Hyperhomocysteinemia as a potential risk factor for unexplained recurrent pregnancy loss: an exploratory case-control study at Damascus University Maternity Hospital.

BACKGROUND: The association between hyperhomocysteinemia and unexplained recurrent pregnancy loss (RPL) remains controversial, with existing studies reporting inconsistent conclusions. OBJECTIVE: This exploratory study aimed to investigate the relationship between elevated serum homocysteine (Hcy) levels and unexplained RPL in a Syrian population. METHODS: A hospital-based case-control study was conducted from August 2024 to December 2025 at Damascus University Maternity Hospital. Ninety-six non-pregnant women were enrolled: 70 with a history of ≥ 2 unexplained miscarriages (case group) and 26 with prior successful pregnancies and no history of miscarriage (control group). Serum homocysteine concentrations were measured using an enzymatic assay on a BS-800 M Mindray analyzer. Statistical analyses included group comparisons, correlation testing, receiver operating characteristic (ROC) curve analysis, and multivariate logistic regression to adjust for potential confounders. RESULTS: The median serum homocysteine level was significantly higher in the RPL group (28.8 µmol/L, IQR 17–43) compared with controls (10.54 µmol/L, IQR 7.23–14.21; p < 0.001). Elevated homocysteine (> 15 µmol/L) was observed in 54.3% of cases versus none of the controls. A positive correlation was found between homocysteine concentration and the number of pregnancy losses (r = 0.318, p = 0.007). homocysteine remained significantly associated with RPL after adjustment for BMI (adjusted OR = 1.40, 95% CI: 1.11–1.75, p = 0.003). A positive correlation was found between homocysteine concentration and the number of prior pregnancy losses (r = 0.318, p = 0.007). ROC analysis suggested an exploratory optimal cutoff of 11.57 µmol/L, yielding 88.6% sensitivity and 70.0% specificity for predicting RPL in this study population. CONCLUSION: This exploratory study shows a significant association between hyperhomocysteinemia and unexplained recurrent pregnancy loss (adjusted for BMI) and a positive correlation with number of miscarriages. However, due to selection bias and quasi‑complete separation, findings are hypothesis‑generating. Future prospective studies with comprehensive confounder assessment are essential to validate these results.