Cytogenetic analyses of culture failures by comparative genomic hybridisation (CGH) - Re-evaluation of chromosome aberration rates in early spontaneous abortions

Comparative genomic hybridisation (CGH) represents an alternative molecular -cytogenetic technique capable of detecting chromosomal imbalances by rever se fluorescence in situ hybridisation. As the technique uses genomic DNA fo r assessment it does not rely on metaphase chromosomes in the test material and thus circumvents technical problems associated with tissue culturing. In the present study, we applied CGH to identify chromosome anomalies in 60 spontaneous abortions of the first trimester, that had failed to grow in c ulture. In 57 out of 60 cases CGH analyses were successful. The overall ane uploidy rate detected was 72%. Trisomy was the predominant chromosome anoma ly accounting for 68.0% of abnormal abortions, followed by triploidy (17.1% ) and monosomy X (9.8%). An unbalanced structural rearrangement was found i n one (2.4%) abortion. Most frequently involved in trisomies were chromosom es 16 (32.1%), 7 and 22 (10.7% each), 4, 13, 15, and 21 (7.2% each). Three triploid cases and one complete mole were detected by microsatellite analys is as supplementary method. CGH data on culture failures were compared with data derived from 4693 successfully karyotyped first trimester spontaneous abortions, resulting in a chromosome aberration rate of 64.8%. The distrib ution of the different chromosome anomalies was similar with the exception of a higher rate of trisomies 7 and of XYY-triploidies in the culture failu res. Based on our data we suggest that the genetic contribution to pregnanc y loss is still underestimated. Investigating abortion tissues hitherto una ssessed by conventional methods, we suggest that the contribution of chromo some aberrations to first trimester pregnancy loss is nearly 70%.