Euploid miscarriage is associated with elevated serum C-reactive protein levels in infertile women: a pilot study

Andrea Weghofer,Vitaly A Kushnir,Norbert Gleicher,David H Barad,David F Albertini,Sarah K Darmon

doi:10.1007/s00404-020-05461-1

Abstract

PurposeIncreased serum C-protein (CRP) levels reduce fecundity in healthy eumenorrheic women with 1–2 pregnancy losses. Subclinical systemic inflammation may impede maternal immune tolerance toward the fetal semi-allograft, compromising implantation and early embryonic development. Some miscarriages with normal karyotypes could, therefore, be caused by inflammation. Whether pre-pregnancy CRP relates to karyotypes of spontaneously aborted products of conception (POCs) was investigated.MethodsA study cohort of 100 infertile women with missed abortions who underwent vacuum aspirations followed by cytogenetic analysis of their products of conception tissue was evaluated at an academically affiliated fertility center. Since a normal female fetus cannot be differentiated from maternal cell contamination (MCC) in conventional chromosomal analyses, POC testing was performed by chromosomal microarray analysis. MCC cases and incomplete data were excluded. Associations of elevated CRP with first trimester pregnancy loss in the presence of a normal fetal karyotype were investigated.ResultsMean patients’ age was 39.9 ± 5.8 years; they demonstrated a BMI of 23.9 ± 4.6 kg/m2 and antiMullerian hormone (AMH) of 1.7 ± 2.4 ng/mL; 21.3% were parous, 19.1% reported no prior pregnancy losses, 36.2% 1–2 and 6.4% ≥ 3 losses. Karyotypes were normal in 34% and abnormal in 66%. Adjusted for BMI, women with elevated CRP were more likely to experience euploid pregnancy loss (p = 0.03). This relationship persisted when controlled for female age and AMH.ConclusionsWomen with elevated CRP levels were more likely to experience first trimester miscarriage with normal fetal karyotype. This relationship suggests an association between subclinical inflammation and miscarriage.

Highlights

The detrimental effects of chronic subclinical inflammation on human health are increasingly becoming apparent
We retrospectively evaluated 100 consecutive infertile women who presented with missed abortions and underwent dilatation and curettage (D and C) with cytogenetic analysis of products of conception (POCs) at The Center for Human Reproduction (CHR) in New York City, NY
There was no significant difference in age, body mass index (BMI), antiMullerian hormone (AMH) levels, semen analysis parameters or white blood cell counts between couples with euploid and aneuploid pregnancy loss (Table 1)

Summary

Introduction

The detrimental effects of chronic subclinical inflammation on human health are increasingly becoming apparent. Biomarkers of micro-inflammation, such as C-reactive protein (CRP), serve as predictive tools for the development and monitoring of the acute coronary syndrome, as inflammation is considered a target that can be therapeutically improved [3, 13] These insights have improved the understanding of how inflammation promotes a variety of pregnancy-induced disorders, such as gestational diabetes and pre-eclampsia [23, 29]. Subclinical inflammations could, serve as a causative factor for the substantial proportion of miscarriages that reveal normal karyotypes after the analysis of products of conception (POCs) [8] If this were, the case, normal POC karyotypes should be more prevalent in women with abnormally high CRP levels. This resulted in 47 women with complete data for final analysis

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Compliance with ethical standards