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Effects of Deslorelin Administration in Vulvar Mucosa, with Removal in 2 Days, in Foal-Heat Mares

Konnie M. Wendt, DVM; Kelly L. Stich, DVM; and Terry L. Blanchard, DVM, MS

Placement of deslorelin implants in vulvar mucosa allowed easy removal 2 days later. Deslorelin treatment in the vulvar mucosa effectively induced within 2 days in foal-heat mares and resulted in normal pregnancy rates. Post-treatment follicular suppression and delayed return to estrus in mares failing to become pregnant were avoided by removing implants 2 days after place- ment. Authors’ addresses: Department of Large Animal Medicine and Surgery, College of Veter- inary Medicine, Texas A&M University, College Station, TX 77843-4475. © 2002 AAEP.

1. Introduction (Ͼ30 days) to treatment too early in the breeding Ovuplant™ was approved for the use of hasten- season (i.e., when mares are not yet ready to begin ing ovulation in mares in the United States in 1999. regular estrous cycles). In one report, wherein re- The drug is marketed as a subcutaneous implant of peated administration (every other day) of deslorelin the -releasing hormone (GnRH) ago- implants was used to hasten onset of the first ovu- nist deslorelin. When administered to mares with lation in transitional mares, it was suggested that an estral follicle Ն30-mm diameter, Ovuplant™ in- those treated mares that re-entered anestrus did so 7 duces ovulation within 48 h in over 88% of because ovulation was forced on them prematurely. mares.1,2 After the first year of commercial avail- Little data are available on the effects of ability in the United States, a number of veterinar- deslorelin administration on reproductive perfor- ians reported that some deslorelin-treated mares mance during the first postpartum estrus (foal-heat) experienced a delayed return to estrus if they failed in mares. The majority of foal-heats in mares to become pregnant.3,4,a Most affected mares expe- result in ovulation,8 usually within 20 days rienced a 3–7 day prolongation of the interestrous postpartum.9 Because early-foaling mares not ex- interval, but some experienced intervals of Ͼ30 posed to artificial lighting may become anovulatory days.3,4 The delayed return to estrus presumably after their foal-heat ovulation,9,10 and delayed re- is caused by down-regulation of pituitary gonado- turn to estrus may be more common in mares trophs by the GnRH agonist,5 with associated sup- treated with deslorelin early in the breeding season, pression of follicular growth.6 Anecdotal reports evaluation of reproductive performance in mares ascribe the more prolonged interestrous intervals treated during foal-heat with deslorelin is war-

NOTES

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Table 1. Mean Values (؎SD) for Foaling Date, Date of Treatment, Day Postpartum at Treatment, Diameter of Largest (Dominant) Follicle at Time of Treatment, and Reproductive Responses of 39 Mares Treated on the First Postpartum Estrus with Either One Deslorelin Implant Administered Beneath the Vulvar Mucosa (Removed 2 Days Later) or No Treatment (Sham-Control)

Deslorelin-Treated Mares Control Mares Variable (n ϭ 19) (n ϭ 20)

Foaling date Feb 11 Ϯ 14 d Feb 12 Ϯ 13 d Date of treatment Feb 21 Ϯ 13 d Feb 19 Ϯ 16 d Day postpartum 9.7 Ϯ 3.0 d 8.3 Ϯ 1.9 d Follicle size at treatment 40 Ϯ 6mm 41Ϯ 6mm Interval to ovulation from treatment 2.6 Ϯ 1.7 da 4.5 Ϯ 1.3 db Ovulations within2doftreatment 84% (16/19)a 10% (2/20)b Date of ovulation Feb 23 Ϯ 13 d Feb 25 Ϯ 13 d Pregnancy rate 74% (14/19) 65% (13/20) Number of covers after treatment 1.3 Ϯ 0.7a 2.1 Ϯ 0.6b Number of 20- to 29-mm follicles 16 d after treatment 1.3 Ϯ 1.4 1.0 Ϯ 1.1 Number of Ն30-mm follicles 16 d after treatment 0.5 Ϯ 0.5 0.4 Ϯ 0.5 Interestrous interval in mares not pregnant 21.2 Ϯ 2.5 d 20.8 Ϯ 2.0 d

a,bMeans are significantly different (p Ͻ 0.01).

ranted. In a recent study, treatment of foal-heat tum. To avoid effects of season, mares in estrus mares with deslorelin (implants placed subcutane- with a follicle Ն35-mm diameter were alternately ously in the neck), during February and March, re- assigned to the following: treatment 1, 2.1 mg duced the number of large follicles 16 days after deslorelinc; or treatment 2, control. Immediately treatment.11 A delayed return to estrus (e.g., 32- to before treatment, the vulva was scrubbed and dried. 55-day interestrous intervals) in those mares failing Lidocaine (2%, 1–2 ml) was injected beneath the to become pregnant on foal-heat breeding, compared dorsal vulvar mucosa, and either one Ovuplant® with human chorionic gonadotropin-treated mares, (treatment 1) or no implant (treatment 2) was in- was also reported.11 Whether the down-regulating jected beneath the desensitized bleb. Two days af- effect of the drug was related to treatment on foal- ter implant placement, a 0.5-to 1-cm incision was heat, or was a result of season, could not be deter- made through the vulvar mucosa directly over the mined in that study. implant, and the implant was removed. Mares Recently, several practitioners and university in- were also re-examined by transrectal ultrasonogra- vestigators have suggested the adverse effects of phy at this time to detect ovulation and again 14 deslorelin can be avoided by removing implants 2 days after ovulation to assess follicular activity and days after administration. Recommendations were pregnancy status. to make a small skin incision beneath the mane, Following treatment, mares were bred every other place the implant in a small subcutaneous pocket day until either ovulation was confirmed or until closed with one skin suture, and remove the implant they ceased behavioral signs of estrus. The major- 2 days later by clipping the suture and retrieving the ity of mares were bred by natural service, with a few a implant. We found the implant difficult to find mares being bred artificially. Eight stallions, all of and remove in some mares when this procedure was which passed a breeding soundness examination in used. Colorado State University investigators rec- January 2002, were used for breeding. Pregnancy ommended the implant be placed under the vulvar rates per cycle did not vary among these stallions for mucosa, because this procedure reportedly makes the previous breeding season. Interestrous inter- removal of the implant quite easy to accomplish.b val for mares not becoming pregnant was calculated Goals of this study were to determine the follow- from the last day of the treated estrus to the last day ing: 1) if placement of deslorelin implants in the of the next estrus. vulvar mucosa would be effective in inducing ovula- Days postpartum at the time of treatment, date of tion in foal-heat mares, and 2) if removal of implants treatment, diameter of the dominant follicle at time 2 days after administration would prevent follicular of treatment, number of 20- to 29-mm and Ն30-mm suppression and delayed return to estrus in early- diameter follicles at time of treatment and at 14 foaling mares treated on their foal-heat. days postovulation, and interestrous intervals were analyzed by analysis of variance procedures. 2. Materials and Methods Categorical data were analyzed by chi-square Palpation and breeding records were examined for procedures. 39 first-postpartum estrus (foal-heat) crossbred (Quarter Horse type) broodmares maintained on 3. Results pasture in southeast Texas. Mares were teased Results are presented in Table 1. Mean date at daily and examined three times weekly by transrec- treatment, size of the dominant follicle at treatment, tal ultrasonography beginning 5–6 days postpar- and day of postpartum ovulation did not differ be-

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REPRODUCTION tween deslorelin-treated and control mares (p Ͼ 24 mares ovulating Ն11 days postpartum became 0.05). Interval to ovulation was shorter, fewer cov- pregnant (75% pregnancy rate; p Ͼ 0.05). Evalua- ers were required, and more mares ovulated within tion of pregnancy rates achieved in mares foaling 2 days of treatment in deslorelin-treated than in later in the spring, when a higher proportion of control mares (p Ͻ 0.01). Pregnancy rates did not ovulations occur earlier in the postpartum period, differ between deslorelin-treated and control mares would be necessary to determine if Loy’s observation (p Ͼ 0.05). Number of follicles 20- to 29-mm or holds true in Quarter Horse-type mares. Ն30-mm diameter present 14 days after ovulation While not a goal of this study, we did note that the and interestrous intervals for mares failing to be- number of covers did not seem to influence preg- come pregnant on foal-heat breedings did not differ nancy rate achieved on foal-heat breedings (i.e., 1 between deslorelin-treated and control mares (p Ͼ cover ϭ 10/16, 63% pregnancy rate; 2 covers ϭ 10/15, 0.05). 67% pregnancy rate; 3 covers ϭ 5/6, 83% pregnancy rate; 4 covers ϭ 2/2, 100% pregnancy rate). Be- 4. Discussion cause mating results in transient postbreeding en- Vulvar mucosal administration of deslorelin im- dometritis,12 repeated contamination from multiple plants with subsequent removal 2 days later was matings during the process of uterine involution easily accomplished. Whereas absorption charac- could result in lowered fertility. Perhaps the teristics and response were not uterus of normal foaling mares is quite resistant to studied, the efficacy of deslorelin implants used in repeated contamination from multiple matings. A this manner was apparent. The 84% ovulation rate number of factors might explain the high foal-heat within 2 days of deslorelin treatment in this group of fertility in this herd. Mares in this herd have a foal-heat mares was similar to that reported for traditionally high seasonal pregnancy rate (typically cyclic mares treated with deslorelin in the United exceed 90%). Mares are kept in good to excellent States.1–5 An ovulation rate of 93% within 2 body condition and are maintained on large pas- days of treatment was reported for 85 lactating tures, ensuring adequate exercise. These com- mares.1 The 84% ovulation rate within 2 days of bined factors might result in an improved treatment was also similar to that reported for foal- postpartum uterine condition and level of fertility heat mares treated with deslorelin implants placed that negated any potential adverse effects of re- subcutaneously in the neck (82%).11 Our results peated matings. indicate that ovulatory response and fertility seem In summary, placement of deslorelin implants in normal for mares treated with vulvar mucosal the vulvar mucosa was an easily performed, safe deslorelin implants on their foal-heat. procedure that reliably induced ovulation in foal- Mares that foal early in the year (January and heat mares within 2 days of treatment. Normal February) have been noted to be more likely to re- pregnancy rates were achieved with deslorelin-in- vert to ovarian inactivity after their foal-heat ovu- duced ovulations on foal-heat. Removal of the im- lation than mares foaling later in the year.9,10 plants 2 days after insertion avoided follicular Mares in this study foaled between January 19 and suppression and delayed return to estrus. March 7. In this same herd during a similar period in 2001, the number of large follicles present 14 days The authors thank the Texas Department for after ovulation was reduced with deslorelin treat- Criminal Justice for providing the horses and facil- ment (subcutaneous implants) compared with hu- ities used in this study, and Fort Dodge Animal man chorionic gonadotropin treatment on foal- Health for graciously providing the Ovuplant™ for heat.11 In addition, return to estrus was delayed in this study. mares failing to become pregnant after deslorelin References and Footnotes (subcutaneous implants) treatment on foal-heat 11 1. Jo¨chle W, Trigg TE. Control of ovulation in the mare with (i.e., 32- to 55-day interestrous intervals). Based Ovuplant™. A short-term release implant (STI) containing on the results of this study, it seems that prolonged the GnRH analogue deslorelin acetate: studies from 1990 to absorption of the GnRH agonist is occurring when 1994. J Equine Vet Sci 1994;14:632–644. implants are not removed, and this demonstrates 2. Jo¨chle W, Merkt H, Waberski D. Control of ovulation in the mare using a subcutaneous implant: effects on stallion use. that removal of deslorelin implants 2 days after Equine Pract 1997;19:10–12. placement will avoid these problems. 3. Morehead JP, Blanchard TL. Clinical experience with For breedings on the foal-heat, conception and deslorelin (Ovuplant™) in a Kentucky Thoroughbred brood- early pregnancy development must occur at the mare practice (1999). J Equine Vet Sci 2000;20:358–402. same time uterine involution is progressing. In a 4. Vanderwall DK, Juergens TD, Woods GL. Reproductive per- 9 formance of commercial broodmares after induction of ovula- landmark study performed on foal-heat mares, Loy tion with hCG or Ovuplant™ to hasten ovulation. In demonstrated that Thoroughbred mares ovulating Proceedings. Ann Mtg Soc Theriogeneol 2000;358–402. Յ10 days postpartum achieved a 45% pregnancy 5. Johnson CA, Thompson DL Jr., Kulinski KM, et al. Pro- rate, whereas those ovulating Ն11 days postpartum longed interovulatory interval and hormonal changes in mares following the use of Ovuplant™ to hasten ovula- achieved a 59% pregnancy rate. In our study, 9 of tion. J Equine Vet Sci 2000;20:331–336. 15 mares ovulating before 11 days postpartum be- 6. Farquhar VJ, McCue PM, Nett TM, et al. Effect of came pregnant (60% pregnancy rate), whereas 18 of deslorelin acetate on gonadotropin secretion and ovarian fol-

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licle development in cycling mares. J Am Vet Med Assoc first postpartum estrus mares. Theriogeneology 2002;58: 2001;218:749–752. 165-169. 7. McKinnon AO, Vasey JR, Lescun TB, et al. Repeated use of a 12. Troedsson MHT, Crabo BG, Ibrahim N, et al. Mating-in- GnRH analogue deslorelin (Ovuplant) for hastening ovulation duced endometritis: mechanisms, clinical importance, and in the transitional mare. Equine Vet J 1996;29:153–155. consequences. In Proceedings. 41st Ann Mtg Am Assoc 8. Ginther OJ. Reproductive biology of the mare: basic and ap- Equine Pract 1995;11–12. plied aspects. Cross Plains, WI: Equiservices, 1992;476–477. 9. Loy RG. Characteristics of postpartum reproduction in mares. Vet Clin North Am [Food Anim Pract] 1980;2:345– aSamper J, McCue PM, Holder RD, et al. Broodmare Repro- 359. duction Forum on Use of Ovuplant, American Association of 10. Palmer E, Driancourt MA. Some interactions of season of Equine Practitioners, San Antonio, TX, November 31, 2000, un- foaling, photoperiod and ovarian activity in the equine. published. Livestock Prod Sci 1983;10:197–210. bMcCue P, Carnevale E. Personal communication. Decem- 11. Blanchard TL, Brinsko SP, Rigby SL. Effects of deslorelin ber 2001. or hCG administration on reproductive performance in cOvuplant®; Fort Dodge Animal Health, Fort Dodge, IA 50501.

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Proceedings of the Annual Convention of the AAEP 2002