GLP-1 Receptor Agonists Improve PCOS Fertility Outcomes, Especially When Combined with Metformin

For women with polycystic ovary syndrome (PCOS) and infertility, current treatments often fall short in addressing both metabolic dysfunction and reproductive challenges. PCOS is characterized by insulin resistance, obesity, and hormonal imbalances, which significantly impair fertility. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for obesity and type 2 diabetes, and their metabolic benefits suggest a potential role in improving PCOS-related reproductive outcomes, warranting a comprehensive review of existing evidence.

This narrative literature review systematically searched PubMed, SciELO, and LILACS for studies published between 2014 and 2025. Researchers used keywords such as "weight loss medication," "GLP-1 receptor agonists," "liraglutide," "semaglutide," "fertility," "PCOS," and "reproductive outcomes." The search yielded 47 relevant articles, which were then synthesized to evaluate the emerging role of GLP-1RAs in preconception care for women with PCOS and infertility.

GLP-1RAs consistently demonstrated metabolic benefits and emerging evidence of improved reproductive outcomes in PCOS. Clinical trials reported increased menstrual regularity, ovulation, and pregnancy rates, especially when co-administered with metformin. Specifically, liraglutide (at 1.2-3.0 mg/day) and exenatide (10 µg twice daily) were associated with enhanced follicular development and endometrial receptivity. Mechanistically, GLP-1R are expressed in reproductive tissues, suggesting direct effects, including anti-inflammatory, antifibrotic, and androgen-lowering actions. Liraglutide was also noted to restore granulosa-oocyte communication by suppressing CXCL10.