Scoping Review of Letrozole in Assisted Reproductive Cycles: Efficacy and Outcomes Across Infertility Causes

Background: Infertility affects 8-12% of couples globally, with causes including hormonal and structural abnormalities. Letrozole, an aromatase inhibitor, is commonly used for ovulation induction, but its role in various assisted reproductive technologies (ARTs) and across different subgroups of infertile women remains unclear. Objective: This scoping review aimed to map the existing evidence on the use of letrozole in assisted reproductive cycles, focusing on reproductive outcomes and its application across different patient populations. Methods: A scoping review was conducted following the PRISMA-ScR guidelines. Twelve studies-including randomized controlled trials and retrospective cohorts-were identified through a structured search strategy. Studies comparing letrozole alone or in combination with gonadotropins/clomiphene to other stimulation protocols were included. Data were charted across multiple outcomes including oocyte yield, implantation, pregnancy, miscarriage, and live birth rates. Results: Evidence suggests that letrozole-based protocols may enhance oocyte yield and improve reproductive outcomes in certain settings. The highest implantation rate (57%) was observed in natural cycles, while the letrozole-only group showed the highest clinical pregnancy (50.57%) and live birth rates (45.58%). Combination protocols achieved the highest ongoing pregnancy rate (58.3%), with the lowest miscarriage rate (14.86%) in the letrozole-only group. Conclusions: Letrozole appears to be a versatile agent in ART, especially for patients requiring reduced gonadotropin doses or estradiol modulation. This scoping review highlights the need for further research to clarify its optimal use across different infertility subgroups and ART modalities.