Acetylsalicylic acid does not prevent first-trimester unexplained recurrent pregnancy loss: A randomized controlled trial

Introduction: Recurrent pregnancy loss occurs in about 1% of fertile couples. Without proper evidence for an effect, different treatments have been used when no etiological factor has been detected. The present trial is the first randomized trial to compare 75 mg acetylsalicylic acid with placebo for women with recurrent pregnancy loss.

Material and methods: This randomized, double-blind, placebo-controlled trial was conducted at a single center between 2008 and 2015. Recurrent pregnancy loss was defined as at least 3 consecutive first-trimester miscarriages within the couple. Women < 40 years old with a body mass index < 35 kg/m² were eligible if the workup was negative. Randomization was through a third party, who manufactured and delivered the study drugs, and occurred when fetal heartbeat was detected, to either 75 mg acetylsalicylic acid or placebo; 200 women in each group. Group allocation was concealed until all the study participants had a pregnancy outcome registered. All women attended the same control program. Primary outcome was live birth. Statistical analyses were according to intention-to-treat.

Results: All 400 women completed the follow up. Live birth rate was 83.0% (n = 166) and 85.5% (n = 171) for the acetylsalicylic acid and placebo groups, respectively (P = 0.58). The difference was -2.5% (95% CI -10.1% to 5.1%). The risk ratio was 0.97 (95% CI 0.89-1.06).

Conclusions: Treatment with acetylsalicylic acid did not prevent recurrent miscarriage in women with at least three consecutive miscarriages in the first trimester, of unknown reasons and in the same relationship. The fertility prognosis is very good, the live birth rate being > 80% with or without acetylsalicylic acid.