Preconception-initiated Low-dose Aspirin Research Articles

The Effect of Preconception-Initiated Low-Dose Aspirin on Human Chorionic Gonadotropin-Detected Pregnancy, Pregnancy Loss, and Live Birth : Per Protocol Analysis of a Randomized Trial.

A previous large randomized trial indicated that preconception-initiated low-dose aspirin (LDA) therapy did not have a positive effect on pregnancy outcomes. However, this trial was subject to nonadherence, which was not taken into account by the intention-to-treat approach. To estimate per protocol effects of preconception-initiated LDA on pregnancy loss and live birth. The EAGeR (Effects of Aspirin on Gestation and Reproduction) trial was used to construct a prospective cohort for a post hoc analysis. (ClinicalTrials.gov: NCT00467363). 4 university medical centers in the United States. 1227 women between the ages of 18 and 40 years who had 1 or 2 previous pregnancy losses and were attempting pregnancy. Adherence to LDA or placebo, assessed by measuring pill bottle weights at regular intervals during follow-up. Primary outcomes were human chorionic gonadotropin (hCG)-detected pregnancies, pregnancy losses, and live births, determined by pregnancy tests and medical records. Relative to placebo, adhering to LDA for 5 of 7 days per week led to 8 more hCG-detected pregnancies (95% CI, 4.64 to 10.96 pregnancies), 15 more live births (CI, 7.65 to 21.15 births), and 6 fewer pregnancy losses (CI, -12.00 to -0.20 losses) for every 100 women in the trial. In addition, compared with placebo, postconception initiation of LDA therapy led to a reduction in the estimated effects. Furthermore, effects were obtained in a minimum of 4 of 7 days per week. The EAGeR trial data for this study were analyzed as observational data, thus are subject to the limitations of prospective observational studies. Per protocol results suggest that preconception use of LDA at least 4 days per week may improve reproductive outcomes for women who have had 1 or 2 pregnancy losses. Increasing adherence to daily LDA seems to be key to improving effectiveness. National Institutes of Health.

Summary for Patients: The Effect of Preconception-Initiated Low-Dose Aspirin on Human Chorionic Gonadotropin-Detected Pregnancy, Pregnancy Loss, and Live Birth.

Summary for Patients: The Effect of Preconception-Initiated Low-Dose Aspirin on Human Chorionic Gonadotropin-Detected Pregnancy, Pregnancy Loss, and Live Birth.

The Safety of Low-Dose Aspirin on the Mode of Delivery: Secondary Analysis of the Effect of Aspirin in Gestation and Reproduction Randomized Controlled Trial.

This study aimed to examine whether prenatal low-dose aspirin (LDA) therapy affects risk of cesarean versus vaginal delivery. This study is a secondary analysis of the randomized clinical effects of aspirin in gestation and reproduction (EAGeR) trial. Women received 81-mg daily aspirin or placebo from preconception to 36 weeks of gestation. Mode of delivery and obstetric complications were abstracted from records. Log-binomial regression models estimated relative risk (RR) of cesarean versus vaginal delivery. Data were analyzed among the total preconception cohort, as well as restricted to women who had a live birth. Among 1,228 women, 597 had a live birth. In the intent-to-treat analysis, preconception-initiated LDA was not associated with risk of cesarean (RR = 1.02; 95% confidence interval [CI]: 0.98-1.07) compared with placebo. Findings were similar in just women with a live birth and when accounting prior cesarean delivery and parity. Preconception-initiated daily LDA was not associated with mode of delivery among women with one to two prior losses. · Aspirin was not associated with risk of cesarean section.. · Aspirin was not associated with mode of delivery.. · No increased risk of bleeding with use of aspirin..

Urinary selective serotonin reuptake inhibitors across critical windows of pregnancy establishment: a prospective cohort study of fecundability and pregnancy loss

To prospectively investigate the association of selective serotonin reuptake inhibitor (SSRI) exposure through critical windows of pregnancy establishment with fecundability and pregnancy loss. Prospective cohort study using longitudinal urine measurements of common SSRIs while women are actively trying to conceive. Four clinical sites. A total of 1,228 women without uncontrolled depression/anxiety, attempting natural conception while participating in a randomized trial of preconception-initiated low-dose aspirin. Not applicable. Urinary SSRIs (fluoxetine, sertraline, escitalopram/citalopram) were measured while trying to conceive and, for women who became pregnant, at weeks 0, 4, and 8 of pregnancy. Fecundability odds ratios and incidence of pregnancy loss and live birth were estimated. A total of 172 women (14%) were exposed to SSRIs while trying to conceive. SSRI exposure was associated with 24% reduced fecundability, and accordingly, a nonsignificant 9% lower live birth incidence, with significantly lower live birth in fluoxetine-exposed women. SSRI exposure was not associated with subsequent pregnancy loss, whether exposure was before conception or at 0, 4, or 8 weeks of gestation, although estimates varied by specific SSRI drug. Women using SSRIs may have more difficulty becoming pregnant, and although SSRI exposure overall was not associated with pregnancy loss, fluoxetine deserves caution and future study. NCT00467363.

Preconception Blood Pressure and Its Change Into Early Pregnancy: Early Risk Factors for Preeclampsia and Gestational Hypertension.

Preeclampsia and gestational hypertension are common complications of pregnancy associated with significant maternal and infant morbidity. Despite extensive research evaluating risk factors during pregnancy, most women who develop a hypertensive disorder of pregnancy are not considered high-risk and strategies for prevention remain elusive. We evaluated preconception blood pressure and its change into early pregnancy as novel risk markers for development of a hypertensive disorder of pregnancy. The EAGeR (Effects of Aspirin in Gestation and Reproduction) trial (2007-2011) randomized 1228 healthy women with a history of pregnancy loss to preconception-initiated low-dose aspirin versus placebo and followed participants for up to 6 menstrual cycles attempting pregnancy and throughout pregnancy if they became pregnant. Blood pressure was measured during preconception and throughout early gestation. The primary outcomes, preterm preeclampsia, term preeclampsia, and gestational hypertension, were abstracted from medical records. Among 586 women with a pregnancy >20 weeks' gestation, preconception blood pressure levels were higher for preterm preeclampsia (87.3±6.7 mm Hg mean arterial pressure), term preeclampsia (88.3±9.8 mm Hg), and gestational hypertension (87.9±9.1 mm Hg) as compared with no hypertensive disorder of pregnancy (83.9±8.6 mm Hg). Change in blood pressure from preconception into very early pregnancy was associated with development of preeclampsia (relative risk, 1.13 [95% CI, 1.02-1.25] per 2 mm Hg increase in mean arterial pressure at 4 weeks' gestation), particularly preterm preeclampsia (relative risk, 1.21 [95% CI, 1.01-1.45]). Randomization to aspirin did not alter blood pressure trajectory or risk of hypertension in pregnancy. Preconception blood pressure and longitudinal changes during early pregnancy are underexplored but crucial windows in the detection and prevention of hypertensive disorders of pregnancy. Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00467363.

Physical activity and incidence of subclinical and clinical pregnancy loss: a secondary analysis in the effects of aspirin in gestation and reproduction randomized trial

To estimate the association between physical activity and risk of subclinical and clinical pregnancy loss among women with a history of pregnancy loss. Prospective cohort study as a secondary analysis of the Effects of Aspirin in Gestation and Reproduction randomized controlled trial of preconception-initiated low-dose aspirin among women with one or two prior pregnancy losses. Four U.S. clinical centers, 2007-2011. Women with confirmed pregnancy (n = 785) as determined from hCG testing in longitudinally collected biospecimens. Subclinical loss of pregnancy detected only by hCG testing and clinically recognized loss. Among 785 women (mean [SD] age, 28.7 [4.6] years) with an hCG-confirmed pregnancy, 188 (23.9%) experienced pregnancy loss. In multivariable models adjusted for confounders, compared with the first tertile of physical activity (median = 7.7 metabolic equivalent of task hours/week), there was a roughly twofold higher risk of subclinical loss in the second (risk ratio=2.06; 95% confidence interval, 1.03-4.14) and third tertiles (risk ratio = 1.92; 95% confidence interval, 0.94-3.90), with median metabolic equivalent of task hours/week of 27.8 and 95.7, respectively. No relations were observed between physical activity and clinically recognized loss. Risk related to physical activity is different for pregnancy failure close to the time of implantation compared with that for later, clinical pregnancy loss. Higher physical activity levels were associated with an elevated risk of subclinical loss (i.e., pregnancies detected only by hCG, n = 55); however, no relationship was observed with clinically recognized loss. Further work is required to confirm these findings, assess generalizability to women without prior losses, and evaluate mechanisms. Each participating center's Institutional Review Board approved the study, and participants provided written informed consent. The trial was registered on ClinicalTrials.gov (NCT00467363), and a Data Safety and Monitoring Board provided oversight.

Effect of preconception low dose aspirin on pregnancy and live birth according to socioeconomic status: A secondary analysis of a randomized clinical trial.

Low socioeconomic status (SES) is associated with adverse pregnancy outcomes and infertility. Low-dose aspirin (LDA) was shown to improve livebirth rates in certain subsets of women, and therefore, may impact pregnancy rates differentially by SES status. Therefore, the aim of the current study was to examine whether daily preconception-initiated LDA affects rates of pregnancy, livebirth, and pregnancy loss differently across strata of socioeconomic status (SES). This is a secondary analysis of The Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial, a multisite, block- randomized, placebo-controlled trial conducted at four U.S. medical centers (n = 1,228, 2007–2012). Women attempting spontaneous conception with a history of pregnancy loss were randomly allocated preconception to 81mg of aspirin + 400mcg of folic acid (n = 615) or placebo + 400mcg of folic acid (n = 613). Study medication was administered for six menstrual cycles or until 36 weeks’ gestation if pregnancy was achieved. For this analysis, women were stratified by SES, which included income (low, mid, high) and a combined grouping of education and income (low-low, low-high, high-low, high-high). Log binomial models with robust variance estimated risks of pregnancy, livebirth, and pregnancy loss for LDA versus placebo. LDA increased pregnancy and livebirth rates (RR 1.23, 95% CI: 1.03, 1.45) in the high-income, but not mid- or low-income groups. LDA increased pregnancy rates in both the low education-low income group (RR 1.22, 95% CI: 1.02, 1.46) and the high education-high income group (RR 1.23, 95%CI: 1.06, 1.42), with no effect observed in mid-SES groupings. LDA, a low-cost and widely available treatment, may be particularly beneficial to women at the highest and lowest ends of the socioeconomic spectrum, though underlying mechanisms of this disparity are unclear. Confirming these findings and identifying factors which may modulate the effectiveness of LDA will ultimately facilitate personalized clinical care and improvements in population-level reproductive health.Trial registration number: ClinicalTrials.gov, NCT00467363.

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

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.

Expanded findings from a randomized controlled trial of preconception low-dose aspirin and pregnancy loss.

What is the association between daily preconception-initiated low-dose aspirin (LDA) treatment and very early pregnancy losses or euploid (chromosomally normal) losses among women with one to two prior losses? Daily LDA initiated preconception was not associated with the rate or type of pregnancy loss among women with a history of one to two prior pregnancy losses. LDA is often used to treat recurrent pregnancy loss with reductions in pregnancy loss generally only observed among women with antiphospholipid antibodies, and null associations observed among women without antiphospholipid antibodies. We previously evaluated the association between LDA and pregnancy loss overall among women with one to two prior losses in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial and found no association, though did not distinguish between potential effects at different stages of pregnancy loss, including implantation failure, or between euploid and aneuploid losses. The EAGeR trial was a multi-site prospective block-randomized double-blind placebo-controlled trial. In total, 1228 women were randomized to daily LDA (81 mg/day) plus folic acid (400 mcg/day), or placebo plus folic acid. Participants were assigned study drug for less than or equal to six menstrual cycles or if they conceived, throughout pregnancy with study drug discontinued at 36 weeks gestation. This analysis includes additional outcome information obtained from chart abstractions after the completion of the trial, as well as testing of stored urine for measurement of hCG and detection of very early pregnancy losses, and karyotyping of the products of conception for assessment of aneuploidy of the losses. Women aged 18-40 with a history of one to two prior losses and actively trying to conceive were randomized (n = 615 LDA and n = 613 placebo) at four clinical centers in the USA (2007-2011). Log-binomial regression was used to estimate risk ratios under the intent-to-treat approach. Daily LDA initiated preconception was not associated with clinically recognized pregnancy losses or implantation failures among women with proved fecundity and a history of one to two prior losses. Specifically, 1088 (88.6%) women completed the trial with 797 having an hCG detected pregnancy (64.9%). Overall there were 133 clinical losses (12.7% LDA versus 11.8% placebo, P = 0.71) and 55 implantation failures (5.2% LDA versus 4.9% placebo, P = 0.89). No differences were found in rate of euploid losses (RR 1.11, 95% confidence interval: 0.99, 1.26). Generalizability of these findings is limited to women with a history of one to two prior losses, and may further be limited to women of white race with higher socioeconomic status as given the rigors of the study protocol participants tended to be white and have higher incomes and more education. We were also missing karyotype information on approximately one-third of the clinically recognized pregnancy losses, which may limit our power to detect effects on euploid losses, though detailed sensitivity analysis showed similar results. Our data do not support the general use of LDA to decrease pregnancy loss and further demonstrate no increased risk of loss for women on LDA treatment. This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract Nos. HHSN267200603423, HHSN267200603424, HHSN267200603426). The authors have no conflicts of interest. The trial was registered at ClinicalTrials.gov #NCT00467363. 27 April 2007. 15 June 2007.

Preconception Low-Dose Aspirin and Pregnancy Outcomes

Women with a history of pregnancy loss are at increased risk of a subsequent loss and other adverse pregnancy outcomes. The pathophysiologic mechanisms responsible for pregnancy loss are unclear. It is believed that decreased blood flow and increased inflammation may play an important role in pregnancy loss and other adverse pregnancy events. Because aspirin can improve blood flow and reduce inflammation in reproductive organs, it has been hypothesized that giving aspirin to women attempting to conceive might improve pregnancy outcomes. Many health care providers prescribe low-dose preconception aspirin therapy for women who have had a pregnancy loss and who would like to get pregnant again. However, the efficacy of this treatment is unproven. The aim of the EAGeR (Effects of Aspirin in Gestation and Reproduction) trial was to determine whether preconception treatment with low-dose aspirin would reduce the risk of pregnancy loss in women with 1 or 2 previous pregnancy losses. The study was a multicenter, block-randomized, double-blind, placebo-controlled trial conducted in women aged 18 to 40 years with a history of pregnancy loss who were attempting to become pregnant. Participants were recruited from 4 university medical centers in the United States. The original stratum included women who had 1 loss at less than 20 weeks’ gestation during the previous year. Because of slow enrollment, the stratum was expanded to include women with 1 to 2 previous losses without any restrictions on gestational age or time of loss. Prior to conception, women were randomized to receive either low-dose aspirin (81 mg/d) plus folic acid or placebo plus folic acid for up to 6 menstrual cycles. Treatment was continued until 36 weeks’ gestation for women who became pregnant. Trial staff, investigators, and participants were masked to the assigned treatment. The primary study outcome was live birth rate. Data were analyzed according to intention to treat. Of the 1228 women randomly assigned between 2007 and 2011, 1078 (88%) completed the trial and were included in the analysis (535 in the aspirin group and 543 in the placebo group). A total of 309 women (58%) in the low-dose aspirin group became pregnant and later gave birth, compared with 286 (53%) in the placebo group (absolute difference, 5.09%; 95% confidence interval [CI], −0.84% to 11.02%; P = 0.10). Pregnancy loss occurred in 68 (13%) of the women in the aspirin group and in 65 (12%) of the women in the placebo group (P = 0.78). Among women in the original stratum, who had a single recent pregnancy loss, live births occurred in 62% (151/242) of women in the aspirin group, compared with 53% (133/250) of those in the placebo group; the absolute difference was 9.2%, with a 95% CI of 0.51% to 17.89%, P = 0. 045. In the expanded stratum, however, no significant difference between treatment groups occurred in live birth rates (54% [158/293] in the low-dose aspirin group vs 52% [153/293] in the placebo group; absolute difference, 1.71%; 95% CI, −6.37% to 9.79%; P = 0.74). Major adverse events in both treatment groups were similar. Low-dose aspirin was associated with increased vaginal bleeding, but this was not associated with pregnancy loss. The use of preconception-initiated low-dose aspirin to prevent recurrent pregnancy loss is not supported by these data. Further studies are needed to investigate the apparent increased birth rate among women who had a single well-documented loss at less than 20 weeks’ gestation during the previous year.

Preconception Low-Dose Aspirin and Pregnancy Outcomes

Summary Background Preconception-initiated low-dose aspirin might positively affect pregnancy outcomes, but this possibility has not been adequately assessed. Our aim was to investigate whether low-dose aspirin improved livebirth rates in women with one to two previous pregnancy losses. Methods In this multicentre, block-randomised, double-blind, placebo-controlled trial, women aged 18–40 years who were attempting to become pregnant were recruited from four medical centres in the USA. Participants were stratified by eligibility criteria—the original stratum was restricted to women with one loss at less than 20 weeks' gestation during the previous year, whereas the expanded stratum included women with one to two previous losses, with no restrictions on gestational age or time of loss. Women were block-randomised by centre and eligibility stratum in a 1:1 ratio. Preconception-initiated daily low-dose aspirin (81 mg per day) plus folic acid was compared with placebo plus folic acid for up to six menstrual cycles; for women who conceived, study treatment continued until 36 weeks' gestation. Participants, trial staff, and investigators were masked to the assigned treatment. The primary outcome was livebirth rate, which was analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00467363. Findings Overall, 1228 women were recruited and randomly assigned between June 15, 2007, and July 15, 2011, 1078 of whom completed the trial and were included in the analysis (535 in the low-dose aspirin group and 543 in the placebo group). 309 (58%) women in the low-dose aspirin group had livebirths, compared with 286 (53%) in the placebo group (p=0·0984; absolute difference in livebirth rate 5·09% [95% CI −0·84 to 11·02]). Pregnancy loss occurred in 68 (13%) women in the low-dose aspirin group, compared with 65 (12%) women in the placebo group (p=0·7812). 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=0·0446; absolute difference in livebirth rate 9·20% [0·51 to 17·89]). 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=0·7406; absolute difference in livebirth rate 1·71% [−6·37 to 9·79]). 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. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development (US National Institutes of Health).

Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial

Preconception-initiated low-dose aspirin might positively affect pregnancy outcomes, but this possibility has not been adequately assessed. Our aim was to investigate whether low-dose aspirin improved livebirth rates in women with one to two previous pregnancy losses. In this multicentre, block-randomised, double-blind, placebo-controlled trial, women aged 18-40 years who were attempting to become pregnant were recruited from four medical centres in the USA. Participants were stratified by eligibility criteria--the original stratum was restricted to women with one loss at less than 20 weeks' gestation during the previous year, whereas the expanded stratum included women with one to two previous losses, with no restrictions on gestational age or time of loss. Women were block-randomised by centre and eligibility stratum in a 1:1 ratio. Preconception-initiated daily low-dose aspirin (81 mg per day) plus folic acid was compared with placebo plus folic acid for up to six menstrual cycles; for women who conceived, study treatment continued until 36 weeks' gestation. Participants, trial staff, and investigators were masked to the assigned treatment. The primary outcome was livebirth rate, which was analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00467363. Overall, 1228 women were recruited and randomly assigned between June 15, 2007, and July 15, 2011, 1078 of whom completed the trial and were included in the analysis (535 in the low-dose aspirin group and 543 in the placebo group). 309 (58%) women in the low-dose aspirin group had livebirths, compared with 286 (53%) in the placebo group (p=0·0984; absolute difference in livebirth rate 5·09% [95% CI -0·84 to 11·02]). Pregnancy loss occurred in 68 (13%) women in the low-dose aspirin group, compared with 65 (12%) women in the placebo group (p=0·7812). 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=0·0446; absolute difference in livebirth rate 9·20% [0·51 to 17·89]). 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=0·7406; absolute difference in livebirth rate 1·71% [-6·37 to 9·79]). 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. 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. Eunice Kennedy Shriver National Institute of Child Health and Human Development (US National Institutes of Health).

A Randomised Trial to Evaluate the Effects of Low‐dose Aspirin in Gestation and Reproduction: Design and Baseline Characteristics

Low-dose aspirin (LDA) has been proposed to improve pregnancy outcomes in couples experiencing recurrent pregnancy loss. However, results from studies of LDA on pregnancy outcomes have been inconsistent, perhaps because most studies evaluated LDA-initiated post-conception. The purpose of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was to determine whether preconception-initiated LDA improves livebirth rates in women with one to two prior losses. We performed a multicentre, block randomised, double-blind, placebo-controlled trial. Study participants were recruited using community-based advertisements and physician referral to four university medical centres in the US (2006-12). Eligible women were aged 18-40 years actively trying to conceive, with one to two prior losses. Participants were randomised to receive daily LDA (81 mg/day) or a matching placebo, and all were provided with daily 400-mcg folic acid. Follow-up continued for ≤6 menstrual cycles while attempting to conceive. For those who conceived, treatment was continued until 36 weeks gestation. The primary outcome was the cumulative livebirth rate over the trial period. There were 1228 women randomised (615 LDA, 613 placebo). Participants had a mean age of 28.7, were mostly white (95%), well educated (86% more than high school education), and employed (75%) with a household income >$100 000 annually (40%). The characteristics of those in the treatment and placebo arms were well balanced. We describe the study design, recruitment, data collection, and baseline characteristics of participants enrolled in EAGeR, which aimed to determine the effect of LDA on livebirth and other pregnancy outcomes in these women.