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How I approach...

Infertility in the queen

Stefano Romagnoli, DVM, MS, PhD, Dipl. ECAR
Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Agripolis, Legnaro, 35020 (PD)
University of Padova, Italy

Dr. Romagnoli graduated in Veterinary Medicine in 1982 from the University of Pisa, Italy, and obtained his Master
of Science in Animal Reproduction at the University of Minnesota, USA in 1986. He then returned to Italy where he
progressed to become Full Professor at the University of Padova in January 2001. During this period he took a
sabbatical to work as Clinical Assistant Professor at the University of Minnesota in Small Animal Reproduction with Prof. Shirley
Johnston. He has authored more than 230 papers on refereed national and international journals, book chapters, congress proceedings,
scientific abstracts. His research interests are the effect of prostaglandins on the canine corpus luteum, and other aspects of canine and
feline reproductive and pediatric medicine. He has been President of the Italian Feline Practitioners Association (1993-1999) and is
currently (2000-2006) President of the European Society of Feline Medicine. Dr. Romagnoli also serves as Secretary of the European
Board of Veterinary Specialization (EBVS, 2004-2006) and the European Association of Establishments for Veterinary Education
(EAEVE, 2004-2006).

ed Surprise, a 2 year-old Maine Coon queen

(Figure 1) was referred for failure to conceive
at two consecutive breedings. She was born
November 30, 2003 and had gone through puberty at
4 months of age. After puberty, she began showing
estrus behavior fairly regularly 1-2 times/month but
was not bred for the first 6 months (February to
August) due to Cat Fancy regulations 1. Estrus episodes
were about 7-10 days long and characterized by very
evident rolling, calling and lordosis behavior upon
manual stimulation of the back. She developed a
serosanguineous vulval discharge around 7 months of
age and was taken to the veterinarian. On abdominal
ultrasound a small amount of fluid was observed in the
uterus: the fluid appeared clear, it was evenly
distributed throughout the body as well as both horns,
the inner uterine diameter was 6 mm, there was no
endometrial thickening and iliac lymphnodes appeared
of normal size and echogenicity. The queen was treated
with a 6-day course of amoxicillin-clavulanic acid
(12.5 mg/kg, orally, BID) and the vulval discharge
disappeared. Between 7 and 10 months of age the
queen continued to show heat behavior regularly and
with the same intensity, and developed a serosanguineous
vulval discharge again at 8 and then at 9 months of
age. On both occasions, the owner instituted the same
antibiotic therapy (6-day course of amoxicillinclavulanic acid, same dosage) without consulting the

veterinarian, and on both times the vulval discharge

disappeared. The queen was bred for the first time in
early September 2004 to Gengis Khan, an adult
Maine Coon tomcat but did not conceive (pregnancy
diagnosis was not performed). Then on November 30,
2004 she was in heat and was bred again to the same
tomcat several times on December 1st and 2nd.
The differential diagnosis for this queen includes
recurrent vulval discharge and failure to conceive.
Are the two problems related to each other? Is this
queen ever likely to conceive? The issue about the
potential future fertility is rather important to the
owner as this is a valuable queen from the
reproductive standpoint and a decision has to be

1. Based on Cat Fancy rules in Italy kittens born from mothers who are younger than 12 months of age cannot have a pedigree.

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Figure 1.
The 2-year old
Maine Coon
queen Red
Surprise.

How I approach... Infertility in the queen

Figure 2.
A feline uterus removed from
a queen with clinical signs of
pyometra, showing an example
of gross anatomic features of
cystic endometrial
hyperplasia with distension
of the uterine lumen.

made whether or not it is worthwhile investing in

expensive diagnostic and therapeutic techniques for this
animal. As we know, vulval discharge and failure to
conceive in the queen may be due to a variety of
different reasons. The first question we need to answer
Why did this queen develop a serosanguineous vulval
discharge? Lets try to answer this question by looking
at the potential causes of vulval discharge in felines as
listed in Table 1.
In general, vulval discharge in the queen is unusual. No
vulval discharge occurs during proestrus and estrus;
furthermore, vaginitis, urogenital neoplasia or trauma as
well as urinary incontinence, although reported, are rare
conditions in felines. If one excludes emission of
normal, parturition-related fluids, the only other reason
why a queen may show a discharge from the
reproductive tract is because of uterine disease such as
pyometra (Figure 2) or metritis. While metritis is a
typical postpartum condition occurring at a time when
serum progesterone concentrations are low, pyometra
develops only in the presence of high serum
progesterone concentrations. The first result of
progesterone stimulation on the endometrium is cystic
endometrial hyperplasia (CEH), which is a growth and
dilatation of the endometrial glands with accumulation
of endometrial fluid within their lumen. CEH develops
normally during a luteal phase and then regresses during
periods of uterine quiescence.
Endometrial secretion is necessary for the nutrition of the
pre-implantation embryos but the accumulated fluid may
contribute to bacterial growth in case of uterine
contamination. Exposure to repeated luteal phases (such
as following clinical use of progestins or repeated
ovulations) may cause a chronic CEH and endometrial
fluid accumulation, which may have been responsible for
the serosanguineous vulval discharge repeatedly observed
in this queen following periods of estrus behavior between
April and October 2004. The queen was observed to
display estrus behavior very frequently between 4 and 10
months of age and was bred on two different cycles
between 10 and 12 months of age. She may have
experienced luteal phases due to either spontaneous (prior

Table 1.
Causes of vulval discharge in the queen
Intact, prepubertal female
Vaginitis
Urogenital trauma
Urogenital neoplasia
Urinary incontinence (post-traumatic)
Intact, postpubertal female
Vaginitis
Pyometra
Uterine disease
Urogenital trauma
Urogenital neoplasia
Urinary incontinence (post-traumatic)
Pregnant female
Fetal loss
Normal placental fluid discharge
Lochia
Metritis
Urogenital trauma
Urogenital neoplasia
Urinary incontinence (post-traumatic)
Ovariectomized female
Vaginitis
Uterine stump infection
Urogenital trauma
Urogenital neoplasia
Urinary incontinence (post-traumatic)
Pyometra and metritis are by large the most common causes, while all the
others have been reported in the queen but are considered extremely rare.

to 10 months of age) or induced (after 10 months of age)

ovulation. Spontaneous ovulation has been reported to
occur in approximately 30-35% of adult queens.
Therefore, endometrial fluid accumulation in this queen is
probably due to a prolonged, repeated period of
progestational stimulation. Whether or not endometrial
fluid justifies antibiotic treatment is debatable. Little is
known about patterns of endometrial fluid accumulation
in the queen. Based on reported ultrasonographic
patterns of the feline uterus we know that some fluid may
be observed in normal queens at certain stages (especially
the luteal phase) of the reproductive cycle, but it has not yet
been established how much fluid is associated with disease.
It may be difficult to draw the line between a physiological
and a pathological fluid accumulation. However, normal
endometrial fluid is generally clear to transparent. The
presence of a blood-tinged vulval discharge probably
signals an inflammatory reaction which may justify a
treatment. In this case, an oral course of antibiotics
apparently helped the queen to recover from her uterine
condition.
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How I approach... Infertility in the queen

Table 2.
Causes of infertility responsible for failure
to conceive in queens
Failure to conceive in the queen
Errors in breeding management
Ovulatory failure due to breeding too early or too late
Diseases or developmental defects of the female reproductive tract
Oviductal hyperplasia and blockage
Partial or complete obstruction of the vulva, vagina,
cervix or uterus
Cystic endometrial hyperplasia-pyometra
Male problems
Retrograde ejaculation
Poor semen quality
Undiagnosed pregnancy
A pregnancy not diagnosed and subsequently lost may
be misdiagnosed as failure to conceive.

The second question is Why did she not conceive after

breeding to a fertile tom on repeated occasions? Potential
causes of failure to conceive are listed in Table 2.
Normal queens may fail to conceive because:
they may fail to ovulate, as demonstrated by lack of
corpora lutea development following repeated matings
during estrus (this is generally due to errors in breeding
management)
ovulation may occur but conception does not occur
due to congenital (partial or complete obstruction) or
acquired (pyometra) defects of the female genital tract;
partial lack of conception has been demonstrated by
looking at the ratio between corpora lutea and
implantation sites/fetuses during studies in which
pregnant queens were ovariohysterectomized at mid
pregnancy
the tomcat may have a problem such as poor semen
quality, low libido or lack of experience (which may
cause failure to achieve a complete intromission
necessary to induce ovulation) or retrograde ejaculation
(a rare defect which in the cat has been demonstrated,
although only following the use of some anesthetic
drugs)
Also, an undiagnosed pregnancy may be lost through
resorption or uterine trauma and rupture (followed by
fetal mummification in the abdomen) thus mimicking
failure to conceive.
Gengis Khan, the tomcat used for the breedings during
the period September-December 2004 was a proven
fertile male whose last litter was fairly recent, therefore
male problems are likely to be ruled out in this case. The
queen was housed at the owners cattery continuously
during the Autumn of 2004, and no trauma or disease
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other than the serosanguineous vulval discharge was

observed to occur during that time. Therefore, it is
highly unlikely that she may have conceived and
subsequently lost a pregnancy. As a consequence, the
only two possible causes of failure to conceive are an
error in breeding management and a reproductive
malformation or disease. Developmental defects of the
reproductive tract causing failure to conceive in the
queen despite regular cycling are rare and include
oviductal hyperplasia and blockage, partial or complete
obstruction (segmental aplasia) of the uterus and/or
cervix, myometrial fusion, and mucometra or hydrometra
due to impatency of the vulva, vagina, cervix or uterus as
a result of congenital anomaly, neoplasia, inflammation,
scarring or accidental ligation (Table 2). Also,
conceptus/es may fail to attach and implant into the
uterus because they find altered endometrial conditions
due to a pre-existent disease or to a disease acquired
during breeding. The most common uterine condition
limiting fertility in the queen is pyometra, which is often
characterized by a serosanguineous vulval discharge.
Although pyometra may very well be the cause of all the
problems of this queen, before we make our diagnosis
we need to assess breeding management, as mating at the
wrong time may be responsible for failure to conceive.
When questioned about breeding management, the
owner replied that the queen was placed in the tomcats
room on day 2 of each estrus where she remained for
several days, during which multiple matings were either
observed or heard to occur. Although this is acceptable
breeding management, queens may occasionally fail to
ovulate if bred in early estrus, especially on the 1st or 2nd
day of heat because follicles have not matured enough to
respond to the LH peak or the pituitary has not been
sensitized enough from circulating estrogens to release
LH following coitus. Failure to ovulate after breeding
on day 1 or 2 of estrus has been reported in queens
presented for infertility. In order to maximize fertility, it
is always advisable to wait at least until the 3rd day of
heat before bringing the queen to the male.
From the clinical perspective, confirming that ovulation
occurred may be important to assess breeding
management. This can be done relatively early after a
breeding simply by drawing a blood sample and assaying
serum progesterone. Because of rapid development of
corpora lutea in the queen, serum progesterone starts
rising as soon as 72 hours after breeding, and lasts for
35-45 days in the non-pregnant female. A serum
progesterone concentration higher than 1.5 ng/mL
indicates that the queen ovulated. Assaying serum
progesterone very soon after breeding obviously does not

How I approach... Infertility in the queen

help towards diagnosing pregnancy. However, a value

<1.5 ng/mL will rule out pregnancy thus focusing the
clinicians attention on breeding management.
Therefore, seeing the queen early following breeding
may be helpful from the practical standpoint as this is a
time when knowing serum progesterone assay can
provide useful information. Conversely, if one waits too
long, a serum progesterone value <1.5 ng/mL after day
35-40 following breeding may not be of help as
corpora lutea already start regressing at this time, and one
may be left with doubt whether the queen actually
ovulated.
After such a long and exhaustive history collection process,
the queen was given a physical examination. She was
found to be in good general condition, her pulse, respiration
rate and body temperature were normal, no physical
abnormalities were found and no medication was being
given. On abdominal palpation, her uterus felt slightly
enlarged. Because of the recent breeding (15 days earlier on
December 1st, 2004) it was decided not to perform an
abdominal ultrasound . A blood sample was collected from
the cephalic vein and aliquoted into plain and EDTA

containing vacutainers, to perform complete blood cell

count, serum chemistry and progesterone assay. Results are
illustrated in Table 3.
Nothing remarkable was observed on the queens
complete blood count or on her biochemistry profile.
Serum progesterone was 0.47 ng/mL, which reflects lack
of corpora lutea development. Two weeks after ovulation
serum progesterone is always >1.5 ng/mL, and very
frequently it is actually >10 ng/mL. Such a low value
indicates that this queen did not ovulate. This
demonstrates that breeding management was responsible
for failure to conceive (at least at the breeding of
December 1st). Whatever the cause for failure to
conceive at previous breedings (be it poor breeding
management or uterine disease) we need to address
breeding management with this owner. The owner was
therefore advised to breed the queen at the following
heat multiple times starting no earlier than on day 3 of
estrus.

Follow-up The queen came back in heat on January 22,

was bred multiple times to Gengis Khan starting on
January 25, conceived and
Table 3.
queened 2 live, normal kittens
Complete blood cell count and serum biochemistry results from a blood sample
on March 27, 61 days after her
collected on day 15 after breeding in a 2-year old Maine Coon queen presented
for failure to conceive
first breeding. One of the kittens
died soon after birth because the
Complete blood cell count
queen caused him extensive
Parameter
Value
Reference range
Leukocytes
15.13 K/L
5-19
abdominal trauma while
Erythrocytes
7.33 M/L
5-10
cleaning him up and chewing
Hemoglobin
11 g/dL
10-15
on his umbilicus. On May 22
Hematocrit
34.9 %
30-45
MCV
47.5 fl
39-55
she was in heat again and was
MCH
15 pg
13-20
bred to Silvestro, a young
MCHC
31.6 g/dL
30-36
Platelets
243 K/dL
156-800
(1-year old) and perhaps
inexperienced tomcat several
Neutrophils
8.35 x103/L (55%)
35-75
times starting on May 25. She
Lymphocytes
5.63 x103/L (37%)
20-55
Monocytes
0.85 x103/L (5%)
1-4
did not conceive, came back in
Eosinophils
0.32 x103/L (1%)
2-10
heat on July 4, was bred again
Basophils
0.03 x103/L (1%)
0-0.5
LUC*
0.25 x103/L (1%)
0.0-0.2
to Silvestro and delivered 7 live,
normal kittens on September
Serum Biochemistry
Glucose
64 mg/dL
73-134
16, 2005.
Urea
Total proteins
Albumin
Total bilirubin
Creatinine
CK
ALP
ALT
AST
GGT

62 mg/dL
78.5 g/L
33.2 g/L
0.07 mg/dL
1.2 mg/dL
171 U/L
99 U/L
57 U/L
30 U/L
2.4 U/L

20-65
54-78
21-33
0.15-050
0.8-1.8
63-273
25-93
6-83
26-43
1.3-5.1

Progesterone
(ovulation)

0.4 ng/mL

> 1.5 ng/mL

* Large Unidentified Cells

As we can see, our advice

produced a change in
breeding management which
was successful. The failure to
conceive at the breeding of
May 25 is difficult to assess.
The 42-day interval between
the two heats of May 22 and
July 4 is compatible with a
luteal phase, but serum
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How I approach... Infertility in the queen

progesterone was not assayed and therefore it is

impossible to ascertain what happened: the queen might
not have ovulated because of lack of libido from the
male, or might have ovulated but not conceived because
of poor semen quality. Lack of libido is actually the
most likely cause given the young age (and presumably
lack of experience) of Silvestro. Failure to ovulate is

often characterized by short interestrus intervals (1-3

weeks), however interestrus intervals longer than 2-3
weeks are sometime observed in non-ovulating queens.
Poor semen quality can be retrospectively ruled out
since the following breeding with Silvestro was
successful.

Further reading
Banks DR, Stabenfeldt G. Luteinizing hormone release in the cat in response
to coitus on consecutive days of estrus. Biol Reprod 1982; 26: 603-611.
Concannon PW, Hodgson B, Lein DH. Reflex LH release in estrous cats
following single and multiple copulations. Biol Reprod 1980; 23: 111-117.
Gudermuth DF, Newton L, Daels P, et al. Incidence of spontaneous ovulation
in young, group housed cats based on serum and faecal concentrations of
progesterone. J Reprod Fertil 1977; S 51: 177-184.
Feldman EC, Nelson RW. Feline reproduction. In: Canine and Feline
Endocrinology and Reproduction. EC Feldman and RW Nelson (eds). WB
Saunders, Philadelphia 2004; 3: 1016.
Johnston SD, Root Kustritz MV, Olson PNS. Clinical approach to the
complaint of infertility in the queen. In: Canine and Feline Theriogenology.
Johnston SD, Root Kustritz MV and Olson PNS (eds). WB Saunders,
Philadelphia 2001. pp. 486-495.

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Vol 16 No 2 2006

Lawler DF, Johnston SD, Hegstad RL, et al. Ovulation without cervical
stimulation in domestic cats. J Reprod Fertil 1993; S47: 57-61.
Lofstedt RM. The estrous cycle of the domestic cat. Comp Cont Educ Pract
1982; 4: 52-58.
Romagnoli S. Clinical approach to infertility in the queen. J Feline Med Surg
2003; 5: 143-146.
Romagnoli S. Failure to conceive in the queen. J Feline Med Surg 2005; 7: 59-64.
Shille VM, Lundstrom KE, Stabenfeldt GM. Follicular function in the
domestic cat as determined by estradiol-17b concentration in plasma: relation
to estrous behavior and cornification of exfoliated vaginal epithelium. Biol
Reprod 1979; 6: 953-963.
Wildt DE, Seager SWJ, Chakraborty PK. Effect of copulatory stimuli on
incidence of ovulation and on serum luteinizing hormone in the cat.
Endocrinology 1980; 107: 1212-1217.