Thrombophilia-Related Gene Polymorphisms and Recurrent Miscarriages in Lebanese Population: A Case-Control Study

Genes associated with cardiovascular diseases are strongly linked to idiopathic recurrent pregnancy loss. Because these genetic mutations often involve coagulation factors, anticoagulant therapy, particularly low-molecular-weight heparin, is increasingly encountered in obstetric practice in Lebanon for selected maternal and pregnancy-related indications. However, data describing the prevalence and prescribing patterns of anticoagulant use among Lebanese obstetricians remain limited. In this multicenter retrospective case-control study, 12 mutations within 10 CVD-related genes in Lebanese women with a history of recurrent pregnancy loss were assessed to uncover further potential genetic links between these two conditions.

Data were collected from a total of 117 women with recurrent pregnancy loss (≥ 2 pregnancy losses with the same partner before the 22nd week of gestation) and 38 women with a history of at least one successful pregnancy. Data were collected from two independent medical centers in Lebanon, Abou Jaoude Hospital and the Lebanese Diagnostic Medical Center, through medical-record review and participant interviews. Twelve mutations were covered employing polymerase chain reaction and reverse-hybridization techniques. Because of the variation in genotyping completeness across assays, the effective sample size for individual polymorphisms ranged from 27 to 38 controls and 78 to 117 cases.

Genetic analysis revealed a significant association between Factor V Leiden (OR = 0.31; p = 0.017), Factor XIII: V34L (OR = 0.3; p = 0.009), plasminogen activator inhibitor-1: 4G/5G (OR = 0.3; p = 0.034), and lower odds of recurrent pregnancy loss. However, these associations did not remain significant after correction for multiple testing and should therefore be considered exploratory. No significant associations were observed for other evaluated polymorphisms, including methylenetetrahydrofolate reductase C677T and A1298C.

Repeated pregnancy loss is multifaceted and not necessarily linked to coagulopathy-related mutations; in the Lebanese population, certain polymorphisms showed nominal associations with lower odds of recurrent pregnancy loss that require confirmation in larger, independent studies, and no statistically significant association was observed between methylenetetrahydrofolate reductase mutations and recurrent pregnancy loss in the present study. These findings suggest that the routine presumption of a thrombophilic etiology in recurrent pregnancy loss may not be universally applicable. Future research should prioritize validating these genetic associations in larger, adequately powered cohorts and exploring the underlying biological mechanisms before any therapeutic implications are considered.