An efficient protocol for the detection of chromosomal abnormalities in spontaneous miscarriages or foetal deaths

Abstract 

Objective

Characterization of chromosomal abnormalities in 232 spontaneous miscarriages or foetal deaths using both classical and molecular cytogenetics.

Study design

Chromosomal abnormalities are responsible for 40–50% of all early pregnancy losses. Conventional cytogenetics is associated with 10–40% of culture failure. Comparative genomic hybridization (CGH) is a DNA-based technique that screens chromosome imbalances in the whole genome and may overcome this problem, although additional methods are required to distinguish between different ploidies, mosaicisms and maternal cell contamination. For a full characterization of chromosomal aberrations in 232 spontaneous miscarriages or foetal deaths we applied a sequential protocol that uses conventional cytogenetics, plus CGH and touch fluorescence in situ hybridization (Touch FISH).

Results

Successful karyotyping was obtained in 173/232 (74.6%) of the cases, 66/173 (38.2%) of which had an abnormal chromosomal complement. CGH and Touch FISH analyses revealed another 19 abnormal cases in the 63 failures of culture. Overall there were 85/233 (36.6%) cases with an abnormal chromosomal complement, with examples from all three trimesters. Comparing cases, with or without chromosomal abnormalities, no statistical differences were found between women with one or recurrent miscarriages. On the contrary, significant differences were found comparing mean maternal ages or mean gestational ages, in cases with or without chromosomes abnormalities.

Conclusion

Adopting this sequential protocol, chromosomal complement information was available even in cases with culture failure.

Keywords: Spontaneous miscarriages, Karyotype, Chromosomal abnormalities, CGH, Touch FISH