What next for preimplantation genetic screening? Beyond aneuploidy

Many published papers suggest a favourable impact of preimplantation genetic screening (PGS) on implantation and pregnancy rates, but more recent randomized studies have not confirmed, or could not conclude, that PGS actually improved implantation rates. Team inexperience in embryo screening has been mentioned as the origin of the discrepancies; thus some clinicians allege a need for more powerful, well-designed, randomized studies performed by specialized teams. However, what if all the contradictory results about the benefits of PGS and implantation were not due to technical problems or team specialization but were biological in origin? The developmental programme of an eight-cell embryo relies on signals of maternal origin retrieved from the cytoplasm to initiate a new transcriptional network that will eventually serve as a filter (checkpoints and apoptosis) for aneuploidy. Thus, the use of PGS with the objective of improving the likelihood of a successful pregnancy based only on nuclear abnormalities (aneuploidies) in an early cleavage stage embryo could be invalid since the information (diagnosis) obtained at the moment of biopsy could be overturned by the transcriptional machinery of the new zygote genome.