Genetics of early miscarriage

Abstract

A miscarriage is the most frequent complication of a pregnancy. Poor chromosome preparations, culture failure, or maternal cell contamination may hamper conventional karyotyping. Techniques such as chromosomal comparative genomic hybridization (chromosomal-CGH), array-comparative genomic hybridization (array-CGH), fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and quantitative fluorescent polymerase chain reaction (QF-PCR) enable us to trace submicroscopic abnormalities. We found the prevalence of chromosome abnormalities in women facing a single sporadic miscarriage to be 45% (95% CI: 38-52; 13 studies, 7012 samples). The prevalence of chromosome abnormalities in women experiencing a subsequent miscarriage after preceding recurrent miscarriage proved to be comparable: 39% (95% CI: 29-50; 6 studies 1359 samples). More chromosome abnormalities are detected by conventional karyotyping compared to FISH or MLPA only (chromosome region specific techniques), and the same amount of abnormalities compared to QF-PCR (chromosome region specific techniques) and chromosomal-CGH and array-CGH (whole genome techniques) only. Molecular techniques could play a role as an additional technique when culture failure or maternal contamination occurs: recent studies show that by using array-CGH, an additional 5% of submicroscopic chromosome variants can be detected. Because of the small sample size as well as the unknown clinical relevance of these molecular aberrations, more and larger studies should be performed of submicroscopic chromosome abnormalities among sporadic miscarriage samples. For recurrent miscarriage samples molecular technique studies are relatively new. It has often been suggested that miscarriages are due to chromosomal abnormalities in more than 50%, but the present review has determined that chromosomal and submicroscopic genetic abnormalities on average are prevalent in maximally half of the miscarriage samples. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.

Chromosome distribution of early miscarriages with present or absent embryos: female predominance

“…It provided direction when encountering these two types of miscarriages. It was known that women with first miscarriage would not raise the rate of chromosome anomaly in the next pregnancy [3]. The first miscarriage was always sporadic.…”

“…More than half of these miscarriages are due to fetal chromosome anomalies, most frequently aneuploidy [2], but some may be due to fetal anomalies and/or maternal factors. Chromosomal analysis of the products of conception, including the number and arrangement of chromosomes, has been used to determine the reasons for miscarriages and recurrent ones [3]. The two methods of chromosomal analysis mostly used are the culture and semi-direct methods.…”

Genetische Untersuchungen bei wiederholten Spontanaborten

“…So lassen sich im ersten Trimenon in etwa 50 % der Aborte Chromosomenaberrationen nachweisen, während die Rate im zweiten Trimenon nur noch bei etwa 30 % liegt [16]. Nach Daten einer systematischen Übersicht [35] beträgt die Prävalenz einer Chromosomenaberration bei einem Spontanabort 45 % und sinkt geringfügig auf 39 % bei Frauen mit mindestens 2 vorangegangenen Aborten. Diese Daten entsprechen auch einer japanischen Studie [29], die eine signifikante Abnahme von abnormen Karyotypen in Abortmaterial mit zunehmender Anzahl von Aborten ermittelte (.…”

“…Der Anteil der nummerischen Chromosomenaberrationen an der Gesamtzahl der Chromosomenaberrationen ist bei einem Abort oder nach mehreren Aborten mit ca. 90 % praktisch identisch [35].…”

“…Polyploidien finden sich bei etwa 15-20 %, eine Monosomie X bei 10-15 % der zytogenetisch auffälligen Aborte [33,35]. Für die Monosomie X und strukturelle Chromosomenaberrationen ist kein Zusammenhang mit dem mütterlichen Alter erkennbar [9,30].…”