• Siobhan Quenby, Katie Booth, Louise Hiller, Arri Coomarasamy, Paulien G de Jong, Eva N Hamulyák, Luuk J Scheres, Thijs F van Haaps, Lauren Ewington, Shreeya Tewary, Mariëtte Goddijn, Saskia Middeldorp, ALIFE2 Block Writing Committee, and ALIFE2 Investigators.
• Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK; University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK. Electronic address: s.quenby@warwick.ac.uk.
• Lancet. 2023 Jul 1; 402 (10395): 546154-61.

BackgroundAnticoagulant therapy might reduce the number of miscarriages and adverse pregnancy outcomes in women with recurrent pregnancy loss and inherited thrombophilia. We aimed to assess use of low-molecular-weight heparin (LMWH) versus standard care in this population.MethodsThe ALIFE2 trial was an international open-label, randomised controlled trial undertaken in hospitals in the UK (n=26), the Netherlands (n=10), the USA (n=2), Belgium (n=1), and Slovenia (n=1). Women aged 18-42 years who had two or more pregnancy losses and confirmed inherited thrombophilia, and who were trying to conceive or were already pregnant (≤7 weeks' gestation), were eligible for inclusion. Women were randomly assigned (1:1) to use low-dose LMWH or not (alongside standard care in both groups) once they had a positive urine pregnancy test. LMWH was started at or before 7 weeks' gestation and continued until the end of pregnancy. The primary outcome measure was livebirth rate, assessed in all women with available data. Safety outcomes included bleeding episodes, thrombocytopenia, and skin reactions, and were assessed in all randomly assigned women who reported a safety event. The trial was registered within the Dutch Trial Register (NTR3361) and EudraCT (UK: 2015-002357-35).FindingsBetween Aug 1, 2012, and Jan 30, 2021, 10 625 women were assessed for eligibility, 428 were registered, and 326 conceived and were randomly assigned (164 to LMWH and 162 to standard care). 116 (72%) of 162 women with primary outcome data in the LMWH group and 112 (71%) of 158 in the standard care group had livebirths (adjusted odds ratio 1·08, 95% CI 0·65 to 1·78; absolute risk difference, 0·7%, 95% CI -9·2% to 10·6%). 39 (24%) of 164 women in the LMWH group and 37 (23%) of 162 women in the standard care group reported adverse events.InterpretationLMWH did not result in higher livebirth rates in women who had two or more pregnancy losses and confirmed inherited thrombophilia. We do not advise use of LMWH in women with recurrent pregnancy loss and inherited thrombophilia, and we advise against screening for inherited thrombophilia in women with recurrent pregnancy loss.FundingNational Institute for Health and Care Research and the Netherlands Organization for Health Research and Development.Copyright © 2023 Elsevier Ltd. All rights reserved.

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