Women with Recurrent Pregnancy Loss More Often Have an Older Brother and a Previous Birth of a Boy: Is Male Microchimerism a Risk Factor?

Caroline Nørgaard-Pedersen,Ulrik Schiøler Kesmodel,Ole B Christiansen

doi:10.3390/jcm10122613

Caroline Nørgaard-Pedersen, Ulrik Schiøler Kesmodel + Show 1 more

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https://doi.org/10.3390/jcm10122613

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Abstract

Known etiologic factors can only be found in about 50% of patients with recurrent pregnancy loss (RPL). We hypothesized that male microchimerism is a risk factor for RPL and aimed to explore whether information on family tree and reproductive history, obtained from 383 patients with unexplained RPL, was supportive of this hypothesis. The male:female sex ratio of older siblings was 1.49 (97:65) in all RPL patients and 1.79 (52:29) in secondary RPL (sRPL) patients, which differed significantly from the expected 1.04 ratio (p = 0.027 and p = 0.019, respectively). In contrast, the sex ratio of younger siblings was close to the expected ratio. Sex ratio of the firstborn child before sRPL was 1.51 (p = 0.026). When combined, 79.1% of sRPL patients had at least one older brother, a firstborn boy, or both. This differed significantly from what we expected based on the distribution of younger siblings and a general 1.04 sex ratio of newborns (p = 0.040). We speculate whether (s)RPL patients possibly acquired male microchimerism from older brother(s) and/or previous birth of boy(s) by transplacental cell trafficking. This could potentially have a detrimental impact on their immune system, causing a harmful response against the fetus or trophoblast, resulting in RPL.

Highlights

IntroductionThe most common pregnancy complication is miscarriage, which, in most cases, can be explained by serious structural malformations or chromosomal abnormalities which are incompatible with life [1], and 2–3% of fertile women suffer from recurrent pregnancy loss (RPL)
The most common pregnancy complication is miscarriage, which, in most cases, can be explained by serious structural malformations or chromosomal abnormalities which are incompatible with life [1], and 2–3% of fertile women suffer from recurrent pregnancy loss (RPL).RPL of unknown etiology includes women with no uterine malformations, endocrine dysfunction or thrombotic disorders, and couples with no parental chromosome abnormalities, and this applies to about 50% of RPL patients
Cell grafts are associated with detrimental actions in at least some women. In this purely clinical study, we aimed to explore if a history of an older brother and/or a first-born boy was more frequent in RPL patients compared to the expected distribution, and if the association was more pronounced in primary or secondary RPL (sRPL)

Summary

Introduction

The most common pregnancy complication is miscarriage, which, in most cases, can be explained by serious structural malformations or chromosomal abnormalities which are incompatible with life [1], and 2–3% of fertile women suffer from recurrent pregnancy loss (RPL). RPL of unknown etiology (uRPL) includes women with no uterine malformations, endocrine dysfunction or thrombotic disorders, and couples with no parental chromosome abnormalities, and this applies to about 50% of RPL patients. The identification of contributing risk factors and underlying causes of uRPL is essential in order to offer the most favorable support and, if possible, curative medical treatment. Immunological disturbances have been suggested to play a pivotal role in the pathogenesis for uRPL, since autoantibodies [2,3], specific human leukocyte antigen (HLA). A potential immunological risk factor for RPL is microchimerism. Microchimerism is defined as small amounts of foreign cells or DNA detectable in a genetically distinct individual

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