Chromosome 21 mosaic human preimplantation embryos predominantly arise from diploid conceptions.
OBJECTIVE
High rates of chromosomal mosaicism in human IVF embryos question the accuracy of preimplantation genetic diagnosis, and, with the majority of embryo transfers still resulting in no pregnancy, chromosomal mosaicism is likely to be a contributing factor to human IVF failure. The aim of this study was to investigate the origin and nature of chromosome 21 (Ch21) cell division errors in human IVF embryos.


METHODS
Perform single cell Ch21 allelic profiling on human IVF embryos.


METHODS
Academic research environment.


METHODS
Women of advanced maternal age (> 35 yrs) (n = 65) undergoing infertility treatment; and amniocytes/chorionic cells from trisomy 21 pregnancies (n = 28).


METHODS
Cells were analyzed by single cell allelic profiling,


METHODS
The origin and nature of cell division errors.


RESULTS
The vast majority of Ch21 mosaic embryos (approximately 80%) originated from diploid conceptions. In contrast, all fetal trisomy 21 originated from aneuploid conceptions. Increasing maternal age was significantly associated with aneuploid conceptions, meiotic cell division error, and adverse pregnancy outcome (P < .05). The mean daily FSH dose that produced embryos with normal Ch21 cell division was significantly lower than the mean daily FSH dose that produced embryos with mitotic Ch21 cell division errors (P < .01) and embryos with meiotic cell division errors (P < .05).


CONCLUSIONS
Chromosomal mosaicism of Ch21 in human IVF embryos predominantly originate from diploid conceptions. Further understanding of chromosomal mosaicism with respect to IVF parameters, such as daily FSH dose, may eventually lead to improvements in IVF outcomes.
Katz-Jaffe
Mandy G
MG
Monash Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia. mkatz-jaffe@colocrm.com
Trounson
Alan O
AO
Cram
David S
DS
D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D001755:Blastocyst / Q000502:physiology*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004171:Diploidy; D005260:Female; D005306:Fertilization / Q000235:genetics*; D005307:Fertilization in Vitro / Q000379:methods; D006801:Humans; D009030:Mosaicism / Q000196:embryology*; D011247:Pregnancy