Effects of deslorelin or hCG administration on reproductive performance in first postpartum estrus mares

Effects of deslorelin or hCG administration on reproductive performance in first postpartum estrus mares

Theriogenology 58 (2002) 165±169 Effects of deslorelin or hCG administration on reproductive performance in ®rst postpartum estrus mares Terry L. Bla...

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Theriogenology 58 (2002) 165±169

Effects of deslorelin or hCG administration on reproductive performance in ®rst postpartum estrus mares Terry L. Blancharda,*, Steven P. Brinskoa, Sherri L. Rigbyb a

Department of Large Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4475, USA b Bayer Corporation, P.O. Box 390, Merriam, KS 66201, USA Received 2 October 2001; accepted 9 January 2002

Abstract A tendency for deslorelin implants to suppress subsequent follicular growth and delay return to estrus following induced ovulation has been documented in nonlactating mares. To investigate this phenomenon in lactating mares, 22 broodmares in southeast Texas were administered either deslorelin or hCG to induce ovulation in the ®rst postpartum estrus during February and March 2001. Mares were teased daily and examined twice weekly (Tuesdays and Thursdays) by transrectal ultrasonography. When a follicle 35 mm diameter was detected on Tuesday, mares were treated with either 2500 U hCG administered intravenously or with one implant (2.1 mg) deslorelin administered subcutaneously. Mares were bred every other day until ovulation was detected or until they ceased behavioral estrus, and were examined 16 days after treatment to detect pregnancy. Follicular measurements were recorded for all mares during each examination, and interestrous intervals were recorded for mares not becoming pregnant. Treatment of mares with either hCG or deslorelin resulted in similar ovulatory responses and pregnancy rates. Deslorelin-treated mares had fewer ovarian follicles 20 mm in diameter 16 days after treatment than hCG-treated mares (P < 0:01). Interestrous intervals for mares failing to become pregnant on foal heat breeding were prolonged in deslorelin-treated compared to hCG-treated mares (P < 0:01). Date of treatment was negatively correlated with length of the interestrous interval in deslorelin-treated mares (P < 0:01), but was not correlated with length of interestrous interval in hCG-treated mares (P > 0:10). All mares failing to become pregnant from foal heat breedings became pregnant from later breedings, but the parturition to conception interval was prolonged in deslorelin-treated compared to hCG-treated mares that did not become pregnant on foal heat (P < 0:01). # 2002 Elsevier Science Inc. All rights reserved. Keywords: Equine; Postpartum; Estrus; GnRH agonist * Corresponding author. Tel.: ‡1-979-845-9137; fax: ‡1-979-847-8863. E-mail address: [email protected] (T.L. Blanchard).

0093-691X/02/$ ± see front matter # 2002 Elsevier Science Inc. All rights reserved. PII: S 0 0 9 3 - 6 9 1 X ( 0 2 ) 0 0 9 1 2 - 3

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1. Introduction OvuplantTM was approved for use to hasten ovulation in mares in the US in 1999. The drug is marketed as a subcutaneous implant of the GnRH agonist deslorelin, and when administered to mares with an estral follicle 30 mm diameter, induces ovulation within 48 h in over 88% of mares [1,2]. After the ®rst year of commercial availability in the US, a number of investigators reported that some deslorelin-treated mares experienced a delayed return to estrus if they failed to become pregnant [3,4].1 Most affected mares experienced a 3±7 days prolongation of the interestrous interval, but some experienced intervals >30 days [3,4]. The delayed return to estrus presumably is due to downregulation of pituitary gonadotrophs by the GnRH agonist [5] with associated suppression of follicular growth [6]. Anecdotal reports ascribe the more prolonged interestrous intervals (>30 days) to treatment too early in the breeding season (i.e. when mares are not yet ready to begin regular estrous cycles), implying prolonged interestrous intervals will occur regardless of the drug used to induce ovulation.2 In one report wherein repeated administration (every other day) of deslorelin implants was used to hasten onset of the ®rst ovulation in transitional mares, it was suggested those treated mares that re-entered anestrus did so because ovulation was forced upon them prematurely [7]. Based on this reasoning, some investigators eliminated interestrous intervals of more than 30 days from analysis in their publications [5±7]2. Information on the effects of deslorelin administration on reproductive performance during the ®rst postpartum estrus in mares is lacking. Due to positive effects of parturition, the majority of ®rst postpartum estrus periods in mares result in ovulation [8], usually within 20 days postpartum [9]. Since early foaling mares may become anovulatory after their ®rst postpartum ovulation [9,10], and delayed return to estrus may be more common in mares treated with deslorelin early in the breeding season, evaluating reproductive performance of mares treated during ®rst postpartum estrus with deslorelin may further elucidate the potential for this drug to prolong interestrous intervals. The purpose of this experiment was to compare effects of treatment of ®rst postpartum estrus mares with deslorelin (OvuplantTM) or hCG on ovulatory response, pregnancy rate, follicular populations, interestrous intervals and foaling to conception intervals. 2. Materials and methods Palpation and breeding records were examined for 22 lactating crossbred (Quarter Horse type) broodmares maintained on pasture in southeast Texas. Mares were teased daily and examined twice weekly (Tuesday and Thursday) by transrectal ultrasonography beginning 5 days postpartum. Mares in behavioral estrus with a follicle 35 mm diameter on Tuesday examinations were treated with either hCG (2500 units, i.v.) (Chorulon1, Intervet Inc., Millsboro, DE, USA) or deslorelin (2.1 mg implant, s.c.) (Ovuplant1, Fort Dodge Animal 1 Broodmare Reproduction Forum on Hormonal Therapy, American Association of Equine Practitioners, Albuquerque, NM, 5 December 1999, unpublished. 2 Samper J, McCue PM, Holder RD, et al. Broodmare Reproduction Forum on Use of Ovuplant, American Association of Equine Practitioners, San Antonio, TX, 31 November 2000, unpublished.

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Health, Fort Dodge, IA, USA). Mares were re-examined on Thursdays to detect ovulation, and again 16 days after treatment to assess follicular activity and pregnancy status. Following treatment, estrus mares were bred every other day until either ovulation was con®rmed or until they ceased behavioral signs of estrus. The majority of mares were bred by natural service, with only a few mares being bred arti®cially. Eight stallions, all of which passed a breeding soundness examination in January 2001, were used for breeding. To ensure stallions did not differentially affect fertility of mares bred, pregnancy rates per cycle were compared for the 2001 breeding season; this did not vary among stallions (data not shown; P > 0:10). Since the twice weekly examination schedule precluded precise determination of day of ovulation, interestrous interval for mares not becoming pregnant was calculated from the last day of the treated estrus to the last day of the next estrus. Foaling to conception intervals were calculated from the date of foaling to 2 days after the last breeding. Days postpartum at the time of treatment, date of treatment, dominant (largest) follicular diameter at time of treatment, number of 20±29 and 30 mm diameter follicles at each examination, interestrous intervals, and foaling to conception intervals were analyzed by analysis of variance procedures. Categorical data were analyzed by Chi-square procedures. Simple correlation coef®cients were constructed for each treatment group to evaluate the relationship between date of treatment and interestrous interval in mares failing to become pregnant. 3. Results Results are presented in Tables 1 and 2. Mean date at treatment, day postpartum treated, size of the largest (dominant) follicle at treatment, and percentage of mares ovulating within 2 days of treatment did not differ between hCG- or deslorelin-treated mares (P > 0:10). Pregnancy rates did not differ between deslorelin- or hCG-treated mares (P > 0:10). Number of follicles 20 or 30 mm in diameter present 16 days after treatment was reduced in deslorelin-treated compared to hCG-treated mares (P < 0:01) (Table 1). Interestrous interval for mares failing to become pregnant was greater for Table 1 Mean values (S.D.) for date of treatment, day postpartum (Day PP) at treatment, diameter of largest (dominant) follicle at time of treatment, and reproductive responses of 22 mares treated on the first postpartum estrus with either 2500 U hCG administered intravenously or one deslorelin implant administered subcutaneously Date treated

hCG

PP treated (days)

2 March 10  4 (10 days) Deslorelin 6 March 11  3 (16 days)

Largest follicle diameter (mm)

Ovulations Pregnancy within 2 days rate (%) of treatment (%)

41  5

91 (10/11)

55 (6/11)

42  6

82 (9/11)

64 (7/11)

Within columns, means are different with different superscripts (P < 0:01).

Number of follicles within size range Diameter at treatment (mm)

Diameter at 16 days (mm)

30

20

30

1.0  0.0

1.4  0.7

0.5  0.5a 2.0  0.8a

1.0  0.0

1.7  2.0

0b

20

0.7  1.1b

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Table 2 Mean (S.D.) interestrous interval and foaling to conception interval in nine lactating mares failing to conceive when bred on the first postpartum estrus after treatment with either 2500 U hCG administered intravenously or one deslorelin implant administered subcutaneously n hCG Deslorelin

5 4

Interestrous interval (days) a

20.8  4.0 40.5  10.1b

Foaling to conception interval 35.4  4.6a 57.0  12.3b

Within columns, means are different with different superscripts (P < 0:01).

deslorelin-treated than for hCG-treated mares (P < 0:01) (Table 2). Interestrous intervals were not correlated with date of treatment with hCG (r ˆ 0:30, P > 0:10), but were negatively correlated with date of treatment with deslorelin (r ˆ 0:98, P < 0:02). All mares which failed to become pregnant from foal heat breedings became pregnant from breedings in subsequent estrous periods (i.e. four of ®ve hCG-treated mares and three of four deslorelin-treated mares became pregnant after breeding during the next estrus, and one mare in each treatment group became pregnant after breeding in two estrous periods). Foaling to conception interval was longer for deslorelin-treated than hCG-treated mares that did not become pregnant from foal heat breedings (P < 0:01) (Table 2). 4. Discussion Percentage of ovulations within 2 days of treatment and pregnancy rates for ®rst postpartum estrus mares in this study were similar to those reported for cyclic mares treated with either hCG or deslorelin in the US [1±5,11]. While few reports of ef®cacy exist for use of deslorelin in lactating mares, an ovulation rate of 93% within 2 days of treatment was reported for 85 lactating mares treated in North America [1]. Our results indicate that ovulatory response and fertility can be expected to be normal for mares treated with deslorelin on their ®rst postpartum estrus. Interestrous intervals in the ®ve hCG-treated mares failing to become pregnant on foal heat breedings were 27 days, but were prolonged (32, 36, 39 and 55 day intervals) for the four deslorelin-treated mares that did not become pregnant on foal heat breedings. The magnitude of the deslorelin-induced delayed return to estrus was only 10% (7/70) in one study that contained some lactating mares, but those mares were not treated on foal heat [3]. Further study is required to determine whether a greater tendency for delayed return to estrus is a phenomenon related to treatment on the ®rst postpartum estrus, or if this observation was confounded by season. Mares which foal early in the year (January and February) have been noted to be more likely to revert to ovarian inactivity following their ®rst postpartum ovulation than mares foaling later in the year [9,10]. Mares in this study foaled between 1 February and 21 March. The length of the interestrous intervals in deslorelin-treated mares failing to become pregnant became progressively shorter when foaling date occurred later in the year (i.e. 55 days interestrous interval when foaled February 3 versus 32 days interestrous interval when foaled 19 March), explaining the high negative correlation between date of treatment with deslorelin and length of the subsequent

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interestrous interval. Season (month) was found to only have a minor effect on the incidence of delayed return to estrus following the use of deslorelin in cyclic mares [3]; however, when repeated (every other day) administration of deslorelin implants was used to hasten onset of the ®rst ovulation in transitional mares, it was suggested those treated mares that re-entered anestrus did so because ovulation was forced upon them prematurely [7]. In summary, treatment of ®rst postpartum estrus mares with deslorelin resulted in follicular suppression, and delayed return to estrus in mares not becoming pregnant, compared to mares treated with hCG. Unlike treatment with hCG, treatment earlier in the year with deslorelin resulted in a more prolonged interestrous interval. Since no differences were detected between treatment groups for ovulatory response or pregnancy rate, we recommend the use of hCG for inducing ovulation of early foaling mares bred on ®rst postpartum estrus. Acknowledgements The authors wish to thank the Texas Department for Criminal Justice for providing use of the horses and facilities utilized in this study, and Fort Dodge Animal Health for graciously providing the OvuplantTM for this study. References [1] JoÈchle W, Trigg TE. Control of ovulation in the mare with OvuplantTM. A short-term release implant (STI) containing the GnRH analogue deslorelin acetate: studies from 1990 to 1994. J Equine Vet Sci 1994;14:632±44. [2] JoÈchle W, Merkt H, Waberski D. Control of ovulation in the mare using a subcutaneous implant: effects on stallion use. Equine Prac 1997;19:10±2. [3] Morehead JP, Blanchard TL. Clinical experience with deslorelin (OvuplantTM) in a Kentucky thorough bred broodmare practice (1999). J Equine Vet Sci 2000;20:358±402. [4] Vanderwall DK, Juergens TD, Woods GL. Reproductive performance of commercial broodmares after induction of ovulation with hCG or OvuplantTM to hasten ovulation. Proceedings of the Annual Meeting of the Society of Theriogenology, Nov. 28 to Dec. 2, 2000. p. 143±4. [5] Johnson CA, Thompson Jr DL, Kulinski KM, Guitreau AM. Prolonged interovulatory interval and hormonal changes in mares following the use of OvuplantTM to hasten ovulation. J Equine Vet Sci 2000;20:331±6. [6] Farquhar VJ, McCue PM, Nett TM, Squires EL. Effect of deslorelin acetate on gonadotropin secretion and ovarian follicle development in cycling mares. J Am Vet Med Assoc 2001;218:749±52. [7] McKinnon AO, Vasey JR, Lescun TB, Trigg TE. Repeated use of a GnRH analogue deslorelin (Ovuplant) for hastening ovulation in the transitional mare. Equine Vet J 1996;29:153±5. [8] Ginther OJ. Reproductive biology of the mare: basic and applied aspects. Equiservices: Cross Plains, WI, 1992. p. 476±7. [9] Loy RG. Characteristics of postpartum reproduction in mares. Vet Clin North Am Large Anim Prac 1980;2:345±59. [10] Palmer E, Driancourt MA. Some interactions of season of foaling, photoperiod and ovarian activity in the equine. Livestock Prod Sci 1983;10:197±210. [11] Barbacini S, Zavaglia G, Gulden P, Marchi V, Necchi D. Retrospective study on the ef®cacy of hCG in an equine arti®cial insemination program using frozen semen. Equine Vet Edu 2000;2:404±10.