Preconception low dose aspirin and time to pregnancy: findings from the effects of aspirin in gestation and reproduction randomized trial

Enrique F Schisterman; Sunni L Mumford; Karen C Schliep; Lindsey A Sjaarda; Joseph B Stanford; Laurie L Lesher; Jean Wactawski-Wende; Anne M Lynch; Janet M Townsend; Neil J Perkins; Shvetha M Zarek; Michael Y Tsai; Zhen Chen; David Faraggi; Noya Galai; Robert M Silver

doi:10.1210/jc.2014-4179

Therapeutics · Anti-Infective and Anti-Inflammatory Agents

Preconception low dose aspirin and time to pregnancy: findings from the effects of aspirin in gestation and reproduction randomized trial

Schisterman EF, Mumford SL, Schliep KC, Sjaarda LA, Stanford JB, Lesher LL, Wactawski-Wende J, Lynch AM, Townsend JM, Perkins NJ, Zarek SM, Tsai MY, Chen Z, Faraggi D, Galai N, Silver RM

Published May 2015 The Journal of clinical endocrinology and metabolism, 100(5), 1785-1791

DOI 10.1210/jc.2014-4179 PMID 25710565 PMC PMC4422888

RRM Academy Synopsis

Low-dose aspirin cut time to pregnancy only after a recent early loss

In a placebo-controlled trial of 1,228 women with past pregnancy losses, daily low-dose aspirin before conception did not significantly shorten time to pregnancy overall. It did shorten it after one early loss in the past year. Pregnancy occurred in 67 of 100 aspirin users and 63 of 100 placebo users.

Key Findings

An hCG detected pregnancy (a positive pregnancy-hormone test) occurred in 410 of 608 women on aspirin (67%) and 382 of 606 on placebo (63%): fecundability odds ratio 1.14 (95% CI: 0.97, 1.33).
Original stratum (one loss before 20 weeks in the past year): 196 of 272 on aspirin (72%) and 173 of 269 on placebo (64%); fecundability odds ratio 1.28 (95% CI: 1.02, 1.62).
Expanded stratum (one or two losses, any gestational age, any time before): 214 of 336 on aspirin (64%) and 209 of 337 on placebo (62%); odds ratio 1.03 (95% CI: 0.83, 1.27).
For clinically confirmed pregnancy, the fecundability odds ratio was 1.13 (95% CI: 0.96, 1.33) overall and 1.29 (95% CI: 1.02, 1.63) in the original stratum.
In the original stratum, cumulative hCG detected pregnancy by cycle six was 77.1% with aspirin and 66.8% with placebo (log rank P = 0.03).

Interpretation

The trial was double-blind and placebo-controlled. The authors cite its size and design as strengths. Time to pregnancy was a planned secondary outcome. The original stratum was a prespecified group. Follow-up lasted at most six cycles. About 95% of participants were white. Women with a known history of infertility were not enrolled. The authors call their mechanism ideas speculation and call general recommendations for preconception aspirin premature.

RRM Context

Restorative reproductive medicine asks what lies behind a delayed pregnancy or a loss. The same trial team reported earlier that aspirin did not reduce clinically confirmed pregnancy loss. The authors judge that any benefit most likely occurs no later than implantation. The authors propose blood flow and inflammation as possible routes. Participants used fertility monitors and completed diaries, the cycle data that cause-based evaluation draws on.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

The objective was to determine the effect of preconception-initiated daily low-dose aspirin (LDA; 81 mg/day) treatment on time to pregnancy in women with a history of pregnancy loss.

Design

This was a multicenter, block-randomized, double-blind, placebo-controlled trial. Participants were block-randomized by center and eligibility stratum.

Setting

The study was conducted at four U.S.A. medical centers (2007-2012).

Participants

Participants women aged 18-40 years actively attempting pregnancy, stratified by eligibility criteria: the "original" stratum, women with one loss <20 weeks' gestation during the previous year; and the "expanded" stratum, women with one or two previous losses of any gestational age regardless of time since loss.

Intervention

Daily LDA was compared with matching placebo for up to six menstrual cycles of attempting pregnancy.

Main Outcome Measures

Time to hCG detected pregnancy and clinically confirmed pregnancy, analyzed by intention-to-treat, was measured.

Results

Of the 1228 women randomly assigned to LDA (n = 615) or placebo (n = 613), 410 (67%) women receiving LDA achieved pregnancy compared to 382 (63%) receiving placebo, corresponding to a fecundability odds ratio (FOR) of 1.14 (95% CI: 0.97, 1.33). Among women in the original stratum (n = 541), LDA was associated with increased fecundability compared to placebo (For: 1.28; 95%CI: 1.02, 1.62).

Conclusions

Preconception-initiated LDA treatment resulted in a nonsignificant increase in fecundability of 14% in women with a history of 1-2 pregnancy losses, and a significant increase of 28% in women with a history of only one pregnancy loss of <20 weeks' gestation in the preceding year. Preconception-initiated LDA may increase fecundability in certain women with a recent early pregnancy loss.

Topics

Therapeutics › Anti-Infective and Anti-Inflammatory Agents › Nonsteroidal Anti-Inflammatory Drugs · Pregnancy › Preconception Care › Preconception Optimization

Enrique F Schisterman, Sunni L Mumford, Karen C Schliep, Lindsey A Sjaarda, Joseph B Stanford, Laurie L Lesher, Jean Wactawski-Wende, Anne M Lynch, Janet M Townsend, Neil J Perkins, Shvetha M Zarek, Michael Y Tsai, Zhen Chen, David Faraggi, Noya Galai, Robert M Silver

E Schisterman, S Mumford, K Schliep, L Sjaarda, Joe Stanford, Joey Stanford, J Stanford, L Lesher, J Wactawski-Wende, A Lynch, J Townsend, N Perkins, S Zarek, Mike Tsai, M Tsai, Z Chen, Dave Faraggi, D Faraggi, N Galai, Bob Silver, Rob Silver, Bobby Silver, R Silver

PMID 25710565 25710565 DOI 10.1210/jc.2014-4179 10.1210/jc.2014-4179 Schisterman et al. 2015, Schisterman 2015

Preconception low dose aspirin and time to pregnancy: findings from the effects of aspirin in gestation and reproduction randomized trial

Low-dose aspirin cut time to pregnancy only after a recent early loss

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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