Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis. A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled. Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66–2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73–2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70–2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78−1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67–2.91). Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction.

Objective. To assess if the luteinizing hormone / human chorionic gonadotropin present in some gonadotropin formulations may be of benefit in protocols with GnRH antagonists. Methods. Open, quasi-experimental, multicenter, prospective, parallel-controlled study compared 136 women undergoing in vitro fertilization – intracytoplasmic sperm injection after stimulation with highly purified human menopausal gonadotropin (hp-hMG) (n = 44), recombinant-follicle stimulating hormone (r-FSH) (n = 46), or a combination of both (r FSH + hp-hMG) (n = 46) following an antagonist protocol. Blood determinations were made on day 6 of stimulation and on the day of ovulation induction, with centralized analysis. Results. No differences were found in the ongoing pregnancy rates between groups [37.0% versus 29.5% (hp-hMG) and 23.9% (r-FSH); p = 0.688]. However, the ratio top-quality embryos / retrieved oocytes (TQE/RO) was higher in the combined therapy group (19.6%) – reaching significance versus the r-FSH group (6.5%) (p = 0.008), but not versus hp-hMG (12.3%) (p = 0.137). Conclusions. An improved TQE/RO ratio was obtained together with a greater percentage of frozen embryos in the patients that incorporated hp-hMG to their stimulation protocol. Despite good results of adding hp-hMG, non statistical differences were found in terms of ongoing pregnancy rate.