Reproductive performance of commercial broodmares after induction of ovulation with HCG or Ovuplant™ (deslorelin)

Abstract

Soon after Ovuplant™, the sustained-release implant containing the gonadotropin releasing hormone (GnRH) agonist deslorelin, was approved for commercial use in the United States for induction of ovulation in mares, anecdotal field observations were reported that some Ovuplant™—treated mares that did not become pregnant experienced a delayed return to estrus and prolonged inter-ovulatory interval. Although those observations have been subsequently confirmed, further data on how mares respond to Ovuplant™ compared to human chorionic gonadotropin (hCG) during the post-treatment period is needed. The objective of this study was to further evaluate the clinical use of Ovuplant™ by comparing the reproductive performance of commercial broodmares treated with hCG or Ovuplant™. This retrospective study was completed by examining the 1999 reproductive records of 106 mares treated with hCG during 134 estrous cycles and 117 mares treated with Ovuplant™ during 151 estrous cycles. There were no differences (P > 0.10) in follicle size at the time of treatment (39.4 ± 0.5 vs. 38.9 ± 0.5 mm), interval from treatment to ovulation (2.2 ± 0.1 vs. 2.2 ± 0.1 days), proportion of mares that failed to ovulate after treatment (3.0 vs. 4.6 %), or per-cycle pregnancy rate (47.7 vs. 51.4 %) between hCG-and Ovuplant™-treated mares, respectively. The interval from ovulation to return to estrus (25.8 ± 1.3 vs. 15.5 ± 0.6 days) and the inter-ovulatory interval (30.4 ± 1.5 vs. 20.8 ± 0.6 days) were longer (P<0.001) for Ovuplant™-compared to hCG-treated mares, and the proportion of non-pregnant mares that failed to return to estrus within 30 days after ovulation (31.4 vs. 1.5 %) was higher (P<0.001) for Ovuplant™-compared to hCG-treated mares, respectively. For Ovuplant™—treated mares, follicle size at the time of treatment tended (P<0.1) to be smaller for mares that failed to return to estrus within 30 days compared to mares that returned to estrus within 30 days (37.1 ± 1.1 vs. 40.1 ± 0.6 mm, respectively). Also, the average date of ovulation during the calendar year was later (P < 0.05) for Ovuplant™—treated mares that failed to return to estrus within 30 days compared to those that returned to estrus within 30 days (May 15 ± 4 vs. April 30 ± 4 days). The results of this study confirm previous reports that although the ovulatory response and fertility were not different for hCG- and Ovuplant™—treated mares, mares treated with Ovuplant™ that did not become pregnant had a significantly delayed return to estrus and prolonged inter-ovulatory interval. Based on recently published information, it appears this effect is due to Ovuplant™—induced down-regulation of the pituitary gland, which suppresses subsequent follicular growth and development. This study also demonstrated that follicle size and/or season may influence the probability that Ovuplant™—treated mares would experience a delayed return to estrus/ovulation; therefore, further work is needed to determine whether these or other factors are related to this specific outcome following Ovuplant™—treatment.

Introduction

Human chorionic gonadotropin has been used extensively for many years for inducing ovulation in mares because of its luteinizing hormone (LH)-like activity. Although administration of hCG to estrous mares with a follicle > 30 mm generally induces ovulation to occur within 36 to 48 hours, the interval from treatment to ovulation can be quite variable especially in older mares.¹ This variability can be problematic when the timing of insemination and ovulation must be carefully coordinated, such as when using cooled or frozen-thawed semen. It has been hypothesized the variability in responsiveness to hCG is related to the development of antibodies against the hCG molecule that form following repeated administration of the hormone²; however, no correlation has been identified between the magnitude of the antibody response and the efficacy of hCG in mares.³ Therefore, the underlying cause(s) of the variable response following hCG treatment remains unknown.

Because the response to hCG treatment can be quite variable, there has been interest in using GnRH or its agonists to induce ovulation in mares. These agents are small, non-antigenic peptides that cause ovulation by stimulating secretion of endogenous LH. Although injectable preparations of GnRH can induce ovulation, multiple injections or continuous administration are necessary making them impractical for routine use (for review see⁴ ). The need for repeated or continuous administration of injectable preparations has been obviated by the development of a sustained-release subcutaneous implant containing 2.1 mg of the GnRH agonist deslorelin (Ovuplant™) that was recently approved for commercial use in the United States.

Although numerous studies have documented the efficacy of Ovuplant™ for inducing ovulation in mares (for review see⁵), after it was introduced into commercial use in the United States anecdotal field reports suggested that mares treated with Ovuplant™ that did not become pregnant were more likely to experience a delayed return to estrus and/or prolonged anovulatory period. Those observations were confirmed by a subsequent field study⁶ that documented the inter-ovulatory interval was significantly longer when mares received Ovuplant™ compared to estrous cycles when the same mares were not treated or received hCG. In addition, two recent controlled studies7, 8 have documented that Ovuplant™—treated mares had significantly longer inter-ovulatory intervals than non-treated control mares. Because Ovuplant™-treated mares apparently respond differently in the post-treatment period, the objective of this study was to further evaluate the clinical use of Ovuplant™ by comparing the reproductive performance of commercial broodmares treated with hCG or Ovuplant™.