LMWH fails to improve pregnancy outcomes in patients with recurrent pregnancy loss and inherited thrombophilia

Low molecular weight heparin has no advantage as it has not increased live birth rates in women who had two or more pregnancy losses and confirmed inherited thrombophilia. The study was published in the journal The Lancet.

Recurrent miscarriages are one of the most common clinical problems in reproduction with no particular etiology. In women who have recurrent miscarriages and hereditary thrombophilia, anticoagulant medication may lessen the frequency of miscarriages and unfavorable pregnancy outcomes. Hence researchers conducted an international open-label, randomized controlled trial called the ALIEF trial to compare the use of low-molecular-weight heparin (LMWH) to standard treatment.

The ALIFE2 trial was undertaken in hospitals in the UK (n=26), the Netherlands (n=10), the USA (n=2), Belgium (n=1), and Slovenia (n=1). Eligible women aged 18–42 years who had two or more pregnancy losses and confirmed inherited thrombophilia, and trying to conceive or were already pregnant (≤7 weeks gestation), were included in the trial. Women with positive pregnancy tests were randomly assigned (1:1) to use low-dose LMWH or not along with standard care in both groups. LMWH was administered at or before 7 weeks gestation and continued throughout the end of pregnancy. The primary outcome measure was assessing the livebirth rate in all women with available data. All randomly assigned women were assessed for their safety outcomes which included bleeding episodes, thrombocytopenia, and skin reactions.

Key findings:

• Out of 10,625 women assessed for eligibility, 428 were registered, and 326 conceived and were randomly assigned.
• There were 164 women randomized to LMWH and 162 to standard care.
• About 116 (72%) of 162 women with primary outcome data in the LMWH group and 112 (71%) of 158 in the standard care group had live births.
• About 39 (24%) of 164 women in the LMWH group and 37 (23%) of 162 women in the standard care group reported adverse events.

Thus, Women who had experienced two or more miscarriages and had hereditary thrombophilia did not have higher livebirth rates when using LMWH. Researchers also did not recommend LMWH usage in women who have experienced repeated miscarriages and hereditary thrombophilia.

Further reading: Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomized controlled trial.https://doi.org/10.1016/S0140-6736(23)00693-1