Regulation of estrus and ovulation in cyclic mares with progesterone and estradiol biodegradable microspheres: effects of different doses of estradiol

Summary An experiment was conducted to determine the most effective dose of estradiol microspheres when used in combination with a 1.25g dose of progesterone microspheres for the regulation of estrus and ovulation in cyclic mares. The treatment preparation consisted of a new single injection controlled release formulation using biocompatible, biodegradable microspheres designed to deliver the entire dose at a controlled rate for a duration of 12 to 14 days. The study was designed so that mares would be pretreated with prostaglandin F 2 alpha (PGF) during the prostaglandin sensitive phase of the cycle (days 7 to 10 post ovulation) so that PGF pretreatment could be used to eliminate endogenous progesterone secretion and challenge the treatment to be effective and prolong the interval to estrus and ovulation with no assistance from endogenous progesterone secretion. Immediately after prostaglandin injection mares received an intramuscular microsphere injection containing 1.25 g progesterone and one of 5 doses of estradiol microspheres: 0, 50, 100, 150 or 200 mg. In addition, two control groups were utilized; an untreated control group that entered the study irrespective of stage of cycle and a vehicle treated positive control group that received PGF during the prostagiandin sensitive phase of the cycle (days 7 to 10 post ovulation) followed by sterile microsphere vehicle. Estradiol added to the treatment regime significantly delayed ovulation compared to the untreated control group. In progesterone treated mares and the vehicle treated group that received PGF pretreatment, days to ovulation was not different compared to untreated controls. In addition, because control of ovulation involves variability of response instead of mean response, Levene's test for equality of treatment variances was also used to examine treatment effects. Based on Levene's test, significant (67%, 70, 70 and 81%) reductions in the treatment variation for days to ovulation were observed in the progesterone + 50 mg, 100 mg and 150 mg estradiol groups and the vehicle control group that received PGF respectively, compared to untreated controls. Days to estrus, the length of estms and the proportion of mares with a normal estrus of more than 2 days in duration did not differ (P>0.05) compared to untreated controls. Because of the importance of mares responding to treatment with the occurrence of both estrus and ovulation together, a clinical response scoring system based on the synchrony of both estrus and ovulation within a treatment group was used as an additional way to measure the effectiveness of the different treatments. Clinical response scores and the proportion of mares with clinical response score of 5 or above were significantly enhanced in the prostaglandin pretreated vehicle control group and the 1.25 g progesterone + 100 mg estradiol group compared to untreated controls.