PR002178 (Project)

Description:Research Question: Are there specific metabolomic alterations in the Follicular fluid (FF) of women with unexplained infertility (UI)? Study Design: This case-control study included 20 women undergoing in-vitro fertilization (IVF), comparing 10 women diagnosed with UI to 10 control women whose male partners had abnormal semen parameters. FF samples were collected during oocyte retrieval and analysed using hydrophilic interaction liquid chromatography and reversed-phase liquid chromatography, coupled with tandem mass spectrometry (MS/MS) on a Q-TOF mass spectrometer. Metabolites were identified using XCMS Online and MetaboAnalyst, followed by pathway enrichment analysis via the KEGG database. Statistical analyses including OPLS-DA and ROC analysis assessed their diagnostic potential. Metabolite levels were correlated with clinical parameters, including embryo development rates, oocyte maturation, and IVF outcomes. Results: In women with UI, 12 metabolites, including Diacylglycerols, Phosphatidic acids, Vitamin D3 glucosiduronate, 1α-hydroxy-2β-(5-hydroxypentoxy) vitamin D3, Asparginyl-Asparagine, Lithocholic acid, Leu-Pro-Ala-Ser-Phe, Triacylglycerols, Phosphatidyl choline, Phosphatidylethanolamine and Lactosyl ceramide were significantly decreased, while Ile-Lys-Val-Val was significantly increased compared to controls. These metabolites were linked to glycerophospholipid metabolism, glycerolipid metabolism, and steroid synthesis pathways. PLS-DA, OPLS-DA, and ROC analysis indicated high diagnostic performance, with AUC values exceeding 0.8. Additionally, Vitamin D3 glucosiduronate levels negatively correlated with embryo development rates, while Asparginyl-Asparagine levels demonstrated a positive correlation with the MII oocyte rate. Conclusion: This study constitutes the first comprehensive characterization of metabolic dysregulation in the FF of women with UI, offering novel insights into the underlying mechanisms contributing to this condition and advocates for routine assessment of vitamin D3 levels in serum/FF of these women.