Anticoagulant 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. The 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). Between 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. LMWH 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. National Institute for Health and Care Research and the Netherlands Organization for Health Research and Development.

中文翻译：

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肝素治疗复发性流产和遗传性血栓形成倾向的女性 (ALIFE2)：一项国际开放标签、随机对照试验

抗凝治疗可能会减少反复流产和遗传性血栓形成倾向女性的流产次数和不良妊娠结局。我们的目的是评估该人群中低分子肝素 (LMWH) 的使用与标准护理的比较。ALIFE2 试验是一项国际开放标签、随机对照试验，在英国 (n=26)、荷兰 (n=10)、美国 (n=2)、比利时 (n=1) 和斯洛文尼亚的医院进行(n=1)。年龄在 18-42 岁、两次或两次以上流产并确诊有遗传性血栓形成倾向、正在尝试怀孕或已怀孕（≤ 7 周妊娠）的女性有资格入选。一旦尿妊娠试验呈阳性，女性就会被随机分配 (1:1) 是否使用低剂量 LMWH（两组均采用标准护理）。LMWH 在妊娠 7 周或之前开始，并持续到妊娠结束。主要结果指标是活产率，根据现有数据对所有妇女进行评估。安全性结果包括出血事件、血小板减少和皮肤反应，并对所有随机分配的报告安全事件的女性进行了评估。该试验已在荷兰试验登记册 (NTR3361) 和 EudraCT (英国：2015-002357-35) 中注册。2012年8月1日至2021年1月30日期间，对10625名妇女进行了资格评估，其中428名妇女进行了登记，326名妇女怀孕并被随机分配（164名妇女接受LMWH，162名妇女接受标准护理）。LMWH 组 162 名有主要结局数据的女性中有 116 名 (72%) 以及标准护理组 158 名女性中有 112 名 (71%) 活产（调整后优势比 1·08，95% CI 0·65 至 1·78；绝对风险差异，0·7%，95% CI –9·2% 至 10·6%）。LMWH 组 164 名女性中有 39 名 (24%) 以及标准护理组 162 名女性中有 37 名 (23%) 报告了不良事件。对于两次或多次流产并确诊患有遗传性血栓形成倾向的女性来说，低分子肝素并没有带来更高的活产率。我们不建议在复发性流产和遗传性血栓形成倾向的女性中使用 LMWH，并且我们建议不要对反复流产的女性进行遗传性血栓形成倾向筛查。国家健康与护理研究所和荷兰健康研究与发展组织。