Attenuation of ovarian response by low-dose ketoconazole during superovulation in patients with polycystic ovary syndrome

Objective: To investigate the clinical efficacy of mild inhibition of ovarian steroidogenesis by very low-dose ketoconazole during induction of ovulation in patients with polycystic ovary syndrome (PCOS). Design: Prospective, randomized, cross-controlled study in consecutive cycles. Setting: Large tertiary care center. Patient(s): Eighteen patients with PCOS undergoing hMG superovulation with or without ketoconazole. Intervention(s): A fixed hMG dosage was initiated on cycle days 5-9 in both of the study cycles. Further hMG adjustment was done according to serum E₂ levels and follicular measurements. Ketoconazole was administered in one of the cycles by two protocols. Main Outcome Measure(s): Serum E₂ and P levels, lead follicles, pregnancy rate, and development of ovarian hyperstimulation syndrome. Result(s): Although higher daily hMG doses were needed in cycles with ketoconazole compared with cycles without the drug, the peak E₂ levels were substantially lower in the ketoconazole cycles. Although the number of lead follicles did not differ between treatments, the addition of ketoconazole significantly reduced the number of hyperstimulated cycles. Consequently, the cancellation rate dropped dramatically, thus yielding a higher pregnancy rate per patient in the ketoconazole protocols. Conclusion(s): Use of a very low dose of ketoconazole during ovulation induction effectively attenuates ovarian steroidogenesis in patients with PCOS. This effect may serve as an adjunct to better control the ovarian response in women who are prone to hyperstimulated cycles.