Embryo toxicity of clomiphene citrate on mouse embryos fertilized in vitro and in vivo.

The effect of the ovulatory agent clomiphene citrate on fertilization and early embryogenesis was investigated with the use of in vitro fertilized mouse oocytes. Alterations in early embryogenesis with clomiphene citrate exposure were further studied with the use of embryos obtained from mouse oocytes fertilized in vivo. In the nontreated group, the fertilization rate was 81%, and 61% of the oocytes reached the blastocyst stage by 96 hours. Both fertilization and blastocyst formation declined in a dose-dependent fashion when clomiphene citrate was added to the culture media in concentrations greater than or equal to 10 micrograms/ml (p less than 0.001). The rate of progressive embryo cleavage was also slower at 48 and 72 hours after drug exposure. Mouse embryos fertilized in vivo demonstrated similar findings, with decreased blastocyst formation and increased degeneration rates, again at clomiphene citrate concentrations greater than or equal to 10 micrograms/ml (p less than 0.01). Exposure to the drug beyond 24 hours had no additional effect. It appears that clomiphene citrate-exposed embryos may undergo subtle changes that later manifest themselves in the form of decreased embryo growth rates and increased embryo degeneration rates.