Non-invasive preimplantation genetic testing for aneuploidies: an update

Aneuploidy is common among preimplantation human embryos used in assisted reproductive technology. Because abnormal chromosome number can negatively affect reproductive outcome, in-vitro-fertilized embryos routinely undergo aneuploidy testing before transfer into the uterus. This testing typically involves an invasive trophectoderm biopsy of a blastocyst-stage embryo. However, emerging evidence indicates that, during in-vitro development, embryos secrete cell-free DNA into their culture medium; this phenomenon suggests the potential for an alternative, non-invasive assay for aneuploidy. Embryonic cell-free DNA-based assays exhibit high concordance with trophectoderm biopsies, inner cell mass and the whole blastocyst. Yet informativity and concordance rates may be influenced by several factors: the culture day when the medium is collected, contamination with external and/or cumulus cell DNA, and previous manipulation of the embryos. This review discusses non-invasive embryonic cellfree DNA analysis as a biomarker to prioritize blastocysts for transfer to help increase implantation rates and reduce miscarriage rates and time to achieve pregnancy. Ongoing research on the mechanisms underlying embryonic cellfree DNA secretion and how this impacts its role as a biomarker of aneuploidy are also discussed.

Automated summary

Aneuploidy is common among preimplantation human embryos used in assisted reproductive technology, and current testing methods involve invasive biopsy. However, emerging evidence suggests that embryos secrete cell-free DNA into their culture medium, indicating the potential for a non-invasive assay for aneuploidy. Embryonic cell-free DNA analysis shows high concordance with current methods and can help prioritize blastocysts for transfer, increasing implantation rates and reducing miscarriage rates and time to achieve pregnancy.