Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphene citrate as adjuvants to recombinant follicle-stimulating hormone in controlled ovarian hyperstimulation: a prospective, randomized, blinded clinical trial

Objective: To study the efficacy of the aromatase inhibitor letrozole as adjuvant to recombinant FSH (rFSH) in controlled ovarian hyperstimulation (COH). Design: Prospective, randomized, and blinded clinical study. Setting: Academic tertiary institute. Patient(s): Forty-one patients with unexplained infertility undergoing intrauterine insemination (IUI) therapy were randomized to receive either letrozole or clomiphene citrate (CC) as adjuvants to rFSH. Intervention(s): From day 3 to 7 of the cycle 2.5 mg/d letrozole or 100 mg/d CC were administered. All patients received 75 IU rFSH starting on day 7 of stimulation until the day of hCG administration. Ovulation was triggered with recombinant hCG (250 mu g) when the leading follicle(s) reached 18 mm in diameter. A single IUI was performed 36 hours later. The luteal phase was supplemented with micronized progesterone vaginally. Main Outcome Measure(s): Ovarian stimulation response (E-2 levels and number of follicles) was our primary outcome. Result(s): There were no differences in demographic characteristics between groups. Although there was a significantly lower peak serum E-2 level in the group receiving letrozole + rFSH compared with CC + rFSH (914 +/- 187 vs. 1,207 +/- 309 pg/mL, respectively, P < .007), there were no differences in the number of mature (> 16 mm) preovulatory follicles. A significantly higher endometrial thickness was observed at the time of hCG administration in patients that received letrozole (9.5 +/- 1.5 mm vs. 7.3 +/- 1.1 mm; P = .0001). The clinical pregnancy rate was similar between groups (23.8% vs. 20%, respectively). Conclusion(s): The aromatase inhibitor letrozole appears to constitute a good alternative to CC in patients with unexplained infertility undergoing gonadotropin-stimulated COH cycles combined with IUI therapy.