Low Molecular Weight Heparin to Achieve Live Birth Following Unexplained Pregnancy Loss: A Meta-Analysis.

The management of recurrent pregnancy loss is uncertain. Some cohort studies have identified an association between inherited thrombophilias and recurrent or late-nonrecurrent pregnancy loss which has prompted investigators to evaluate the benefit of low molecular weight heparin to achieve live birth. A similar benefit for low molecular weight heparin has also been proposed independent of thrombophilia status. A recent Cochrane Review on this topic included the results of a single randomized trial in their analysis. As there are several recent randomized trials using low molecular weight heparin in women with recurrent pregnancy loss published in the obstetrical literature, we performed a meta-analysis to evaluate the benefit of low molecular weight heparin in women who experienced unexplained recurrent or late-nonrecurrent pregnancy loss.

We conducted a meta-analysis of randomized controlled trials investigating the benefit of low molecular weight heparin versus a non-anticoagulant control arm in women with a history of ≥2 early pregnancy losses or ≥1 late pregnancy loss; we excluded women with antiphospholipid antibodies and those with an underlying cause of recurrent fetal loss, except for the hereditary thrombophilias. We planned to use random-effects analysis as the primary summary model due to the anticipated variations in enrollment criteria and interventions between the studies.

A total of 757 women were enrolled in five studies that satisfied the eligibility criteria. Using the random effects model, the risk ratio of fetal loss for low molecular weight heparin versus control was 0.49 (0.25-0.97 95% CI, P=0.04). There was significant heterogeneity observed between studies (Q-value was 15.59, P=0.004, and I²=74.33%). A priori, we identified the presence or absence of a hereditary thrombophilia as a potential source of heterogeneity. However, subgroup analysis of the studies according to the inclusion or exclusion of women with hereditary thrombophilia did not resolve the observed heterogeneity between studies. Exclusion of the only trial that enrolled women following a non-recurrent pregnancy loss improved the observed heterogeneity but diminished the apparent benefit of low molecular weight heparin (0.63, 95% CI 0.34-1.16, P=0.14). In this trial, the observed birth rate in the control arm was significantly lower than in the other two trials included in this meta-analysis with aspirin-only controls (29% versus 84% or 87% in aspirin-only arms, P<0.001).

There is a trend for increased live births when using low molecular weight heparin for the prevention of recurrent pregnancy loss. However, considering the observed heterogeneity across studies, there is insufficient evidence to support the routine use of low molecular weight heparin to improve pregnancy outcomes in women with a history of pregnancy loss.

Off Label Use: low molecular weight heparin to prevent pregnancy loss. Bauer:Bayer Healthcare: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Speakers Bureau; GTC Biotherapeutics: Membership on an entity's Board of Directors or advisory committees. Zwicker:Sanofi-Aventis: Research Funding.