Immunological effects of GLP-1 analogs on female reproduction: Therapeutic perspectives for infertility and recurrent pregnancy loss

Abstract

This review evaluates the role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in treating obesity-related infertility and recurrent pregnancy loss (RPL). Originally developed for managing type 2 diabetes mellitus (T2DM) and obesity, GLP-1RAs demonstrate potential in improving reproductive outcomes through their metabolic, vascular, and immunological effects. Obesity, a significant contributor to infertility and RPL, disrupts endocrine balance, promotes chronic inflammation, and impairs endometrial receptivity. GLP-1RAs alleviate these challenges by facilitating substantial weight loss, enhancing insulin sensitivity, and modulating immune responses. Research suggests that the immunological benefits of GLP-1RAs extend beyond their weight-loss effects. Key mechanisms associated with their impact on reproductive outcomes include macrophage polarization toward an anti-inflammatory phenotype, suppression of pro-inflammatory cytokine production, and restoration of maternal-fetal immune tolerance through increased regulatory T-cell activity. Emerging evidence highlights their role in enhancing vascularization and reducing oxidative stress at the maternal-fetal interface, critical processes for implantation and placental development. Despite these promising benefits, the use of GLP-1RAs during pregnancy remains contraindicated due to safety concerns. While they show promise in preconception protocols, further clinical trials are needed to establish their efficacy and safety in reproductive health. This review underscores the potential of GLP-1RAs as a multidimensional approach to managing infertility and RPL, particularly in obese women, and advocates for their integration into personalized therapeutic strategies to optimize reproductive outcomes.