A review of immunometabolic crosstalk in PCOS-related pregnancy loss: mechanisms and emerging therapeutic strategies
Abstract
Background: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder affecting up to 18% of reproductive-aged women globally. Women with PCOS exhibit a significantly increased risk of miscarriage, independent of obesity and assisted reproduction variables. The etiology of PCOS-related pregnancy loss is multifactorial. Nevertheless, current clinical interventions target isolated mechanisms and demonstrate limited efficacy in reducing miscarriage rates.
Objective: This review synthesize recent evidence connecting metabolic and immune dysregulation to pregnancy loss in PCOS and evaluate novel therapeutic strategies targeting immunometabolic pathways.
Content: This review first presents an overview of the mechanistic pathways implicated in PCOS-related miscarriage, including endocrine-metabolic dysfunction, immune-inflammatory imbalance, oxidative stress and ferroptosis, vascular and coagulation defects, and uterine-placental abnormalities. Both translational and clinical for interventions with dual metabolic-immune effects are highlighted, such as metformin, antioxidants likeN-acetylcysteine, anti-androgens, and combination regimens including aspirin with low-molecular-weight heparin (LMWH). Agents with mechanistic promise but limited exploration, such as glucagon-like peptide-1 (GLP-1) receptor agonists, selenium nanoparticles, and stem cell-based therapies, are also discussed. Future directions for PCOS pregnancy care are outlined, emphasizing the integration…
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