The letrozole use in reproductive medicine: Beyond aromatase inhibition - a comprehensive review

Letrozole and other aromatase inhibitors are increasingly recognized as first-line ovulation induction (OI) medications, offering an efficient and physiologic approach to ovarian stimulation that enhances outcomes in reproductive medicine. By selectively inhibiting aromatase and maintaining lower peripheral estrogen levels, letrozole supports mono- or bi-follicular development while reducing the risk of supraphysiologic estradiol exposure seen with traditional gonadotropin regimens. These pharmacological characteristics have contributed to its expanding use not only in OI but also in various assisted reproductive technologies. To evaluate the clinical benefits, effectiveness, and safety of using letrozole in in vitro fertilization (IVF), in vitro maturation (IVM), and OI, with particular attention to reproductive outcomes, ovarian response, endometrial effects, cycle characteristics, and treatment-related adverse events. A comprehensive systematic search covering the period from December 2000 to November 2025 was conducted across major electronic databases including PubMed, Embase, the Cochrane Library, and Google Scholar. The search strategy incorporated predefined keywords related to letrozole, aromatase inhibition, OI, IVF, and IVM. Studies involving randomized controlled trials, observational cohorts, and meta-analyses were included, while non-clinical and non-reproductive data were excluded. Relevant outcomes were extracted and synthesized qualitatively. Letrozole demonstrates broad clinical utility in reproductive medicine, spanning assisted reproductive techniques, ovarian stimulation strategies, and the management of ovarian hyperstimulation syndrome risk, ectopic pregnancy, and endometriosis-related infertility. Its targeted estrogen suppression, cost-effectiveness, and favorable safety profile make it a valuable component of individualized treatment protocols. Nonetheless, further high-quality research is required to refine optimal dosing strategies, identify ideal patient populations, and clarify long-term reproductive and obstetric safety.