Effect of clomiphene isomers on oestradiol synthesis in cultured human granulosa cells

Abstract

The effects of en-clomiphene and zu-clomiphene (10(-7) - 10(-5) M) on oestradiol synthesis in human granulosa cells were studied. Granulosa cells were obtained from stimulated cycles in women undergoing oocyte retrieval, in the course of in-vitro fertilization/embryo transfer due to mechanical infertility. En-clomiphene and zu-clomiphene (10(-5) M) significantly reduced basal and LH-stimulated oestradiol synthesis after 2-4 days of culture. The LH-stimulated synthesis was also significantly and reversibly reduced by zu-clomiphene at lower concentrations (10(-6) - 10(-7) M) and by a mixture of en- and zu-clomiphene (10(-6) M). It is concluded that both the mixture of en- and zu-clomiphene and the isomers alone have direct inhibitory effects on oestradiol synthesis in human granulosa cells in vitro. Furthermore, it cannot be excluded that the LH-stimulated oestradiol synthesis is inhibited by zu-clomiphene at concentrations found in follicular fluid after administration of clomiphene citrate.