Preconception low-dose aspirin restores diminished pregnancy and live birth rates in women with low-grade inflammation: A secondary analysis of a randomized trial

Context: Inflammation is linked to causes of infertility. Low-dose aspirin (LDA) may improve reproductive success in women with chronic, low-grade inflammation. Objective: To investigate the effect of preconception-initiated LDA on pregnancy rate, pregnancy loss, live birth rate, and inflammation during pregnancy. Design: Stratified secondary analysis of a multicenter, block-randomized, double-blind, placebocontrolled trial. Setting: Four US academic medical centers, 2007 to 2012. Participants: Healthy women aged 18 to 40 years (N = 1228) with one to two prior pregnancy losses actively attempting to conceive. Intervention: Preconception-initiated, daily LDA (81 mg) or matching placebo taken up to six menstrual cycles attempting pregnancy and through 36 weeks' gestation in women who conceived. Main Outcome Measures: Confirmed pregnancy, live birth, and pregnancy loss were compared between LDA and placebo, stratified by tertile of preconception, preintervention serum high-sensitivity C-reactive protein (hsCRP) (low, ,0.70 mg/L; middle, 0.70 to ,1.95 mg/L; high, $1.95 mg/L). Results: Live birth occurred in 55% of women overall. The lowest pregnancy and live birth rates occurred among the highest hsCRP tertile receiving placebo (44%live birth). LDA increased live birth among high-hsCRPwomen to 59%(relative risk, 1.35; 95%confidence interval, 1.08 to 1.67), similar to rates in the lower and mid-CRP tertiles. LDA did not affect clinical pregnancy or live birth in the low (live birth: 59% LDA, 54% placebo) or midlevel hsCRP tertiles (live birth: 59% LDA, 59% placebo). Conclusions: In women attempting conception with elevated hsCRP and prior pregnancy loss, LDA may increase clinical pregnancy and live birth rates compared with women without inflammation and reduce hsCRP elevation during pregnancy. (J Clin Endocrinol Metab 102: 1495-1504, 2017).