Embryonic chromosome abnormalities

Santiago Munne

Reprogenetics, West Orange, NJ

The presence of numerical chromosome abnormalities in human embryos was studied using fluorescence in situ hybridization with up to 9 chromosome specific probes. When most cells of an embryo are analyzed, this technique allows to differentiate aneuploidy, mosaicism, haploidy, and polyploidy. Abnormal types of fertilization, such as unipronucleated, tripronucleated zygotes, zygotes with uneven pronuclei, and different pronuclear configurations have been studied. Also dysmorphisms occurring at the cleavage stage such as the presence of multinucleated blastomeres, fragmentation, and uneven blastomeres has also been studied. All dysmorphisms, from zygote stage to cleavage-stage are strongly correlated with chromosomal abnormalities, specifically mosaicism.   In addition, the more impaired the development of an embryo the more chromosome abnormalities were detected in those embryos, and again, the increase was mostly on mosaicism and polyploidy.   

Maternal age and other factors were linked to an increase in chromosome abnormalities (hormonal regimes, temperature changes) but not ICSI. Maternal age affected mostly aneuploidy but also aneuploid mosaicism.

Blastocyst stage studies have shown that some abnormalities, such as monosomies   and haploidies seldom reach that stage, while disomic/tetraploid mosaics are very common. The ratio of abnormal cells in mosaic blastocysts was similar between the inner cell mass and the trophectoderm.

Regarding PGD, one third of the abnormalities detected occur post-meiotically, and are not detected by PB biopsy but are by embryo biopsy. The risk of misdiagnosis due to mosaicism is lower than expected since most of these mosaics have all or most of their cells abnormal. The risk of a first trimester chromosomally abnormal conception has been so far of 0.6% after PGD for a population with an expected risk of 2.8%. In most of the misdiagnoses mosaicism was the most likely cause. Two cell embryo biopsy may reduce the misdiagnosis rate but also the implantation rate.