What next for preimplantation genetic screening (PGS)? Experience with blastocyst biopsy and testing for aneuploidy

Abstract

Blastocysts more commonly have a normal karyotype than cleavage-stage embryos do. Moreover, blastocysts have also made a metabolic transition from catabolism and recycling of the oocyte's reserves and resources, processes that fuel the first 3 days of cleavage. Although not all blastocysts are karyotypically equal, it is still to be determined to what extent a mosaic karyotype might be a normal feature among embryos, both at the cleavage stage and the blastocyst stage--and when looking for karyotypic abnormalities by embryo biopsy might help the chance of implantation rather than harm it. It is also still impractical to look at all the chromosomes that can, through their aneuploidy, stand in the way of successful embryonic and fetal development. We report a randomized clinical trial of blastocyst biopsy followed by preimplantation genetic screening (PGS) for aneuploidy using 5-colour FISH. The trial was suspended and then terminated early when we were unable to show an advantage for PGS. If we are correct in assuming that mitotic non-disjunction is common by the stage of the blastocyst (and that it is much less ominous than meiotic non-disjunction), then further studies of effective PGS of blastocysts for aneuploidy require methods of analysis that cover all the chromosomes and can differentiate the triallelic and monoallelic states of meiotically derived aneuploidies from the biallelic state of mitotic aneuploidies.

Selecting a Single Embryo for Transfer after In-vitro Fertilization: A Translational Medicine Perspective

“…Contrary to expectation, results from numerous studies did not show that the PGS-FISH was capable of improving live birth rates in patients of advanced maternal age, with recurrent implantation failure or repeated pregnancy loss [35][36][37][38][39][40][41][42][43][44][45][46]. This is because FISH screening does not make it possible to test for all 23 chromosome pairs.…”

IVF/ICSI with or without preimplantation genetic screening for aneuploidy in couples without genetic disorders: a systematic review and meta-analysis

“…Ten prospective, randomized, parallel-group, controlled studies evaluating PGS for aneuploidies in IVF/ICSI versus IVF/ICSI met the inclusion criteria [10][11][12][13][14][25][26][27][28][29][30].…”

“…PGS was performed for advanced maternal age defined as ≥35 or ≥37 years [10], 35 to 41 years [26], ≥38 years [30] and ≥35 years [27]. In one study, PGS was performed for failed IVF cycles and recurrent pregnancy loss [25], whereas in other four studies, PGS was indicated in infertile couples without poor prognosis (general IVF population) [10,11,28,29] or for embryo single transfer [11]. The technique of PGS was broadly similar across the included trials.…”

Quantitative decision-making in preimplantation genetic (aneuploidy) screening (PGS)

“…Overall, the results of these studies did not support a role for PGS in women of advanced maternal age. Two recent studies of younger women undergoing PGS also failed to show a benefit [24,25]. The latter study used trophectoderm biopsy of day 5-6 blastocysts.…”

“…Some clinicians have argued of the need for larger RCTs [25,26,[30][31][32]. And yet others have reasoned there is no need to undertake additional RCTs as well-designed studies (cited above) have already demonstrated no benefit of PGS and to undertake additional studies is unethical in light of the findings from some of the studies that performing PGS may, in fact, be harmful [33,34].…”