Factor V Leiden 1691G > A mutation and the risk of recurrent pregnancy loss (RPL): systematic review and meta-analysis

BACKGROUND: Although numerous replication case-control studies have attempted to determine the association between Factor V Leiden (FVL) 1691G > A mutation and susceptibility to Recurrent pregnancy loss (RPL), there have been confliction among the results of various ethnic groups. To address this limitation, here we implemented first meta-analysis to provide with consistent conclusion of the association between FVL 1691G > A mutation and RPL risk. METHODS: After a systematic literature search, pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were used to evaluate the strength of the association. Additionally, meta-regression analyses were performed to find potential source of heterogeneity. RESULTS: In this meta-analysis, 62 studies, containing 10,410 cases and 9406 controls, were included in quantitative analysis. Overall population analysis revealed a significant positive association in the dominant (OR = 2.15, 95% CI = 1.84–2.50, P < 0.001), over-dominant (OR = 1.88, 95% CI = 1.61–2.19, P < 0.001), allelic (OR = 2.05, 95% CI = 1.79–2.35, P < 0.001), and heterozygote (OR = 1.97, 95% CI = 1.68–2.30, P < 0.001) models. Moreover, a significant association of dominant (OR = 3.04, 95% CI = 2.04–4.54, P < 0.001), over-dominant (OR = 2.65, 95% CI = 1.74–4.05, P < 0.001), and heterozygote (OR = 2.67, 95% CI = 1.81–4.22, P < 0.001) models was found in the Iranian population. The subgroup analysis indicated strong significant association in Asian, European, Africa population, and case-control studies but not in South Americans and cohort studies. CONCLUSION: The FVL 1691G > A mutation and the risk of RPL confers a genetic contributing factor in increasing the risk of RPL, particularly in Iranians, except for South Americans.