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

Abstract

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.

Extensive serum biomarker analysis in the prethrombotic state of recurrent spontaneous abortion

“…As one of the most prevalent obstetric complications, recurrent spontaneous abortion affects more than 30% of pregnancies. 16 Although RSA has been the focus of the majority of research, in most cases the cause of RSA is not clear. Recently, the relationship between RSA and the prethrombotic state has become a focus of attention.…”

Understanding recurrent pregnancy loss: recent advances on its etiology, clinical diagnosis, and management

“…Recently, Eslami et al. [ 86 ] have performed a large scale meta-analysis which includes 10,410 RPL cases and 9,406 controls, and their results indicated that FLV presents a significant association with RPL in overall population analysis, and the positive association was also observed in Asian, European, Africa populations but not in south Americans. In addition, the prothrombin G20210A mutation, giving rise to elevated mRNA and protein expression of prothrombin, is associated with an increased risks of thrombosis [ 87 ].…”

Genetic variation in placental insufficiency: What have we learned over time?

“…The Leiden mutation in the Factor V gene has been associated with PE, and the mechanism is possibly due to increased thrombosis in the placenta (Dizon-Townson et al, 1996). This mutation has also been implicated in RPL, but the association is only observed in certain populations (Eslami et al, 2020) but not others (Reddy et al, 2019). Overall, thrombophilia may be implicated in pregnancy complications but is unlikely to be their primary cause.…”