As compared to day 3 blastomere (spp) biopsy followed by fluorescence in situ hybridization (FISH), PGS 1.0 [1], the utilization of trophectoderm biopsy (days 5-6 embryos) combined with comprehensive chromosome screening (CCS) tests for embryonic aneuploidy, PGS 2.0, has been suggested to improve in vitro fertilization (IVF) outcome [2], though not without criticisms [3,4]. Here, we draw attention to several underlying factors that will influence decisions to employ PGS 2.0 in routine clinical practice.
PGS and mosaicismThough excessive mosaicism in cleavage stage in comparison to blastocyst stage embryos was given as a principal reason for the potential superiority of PGS 2.0 over PGS 1.0 [5], mosaicism has been reported in cleavage-and blastocyst-stage embryos derived from IVF [6], with mitotic rather than meiotic errors as main causes [7]. Liu et al. [8] reported that 69 % of blastocyst-stage embryos from women of advanced age are mosaic for inner cell mass as well as trophectoderm, while Johnson et al. [9] reported that in younger women only 20 % of blastocyst stage embryos are aneuploid, with a majority in addition presenting with only one or two structural chromosome abnormalities. Their observation would suggest at younger ages a lower, but still, clinically critical level of mosaicism at the blastocyst stage [6]. These data were to a degree confirmed by Munné's group who at the 2015 ASRM meeting reported clearly increasing aneuploidy rates with advancing female age but surprisingly similar mosaicism rates at all ages at an average of 30.2 %, with actually the youngest women below age 35, quite surprisingly, demonstrating highest rates among all age groups at 33.2 % [10].In assessing the potential clinical value of PGS 2.0 in improving IVF outcomes, before discussing costs, complexities, and the obvious lack of properly conducted prospective clinical trials based on Bintent to treat^ [3], one really has to assess whether the basic biology of the early human embryos allows for the accurate diagnosis of euploidy versus aneuploidy based on as single trophectoderm biopsy at blastocyst stage.In this issue of JARG, Tortoriello et al. report highly divergent outcomes when trophectoderm biopsies from the same embryos were referred for PGS 2.0, at different laboratories, using varying assay platforms [11]. Chromosomal analyses after two sequential trophectoderm biopsies from the same embryos revealed only 11 % (3/27) ploidy detection concordance between microarray-based comparative genomic hybridization (aCGH) and next-generation sequencing (NGS). Moreover, 9/27 (33 %) of originally reported aneuploid embryos, upon repeat assessment, were found to be euploid. The predicted mosaicism rate was 51 % (19/37).Such findings can have only three possible explanations: either laboratory techniques applied in one or more of the utilized PGS laboratories are disappointingly inaccurate; an inherent lack of concordance between platforms; or individual trophectoderm biopsies submitted for analyses differed in Capsule Concerns r...