ABSTRACT
This chapter is an update to our previous review on this subject.1 In that review we explained that when an in vitro fertilization (IVF) clinic successfully attains a high implantation rate, it can be faced with the problem of excessive multiple pregnancies. Also, women of advanced maternal age may lose many pregnancies to spontaneous abortions. Therefore, oocyte, zygote, and embryo selection becomes of central importance. Here we review the latest methods using numerical chromosome assessment as one of the main criteria for selection for these women. To study numerical chromosome abnormalities in human preimplantation embryos certain conditions need to be met. First, individual chromosomes need to be assessed to determine specific aneuploidy rates. Second, all or most blastomeres in some embryos should be analyzed to differentiate mosaicism from other abnormalities. Third, developmentally arrested embryos should also be fully analyzed, and finally, abnormalities should be assessed at different times of development (cleavage, morula, blastocyst stage). Classical cytogenetic techniques are limited because they require metaphase stage chromosomes, but only one third of all embryos analyzed show good quality metaphases. Of these, only one quarter will have all their cells analyzed, or less than 8% overall.2,3 This means that mosaicism can be severely underestimated; furthermore, while arrested, embryos cannot be analyzed. Fluorescence in situ hybridization (FISH) has been used with much higher efficiencies (90%) to study the chromosomal constitution of cleavage stage human embryos, arrested or not.4-11 FISH with multiple probes can differentiate polyploidy from aneuploidy; also haploidy from monosomy, and when most or all cells of an embryo are analyzed, mosaicism can be differentiated from FISH or fixation failure, as well as from aneuploidy.12,13 But FISH supplies information only about a limited number of chromosomes for which the probes are specific. Other approaches such as comparative genome hybridization (CGH),14 quantitative polymerase chain reaction (PCR),15 or chip DNA technology cannot as yet perform single cell analysis with enough accuracy to be applied clinically, but show potential for the future.16 Finally, spectral
karyotyping (SKY) based on FISH technology, has been able to karyotype poor quality metaphases of polar bodies, oocytes and blastomeres, but still requires those cells to be at metaphase stage and those metaphases to be well spread.17
