Cytogenetic results from the U.S. collaborative study on CVS

Abstract

Cytogenetic data are presented for 11,473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained from the direct method only (26 per cent), culture method only (42 per cent), or a combination of both (32 per cent). A total of 1.1 per cent of patients had a second CVS or amniocentesis procedure for reasons related to the cytogenetic diagnostic procedure, including laboratory failures (27 cases), maternal cell contamination (4 cases), or mosaic or ambiguous cytogenetic results (98 cases). There were no diagnostic errors involving trisomies for chromosomes 21, 18, and 13. For sex chromosome aneuploidies, one patient terminated her pregnancy on the basis of non-mosaic 47,XXX in the direct method prior to the availability of results from cultured cells. Subsequent analysis of the CVS cultures and fetal tissues showed only normal female cells. Other false-positive predictions involving non-mosaic aneuploidies (n = 13) were observed in the direct or culture method, but these cases involved rare aneuploidies: four cases of tetraploidy, two cases of trisomy 7, and one case each of trisomies 3, 8, 11, 15, 16, 20, and 22. This indicates that rare aneuploidies observed in the direct or culture method should be subjected to follow-up by amniocentesis. Two cases of unbalanced structural abnormalities detected in the direct method were not confirmed in cultured CVS or amniotic fluid. In addition, one structural rearrangement was misinterpreted as unbalanced from the direct method, leading to pregnancy termination prior to results from cultured cells showing a balanced, inherited translocation. False-negative results (n = 8) were observed only in the direct method, including one non-mosaic fetal abnormality (trisomy 18) detected by the culture method and seven cases of fetal mosaicism (all detected by the culture method). Mosaicism was observed in 0.8 per cent of all cases, while pseudomosaicism (including single trisomic cells) was observed in 1.6 per cent of cases. Mosaicism was observed with equal frequency in the direct and culture methods, but was confirmed as fetal mosaicism more often in cases from the culture method (24 per cent) than in cases from the direct method (10 per cent). The overall rate of maternal cell contamination was 1.8 per cent for the culture method, but there was only one case of incorrect sex prediction due to complete maternal cell contamination which resulted in the birth of a normal male.(ABSTRACT TRUNCATED AT 400 WORDS)

Human embryo mosaicism: did we drop the ball on chromosomal testing?

“…When mosaicism occurs during the cleavage state, for example, the mosaicism will be more pronounced (a greater percentage of the total embryo involved) than if the mosaicism occurs later in development. This suggestion is supported by a comparison of the rates of mosaicism seen in prenatal diagnosis (1-2 %) versus the broad range (50-90 %) of mosaicism seen in cleavage stage embryos [10,36].…”

Counseling parents before prenatal diagnosis: Do we need to say more about the sex chromosome aneuploidies?

“…The major advantage of CVS over amniocentesis is that it can be performed at a much earlier stage of pregnancy and entails a minor physical and probably smaller emotional risk to the woman who receives a positive result and requests a TOP. However, compared with amniocentesis, when CVS is used for a fetal karyotype there is a greater likelihood of needing a repeat test because of unclear results, mainly mosaicisms, which are detected in one case out of 50 [Ledbetter et al, 1992;Baffero et al, 2012].…”

Positive cell-free fetal DNA testing for trisomy 13 reveals confined placental mosaicism

“…10 Large, multicenter studies have determined that the frequency of mosaicism in either direct or cultured analysis of CVS tissue to be 1-2%. 8,11 When trisomy mosaicism was detected by CVS in these studies, in ~80% of the cases the chromosome abnormalities were confined to the placenta with normal fetal chromosome constitution. Furthermore, these studies indicated that if the chromosome abnormality were detected by the direct method and therefore confined to the cytotrophoblast tissue and not detected in the cultured chorionic villi, then the chromosome abnormality was never confirmed in fetal tissues (i.e., amniocentesis, cord blood).…”