Recombinant equine FSH superovulation in the mare

Inducing ovulation of multiple follicles has been an elusive goal in equine reproduction. Administration of porcine FSH, ovine FSH or GnRH agonists only yield a marginal increase in ovulation rate in mares. Early studies utilizing single chain recombinant equine FSH (reFSH) reported stimulation of follicular development in anestrous mares and increased ovulation rates in cycling mares. Unfortunately, the original reFSH product from AspenBio Pharma, Inc. (Castle Rock, CO USA) is no longer in production. The goal of the current study was to evaluate the efficacy of a new single chain recombinant equine FSH (reFSH-FP; FertilPlus Partners, LLC; Conroe, TX USA) in stimulation of follicular development in mares in two pilot studies as compared to the original reFSH (reFSH-AB; AspenBio Pharma). Study 1. Nine seasonally anestrous mares (follicle diameter 19 ± 3.7 mm) were randomly assigned to one of 3 treatment groups (n=3/group): saline placebo, reFSH-AB (0.65 mg, IM, q12), reFSH-FP (0.65 mg, IM, q 12h) for a maximum of 7 days. A dose of hCG (2,500 units, IV) was administered after a 36-hour coast period once one or more follicles attained a diameter of ≥ 35 mm. The ovulation rates for the three treatment groups were 0, 10.3 ± 3.5, and 6.0 ± 2.0 ovulations for the saline placebo, reFSH-AB and reFSH-FP, respectively. Study 2. Twelve normally cycling mares were randomly assigned to one ofthe same treatment protocols as described for Study 1 above (n=4 per group). All mares were in mid-diestrus at the onset of treatment and a dose of cloprostenol (250 µg, IM) was administered on the second day of treatment. Mares were treated for a maximum of 7 days. HCG (2,500 units, IV) was administered after a coast period of 36 hours when one or more follicles attained a diameter of ≥ 35 mm. Ovulation rates were 1.3 ± 0.5, 5.5 ± 5.3, and 5.3 ± 1.0 ovulations for the saline placebo, reFSH-AB and reFSH-FP, respectively. All mares ovulated in the placebo and reFSH-FP groups after administration of hCG; one mare in the reFSH-AB group developed 12 follicles > 35 mm in diameter, but failed to ovulate after administration of hCG. Collectively, these studies confirm that the new recombinant equine FSH product (reFSH-FB; FertilPlus) has biological activity in the mare similar to that of the original reFSH product (reFSH-AB; AspenBio Pharma) and is capable of stimulating development of multiple large follicles in deep anestrus and cycling mares. However, significant hurdles remain before a recombinant equine FSH product could be available for commercial production, distribution and clinical use. Additional research will be needed to evaluate safety, dosage, frequency of administration, timing of administration of an ovulation induction agent, and fertility following reFSH treatment.