Outcome of the subsequent pregnancy after a first loss in women with the factor V Leiden or prothrombin 20210A mutations

Abstract

Summary. Background: The factor V Leiden (FVL) and prothrombin 20210A (PTm) mutations are associated with single late pregnancy loss and recurrent early pregnancy loss. The prognosis after an initial loss in women with thrombophilia is uncertain. Objective: To assess the pregnancy outcome of the second pregnancy after a first loss in women with and without either FVL or PTm mutations. Methods: We selected women with a first pregnancy loss out of two family cohorts of first degree relatives of probands with FVL or PTm mutations and a history of documented venous thromboembolism or premature atherosclerosis. Results: Ninety-three women had had a first pregnancy loss and became pregnant a second time. Their risk of loss of the subsequent pregnancy was higher than in 825 women with a successful first pregnancy [25 vs. 12%, relative risk (RR) 2.0, 95% CI 1.4-3.0]. The live birth rate of the second pregnancy after an early first loss (£ 12 weeks of gestation) was 77% (95% CI 62-87) for carriers and 76% (95% CI 57-89) for non-carriers (RR 1.0, 95% CI 0.8-1.3). After a late first loss (> 12 weeks), the live birth rates were 68% (95% CI 46-85) and 80% (95% CI 49-94) for carriers and non-carriers, respectively (RR 0.9, 95% CI 0.5-1.3). Conclusions: Women with a first pregnancy loss have a 2-fold increased risk of loss of the subsequent pregnancy, regardless of their carrier status. More importantly, the outcome of the second pregnancy is rather favorable in absolute terms, even for those with thrombophilia and a late loss, which raises concern regarding the risks and presumed benefits of anticoagulant therapy in these women.

Factor V Leiden and prothrombin G20210A in Portuguese women with recurrent miscarriage: is it worthwhile to investigate?

“…Recent investigations have focused on a higher prevalence of certain inherited thrombophilias, such as factor V Leiden (FVL) and prothrombin (PT) G20210A mutations, in women with unexplained recurrent pregnancy losses [16][17][18][19][20][21]. Nevertheless, these reports have produced conflicting results [22][23][24][25] and this heterogeneity is reflected in existing meta-analyses [17,20,26,27].…”

“…Two prospective multicenter studies, involving each over 4,000 first trimester pregnant women, did not find an increased miscarriage rate in carriers of these mutations [37,38]. A European prospective research, conducted in women with a previous miscarriage, has also found a similar outcome between subsequent pregnancies of FVL and PT G20210A carriers and noncarriers [22]. However, other studies revealed discordant results and clinicians continue to incorporate these tests in RM investigation protocol [17,21,26,33,34].…”

Can Factor V Leiden and prothrombin G20210A testing in women with recurrent pregnancy loss result in improved pregnancy outcomes?: Results from a targeted evidence-based review

“…The summary F2 OR was 1.77 (95% CI: 0.87-3.61; P = 0.11), with high heterogeneity (I 2 = 62%; P = 0.049). Three cohort studies 85,115,123 were rated Level 2, Good; all others were rated Level 3, Fair. [120][121][122][124][125][126] summary These casecontrol and cohort studies reflect methodologi cal diversity and clinical heterogeneity.…”

“…Of 23 identified cohort studies, only four met this initial inclusion criterion that study subjects meet the definition of RPL. [115][116][117][118] Two studies prospectively followed pregnant white women with a history of ≥3 pregnancy losses occurring at ≤12 weeks' gestation 116,118 and a third 117 reviewed pregnancy outcomes in a retrospective cohort of women having ≥3 pregnancy losses at ≤13 weeks. All showed an effect on loss rates in carrier women with RPL, and two individually reached significance ( Table 3).…”

“…Ten were excluded based on design or execution issues (see eTable 2, Supplementary Data online). Eight studies 85,115,[119][120][121][122][123][124] were analyzed to provide information about the occurrence rate of pregnancy losses among F5 carriers. The summary OR was 2.03 (95% CI: 1.29-3.17; P = 0.002; eFigure 1, Supplementary Data online), with high heterogeneity (I 2 = 66%; P = 0.004).…”