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Review
. 2019 Mar;97(3):187-192.
doi: 10.1139/cjpp-2018-0368. Epub 2018 Dec 18.

The role of aspirin and inflammation on reproduction: the EAGeR trial 1

Lindsay D Levine  1   1 , Tiffany L Holland  1   1 , Keewan Kim  1   1 , Lindsey A Sjaarda  1   1 , Sunni L Mumford  1   1 , Enrique F Schisterman  1   1
Affiliations
Review

The role of aspirin and inflammation on reproduction: the EAGeR trial 1

Lindsay D Levine et al. Can J Physiol Pharmacol. 2019 Mar.

Abstract
in English, French

Inflammation has been linked to several complications in pregnancy, including pregnancy loss. Due to its anti-inflammatory properties, aspirin, a widely available and inexpensive therapy, has potential to help mitigate the negative effects of inflammation along the reproductive pathway. Therefore, the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was designed to elucidate whether preconception-initiated daily low-dose aspirin would increase the live birth rate in women with 1-2 prior pregnancy losses and no infertility diagnosis and attempting unassisted conception. Here, we present an overview of the collected findings. Low-dose aspirin was associated with an increased live birth rate among women with a single loss at <20 weeks gestation within the past year. When stratified by tertile of C-reactive protein (CRP), a biomarker of inflammation, treatment with aspirin restored a decrement in the live birth rate in women in the highest CRP tertile (relative risk 1.35, 95% confidence interval 1.08-1.67), increasing to similar rates as women of the lower and mid-CRP tertiles. The same effect modification by inflammation status was observed when examining the effect of low-dose aspirin on offspring sex ratio. These results suggest that inflammation plays an important role in reproduction, and that chronic, low-grade inflammation may be amenable to aspirin treatment.

L’inflammation a été liée à plusieurs complications de grossesse, notamment les fausses couches. En raison de ses effets anti-inflammatoires, l’aspirine, un médicament librement accessible et peu coûteux, pourrait contribuer à atténuer les effets négatifs de l’inflammation le long des voies reproductrices. Par conséquent, nous avons conçu l’essai EAGeR (pour « Effects of Aspirin in Gestation and Reproduction ») en vue d’élucider si un traitement quotidien par de l’aspirine à faible dose (AFD) commencé avant la conception pourrait entraîner une augmentation des taux de naissances vivantes chez des femmes ayant subi une ou deux fausses couches tentant une conception non assistée sans diagnostic d’infertilité. Nous présentons ici un aperçu des résultats obtenus. L’AFD a été associée à une augmentation du taux de naissances vivantes parmi les femmes ayant subi une fausse couche unique à moins de 20 semaines de gestation au cours de l’année précédente. En stratifiant par tertiels des taux de protéine C réactive (PCR), un biomarqueur de l’inflammation, l’administration d’aspirine permettait de rétablir une diminution des taux de naissances vivantes à celui des femmes dont les taux de PCR se situaient dans le tertiel le plus élevé (risque relatif de 1,35 avec un intervalle de confiance à 95 % de 1,08 à 1,67), et ce, à des taux similaires chez les femmes dont les taux de PCR se situaient dans les tertiels inférieur et moyen. Nous avons observé le même effet de modifications par l’état inflammatoire en étudiant l’effet de l’AFD sur le ratio entre les sexes de la progéniture. Ces résultats laissent entendre que l’inflammation jouerait un rôle important dans la reproduction, et que l’inflammation à bas bruit sur le long terme pourrait se plier au traitement par l’aspirine.

Keywords: C-reactive protein; aspirin; aspirine; fausse couche; grossesse; inflammation; live birth; miscarriage; naissance vivante; perte de grossesse; pregnancy; pregnancy loss; protéine C réactive.

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Figures

Fig. 1.
Fig. 1.
The effect of low-dose aspirin (LDA, 81 mg) versus placebo on live birth rate in the Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial (2006–2012). Original stratum includes women aged 18–40 years who were attempting pregnancy with 1 documented pregnancy loss <20 weeks gestation that occurred in the previous 12 months. Expanded stratum includes women with 1–2 documented pregnancy losses regardless of gestational age or the date of the loss.
Fig. 2.
Fig. 2.
Live birth rates among women in highest high-sensitivity C-reactive protein (hsCRP) tertile (≥1.95 mg/L), stratified by measures of obesity. BMI, body mass index (kg/m2); CI, confidence interval; LDA, low-dose aspirin; RR, relative risk.
See this image and copyright information in PMC

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