Aspirin might have antioxidant properties and plays an important role in inflammation. Promising evidence from the in vitro fertilization (IVF) literature suggests that low-dose aspirin may improve fecundity, possibly due to improved perfusion early in pregnancy. We conducted a meta-analysis of randomized IVF clinical trials that suggested that aspirin during early gestation may reduce the risk of preterm birth and small-for-gestational-age babies. The EAGeR study is a multi-site, double-blinded randomized trial designed to assess the effects of low-dose aspirin on implantation and pregnancy outcome. It is the largest such study to-date, enrolling 1,228 (535 in the low-dose aspirin group and 543 in the placebo group) women experiencing a recent pregnancy loss who are planning subsequent pregnancies. Each woman was randomly assigned to the treatment group with 81 mg aspirin plus 0.4 mg folic acid daily or the placebo group with 0.4 mg folic acid only. Treatment/placebo administration started prior to conception and continued during pregnancy. Fertility monitors were used to assist with timing of intercourse, home digital pregnancy testing kits were used to determine pregnancy, and daily urine samples were collected to monitor very early pregnancy and pregnancy loss. Pregnancy loss, pregnancy complications and perinatal outcomes were monitored throughout pregnancy. We hypothesized that low-dose aspirin may reduce oxidative stress and inflammation and, therefore, reduce vascular resistance and improve blood flow and placental perfusion. An increased supply of oxygen and nutrients should promote placental and fetal growth, enhance conception rates, reduce pregnancy loss and pregnancy complications and, thereby, improve perinatal outcomes. Using intent to treat analysis, 309 (58%) women in the low-dose aspirin group had livebirths, compared with 286 (53%) in the placebo group (p=00984;absolute difference in livebirth rate 509% 95% CI −084 to 1102). Pregnancy loss occurred in 68 (13%) women in the low-dose aspirin group, compared with 65 (12%) women in the placebo group (p=07812). In the original stratum, 151 (62%) of 242 women in the low-dose aspirin group had livebirths, compared with 133 (53%) of 250 in the placebo group (p=00446;absolute difference in livebirth rate 920% 051 to 1789). In the expanded stratum, 158 (54%) of 293 women in the low-dose aspirin group and 153 (52%) of 293 in the placebo group had livebirths (p=07406;absolute difference in livebirth rate 171% −637 to 979). Major adverse events were similar between treatment groups. Low-dose aspirin was associated with increased vaginal bleeding, but this adverse event was not associated with pregnancy loss. Interpretation Preconception-initiated low-dose aspirin was not significantly associated with livebirth or pregnancy loss in women with one to two previous losses. However, higher livebirth rates were seen in women with a single documented loss at less than 20 weeks gestation during the previous year. Low-dose aspirin is not recommended for the prevention of pregnancy loss. Findings from this trial will have important implications not only for women trying to conceive but also for women who want to maintain a healthy pregnancy and achieve optimal perinatal outcomes.

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
U.S. National Inst/Child Hlth/Human Dev
Department
Type
DUNS #
City
State
Country
Zip Code
Russo, Lindsey M; Whitcomb, Brian W; Mumford, Sunni L et al. (2018) A prospective study of physical activity and fecundability in women with a history of pregnancy loss. Hum Reprod 33:1291-1298
Kim, Keewan; Schisterman, Enrique F; Silver, Robert M et al. (2018) Shorter Time to Pregnancy With Increasing Preconception Carotene Concentrations Among Women With 1-2 Previous Pregnancy Losses. Am J Epidemiol 187:1907-1915
Radin, Rose G; Sjaarda, Lindsey A; Silver, Robert M et al. (2018) C-Reactive protein in relation to fecundability and anovulation among eumenorrheic women. Fertil Steril 109:232-239.e1
Radin, R G; Mumford, S L; Sjaarda, L A et al. (2018) Recent attempted and actual weight change in relation to pregnancy loss: a prospective cohort study. BJOG 125:676-684
Sjaarda, Lindsey A; Ahrens, Katherine A; Kuhr, Daniel L et al. (2018) Pilot study of placental tissue collection, processing, and measurement procedures for large scale assessment of placental inflammation. PLoS One 13:e0197039
Kuhr, Daniel L; Sjaarda, Lindsey A; Alkhalaf, Zeina et al. (2018) Vitamin D is associated with bioavailability of androgens in eumenorrheic women with prior pregnancy loss. Am J Obstet Gynecol 218:608.e1-608.e6
Mumford, Sunni L; Garbose, Rebecca A; Kim, Keewan et al. (2018) Association of preconception serum 25-hydroxyvitamin D concentrations with livebirth and pregnancy loss: a prospective cohort study. Lancet Diabetes Endocrinol 6:725-732
Sjaarda, Lindsey A; Mumford, Sunni L; Kuhr, Daniel L et al. (2018) Association of testosterone and antim├╝llerian hormone with time to pregnancy and pregnancy loss in fecund women attempting pregnancy. Fertil Steril 109:540-548.e1
Sjaarda, Lindsey A; Radin, Rose G; Swanson, Chandra et al. (2018) Prevalence and Contributors to Low-grade Inflammation in Three U.S. Populations of Reproductive Age Women. Paediatr Perinat Epidemiol 32:55-67
Nobles, Carrie J; Mendola, Pauline; Mumford, Sunni L et al. (2018) Preconception Blood Pressure Levels and Reproductive Outcomes in a Prospective Cohort of Women Attempting Pregnancy. Hypertension 71:904-910

Showing the most recent 10 out of 49 publications