Domestic Animal Endocrinology 23 (2002) 243–254

Strategies to optimize reproductive efficiency

by regulation of ovarian function
W.W. Thatcher a,∗ , F. Moreira a , S.M. Pancarci a ,
J.A. Bartolome a , J.E.P. Santos b
a
Department of Animal Sciences, University of Florida, Gainesville, FL 32611-0910, USA
b
Veterinary Medicine Teaching and Research Center, University of California-Davis, Tulare, CA 93274, USA

Abstract
Pregnancy rate to the Ovsynch protocol can be improved if cows are presynchronized (i.e., two
PGF2␣ injections given 14 days apart and the second injection of PGF2␣ given 12 days prior to the
first GnRH of the Ovsynch program) so that a greater proportion of cows during the Ovsynch protocol
ovulate to the first GnRH injection and have a CL at PGF2␣ injection. Pregnancy rates were normal
in anestrous cows (39.6%) if they ovulated to both injections of GnRH. Estradiol cypionate (ECP)
can be used to replace GnRH to induce ovulation as a modification of the Presync-Ovsynch program
(i.e., Presync-Heatsynch). Pregnancy rates after TI were 37.1 ± 5.8% for Presync-Ovsynch compared
to 35.1 + 5.0% for Presync-Heatsynch. Use of ECP to induce ovulation was an alternative to GnRH
in which greater uterine tone, ease of insemination and occurrence of estrus, improved acceptance by
inseminators. A GnRH agonist (Deslorelin; 750 ␮g) implant inserted at 48 h after injection of PGF2␣ ,
as a component of the Ovsynch protocol, induced ovulation, development of a normal CL and delayed
follicular growth until 24 d after implant insertion. Utilization of Deslorelin implants (450 ␮g and
750 ␮g) to induce ovulation compared to GnRH (100 ␮g) within the Ovsynch protocol resulted in
27 d pregnancy rates (GnRH 100 ␮g, 39%; Deslorelin implants 450 ␮g, 40% and 750 ␮g, 27.5%) with
12.7%, 5.0% and 9.5% embryonic losses by 41 d of pregnancy, respectively. Induction of an accessory
CL with injection of hCG on day 5 after insemination improved conception rates by 7.1%. Bovine
somatotrophin injected at first insemination following a Presync-Ovsynch program in cycling-lactating
dairy cows increased 74 days pregnancy rates (57.1% > 42.6%).
© 2002 Elsevier Science Inc. All rights reserved.

∗
Corresponding author. Tel.: +1-859-257-7541; fax: +1-859-257-7537.
E-mail address: thatcher@animal.ufl.edu (W.W. Thatcher).

0739-7240/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved.
PII: S 0 7 3 9 - 7 2 4 0 ( 0 2 ) 0 0 1 6 0 - 1
244 W.W. Thatcher et al. / Domestic Animal Endocrinology 23 (2002) 243–254

1. Introduction

In high producing dairy cows, herd pregnancy rates are reduced due to poor heat expression
and/or detection, anestrus, low conception rates, and increased embryo mortality. Further-
more, these impediments to optimal reproductive performance are exacerbated under stressful
environmental conditions such as heat stress, which is even more detrimental in higher milk
producing cows [1]. Reproductive performance has decreased in North America, Europe,
and Australia. Reasons for the decline are multi-factorial and not entirely associated with an
increase in milk production [2]. Epidemiology studies indicate that other factors such as re-
productive diseases (i.e., retained placenta, metritis, and ovarian cysts) or season of calving
were relatively more important than milk yield on reproductive performance [1,3]. In fact,
higher producing herds may have a greater reproductive performance because of better feed-
ing, reproductive management, and healthier cows. Nevertheless, the physiological state of
lactation is associated with a lower reproductive rate compared to heifers [4]. In lactating
dairy cows, the proestrous concentrations of estradiol are lower as are luteal phase concentra-
tions of progesterone compared to non-lactating cows [5]. Altered functional competence of
follicles may be due to altered concentrations of LH and IGF-I [6] in lactating cows. Increased
liver metabolism of progesterone associated with dry matter intake may limit progesterone
availability [7]. These altered endocrine conditions may impede optimal reproductive perfor-
mance. Major advancements have been made in the regulation of ovarian function such that
systems are now available to control and coordinate ovarian follicular, corpus luteum, and
uterine functions in a manner that is conducive to normal fertility in lactating dairy cows. Ob-
jectives of the present work are to examine various pharmacological approaches to optimize
reproductive efficiency by coordinating and regulating ovarian follicular and CL function in
lactating dairy cows.

2. Development and optimization of timed insemination programs

The ability to control the time of ovulation precisely following a period in which follic-
ular development and CL regression have been programmed sequentially permits a timed
insemination. Such programs are essential in high producing dairy cows that experience a
reduction in estrus intensity that contributes to undetected heats, re-occurring luteal phases
without estrus expression, or re-occurring waves of follicles that fail to ovulate. Develop-
ment of timed insemination programs has been based upon a thorough understanding of
the factors controlling ovarian follicular growth [8]. One program that has been extremely
successful for insemination of cows at a fixed time for first service without the need for
detection of estrus is the Ovynch program in which injections of GnRH are given 7 days
before and 48 h after an injection of PGF2␣ , and cows are inseminated 16–20 h after the sec-
ond injection of GnRH. This system synchronizes follicle maturation with regression of the
corpus luteum before the GnRH-induced ovulation and timed insemination. Numerous stud-
ies indicate that pregnancy rates (proportion of all treated cows that were pregnant) to the
Ovsynch program were comparable and in some studies greater than the appropriate control
group [9–17].
 W.W. Thatcher et al. / Domestic Animal Endocrinology 23 (2002) 243–254 245

There are several stages of the estrous cycle when initiation of the Ovsynch program causes
reduced pregnancy rates [18–20]. Initiation of the program between days 13 and 17 of the
cycle is a time in which spontaneous regression of the CL occurs prior to the time that PGF2␣
is injected at 7 days after the injection of GnRH. These cows will be asynchronized in that they
may ovulate prior to the time of insemination, and insemination will be to late for the cow to
conceive. During the early stages of the cycle (e.g., days 2–4), the recruited dominant follicle
is not sufficiently developed to ovulate in response to GnRH. As a consequence, the dominant
follicle at the second injection of GnRH is considered aged and has expressed dominance for
5 days or longer. Follicles that have periods of dominance longer than 5 days are less fertile
[21] and some of these aged follicles fail to ovulate in response to the ovulatory injection
of GnRH [19]. An additional point to consider is that GnRH-induced turnover of follicles or
induction of a new follicular wave is most efficient if ovulation is induced in response to the
first injection of GnRH. Collectively, these findings indicate that presynchronization of cows
prior to implementation of the Ovsynch program should improve pregnancy rates if cows enter
the Ovsynch program at the most favorable period of the estrous cycle (i.e., days 5–12 of the
cycle).
A program defined as Presync-Ovsynch was developed in which presynchronization is
achieved with a standard estrous synchronization protocol (PGF2␣ given twice at a 14-day
interval) with the Ovsynch program initiated 12 days after the second injection of PGF2␣ .
A Presynch-Ovsynch program increased pregnancy rates 12 percentage units (i.e., 37–49%;
[23]) and 18 percentage units (i.e., 25–43%; [22]) in lactating cyclic cows. This stimulation in
pregnancy rates was attributed to manipulation of the estrous cycle such that the Ovsynch, timed
insemination program was initiated at the most favorable stages of the estrous cycle. Future
programs for further optimization of fertility likely will consider programs that manipulate
ovarian function such that follicular turnover via ovulation or induced follicular atresia occurs
in all cows, and luteal phase like progesterone concentrations are sustained until the time of
induced CL regression. These future systems in lactating dairy cows may include insertion
of intravaginal devices containing progesterone and acute injections of estrogens. However,
inclusion of these strategies will require acceptance by regulatory agencies and consumers.
For example, the two approved classes of pharmaceuticals for use in lactating dairy cows in
the USA are the GnRH and PGF2␣ drugs.
Success of the Ovsynch program is dependent on whether lactating dairy cows are anestrus
or cycling [22]. Pregnancy rates were less in cows that were not cycling at the time the Ovsynch
program was initiated (e.g., 22 versus 42%). Overall, the TAI protocol was able to induce cycles
in 75% of anestrous cows, based upon the number of anestrous cows which were classified as
ovulating to either the first and/or second injection of GnRH. If anestrous cows ovulate to the
first and second GnRH injections of the Ovsynch program then pregnancy rates appeared to be
normal (e.g., 39%). Thus, the Ovsynch protocol was successful in regulating ovarian function
in certain anestrous cows such that they conceived. Pregnancy rates to the second service for
anestrous cows were similar to those obtained for cyclic cows and constitute further evidence
for a beneficial effect of the Ovsynch protocol, when used on anestrous cows in response to
two GnRH injections over a 9-day period. Many anestrous cows have re-occurring anovulatory
follicles that are not estrogenic [6] and fail to induce a preovulatory surge of LH. The timely
injections of GnRH to induce LH and FSH, as part of the Ovsynch protocol, appear to induce
246 W.W. Thatcher et al. / Domestic Animal Endocrinology 23 (2002) 243–254

functional follicle development and ovulations that permit initiation of a pregnancy in some
anestrous cows with anovulatory follicles.
An alternative strategy to control the time of ovulation is the ability of exogenous estradiol
to induce a LH surge by stimulating hypothalamic secretion of GnRH when given in a low
progesterone environment during late diestrus and proestrus. An estradiol induced LH surge
lasts for approximately 10 h, which is comparable to a spontaneous LH surge and longer than
the LH surge induced by GnRH. Estradiol cypionate (ECP), an esterified form of estradiol-17␤
that is available commercially for use in cattle, has been used as part of a timed insemination
program in lactating dairy cows to replace the second GnRH injection of an Ovsynch program
[24].
Pregnancy rates were evaluated in lactating dairy cows when ECP was used to induce
ovulation as part of a timed insemination protocol in comparison to Ovsynch for lactating dairy
cows in Florida (n = 371) and Texas (n = 321). In two studies in Florida and Texas, cows were
presynchronized with two injections of PGF2␣ given 14 days apart with timed insemination
protocols beginning 14 days after the second injection of PGF2␣ [24]. The protocols consisted
of an injection of GnRH followed by PGF2␣ 7 days later. Cows were injected either with
GnRH (Ovsynch) at 48 h after PGF2␣ and inseminated 16–24 h later or with ECP (1 mg, i.m.)
at 24 h after PGF2␣ , Heatsynch) and inseminated 48 h later. Pregnancy rates did not differ
between Heatsynch and Ovsynch programs at either site (Table 1). In lactating dairy cows,
the frequencies of detected estrus and ovulation after ECP were 75.7 and 86.5%, respectively.
Estrus occurred at 29.0±1.8 h (n = 28) after ECP. Mean intervals to ovulation were 55.4±2.7 h
after ECP and 27.5 ± 1.1 h after onset of estrus. Since 75% of the ovulations occurred between
≥48 and ≤72 h after ECP, it is recommended that any cow detected in estrus by 24 h after
ECP injection be inseminated at 24 h, and all remaining cows be inseminated at 48 h. Based
on synchronization of ovulation and pregnancy rates, ECP can be utilized as an alternative
to induce ovulation in place of GnRH for a timed insemination. Timing of ECP injection
to induce ovulation for a Heatsynch program differs compared to the use of GnRH in an
Ovsynch program. The timing differences between ECP injection and insemination (i.e., 24
or 48 h) of the Heatsynch program versus GnRH injection and insemination (i.e., 12–16 h)
of the Ovsynch program makes the Heatsynch protocol more easily applied relative to the
sequence of injections and insemination being made at the same time of day. Greater uterine
tone, ease of insemination and occurrence of estrus with the use of the Heatsynch program are
well received by inseminators. Alternatively, in facilities with concrete flooring, the reduced

Table 1
Pregnancy rates (LSM ± SE) of lactating dairy cows to a timed insemination following Ovsynch or Heatsynch
programs
Location Ovsynch group Heatsynch group Overall
(n = 179)a (n = 192)b (n = 371)
Florida (n = 371) 37.1 ± 5.8 35.1 ± 5.0 39.6 ± 2.5
Texas (n = 321) 28.2 ± 3.6 29.0 ± 3.5 26.8 ± 2.4
a
Ovsynch: GnRH (day 10), PGF2␣ (day 3), and GnRH (day 1) with timed AI on day 0.
b
Heatsynch: GnRH (day 10), PGF2␣ (day 3), and ECP (day 2) with timed AI on day 0.
 W.W. Thatcher et al. / Domestic Animal Endocrinology 23 (2002) 243–254 247

estrous expression associated with the Ovsynch program may be preferred. Since fertility
between the two programs appears to be comparable, producers have a choice, which also
includes relative costs of drugs (i.e., ECP < GnRH).

3. Alterations in ovarian function to improve embryo survival

A major impediment to acceptable herd pregnancy rates in lactating dairy cows is the high
rate of embryo mortality (e.g., 44%; [25,26]). The ability to control either the occurrence of
estrus or the time of ovulation precisely reduces the problem of poor heat detection consid-
erably and permits investigators to focus on strategies to improve conception rates following
insemination.

3.1. Bovine somatotropin

In cycling-lactating dairy cows [22], injection of bovine somatotropin (500 mg Posilac,

Monsanto Co., St. Louis, MO) at the time of the first GnRH injection or at insemination in
cows of a Presynch-Ovsynch program increased pregnancy rates (57% > 42.6%). Since bST
was effective at insemination, it is likely that bST stimulated embryonic development and
survival following insemination in lactating dairy cows. There was no evidence that bST given
at the nineth week of lactation is detrimental to fertility when used with a timed breeding
protocol such as Ovsynch. A study in Mexico reported, that in cows identified as having three
or more prior services, bST given at estrus and again 10 days later stimulated pregnancy
rates [27]. The ability to detect this bST beneficial effect likely is attributable to the fact that
bST was given at a physiologically important window in which occurrence of estrus and or
ovulation was controlled. Several studies [28,29] showed that bST stimulated bovine in vitro
maturation of oocytes and embryonic development. Furthermore, administration of bST at
artificial insemination (AI) to superovulated donor cows decreased the number of unfertilized
ova, increased the percentage of transferable embryos, and stimulated embryonic development
to the blastocyst stage. Moreover, bST affected both early embryonic development and recipient
components to increase pregnancy rates following embryo transfer [30]. Additional research
is warranted to examine the effects of bST on the endometrium and the potential cross-talk
between signal transduction systems elicited by bST and IFN-␶ that may improve embryo
survival.

3.2. HCG induction of accessory CL

The opportunity to regulate ovarian function after insemination to improve pregnancy rates
is an additional production management strategy. The ability to induce ovulation of the healthy
first wave follicle either at day 5 of the cycle or after insemination results in two altered en-
docrine states. The administration of hCG induces ovulation with the subsequent formation
of a functional accessory CL [31–33]. The majority of the increase in plasma progesterone
after hCG was due to the accessory CL [33]. Size of CL, in vitro production of progesterone,
and plasma concentrations of progesterone were greater in accessory CL induced by hCG
248 W.W. Thatcher et al. / Domestic Animal Endocrinology 23 (2002) 243–254

than GnRH. Due to the induction of ovulation at day 5, cows will experience three follicular
wave cycles due to the earlier emergence of the second wave [31]. Furthermore, the third
follicular wave is delayed. Development of the conceptus is related to higher concentrations of
progesterone and ability of the conceptus to secrete IFN-␶ [34]. Therefore, hCG induction of
an accessory CL with increased progesterone may enhance embryo survival. Since a greater
number of cows conceived that had three follicular waves after insemination compared with
cows having two follicular waves [35], hCG induction of three wave cycles also may contribute
to higher pregnancy rates. Following synchronization of estrus and AI in a field study, 406
cows were injected with either hCG or saline on day 5 after AI [36]. Treatment with hCG re-
sulted in 86.2% of the cows with more than one CL compared with 23.2% in controls. Plasma
progesterone concentrations were increased by 5.0 ng/mL in hCG-treated cows. Presence of
more than one CL increased progesterone concentration in hCG-treated cows but not in con-
trols. Conception rates were higher for hCG-treated cows on day 28 (45.8% > 38.7%), day
45 (40.4% > 36.3%), and day 90 (38.4% > 31.9%) after AI. Of practical importance was
the observation that treatment with hCG improved CR in cows losing BCS between AI and
day 28 after AI. Pregnancy losses were similar between treatment groups. It was evident that
hCG on day 5 after AI induced an accessory CL, which contributed to an increase in plasma
progesterone concentration, and improved conception rates in high producing dairy cows.

4. Regulation of ovarian function with a GnRH agonist implant

A GnRH agonist implant (Deslorelin, 700 ␮g; implant releases Deslorelin over a 4 days
period in vitro) altered CL function and follicular dynamics when administered on day 0 (day
1 = day of ovulation; [37]). The increase in plasma progesterone between days 0 and 15
was greater for the GnRH agonist implant group, than either a non-treated Control or a stan-
dard GnRH injection. These results support the hypothesis that GnRH agonist via an implant
induces development of a more functional CL. Furthermore, development of the first wave
dominant follicle was delayed. It appears that early LH secretion was stimulated in the GnRH
agonist implant group to increase CL development. However, subsequent secretion of FSH
and LH appeared to be reduced due to desensitization of the pituitary in a manner that delays
development of the dominant follicle but does not compromise CL function. The opportunity
to insert a GnRH agonist implant to induce ovulation, stimulate development of a more func-
tional CL, and delay functional maturation of dominant follicles until after development of the
antiluteolytic mechanism, is a potentially novel means to improve conception rates as part of a
timed insemination program to increase conception rate and embryo survival. However, doses
of the GnRH agonist implant need to be evaluated to avoid prolonged periods of suppressed
follicular development and returns to estrus in cows that do not conceive.
The following experiment was designed to test the effects of 750 and 1000 ␮g GnRH agonist
(Deslorelin) implants on follicle dynamics and CL function following an induced ovulation and
subsequent induction of CL regression. Non-lactating dairy cows (n = 20) were injected on day
9 with 100 ␮g GnRH i.m. and with two doses of PGF2␣ (25 mg, i.m.) given 8 h apart on day 2. On
day 0, cows were assigned randomly to receive 100 ␮g GnRH (Control, n = 6), a 750 ␮g GnRH
agonist implant (Deslorelin, n = 7; s.q.) or a 1000 ␮g implant (Deslorelin, n = 7; s.q.). On
 W.W. Thatcher et al. / Domestic Animal Endocrinology 23 (2002) 243–254 249

day 16, cows were injected with PGF2␣ (two 25 mg doses given 8 h apart) to induce luteolysis.
Ovaries were evaluated by ultrasonography daily from day 0 until GnRH-induced ovulations,
and then every other day until day 36. Daily blood samples were collected from day 0 until
either ovulation after PGF2␣ given on day 16, or until day 36 to monitor plasma progesterone
concentrations. The Heat Watch® system was used to monitor estrus. After day 16 if cows
did not have a spontaneous ovulation regardless of estrus activity, the Ovsynch protocol was
initiated when a 20 mm ovarian follicle was detected. The following responses were evaluated
during two periods (days 0–16 and >day 16): days 0–16, plasma P4 concentrations (ng/mL),
size of first and second wave dominant follicles (mm), number of class 2 (5–9 mm) and class
3 (>10 mm) follicles; >day 16, size of the dominant follicle (mm), rate of follicular growth
(mm/day), expression of estrus, number of class 2 and 3 follicles, and response to Ovsynch
for cows that did not ovulate after day 16.
All cows ovulated and formed a CL after treatments on day 0. Overall mean concentrations
of progesterone from days 0 to 16 were not different between cows in Control group (5.9 ±
0.6 ng/mL), Deslorelin 750 ␮g (6.4 ± 0.6 ng/mL), and Deslorelin 1000 ␮g (6.3 ± 0.6 ng/mL)
groups. However, progesterone concentrations were higher on day 11 for cows in the Deslorelin
1000 ␮g group (11.1±1.0 ng/mL) compared to the Control group (8.2±1.1 ng/mL; P < 0.05)
and on day 12 for cows in Deslorelin 750 ␮g group (12.4 ± 1.0 ng/mL) compared to cows in
Control group (9.0 ± 1.1 ng/mL; P < 0.05; Fig. 1). There was no evidence that the GnRH
agonist implant compromised CL function and appeared to have a slight stimulatory effect.
Size of the first wave dominant follicle was greater for the Control group than the 1000 ␮g
Deslorelin implant group (P < 0.05) with dominant follicle size being intermediate for the
750 ␮g Deslorelin group (Fig. 2). Up to the time of PGF2␣ injection on day 16, a second wave
dominant follicle had developed to a preovulatory size (i.e., >10 mm) for the Control group but
not for the 750 and 1000 ␮g Deslorelin implant groups. Clearly, follicular development was
attenuated in cows treated with the GnRH agonist implants, and this is further substantiated by
the decrease in number of class 2 follicles for both of the Deslorelin implant groups compared

Fig. 1. Concentrations of progesterone between days 0 and 16 for cows receiving Control (䊏) or GnRH agonist
implants (Deslorelin 750 ␮g (䊉) and 1000 ␮g (䉱)) on day 0. Least squares means and standard errors. ∗ , P < 0.05
day 11, Control vs. 1000 ␮g Deslorelin implant and day 12, Control vs. 750 ␮g Deslorelin implant.
250 W.W. Thatcher et al. / Domestic Animal Endocrinology 23 (2002) 243–254

Fig. 2. Size (mm) of first and second wave dominant follicles between days 0 and 16 for cows receiving Control (䊏)
or GnRH agonist implants (Deslorelin 750 ␮g (䊉) and 1000 ␮g (䉱)) on day 0. Least squares means and standard
errors.

to the cyclic pattern of an increase in number of class 2 follicles in the Control group. This
increase in controls was associated with recruitment of the first wave follicle followed by
attenuation with development of follicle dominance after day 3 (Fig. 3).
Average diameter of the largest follicle from days 16 to 20 was larger (P < 0.001) in cows
of Control group (16.1±0.9 mm) compared to cows of the 750 ␮g (6.3±0.8 mm), and 1000 ␮g
(4.7 ± 0.8 mm; Fig. 4) Deslorelin implant groups. The number of cows expressing estrus and

Fig. 3. Number of class 2 follicles (2–5 mm) follicles between days 0 and 16 for cows receiving Control (䊏) or
GnRH agonist implants (Deslorelin 750 ␮g (䊉) and 1000 ␮g (䉱)) on day 0. Least squares means and standard
errors.
 W.W. Thatcher et al. / Domestic Animal Endocrinology 23 (2002) 243–254 251

Fig. 4. Size (mm) of dominant follicles following injection of PGF2␣ on day 16 in cows receiving Control (䊏)
or GnRH agonist implants (Deslorelin 750 ␮g (䊉) and 1000 ␮g (䉱)) on day 0. Least squares means and standard
errors. Occurrence of estrus for Control ( ), Deslorelin 750 ␮g ( ), and 1000 ␮g ( ) treated cows.

ovulating 4 days after PGF2␣ on day 16 was higher (P < 0.001) in the Control group (6/6)
compared to cows of the Deslorelin 750 ␮g (1/7) and 1000 ␮g (0/7) groups. Subsequent rate of
follicular growth from days 16 to 36 was greater in the Deslorelin 750 ␮g group (0.67 mm/day)
than in the Deslorelin 1000 ␮g (0.4 mm/day; P < 0.01) group. Out of 14 cows, 12 cows (86%)
in Deslorelin 750 and 1000 ␮g groups expressed estrus between days 24 and 36 (one cow was
in estrus on day 19 and one did not show estrus) but failed to ovulate. The 12 cows that
failed to ovulate underwent an Ovsynch protocol when the largest follicle reached 20 mm in
diameter; 9/12 (75%) ovulated synchronously in response to the second GnRH injection of
the Ovsynch protocol. Deslorelin implants have the potential to induce ovulation, stimulate
development of a normal CL, and delay follicular growth during the subsequent diestrus period
after insemination. Since follicular development is attenuated during pregnancy [38,39] and
follicular wave dynamics are associated with pregnancy rates [35], than an induced attenuation
of follicular development may further reduce endometrial secretion of PGF2␣ at the time the
conceptus decreases PGF2␣ to maintain the CL.
A study was conducted to evaluate pregnancy rates using a 450 or 750 ␮g Deslorelin implant
in comparison to a 100 ␮g GnRH injection to synchronize ovulation in the Presync-Ovsynch
protocol with lactating dairy cows. Cows in the Deslorelin implant groups received PGF2␣ on
d0 (30 days postpartum), PGF2␣ on d14, GnRH (100 ␮g) on d28, PGF2␣ on d35, Deslorelin
implants (450 or 750 ␮g) on d37 and time insemination (TAI) on d38 (16 h after implant
insertion). Cows in the control group received PGF2␣ on d0 (30 days postpartum), PGF2␣ on
d14, GnRH on d28, PGF2␣ on d35, GnRH on d37 and a timed insemination on d38 (16 h
after GnRH). Cows were diagnosed for pregnancy on d27 by ultrasonography, and pregnant
cows re-examined by rectal palpation on d41 after insemination to evaluate pregnancy losses.
Pregnancy rates at day 27 for a total of 596 cows differed between the Deslorelin implant groups
and the control (Table 2), with the 750 ␮g Deslorelin implant group having a lower pregnancy
rate than the 450 ␮g implant group (P < 0.01). The GnRH control group and the 450 ␮g
implant group had good pregnancy rates of approximately 40%. Pregnancy rates at 41 days
had decreased with possible differences in pregnancy losses of 5.0% for the 450 ␮g Deslorelin
252 W.W. Thatcher et al. / Domestic Animal Endocrinology 23 (2002) 243–254

Table 2
Reproductive responses of lactating dairy cows to a Presynch-Ovsynch Program utilizing a Deslorelin implants
(450 ␮g and 750 ␮g) or GnRH injection to induce ovulation
Response GnRH control Deslorelin implants
100 ␮g 450 ␮g 750 ␮g

Number of cows 293 150 153

Pregnancy rate %, d 27 39.0a 40.0a 27.5b
Pregnancy rate %, d 41 33.5a 38.0a 24.8b
Pregnancy loss %, d 27–41 12.7c 5.0d 9.5c,d
a ,b
Superscripts within the same row differ (P < 0.01).
c,d
Superscripts within the same row differ (P < 0.13).

implant versus 12.7% for the GnRH control (P < 0.13; Table 2). The percent of non-pregnant
animals at day 27 that were re-inseminated by day 27 was less for the Deslorelin implant groups
(450 ␮g, 28.7%; 750 ␮g, 11.7%) compared to GnRH control (51.4%, P < 0.01). The potential
reduction in pregnancy losses attributable to the 450 ␮g Deslorelin implant needs verification
with additional numbers of cows to detect a possible increase in embryo survival. Present
findings support the hypothesis that the Deslorelin implant may improve embryo survival,
and additional research is warranted relative to lower doses of the Deslorelin implant and
applications in the postpartum period to regulate ovarian activity [40].

5. Implications

Several reproductive management strategies (e.g., Ovsynch and Heatsynch programs) have
been developed to implement a timed insemination with normal fertility in lactating dairy
cows. Essential for the implementation of such programs is that producers have a thorough
biological understanding of how the programs work in order to achieve on farm compliance.
This programs allow producers to precisely control the time for insemination in the postpartum
period, which permits a delay in the time of first insemination to achieve better body condi-
tion and reduce the incidence of anestrus. Future research challenges to improve reproductive
management of lactating dairy cows are to improve embryo survival (e.g., induction of ac-
cessory CL, timely administration of bST, etc.), promptly identify pregnant and non-pregnant
animals, and target the non-pregnant cow for a programmed re-synchronization of ovulation
for re-insemination.

Acknowledgments

Research conducted by the authors was partially supported by: Research Grant No. IS-3000-
98R from BARD, The United States-Israel Binational Agricultural Research and Development
Fund; Florida Milk Checkoff Program; Pharmacia Co. (Kalamazoo, MI); Monsanto Company,
Agricultural Sector, Dairy Business (St. Louis, MO). This is Florida Agriculture Experimental
Station Journal Series No. R-08749.
 W.W. Thatcher et al. / Domestic Animal Endocrinology 23 (2002) 243–254 253

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