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

May 13, 2025Journal of reproductive immunology

Immune effects of GLP-1 drugs on female reproduction and their potential for treating infertility and repeated pregnancy loss

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Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may improve reproductive outcomes in obesity-related infertility and recurrent pregnancy loss.

Obesity disrupts endocrine balance and promotes chronic inflammation, contributing to infertility and recurrent pregnancy loss.
GLP-1RAs may facilitate substantial weight loss and improve insulin sensitivity.
The immunological effects of GLP-1RAs include shifting immune responses toward an anti-inflammatory state and enhancing maternal-fetal immune tolerance.
Key mechanisms include macrophage polarization, reduced pro-inflammatory cytokine production, and increased regulatory T-cell activity.
GLP-1RAs may enhance vascularization and decrease oxidative stress at the maternal-fetal interface, processes important for implantation and placental development.
Despite potential benefits, GLP-1RAs are contraindicated during pregnancy due to safety concerns, and further clinical trials are needed to confirm their efficacy in reproductive health.

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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.

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

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