Low-Dose Aspirin and Sporadic Anovulation in the EAGeR Randomized Trial

Abstract

Context: Among women with a single, recent pregnancy loss, daily preconception low-dose aspirin (LDA) increased the live birth rate with no effect on pregnancy loss. Ovulation is a potential mechanism underlying this effect.

Objective: We estimated the effect of LDA on the per-cycle risk of anovulation among eumenorrheic women.

Design: Multicenter, randomized, double-blind, placebo-controlled trial of daily LDA on reproductive outcomes. Preconception follow-up lasted 1 to 6 menstrual cycles (ClinicalTrials.gov, NCT00467363).

Setting: Four US medical centers during 2007 to 2011.

Patients or other participants: Healthy women (n = 1214), age 18 to 40, were attempting pregnancy, had regular menstrual cycles (21 to 42 days), and had a history of 1 to 2 documented pregnancy losses, ≤2 live births, and no infertility. All participants completed at least 1 menstrual cycle of follow-up; none withdrew due to adverse events.

Intervention: Aspirin (81 mg) daily for 1 to 6 menstrual cycles.

Main outcome measure: Per-cycle risk of anovulation, defined as the absence of both a positive spot-urine pregnancy test and a luteinizing hormone (LH) peak (2.5-fold increase in daily urinary LH). Hypothesis formulation preceded data collection.

Results: Among 4340 cycles, LDA was not associated with anovulation (LDA: 13.4%, placebo: 11.1%; risk ratio = 1.16, 95% confidence interval, 0.88 to 1.52). Results were similar among women with a single, recent loss.

Conclusions: Daily LDA had no effect on anovulation among women with a history of 1 to 2 pregnancy losses. LDA may affect fertility via other pathways, and these warrant further study.

Figure 1.

Consolidated Standards of Reporting Trials algorithm, the EAGeR Trial (United States, 2007 to 2011).