Altered follicular development in clomiphene citrate versus human menopausal gonadotropin-stimulated cycles for in vitro fertilization

The pattern of periovulatory and luteal phase serum estradiol (E₂) and progesterone (P) as well as follicular fluid (FF) E₂, P, androgen, gonadotropin, and prolactin concentrations of eight women undergoing clomiphene citrate (CC)/human chorionic gonadotropin (hCG) stimulation and eight women undergoing human menopausal gonadotropin (hMG)/hCG stimulation of follicular development for the purpose of in vitro fertilization were compared. Ovulation was induced with either a 5-day course of CC (100 mg/day beginning on day 5 of the cycle) or an individualized hMG regimen, and laparoscopy was performed 36 hours after hCG administration. The length of the luteal phase was significantly longer (P < 0.05) in the CC-treated group as compared with the hMG-treated group. The pattern of serum E₂ levels differed significantly (P < 0.01) in that E₂ levels were lower in the early and midluteal phase in CC-stimulated cycles; in addition, a delayed second E₂ peak was observed in the late luteal phase in these women. Serum P levels, however, were lower in the hMG-stimulated group. Analysis of FF hormone concentrations revealed significantly (P < 0.05) higher concentrations of E₂ and androsterone in the FF of hMG-treated patients. It is concluded that follicular development in CC-stimulated cycles differs markedly from that in hMG-stimulated cycles. These differences may reflect either an altered follicular maturational process or may represent a direct inhibitory effect of CC on follicular steroidogenesis.