A review of immunometabolic crosstalk in PCOS-related pregnancy loss: mechanisms and emerging therapeutic strategies.

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 of immunometabolic biomarkers, advanced animal models, and mechanism-informed combination trials.

CONCLUSION

PCOS-related miscarriage is increasingly recognized as resulting from dysregulation of immune-metabolic crosstalk. Mechanism-based, multidimensional strategies targeting this dual pathology represent a promising paradigm for preventing and managing pregnancy loss in women with PCOS.