Preconception Low-Dose Aspirin Restores Diminished Pregnancy and Live Birth Rates in Women With Low-Grade Inflammation: A Secondary Analysis of a Randomized Trial

Abstract

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, placebo-controlled 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-hsCRP women 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.

Trial registration: ClinicalTrials.gov NCT00467363.

Figure 1.

Participant flow of the EAGeR trial and analysis of LDA effect on live birth stratified by baseline hsCRP. *Lost to follow-up defined as women who withdrew without achieving pregnancy in six cycles of preconception follow-up (nonpregnant) or withdrew during pregnancy prior to observing birth outcome (pregnant). CRP, C-reactive protein.

Figure 2.

Proportion of women with clinically confirmed pregnancy and live birth by baseline hsCRP concentrations and treatment group. Data indicate percentage of pregnancy or live birth in women having hsCRP <10 mg/L.

Figure 3.

Difference in hsCRP concentrations in LDA vs placebo groups during pregnancy. Symbols indicate geometric means of log-transformed hsCRP at baseline (prerandomization) and throughout pregnancy. Squares indicate the lower hsCRP tertile (closed, LDA; open, placebo), triangles indicate the middle hsCRP tertile (closed, LDA; open, placebo), and diamonds indicate the higher hsCRP tertile (closed, LDA; open, placebo). *Notation of significance indicates treatment group (LDA vs placebo) difference across pregnancy (excluding baseline) from generalized estimating equations models within each hsCRP tertile (assigned at baseline).