Comparative genomic hybridization in combination with flow cytometry improves results of cytogenetic analysis of spontaneous abortions

More than 50% of spontaneous abortions (SAs) have abnormal chromosomes; the most common abnormalities are trisomy, sex chromosome monosomy, and polypl oidy. Conventional cytogenetic analysis of SAs depends on tissue culturing and is associated with a significant tissue culture failure rate and contam ination by maternally derived cells. Comparative genomic hybridization (CCH ), in combination with flow cytometry (FCM), can detect numerical and unbal anced structural chromosomal abnormalities associated with SAs while avoidi ng the technical problems associated with tissue culture. Routine cytogenet ic and CGH analysis was performed independently on tissue from 301 SAs. Sam ples shown to be chromosomally balanced by CGH were analyzed by FCM to dete rmine ploidy. Of 253 samples successfully analyzed by both approaches, ther e was an absolute correlation of results in 235 (92.8%). Of the 18 cases wi th discrepancies between cytogenetic and CGH/FCM results, an explanation co uld be found in 17. Twelve samples produced a 46,XX karyotype by cytogeneti cs, whereas CGH/FCM demonstrated aneuploidy/polyploidy or a male genome, in dicating maternal contamination of the tissue cultures. In two cases, where tetraploidy was demonstrated by cytogenetics and diploidy by FCM, tissue c ulture artifact is implied. In three cases, CCH demonstrated an aneuploidy, and cytogenetics demonstrated hypertriploidy. In one unexplainable case, a neuploidy demonstrated by CGH could not be detected by repeat CGH analysis, conventional cytogenetic, or FISH analysis. These results demonstrate that CGH supplemented with FCM can readily identify chromosomal abnormalities a ssociated with SAs and, by avoiding maternal contamination and tissue cultu re artifacts, can do so with a lower failure rate and more accuracy than co nventional cytogenetic analysis.