Kinetic studies and production rate of equine (e) FSH in ovariectomized pony mares. Application to the determination of a dosage regimen for eFSH in a superovulation treatment

Abstract

The appropriate dosage regimen for equine FSH (eFSH) (dose, dosing interval) administration in a superovulation treatment in pony mares was determined by a kinetic approach using production rates and kinetic parameters of elimination of the hormone. Two dosage regimens were then tested in superovulation protocols. The eFSH production rates were determined by sampling four ovariectomized pony mares every 10 min for 8 h during the breeding season. Kinetic parameters were determined by administering four dose levels of a preparation of eFSH (4·4, 8·8, 17·6 and 35·2 µg/kg) by the i.v. route to the same mares, in a randomized 4 4 Latin Square protocol. The overall mean plasma clearance was 0·256 0·07 ml.kg 1 .min 1 , and was independent of the dose. The mean residence time ranged from 5·5 to 10·8 h and increased with the dose. The estimated FSH production rates were 8·6 to 15·3 µg.kg 1 .day 1 (i.e. 2·89 to 3·45 mg per day per mare). Two dosage regimens of eFSH were then tested in cyclic mares (ten treated mares in each trial): 3·45 mg per day (4·4 µg/kg three times a day by the i.v. route), which corresponds to the maximal daily production rate of the native hormone in ovariectomized mares, and 1·72 mg per day (2·2 µg/kg three times a day), which corresponds to half of that production rate. The dosage regimen of 2·2 µg/kg three times a day gave satisfactory results in terms of efficacy (numbers of ovulations and embryos) with minimal unwanted effects (luteinized or anovulatory follicles).

Equine embryo transfer: review of developing potential

“…This variability may, in part, relate to one of the intrinsic limitations of a brain extract such as eFSH; the exact gonadotrophin composition, in particular the ratio of FSH to LH, is likely to differ between batches and this may contribute to variability in response. Too low a dose of FSH would result in a poor superovulatory response, while too high a dose (or too high an LH:FSH ratio) may predispose to luteinisation of follicles without ovulation (Briant et al 2004).…”

Superovulation in Mares

“…If the dose is too high, the ovaries become overstimulated and many of the follicles do not ovulate but become luteinized or develop an anovulatory follicle. Briant and coworkers [29] reported that if the dose of eFSH was too high, progesterone concentrations higher than 1 ng/mL were detected in treated mares before ovulation. This premature progesterone concentration was attributable to elevated LH, which resulted in premature ovulation or luteinization of follicles.…”

Cloning and Expression of Iranian Turkmen-thoroughbred Horse Follicle Stimulating Hormone in Pichia pastoris

“…Superovulation in horses is much less successful than in other domestic species. In addition to superovulation rate, the number of embryos are typically negligible (1). Hence, there is a great demand to develop products that induce multiple ovulations in mares due to changes in the governance of the horse reproduction industry (2).…”