The Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial: A Story of Discovery

Abstract

Human reproduction is an inefficient process. There are several drivers of complications along the path to and during pregnancy, one of which is inflammation. Treatments to mitigate the deleterious effects of aberrant inflammation with something inexpensive and widely available like aspirin could have dramatic global impact. The Effects of Aspirin in Gestation and Reproduction (EAGeR) trial enrolled women aged 18 to 40 years with one to two prior pregnancy losses and no diagnosis of infertility. Patients were randomized to either low-dose aspirin or placebo. Here, we review the collective findings of the EAGeR trial to date and discuss several important lessons learned from the unique data resulting from this groundbreaking trial. Findings reported from this trial provide significant advances in the understanding of aspirin’s potential mechanisms in modulating reproductive processes and the role of inflammation in these processes. This review describes the collective findings of the EAGeR trial in the context of the existing literature regarding aspirin and inflammation in reproduction to inform relevant next steps in fertility and obstetric research, as well as potential implications for clinical care.

Fig. 1

(a) Overall cohort by pregnancy outcome. There is a slight nonstatistically significant increase in live births with low-dose aspirin (LDA) compared with placebo, with no difference in pregnancy loss. (b). Original stratum by pregnancy outcome. There is a statistically significant increase in live births with LDA compared with placebo, with no difference in pregnancy loss. (Adapted from Schisterman et al.)

Fig. 2

Clinical pregnancy based on tertile of high-sensitivity C-reactive protein (hsCRP). In the highest tertile, clinical pregnancy was restored in the low-dose aspirin (LDA) group versus the placebo group. In the lower two tertiles, there was no difference between LDA and placebo. (Reprinted with permission from Sjaarda et al.)

Fig. 3

Percentage of male live births by high-sensitivity C-reactive protein (hsCRP) tertile. In the highest tertile, the placebo group was less likely to have a male live birth than the low-dose aspirin (LDA) group. (Adapted from Radin et al.)

Fig. 4

Difference in high-sensitivity C-reactive protein (hsCRP) concentrations in low-dose aspirin (LDA) versus placebo groups during pregnancy. Symbols indicate geometric means of log-transformed high-sensitivity C-reactive protein (hsCRP) baseline (pre-randomization) and throughout pregnancy. Squares indicate the lower hsCRP tertile (closed, LDA; open, placebo), triangles indicate middle hsCRP tertile (closed, LDA; open, placebo), and diamonds indicate 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 (GEE) models within each hsCRP tertile (assigned at baseline). (Reprinted with permission from Sjaarda et al.)