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

Lindsey A Sjaarda; Rose G Radin; Robert M Silver; Emily Mitchell; Sunni L Mumford; Brian Wilcox; Noya Galai; Neil J Perkins; Jean Wactawski-Wende; Joseph B Stanford; Enrique F Schisterman

doi:10.1210/jc.2016-2917

Therapeutics Anti-Infective and Anti-Inflammatory Agents

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

Sjaarda LA, Radin RG, Silver RM, Mitchell E, Mumford SL, Wilcox B, Galai N, Perkins NJ, Wactawski-Wende J, Stanford JB, Schisterman EF

Published May 2017 The Journal of clinical endocrinology and metabolism, 102(5), 1495-1504

DOI 10.1210/jc.2016-2917 PMID 28323989 PMC PMC5443323

RRM Academy Synopsis

Low-dose aspirin linked to more live births in low-grade inflammation

In a randomized trial of women with prior pregnancy losses, low-dose aspirin was associated with more live births in women with the highest inflammation marker levels. In that group, 59 out of 100 on aspirin had a live birth, against 44 out of 100 on placebo.

Study at a glance, randomized trial of 1228 women: Low-dose aspirin linked to more live births in high inflammation. Source: Sjaarda LA et al., 2017, PMID 28323989.

Key Findings

In the highest hsCRP group, live birth occurred in 59% of women on low-dose aspirin and 44% on placebo, a 35% increase associated with aspirin.
Clinical pregnancy in the highest hsCRP group was 71% with aspirin and 54% with placebo. Live birth was 59% vs 54% in the lowest group, 59% vs 59% in the middle.
The number needed to treat was seven women (95% CI, 3.9 to 23.8) in the highest hsCRP group per additional live birth. The full trial group showed no statistically significant effect.
In high-hsCRP women, live birth with aspirin vs placebo was 76% vs 50% in normal-weight women and 49% vs 42% in overweight or obese women (RR, 1.16; 95% CI, 0.88 to 1.53).
Across pregnancy, hsCRP was lower with aspirin than placebo in the highest baseline group (P = 0.04), with no treatment difference in the other groups.

Interpretation

This randomized trial followed 1228 women with one or two prior pregnancy losses for up to six cycles. A secondary analysis split them into three groups based on hsCRP, a blood marker of low-grade inflammation, after leaving out 55 women with signs of a recent illness or injury. In the group with the highest hsCRP, low-dose aspirin was linked with more pregnancies and more live births than placebo. The authors say the findings apply to women with prior pregnancy loss and may not extend to couples with infertility. The results support larger studies of hsCRP as a way to find women who benefit from aspirin.

RRM Context

Restorative reproductive medicine looks for the cause of a pregnancy loss. This trial checked whether a marker of inflammation in blood work points to women who do better on aspirin. Inflammation also shows up in two conditions linked to fertility, endometriosis and PCOS. PCOS is now also called PMOS, short for polyendocrine metabolic ovarian syndrome.

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

Abstract

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.

Topics

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

Lindsey A Sjaarda, Rose G Radin, Robert M Silver, Emily Mitchell, Sunni L Mumford, Brian Wilcox, Noya Galai, Neil J Perkins, Jean Wactawski-Wende, Joseph B Stanford, Enrique F Schisterman

L Sjaarda, R Radin, Bob Silver, Rob Silver, Bobby Silver, R Silver, E Mitchell, S Mumford, B Wilcox, N Galai, N Perkins, J Wactawski-Wende, Joe Stanford, Joey Stanford, J Stanford, E Schisterman

PMID 28323989 28323989 DOI 10.1210/jc.2016-2917 10.1210/jc.2016-2917 Sjaarda et al. 2017, Sjaarda 2017

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

Low-dose aspirin linked to more live births in low-grade inflammation

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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