Assisted reproductive technologies (ART) have become the standard of care for the treatment of infertility. Within this realm, reliable prediction of the developmental potential of the pre‐implantation human embryo remains an overriding priority. One such technology, pre‐implantation genetic screening (PGS), is being increasingly deployed to select against embryonic aneuploidy [1]. However, a growing number of seemingly contradictory outcome reports are forcing a reevaluation of this approach. Here, we discuss how biological factors, notably mitotic aneuploidy during early embryonic development, limit the very rationale for PGS as a clinical diagnostic method.
… PGS is an example of technology compromised by biology
The development of safe and efficient methods to select healthy euploid embryos constitutes a pressing need to improve the success of ART. PGS, as one strategy to achieve this, relies on the ploidy status of the trophectoderm layer of the blastocyst‐stage embryo [1] (Table 1). Considerable numbers of patients are undergoing PGS: In the USA alone, more than 5% of 106,902 non‐donor assisted reproduction cycles resorted to PGS during 2011 and 2012 [2]. However, the capacity of PGS to select euploid embryos has recently been questioned by the birth of healthy newborns whose originating blastocysts were deemed mosaic (euploid–aneuploid) [3]. Similar inconsistencies have previously been reported for euploid human embryonic stem cell lines, which have been derived from purportedly aneuploid blastocysts. We suggest herein that the utility of PGS is undermined by innate karyotypic mosaicism, the ontogeny and significance of which in early human development remain uncertain. Viewed in this light, PGS is an example of technology compromised by biology. It follows that the ability of PGS to reliably predict the ploidy status of the human embryo and its developmental potential is limited.
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The causes of embryonic aneuploidy
Following fertilization and karyogamy, the human zygote undergoes 8–9 …
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