THE EFFECT OF CLOMIPHENE CITRATE ISOMERS ON HUMAN GRANULOSA LUTEIN CELLS IN CULTURE

The effect of racemic clomiphene citrate and its two individual isomeric forms (i.e. en and zu) on corpus luteum function was evaluated. Granulosa-lutein cells were obtained from three normal ovulatory women undergoing oocyte retrieval following ovulation induction with agents other than clomiphene citrate for in vitro fertilization-embryo transfer (IVF-ET). The granulosa cells were cultured in the presence and absence of the three forms of clomiphene citrate, and in the presence and absence of human chorionic gonadotropin (hCG). Patients were recruited from the unit for assisted reproductive technology in a university hospital. The main outcome measured was the production of estradiol and progesterone by cultured human granulosa cells under the various conditions described above. The production of estradiol and progesterone by the cultured granulosa cells was dose-dependently reduced to a similar extent by all three forms of clomiphene citrate. The addition of hCG augmented steroidogenesis in all groups at all concentrations, but this still remained lower in all clomiphene citrate-treated groups compared to controls. The data suggest that all three types of clomiphene citrate (racemic, en, and zu) have inhibitory effects on the production of estradiol and progesterone by cultured human granulosa-lutein cells.