title: The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists.
abstract: We wanted to probe the opinions and current practices on preimplantation genetic screening (PGS), and more specifically on PGS in its newest form: PGS 2.0?
  
  
  
  Consensus is lacking on which patient groups, if any at all, can benefit from PGS 2.0 and, a fortiori, whether all IVF patients should be offered PGS.
  
  
  
  It is clear from all experts that PGS 2.0 can be defined as biopsy at the blastocyst stage followed by comprehensive chromosome screening and possibly combined with vitrification. Most agree that mosaicism is less of an issue at the blastocyst stage than at the cleavage stage but whether mosaicism is no issue at all at the blastocyst stage is currently called into question.
  
  
  
  A questionnaire was developed on the three major aspects of PGS 2.0: the Why, with general questions such as PGS 2.0 indications; the How, specifically on genetic analysis methods; the When, on the ideal method and timing of embryo biopsy. Thirty-five colleagues have been selected to address these questions on the basis of their experience with PGS, and demonstrated by peer-reviewed publications, presentations at meetings and participation in the discussion. The first group of experts who were asked about 'The Why' comprised fertility experts, the second group of molecular biologists were asked about 'The How' and the third group of embryologists were asked about 'The When'. Furthermore, the geographical distribution of the experts has been taken into account. Thirty have filled in the questionnaire as well as actively participated in the redaction of the current paper.
  
  
  
  The 30 participants were from Europe (Belgium, Germany, Greece, Italy, Netherlands, Spain, UK) and the USA. Array comparative genome hybridization is the most widely used method amongst the participants, but it is slowly being replaced by massive parallel sequencing. Most participants offering PGS 2.0 to their patients prefer blastocyst biopsy. The high efficiency of vitrification of blastocysts has added a layer of complexity to the discussion, and it is not clear whether PGS in combination with vitrification, PGS alone, or vitrification alone, followed by serial thawing and eSET will be the favoured approach. The opinions range from in favour of the introduction of PGS 2.0 for all IVF patients, over the proposal to use PGS as a tool to rank embryos according to their implantation potential, to scepticism towards PGS pending a positive outcome of robust, reliable and large-scale RCTs in distinct patient groups.
  
  
  
  Care was taken to obtain a wide spectrum of views from carefully chosen experts. However, not all invited experts agreed to participate, which explains a lack of geographical coverage in some areas, for example China. This paper is a collation of current practices and opinions, and it was outside the scope of this study to bring a scientific, once-and-for-all solution to the ongoing debate.
  
  
  
  This paper is unique in that it brings together opinions on PGS 2.0 from all different perspectives and gives an overview of currently applied technologies as well as potential future developments. It will be a useful reference for fertility specialists with an expertise outside reproductive genetics.
  
  
  
  none.
  
  
  
  No specific funding was obtained to conduct this questionnaire.
authors.affiliation: Research Group Reproduction and Genetics, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium karen.sermon@uzbrussel.be.
authors.forename: Karen
authors.initials: K
authors.lastname: Sermon
authors.affiliation: GENETYX, Molecular Genetics Laboratory, Via Fermi 1, 36063 Marostica (VI), Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Capalbo
authors.affiliation: ART Institute of Washington at Walter Reed National Military Medical Center, Bethesda, MD, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Department of Reproductive Medicine, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands Department of Clinical Genetics, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.
authors.forename: Edith
authors.initials: E
authors.lastname: Coonen
authors.affiliation: Centre for Medical Genetics, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: De Rycke
authors.affiliation: Centre for Reproductive Medicine, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
authors.forename: Anick
authors.initials: A
authors.lastname: De Vos
authors.affiliation: University College London Centre for PGD, UCL, 86-96 Chenies Mews, London WC1E 6HX, UK.
authors.forename: Joy
authors.initials: J
authors.lastname: Delhanty
authors.affiliation: GENOMA-Molecular Genetics Laboratories, Via di Castel Giubileo, 11 00138, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fiorentino
authors.affiliation: The Center for Human Reproduction, New York, NY 10021, USA The Foundation for Reproductive Medicine, New York, NY 1022, USA The Rockefeller University, New York, NY 10065, USA.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gleicher
authors.affiliation: Department of Reproductive Medicine and Gynecological Endocrinology, University Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Griesinger
authors.affiliation: NYU Fertility Center, NYU Langone Medical Center, 660 1st Ave, New York, NY 10016, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Grifo
authors.affiliation: The Bridge Centre, London SE1 9RY, UK Illumina Cambridge Ltd, Capital Park CPC4, Fulbourn, Cambridge CB21 5XE, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Handyside
authors.affiliation: University College London Centre for PGD, UCL, 86-96 Chenies Mews, London WC1E 6HX, UK.
authors.forename: Joyce
authors.initials: J
authors.lastname: Harper
authors.affiliation: Centre for Human Reproduction, Reproductive Medicine Unit, Genesis Athens Clinic, Papanicoli 14-16, Chalandri, 152-32, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Kokkali
authors.affiliation: Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Mastenbroek
authors.affiliation: Division of Reproductive Endocrinology and Infertility, University of California San Diego, San Diego, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Meldrum
authors.affiliation: Instituto Valenciano de Infertilidad (IVI) Clinic Valencia, Valencia, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Meseguer
authors.affiliation: ilabcomm GmbH, Eisenachstr. 34, 53757 Sankt Augustin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Montag
authors.affiliation: Reprogenetics, Livingston, NJ 07039, USA.
authors.forename: Santiago
authors.initials: S
authors.lastname: Munné
authors.affiliation: GENERA, Centres for Reproductive Medicine, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Rienzi
authors.affiliation: Igenomix, and IVI Fundation, Parc Cientific Universitat de Valencia, Catedrático Agustín Escardino 9, 46980 Paterna, Valencia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rubio
authors.affiliation: Foundation for Embryonic Competence, Basking Ridge, NJ, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Scott
authors.affiliation: Reproductive Medicine Associates (RMA) of New Jersey, 140 Allen Road, Basking Ridge, NJ 07920, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Scott
authors.affiliation: Fundación Instituto Valenciano de Infertilidad, Department of Obstetrics and Gynecology, University of Valencia, Valencia, Spain INCLIVA Health Research Institute, Valencia, Spain IGenomix, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simon
authors.affiliation: CCRM IVF Laboratory Network, Englewood, CO 80112 USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Swain
authors.affiliation: Reproductive Medicine Associates (RMA) of New Jersey, 140 Allen Road, Basking Ridge, NJ 07920, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Treff
authors.affiliation: GENERA, Centres for Reproductive Medicine, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Ubaldi
authors.affiliation: Clinica EUGIN, Travessera de Les Corts 322, 08029 Barcelona, Spain.
authors.forename: Rita
authors.initials: R
authors.lastname: Vassena
authors.affiliation: Department of Human Genetics, Katholic University Leuven (KUL), Leuven, Belgium.
authors.forename: Joris Robert
authors.initials: JR
authors.lastname: Vermeesch
authors.affiliation: Centre for Reproductive Medicine, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
authors.forename: Willem
authors.initials: W
authors.lastname: Verpoest
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK Reprogenetics UK, Institute of Reproductive Sciences, Oxford Business Park, Oxford OX4 2HW, UK.
authors.forename: Dagan
authors.initials: D
authors.lastname: Wells
authors.affiliation: Department of Reproductive Medicine, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands Department of Clinical Genetics, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: Geraedts
mesh_terms: D000782:Aneuploidy; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D055028:Comparative Genomic Hybridization; D010064:Embryo Implantation; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods
keywords: array comparative genomic hybridization; blastocyst biopsy; chromosomal abnormalities; massive parallel sequencing; preimplantation embryo; preimplantation genetic screening; vitrification