The effects of enclomiphene and zuclomiphene citrates on mouse embryos fertilized in vitro and in vivo.

The ovulatory agent clomiphene citrate, a racemic mixture of the estrogenic zuclomiphene and antiestrogenic enclomiphene isomers, has been associated with gamete/embryo toxicity in various animal models. To assess the potential effects of these isomers on fertilization and early embryogenesis, 3200 embryos were obtained from mouse oocytes fertilized in vivo and in vitro and exposed to increasing concentrations of zuclomiphene, enclomiphene, and clomiphene citrate in culture. Fertilization rates (p less than 0.01), blastocyst formation rates (p less than 0.02), and degeneration rates (p less than 0.005) were all adversely affected in a dose-dependent fashion. There were no statistically significant differences between the two isomers. Preincubation with 17 beta-estradiol did decrease the degenerative changes induced by clomiphene citrate but did not improve the decreased rate of blastocyst formation. These findings suggest adverse effects of a high concentration of clomiphene citrate and its isomers on fertilization and early mouse embryo growth that may have implications in the clinical use of this drug.