Immunometabolic Dysregulation in Female Obesity: Mechanistic Links to Ovarian Dysfunction, Implantation Failure, and Preeclampsia

Obesity is one of the most pressing public health challenges of our time, with a growing impact on metabolic and reproductive dysfunction in women. The expansion of visceral adipose tissue drives a chronic, low-grade systemic inflammatory state that has been associated with functional changes in the ovary, the endometrium, and the placenta across different stages of the reproductive process. This structured narrative review, guided by a PICo-framed research question and literature searches across PubMed/MEDLINE, Scopus, Web of Science, Embase, and ScienceDirect, examined the main immunometabolic mechanisms underlying female obesity and their reported associations with ovarian dysfunction, implantation failure, placental dysfunction, infertility, and preeclampsia. The evidence indicates that chronic low-grade inflammation, insulin resistance (IR), and functional hyperandrogenemia may impair folliculogenesis, oocyte quality, and ovarian reserve, while cytokine and adhesion-molecule dysregulation in the endometrium has been linked to impaired decidualization and a narrower implantation window. At the maternal–fetal interface, this same inflammatory substrate has been associated with deficient trophoblast invasion, inadequate spiral artery remodeling, and angiogenic imbalance, mechanisms widely implicated in the pathophysiology of preeclampsia. Rather than demonstrating a proven longitudinal chain within the same individual, the evidence reviewed here, drawn from heterogeneous populations, study designs, and experimental models, supports a conceptual, hypothesis-generating model in which obesity-related systemic inflammation may contribute to dysfunction across the ovary, endometrium, and placenta. Clinically, these findings support further investigation of reproductive biomarkers and early screening strategies for women with obesity, particularly in the context of assisted reproduction, alongside emerging preconception therapeutic approaches that remain largely investigational. Female obesity should therefore be understood not merely as a metabolic disorder, but as an immunometabolic condition potentially associated with dysfunction across the ovary–endometrium–placenta axis, an integrative framework that may help guide future preventive and therapeutic strategies for reproductive health, pending confirmation in longitudinal studies.