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. Patients: 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. Interventions: From day 3 to 7 of the cycle 2.5 mg/d letrozole or 100 mg/d CC were administrated. 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 microg) 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 Measures: Ovarian stimulation response (E(2) levels and number of follicles) was our primary outcome.
Results: 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; p16 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=0.0001). The clinical pregnancy rate was similar between groups (23.8% vs. 20%, respectively).
Conclusion: 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.