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Biochimica et Biophysica Acta 1822 (2012) 1951–1959

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Genetics of early miscarriage☆
Merel M.J. van den Berg a,⁎, Merel C. van Maarle b, Madelon van Wely a, Mariëtte Goddijn a a b

Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, The Netherlands
Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, The Netherlands

a r t i c l e

i n f o

Article history:
Received 30 January 2012
Received in revised form 11 May 2012
Accepted 6 July 2012
Available online 13 July 2012
Recurrent miscarriage
Submicroscopic abnormalities
Molecular genetic abnormalities

a b s t r a c t
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.
© 2012 Elsevier B.V. All rights reserved.

1. Introduction
Miscarriage is the spontaneous loss of a clinically established intra-uterine pregnancy before the fetus has reached viability. It includes pregnancy losses until the maximum of 24 weeks of gestation
[1]. It is the most frequent complication of a pregnancy. Between 10 and
15% of all clinically recognized pregnancies result in a spontaneous miscarriage. The overall prevalence of pregnancy losses, including biochemical pregnancies is generally assumed to be 4–5 times higher
[1]. Around a quarter of all women experience at least one miscarriage during their lives [2,3].
Up to 5% of all couples will face recurrent miscarriage. The definition may vary but starts when at least two or more miscarriages have occurred [4,5]. The sequence of the miscarriages does not necessarily

☆ This article is part of a Special Issue entitled: Molecular Genetics of Human
Reproductive Failure.
⁎ Corresponding author at: Centre for Reproductive…