Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro.
In all, 143 human embryos obtained 3 days (day 3) after insemination or intracytoplasmic sperm injection (ICSI) were biopsied and a single nucleated cell removed for identification of aneuploidy by fluorescent in-situ hybridization (FISH) for chromosomes X, Y, 13, 16, 18 and 21. Fifty-one per cent of embryos were aneuploid and significantly more aneuploid embryos blocked in further development to morulae and blastocysts than euploid embryos (59 versus 34%; P < 0.001). Chromosomal analysis of the generated blastocysts revealed 40% were aneuploid (16 of 40 generated blastocysts). Re-examination of cells by FISH for the same chromosome probes of the inner cell mass (ICM) of expanded and hatching blastocysts derived from the aneuploid embryos revealed a high incidence of mosaicism of ICM cell lineages that were usually predictable from observations of day 3 single-cell biopsies. These data would not support the hypothesis of a preferential allocation of euploid cells to the ICM and aneuploid cells to the trophectoderm. A high concordance between day 3 aneuploidy diagnosis and ICM cell lineages was observed with trisomies (97%), and multiple complex chromosome numerical abnormalities (100%). A reduced concordance was observed with monosomies (65%) and haploidy (18%). Concomitantly, the proportion of ICM cell lineages was increased in blastocysts whose chromosomal condition was diagnosed as haploid (21%) or with complex numerical abnormalities (50%).
Magli
M C
MC
SISMER, Reproductive Medicine Unit, Bologna, Italy.
Jones
G M
GM
Gras
L
L
Gianaroli
L
L
Korman
I
I
Trounson
A O
AO
D000782:Aneuploidy; D001755:Blastocyst / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D002877:Chromosomes, Human; D004622:Embryo, Mammalian / Q000502:physiology*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009030:Mosaicism; D019836:Preimplantation Diagnosis