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EB Research - Reproductive Epidemiology

Effects of Aspirin in Gestation and Reproduction (EAGeR) Study

Study Objective

The EAGeR Trial is a multisite, block-randomized placebo-controlled clinical trial designed to evaluate the effect of daily low-dose aspirin (LDA) on live-birth rates.

Background

Maximally fertile couples have only an approximately 30-percent chance of conception in a given menstrual cycle, and average monthly fecundity is 20 percent. Estimates of miscarriages and early pregnancy loss vary, ranging from about 15 percent to 30 percent. Available data suggest that LDA has the potential to favorably impact several aspects of reproduction, including conception, implantation, early pregnancy loss, late fetal death, low birth weight, placental insufficiency, and preterm birth. LDA is widely available, inexpensive, and has few maternal side effects. Prior studies focused on narrow aspects of the effects of LDA, such as in vitro fertilization outcome or development of preeclampsia; such studies have also generally begun therapy mid or late gestation. Reproduction is unique in that each stage is inextricably linked. Therefore, better blood flow at the time of conception and implantation may ultimately lead to improved placental function and a reduced risk of preeclampsia, small-for-gestational-age infants, and preterm birth.

Study Design & Progress

The EAGeR trial is a multi-site, prospective, double-blind, block-randomized trial designed to assess the effects of low-dose aspirin on implantation and pregnancy outcomes. A total of 1228 regularly menstruating women age 18-40 years with up to two recent miscarriages and who planned to become pregnant again were randomized for this trial. 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 began 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 indicate pregnancy; and daily urine samples were collected to monitor very early pregnancy and pregnancy loss. Women were followed for up to six menstrual cycles while trying to become pregnant and if they became pregnant, throughout pregnancy.

The EAGeR trial was recently completed and the study results have been published. Overall, we found that a daily low dose of aspirin does not appear to prevent subsequent pregnancy loss among women with a history of one or two prior pregnancy losses. However, in a smaller group of women who had experienced a single recent pregnancy loss, aspirin increased the likelihood of becoming pregnant and having a live birth, and decreased the risk of preterm birth. We have also found that initiation of low-dose aspirin prior to conception was associated with the sex ratio among live born infants, and specifically that low-dose aspirin restored the numbers of male live births and pregnancy with male offspring among women with 1 to 2 prior pregnancy losses. These results suggest that LDA modulates inflammation that would otherwise reduce the conception or survival of male embryos.

We have also evaluated the utility of routine AMH testing for prediction of pregnancy loss and preconception counseling in young, fecund women and have found that AMH levels were not associated with fecundability or pregnancy loss. Thus, our data do not support routine AMH testing. Moreover, our data also suggest that the current recommendations for delaying pregnancy attempt after an early loss may be unwarranted. The team intends to build upon its current findings from the EAGeR Trial to fill critical research gaps in its quest to answer important public health questions for women of reproductive age.

Principal Investigator

Enrique F. Schisterman, Ph.D.

DIPHR Collaborators

Contact Information

Name: Dr Enrique Fabian Schisterman
Chief and Senior Investigator
Epidemiology Branch
Phone: 301-435-6893
Fax: 301-402-2084
E-mail: schistee@mail.nih.gov

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