Younger Patients Are More Likely to Have Mosaic-Only Embryos Due to Their Lower Likelihood of Age-Related Whole Chromosome Aneuploidy

Abstract

MATERIALS AND METHODS: This was a blinded prospective cohort study of 300 embryos with a previous clinical PGT-A result; embryos were chosen to include adequate numbers of specific initial diagnoses. Embryos were re-biopsied 4 times and individually tested by PGT-A in a blinded manner. Event concordance was determined according to partial confirmation rate (confirmed in some re-biopsies) and total confirmation rate (confirmed in all biopsies) in five categories: euploid, aneuploid, segmental aneuploid, whole chromosome mosaic, segmental mosaic.RESULTS: An initial TE biopsy result of euploidy or whole chromosome aneuploidy reconfirmed in >99% of re-biopsies. Approximately 97% of euploid or aneuploid embryos had initial biopsy results confirmed in all rebiopsies. In contrast, an initial result of whole chromosome mosaicism or segmental mosaicism confirmed in 15-18% of subsequent re-biopsies and segmental aneuploidy confirmed in 56.6% of re-biopsies. New secondary findings were identified in 7.2% of biopsies and 20.7% of embryos.CONCLUSIONS: An initial euploid or aneuploid result reconfirms in the rest of the embryo in almost all instances, affirming that meiotic errors -or lack thereof -are manifested in almost the entire embryo. The observed discordant rate of 2% is consistent with the mosaic rate in the general population. Mosaic abnormalities tend to be found in only limited areas of the embryo with the majority of the remaining embryo typically being normal. This may explain why these embryos have overall normal implantation and delivery rates. In contrast, segmental errors appear to be largely mitotic in nature. This is true even when they appear to impact all cells in the original biopsy. The high prevalence of mitotic errors explains why embryos with segmental abnormalities have ½ the implantation rates of euploids.IMPACT STATEMENT: Combining a reliable analytical platform and this new understanding of the biology of errors in human embryos should empower great confidence in PGT-A results.

The nature of embryonic mosaicism across female age spectrum: an analysis of 21,345 preimplantation genetic testing for aneuploidy cycles

“…The observed decline in the mosaicism rate with age is consistent with prior research showing that younger patients are more likely to have mosaic embryos without a full chromosome aneuploidy, whereas older patients may have mosaicism concurrent with a whole chromosome aneuploidy ( 11 , 17 ). Younger patients are more likely to have mosaic embryos without full chromosome aneuploidies, given the young oocytes are less likely to cause meiotic nondisjunction ( 17 ).…”

“…The observed decline in the mosaicism rate with age is consistent with prior research showing that younger patients are more likely to have mosaic embryos without a full chromosome aneuploidy, whereas older patients may have mosaicism concurrent with a whole chromosome aneuploidy ( 11 , 17 ). Younger patients are more likely to have mosaic embryos without full chromosome aneuploidies, given the young oocytes are less likely to cause meiotic nondisjunction ( 17 ). It is possible that single whole chromosome and complex abnormal mosaic embryos are more common with increasing age because they originated as aneuploid embryos that underwent partial “self-correction” by aneuploid cell death or reduced cell division rate ( 18 ).…”