Abstract / Summary
Follicular-fluid (FF) organic acid concentrations may differ among women with normal ovarian reserve (NOR), polyendocrine metabolic ovarian syndrome (PMOS), and poor ovarian response (POR), reflecting alterations in central carbon and amino-acid-related metabolic pathways. PMOS and POR are common but mechanistically distinct female-factor causes of infertility, and FF, because of its direct contact with the oocyte, may capture local metabolic differences within the ovarian microenvironment. In this single-centre, exploratory cross-sectional study, FF samples obtained at oocyte retrieval from women with NOR, PMOS, and POR ( n = 40 per group) were analysed using LC–MS-based targeted organic acid profiling. The primary outcome was between-group differences in FF organic acid concentrations, interpreted using age-adjusted general linear modelling and FDR correction. Secondary analyses included PCA, PLS-DA, PERMANOVA, pathway enrichment/topology analysis, and metabolite–metabolite correlations. Multivariate analyses showed separation between NOR and PMOS and between NOR and POR groups (PERMANOVA p = 0.001). Eighteen metabolites differed robustly across analytical pipelines. Enriched pathways included the TCA cycle, pyruvate metabolism, glyoxylate–dicarboxylate metabolism, and alanine–aspartate–glutamate metabolism, whereas PMOS–POR differences were modest. These findings suggest coordinated pathway-level associations between FF organic acid profiles and ovarian phenotype, mainly involving mitochondrial energy and amino-acid metabolism. The results are hypothesis-generating; oocyte competence and clinical outcomes were not assessed.