports for individual stallions or
the stud farm as a whole. This information can then be tallied
to evaluate breeding efficiency and/or factors associated with
poor performance.
Physical Examination
Stallions should be sound in both mind and body to be suit-
able for breeding. Organ systems should be evaluated for signs
of diseases or disorders that could adversely affect breed-
ing performance. In particular, diseases of the musculoskel-
etal system can significantly impede reproductive efficiency,
and chronic disorders (e.g., arthritis, laminitis) can drasti-
cally shorten a stallion’s breeding career. When or if possible,
Visual and manual inspection of the entire penis, sheath, and
scrotum for size, texture, consistency, and signs of dermatitis
are indicated. Measurement of total scrotal width using cali-
pers or ultrasonography is useful for measuring reproductive
efficiency. As will be discussed in the next section, ultrasonog-
raphy is a highly useful means to assess the internal anatomy
of the stallion, especially the testes.
Evaluation of the External Genitalia
Ultrasonography of the testes is a useful diagnostic tool for
screening for pathology, monitoring progression of disease,
and predicting reproductive capacity. Pathology of the tes-
tes will be discussed later, but at a minimum ultrasound and

LeBlanc Reproduction Center

2150 Georgetown Road
Lexington, KY 40511

Stallion Reproductive Evaluation Form

Stallion Information
Name: Choose an item. Year of Birth: Choose an item.
Breed: TB Color: Choose an item.
Current Use: Choose an item. Tattoos or Microchip: Click here to enter text.
Location of Evaluation:
Evaluator:

Health History
Vaccinations Deworming History
Diseases: Choose an item. Last PEC: Click here to enter a date.
Product: Choose an item. Result of PEC: Click here to enter a text.
Date Given: Click here to enter a date. Last Dewormed: Click here to enter a date.
Deworming Product: Choose an item.
Diseases: Choose an item. Last Coggins: Click here to enter a date.
Product: Choose an item. Result: Choose an item.
Date Given: Click here to enter a date. Lab and it: Click here to enter a text.
Diseases: Choose an item. Last CBC/Fib: Click here to enter a date.
Product: Choose an item. Result/Interpretation:
Date Given: Click here to enter a date.
Diseases: Choose an item. Last Biochemistry: Click here to enter a date.
Product: Choose an item. Result/Interpretation: Click here to enter a text.
Date Given: Click here to enter a date.
Diseases: Choose an item. Last Endocrine Testing: Click here to enter a date.
Product: Choose an item. Result/Interpretation: Click here to enter a text.
Date Given: Click here to enter a date.
Diseases: Choose an item. Aerobic Bacterial Cultures
Product: Choose an item. Penis: Click here to enter text.
Date Given: Click here to enter a date. Fossa Glandis: Click here to enter text.
Diseases: Choose an item. Pre-Ejaculatory Urethra: Click here to enter text.
Product: Choose an item. Post-Ejaculatory Urethra: Click here to enter text.
Date Given: Click here to enter a date.
Diseases: Choose an item. Past-Lameness Issues: Click here to enter text.
Product: Choose an item.
Date Given: Click here to enter a date.
Diseases: Choose an item. Past Surgeries: Click here to enter text.
Product: Choose an item.
Date Given: Click here to enter a date.
Diseases: Choose an item. Current Medications: Click here to enter text.
Product: Choose an item.
Date Given: Click here to enter a date.

FIG. 19.25 Example of a stallion reproductive evaluation (SRE) form.

Continued
 1320 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
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Reproductive History
Previous Season Past Reproductive Issues
Total No. Mares Bred = Click here to enter text. Issue #1: Click here to enter text.
Total No. Covers = Click here to enter text. Issue #2: Click here to enter text.
Seasonal Pregnancy Rate = Click here to enter text. Issue #3: Click here to enter text.
Pregnancy Rate / Cycle = Click here to enter text. Issue #4: Click here to enter text.
No. Covers / Pregnancy = Click here to enter text. Past Breeding Behavior: Choose an item.
No. Covers / Mare = Click here to enter text. Typical No. Jumps per Mare: Choose an item.

External Genital Examinations

Date Performed: Sunday, March 06, 2016
Palpation and Visual Inspection
Penis/Prepuce Scrotum Left Testis Right Testis
Size Choose an item. Choose an item. Choose an item. Choose an item.
Cinsistency Choose an item. Choose an item. Choose an item. Choose an item.
Other Findings Click here to enter Click here to enter Click here to enter Click here to enter
text. text. text. text.

Ultrasonographic Findings
Left Testicle Right Testicle
Length (cm) 0 0
Width (cm) 0 0
Height (cm) 0 0
Volume (cm3) 0.0 0.0
DSO (x103) -1.26

Accessory Sex Gland Examination

Date Performed:
Method Used: Choose an item.
Bulbourethral Glands Click here to enter text.
Prostate Click here to enter text.
Seminal Vesicles Click here to enter text.
Ampullae Click here to enter text.
Bladder Click here to enter text.

FIG. 19.25, Cont’d

palpation of the testes should be performed to determine the
size, tone, orientation, and character of the testes and associ-
ated structures. Measurements of the height, width, and length
of each testis can be obtained with a standard 5-MHz or 7.5-
MHz linear rectal probe. These values can be used to calculate
testicular volume and then the estimated DSO980 and breeding
frequency expected for testes of that size.981 Table 19.11 shows
the relationship among testicular volume, DSO, and expected
number of daily breedings determined in Thoroughbred stal-
lions performing in a commercial live-cover program.
Specific techniques for examination of the testis have been
previously discussed.982,983 Beginning at the proximolateral
aspect of the scrotal neck with the long axis of the probe parallel
to the ground, the spermatic cord can be imaged. The arrange-
ment of the pampiniform plexus results in the mottled, hetero-
geneous appearance of the spermatic cord, and the testicular
artery and veins are identifiable in cross-sectional images. If
the ultrasound machine is equipped with a power Doppler
function, then evaluation of the vasculature can be performed
and compared with previously established values.984,985 Slowly
moving distal and cranial toward the cranial pole of the testis,
the probe can then be oriented in a vertical position (i.e., long
axis perpendicular to the ground) and moved caudad. Visual-
ization of the scrotum reveals a thin, echogenic uniform layer.
Minimal, if any, fluid is visible between the scrotal skin and
testicular parenchyma in the normal stallion. In the cranial
third of the scrotum, the head of the epididymis, testicular
parenchyma, blood vessels of the spermatic cord, and central
vein of the testis are visible.
As the probe is moved caudal, the spermatic cord vessels
disappear, and the head of the epididymis continues into the
body of the epididymis. The head and body of the epididymis
appear as heterogeneous areas just below the spermatic cord.
Further caudad, the body of the epididymis becomes indis-
tinct. With the exception of the central vein, the testicular
parenchyma appears uniformly echogenic and homogeneous.
The central vein appears as a small anechoic area within the
testicular parenchyma at the cranial third of the testis and
should not be mistaken for a pathologic lesion. Dilation of the
central vein may be visible in cases of varicocele or spermatic
cord torsions and usually is accompanied by detectable dila-
tions of the vessels of the spermatic cord. Well-defined and
hypoechoic or hyperechoic lesions within the parenchyma
suggest testicular tumors.
 CHAPTER 19 Disorders of the Reproductive Tract 13211321
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Semen Collection and Evaluation

Date Performed: Click here to enter a date.
Method of Semen Collection: Choose an item.
Use of Jump Mare or Phantom: Choose an item.
Method of Concentration Determination: Choose an item.
Method of Motility Evaluation: Choose an item.
Use of Semen Extender: Choose an item. Semen Extender Used: Choose an item.
Ejaculate 1 Ejaculate 2 Ejaculate 3
Date and Time
Libido Choose an item. Choose an item. Choose an item.
Erection Choose an item. Choose an item. Choose an item.
No. Mounts Choose an item. Choose an item. Choose an item.
Breeding Ability Choose an item. Choose an item. Choose an item.
Gross Appearance Choose an item. Choose an item. Choose an item.
Volume Gel
Volume (gel free; mL)
Concentration (x 106/mL)
Total No. Sperm
Total Motility (%)
Progressive Motility (%)
Velocity
Sperm Morphology
Method of Morphology: Choose an item.
Ejaculate 1 Ejaculate 2 Ejaculate 3
%Normal Sperm
%Detached Heads
%Abnormal Heads
%Abnormal Acrosomes
%Abnormal Midpieces
%Tail Bent
%Tail Coiled
%Proximal Droplets
%Distal Droplets
%Round Cells
%Other
Sperm Longevity
Ejaculate 1 Ejaculate 1
Method Used: Choose an item. Method Used: Choose an item.
Date/Time Date/Time
Total/Progressive Motile Total/Progressive Motile
Date/Time Date/Time
Total/Progressive Motile Total/Progressive Motile
Date/Time Date/Time
Total/Progressive Motile Total/Progressive Motile
Adjunctive Tests
Scanning Electron Microscopy
Membrane Integrity
Sperm Chromation Structure Assay
Acrosomal Status
Semen Cytology

FIG. 19.25, Cont’d

Continued

After reaching the most caudal aspect of the testis, the
clinician rotates the probe to face cranially in a vertical
position to allow examination of the tail of the epididymis.
This structure appears as a heterogeneous area with a Swiss
cheese–like appearance. Identification of the epididymal
tail may assist in diagnosis of testicular rotations. In horses
with 360-degree torsions, the tail of the epididymis,
although in its caudal position, is more dorsal because of
the tension on the ligament of the tail of the epididymis by
the deferent duct.
 1322 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
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Overall Evaluation
Based upon the above indings, including—but not limited to—a careful physical
examination, a thorough review of past and present breeding ability, and a
systematic evaluation of the genitalia and seminal characteristic of this stallion, it is
my professional opinion that this stallion:

Sincerely,

FIG. 19.25, Cont’d

TABLE 19.11 Relationship Between Testicular Volume, Daily Sperm Output, and Expected Daily Breeding Frequency in
Thoroughbred Stallions in a Commercial Live-Cover Breeding Operation981
Estimating Breeding Book Size Based on Testicular Measurements

Testicular Volume (mL) Range in Predicted Daily Sperm Output (x 109) Number of Covers per Day
200 3.54–4.04 2.36–2.69
250 4.74–5.24 3.16–3.49
300 5.97–6.44 3.96–4.29
350 7.14–7.64 4.76–5.09
  

Some stallions may have only a single testicle because the
other one is either retained or removed. Most of these stallions
can perform adequately as breeding stallions. The functional
testis will grow in size (i.e., hypertrophy) and usually produce
adequate numbers of sperm. The developmental disorder of
cryptorchidism will be discussed in a later section.
Evaluation of the Internal Genitalia
The majority of the internal reproductive structures of inter-
est can best be evaluated and imaged using rectal palpation
and ultrasonography. Most stallions tolerate transrectal palpa-
tion well with adequate restraint. The important structures are
located relatively close to the anus in the caudal pelvic region,
usually requiring the operator to insert only the hand into the
rectum. The accessory sex glands, ampullae, and pelvic urethra
are much easier to palpate and visualize on sexually stimulated
stallions. Next are descriptions of the appearance of these
structures, and the reader is referred to several publications
for more detailed information.986 Thorough evaluation of the
urethra is best accomplished using endoscopy, although ultra-
sonography can be used to supplement endoscopic findings.
Bulbourethral Glands. The paired bulbourethral glands, al-
though not usually palpable rectally because of the urethralis
and bulboglandularis muscles close to the ischiatic arch, are
easy to evaluate by ultrasonography. They are located 3 to 4
cm cranial to the anus, lateral to the pelvic urethra, and will
appear as variably sized yet distinct ovoid structures with mul-
tiple hypoechoic regions throughout the parenchyma.
Prostate Gland. In the stallion, the prostate is formed by a
central isthmus and two lateral lobes located on the caudola-
teral borders of each vesicular gland. Although not always
palpable rectally, the prostate is lobulated or nodular and
firm, distinguishing it from the smooth, thin-walled vesicular
glands lying medial to the prostatic lobes. Each prostatic lobe
measures 5 to 9 cm long, 2 to 6 cm wide, and 1 to 2 cm thick.
They appear as two symmetric and homogeneously echogenic
lobes visible lateral to the area in which the penile urethra
merges with the neck of the bladder. Hypoechoic dilations
within the gland’s parenchyma are usually evident in a teased
stallion.
Ampullae. The ampullae are the enlarged distal portions
of the deferent ducts measuring 1 to 2 cm in diameter and 10
to 25 cm in length. Palpable along the midline of the pelvic
floor over the neck of the bladder, they converge caudally and
pass beneath the prostatic isthmus to terminate in the seminal
colliculus in the dorsal wall of the pelvic urethra. Because of
the longitudinal orientation of the ampullae, sometimes they
are easier to find on rectal palpation. One can identify them
by ultrasonography by their hypoechoic central lumen sur-
rounded by a uniformly echogenic wall and a hyperechogenic
outer muscular layer. Orienting the transducer in a transverse
position inside the rectum can provide a good cross-sectional
image of the ampullae.
Seminal Vesicles. Palpation of the vesicular glands may be
easier after considerable teasing of the stallion. With adequate
stimulation, the vesicular glands can be felt as dilated and
elongated structures measuring 12 to 20 cm long and 5 cm in
diameter. The glands also are readily palpable in instances of
pathologic enlargement. With ultrasonography the vesicular
glands appear in a longitudinal section as a flattened oval to
triangular sacs, depending on the degree of sexual stimulation.
A thin echogenic wall surrounds a lumen containing fluid of
 CHAPTER 19
variable echogenicity. Increased echogenicity of vesicular
gland fluid is associated with the highly viscous gel fraction
produced by some stallions. The seminal vesicles are the acces-
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sory sex glands most prone to bacterial infections. Diagnosis is
based on the cytologic evaluation of the semen with the pres-
ence of leukocytes, which are often most elevated in the gel
fraction of the ejaculate.
Pelvic and Penile Urethra. Although the pelvic urethra can
be evaluated by transrectal ultrasonography, in most cases lit-
tle to no pathology is identified. Endoscopic examination is
often more reliable in identifying sites of hemorrhage, rents, or
abnormal mucosal surfaces, as well as allowing excellent visu-
alization of the bladder.987,988 The procedure is performed by
gently passing a 1-m endoscope with an outer diameter of 8 to
9 mm into the urethra of a sedated horse. The penis is washed,
and lidocaine gel and/or sterile lubricant are applied to the en-
doscope to facilitate passage. The clinician applies gentle and
constant pressure to pass 70 to 80 cm of the endoscope into the
urethra. Care must be taken not to inflate the bladder with too
much air because of a slight risk of rupture.
The ductules to the bulbourethral glands, which are con-
duits from the gland to the urethral lumen, are arranged as
two rows of 6 to 10 small openings dorsal and abaxial along
the urethra. The prostatic ductules are arranged in a similar
way and are visible as two groups of small openings lateral to
the ejaculatory orifices of the seminal colliculus. The ductules
to the bulbourethral gland are grouped about 2.5 to 3 cm cau-
dal to the prostatic openings.
One can identify the colliculus seminalis as a rounded
prominent structure found on the medial aspect of the dorsal
wall of the urethra approximately 5 cm caudal to the internal
opening of the urethra from the bladder. On either side of the
colliculus is an ejaculatory duct orifice, which is a small slit-
like diverticulum within which the ampullary ducts and ducts
of the seminal vesicles open. By passing the endoscope into
this orifice, one can visualize and evaluate the seminal vesicles.
Samples can be collected for culture in cases of suspected sem-
inal vesiculitis.989 Ventral and cranial to the seminal colliculus
are the openings of the urethral glands. These are visible lat-
erad on the widened pelvic portion of the urethra at the level
of the prostatic gland openings.
Endoscopic examination of the urethra is indicated in stal-
lions with clinical signs suggestive of pathology of the urethra
and accessory sex glands. In cases of hemospermia the bleed-
ing area may be visualized with the endoscope. These lesions
are most readily identified in the region of the ischiatic arch
and distal urethra. One should take care to assess the urethral
mucosa as the endoscope is passed forward because some irri-
tation and erythema of the mucosal lining often results from
the endoscopic examination. A false diagnosis of urethritis
may result if one assesses the mucosa while withdrawing the
endoscope.
Semen Collection and Evaluation
When a reproductive evaluation of a stallion is performed, two
ejaculates are collected approximately 1 hour apart. Semen
samples are collected with the use of an artificial vagina (AV).
Ejaculates are collected either with the stallion mounted on an
estrous mare or a breeding mount/phantom. Some stallions
will not ejaculate into an AV, in which case they are allowed
to breed a mare in estrus, and the drippings are collected from
the stallion as he dismounts the mare. Other means of semen
collection include aspiration of semen from the uterus and
Disorders of the Reproductive Tract 13231323
vagina of a recently bred mare, use of a large condom, and
pharmacologically induced ejaculation.
Artificial Vaginas
Several different types of AVs are commercially available.
Considerations for selecting an AV include size, cost, fre-
quency of use, and stallion preference. Temperature and pres-
sure of the AV are two important factors, and these can be
adjusted accordingly for individual stallions. Most stallions
favor warmer temperatures, such as 44°C to 48°C, for adequate
stimulation. Adequate pressure and nonspermicidal lubrica-
tion are also necessary and important factors for successfully
collecting semen.
If experiencing difficulty in obtaining an ejaculate, trou-
bleshooting the various aspects of the process is useful for
identifying the problem(s). Some instances can be caused by
incorrect positioning of the AV, which places the penis at an
awkward angle. Other instances include low AV temperature,
poor lubrication, or inadequate size. Manual pressure to the
glans and/or base of the penis or use of a warm compress can
increase stimulation. Jump mare selection can also be impor-
tant in that some stallions may prefer a mare in natural estrus
as opposed to an ovariectomized mare receiving exogenous
estrogen.
Colorado State University Model Artificial Vagina. The
Colorado State University (CSU) model is essentially a large
piece of PVC piping with a water bladder and a removable lin-
er. It has an inline filter to remove debris and the gel fraction
from the ejaculate. Advantages include its size and ability to
maintain proper temperatures in cold weather and for extend-
ed periods. Additionally, the relative rigidity of the CSU model
provides the operator better control over particularly aggres-
sive stallions. However, the size is also a disadvantage, making
it heavy and cumbersome. Heat shock is also a concern when
using this model because ejaculated semen is exposed to the
liner inside the AV (∼46°C), which is hotter than normal and
enough to cause thermal damage to spermatozoa. Finally, the
CSU model requires fairly precise assembly before use, caus-
ing it to be somewhat higher maintenance than other models
discussed below.
Missouri Model Artificial Vagina. The Missouri equine AV
is likely the most popular type of AV in the United States. Un-
like the CSU model, it requires less assembly and is made by
two molded layers of latex forming a water jacket. It also can be
fitted with an inline filter and is held in place with a leather or
neoprene case. The Missouri model is much less rigid than the
CSU model, and most stallions will ejaculate beyond the wa-
ter jacket, preventing semen from being exposed to increased
temperatures. This AV also allows for application of pressure
on the glans or base of the penis, which can be difficult with
the CSU model due to its relative rigidity.
Hanover Model Artificial Vagina. The Hanover model AV
is more common in Europe, is shorter and smaller in diameter
than the CSU AV, and is made of a hard rubber casing and in-
ner rubber liner. This AV should work well for most stallions.
Ejaculation occurs at or near the end of the water jacket. Pres-
sure of the Hanover model AV is critical. This AV has an ec-
centric opening. If the AV is too loose, then the nonengorged
glans can come through the ring, and glans dilation occurs on
the other side of the opening, which is painful for the stallion.
Polish or Open-Ended Model Artificial Vagina. The Polish
model is substantially different from other models on the mar-
ket. Using the open-ended AV, one can visualize the process of
 1324 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
ejaculation and can collect individual jets of presperm, sperm-
rich, or gel fraction of the ejaculate. This AV has been valuable
in the diagnosis of hemospermia, urospermia, internal genital
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tract infections, and ejaculatory failure.990 Additionally, this
AV has been useful in obtaining semen for commercial use
from stallions with hemospermia and urospermia, because
most of these affected stallions ejaculate the blood or urine
after the initial jets of sperm-rich semen. The open-ended
AV also has been useful in cryopreservation programs for
obtaining sperm-rich and bacteria-free ejaculates from stal-
lions. This method of collection is also used to obtain “clean”
ejaculates from stallions that are untrained and intolerant of
penile washing. The Polish AV also allows the use of high in-
ternal AV temperatures without the risk of sperm cell damage
because the ejaculate usually is emitted directly into a funnel
with an attached receptacle held by a second person. Open-
ended AVs are not currently available in the United States but
can be made by hand from plastic or polyvinyl chloride tubing
or by removing the coned portion of the Missouri University
model AV and using only the innermost rubber liner to form
a water jacket.
Disposable Artificial Vagina Liners. Sterile, plastic dispos-
able liners have become commercially available for most types
of AVs. These can be useful to reduce the risk of semen being
exposed to chemical residues or latex. Many stallions object to
these liners, however, and the number of mounts per ejacula-
tion increases. Breakage of the plastic liner may occur during
thrusting, and complete eversion of the liner may occur dur-
ing dismount. If stallions ejaculate on first entry into an AV
fitted with a disposable liner, the bacterial contamination of
semen is reduced sharply. As the number of entries into the
AV or the number of thrusts in the AV increases, however,
the bacterial contamination of semen also increases. As such,
ensuring that the stallion is properly stimulated and prepared
to breed is useful for limiting the number of mounts.
Care of Artificial Vaginas. The AV should be cleaned im-
mediately after each use, rinsed thoroughly with hot water,
and wiped clear of dirt, debris, and smegma. If disposable lin-
ers are not used, then the rubber liners should be immersed in
70% alcohol for 1 hour or more, rinsed thoroughly with hot
water, and hung in a dust-free, dry environment. To prevent
the accumulation of chemical residue, soaps and disinfectants
should not be used on the rubber equipment. If disposable
AV liners are not used or the AV and its liners are not thor-
oughly cleaned, then the AV may become an effective fomite
for spread of infectious or venereal disease. For these reasons,
many farms maintain an individual AV for each stallion at the
breeding farm.
Pharmacologically Induced Ejaculation
Several protocols have been published for the ex copula ejacu-
lation of stallions using various pharmacologic agents alone
or in tandem. The most commonly used drugs include xyla-
zine, imipramine, and prostaglandins.991-994 Semen collected
in this fashion is generally of low volume and high concentra-
tion because of the decreased contribution from the accessory
sex glands. One can use the resulting ejaculate for evaluation,
AI, or cryopreservation. The inability to obtain ejaculates on
a predictable schedule limits the commercial usefulness of
these methods. In one experiment, ponies were collected in 10
of 24 attempts using imipramine and xylazine.992 In selected
cases in which the stallion is physically unable to mount and
copulate, it is possible to obtain semen specimens with the
aid of pharmacologic agents. Under farm conditions, semen
is obtained in 25% to 30% of attempts. Keeping the stallion
quiet and undisturbed is important, especially after xylazine
has been administered.
A common protocol is to administer imipramine (2.2 mg/
kg, PO, once) approximately 2 hours before anticipated semen
collection.995 Xylazine (0.2–0.3 mg/kg, IV) is then given. Ejac-
ulation typically occurs shortly after xylazine administration
(e.g., 1–3 minutes) or as the stallion begins to wake up from
sedation (15–20 minutes). Although successful about 25% of
the time, the procedure is time consuming and unpredictable
for mare owners. The success rate may increase if the dosages
are altered for individual stallions.
Miscellaneous Methods of
Semen Collection
Condoms have been used in stallions that have an aversion to
ejaculating into an AV. Condoms should be large and nonsper-
micidal. Disadvantages of this method are the high risk of the
condom rupturing and contamination with debris. Aspiration
from the uterus and vagina of recently bred mares is another
option, but it is prone to contamination and does not lend well
for achieving an accurate volume of the ejaculate.
Semen Evaluation
This process involves the collection of stallions’ ejaculates and
analysis of various seminal parameters as follows:
1. Volume and color: One should record the color and vol-
ume (in milliliters) of the ejaculate. Generally the color of
the normal ejaculate ranges from watery to creamy white
opalescent and depends on the sperm concentration per
milliliter. Abnormal colors or volumes can indicate con-
tamination of the ejaculate with blood, urine, or white cells.
Normal volumes of light horse ejaculates range from 20 to
250 mL, with an average of 50 to 60 mL.996 Factors influ-
encing the volume are degree of sexual stimulation before
collection, breeding conditions, and foreign material in
the ejaculate. The volume of the ejaculate does not always
reflect the quality of the ejaculate, and other parameters
should be considered in light of the volume. When possi-
ble, distinction should be made between the volume of the
gel and gel-free portions of the ejaculate. Most AVs can be
fitted with an inline filter to separate these two fractions.
2. Sperm concentration: The number of sperm per milliliter
must be accurately estimated to calculate total sperm num-
bers in the ejaculate and how best to process semen for
further use. Sperm concentration, or density, is reported in
millions of sperm cells per milliliter. Average counts are be-
tween 100 and 300 million, but there are many factors that
can influence concentration, including season, frequency
of collection, testicular size, and age. Although subject to
as high as 10% variation, the Neubauer chamber or hemo-
cytometer is regarded as the gold standard for evaluation of
sperm concentration.997 Even though the hemocytometer
is regarded as the most accurate method to measure sperm
concentration, it is time consuming and therefore not regu-
larly used for routine counting of raw semen. The Nucleo­
Counter SP-100 (Chemometec, Allerod, Denmark) counts
sperm cell nuclei stained with the DNA-specific fluorescent
dye propidium iodide.997 The primary advantage to the
NucleoCounter is that it retains its accuracy even when
samples are contaminated with other debris, such as blood
or urine. It is also capable of evaluating sperm viability via
 CHAPTER 19
detection of nonmembrane intact spermatozoa. The main
disadvantage of this system is its significant cost. Other
systems, such as the SpermaCue (MiniTube, Tieffenbach
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Germany), Equine Densimeter (Animal Reproduction Sys-
tems, Chino, CA,USA, or the Accucell (IMV Technologies,
L’Aigle, France), are used. With all these systems it is critical
to have a very clean sample free of foreign particles, debris,
or extender. All these systems are accurate and repeatable at
the 100 to 300 million sperm range, but their accuracy di-
minishes out of this range.997 The computer-assisted sperm
analysis (CASA) systems can also be used for concentration
determination with an accuracy comparable to densimetry
methods. In addition to providing sperm numbers, the
CASA system reports sperm motility and the number of
fast-moving and progressively motile sperm.
3. Osmolarity and pH: Osmolarity of stallion semen ranges
between 290 and 310 mOsm. Values greater than 350
mOsm may indicate urospermia, and one should measure
the level of creatinine (normal semen creatinine concentra-
tion <2 ng/mL). Values less than 250 mOsm suggest water
contamination, and values over 500 mOsm reflect possible
lubricant contamination. Seminal pH ranges between 6.9
and 7.5, and values higher than those should warn the cli-
nician that there may be extraneous material in the ejacu-
late or an infectious process in the reproductive tract of the
stallion.
4. Spermatozoal motility: Sperm motility has long been used
as a method to estimate the percentage of viable sperm in
the ejaculate. Several methods have been used to evaluate
sperm motility, but all are used to determine the percentage
of total motile sperm (the percentage of sperm in the ejacu-
late with any movement) and the percentage of progressively
motile sperm (the percentage of sperm in the ejaculate
moving in a linear or progressive line). The CASA system
is the gold standard by which equine spermatozoal motility
is evaluated. This modality generates objective values for
sperm motility by counting and measuring individual cells
in set frames. It also provides data on sperm characteristics
such as linear velocity, linearity, path velocity, and lateral
head displacement. The relative expense of the CASA sys-
tem may preclude its use by some practitioners. Another
common method is visual assessment of sperm motility.
This involves placing a drop of semen on a microscope
slide with a coverslip and evaluating cell movement at 200
to 400× magnification using phase contrast microscopy.
This is the most widely used assay for evaluating sperm
motility because of its simplicity and low cost. However,
many factors can influence this mode of evaluation: indi-
vidual judgment, volume of the drop used, concentration
of sperm in the ejaculate, degree of contamination, degree
of agglutination, and temperature. Even under the most
tightly controlled conditions, repeatability of visual motil-
ity assessment is poor between technicians and laborato-
ries. Visual motility estimates of freshly ejaculated stallion
sperm have been reported to account for only 50% to 70%
of the variation of fertility in that sample. The correlation
is even worse (r = 0.3) when trying to predict fertility of a
frozen-thawed sample of semen based on postthaw motil-
ity.998 Although analysis of sperm motion with a computer
is more objective and provides a highly consistent way
of evaluating spermatozoa, the motility is but one factor
influencing stallion fertility and should not be overinter-
preted. In addition the formulas or settings for calculating
Disorders of the Reproductive Tract 13251325
the various motility parameters can differ between CASA
systems, so analysis of one ejaculate may differ between the
CASA systems used for each ejaculate.
5. Longevity of sperm motility: Duration of sperm motility
can be determined using raw, undiluted semen or extended
semen. For raw semen, a sample should be held at room
temperature and evaluated every hour until <10% motility
is observed. Semen from most normal stallions will main-
tain >10% motility for at least 4 hours. For extended semen,
it should be processed, cooled, and stored appropriately. It
can then be evaluated every 24 hours for the percentage of
total and progressively motile spermatozoa.
6. Sperm morphology: For any sperm morphology evalua-
tion, a minimum of 200 cells should be counted. Normal
sperm cells, as well as those with acrosomal, head, mid-
piece, droplet, and tail defects, should be recorded, with the
specific type of defect noted for each part. Although only
200 cells are counted routinely, sperm cells with more than
one defect should be recorded as such to help the clinician
evaluate the incidence of defects in a particular semen sam-
ple. One can evaluate cells as wet mounts under phase-con-
trast microscopy or differential interference contrast (DIC)
microscopy after fixation in buffered formal saline or 4%
glutaraldehyde. An antibiotic should be added to the fixa-
tive if samples are to be preserved for longer periods. Alter-
natively, cells can be evaluated after staining. One drop of
semen is well mixed with the stain and smeared on a glass
slide. Common stains currently used include India ink,
eosin-nigrosin, eosin-aniline blue, Giemsa, Wright, and
several others. The clinician should be aware that severe
changes in the osmolarity of the stain as well as mechanical
damage to the sperm could alter the normal morphology of
the cells. Morphologic assessment of the sperm may aid in
the diagnosis of certain pathologies because some defects
are associated with different anatomic regions or suggest a
specific reproductive pathology. Several attempts have been
made to try to correlate the percentage of morphologically
normal sperm present in a given ejaculate with fertility.
Unfortunately, there appears to be a lack of consistency
among clinicians in reporting sperm morphology. Among
the problems that clinicians encounter are the definition of
normal and abnormal in light of the tremendous range of
normality and the fact that little knowledge exists regard-
ing specific sperm defects that interfere with fertility. This
problem is even more vexing when a clinician is trying to
interpret the results from a referring veterinarian or a vet-
erinary technician. Some of these inconsistencies can be
avoided by recording specific morphologic defects rather
than grouping defects into primary and secondary, because
this last method erroneously assumes the origin of sperm
defects (testis and posttesticular, respectively).
Semen evaluation thus provides a slew of data to supple-
ment other examination findings. Calculation of the ejaculate’s
total volume and concentration will yield the total number of
sperm cells in the ejaculate. Determination of concentration
can be determined by manual, photometric, and fluorescence-
based studies. Assessment of individual sperm cells (i.e., mor-
phology) is performed to determine the number of normal
looking sperm cells. Longevity studies are useful when plan-
ning matings and frequency of collections, but caution should
be exercised in interpreting results because they do not ade-
quately represent the environment within the mare’s repro-
ductive tract.
 1326 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
More advanced techniques exist for evaluation of stallion
spermatozoa. These include testing the function of spermato-
zoa using the sperm chromatin structure assay, hyperosmotic
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swelling test, acrosomal reaction, and mitochondrial activity.
Alternatively or in addition, transmission electron microscopy
is useful for ultrastructural evaluation of individual sperm. It
is capable of identifying subtle yet serious lesions within indi-
vidual spermatozoa.
Hematologic and Endocrine Testing
Blood is commonly collected for evaluation as part of the
BSE and typically consists of a complete blood count (CBC),
fibrinogen, biochemistry profile, and testing for equine arte-
ritis virus (EAV) if indicated. Endocrine testing is also com-
monly performed and concentrations of resting testosterone,
estradiol, FSH, and LH are evaluated. In addition to screening
for underlying diseases or disorders, these tests are also useful
for establishing a baseline of normal values should an illness
arise at some separate point in time.
Endocrine testing is often considered an adjunctive test but
is nonetheless useful in the diagnosis of specific disorders. In
particular, it allows for detection of primary testicular issues
such as testicular degeneration. Because spermatogenesis
relies on an intricate network of various autocrine, paracrine,
and endocrine signals, aberrations in circulating gonadotro-
pins and sex steroids may signal the onset of testicular dys-
function. Shown in Table 19.12 are examples of how serum
concentrations of LH, FSH, testosterone, and estrogen conju-
gate can differ by season in normal stallions. Differences are
also seen when comparing the concentrations of these hor-
mones between fertile and subfertile stallions. Subfertile stal-
lions have higher circulating gonadotropin concentrations,
whereas estrogen conjugate is lower and testosterone remains
relatively steady regardless of season.999
Microbiologic Testing
Screening for STDs should also be performed. Specific dis-
ease screening recommendations depend on the country
where the horse has lived, currently resides, or where the
horse may be shipped following the evaluation. Gener-
ally culture swabs of the penis/prepuce, urethral fossa, and
urethra (both preejaculation and postejaculation) are taken
TABLE 19.12 Seasonal Effects of Luteinizing Hormone, Follicle-Stimulating Hormone, Testosterone, and Estrogen Conjugate
in Fertile and Subfertile Stallions
Fertile (n = 8)
Hormone Nonbreeding Breeding
(ng/mL) Season Season
Luteinizing 2.4 ± 0.8 6.6 ± 0.8
hormone
Follicle- 4.7 ± 0.5 6.1 ± 0.7
stimulating
hormone
Testosterone 0.69 ± 0.14 1.14 ± 0.17
Estrogen 232 ± 29 216 ± 20
conjugate
Values are presented as the mean ± SEM.
Adapted from Roser JF, Hughes JP. Seasonal effects on seminal quality, plasma hormone concentrations, and GnRH-induced LH response in fertile and
subfertile stallions. J Androl. 1992;13:214-223.
and submitted for aerobic culture as a minimum in an SRE.
During the breeding season, serial testing is performed to
monitor for potentially pathogenic agents, such as Klebsiella
spp. and P. aeruginosa. In certain areas of the United States,
novice stallions will need a negative EVA serum titer either
periodically or immediately before vaccination. Recently
imported stallions will be subject to testing mandated by
the USDA-APHIS as described earlier. Imported stallions
are routinely tested for CEM by collecting swab samples of
the external genitalia. In accordance with the USDA-APHIS,
previously active breeding stallions also require test breed-
ing of at least two mares, from which serial swabs are col-
lected before and after breeding. Twenty-one days after the
last test breeding, serum is collected for a CF test. The reader
is directed to the USDA-APHIS Contagious equine metritis
fact sheet1000 for more information on the testing protocol.
Again, the clinician is referred to the country’s regulating
body and regulations regarding sexually transmissible dis-
eases of stallions when it comes to determining what testing
must be performed.
Cytogenetic Testing for Markers of Fertility
This particular means of evaluating the breeding potential
and soundness of stallions is still in its infancy. Since the horse
genome project was completed in 2007, equine researchers
are now discovering key relationships between DNA and the
onset of certain diseases and disorders. This has allowed for
the development of sensitive testing techniques to monitor
or diagnose various hereditary diseases. These will all be
discussed in another chapter, but one important disorder
is a genetic link that has been found for impaired acrosome
reaction (IAR), which is a known cause of infertility in many
mammalian species. Researchers at Texas A&M University
recently identified a susceptibility gene in horse chromo-
some 13 in FK506 binding protein 6 (FKBP6) in horses with
IAR.1001 This test can be useful as either a screening test for a
prospective stallion or a diagnostic test in cases of unknown
subfertility. The author currently uses the Animal Genetics
Inc. (Tallahassee, FL) laboratory for most genetic testing,
whereas the testing for IAR is done exclusively at the Depart-
ment of Integrative Biosciences, Texas A&M University
(College Station, TX).
Subfertile (n = 6)
Nonbreeding Breeding
Season Season
9.2 ± 1.4 12.6 ± 2.8
13.6 ± 3.1 14.5 ± 3.3
0.75 ± 0.08 0.88 ± 0.13
169 ± 45 186 ± 59
 CHAPTER 19
Summary and Epicrisis for Stallion Reproductive
Evaluations
As mentioned at the beginning of this section, stallion repro-
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duction involves many different factors. Attempting to account
for all of them and predict fertility is currently impossible.
Consequently, it now seems common practice not to assign
stallions a particular status (e.g., satisfactory, unsatisfactory,
status deferred) but to summarize the findings and offer rec-
ommendations for future management.
Y MANAGEMENT OF BREEDING
STALLIONS
Nutrition
Specific feeding programs are at the discretion of the stud farm.
General horse husbandry practices apply, and it is important
to account for the method of breeding (e.g., in-hand, pasture,
collection with an AV). Stallions in live-cover programs with
book sizes of 60 or more mares may be asked to breed two to
three times a day for several days in a row, creating a significant
caloric demand. Providing adequate forage, a balanced con-
centrate, and fresh water ad libitum is the principal concern
in the management of stallions. Average breeding stallions
(500–600 kg) will usually consume 6 to 10 quarts of concen-
trate (12%–14% protein) a day. New rations and supplements
should be introduced gradually to avoid gastrointestinal upset.
Healthy and active stallions should enter the breeding sea-
son approximately one body condition score higher (on a scale
of 1–9) than normal, realizing they shed this weight quickly.
For most stallions, an ideal body score is 5 to 5.5 of 9, so start-
ing out at 6 to 6.5 of 9 is generally acceptable and unlikely to
have ill effects if the stallion is otherwise healthy.
Care should be taken not to overfeed stallions. Obesity can
have negative and often serious consequences (e.g., predispo-
sition to colic, laminitis, metabolic disease) that can adversely
affect a stallion’s breeding performance. Moreover, stallions
should not experience extreme weight fluctuations because
dramatic swings can hinder both health and fertility.
There is some evidence supporting the efficacy of certain
supplements to improve seminal quality in stallions. Feeding
OM3FAs is supported by evidence-based research demonstrat-
ing their positive effects. For example, Brinsko et al. reported
improvement in sperm motion characteristics in cooled
and frozen semen after stallions were fed a DHA-enriched
nutraceutical for 14 weeks.301 Another study demonstrated
increased concentrations of OM3FAs in seminal plasma and
total sperm output in stallions fed an OM3FA supplement
but no improvement in sperm motility. Both of these stud-
ies used a marine-based source of OM3FAs.1002 Algae-based
supplements and flaxseed are other sources of OM3FAs and,
at least anecdotally, appear more palatable than those that are
marine based. Studies describing a direct relationship of feed-
ing OM3FAs and improved fertility are lacking.
Other nutritional supplements used in the breeding man-
agement of stallions are antioxidants (e.g., vitamins C and
E) and acetyl-l-carnitine. The former may be beneficial in
reducing oxidative stress on spermatozoa, whereas the latter is
thought to enhance motility by stimulating β-lipid oxidation
in sperm mitochondria. Scientific evidence supporting the use
of these products is lacking, but anecdotal reports are mostly
favorable. The efficacy of antioxidants is somewhat curious in
Disorders of the Reproductive Tract 13271327
that one study showed that the most fertile ejaculates from dis-
mount samples collected from live-cover matings were those
with the highest level of oxidative stress.1003 Nevertheless a
plasma membrane surrounds the entire spermatozoon, so the
relative intactness of this membrane is thought to be closely
related to sperm quality. Because antioxidants may suppress or
quench the damaging effects of free radicals on lipid peroxida-
tion,1004 supplementation, in theory, may assist in improving
sperm quality.
Exercise
Exercise is an important yet sometimes overlooked part of
stallion management. Programs should be based on the indi-
vidual stallion and account for his current and desired weight,
soundness, anticipated book size, environment, and other
health issues that may preclude the stallion from receiving
adequate exercise. Methods for exercise include forced (e.g.,
riding, lunging, mechanized walkers) and passive (e.g., turn-
out in a large paddock for several hours a day). The means of
exercise will vary from farm to farm, but the objective should
be to keep stallions fit and their mind occupied, because exer-
cise engages them both mentally and physically. In humans,
physical fitness has proven advantages in maintaining vigor
and preventing disease. It thus seems logical, albeit a bit
anthropomorphic, that horses can reap the same benefits.
Length of forced exercise is usually predicated on the
horse’s level of fitness, whereas turnout should be kept on a
regular schedule and consist of several hours of free grazing.
Numerous large-scale breeding operations keep their stallions
in training or continue to exercise them throughout their stud
careers. One experiment showed stallions subjected to a mod-
erate amount of exercise had a decline in number of morpho-
logically normal spermatozoa post exercise compared with
those obtained preexercise. No other seminal parameters (e.g.,
concentration, gel volume, total sperm) differed between the
preexercise and postexercise samples.1005
If farm management practices or the horse’s physical con-
dition preclude active exercise, then paddock or round-pen
turnout can be used. Paddock size is usually relegated to no
more than a few acres. It can be helpful to place water and feed
buckets in different areas to encourage increased movement.
Turnout during inclement weather is at the discretion of the
farm, but most horses are very resilient to adverse environ-
mental conditions.
Herd Health Management
Routine hoof and dental care, as well as targeted vaccinations
and dewormings, provide a solid foundation to manage the
overall health of stallions. Similar to the previous consider-
ations, herd health management will vary based on the par-
ticular farm and location.
Timing of vaccinations is important when managing active
breeding stallions. Although a relatively low risk, especially
considering the advancements made in vaccine quality over
the past two decades, adverse events can still occur following
immunizations. Untoward effects, whether local or systemic
in nature, can hinder breeding performance. For example,
local swelling at the site of an injection can cause soreness and
reluctance to breed. Alternatively or in addition, a fever can
negatively affect spermatogenesis because of secondary ther-
mal stress.
Some practitioners choose to limit or postpone vaccinations
during the breeding season. The author usually gives booster
 1328 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
vaccines in late December or early January so that any issue
resulting from vaccination can be resolved before the begin-
ning of the breeding season (mid-February). Boosters are also
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given, but evenly spaced out, in the summer and fall. Since
stallions are at risk for acquiring infectious diseases because of
contact with outside mares, vaccination against equine rhino-
pneumonitis can be performed every 2 to 3 months.
Vaccination against EAV, the causative agent of EVA, is
required in some states for active breeding stallions because
this virus can be shed in bodily fluids such as semen and respi-
ratory secretions. The most pressing concern with EAV is the
potential to cause abortion storms or neonatal death in naive
pregnant mares.243 The reader is encouraged to contact his or
her state veterinarian’s office for rules and requirements per-
taining to vaccination against EVA in breeding stallions. Some
stallions can transmit EAV in their semen (i.e., shedding stal-
lions), so the stud farm should disclose if a stallion is a chronic
shedder of EAV. Guidelines for breeding a mare to an EAV-
shedding stallion are provided by the American Association of
Equine Practitioners.1006
Breeding Methods
Live Cover
Also referred to as natural service or in-hand mating, live-
cover breedings are commonly performed in commercial
Thoroughbred operations throughout the world. Briefly, when
an estrous mare is identified and deemed suitable for mating,
she is brought to the breeding shed where she is teased and
prepared routinely for breeding by washing of the perineum.
Mares are usually restrained with a lead shank and a nose
twitch, and padded leather “kick” boots are placed on the
hind feet. Some sheds apply a neck shield or “cape” around
the mare’s cervical spine to provide extra protection. An exam-
ple of typical preparation of a mare for a live-cover mating is
shown in Fig. 19.26. The stallion is presented to the mare and
teased until properly stimulated. He is then given a cue to
mount, and, on doing so, an attendant will direct his penis into
the mare’s vagina. When ejaculation occurs, the attendant will
apply his fingers to the base of the penis to feel for character-
istic pulsations and fremitus of emission and ejaculation. As
the stallion dismounts, the attendant will collect the drippings
from the penis, which will undergo microscopic evaluation for
the presence of live sperm, offering further confirmation of
ejaculation. The sequence of events is shown in Fig. 19.27.
Semen Collection Using a Live Mare as a
Mount
Selection of a suitable mount or “jump” mare depends on the
experience and breeding mannerisms of the stallion and farm
resources. For example, the inexperienced stallion may need to
be taught to mount the mare from the rear quarters. This train-
ing requires a disciplined, cooperative mare that will tolerate
being mounted from the side. Some stallions vocalize loudly
in the breeding shed and may frighten maiden or timid mares.
The mount mare needs to tolerate a certain amount of nipping
and biting of the neck, shoulders, flank region, and hocks to be
suitable for some stallions. Mares with foals at their sides are
frequently protective of their foals and less cooperative than
barren mares. The mount mare also should be an appropriate
size match for the stallion. For routine breeding farm activi-
ties, the reliance on an estrous mare as a mount has signifi-
cant shortcomings because the mare must be followed with
FIG. 19.26 Example of a mare being restrained for a live-cover mating.
teasing and ultrasound to ensure she is in estrus. Addition-
ally, in a cooled, shipped semen program, the breeding farm
may not have access to nonpregnant mares, particularly at the
end of the breeding season. Therefore some breeding farms
maintain one or more ovariectomized mares as mount mares.
One should select from these ovariectomized mount mare
candidates based on their size, tolerant attitude toward han-
dling, and strong estrous behavioral signs as intact mares. A
mare with gonadal dysgenesis, karyotype (XO), may be a good
mount mare candidate without requiring an ovariectomy.
Most ovariectomized mares perform well as mount mares
while being restrained with a twitch or lip chain placed on the
upper gum. In some cases it may be necessary to administer a
low dose of estradiol cypionate (0.5–4 mg, IM) at intervals of 3
days to 3 weeks to maintain receptivity by the mare.
During the semen collection process, the mount mare usu-
ally is restrained using a twitch. Hobbles also may be applied
to rear pasterns or hocks, but there is risk of the stallion
becoming entangled in the hobbles if the collection procedure
goes awry. Protective boots can also be placed on the hind feet
to minimize damage if the mare does kick, and hind shoes
should always be removed. The long tail hairs at the base of
the mount mare should be wrapped to prevent the tail from
interfering with deflection and entry of the penis into the AV.
Breeding Phantom
The breeding phantom, dummy, or mount consists of a struc-
ture suitable for stallion mounting that is usually a cylindri-
cal barrel or tube mounted in a stationary position that is the
approximate size of the body of a mare the stallion would
breed (Fig. 19.28). The barrel is usually covered with 1 to 2
inches of firm padding. The padded cylinder then is covered
by a tough, nonabrasive cover that is free of wrinkles. Stallions
that repeatedly mount and dismount a phantom can abrade
the medial aspects of their forearms and carpi. Wraps can be
applied to minimize trauma. The stallion should be taught to
dismount the phantom in a controlled manner by backing off
of the mount rather than making a side dismount. The diam-
eter, length, and height of the phantom should be dictated by
stallion size and preference, with most light horse stallions tol-
erating a total diameter of 20 to 24 inches. The struts of the
phantom should be far enough from the mounting end to pre-
vent injury to the hindlegs of the stallion during mounting and
 CHAPTER 19 Disorders of the Reproductive Tract 13291329
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A B

C D

FIG. 19.27 Sequence of events for a live-cover mating.

dismounting. The height and the angle of the phantom should
be adjustable to accommodate older stallions, stallions with
hindlimb lameness or musculoskeletal issues, and stallions of
varying stature.970,1007
Adequate space should surround the phantom for the safety
of the handlers and to allow a teaser mare to be positioned
alongside or in front of the phantom if additional stimulation
is needed. Many stallions are trained to mount the phantom
even when the teaser mare is not close to it.
When a phantom is used to collect semen from a stal-
lion, the stallion should approach the mount in a controlled
fashion, mount the rear of the phantom, and use his fore-
limbs to stabilize himself by grasping the padded barrel of
the mount. Once the stallion is properly situated, the oper-
ator approaches from the left or near side of the stallion,
deflects the penis into the AV using a right, overhand grip,
and stabilizes him- or herself on the near side of the phan-
tom as the stallion services the AV. While on the left side of
 1330 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
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FIG. 19.28 Example of a breeding phantom used for collection of stal­
lion semen in an artificial insemination program. The phantom is secured
in the ground by a single and sold strut. The body or barrel of the phan­
tom is reinforced with soft, nonabrasive material for comfort.
the stallion (and phantom), the operator deflects and stabi-
lizes the base of the penis with the right hand. This prac-
tice minimizes potential injury to the penis and prepuce
during thrusting by the stallion. Some phantom mounts are
fitted with an AV installed within the posterior end, which
works well for some stallions and requires only one per-
son for the collection procedure. The only disadvantage of
indwelling AVs is that occasionally the stallion’s penis can
be traumatized by incorrect insertion. In addition, some
stallions need manual stimulation of the glans penis, which
is easier to provide when the operator has control of the
AV. Stallions regularly used for live-cover breedings can be
difficult to train to a phantom. For this reason, certain cir-
cumstances may require access to an estrous mare to facili-
tate semen collection.
Measuring Reproductive Performance
Formulas for evaluating reproductive efficiency of stallions
are presented below. These measures are useful for comparing
stallions among and within farms. They also offer insight into
breeding and farm management and can help identify areas of
concern.
Per Cycle Pregnancy Rate = No in Foal / No Covers
No Doubles 100 %
Seasonal Pregnancy Rate = Total No Pregnancies /
Total No Mares Bred 100 %
Total No. Covers
Covers Per Pregnancy =
Total No. Pregnancies
Organization and tabulation of these data are most commonly
done electronically. Computerized spreadsheets can assist
with data collection and analysis. Charts and graphs compar-
ing various reproductive parameters are useful for summariz-
ing and comparing findings in a concise yet comprehensive
manner and can be used to monitor patterns of breeding
performance.
Novice or Maiden Stallion
The arrival of a new stallion to a breeding farm is usually an
exciting time. These stallions have proven superior in their
respective disciplines and are thus of high value both finan-
cially and emotionally. Although the urge exists to “see what
they’re made of ” with respect to breeding behavior, good
managers believe it is best to give them time to familiarize
themselves with their surroundings before initiating breeding
activity. Documenting and addressing previous health issues
or injuries should also be done so that the stallion remains fit
and sound for breeding. This transition, or let-down, period
is variable (2 weeks to 2 months) and should remain fluid to
allow the stallion to settle into his new career. The let-down
period typically includes the following:
• Quarantine to reduce risk of transmissible disease
• Conditioning and acclimatization to new surroundings
• Establishment of a routine
• Diagnostic testing
Most stallion managers are also cognizant of the vari-
ous mental adjustments that a stallion goes through as he
transitions to a new environment. Moreover, each stallion is
an individual and should be treated as such. Stallions must
remain respectful to prevent aggression toward their han-
dlers and other horses.1008 Novice stallions must be treated
with patience, positive reinforcement, and in some instances,
perseverance. Unnecessary punishment and rough han-
dling can aggravate a problem and may result in breeding
disinterest.
Following the let-down period, maiden stallions are intro-
duced to mating via test breeding of estrous mares. This
process allows for conditioning of the stallion to the farm’s
breeding procedure and for evaluation of the stallion’s breed-
ing behavior and seminal characteristics. A test mare recently
screened for EVA and CEM is prepared as for a normal live
cover. The stallion is introduced to the mare and allowed to
sniff and interact with the mare in a respectful manner. Both
patience and repetition are required during the test breeding
process because mating is a new experience for these stallions.
Some stallions may require only a few breeding sessions before
management is adequately satisfied that the stallion is trained;
others may require several attempts before they display any
interest in breeding. Dismount samples are routinely evaluated
for the presence of live, motile, and morphologically normal
spermatozoa. A stallion is considered “trained” once he will-
ingly breeds a mare in an efficient and proper manner. Shown
in Video 19.3 is a novice stallion presented to an estrous mare
for the first time. This stallion displayed excellent libido and
bred the mare in the relatively short period. For stallions des-
tined for live-cover operations, the author prefers to train stal-
lions to the mare first. The collection of entire ejaculates via an
AV can be performed at a later date.
Starting novice stallions under lights is used in some pro-
grams. No proven benefits have been demonstrated from
this practice. Anecdotally, and as discussed previously, the
additional photoperiod may stimulate reproductive func-
tion and prepare the stallion for success early in the breeding
season.
 CHAPTER 19
Y DISEASES AND DISORDERS OF
INTACT MALE HORSES
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Abnormal Behavior
Manifestations of abnormal behavior are numerous. Examples
are provided in Table 19.13 along with potential causes for
deviant sexual behavior. McDonnell reviewed the incidence of
behavioral problems in 250 stallions over a 5-year period.978
More than 50% of the cases had complaints related to poor
libido or excessive aggressiveness. Of those, nearly half were
described in stallions with no previous sexual experience. The
rest were divided evenly between experienced stallions with
low sexual interest and those with increased aggressiveness.
Mounting and erection dysfunction accounted for 11% of
complaints, whereas ejaculatory problems accounted for 25%
of the total cases. Other problems, such as self-mutilation and
various stereotypies accounted for 11% of the reported cases.978
For clinicians, it is important that dysfunctional behavior
is interpreted relative to the expectations of the breeding out-
fit.1009 For example, stallions requiring 30 minutes or more to
mount and ejaculate or those needing several mounts before
ejaculation may be considered unacceptable in some inten-
sive management situations. On the other hand, a stallion
that takes several hours to achieve an erection, mount, and
ejaculate may be considered normal if he breeds only two
or three mares during the entire breeding season in pasture
conditions.
Low Libido
Lack of adequate sex drive is the most common behavioral
issue in breeding stallions.978 Many factors can be at play,
including management practices and environmental cues. For
example, timid stallions housed next to dominant stallions
may show a lack of libido because of perceived subordination
to the dominant stallion. Other stallions may have an aversion
to or preference for a particular color of mare. Lack of libido
may be observed in experienced stallions toward the end of
the breeding season, particularly in heavily used or overused
animals. This problem can be corrected by decreasing the fre-
quency of service or collection. Stallions that have been kicked
by mares or negatively reinforced for displaying sexual behav-
ior during performance may demonstrate reduced sexual
desire. It is thus prudent to consider the history, health, and
management of the stallion from many different perspectives
when determining the cause of low libido.
Treatment of a stallion with low sexual drive is best directed
at correction of the underlying problem, but assessment of the
nature of the problem is often difficult. One may try several
alternatives, including
TABLE 19.13 Signs of Abnormal Stallion Behavior and
Potential Causes
Signs Causes
Low libido Pain
Paraphilia Secondary health issues
Timidness Mare preference
Erectile failure Environmental changes
Ejaculatory failure Management changes
Self-mutilation Previous adverse experience
  
Disorders of the Reproductive Tract 13311331
• C hange of stimulus mare or environment
• Breeding or collecting another stallion in the presence of
the low-libido animal
• IV administration of GnRH, 50 μg, 1 to 2 hours before
breeding or hCG, 5000 to 10,000 IU, 1 hour before breeding
• IV administration of diazepam or midazolam at a dosage
of 0.05 mg/kg (maximum 20 mg) 10 to 15 minutes before
breeding to reduce inhibition of sexual behavior in some
stallions
• Single injection of a short-acting testosterone
The efficacy of most of these treatments is dependent on the
individual stallion and the primary problem(s). Some of these
treatments may have adverse effects. For example, chronic
administration of steroids, particularly androgens, is well doc-
umented to negatively affect spermatogenesis.970 Therefore
treatment of stallions with exogenous steroids and particularly
androgens to improve libido should be measured carefully
with respect to the risks and potential benefits. Consequently,
treatment is typically reserved for use when other means of
increasing arousal have failed. Current recommendations are
treatment with an initial dose 80 to 100 mg (IM) of testoster-
one cypionate and maintaining serum concentrations at 2 to
4 ng/mL. The effect typically lags a significant time following
treatment (5–8 days). Anecdotal reports of topical application
of testosterone cream to the penis to improve tactile stimula-
tion have been reported but not rigorously studied.
Erection Failure
The inability of a stallion to develop and maintain a normal
erection despite normal libido may be related to anatomic
issues. Possible problems include vascular damage associated
with traumatic injuries or neurologic problems associated
with other penile or lumbosacral compromise.991
Medical (e.g., administration of vasoactive substances) and
surgical (e.g., penile implants) options may be considered.
Unfortunately, evidence-based research supporting these
methods is lacking. Sildenafil (Viagra, Pfizer, New York, NY)
has long been discussed but does not currently have a reported
dose or effect in horses.
Ejaculatory Failure
Some stallions show normal precopulatory behavior, mount-
ing, and intromission but fail to ejaculate. These stallions may
become exhausted or frustrated, displaying aggressiveness to
the mare or handler. For this condition it is important to rule
out musculoskeletal or orthopedic pain such as degenerative
joint disease. If suspected, trial treatment with an appropri-
ate dose of a nonsteroidal agent can be of benefit. Circulatory
disorders, such as iliac thrombosis, have also been associated
with ejaculatory failure.
Despite being difficult to diagnose, psychological problems
can lead to ejaculatory dysfunction. In many instances, a his-
tory of a traumatic incident while breeding is closely associ-
ated with the onset of ejaculatory failure. If the stallion refuses
to ejaculate only under specific circumstances, such as into an
AV or when breeding a mare, then a systematic approach is
important to determine the problem.
A variety of behavioral and managerial aids have been used
to help stallions ejaculate.1010 One should adapt these aids
according to the physical condition of the stallion (i.e., stal-
lions that cannot achieve a full erection; stallions that have
difficulty mounting; stallions that refuse to ejaculate after nor-
mal erection, mounting, thrusting, and belling of the glans).
 1332 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
Neither mounting nor full erection is necessary for ejacula-
tion. Stallions that have difficulty mounting can be taught to
ejaculate on the ground by manual stimulation of the penis
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or with an AV. Stallions with erection problems can ejaculate
if proper stimulation is given to the penis. One can achieve
proper stimulation to the penis by raising the temperature
of the AV or by applying hot towels to the base of the penis
during thrusting. It is also important to consider changes in
footing and surroundings, stimulus mare, and handlers before
implementing pharmacologic therapy.
Therapeutic regimens for ejaculatory dysfunction are
empirical and include those already mentioned for the treat-
ment of low-libido stallions. In addition, PGs, oxytocin, and
xylazine have been used to aid stallions in the process of
ejaculation. Oxytocin and PG also have been used to treat
azoospermia caused by ampullary blockage.1011 The tricyclic
antidepressant imipramine can be given to lower the thresh-
old for ejaculation in stallions.995 As discussed previously,
varying success rates are obtained when using these agents
for either short-term or long-term management of ejacula-
tory failure.
Self-Mutilation
Self-mutilation is a highly complex behavioral syndrome that
can include self-biting, stomping and kicking, rubbing, and
lunging at objects. According to McDonnell, three distinct
types of self-mutilation occur.1012 Type I represents a normal
behavioral response to continuous or intermittent unrelieved
physical discomfort. Type II, seen in stallions and geldings,
can be recognized as self-directed intermale aggression. This
behavior includes certain elements of the natural interactions
typical of encounters between two stallions, except that the
stallion himself is the target of his intermale behavior. Type III
involves a quieter, often rhythmically repetitive or methodical
behavioral sequence of a stereotypy (e.g., nipping at various
areas of the body in a relatively consistent pattern, stomping or
kicking rhythmically against an object). Some researchers have
speculated that self-mutilation has a genetic component. The
prevalence of self-mutilation of one form or another has been
observed in as many as 2% of domestic stallions.1013 Among
and between stallions, self-mutilation varies in frequency and
intensity and can reach levels that threaten the stallion’s fertil-
ity and even his life.
Careful evaluation of the horse’s behavior is often neces-
sary to distinguish the specific type of self-mutilation. Type
I self-mutilation can be eliminated by relieving the source of
discomfort. For types II and III, understanding of intermale
interactive behavior of horses and the environmental factors
triggering the self-mutilating form can be useful in guiding
humane management or behavior modification. Pharmaco-
logic manipulation and nutritional changes may be useful
adjuncts in the management of this condition.
Although self-mutilation is usually limited to postpubertal
horses in type II or type III, it is not limited to confined ani-
mals like some stereotypies. In some animals the problem is
exacerbated on presentation of a mare to a confined stallion or
breeding in the presence of another stallion.1014 The compul-
sive behavior seems to be more dramatic during the breeding
season.
Self-mutilation may be a problem exacerbated by olfactory
stimuli. In some horses, smelling their manure triggers this
behavior. The stallions often mistakenly recognize themselves
as a threat, triggering the compulsive behavior.
Therapy of this complex syndrome depends on the type of
self-mutilation and its underlying causes. Potential strategies
include pain management, surgery, regular exercise, stall toys,
and companion animals. Products to reduce the olfactory
stimuli can be used, and diet modification to decrease carbo-
hydrates have been used with some success. Treatment with
behavior supplements, such as a milk-protein–based product
(Zylkene; Vetoquinol USA, Inc., Fort Worth, TX) or phero-
mone mimic (Confidence EQ; Ceva Animal Health, Lenexa,
KS) may help some stallions, but their efficacy is unproven.
Physical restraints such as head cradles or muzzles most likely
lead to development of another self-mutilating behavior. In
extreme, inhumane, and refractory cases, castration of the
stallion has eliminated the problem for type III self-mutilation
but not for the other types. Therefore an accurate diagnosis is
a critical component of the treatment protocol.
Other Behavioral Problems
Some stallions may have behavioral traits or vices that adversely
affect their breeding ability. Overly aggressive stallions may be
too dangerous to handle because of savaging the handlers or
the mare. This aggression may be caused by frustration, past
breeding experience, and/or potentially paraphilia. Aggres-
sion is best managed with an experienced and patient handler
and identification and elimination of potential management
and environmental cues that lead to adverse behavior.
Stereotypies can also affect reproductive performance.
Cribbing, weaving, stomping, and wall kicking are all exam-
ples that can lead to secondary health issues (e.g., colic, weight
loss, lameness). Because these are thought to be born of bore-
dom, providing mental stimulation via enrichment activities
(e.g., rubber ball, companion animal) may help. Some stereo-
typies are a result of physical discomfort (ulcers, laminitis, and
neuropathic pain), and general health causes for discomfort
should always be ruled out.
Abnormalities of the Penis and Prepuce
Clinicians must be able to accurately identify pathologic
conditions of the external genitalia to make sound decisions
regarding the therapy and management of stallions. Acquired
conditions may be reversible by surgical or other means, but
diagnosis of irreversible or terminal conditions must be well
substantiated because they could have a significant effect on
the viability of the breeding operation. Ethical considerations
are also pertinent because some genetic diseases can have a
significant effect on the breed as a whole.
Developmental Conditions
As reviewed previously, the sexual development of the equine
embryo to a mature normal stallion capable of successfully
breeding requires multiple genetic factors, pathways, and
endocrine events to occur and proceed normally. Horses with
genetic abnormalities can vary in their genotype, anatomic
features, and behavior. The most common causes of congenital
defects are hermaphroditism, XY sex reversal, and testicular
feminization or androgen insensitivity. Previously described
as intersex conditions, they are now referred to as disorders of
sexual development (DSD).1015,1016
Hermaphrodites are classified on the basis of the type of
gonadal tissue present. True hermaphrodites have testicu-
lar and ovarian tissue, whereas pseudohermaphrodites have
either testes (male pseudohermaphrodite) or ovaries (female
pseudohermaphrodite). Various combinations of male and
 CHAPTER 19
female internal and external reproductive organs can exist
and have been described.1017,1018 The most commonly diag-
nosed DSD is the male pseudohermaphrodite, which has a
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mostly female phenotype but testes instead of ovaries. A com-
mon clinical presentation is a “mare” with a small vulva and
an extremely large clitoris or what appears to be a glans penis
with an increased anogenital distance. Behaviorally, the horse
may display stallion-like behavior because of the presence of
testicular tissue. Female pseudohermaphrodites are much less
common and are characterized by a male phenotype, but the
animal’s internal gonads are ovaries instead of testes.
Horses with XY sex reversal syndrome are characterized
by female external genitalia but a normal 64XY karyotype.
Androgen insensitivity or testicular feminization syndrome is
a well-characterized genetic disease in human beings and in
some domestic species. Animals have a normal XY karyotype
and display male behavior but have a female phenotype. The
syndrome has two possible causes: a mutation at the level of
the gene that codes for the androgen receptor or a deficiency
in 5α-reductase, the enzyme responsible for conversion of tes-
tosterone to the active androgen DHT.1019 In either situation
the reproductive tract is underdeveloped and the female phe-
notype predominates.
Genetic defects can be tentatively diagnosed by visual
inspection of the external genitalia, rectal palpation, and ultra-
sonography. However, a definitive diagnosis requires cytoge-
netic evaluation by a commercial molecular and cytogenetics
laboratory.
Segmental aplasia of the vas deferens or the epididymal
duct has also been reported.1020 These conditions can render
the stallion sterile in the case of bilateral aplasia, due to the
inability to emit and ejaculate spermatozoa. Other aberrations
in gonadal development can potentially lead to improper germ
cell development and/or maturation.
Phimosis is the inability to protrude the penis and can be
congenital. In neonatal colts, the penile frenulum is com-
monly broken down early in life but can occasionally persist.
The most common presenting complaint is an abnormal urine
stream; inspection of the colt’s prepuce and penis reveals a pal-
pable frenulum and the glans penis is reflected caudally. This
condition is usually self-limiting, but transection of the band
can be performed to hasten resolution.
Acquired Conditions
Paraphimosis occurs when the penis is unable to retract back
into the sheath. This condition is seen in cases of severe mal-
nourishment or exhaustion, neurologic disease, adminis-
tration of certain psychoactive drugs, and trauma. Whether
alone or in combination, these causes culminate in chronic
flaccidity and extensive edema of the penis.1021,1022 Because
venous return is impaired, the condition can progress to bala-
noposthitis, which includes the development of skin ulcer-
ations, secondary infections, and penile necrosis. Treatment
aims are to restore venous blood flow and reduce swelling and
inflammation. Hydrotherapy, massage, application of topical
emollients, antiinflammatory drugs, and diuretics can all be
useful therapies. Antimicrobials and corticosteroids may also
be indicated to prevent secondary infections and manage the
edema. Support of the penis and prepuce are important to
prevent microthrombi from forming and can be accomplished
using mesh support, a probang device, or purse-string suture
(as shown in Fig. 19.29).1023,1024 In some instances flushing of
the CCP with heparinized saline or intracavernous injection
Disorders of the Reproductive Tract 13331333
FIG. 19.29 Example of a penile sling using women’s undergar­
ments. Lacy material is ideal to allow for passage of urine and exudate.
The sling is secured with rubber tubing.
of phenylephrine may aid in blood drainage and penile retrac-
tion. Traumatic accidents involving the penis are not uncom-
mon. Cuts with mare tail hair, poorly constructed breeding
phantoms with fixed AVs, and severe bending of the erect
penis may result in abrasions, lacerations, and severe hema-
tomas. These wounds are treated with supportive therapy and
surgery, when indicated. Prevention of secondary contamina-
tion and adhesion formation is important. It is also essential
in cases of paraphimosis that the stallion’s ability to urinate
is assessed and addressed, because this can quickly become a
life-threatening condition if the damage to the penile urethra
prevents urination.
Acquired conditions causing phimosis, or the inability to
extrude the penis from the prepuce, include those conditions
that cause stenosis of the preputial orifice. Strictures can arise
from trauma or neoplastic growths. Horses experience diffi-
culty urinating or have an inappropriate urine stream. Surgi-
cal resection of the stricture and/or debulking of the growths
and lesions can help resolve the condition. Some breeding
stallions may achieve an erection before full protrusion from
the sheath. This condition can cause mild discomfort and even
self-trauma. This condition is resolved by calming the stallion
via removing the sexual stimulus and allowing the penis to
detumesce.
Priapism is a persistent erection in the absence of sexual
stimulation. It has been commonly associated with pheno-
thiazine-derivative tranquilizers,1021,1025,1026 but it can occur
following the administration of any sedative or tranquilizer
(though this is uncommon). Medical management with the IV
administration of benztropine mesylate (8 mg, IV) or direct
injection of the CCP with 1% phenylephrine (10 mg diluted
in 10 mL physiologic saline) have been used successfully to
resolve this condition. Surgical treatment is usually instituted
when medical therapy fails. It consists of evacuating and flush-
ing the CCP with heparinized saline. A partial phallectomy
can also be used to manage this condition in geldings.
Neoplastic Conditions
The most common form of neoplasia affecting the penis is
squamous cell carcinoma. Smegma accumulation on the penis
may be a predisposing factor for this type of neoplasia.1027 The
 1334 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
tumors start as small, keratinized plaques that slowly progress
into necrotic foci with foul-smelling exudate from secondary
bacterial contamination. The papillomavirus has been sug-
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gested as a predisposing factor, which is a hypothesis that war-
rants further investigation.1028 Conclusive diagnosis is based
on histopathologic examination of tissue from the affected
region. The condition is treated with cryosurgery, reefing, or
phallectomy.
Warts or squamous papillomas, sarcoids, melanomas, fibro-
mas, and lipomas may also occur on the penis. Cryotherapy,
autogenous vaccines, chemotherapeutic agents, and surgical
debulking have been used with varying degrees of success to
treat these conditions.
Infectious Conditions
The most common infections involving the penises of stallions
are habronemiasis, EHV-3, and bovine papillomavirus (BPV).
Dermatologic lesions secondary to Habronema spp. and the
microfilaria Onchocerca cervicalis result in characteristic
lesions commonly referred to as “summer sores.” Diagnosis of
habronemiasis is usually straightforward by observing char-
acteristic lesions on the urethral process, glans, and sheath.
Enteral and topical therapy with ivermectin is often useful.
Affected horses are prone to recurrence, and severely affected
horses may benefit from treatment with corticosteroids. While
the occurrence of habronemiasis waned with the advent and
ubiquitous use of avermectin anthelmintics, this disease has
seen a mild reemergence in recent years that has been attrib-
uted at least in part to possible resistance of the organisms to
common dewormers.
Coital exanthema caused by EHV-3 is a contagious vene-
real disease affecting stallions and broodmares. It causes char-
acteristic lesions and can be readily transmitted by both horses
and fomites. EHV-3 and other venereal diseases are covered in
a separate section.
Infection with BPV is an interesting concept because it has
been implicated in the onset of equine sarcoids.1029 Conse-
quently, treatment with topical antiviral agents (e.g., acyclovir)
may be of benefit in arresting and even reducing growth.
Bacterial infections of the penis should always be inter-
preted in light of both clinical signs and breeding records. For
example, the external genitalia of commercial Thoroughbred
stallions are cultured routinely to screen for potential patho-
gens. It is not uncommon to obtain positive growth of various
organisms, including E. coli, S. zooepidemicus, S. equisimilis,
Staphylococcus aureus, Bacillus spp., K. pneumoniae, and P.
aeruginosa.1030 Despite positive growth, many stallions will
remain unaffected as evidenced by a lack of clinical signs and
adequate pregnancy rates. However, when the normal flora
is disrupted, potentially pathogenic bacteria, particularly P.
aeruginosa and K. pneumoniae, can colonize the penis and
prepuce. These organisms rarely produce clinical disease in
stallions, but controversy exists regarding the risk of trans-
mission to the mare at the time of breeding and the potential
for causing IE and associated subfertility. Factors contribut-
ing to the colonization of the penis by these bacteria have not
been clearly determined. Normal bacterial microflora of the
external genitalia of the stallion may combat proliferation of
pathogens, and frequent washing of the penis, especially with
soaps, may remove these nonpathogenic resident bacteria,
increasing the susceptibility of the penis and prepuce to colo-
nization by pathogenic organisms.1031 Others dispute this con-
cept, asserting that repeated washing of the external genitalia
alone does not contribute to overgrowth of pathogenic micro-
organisms. The environment in which a stallion is housed
may influence the types of organisms harbored on the exter-
nal genitalia. The stallion also can acquire these organisms at
the time of coitus with a mare that has a genital infection.1008
Diagnosis of pathogenic colonization of the stallion’s penis
begins with careful evaluation of breeding records and early
pregnancy rates. A sudden and unexplained drop in repro-
ductive efficiency should warn the stallion manager about a
possible problem. Definitive diagnosis requires isolation of the
pathogenic microorganisms from cultures of the genitalia. In
addition, isolation of the same microorganism with a similar
sensitivity pattern from recently bred mares may help confirm
the diagnosis.
Treatment of pathogenic bacterial colonization of the penis
depends on the type of bacteria isolated and method of breed-
ing. For stallions breeding by AI, a thorough penile wash
before semen collection is recommended. Collected semen
should be filtered and diluted appropriately in extender con-
taining an antibiotic to which the bacteria is sensitive. Stal-
lions breeding by live cover should have their penis washed
and dried before or after mating. Aggressive management of
the mare may also be pursued (e.g., uterine lavage, antibiotic
infusions, and/or systemic antimicrobials) if growth is of sig-
nificant concern and/or the mare is susceptible to postmat-
ing-induced endometritis. Stallions with penile colonization
by Klebsiella or Pseudomonas spp. can be washed with a weak
solution of HCl or sodium hypochlorite. Systemic treatment is
not recommended because it has proved unrewarding in most
cases.
Abnormalities of the Scrotum
The scrotum in the horse is a pliable and thin-skinned pouch
with a fine layer of short hair, numerous sweat glands, and the
thick muscular layer (tunica dartos). The scrotum is usually
darkly pigmented. Functional integrity of the scrotum is vital
because of its role in thermoregulation of the testes.1032 Abnor-
mal conformation, trauma, and increased thickness can have
a dramatic and deleterious effects on spermatogenesis. The
scrotum is easily accessible for examination by visual inspec-
tion and palpation, and most stallions allow evaluation and
palpation with mild restraint.
Developmental Conditions
The most common developmental condition of the scrotum
is a reduction in size secondary to unilateral or bilateral cryp­
torchidism (discussed later). Stallions affected with DSDs may
also display smaller than expected scrotal size or an unusual
location of the scrotum.
Acquired Conditions
Traumatic insults to the scrotum or the scrotal area and other
inflammatory processes in the genital area often result in scro-
tal edema. The clinician must identify the causes of the swell-
ing to initiate adequate therapy. Chronic edema of the scrotum
can result in abrasions or wounds that can be complicated
further by bacterial contamination. Differential diagnoses for
scrotal swelling include systemic infectious processes, scrotal
herniae, spermatic cord torsion, scrotal abscess or hematoma,
hemorrhagic processes associated with the testes or spermatic
cords, and ascites or peritonitis.
An ultrasonographic study is indicated in stallions with
scrotal edema or swelling to evaluate the scrotal tissues and
 CHAPTER 19
contents. Percutaneous aspiration of fluid in the scrotal tissue
or between the visceral and parietal vaginal tunics can prove
useful for further characterization of the fluid but does carry
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risk of iatrogenic infection.
Therapy is directed toward removing the primary cause of
scrotal swelling and controlling any ongoing inflammation
and edema. Antiinflammatory drugs (e.g., NSAIDs, cortico-
steroids), diuretics, and frequent hydrotherapy are all mea-
sures that should be implemented to counteract swelling and
reestablish circulation. Broad-spectrum antibiotic therapy can
be instituted, and application of lubricants and emollients is
useful for preventing dermatitis and countering secondary
bacterial infection.1033
Quick resolution of scrotal edema and swelling is of par-
amount importance. Acute systemic (e.g., fever) or local
inflammation can lead to thermal insult of the testes, which
can adversely affect spermatogenesis and translate into poor
semen quality and reproductive efficiency. Chronic inflamma-
tion can also be detrimental, leading to fibrosis and testicular
degeneration.
Neoplastic Conditions
Cancers of the scrotum are similar to those affecting the skin.
Sarcoids, squamous cell carcinoma and papillomas, and mela-
noma have all been reported.1034 Diagnosis is made based on
both clinical signs and histopathology of the affected tissue.
Combination therapy with surgical removal and chemo-
therapeutic agents appears to be the most common mode of
treatment.1035
Infectious Conditions
EIA or other infectious diseases causing severe hypoprotein-
emia can result in scrotal edema and affect stallion fertility.
The acute phase of EVA can cause different degrees of ventral
or dependent abdominal edema that may involve the scrotum.
Coital exanthema caused by EHV-3 can also affect the scro-
tum and is discussed later.
Infection with T. equiperdum, the causative agent of dou-
rine, can also cause scrotal edema. It is considered an FAD
in the United States but is found in equids located in parts
of Africa, Asia, and possibly South America.246 As will be
discussed later, dourine is transmitted almost exclusively by
coitus. Habronemiasis is another parasitic disease that infre-
quently affects the scrotum and can be managed as described
for similar lesions affecting the penis.
Abnormalities of the Testes
As previously reviewed, the major cell types of the testes are
Sertoli, Leydig, myoid, and germ (sperm) cells. Congenital,
acquired, neoplastic, and infectious conditions affecting these
cells, whether alone or in combination, can have significant
consequences on fertility. Early diagnosis and management
are key to a resolution.
Developmental Conditions
Discussed next are various developmental disorders of the
testes. In addition to these, monorchidism, anorchidism, and
polyorchidism have been described in stallions.1036
Ectopic Testis. A gonad that fails to reach the scrotum and
deviates from the normal path of descent is termed an ectop-
ic testis. These testes may be located in subcutaneous tissues
within the inner thigh, abdomen, or perineal region. Cryp-
torchid testes are sometimes referred to as ectopic testes.1037
Disorders of the Reproductive Tract 13351335
Splenic-testicular fusion has also been reported and represents
an extreme case of ectopic testis.
Cryptorchidism. This condition refers to the failure of one
(unilateral) or both (bilateral) testes to fully descended into
the scrotum by 2 years of age. Cryptorchidism is a fairly com-
mon congenital defect of horses and is further characterized
by the location of the retained testis (inguinal or abdominal).
Two retrospective studies documented 350 cases over a 14-
year period1038 and 500 cases over a 23-year period.1039 Diag-
nosis is fairly straightforward and involves both palpation and
ultrasonography. The former is useful for confirming the lack
of a testis or testes, whereas the latter aids in locating the re-
tained testicle, which is beneficial when planning a particular
surgical approach.
When the castration status of a horse is unknown, endo-
crine analyses are relatively sensitive methods for detecting
the presence of testicular tissue. Evaluation of resting testos-
terone concentration, hCG stimulation test, estrone sulfate
concentrations, and AMH serum concentrations have all
been described. The most common endocrine test performed
to evaluate whether testicular tissue is present is baseline
testosterone concentrations, with values <50 pg/mL sug-
gesting an absence of functional testicular tissue, 50 to 100
pg/mL being inconclusive, and values >100 pg/mL suggest-
ing the presence of functional testicular tissue. If this test is
inconclusive, then an hCG stimulation test is performed that
induces an increase in testosterone secretion and production
from the Leydig cells within the testes. This test involves col-
lection of a baseline serum sample, followed by IV adminis-
tration of 5000 to 10,000 IU hCG and collection of serum at
24 and 48 hours later. A 2- to 3-fold increase in circulating
testosterone concentration from baseline indicates the pres-
ences of active testicular tissue. Unfortunately, this test can
yield equivocal results when posttreatment samples are col-
lected too early.1040 The current recommendation for those
using this test is to collect the posttreatment sample 2 days
after hCG stimulation.1041 Detection of AMH is proving to be
just as—if not more—sensitive for the diagnosis of cryptor-
chidism.968 This test only requires a single serum sample but
is subjected to seasonal influences.1040
Nonsurgical treatment for cryptorchidism should be ini-
tiated early and cases selected appropriately to increase the
likelihood of success.1042 When the testis is located within
the abdomen, surgical removal is the only means of removal.
Retained testicles should be dealt with at an early age for the
following reasons:
1. Trainers believe the retained testicle can be a periodic
source of discomfort.
2. A retained testicle, while unlikely to produce viable sper-
matozoa, remains hormonally active, which can have sup-
pressive effects on the descended testis.
3. Retained testes can become neoplastic with advancing age.
To further the last point, the relative incidence of testicu-
lar cancer in stallions is difficult to precisely quantify because
of the relatively low number of older intact males. Neverthe-
less, neoplasia of the testes can have serious consequences
on breeding efficiency and overall health. Surgical removal is
often curative, with the risk of metastatic disease relatively low,
although not entirely uncommon.
Breeding stallions with only one functional testis can
often be managed successfully. Generally speaking, the func-
tional testis will hypertrophy. Young fertile stallions can
often perform adequately with only one testicle. Appropriate
 1336 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
management of book size and selecting young mares can all
favor a stallion, especially early in his career.
Gonadal Hypoplasia. Small testes may result from a num-
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ber of underlying complex processes such as spermatogenic
arrest and germ cell deficiencies. Testicular hypoplasia is the
failure of the gonads to reach their full adult size and must
be differentiated from gonadal atrophy or testicular degenera-
tion, which is the reduction in testicular size after the gonad
has reached full adult size. The cause of the hypoplastic go-
nad is complex and is thought to be congenital or acquired.
Although not clear for horses, a genetic component has been
identified in other species.1016 Generally testicular hyperther-
mia, malnutrition, and endocrine imbalances—particularly in
steroid-treated young stallions—can negatively affect testicu-
lar size. It is important to remember that the testes do not start
to enlarge until 15 to 18 months of age, and they continue to
increase in size until 4 to 5 years of age. Testicular hypoplasia
should not be confirmed before the stallion is 2 to 3 years old.
The breeding of mares to stallions with hypoplastic gonads
is discouraged, but the value and performance record often
trump breeding soundness. In these cases, implementation
of managerial practices to maximize the reproductive perfor-
mance of the animal is important and should include reduc-
ing the number of mares in the book and breeding mares only
once when they are close to ovulation.
Gonadal Atrophy. Also known as testicular degeneration,
gonadal atrophy is most common in the mature stallion and
can lead to profound disruptions in spermatogenesis. Go-
nadal atrophy and gonadal hypoplasia must be differentiated
because they represent distinct disease processes. A thorough
reproductive examination and an accurate history are funda-
mental in differentiating the two conditions. One should note
inconsistencies between measured sperm output and esti-
mated sperm output (DSO) based on testis size. Small testes
in relation to the epididymis indicate atrophy. However, de-
velopmental abnormalities such as a small penis and enlarged
inguinal rings associated with small testicular size often indi-
cate hypoplasia. Atrophy or degeneration is considered an ac-
quired condition that may or may not be reversible, depending
on the cause.
Testicular atrophy can be caused by exogenous hormone
administration. Historically, colts or stallions given anabolic
steroids to improve recovery and muscle mass experienced
reduction in testicular size caused by suppression of endog-
enous testosterone production. The use of anabolic steroids is
no longer common in the United States. The synthetic pro-
gestin, altrenogest, can also cause testicular atrophy and a
reduction in seminal quality and quantity.1043 The detrimental
effects on spermatogenesis are caused by an increase in the
circulating levels of androgens, which in turn provide negative
feedback on LH secretion by the pituitary with a consequent
decline in testosterone production. As a consequence, testicu-
lar function is compromised, leading to a significant reduc-
tion in sperm production. Fortunately, the negative effects of
steroids on testicular function are generally considered to be
reversible, at least with respect to short-term use.123 Long-term
effects are unknown and need further study.
Diagnosis of gonadal atrophy requires a multimodal
approach consisting of an accurate history, physical examina-
tion, evaluation of the external genitalia, semen analysis, and
endocrine testing. An early indication of testicular degen-
eration is poor spermatogenic efficiency or decreased sperm
output relative to what is expected based on calculations from
testis size. More specifically, these stallions can have adequate-
sized testes, but the quantity and/or quality of spermatozoa
within the ejaculate is low or unusually poor, and during the
initial phases the testes can feel softer. With chronicity, the
testicular parenchyma is replaced by connective tissue, which
makes the testes feel firmer. Leydig and Sertoli cells and sper-
matogonia and spermatozoa are more resistant to degenera-
tion than cells of the intermediate stages of spermatogenesis;
therefore semen analysis varies depending on the extent of
damage. In most cases gonadal atrophy does not affect libido.
Endocrine testing can help confirm a diagnosis of gonadal
atrophy. In many instances stallions will have increased cir-
culating FSH concentrations but decreased concentrations of
other sex hormones, such as LH, estradiol, testosterone, and
inhibin.1044 The use of AMH is an interesting concept, but to
the author’s knowledge, the usefulness of this endocrine assay
in evaluating stallions with possible testicular degeneration
has yet to be determined.968
Treatment of gonadal atrophy revolves around determin-
ing the cause of degeneration. Resumption of normal testic-
ular function can be expected in instances in which damage
was mild and relatively short lived. Chronic disease and idio-
pathic causes carry a more guarded prognosis. Reduction in
book size, maintaining a selective book, and advanced semen
processing and insemination techniques may help achieve
acceptable pregnancy rates. Administration of GnRH has
anecdotally been reported to be of benefit in early cases but is
unlikely to be of benefit in reversing degenerative changes. For
further information on management strategies for gonadal
atrophy the reader is directed to an excellent review.1045
Acquired Conditions
Any condition causing hyperthermia or hypothermia can lead
to damage and abnormal testicular function. Examples of con-
ditions implicated as possible causes of testicular degeneration
include prolonged recumbency, trauma, torsions of the sper-
matic cord, disruption of the blood-testis barrier and the con-
sequent production of antisperm antibodies, inappropriate or
prolonged steroid therapy, accumulations of fluids such as in
hydroceles, and advanced age. Scrotal lesions that impair the
normal testicular thermoregulation may be a significant fac-
tor causing gonadal atrophy. Other acquired disorders of the
testes include radiation exposure; nutritional disorders, par-
ticularly those of vitamin A and zinc; and toxicity with heavy
metals or nitrogen, phosphorus, and halogenated compounds.
Immune-mediated orchitis is rare in stallions. As soon as
spermatogonia enter the leptotene stage during the meiotic
phase, they become isolated from the general immune system
by tight junctions between adjacent Sertoli cells. As mentioned
previously, these gap junctions form the blood-testis barrier.
A fine balance is maintained so that maturing spermatids can
migrate toward the adluminal compartment without elicit-
ing an immunologic response. In addition to the blood-testis
barrier, local immunosuppressors are present in the testicular
interstitium. Factors that disrupt the blood-testis barrier with
the consequent formation of antisperm antibodies include
tumors, trauma, biopsies, and spermatic cord torsions of more
than 360 degrees. The association between antisperm antibod-
ies and infertility, although reported for the stallion, warrants
further investigation.1046
Hypertrophy refers to a condition in which the individual
cells of the testes increase in size. The most common cause of
testicular hypertrophy is removal of one testis or the abdominal
 CHAPTER 19
retention of one that triggers a compensatory growth of the
contralateral gonad. Hyperplasia refers to an increase in the
number of cells and can be focal or generalized. Testicular
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hyperplasia is rare in stallions.
Neoplastic Conditions
With an estimated frequency of approximately 4%, testicular
cancer in stallions is relatively rare. The low occurrence is likely
related to the relatively low number of sexually mature intact
males compared with females. Teratomas were the most com-
mon (37%), followed by interstitial cell tumors (30%), semi-
nomas (23%), lipomas (7%), and mast cell tumors (3%).1047
Teratomas are commonly found in juvenile colts at the time of
castration, which may explain their overrepresentation in inci-
dence. Cryptorchid testes appear to have a predisposition for
neoplasia, especially germ cell tumors, such as seminomas.1047
Risk of metastasis is generally considered low, but one author
has known two stallions that experienced secondary compli-
cations and subsequent death from malignancies arising from
confirmed seminomas. Consequently, ensuring adequate
excisional margins by histopathologic evaluation of excised
tissue and evaluating regional lymph nodes provide useful
information related to prognosis for that stallion.
Diagnosis of testicular neoplasia is based on a careful
examination of the testes and related structures. One should
palpate the scrotal contents and note soft or firm spots, nod-
ules, or asymmetry. Ultrasonographic examination is cru-
cial for the identification of fluid-filled or solid nonpalpable
lesions embedded deep in the testicular stroma. The spermio-
gram often yields nonspecific findings but can demonstrate
a high incidence of teratozoospermia (abnormal morphol-
ogy), asthenozoospermia (poor motility), and/or the presence
of round spermatids and other testicular cells. Abdominally
retained testes can be diagnosed by transrectal and transab-
dominal palpation and ultrasonography. Unilateral or bilateral
orchiectomy is the treatment of choice regardless of the type
of tumor. Depending on the size and location of the testis, an
inguinal, flank, or ventral midline incision is recommended.
Ligation and removal of as much of the cord as possible are
strongly recommended, and sampling of regional lymph
nodes can be useful for determining the risk of metastatic
disease. The gross appearance of testicular neoplasia can vary
with the primary cell type. Interstitial cell tumors are usually
soft, orange, and nodular, with no clear demarcation with the
adjacent testicular tissue. Seminomas can vary in color from
white to dark gray with a glistening appearance; the neoplas-
tic area frequently bulges above the adjacent testicular tissue.
Fluid-filled cysts often are present. Sertoli cell tumors are usu-
ally firm, nodular, and pale gray. Teratomas are easily identifi-
able by the presence of tissue of different origins (e.g., bone,
hair). Ultimately, diagnosis is confirmed by histopathologic
examination of the affected tissue.
Infectious Conditions
Inflammation of one or both testes is referred to as orchitis.
Causes may be bacterial, viral, parasitic, or aseptic after trauma.
Orchitis can be primary or secondary to another disorder. It is
important to differentiate this condition from the more com-
mon conditions of periorchitis or scrotal edema, although
the two conditions may be present simultaneously. Bacterial
orchitis in horses may be caused by Brucella abortus, Actinoba-
cillus equuli, Pseudomonas pseudomallei, S. zooepidemicus, S.
equisimilis, Salmonella spp., E. coli, and Staphylococcus spp.1048
Disorders of the Reproductive Tract 13371337
The viral diseases EVA and EIA affect the testes because of
associated fevers and edema. These agents can also be shed
in the semen of affected stallions. Focal lymphocytic infiltra-
tions may be observed in affected stallions. Parasitic orchitis is
usually a sequela of migratory larvae of the parasite Strongylus
spp.1049 The condition can affect descended or undescended
testicles and the tunics and spermatic cords. A possible sec-
ondary lesion associated with larvae is known as focal lym-
phocytic orchitis, which occurs around the seminiferous
tubules.1050 It is different from the condition of autoimmune
orchitis reported for the mouse in which foci of lymphocytes
are localized exclusively at the rete testis and efferent ductules.
Initial diagnosis of the granulomatous-type lesions in the tes-
ticle caused by strongylosis sometimes can be done by ultraso-
nography, but histopathologic identification is necessary for a
definitive diagnosis. Regular deworming programs with iver-
mectin can help control both of these conditions.
Abnormalities of the Epididymides
Congenital Conditions
Blind-ended ductules can form within the epididymis and
likely represent failure of fusion of the ducts during embry-
onic or fetal development. If sufficient numbers of tubules
are blocked, then the condition may lead to spermiostasis
with development of cystic dilations, formation of epididy-
mal sperm granulomas, and reduction of fertility. These cystic
dilations may be diagnosed by palpation and ultrasonography.
Segmental aplasia of the mesonephric duct or epididymal
agenesis is rarely reported in horses. Interestingly, the epididy-
mis in the stallion is not fused completely with the testicle as
in other species, which may predispose them to epididymal
pathology such as spermatoceles and cystic dilations. Other,
less common conditions include adenomyosis and tumors.1051
Palpation and ultrasonography may be useful in diagnosis of
these conditions.
Acquired Conditions
Other causes of epididymal dysfunction can manifest as abnor-
mal accumulation of sperm in the cauda epididymides or gen-
eralized dysfunction of the epididymal epithelium associated
with deficiencies in electrolyte, protein, or steroid secretion
or resorption. Accumulated material may become inspissated
and clog the normograde flow of sperm. Epididymal dysfunc-
tion, whether primary or secondary, can create changes in pH
and osmolarity of the seminal plasma that might adversely
affect maturation and viability of sperm. These conditions can
be diagnosed by frequent semen collections (once or twice
daily for 7–10 days) and evaluation of sperm morphology and
motility, as well as seminal pH and metabolite analysis. Oligo-
spermia and varying degrees of teratospermia are common.
Morphologies from stallions with plugged cauda epididy­
mides often have an unusually high percentage of detached
heads and clumps of spermatozoa. Normal stallions ejaculate
semen with a pH of 7.4, whereas those with decreased circu-
lating testosterone and estradiol concentrations tend to have
higher pH levels.1052 Because the accessory sex glands contrib-
ute a significant portion of volume to semen, disorders affect-
ing these structures also need to be ruled out.
Infectious Conditions
Bacteria or trauma to the scrotal area may cause inflamma-
tion of the epididymides. Infectious epididymitis as a primary
 1338 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
disease is rare in stallions and is considered a sequela to orchi-
tis or to deep lacerations of the scrotal area. Migration of
Strongylus edentatus larvae also may cause epididymitis with
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the consequent formation of granulomas.1053 One confirms a
diagnosis of epididymitis by palpation, ultrasonography, the
presence of inflammatory cells in the ejaculate, and bacterial
growth on culture.
Abnormalities of the Spermatic Cord
Congenital Conditions
The terms inguinal hernia and scrotal hernia are often used
interchangeably. These involve protrusion of intestines or
omentum through the vaginal ring and into the vaginal cavity.
Ruptures of the vaginal sac can also occur. Inguinal hernias
are more common in intact males because of the rapid closure
of the rings following castration. Congenital and hereditary
causes have been identified,1054 and one of the authors (CFS)
has seen them most often in Standardbred horses. Percutane-
ous and transrectal palpation and ultrasonography are ideal
for diagnosing inguinal hernias and ruptures. In foals, many
will spontaneously resolve by 6 months of age. Application of
a truss or frequent manual reduction may hasten resolution
in some affected horses. Occasionally, the bowel may become
incarcerated and undergo ischemic insult, necessitating surgi-
cal closure of the rings and possible resection of bowel.
Acquired Conditions
Vascular problems associated with the cord include torsion,
varicoceles, and thrombosis.1055,1056 Torsion of the cord is sig-
nificant when the cord has rotated more than 180 degrees. Tor-
sions of less than 180 degrees are usually an incidental finding
in young horses and are usually transient but occasionally
permanent. Oftentimes torsions of less than 180 degrees are
of little clinical significance, especially when no other clinical
signs are evident. Torsions greater than 270 degrees are asso-
ciated with scrotal swelling, pain on palpation, an abnormal
gait, and acute abdominal pain. Diagnosis is made by a com-
bination of clinical signs, palpation, and ultrasonography. The
latter modality is very useful in differentiating spermatic cord
torsions from scrotal hernias. The treatment of choice in sper-
matic cord torsion is hemiorchiectomy because the affected
testicle will likely necrose and become nonfunctional.
Varicoceles in stallions are of questionable significance,
especially if unilateral. Nevertheless, they have been associ-
ated with poor seminal quality and subfertility in other spe-
cies.1057,1058 If severe enough, the function of the pampiniform
plexus (the mechanism responsible for countercurrent heat
exchange of blood entering and exiting the testes) can be
altered, predisposing the developing sperm cells to hyperther-
mia. Thrombosis of the cord is a more serious condition. The
clinical signs resemble those of pathologic spermatic cord tor-
sions, and unilateral castration is recommended. Ultrasonog-
raphy is a useful means of diagnosis, and color flow Doppler
can be used to evaluate blood flow when restriction, thrombo-
sis, or infarction is suspected.
Infectious Conditions
Diseases and disorders of the spermatic cord involving older
horses are primarily limited to infections and vascular issues.
In intact horses, the most common infectious causes would
be aberrant parasite migration and vasculitis secondary to
local or generalized sepsis. Infection of the spermatic cord can
occur following castration and is referred to as septic funicu-
litis, scirrhous cord, or champignon. Treatment consists of sys-
temic broad-spectrum antibiotic therapy and supportive care.
Surgical debridement and removal of the necrotic foci are also
necessary because most cases do not resolve with medical
management only.
Aberrant parasite migration into the pampiniform plexus
can occasionally occur. However, it is now uncommon because
of the widespread use of the avermectins, which have effec-
tively resolved large strongyle infections.
Neoplastic Conditions
Neoplastic conditions are rare and usually secondary to inva-
sion or metastases. Seminomas can invade the cord, and
blood-borne cancers such as lymphoma may also metastasize
to the spermatic cord. Diagnosis is made based on accompa-
nying clinical signs, imaging, and histopathology.
Abnormalities of the Accessory Sex Glands
Congenital Conditions
Congenital disorders of the accessory sex glands in intact
male horses are rare. In cases of DSDs, infantile or hypoplastic
glands may be noted in the absence of androgen stimulation.
Acquired Conditions
The most common acquired condition of the accessory sex
glands is spermiostasis or plugged ampullae. Stallions with
this condition are referred to as sperm accumulators. Current
theory holds that these stallions, when subject to prolonged
periods of sexual rest, accumulate an abnormal amount of
sperm and seminal secretions in their ampullae and deferent
ducts. The incidence is estimated at ∼25% (DD Varner, per-
sonal communication, 2015), and Thoroughbred stallions are
overrepresented in most estimates. Possible causes include
stallions failing to void “stale” sperm in their urine (uncon-
firmed observation) and/or anatomic variations causing nar-
rowing of the lumen of the deferent ducts.83,86
Diagnosis entails collection of sequential semen samples
and evaluation of the spermiogram. Ejaculates can range from
oligospermic to containing unusually high (>30 billion) total
sperm cells. In stallions producing a large amount of sperm,
a characteristic finding is a high frequency of detached heads
as determined by DIC microscopy. “Clumps” of sperm aggre-
gates may also be seen. Ultrasonography per rectum can also
be used to evaluate the accessory sex glands. Blocked ampul-
lae can have a distended lumen and even hyperechoic regions
proximal to the seminal colliculus, suggesting inspissation of
seminal material.
The most common treatments for spermiostasis are frequent
and consistent collections or breedings. Stallions initially diag-
nosed with this condition may take 1 to 2 weeks for seminal
quality to improve. It is important to maintain accumulating
stallions on a regular breeding schedule when possible. Other
treatment strategies include administration of ecbolic agents
(oxytocin [10–20 IU, IM/IV] or PGF2α [cloprostenol; 25–250
μg, IM]) and manual massage of the ampullae per rectum.
Severe cases can be treated with normograde or retrograde
flushing of the ampullae and deferent ducts. One author (CFS)
has used phenylephrine (20 mg, diluted in 1 L LRS, IV) in a
horse with refractory plugged ampullae with positive results.
This treatment, however, did cause moderate colic-like signs
and intense full-body contractions during and shortly after
 CHAPTER 19
treatment and should only be administered with caution and
informed consent from owners.
Neoplastic Conditions
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Neoplasia of the accessory sex glands is rare. A recent report
from the University of Pennsylvania described two cases of
prostatic masses that were confirmed as either prostatic cyst-
adenoma or adenocarcinoma.1059 Surgical debulking was per-
formed in one horse, but both horses died within 9 months of
diagnosis.
Infectious Conditions
Although infections of the accessory sex glands are uncom-
mon, unilateral or bilateral seminal vesiculitis can occur.
Bacterial infection of the seminal vesicles is usually not accom-
panied by any external clinical signs. The ejaculate, however,
is often turbid and discolored, and evaluation reveals a sig-
nificant number of degenerate white blood cells. The glands
may be enlarged, firm, and painful on palpation if the condi-
tion is acute. Ultrasonography can be used, but results need
to be interpreted with caution because the size of the seminal
vesicle can vary with breed, season, and sexual stimulation.
Diagnosis of seminal vesiculitis is best made by rectal palpa-
tion, observation of large numbers of neutrophils in the semen
(gel fraction), bacterial culture of semen and/or gel fraction,
and endoscopy of the urethra and seminal vesicles. Direct cul-
ture of the seminal vesicles during endoscopy increases the cli-
nician’s confidence in the significance of organisms cultured.
Treatment is difficult, and the prognosis is guarded. Reported
treatments include systemic and local antibiotic therapy as
well as the addition of extenders containing appropriate anti-
biotics to the semen of the affected stallion. Endoscopic evalu-
ation is highly useful and can be followed by lavage and local
antibiotic infusion.
Sexually mature stallions can harbor EAV in their acces-
sory sex glands. This leads to chronic shedding and transmis-
sion of the virus to mares. This virus and its disease (EVA)
will be discussed later in a separate section on equine venereal
disease.
Abnormalities of Semen and Spermatozoa
Azoospermia and oligospermia describe the absence or abnor-
mally low numbers of spermatozoa in an ejaculate, respec-
tively. Teratospermia refers to the presence of an unusually
large number of individual sperm defects, whereas astheno-
spermia refers to sperm with poor motility. Causes can be
characterized as developmental, acquired, and infectious.
Developmental Conditions
Azoospermia is usually secondary to a gonadal or epididymal
disorder. Cryptorchidism, anorchidism, and testicular hypo-
plasia secondary to a DSD can lead to low sperm production.
Hypoplasia of the epididymides and deferent ducts leading to
outflow obstructions can also lead to little to no sperm cells
within an ejaculate. Diagnosis and treatment of cryptorchi-
dism have previously been discussed. Developmental abnor-
malities are often diagnosed via exclusion and genetic testing
(e.g., karyotyping and molecular studies).
Infectious and Acquired Conditions
Pyospermia. The hallmark of this condition is the presence
of purulent debris, white blood cells, and pathogenic organ-
isms in an ejaculate. This condition is usually secondary to
Disorders of the Reproductive Tract 13391339
infection or inflammation of the deferent ducts, accessory
sex glands (e.g., seminal vesicles), and/or urethra. Following a
live-cover, normal dismount, samples may be “contaminated”
with cellular debris and microorganisms. Caution should thus
be exercised not to overinterpret the findings in these samples,
which should be analyzed with respect to current reproduc-
tive performance. Aerobic cultures of the stallion’s penis, fossa
glandis, urethral sinus, and preejaculate and postejaculate
urethra can help with localization of the infection. Further
characterization of the source can be aided by fractionation
of the ejaculate using an open-ended AV. If the clinician sus-
pects that the stallion is the cause of bacteria-related fertility
problems in a group of mares, then it is important to culture
the mares to determine whether the mares are harboring the
same pathogens as the stallion. Giemsa, Wright, or Diff-Quik
stains of the semen aid in identifying the type of white blood
cell present. Treatment of pyospermia consists of resolving the
primary issue, use of semen extenders with appropriate antibi-
otics, and isolation of the sperm-rich fraction using centrifu-
gation or filtration.
Urospermia. General causes of urospermia include neuro-
logic disease, orthopedic conditions, psychogenic or behav-
ioral problems, and idiopathic causes. Although uncommon,
retrograde ejaculation can also occur.1060 Urine-contaminated
semen is often readily detectable because of changes in color
(yellow), odor (urea), and volume (increased). However, when
urine is not obvious but suspected to be a contaminant, the
concentrations of urea nitrogen >30 mg/dL and creatinine >2
mg/dL in the semen are diagnostic of urospermia. The effect
of urine on the sperm cells is not well documented. However,
the reduction in motility and fertility is significant because
of the effects of hyperosmotic medium and water removal
from the sperm cells. One author (JCS) has observed several
cases of urospermia associated with self-mutilating stallions.
Pharmacologic therapy of the problem is purely empiric and
limited to drugs that act to close the neck of the bladder, such
as β-blockers. A more common approach is to use managerial
procedures such as encouraging urination before semen collec-
tion and the collection of semen directly into an extender and
immediate centrifugation. The ideal procedure is to fraction-
ate the ejaculate during collection with an open-ended AV. In
breeds for which AI is not allowed, an extender may be infused
into the uterus and flushed out 4 to 6 hours later. Holding stal-
lions in a freshly bedded stall or placing feces from another
stallion in their stall before semen collection can sometimes
stimulate the stallion to void urine and can thus be used to
limit the risk of urospermia.
Hemospermia. Hemospermia is typified by an unusually
large amount of blood (fresh or dried) in an ejaculate. The
presence of erythrocytes in semen can adversely affect seminal
quality and subsequent fertility.1061 Decreased progressive mo-
tility and plasma membrane integrity were lower in ejaculates
incubated in whole blood compared with controls. In a recent
report on eight cases, causes of hemospermia included ure-
thral rents (3), urethral process lesions (2), squamous cell car-
cinoma (1), kick to the penis (1), and unknown origin (1).1062
Penile lacerations and habronemiasis are other potential
causes of hemospermia. Interestingly, stallions collected for
AI were overrepresented in reviews on this condition.1062,1063
If the bleeding site cannot be found externally, another com-
mon site is where the pelvic urethra folds over the ischium.
Urethroscopy performed immediately after ejaculation can be
used to visualize the penile and pelvic urethra and identify the
 1340 PART 2 DISORDERS OF SPECIFIC BODY SYSTEMS
location of a rent. If the source of bleeding can be identified in
the urethra, a common approach to treatment is sexual rest to
allow for tissue remodeling. Alternatively, a urethrostomy of
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the area is indicated for horses that fail to respond with con-
servative therapy. The urethrostomy relieves pressure and al-
lows the rent in the urethra to heal by second intention. Some
of the management procedures described for urospermia,
such as fractionation and extension, also may be considered.
Sexually Transmitted Diseases
There are several STDs that are relevant from both clinical
and regulatory standpoints. Readers are strongly encouraged
to contact their local regulatory official for updated informa-
tion or whenever a reportable or foreign animal disease (FAD)
is suspected. Questions pertaining to handling of potentially
infected gametes (e.g., spermatozoa, embryos) should be
directed to local regulatory officials.
Contagious Equine Metritis
CEM is a true venereal disease caused by the bacterium T.
equigenitalis, a highly contagious gram-negative coccobacil-
lus.240 Transmission via fomites is possible and was implicated
in a recent outbreak in the United States.1064 Clinical signs vary
from relatively inapparent to copious vulvar discharge origi-
nating from the uterus.241 Stallions rarely display clinical signs
but are unapparent carriers and are the most common means
of transmission because they are much more sexually active.
Significant drops in reproductive efficiency ensue, leading to
increased costs associated with management and veterinary
care. Diagnosis is made by isolation of the organism. Because
of the organism’s rather fastidious nature, samples should be
sent to laboratories familiar with culturing techniques. Treat-
ment for T. equigenitalis is fairly straightforward and consists
of careful cleansing of the internal and external genitalia and
application of local antiinfective agents. The United States has
undergone a reclassification in its status as a CEM-free coun-
try because of the previously mentioned outbreak. Readers are
thus encouraged to contact their local USDA official for cur-
rent recommendations. All breeding activity should be with-
held until proper screening and prophylactic treatments have
been performed before introduction of the animal into a local
breeding population.
Equine Viral Arteritis
EVA is another disease that has important regulatory impli-
cations. The causative agent is EAV, which is an enveloped,
single-stranded RNA virus.242 Clinical signs include vascu-
litis, distal limb edema, pyrexia, rhinitis, conjunctivitis, and
anorexia. The virus can also cause abortion outbreaks and
severe neonatal pneumonia in naïve herds. It is transmitted via
respiratory secretions and other body fluids, including semen
and fetal fluids/tissues, and fomites. Current estimates suggest
that 30% to 70% of exposed stallions will become persistently
infected when exposed to the virus, and they are referred to as
shedder stallions.243 Consequently, prevention of the disease is
key and has even been nearly eradicated in commercial North
American Thoroughbreds by screening and vaccination. A
modified-live virus vaccine is commercially available in the
United States (Arvac; Zoetis, Parsippany, NJ) and approved
for use in breeding stallions. In some breeds that allow AI,
breeding with EAV-infected semen is permissible with proper
documentation of the mare’s vaccination status. Certain breed
registries and state agricultural departments have restrictions
regarding vaccination of breeding stock and use of EAV-
infected semen. State requirements can be obtained by con-
tacting local regulatory officials.
Equine Herpesvirus Type 3
EHV-3 is the causative agent of equine coital exanthema, char-
acterized by vesicular or poxlike lesions on the genitalia that
eventually progress to depigmented regions of skin. It is not
currently considered a reportable disease in the United States.
Transmission is most common via coitus but can also occur
via fomites. Clinical disease is primarily manifested as vesicu-
lar and painful lesions on the external genitalia of both mares
and stallions. During the acute phase, these lesions can cause
discomfort during reproductive evaluations and during live-
cover matings, but infection has no lasting or impressionable
effects on fertility.244 Lesions will take 4 to 6 weeks to heal and
are characterized by focal areas of depigmentation. Gentle
cleansing of active lesions may soothe and reduce inflamma-
tion. Reports of antiviral treatments are sparse. One author
(CFS) has used docosanol cream (Abreva; Zoetis, Florham
Park, NJ) in four cases with seemingly good results in resolving
the acute inflammation associated with the lesions. However,
no comparison was made regarding the length of the convales-
cent period between treated and control groups. Transmission
to other animals is a concern and seems to be highest during
the acute phase of this disease. A period of 4 to 6 weeks of
sexual rest is recommended to prevent further transmission
and allow the lesions to heal. Resumption of breeding activity
can occur once the lesions have healed. Natural recrudescence
of this particular herpesvirus is unknown,245 but experimen-
tal administration of dexamethasone has been shown to cause
reactivation of the virus.1065 Control is aimed at early detection
and sexual rest until lesions have subsided. There is no com-
mercially available vaccine against EHV-3 in the United States.
Dourine
Dourine is a venereal disease of significance because of its high
level of morbidity and its effect on international transport of
equids. The etiologic agent is the protozoa T. equiperdum. Clin-
ical signs include intermittent fever, swelling of and discharge
from the genitalia, cutaneous plaques, and neurologic signs.246
Generally considered a chronic and progressive disease, the
onset of recumbency usually indicates terminal disease. Dou-
rine has been eradicated in the United States, but it is still pres-
ent in Africa, the Middle East, South America, and Central
America. Sporadic outbreaks have been reported in Asia and
Germany.240 Diagnosis is made via compatible clinical signs
and laboratory testing. The CF test is prone to false positives
from other species of Trypanosoma, and newer methods of
diagnostics, including ELISA and PCR technologies, are cur-
rently being explored for both testing and screening purposes.
Infected animals should be removed from breeding and culled.
Treatment with antiprotozoal drugs has been performed in
some endemic areas, but they are unproven and even discour-
aged because of concern about inapparent shedding animals.
Suspected cases of dourine should be reported immediately to
local regulatory officials.
Piroplasmosis
Previously eradicated in the United States, cases of piroplas-
mosis have sporadically occurred over the past few years.
This disease is caused by the protozoa Theileria equi (formerly
Babesia equi) and B. caballi. Transmission occurs either via
 CHAPTER 19
an insect vector (e.g., ticks) or mechanically (e.g., improperly
sanitized instruments). It also has the potential to be transmit-
ted venereally in cases of hemospermia. Piroplasmosis creates
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disturbances in several body systems. Clinical signs are often
nonspecific and vary based on the severity of disease and chro-
nicity. Horses surviving the acute phase can become carriers.
Diagnosis is confirmed based on observation of the organism
on blood smears and serologic testing. Treatment with anti-
protozoan medications is unproven, and recrudescence is a
concern.240 Similar to other reportable diseases, suspect cases
should be directed to the local USDA-APHIS office.
Opportunistic Pathogens
Several aerobic bacteria have been associated with poor
reproductive efficiency. These include β strep, E. coli, P. aeru-
ginosa, and Klebsiella spp. Although rarely a cause for clini-
cal disease,1066 overgrowth of these bacteria may occasionally
influence pregnancy rates in, for example, susceptible mares.
Serial collection of aerobic cultures of the external genita-
lia (e.g., penis/prepuce, urethral fossa, and preejaculate and
postejaculate urethra) is common to monitor for pathogens.
Cleansing with lukewarm water and drying the penis before
and after breeding are useful preventive measures, and they
also allow for inspection of the genitalia for abnormalities.
Treatment with local and/or systemic antibiotics is usually
not indicated for fear of disrupting the normal flora on the
genitalia. Washing with soaps or antiseptics may remove the
normal flora and select for more resistant and pathogenic
strains. The environment in which a stallion is housed may
influence the types of microorganisms harbored on the exter-
nal genitalia and should also be considered. When there is
concern about transmission of potentially pathogenic bacte-
ria, breeding strategies can be implemented to abate the risk.
In the case of stallions used for live cover, semen extender
containing an appropriate antibiotic can be infused into the
uterus before or after mating. Semen from stallions used for
AI should be screened for microorganisms and extended in
an appropriate semen extender. For mares bred to these stal-
lions, postbreeding management could entail uterine lavages,
infusions, and ecbolics.
Conclusion
Whether developmental or acquired in nature, there are many
conditions that can affect the reproductive tract of intact male
horses. Careful evaluation of all body systems is indicated
when disorders of the reproductive tract are suspected because
of its interrelationship with other organs. This also holds true
when examining a breeding stallion for fertility issues. In these
particular cases, the sense of immediacy is ratcheted up a few
notches to obtain a timely diagnosis and implement effective
management strategies to improve reproductive efficiency.
Clinical examination, diagnostic imaging, endocrine testing,
and semen evaluation are all useful in meeting these goals.
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