Letrozole versus clomiphene citrate for superovulation in Egyptian women with unexplained infertility: a randomized controlled trial.

Objectives: To compare the efficacy of letrozole with clomiphene citrate (CC) in Egyptian women with unexplained infertility.

Study Design: This randomized controlled trial was conducted at Ain Shams University Hospital and Dar Al Hekma hospital between February 2010 and May 2011.

Patients And Methods: Two hundreds and seventy women with unexplained infertility were randomized into two groups using computer-generated randomization plan, and were given letrozole 2.5 mg/day from cycle day 3 to 7 (Letrozole group, n=136) or CC 100 mg/day from cycle day 3 to 7 (CC group, n=134). On day 9, the participants underwent a transvaginal sonography (TVS) every other day to monitor their ovulation and measure both endometrial thickness and Doppler flow indices of uterine and subendometrial vessels. Single injection of 10,000 IU of human chorionic gonadotropin (hCG) was given when the mean diameter of at least one ovarian follicle was ≥18 mm, quantitative βhCG was done 2 weeks after hCG injection to diagnose chemical pregnancy. Clinical pregnancy was confirmed by observing a gestational sac with fetal echoes and pulsation 4 weeks after positive pregnancy test by TVS.

Results: Both groups were comparable with regard to the day of hCG administration (letrozole 13.4±5 vs CC 12.1±4.9, respectively, p=0.06). The mean number of mature follicles was significantly higher in CC group (2±0.9 vs 1±0.0, P=0.02). Serum estradiol was significantly greater in CC group (817±299 vs 364±149 pg/ml, P<0.001). The clinical pregnancy rate was significantly higher in letrozole group (23.07 vs 10.68%, P<0.001). There was statistically significant increase in endometrial receptivity in letrozole group as assessed by endometrial thickness and Doppler flow indices of uterine and subendometrial vessels. No serious side effects were reported in either group.

Conclusion: Letrozole has beneficial effect on endometrium, an action that may improve the implantation and pregnancy rates in women with unexplained infertility.