JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):149
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263940

P-137. Impact of Obesity on Endometrial Receptivity: Molecular and Functional Evidence

Maiara Peixoto Paiva¹, Amanda Lopes de Faria¹, Rivia Mara Lamaita¹, Bruna Schettino Morato Barreira¹, Mariana Rodrigues Tolentino¹

¹ MATERDEI S/A - Belo Horizonte - MG - Brasil

Objective: To evaluate the impact of obesity on endometrial receptivity in infertile patients, correlating molecular and functional alterations with adverse reproductive outcomes such as implantation failure and increased miscarriage rates, as well as discussing the biological pathways involved and potential intervention strategies.
Methods: A literature review was conducted in PubMed, Cochrane Library, and Embase databases, including publications in English that assessed endometrial receptivity during the window of implantation (WOI) in obese women. Studies with other associated female factors and those without specific analysis of endometrial alterations were excluded. Clinical studies using Endometrial Receptivity Array (ERA) and proteomic analyses were prioritized. Evidence from animal models was used only to contextualize biological mechanisms.
Results: Analysis of the studies demonstrated that obesity consistently promotes changes during the WOI. Transcriptomic evaluation (ERA) revealed downregulation of genes such as COL16A1, COTL1, HMHA1, KLRC1, XCL1, and XCL2, and upregulation of KRT7, MFAP5, and S100A1 in the receptive endometrium of obese women compared to eutrophic controls. These changes affect immune signaling and extracellular matrix remodeling pathways, suggesting a microenvironment less favorable to embryo implantation. In both humans and animal models, obesity has been associated with overexpression of chemokines (CCL2, CCL5, CCL7, CXCL10) and regulators (TLR2, CD14, CCR1), resulting in persistent recruitment of monocytes/macrophages, NK cells, and T lymphocytes to the endometrium. This cellular infiltration maintains a chronic inflammatory state mediated by NF- κB pathway activation, impairing progesterone action on stromal cells and compromising decidualization. In addition, there is abnormal extracellular matrix remodeling and altered function of uterine NK cells, which may acquire a cytotoxic profile toward the blastocyst. The presence of advanced glycation end-products (AGEs) and activation of their receptor (RAGE) further intensify inflammation and oxidative stress, exacerbating impaired endometrial receptivity and contributing to higher implantation failure and miscarriage rates. Supporting this evidence, weight loss studies in women with polycystic ovary syndrome (PCOS) have shown favorable changes in the endometrial microenvironment, including increased proteins associated with receptivity (legumain, IGFBP-7, hepatocyte growth factor receptor, cytokeratin type II 7, and cystatin-B) and reduced CD20 antigen, findings consistent with functional improvement. Furthermore, transcriptomic analysis by ERA demonstrated, in addition to altered expression of receptivity-related genes, a possible shift in the WOI in women with elevated BMI, even when molecular profiles were classified as receptive. This suggests a functional dysfunction that may not be detected by conventional receptivity tests but that compromises embryo–endometrium synchrony.
Conclusion: Evaluating endometrial receptivity in obese patients can support more precise and individualized embryo transfer strategies, taking into account the molecular and functional alterations associated with obesity, such as chronic inflammation, altered immune cell profiles, and extracellular matrix remodeling. Although tools like the Endometrial Receptivity Array (ERA) may not directly increase implantation rates, they provide critical insights into the endometrial microenvironment, enabling clinicians to tailor interventions and optimize the timing of embryo transfer, ultimately supporting personalized approaches in assisted reproduction.