Logo of ajhgLink to Publisher's site
Am J Hum Genet. May 2000; 66(5): 1516–1521.
Published online Mar 30, 2000. doi:  10.1086/302878
PMCID: PMC1378008

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 polyploidy. Conventional cytogenetic analysis of SAs depends on tissue culturing and is associated with a significant tissue culture failure rate and contamination by maternally derived cells. Comparative genomic hybridization (CGH), in combination with flow cytometry (FCM), can detect numerical and unbalanced structural chromosomal abnormalities associated with SAs while avoiding the technical problems associated with tissue culture. Routine cytogenetic and CGH analysis was performed independently on tissue from 301 SAs. Samples shown to be chromosomally balanced by CGH were analyzed by FCM to determine ploidy. Of 253 samples successfully analyzed by both approaches, there was an absolute correlation of results in 235 (92.8%). Of the 18 cases with discrepancies between cytogenetic and CGH/FCM results, an explanation could be found in 17. Twelve samples produced a 46,XX karyotype by cytogenetics, whereas CGH/FCM demonstrated aneuploidy/polyploidy or a male genome, indicating maternal contamination of the tissue cultures. In two cases, where tetraploidy was demonstrated by cytogenetics and diploidy by FCM, tissue culture artifact is implied. In three cases, CGH demonstrated an aneuploidy, and cytogenetics demonstrated hypertriploidy. In one unexplainable case, aneuploidy 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 associated with SAs and, by avoiding maternal contamination and tissue culture artifacts, can do so with a lower failure rate and more accuracy than conventional cytogenetic analysis.

Full Text

The Full Text of this article is available as a PDF (157K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bell KA, Van Deerlin PG, Haddad BR, Feinberg RF. Cytogenetic diagnosis of "normal 46,XX" karyotypes in spontaneous abortions frequently may be misleading. Fertil Steril. 1999 Feb;71(2):334–341. [PubMed]
  • Berezowsky J, Zbieranowski I, Demers J, Murray D. DNA ploidy of hydatidiform moles and nonmolar conceptuses: a study using flow and tissue section image cytometry. Mod Pathol. 1995 Sep;8(7):775–781. [PubMed]
  • Bouié J, Philippe E, Giroud A, Boué A. Phenotypic expression of lethal chromosomal anomalies in human abortuses. Teratology. 1976 Aug;14(1):3–19. [PubMed]
  • Bryndorf T, Kirchhoff M, Rose H, Maahr J, Gerdes T, Karhu R, Kallioniemi A, Christensen B, Lundsteen C, Philip J. Comparative genomic hybridization in clinical cytogenetics. Am J Hum Genet. 1995 Nov;57(5):1211–1220. [PMC free article] [PubMed]
  • Creasy MR, Crolla JA, Alberman ED. A cytogenetic study of human spontaneous abortions using banding techniques. Hum Genet. 1976 Feb 29;31(2):177–196. [PubMed]
  • Daniely M, Aviram-Goldring A, Barkai G, Goldman B. Detection of chromosomal aberration in fetuses arising from recurrent spontaneous abortion by comparative genomic hybridization. Hum Reprod. 1998 Apr;13(4):805–809. [PubMed]
  • Hedley DW, Friedlander ML, Taylor IW, Rugg CA, Musgrove EA. Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry. J Histochem Cytochem. 1983 Nov;31(11):1333–1335. [PubMed]
  • Henderson KG, Shaw TE, Barrett IJ, Telenius AH, Wilson RD, Kalousek DK. Distribution of mosaicism in human placentae. Hum Genet. 1996 May;97(5):650–654. [PubMed]
  • Kajii T, Ferrier A, Niikawa N, Takahara H, Ohama K, Avirachan S. Anatomic and chromosomal anomalies in 639 spontaneous abortuses. Hum Genet. 1980;55(1):87–98. [PubMed]
  • Kallioniemi OP, Kallioniemi A, Piper J, Isola J, Waldman FM, Gray JW, Pinkel D. Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors. Genes Chromosomes Cancer. 1994 Aug;10(4):231–243. [PubMed]
  • Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 1992 Oct 30;258(5083):818–821. [PubMed]
  • Kalousek DK, Pantzar T, Tsai M, Paradice B. Early spontaneous abortion: morphologic and karyotypic findings in 3,912 cases. Birth Defects Orig Artic Ser. 1993;29(1):53–61. [PubMed]
  • Kohn G, Robinson A. Tetraploidy in cells cultured from amniotic fluid. Lancet. 1970 Oct 10;2(7676):778–779. [PubMed]
  • Lestou VS, Lomax BL, Barrett IJ, Kalousek DK. Screening of human placentas for chromosomal mosaicism using comparative genomic hybridization. Teratology. 1999 May;59(5):325–330. [PubMed]
  • Levy B, Dunn TM, Kaffe S, Kardon N, Hirschhorn K. Clinical applications of comparative genomic hybridization. Genet Med. 1998 Nov-Dec;1(1):4–12. [PubMed]
  • Lomax BL, Lestou VS, Barrett IJ, Kalousek DK. Confined placental mosaicism for chromosome 7 detected by comparative genomic hybridization. Prenat Diagn. 1998 Jul;18(7):752–754. [PubMed]
  • Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. [PMC free article] [PubMed]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...