Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate☆

Objective: To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful.

Design: Prospective trial in infertility patients treated with CC.

Setting: Two tertiary-referral infertility clinics associated with the Division of Reproductive Sciences, University of Toronto.

Patient(s): Twelve patients with anovulatory polycystic ovary syndrome (PCOS) and 10 patients with ovulatory infertility, all of whom had previously received CC with an inadequate outcome (no ovulation and/or endometrial thickness of ≤0.5 cm).

Intervention(s): The aromatase inhibitor letrozole was given orally in a dose of 2.5 mg on days 3–7 after menses.

Main Outcome Measure(s): Occurrence of ovulation, endometrial thickness, and pregnancy rates.

Result(s): With CC treatment in patients with PCOS, ovulation occurred in 8 of 18 cycles (44.4%), and all ovulatory cycles for the women included in this study had endometrial thickness of ≤0.5 cm. In 10 ovulatory patients, 15 CC cycles resulted in a mean number of 2.5 mature follicles, but all cycles had endometrial thickness of ≤0.5 cm on the day of hCG administration. With letrozole treatment in the same patients with PCOS, ovulation occurred in 9 of 12 cycles (75%) and pregnancy was achieved in 3 patients (25%). In the 10 patients with ovulatory infertility, letrozole treatment resulted in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm. Pregnancy was achieved in 1 patient (10%).

Conclusion(s): Oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility. Letrozole appears to avoid the unfavorable effects on the endometrium frequently seen with antiestrogen use for ovulation induction.