DOI: https://doi.org/10.36347/sjmcr.2025.v13i11.027

Pages: 2783-2787

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) have revolutionized the management of type 2 diabetes mellitus (T2DM) and obesity. Their expanding clinical use, particularly that of the single-agonist semaglutide (Ozempic/Wegovy) and the dual GLP-1/GIP agonist tirzepatide (Mounjaro/Zepbound), has led to increased exposure in the reproductive-age population, raising critical questions about their impact on human fertility. Objective: To summarize the mechanistic and clinical evidence regarding the effects of semaglutide and tirzepatide on human fertility in both sexes, focusing on the interplay between metabolic improvement and direct reproductive signaling. Methods: This narrative review synthesizes studies published between 2015 and 2025 in PubMed, Scopus, and Embase, focusing on the reproductive and endocrine effects of semaglutide and tirzepatide in men and women. Results: GLP-1 RAs show potential beneficial effects on fertility, primarily via indirect mechanisms, including significant weight reduction, improved insulin sensitivity, and subsequent hormonal normalization. Direct effects are suggested by GLP-1 receptor expression in the gonadal tissues. However, while clinical evidence points to improved ovulation rates in women with obesity/PCOS and better sperm parameters in men with obesity-related hypogonadism, reproductive safety data, particularly long-term safety and pregnancy outcomes, are limited. Conclusion: Evidence suggests possible fertility improvement in cases of metabolic-related infertility. However, the lack of robust human data, coupled with preclinical findings of teratogenicity, necessitates a cautious approach. Long-term safety and pregnancy outcomes require urgent further research, and clinicians must counsel patients on preconception discontinuation.