Enoxaparin for prevention of unexplained recurrent miscarriage: A multicenter randomized double-blind placebo-controlled trial

Abstract

It is common practice in many centers to offer antithrombotic medications to women with unexplained recurrent miscarriage, in the presence or absence of inherited thrombophilia. Although no benefit of aspirin vs placebo has been clearly demonstrated, a doubleblind placebo-controlled trial on the effect of low-molecular-weight heparin is lacking. We enrolled 258 pregnant women with a history of unexplained recurrent miscarriage (>2 consecutive miscarriages before 15 weeks' gestation) and a negative thrombophilia workup. They were randomly assigned to receive one daily subcutaneous injection of enoxaparin 40 mg or placebo until 35 weeks' gestation. We included 256 women (mean age 32 years, ≥3 miscarriages: 72%; mean gestational age 39 days of amenorrhea) in the intention-to-treat analysis; 66.6% of 138whoreceived enoxaparin had a live birth vs 72.9% of 118 who received placebo. The absolute difference was 26% (95% CI, 217.1 to 5.1), excluding a 10% increase in the rate of live-birth on enoxaparin (P 5.34). In this first randomized, double-blind, placebo-controlled trial, enoxaparin (40mgonce daily) did not improve the chance of a live birth in nonthrombophilicwomenwith unexplained recurrent miscarriage. This trial is registered at www.ClinicalTrials.gov as #NCT00740545 and the French National Health and Drug Safety Agency (EudraCT #2006-003350-18). (Blood. 2015;125(14):2200-2205)