Use of granulosa-luteal cell culture to evaluate low and high clinical responses to menotropin stimulation

The cause of a poor response to human menopausal gonadotropin (hMG) remains unexplained. To determine whether aromatase activity of cultured granulosa cells obtained from relatively low estradiol (E₂) responders (serum E₂ <1000 pg/ml) to hMG therapy differed from that of good responders (E₂≥1000 pg/ml), we prospectively compared serum E₂ on the day of human chorionic gonadotropin administration to in vitro aromatase activity following a 72-h culture. Granulosa cells were obtained from seven women undergoing hMG therapy and oocyte aspiration. Follicle stimulating hormone (FSH) was added to one-half of the cultures. Serum E₂ was determined by radioimmunoassay, and aromatase activity was determined indirectly by measuring tritiated water formed by aromatization of 1-ß [³H] androstenedione to estrogen in 1 h. In this study, luteinized granulosa cells from patients with a relatively low serum E ₂ produced less estrogen in cultures when compared to cells from higher responders (p<0.01). Aromatase activity was not significantly increased by FSH in the relatively high responders, whereas FSH stimulated a significant increase in aromatase activity in cells from lower responders (p<0.001). Our results indicate that the clinical response to hMG is at least partly due to the “quality” of granulosa cell aromatase activity. A clinically relevant “block” to FSH action may be present in vivo in low responders which can be reversed in culture by addition of FSH.