Effects of co administration of gonadotropins and letrozole during the ovarian stimulation on IVF outcome for poor responders: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Letrozole utilizing, an aromatase inhibitor, has been examined to improve pregnancy rate in poor ovarian response women. Increasing the dose of gonadotropins and enhancement of follicles' sensitivity to androgens, are the possible mechanism of letrozole. This meta-analysis aimed to evaluate the effect of co-administration of letrozole and gonadotropin on IVF/ICSI outcomes in poor ovarian response women. METHOD: Relevant randomized controlled trials were obtained through search in several databases including PubMed, Scopus, Clinicaltrials.gov, Google scholar, and Cochrane Library. The RCTs investigating the effect of letrozole + gonadotropin versus gonadotropin reporting pregnancy outcome were selected. RESULTS: After analyzing 13 RCTs comprising 1692 patients, letrozole was associated with a reduction in the dose (SMD: -147.96 (-180.49, -115.42), P < 0.01) and duration (SMD: -2.82 (-4.21, -1.42), P < 0.01 of gonadotropin administration. There was no evidence of a difference between groups in the number of retrieved oocytes, clinical pregnancy rate, or live birth rate. A small reduction in the number of transferred embryos was observed (SMD: -0.26 (-0.49, -0.02), P = 0.03), though this finding should be interpreted with caution given heterogeneity across studies. Overall, no significant improvement in reproductive outcomes was demonstrated. CONCLUSIONS: Despite the lack of significant improvement in pregnancy and live birth rate in the letrozole group, the dose and duration of gonadotropins decreased. This has the potential to reduce the side effects of gonadotropins. However, further studies are necessary to confirm its safety and whether its use translates into clinically meaningful benefits.