Aspirin Plus Heparin or Aspirin Alone in Women With Recurrent Miscarriage

Abstract

Despite intensive investigation, an underlying cause of miscarriage has not been found in a high proportion of women with a history of recurrent miscarriage. No effective intervention has been identified that improves rates of live birth. Some investigators have suggested that treatment of women with unexplained recurrent miscarriage with aspirin and low-molecular-weight heparin may increase the proportion of live births; the limited data available from randomized controlled trials have been inconsistent. This multicenter, randomized, placebo-controlled trial investigated whether a combination of aspirin with low-molecular-weight heparin or aspirin alone, compared with placebo, would improve the live-birth rate in women with a history of unexplained recurrent miscarriage. The study subjects were 364 women aged 18 to 42 years with a history of unexplained recurrent miscarriage who were trying to conceive or were pregnant less than 6 weeks. Women were randomly assigned to receive combined therapy (n = 123) consisting of daily doses of aspirin 80 mg plus open-label subcutaneous low-molecular-weight heparin (nadroparin) at a dose of 2850 IU, or 80 mg of aspirin alone (n = 120), or placebo (n = 121) either before conception or at a gestational age of less than 6 weeks. The main study outcome measure was the rate of live birth. Secondary outcome measures included rates of miscarriage, obstetrical complications, and maternal and neonatal adverse events. No significant difference between the 3 study groups was found in the proportion of live births (combined therapy, 54.5%; aspirin only, 50.8%; and placebo, 57%); the absolute difference in live-birth rate for combined therapy versus placebo was −2.6 percentage points, with a 95% confidence interval of −15.0 to 9.9; and for the aspirin only versus placebo was −6.2, with a 95% confidence interval of −18.8 to 6.4 (P = 0.63). There was also no significant difference in the live-birth rates among the 299 women in these 3 groups who became pregnant; the rates were 69.1% in the combined therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (P = 0.52). Compared to the other 2 groups, the combined therapy group had a significantly increased tendency for bruising and swelling or itching at the injection site (P < 0.001). These findings demonstrate that neither aspirin combined with nadroparin nor aspirin alone increase the likelihood of a live birth in comparison with placebo among women with unexplained recurrent miscarriage.