JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):136
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263771

P-124. Immunological impacts of GLP-1 analogues on female reproduction: therapeutic perspectives for infertility and recurrent pregnancy loss

Ana Clara Muniz Tavares¹, Maria Beatriz Leopoldino¹, Bruna Maia Furtado Figueiredo¹, Vinicius Salles¹, Marcelo Cavalcante¹

¹ UNIFOR - Universidade de Fortaleza – Fortaleza - CE - Brasil

Objective: The present study aims to analyze current evidence regarding the impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on female reproduction, focusing on their metabolic and immunological effects, as well as their potential in the management of infertility and recurrent pregnancy loss.
Methods: This is a narrative review conducted in the SciELO, PubMed, and Embase databases, using the following descriptors: "Glucagon-like peptide-1 receptor agonists," "Obesity," "Infertility," and "Habitual Abortion." Review articles published in the last 10 years in English or Portuguese were included. From this search, seven articles were selected and included in this study.
Results: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally indicated for type 2 diabetes and obesity, have shown promising effects on female reproductive health, especially in cases of infertility and recurrent pregnancy loss associated with obesity. In addition to promoting significant weight loss, these drugs exert important immunological and metabolic actions that contribute to the restoration of reproductive function. Among the main mechanisms observed are improved insulin sensitivity and reduced systemic inflammation, conditions that are often altered in women with polycystic ovary syndrome (PCOS) and obesity. Immunologically, GLP-1RAs act by favoring the polarization of macrophages to the M2 (anti-inflammatory) phenotype, increasing the activity of regulatory T cells (Tregs) and reducing the cytotoxicity of natural killer (NK) cells. These effects modulate the uterine environment, promoting the immune tolerance necessary for embryo implantation and pregnancy development. In addition, GLP-1RAs contribute to improved endometrial receptivity, uterine vascularization, and oocyte quality by decreasing inflammatory cytokines such as TNF-α and IL-6 and reducing oxidative stress. Clinical studies show that in women with PCOS and obesity, the use of these drugs promoted not only significant weight loss—especially tirzepatide, which achieved up to a 20% reduction in body weight—but also improvements in hormone levels, increased frequency of ovulatory cycles, and increased rates of spontaneous and assisted reproduction conception. Although there are still no specific clinical trials confirming all the immunological benefits in fertility, the use of GLP-1RAs in the preconception period has been shown to be safe, provided it is discontinued before pregnancy, due to the lack of robust data on fetal safety. Thus, GLP-1RAs emerge as an innovative and promising therapeutic strategy, combining metabolic control, immune modulation, and potential improvement in reproductive outcomes for women with infertility and pregnancy losses associated with immunometabolic dysfunction. However, further clinical studies are needed to consolidate their use in personalized reproductive protocols.
Conclusion: GLP-1 receptor agonists represent an innovative therapeutic approach for the management of infertility and recurrent pregnancy loss, especially in cases associated with obesity. Despite these promising benefits, the use of these medications during pregnancy remains contraindicated due to safety concerns, and planning for preconception use in patients who may benefit is essential. Further studies are needed to expand our understanding of the role of this medication for patients with reproductive desires and thus develop evidence-based protocols to guide its use.