CLINICAL AND PATHOGENETIC SIGNIFICANCE OF CIRCULATING METABOLOMIC ALTERATIONS IN RELATION TO REPRODUCTIVE MARKERS IN WOMEN WITH INFERTILITY
Abstract
Female infertility is a complex and heterogeneous condition influenced by endocrine, metabolic, and mitochondrial factors. Although anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) are widely used to assess ovarian reserve, they do not fully capture the underlying metabolic processes involved in reproductive dysfunction. Objective: To investigate the association between circulating metabolomic alterations and reproductive hormonal markers in women with infertility, and to evaluate whether integration of metabolomic variables improves discrimination of infertility status. Methods: This retrospective case-control study included 162 reproductive-aged women (21–38 years), comprising 112 women with infertility and 50 fertile controls. Data were obtained from clinical records at the IVF center of the Department of Obstetrics and Gynecology, Tashkent State Medical University, between December 2024 and January 2026. Results: Infertile women had significantly lower AMH levels (median 1.8 vs 3.1 ng/mL, p<0.001) and higher basal FSH levels (8.2 ± 1.9 vs 6.8 ± 1.4 IU/L, p<0.001) compared with fertile controls. Metabolomic profiling revealed higher concentrations of lactate, glutamate, palmitate, and acylcarnitine C16, alongside lower citrate, glycine, and tryptophan (all q<0.05). In adjusted analyses, AMH was independently associated with citrate (β=0.28, p<0.001), lactate (β=−0.23, p=0.003), palmitate (β=−0.20, p=0.009), and tryptophan (β=0.14, p=0.038). A combined endocrine–metabolite model improved discrimination of infertility compared with a hormone-only model (AUC 0.839 vs 0.768), with internal validation demonstrating minimal overfitting. Conclusion: Infertility is associated with a coordinated pattern of metabolic alterations involving mitochondrial energetics, lipid metabolism, and amino acid pathways. Integration of metabolomic and endocrine markers enhances discrimination beyond conventional hormonal assessment and may improve biological characterization of female infertility.
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