Low-dose aspirin and sporadic anovulation in the EAGeR randomized trial

• Published in: The journal of clinical endocrinology and metabolism 2017-01, Vol.102 (1), p.86-92
• Main Authors: Radin, Rose G, Sjaarda, Lindsey A, Perkins, Neil J, Silver, Robert M, Chen, Zhen, Lesher, Laurie L, Galai, Noya, Wactawski-Wende, Jean, Mumford, Sunni L, Schisterman, Enrique F
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anovulation - drug therapy; Aspirin; Aspirin - therapeutic use; Clinical s; Data collection; Double-Blind Method; Female; Fertility; Follow-Up Studies; Health care facilities; Health risk assessment; Humans; Infertility; Live Birth; Luteinizing hormone; Luteinizing Hormone - blood; Menstrual cycle; Menstrual Cycle - drug effects; Menstruation; Ovulation; Ovulation - drug effects; Platelet Aggregation Inhibitors - therapeutic use; Pregnancy; Pregnancy Outcome; Urine; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2016-2095

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. The mechanism underlying this effect is unclear, but it may work through ovulation. Objective: We estimated the effect of LDA on the per-cycle risk of anovulation among eumenorrheic women. Design: The Effects of Aspirin in Gestation and Reproduction trial, a multi-center, randomized, double-blind, placebo-controlled trial of daily LDA on reproductive outcomes. Preconception follow-up lasted 1–6 menstrual cycles (ClinicalTrials.gov, NCT00467363). Setting: Four US medical centers, 2007–2011. Patients or Other Participants: Healthy women (n=1,214), age18–40, were attempting pregnancy, had regular menstrual cycles (21–42 days), and had a history of 1–2 documented pregnancy losses, ≤2 live births, and no infertility. All participants completed at least one menstrual cycle of follow-up; there were no withdrawals due to adverse events. Intervention: Daily, 81 mg aspirin for 1–6 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, as indicated by a 2.5-fold increase in daily urinary LH. The hypothesis was formulated before data collection. Results: Among 4,340 cycles, LDA was not associated with anovulation (LDA: 13.4%, placebo: 11.1%; risk ratio=1.16, 95% confidence interval: 0.88, 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 1–2 pregnancy losses. LDA may affect fertility via other pathways, and these warrant further study. Secondary Abstract: Using daily measures of luteinizing hormone from 1,214 eumenorrheic women (3,430 menstrual cycles) in the EAGeR trial, we observed no effect of low-dose aspirin versus placebo on anovulation.