Estradiol reverses the limiting effects of clomiphene citrate on early embryonic development in the in vitro perfused rabbit ovary.

This study examined whether the addition of estradiol (E2) to the perfused rabbit ovary would reverse the deleterious effects of clomiphene citrate (CC) on early embryonic development. Ovaries were perfused with CC (10(-5) M) or CC + E2 (1 to 1000 ng/ml). Human chorionic gonadotropin (hCG, 50 IU) was added to the perfusate of each ovary. In vitro ovulated ova in cumulus were retrieved and inseminated in vitro. E2 significantly increased the percentage of ovulated ova achieving (1) the 2-cell stage at 36 hours, (2) the morula stage by 84 hours, and (3) the blastocyst stage at 132 hours. The percentage of inseminated ova showing evidence of degeneration was reduced in ovaries treated with E2. These data suggest that CC may exert an antiestrogenic effect on the intrafollicular oocyte, which interferes with postfertilization development.