Letrozole in ectopic pregnancy: exploring a promising frontier in non-surgical therapy - a narrative review.

BACKGROUND: Ectopic pregnancy (EP) is a potentially life-threatening condition affecting 1-2% of pregnancies, traditionally managed via surgical or methotrexate (MTX)-based medical approaches. However, MTX is associated with significant systemic side effects and potential impairment of ovarian reserve. Aromatase inhibitors (AIs), particularly letrozole, have recently emerged as promising fertility-preserving alternatives. OBJECTIVE: To synthesize and evaluate the available evidence regarding the efficacy, safety, and mechanistic rationale for the use of letrozole in the medical management of EP, and to compare outcomes with those of conventional MTX therapy. METHODS: A systematic search of PubMed, Scopus, ScienceDirect, and Web of Science was conducted for English-language studies published from 1990 to April 2025. Eligible studies included randomized trials, prospective cohorts, or case reports that evaluated letrozole, MTX, or their combination for the treatment of tubal ectopic pregnancy and reported extractable clinical outcomes. Descriptive statistics and chi-square tests were used for comparative analysis. RESULTS: Seven studies met the inclusion criteria, encompassing 249 patients treated with letrozole and 206 with MTX. The overall treatment success rate was 74.7% for letrozole and 80.1% for MTX (p = 0.172), with comparable surgical intervention rates (13.1% vs 13.4%, p = 0.941). The highest success rate with letrozole (90.5%) was observed with a 10-day 5 mg twice-daily regimen. Combination therapy with MTX and letrozole demonstrated superior outcomes (90.6% success, 9.4% surgery) compared to monotherapy. Letrozole was associated with minimal side effects and no observed detriment to ovarian reserve. CONCLUSION: Letrozole represents a safe, non-cytotoxic alternative to MTX for managing selected cases of unruptured ectopic pregnancy, particularly in fertility-conscious populations. While current evidence is encouraging, further randomized controlled trials are essential to establish optimal dosing regimens, long-term reproductive outcomes, and treatment algorithms.