Alteration in Lipid Metabolism Associated With Recurrent Pregnancy Loss: An Observational Case-Control Study.

PURPOSE: No biomarkers specific to true unexplained recurrent pregnancy loss (RPL) have yet been identified. This study aimed to investigate the lipid profile of patients with unexplained RPL using metabolomic analyses. METHODS: Comprehensive serum metabolomic profiling was performed using liquid chromatography-tandem mass spectrometry. Lipid metabolites were analyzed using orthogonal partial least squares discriminant analysis. RESULTS: The final analysis included serum samples from 31 healthy non-pregnant controls, 15 healthy pregnant controls, 32 non-pregnant patients with RPL, 19 pregnant patients with RPL and euploid miscarriage, and 30 pregnant patients with RPL and aneuploid miscarriage. Compared with controls, the non-pregnant RPL group exhibited higher levels of inflammation-related metabolites, including 11-dehydro-thromboxane B2 (11-dehydro-TXB2), 12-hydroxyeicosatetraenoic acid (HETE), and prostaglandin E2 (PGE2). Pregnant controls showed increased arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid metabolites. Comparisons between pregnant controls and patients with euploid or aneuploid miscarriages showed no clear separation. Enzyme-linked immunosorbent assay confirmed elevated serum 11-dehydro-TXB2 in non-pregnant patients with RPL. CONCLUSION: Patients with RPL display a distinct serum lipid signature in the non-pregnant state, characterized by elevated levels of pro-thrombotic and pro-inflammatory eicosanoids, including 11-dehydro-TXB2, 12-HETE, and PGE2. Further studies are warranted to clarify the potential utility of 11-dehydro-TXB2 as biomarkers for RPL.