Cheap, Safe Way to Boost Chance for Live Birth After Pregnancy Loss?


Women who adhered to a low-dose aspirin regimen after pregnancy loss had a higher likelihood of achieving a subsequent live birth, secondary analysis of randomized trial data indicated.

Taking low-dose aspirin at least 5 days a week led to 15 more live births per 100 women (95% CI 7.65-21.15) compared with a placebo group, reported Ashley Naimi, PhD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Rockville, Maryland, and colleagues.

Those in the aspirin group also had eight more human chorionic gonadotropin (hCG)-detected pregnancies (95% CI 4.64-10.96) and six fewer pregnancy losses (95% CI -12.00 to -0.20) per 100 women, they noted in the Annals of Internal Medicine.

The effects of aspirin were stronger the earlier it was administered, with the greatest benefits observed in women who took it before getting pregnant. The effect of a low-dose aspirin regimen became weaker if it was initiated after 6 weeks of gestation, researchers noted.

“We found that aspirin use at least 4 times per week before conception through gestation week 36 was associated with increased hCG-detected pregnancies and reduced pregnancy losses, thereby increasing live births by more than 30%,” Naimi and colleagues wrote. “This evidence supports the need to focus on improving adherence to daily [low-dose aspirin] to maximize the efficacy on pregnancy outcomes.”

Naimi and colleagues conducted a per-protocol analysis of data from the EAGeR (Effects of Aspirin in Gestation and Reproduction) study, a multicenter, randomized, double-blind, placebo-controlled trial from four university medical centers in the U.S.

Previous findings from EAGeR showed that aspirin might increase a woman’s chance of pregnancy after a recent miscarriage that occurred before 20 weeks’ gestation. However, the effect did not carry over to a broader group of women; thus, the trial failed.

In a post-hoc analysis of the trial, Naimi’s group looked at 1,227 women ages 18 to 40 with no history of infertility, who had one or two previous pregnancy losses and were trying to conceive.

Women in this analysis had higher medication adherence, reflecting the best potential effect of aspirin if patients stuck to a regular low-dose regimen. These findings supplement previous results by adjusting for nonadherence to study protocol.

Participants were randomized to receive either 81 mg of aspirin or placebo. They were instructed to take their assigned medication, as well as 400 mcg of folic acid, each day through six menstrual cycles, and up until week 36 of their pregnancy if they conceived. The researchers evaluated medication adherence by measuring bottle weights regularly in follow-up.

Of the 615 women in the aspirin cohort and 612 in the placebo group, there was no difference in overall medication adherence (68% vs 66%). However, among study participants who conceived, adherence dropped from 74% before conception to 64% after conception. More than half of the women adhered to study protocol for 70% or more of the study period.

Those who took aspirin for the entire follow-up period had more hCG-detected pregnancies (risk ratio [RR] 1.12, 95% CI 1.02-1.23) and live births (RR 1.33, 95% CI 1.08-1.64) compared with those in the placebo group. Additionally, participants who adhered to a low-dose aspirin regimen had about a 30% decreased risk of pregnancy loss (RR 0.69, 95% CI 0.50-0.95).

While taking aspirin had an effect both before and after conception, the effects were stronger when women took it earlier, especially for pregnancy loss outcomes. The RR of pregnancy loss ranged from 0.70 (95% CI 0.47-1.04) if treatment was initiated 6 weeks after conception to 0.93 (95% CI 0.65-1.33) when treatment was started 20 weeks after conception.

Naimi and colleagues recognized that the EAGeR trial consisted of women who were mostly well educated and from higher-income households, which may limit the generalizability of their findings. Additionally, there were too few cases of adverse events, such as preterm birth and preeclampsia, for the study authors to evaluate the effect of aspirin on those outcomes.

They concluded that based on the changes in adherence before and after conception, clinicians should be aware of when patients are most likely to stick to their medication regimen. Future studies, they added, should focus on efforts to improve adherence, including alternate medication delivery routes and provider and patient education.

  • Amanda D’Ambrosio is a reporter on MedPage Today’s enterprise & investigative team. She covers obstetrics-gynecology and other clinical news, and writes features about the U.S. healthcare system. Follow


This trial was funded by the National Institutes of Health (NIH).

Naimi and colleagues reported receiving funds from the NIH and the Canadian Institutes of Health Research during the study period.

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