Hyperhomocysteinemia as a Risk Factor for Unexplained Recurrent Pregnancy Loss: A Case- Control Study at the 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 study aimed to investigate the relationship between elevated serum homocysteine (Hcy) levels and unexplained RPL. 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-800M Mindray analyzer. Statistical analyses included group comparisons, correlation testing, and receiver operating characteristic (ROC) curve analysis. Results The mean 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). ROC analysis identified an optimal cutoff of 11.57 µmol/L, yielding 88.6% sensitivity and 70.0% specificity for predicting RPL. Conclusion This study demonstrates a significant association between hyperhomocysteinemia and unexplained recurrent recurrent pregnancy loss. A strong, statistically significant positive correlation existed between the level of serum homocysteine and the number of miscarriages, suggesting a dose-response relationship. Homocysteine assessment could be considered screening and metabolic interventions in RPL management and warrants further investigation.