Preimplantation genetic screening 2.0: the theory

Abstract

During the last few years a new generation of preimplantation genetic screening (PGS) has been introduced. In this paper, an overview of the different aspects of this so-called PGS 2.0 with respect to the why (what are the indications), the when (which developmental stage, i.e. which material should be studied) and the how (which molecular technique should be used) is given. With respect to the aims it is clear that PGS 2.0 can be used for a variety of indications. However, the beneficial effect of PGS 2.0 has not been proved yet in RCTs. It is clear that cleavage stage is not the optimal stage for biopsy. Almost all advocates of PGS 2.0 prefer trophectoderm biopsy. There are many new methods that allow the study of complete aneuploidy with respect to one or more of the 24 chromosomes. Because of the improved vitrification methods, selection of fresh embryos for transfer is more and more often replaced by frozen embryo transfer. The main goal of PGS has always been the improvement of IVF success. However, success is defined by different authors in many different ways. This makes it very difficult to compare the outcomes of different studies. In conclusion, the introduction of PGS 2.0 will depend on the success of the new biopsy strategies in combination with the analysis of all 24 chromosomes. It remains to be seen which approach will be the most successful and for which specific groups of patients.

Keywords: aneuploidy; array comparative genomic hybridization; blastocyst biopsy; blastomere biopsy; chromosomal abnormalities; comprehensive chromosome screening; polar body biopsy; preimplantation genetic screening.

© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Figures

Figure 1

All aspects of preimplantation genetic screening (PGS) 1.0 and PGS 2.0. Biopsy can be performed at three different stages, either polar bodies (PB) can be biopsied from the oocyte, one or two blastomeres can be biopsied from a cleavage stage embryo, or the trophectoderm of the blastocyst can be biopsied. Finally, a small volume of the blastocoelic fluid can be aspirated. These samples can be analysed using different technologies. fluorescence in situ hybridization (FISH) and quantitative PCR (qPCR) do not require a pre-amplification step. Metaphase-comparative genomic hybridization (mCGH), array-CGH (aCGH), single nucleotide polymorphism arrays (SNP) and massive parallel sequencing (MPS) do require a first step of whole genome amplification (WGA). Only euploid embryos are transferred, sometimes after a period of vitrification to allow for the diagnostic procedure to take place. 2PN, two pronuclei; d1: Day 1.