EVALUATION OF BIODEGRADABLE MICROSPHERES FOR THE CONTROLLED-RELEASE OF PROGESTERONE AND ESTRADIOL IN AN OVULATION CONTROL PROGRAM FOR CYCLING MARES

A series of experiments were conducted to examine the effectiveness of two formulations of progesterone and estradiol for use in an ovulatio n control program. The first formulation required daily injections of 150 mg progesterone and 10 mg of estradiol for 10 days combined with p rostaglandin F2 alpha (PGF) on the last day of the regime. The second formulation used a new controlled release preparation consisting of mi crospheres made from a biocompatible, biodegradable polymeric excipien t poly(DL-lactide) designed so that a single injection would deliver t he entire dose of 1.5 g progesterone and 100 mg estradiol at a control led rate for a duration of 12 to 14 days and was followed by 10 mg PGF 14 days later. All of the mares treated with either formulation respo nded with ovulation occurring 18 to 24 days (n=50) or 21 to 25 days (n =13) following the beginning of treatment for mares receiving the dail y or single injection microsphere formulations, respectively. Because control of ovulation involves variability of response instead of mean response, Levene's test for equality of treatment variances was also u sed to ''amine treatment effects which were not different (P>0.05) for any of the endpoints studied. The length of estrus following treatmen t was not different (P>0.05) and averaged 5.3 and 4.7 days for mares r eceiving the daily injections or single injection formulations, respec tively. The proportion of mares with a normal estrus of more than 2 da ys in duration also did not differ (P>0.05). Furthermore, because of t he importance of mares responding to treatment with the occurrence of both estrus and ovulation together, a clinical response scoring system was used to measure the effectiveness of each of the treatments. Clin ical response scores and the proportion of mares with clinical respons e score of 5 or above were not different (P>0.05). Lastly, conception rates for mares bred on the estrus after treatment were not different (P>0.05) and averaged 53% (8/15) for mares treated daily and 80% (4/5) for mares that received the controlled release formulation. These res ults indicate that both daily injections of progesterone and estradiol for 10 days or the use of the new controlled release formulation for steroid administration when followed by PGF at the end of the treatmen t period, provided reasonably precise control of fertile ovulations.