Effects of estradiol cypionate (ECP) on ovarian follicular dynamics, synchrony of ovulation, and fertility in CIDR-based, fixed-time AI programs in beef heifers

doi:10.1016/S0093-691X(03)00091-8

Theriogenology

Volume 60, Issue 5, 15 September 2003, Pages 855-865

https://doi.org/10.1016/S0093-691X(03)00091-8 Get rights and content

Abstract

Estradiol cypionate (ECP) was used in beef heifers receiving a controlled internal drug release (CIDR; insertion=Day 0) device for fixed-time AI (FTAI) in four experiments. In Experiment 1, heifers (n=24) received 1 mg ECP or 1 mg ECP plus 50 mg commercial progesterone (CP) preparation i.m. on Day 0. Eight or 9 days later, CIDR were removed, PGF was administered and heifers were allocated to receive 0.5 mg ECP i.m. concurrently (ECP0) or 24 h later (ECP24). There was no effect of treatment (P=0.6) on mean (±S.E.M.) day of follicular wave emergence (3.9±0.4 days). Interval from CIDR removal to ovulation was affected (P<0.05) only by duration of CIDR treatment (88.3±3.8 h versus 76.4±4.1 h; 8 days versus 9 days, respectively). In Experiment 2, 58 heifers received 100 mg progesterone and either 5 mg estradiol-17β or 1 mg ECP i.m. (E-17β and ECP groups, respectively) on Day 0. Seven (E-17β group) or 9 days (ECP group) later, CIDR were removed, PGF was administered and heifers received ECP (as in Experiment 1) or 1 mg EB 24 h after CIDR removal, with FTAI 58–60 h after CIDR removal. Follicular wave emergence was later (P<0.02) and more variable (P<0.002) in heifers given ECP than in those given E-17β (4.1±0.4 days versus 3.3±0.1 days), but pregnancy rate was unaffected (overall, 69%; P=0.2). In Experiment 3, 30 heifers received a CIDR device and 5 mg E-17β, with or without 100 mg progesterone (P) i.m. on Day 0. On Day 7, CIDR were removed and heifers received ECP as described in Experiment 1 or no estradiol (Control). Intervals from CIDR removal to ovulation were shorter (P<0.05) in ECP0 (81.6±5.0 h) and ECP24 (86.4±3.5 h) groups than in the Control group (98.4±5.6 h). In Experiment 4, heifers (n=300) received a CIDR device, E-17β, P, and PGF (as in Experiment 3) and after CIDR removal were allocated to three groups (as in Experiment 2), with FTAI 54–56 h (ECP0) or 56–58 h (ECP24 and EB24) after CIDR removal. Pregnancy rate did not differ among groups (overall, 63.6%, P=0.96). In summary, although 1 mg ECP (with or without progesterone) was less efficacious than 5 mg E-17β plus 100 mg progesterone for synchronizing follicular wave emergence, 0.5 mg ECP (at CIDR removal or 24 h later) induced a synchronous ovulation with an acceptable pregnancy rate to fixed-time AI.

Introduction

Estradiol-17β (E-17β) and estradiol benzoate (EB) are commonly used to synchronize follicular wave emergence [1], [2], [3], [4] and ovulation [5], [6], [7], [8] in controlled internal drug release (CIDR)-treated cattle. However, estradiol cypionate (ECP), an ester of estradiol with a low water solubility that delays its release from the site of injection, is the only estrogen ester licensed for use in cattle in North America. Plasma concentrations of estradiol were prolonged (98–170 h) after intramuscular administration of large doses (5–10 mg) of ECP [9], [10]. However, when ovariectomized beef heifers were treated with only 2 mg ECP, the duration of estrus (15.8±1.1 h) was not different from heifers with a spontaneous estrus [11], suggesting that reduced doses of ECP may be useful in estrus synchronization regimens.

The effects of ECP on ovarian follicular wave emergence and ovulation have been studied in lactating Holstein cows [12]. Although 1 mg ECP was more efficacious than 0.5 mg in synchronizing follicular wave emergence, the authors concluded that the prolonged half-life of ECP made it far less efficacious than E-17β for synchronizing both follicular wave emergence and ovulation in CIDR-treated dairy cattle. However, Lopes et al. [13] used ECP successfully to replace the second treatment with GnRH to synchronize ovulation for fixed-time AI (FTAI) in an Ovsynch-type program in dairy cattle. Furthermore, Ambrose et al. [14] reported that 0.5 mg ECP administered concurrently with CIDR removal synchronized ovulation in Holstein heifers that had received PGF 24 h before CIDR removal. To our knowledge, the use of ECP in comparison or combination with E-17β or EB for FTAI in beef cattle has not been reported.

Four experiments were designed to study and compare the effects of ECP (with or without injectable progesterone), E-17β, and EB on follicular dynamics, time of ovulation, and pregnancy rate to FTAI in CIDR-based protocols. In addition, the duration of CIDR treatment (8 days versus 9 days) on the interval from CIDR removal to ovulation was determined.

Section snippets

Experiment 1

Puberal, crossbred beef heifers 18–20 months of age (n=24), received a once used intravaginal progesterone releasing device (CIDR; Bioniche Animal Health; Belleville, Ont., Canada) at random stages of the estrous cycle, and were randomly assigned to two groups to concurrently receive either 1 mg estradiol cypionate i.m. (ECP; Pharmacia Animal Health, Orangeville, Ont., Canada; n=13) or 1 mg ECP plus 50 mg commercial progesterone preparation (CP; Progesterone 5%^®, J Webster Lab Inc., Victoriaville,

Experiment 1

Two heifers, one in each treatment group, did not respond to treatment to induce follicular wave emergence at CIDR insertion and they were excluded from the calculation of the interval from treatment to wave emergence. There was an effect of day (P<0.0001) on diameter of the regressing follicle, but the effects of treatment (P=0.17), and the treatment by day interaction (P=0.66) were not significant. Similarly, the effects of day (P=0.35), treatment (P=0.99) and the treatment by day interaction

Discussion

Although the administration of 1 mg ECP resulted in relatively synchronous follicular wave emergence in the present study, synchrony was less precise than with 5 mg E-17β; this is consistent with a previous study in which the administration of ECP to dairy cows resulted in relatively asynchronous follicular wave emergence [12]. In this regard, Bó et al. [16] reported delayed or asynchronous emergence of a new follicular wave when 5 mg EB (another estradiol ester) was administered. However,

Acknowledgements

Marcos Colazo was supported by FOMEC (Universidad de La Pampa, Argentina) and the University of Saskatchewan. The Saskatchewan Agriculture Development Fund, Strategic Research Program provided financial support. The authors thank Bioniche Animal Health for CIDR devices, Schering-Plough Animal Health for Estrumate, and Pharmacia Animal Health for Lutalyse. The authors also wish to thank Dr. Leonardo Brito, Dr. Cristal Deyo, Mr. Quinn Gavaga, Mr. Ken Piller (Neudorf, SK), Mr. William Kerr and the

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Estrogens have proven to be effective in bovine estrus induction protocols. Considering the extensive use of these products in large-scale estrus synchronization, the primary objective of the present study was to assess their effects on pregnancy rate (PR) using a meta-analysis approach. A total of 797 papers were screened from three major databases (PubMed, Web of Science, Scopus). Sixty-one studies were eligible for inclusion in the meta-analysis. The pregnancy status (success or failure) at 30 days post-insemination was considered as the effect size data. The odds ratios (OR) of PR were evaluated by considering the effects of estrogens in groups with or without estrogen intervention. The impact of estrogen (including factors such as type, dose, and time of administration) and animal characteristics (such as breed, type, and parity) was taken into account when assessing the effectiveness of estrogen response as PR. The results showed an OR of 1.25 (95% CI: 1.15–1.36; P = 0.000) for PR in animals that received estrogen compared to cattle that did not receive estrogen. Estradiol benzoate (OR = 1.3) and estradiol cypionate (OR = 1.2), with doses ranging from 1 to 3 mg (OR = 1.13–1.7), significantly increased the OR of PR. In terms of PR, beef cattle exhibited a higher odds ratio (OR = 1.4; P = 0.000) compared to dairy cattle (OR = 1.1; P = 0.09). The administration of estrogens in the estrus synchronization protocol significantly improved PR in both artificial insemination (OR = 1.2; P = 0.000) and embryo transfer (OR = 1.3; P = 0.033) programs. In summary, incorporating estrogens into estrus induction protocols led to an enhancement of the OR of PR among cattle.
Is estradiol valerate an alternative to estradiol benzoate in promoting the synchronization of ovulation and timed artificial insemination in suckled Bos indicus beef cows?
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The objective of the present study was to evaluate the effect of estradiol valerate administered at the beginning of the ovulation synchronization protocol on the pregnancy rate of Bos indicus cows. In the experiments, the following products from MSD, Sao Paulo, Brazil were used: estradiol valerate (EV), estradiol benzoate (EB), intravaginal progesterone device (P4), estradiol cypionate (EC), equine chorionic gonadotropin (eCG) and cloprostenol (PGF). In Experiment 1, Bos indicus cows (n=899) with a body condition score (BCS) of 2.76 ± 0.01 were included in a 3 (device) × 2 (protocol: 5 mg of EV or 2 mg of EB) factorial design. There were three types of P4 devices: a new device (New), a device previously used for 9 days (1×), and a device previously used for 18 days (2×). Nine days later (D9), the P4 device was removed, and cows received 300 IU of eCG. In addition, cows in the EB group received 1 mg of EC and 265 μg of PGF. Timed artificial insemination (TAI) was performed 48 h after P4 device removal in the EB group (TAI48) and 54 h after P4 device removal in the EV group (TAI54). In Experiment 2, Bos indicus cows (n=434) with a BCS of 2.62 ± 0.01 received a new P4 device or one previously used for 9 days and 5 mg of EV. On D9, all cows received 300 IU of eCG, and the P4 devices were removed and distributed in TAI48 and TAI54 cows. In Experiment 3, Bos indicus cows (n=429) with a BCS of 2.80 ± 0.01 were divided into the control and EV/EC groups. All cows received a P4 device. In addition, cows in the control group received 2 mg of EB, and cows in the EV/EC group received 5 mg of EV on D0. On D9, all cows received 1 mg of EC and 300 IU of eCG, and the P4 devices were removed. Cows in the control group also received 265 μg of PGF. All cows were inseminated 48 h after the removal of the P4 device. In Experiment 1, there was no effect of the interaction between protocol and P4 device on the occurrence of estrus (P=0.45) or on the pregnancy per artificial insemination ratio (P/AI; P=0.30). In addition, the occurrence of estrus and P/AI were not different between in the two estradiol groups (P=0.12 and P=0.82) and across the types of intravaginal P4 device (P=0.91 and P=0.47). In Experiment 2, the pregnancy rate was lower (tendency) in TAI48 cows (P=0.07). In Experiment 3, the estrus rate (P=0.12) and P/AI (P=0.56) were similar between the experimental groups. In summary, protocols using estradiol valerate without exogenous ovulation induction require adjustments in the timing of AI from 48 to 54 h after P4 device removal. However, a combination of estradiol valerate at the beginning of the protocol and estradiol cypionate nine days later successfully induced ovulation in Bos indicus cows inseminated 48 h after P4 device removal.
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Two experiments were performed to evaluate the effects of GnRH treatment on the fertility of suckled Nelore beef cows treated with an estradiol/progesterone (E2/P4)-based protocol for timed artificial insemination (TAI). Experiment 1 focused on determining the effects of estradiol cypionate (EC) on ovulation in TAI cows treated with GnRH 34 h after removal of the intravaginal P4 device (IPD). Suckled cows (n = 26) were treated with 2 mg estradiol benzoate (EB) and IPD containing 1 g P4. After 8 days, IPDs were removed, and all cows were treated with 150 μg of d-cloprostenol (prostaglandin F2 alpha analog) and 300 IU of equine chorionic gonadotropin (eCG), then separated into two treatment groups consisting of cows who received 1) saline 0.9% i.m. (GnRH34 group) or 2) 0.6 mg i.m. of EC (EC-GnRH34 group). On day 9 (05:00 p.m.), all cows were given GnRH (10.5 μg of buserelin acetate) i.m. No differences were observed between the groups (P > 0.05) in the time of ovulation after IPD removal or in the proportion of cows ovulating. Experiment 2 focused on determining the effects of GnRH34 along with or in the absence of EC on day 8 on pregnancy per AI (P/AI) in postpartum beef cows. Cows (n = 981) were treated similarly to those in Experiment 1, but an additional group, the EC-GnRH48 group, was included, in which cows received EC on day 8 whereas those that did not show estrus received GnRH at TAI. Thus, in this experiment, groups consisted of GnRH34 (n = 322), EC-GnRH34 (n = 335), and EC-GnRH48 (n = 324). A higher rate of estrus expression was observed in cows treated with EC following IPD removal (EC-GnRH34: 69%, EC-GnRH48: 64.8%) than in cows in the GnRH34 group (45.6%). No difference in P/AI was observed between the treatment groups (P = 0.45), but P/AI in cows in the EC-GnRH34 group (64.2%) tended to be greater (P = 0.1) than in cows in the GnRH34 group (58%). In summary, although ovulation synchrony did not differ among the groups, P/AI in cows treated with EC and GnRH 34 h after IPD removal tended to be greater than in cows treated solely with GnRH; this was most likely due to a shorter proestrus/estrus period, considering the lower proportion of cows that displayed estrus in the GnRH34 group. Finally, given that P/AI did not differ between the EC-GnRH34 and EC-GnRH48 groups, our results suggest that, for cows not displaying estrus, administration of EC at the time of IPD removal followed by treatment with GnRH 48 h afterward represents the most cost-efficient TAI strategy for South American Zebu-based beef operations.
Sucrose Acetate Isobutyrate (SAIB) as a Delivery Vehicle for Estradiol and Sulpiride: Evaluation of Endocrine Responses in Geldings and Ovarian Response in Seasonally Anovulatory Mares
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Citation Excerpt :
Most mares fail to have an ovarian response to estradiol-sulpiride if LH is not stimulated; however, a threshold LH concentration or critical time to LH stimulation has yet to be determined. Estradiol benzoate has been shown to stimulate an earlier LH rise than ECP in beef cows [17, 18]. Earlier stimulation of LH may promote an ovarian response in mares that might otherwise fail to respond.
Sulpiride in vegetable shortening (VS) stimulates prolactin in horses for up to 10 days. Although effective, a pharmaceutical grade vehicle is needed for clinical application of sulpiride in horses. Sucrose acetate isobutyrate (SAIB), a hydrophobic polymer, may be an alternative to VS. Four in vivo experiments assessed the efficacy of SAIB for delivery of sulpiride, estradiol cypionate (ECP), and estradiol benzoate (EB). The first three studies utilized geldings to compare prolactin and luteinizing hormone (LH) concentrations between sulpiride delivered in VS and SAIB, and ECP or EB delivered in SAIB. Sulpiride stimulated (P < .01) prolactin similarly between vehicles. Geldings pretreated with EB had higher (P < .05) prolactin responses to sulpiride compared to ECP-treated geldings on days 5, 6 and 9. Both estradiol-sulpiride treatments stimulated LH with no differences between ECP and EB. Experiment 3 compared a simultaneous injection of EB-sulpiride to a non-simultaneous injection (one day apart) of EB-sulpiride. Prolactin was stimulated (P < .05) in both treatment groups, but the response lasted 2 days longer in geldings treated a day apart. Plasma LH increased (P < .01) in both groups equally for 10 days. Experiment 4 applied simultaneous and non-simultaneous EB-sulpiride treatments to seasonally anovulatory mares to induce ovarian activity. Prolactin and LH were stimulated similarly between treatments; however, non-simultaneously treated mares tended (P = .07) to have an ovarian response earlier. In conclusion, SAIB was a suitable vehicle for administration of estradiol and sulpiride and could be an alternative to VS for sustained-release drug delivery.
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Two experiments evaluated the effects of gonadotropin releasing hormone (GnRH) treatment on fertility of suckled Nelore beef cows treated with an estradiol/progesterone (P4)-based protocol for timed artificial insemination (TAI). Experiment 1 was designed to determine the effect of GnRH administered 34 h after P4 insert removal (GnRH34) on time of ovulation. Suckled cows (n = 34) were treated with 2 mg estradiol benzoate (EB) and an intravaginal insert containing 1.9 g of P4. Eight days later, P4 inserts were removed, and all cows received 150 μg of d-cloprostenol (prostaglandin F2 alpha analogue), 300 IU of eCG, and 1 mg of estradiol cypionate (ECP). On Day 9 (05:00 p.m.), cows were randomly distributed, according to the diameter of the pre-ovulatory follicle, in two treatments: 1) GnRH (n = 17) cows that received 10.5 μg of buserelin acetate, or 2) no further treatment (control, n = 17). Cows treated with GnRH 34 h after P4 insert removal ovulated earlier (P = 0.02) than control cows (66 ± 0.0 and 77.2 ± 4.3 h). Experiment 2 was designed to determine the effect of GnRH34 on the fertility of suckled beef cows. Nelore cows (n = 506) were treated as Experiment 1. On Day 8, cows were painted in the sacrocaudal region to identify cows that displayed estrus. On Day 9 (05:00 p.m.), cows were randomized to receive same treatment as Experiment 1, control (n = 252), or GnRH (n = 254). All cows were TAI 48 h after P4 insert removal. At TAI, estrus was evaluated, and deemed to have occurred in cows without a tail-head chalk mark (>75% paint loss). Cows treated with GnRH 34 h after P4 insert removal had greater (P = 0.01) pregnancy per AI (P/AI) than cows that only received ECP (63.0% and 50.4%). No difference (P = 0.5) was observed in the proportion of cows that displayed estrus between treatments. Furthermore, cows that displayed estrus had greater (P < 0.01) P/AI than cows that did not. Treatment with GnRH, given at 34 h after P4 insert removal, increased (P < 0.05) P/AI in cows that did not show estrus at TAI. In summary, treatment with GnRH 34 h after P4 insert removal was associated with earlier ovulation and resulted in greater P/AI in suckled Nelore cows treated with an estradiol/P4-based protocol for TAI.
Estradiol cypionate treatment in suckling/weaning and estrous cycling/anestrous beef cows subjected to fixed-time artificial insemination
2021, Animal Reproduction Science
This study was conducted to evaluate the interaction between dose of estradiol cypionate (ECP) and ovarian status in beef cows on which different weaning/suckling regimens were imposed before fixed-time artificial insemination (FTAI). A total of 8070 estrous cycling and anestrous cows were subjected to three experiments, when calves were weaned early (Experiment 1), anti-suckling nose plates were applied for 9 or 10 days (Experiment 2), or there was continued suckling (Experiment 3). The cows were administered an estradiol/progesterone–based treatment regimen for FTAI and were treated with 0.5 or 1.0 mg of ECP im at the time of progesterone intravaginal device removal. Artificial insemination was performed from 46 to 56 h after the time of ECP treatment. Pregnancy per artificial insemination (P/AI) was affected by dose of ECP differentially in early-weaned and suckled cows. Whereas P/AI percentage was greater in early-weaned cows treated with 0.5 than 1.0 mg ECP (P < 0.05), P/AI percentage was greater for suckled cows treated with 1.0 than 0.5 mg ECP (P < 0.05). Although there were greater P/AI percentages in estrous cycling than anestrous cows (P < 0.05) when there was nose plate weaning and continuation of suckling, there was no difference between estrous cycling and anestrous cows (P = NS) when there was early weaning. Overall results indicate ECP administration affects fertility in a dose-dependent manner, suggesting an interaction between suckling and estrous cycling effects. As more critical the condition was (i.e., suckling anestrous cows), larger dose of estradiol was required.

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Effects of estradiol cypionate (ECP) on ovarian follicular dynamics, synchrony of ovulation, and fertility in CIDR-based, fixed-time AI programs in beef heifers

Abstract

Introduction

Section snippets

Experiment 1

Experiment 1

Discussion

Acknowledgements

Theriogenology

Theriogenology

Theriogenology

Theriogenology

Br. Vet. J.

J. Dairy Sci.

Theriogenology

Anim. Reprod. Sci.

Theriogenology

Anim. Reprod. Sci.

Anim. Reprod. Sci.

Follicular wave dynamics after estradiol 17β treatment of heifers with or without a progestogen implant

Theriogenology

Estrus synchronization and pregnancy rates in beef cattle given CIDR-B, prostaglandin and estradiol, or GnRH

Can. Vet. J.

Induction of follicular wave emergence for estrus synchronization and artificial insemination in heifers

Theriogenology