The in vivo and in vitro effects of clomiphene citrate on ovulation, fertilization, and development of cultured mouse oocytes

Clinical data indicate a high rate of discrepancy between ovulation and pregnancy rates and a high abortion rate in anovulatory women treated with clomiphene citrate. An animal model was used to examine the in vivo and in vitro effects of the drug on fertilization and preimplantation development. This work indicates that mice treated with clomiphene in the early follicular phase of pregnant mare's serum-induced cycles show a dose-dependent decrease in ovulated oocytes. No effect was seen on the further development of these ova. When the drug was administered in the late follicular phase, a dose-dependent decrease was seen in the rate of successful copulation, ovulation, and embryo development. Concomitant 17β-estradiol treatment reversed the copulatory, ovulatory, and developmental effects of clomiphene. A short in vitro treatment of oocytes with clomiphene prior to in vitro fertilization resulted in an increased proportion of degenerated and unfertilized ova. Moreover, this treatment caused a dose-dependent decrease in blastocyst formation.