Natural Course of the Subsequent Pregnancy after a Single Loss in Women with and without the Factor V Leiden or Prothrombin 20210A Mutations.

In previous case control studies factor V Leiden and the prothrombin 20210A mutation have been associated with pregnancy loss, in particular recurrent and late (>12 weeks of gestation) losses in women carriers¹. The prognosis of a second pregnancy after an initial late pregnancy loss in women with inherited thrombophilia is uncertain; the live birth rate reported in different cohort studies varied from 11 to 98%^2 –4. This has led to a debate about whether low-molecular-weight heparin should be prescribed to women with thrombophilia and pregnancy loss, despite the absence of evidence about its effectiveness from placebo-controlled trials.

We determined the live birth rate of the 2nd pregnancy following a first loss in a large family study that included patients with documented venous thromboembolism or premature atherosclerosis and carriership of the factor V Leiden or prothrombin 20210A mutations and their 1st degree relatives. Ectopic or terminated pregnancies and pregnancies lost due to known chromosomal abnormalities were excluded, as well as pregnancies during which anticoagulants were used. A total of 993 women (498 carriers) who had had 2809 pregnancies (1420 in carriers) were analyzed. After an early pregnancy loss in the 1st pregnancy, the live birth rate of the 2nd pregnancy was 77% (95%CI 62–87) in carriers and 76% (95%CI 57–89) in non-carriers. After a late pregnancy loss in the 1st pregnancy, the live birth rate of the 2nd pregnancy was 68% (95%CI 46–85) in carriers and 80% (95%CI 49–94) in non-carriers (OR 0.9, 95%CI 0.5–1.3).

We conclude that the pregnancy outcome in women with either factor V Leiden or the prothrombin 20210A mutation is fairly similar to the outcome in women without these mutations. After a late pregnancy loss in the first pregnancy, the live birth rate in the second pregnancy tended to be somewhat lower for carriers than for non-carriers. The live birth rates for both carriers and non-carriers in this study was substantially higher than in some other cohorts, which may be due to the fact that the cohort was not selected based on obstetric indications. Given the observed favourable prognosis after a first pregnancy loss even in women with known thrombophilia and a late loss, low-molecular-weight heparin to improve pregnancy outcome should not be used before results from ongoing randomized placebo controlled trials have shown its effectiveness and safety.