Array comparative genomic hybridization and flow cytometry analysis of spontaneous abortions and mors in utero samples

Björn Menten,Barbara Delle Chiaie,Jan Philippé,Frank Speleman,Karen Buysse,Katrien Swerts,Sandra Janssens

doi:10.1186/1471-2350-10-89

Björn Menten, Barbara Delle Chiaie + Show 5 more

Open Access

https://doi.org/10.1186/1471-2350-10-89

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Abstract

BackgroundIt is estimated that 10-15% of all clinically recognised pregnancies result in a spontaneous abortion or miscarriage. Previous studies have indicated that in up to 50% of first trimester miscarriages, chromosomal abnormalities can be identified. For several decades chromosome analysis has been the golden standard to detect these genomic imbalances. A major drawback of this method is the requirement of short term cultures of fetal cells. In this study we evaluated the combined use of array CGH and flow cytometry (FCM), for detection of chromosomal abnormalities, as an alternative for karyotyping.MethodsIn total 100 spontaneous abortions and mors in utero samples were investigated by karyotyping and array CGH in combination with FCM in order to compare the results for both methods.ResultsChromosome analysis revealed 17 abnormal karyotypes whereas array CGH in combination with FCM identified 26 aberrations due to the increased test success rate. Karyotyping was unsuccessful in 28% of cases as compared to only two out of hundred samples with inconclusive results for combined array CGH and FCM analysis.ConclusionThis study convincingly shows that array CGH analysis for detection of numerical and segmental imbalances in combination with flow cytometry for detection of ploidy status has a significant higher detection rate for chromosomal abnormalities as compared to karyotyping of miscarriages samples.

Highlights

It is estimated that 10-15% of all clinically recognised pregnancies result in a spontaneous abortion or miscarriage
Samples Hundred miscarriages and mors in utero samples were investigated by conventional chromosome analysis, flow cytometry and molecular karyotyping using ~1 Mb BAC microarrays
Conventional cytogenetic analysis Hundred products of conception were investigated with conventional cytogenetic analysis using G-banding [see Additional file 1]

Summary

Introduction

It is estimated that 10-15% of all clinically recognised pregnancies result in a spontaneous abortion or miscarriage. Previous studies have indicated that in up to 50% of first trimester miscarriages, chromosomal abnormalities can be identified. 10 to 15% of all clinically recognised pregnancies end up in a spontaneous abortion. The vast majority of these chromosomal abnormalities are numerical aberrations (~86%), including trisomies, monosomies and polyploidies. It has been assumed that most products of conception are lost even before the pregnancy is clinically recognised as such. These preclinical losses are due to failure of development, early arrest in cell division or implantation failure of the developing embryo

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