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

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.

Prevalence and Contributors to Low‐grade Inflammation in Three U.S. Populations of Reproductive Age Women

“…26,27 Furthermore, hsCRP 2-9.9 mg/L was the range that was associated with lower pregnancy rates in the EAGeR trial. 12 Women with hsCRP ≥10 mg/L were excluded from bivariate analyses, as well as regression modelling described below, as hsCRP ≥10 mg/L prompts retesting in clinical cardiovascular risk assessment and is consistent with acute phase inflammatory events (e.g. infection), as opposed to chronic low-grade inflammation.…”

“…Cut‐points of hsCRP with demonstrated clinical utility for predicting cardiovascular disease risk in middle‐aged adults define high risk as hsCRP ≥3 mg/L; however, a lower cut‐point of hsCRP ≥2 mg/L has been used to define ‘high’ hsCRP among adults considered to have low risk of cardiovascular disease (perhaps a more relevant population to presumably healthy premenopausal women) . Furthermore, hsCRP 2–9.9 mg/L was the range that was associated with lower pregnancy rates in the EAGeR trial . Women with hsCRP ≥10 mg/L were excluded from bivariate analyses, as well as regression modelling described below, as hsCRP ≥10 mg/L prompts retesting in clinical cardiovascular risk assessment and is consistent with acute phase inflammatory events (e.g.…”

“…Better understanding the role of low‐grade inflammation in reproduction may have significant value, given the potential for therapeutic use of widely available and effective anti‐inflammatory treatments, for example aspirin or statins, which are successfully used to prevent cardiovascular events in middle‐aged adults with higher hsCRP . Moreover, preconception treatment with daily low‐dose aspirin restored an observed decrement in pregnancy rates among women with low‐grade inflammation, specifically resulting in a 31% increase in the clinical pregnancy rate in women with hsCRP ≥2 mg/L at study entry …”

“…inflammation, specifically resulting in a 31% increase in the clinical pregnancy rate in women with hsCRP ≥2 mg/L at study entry. 12 However, the prevalence of low-grade inflammation among women of reproductive potential, as opposed to middle-aged adults at risk for cardiovascular disease, and the factors which may contribute to moderately elevated hsCRP in this population are uncertain. Thus, in the current era of personalized medicine and available anti-inflammatory treatments, the goal of the present investigation was to identify presently undetected groups susceptible to low-grade inflammation, a potential treatment target to ultimately improve fertility and pregnancy health.…”

Arachidonic acid alleviates the detrimental effects of acetylsalicylic acid on human granulosa cells performance in vitro

“…While it is believed that ASA could increase the outcome of IVF, previous conventional meta‐analyses on this subject are however conflicting (Wang et al, 2017). To our knowledge, there were no reports on the effect of low‐dose aspirin on pregnancy loss at any stage of pregnancy, live birth and the rate of euploid pregnancy loss or anovulation overall (Sjaarda et al, 2017). On the other hand, the administration of NSAIDs had no beneficial effects on pregnancy outcome in patients undergoing IVF (Kumbasar, Gül, & Şık, 2017).…”