A Statement on the use of Preimplantation Genetic Screening (PGS) of chromosomes for IVF patients

On September 26th and 27th 2015, under the auspices of The Virtual Academy of Genetics, COGEN held its 1st meeting on Controversies in Preconception, Preimplantation and Prenatal Genetic Diagnosis.

This meeting gathered together Key Opinion Leaders from around the world to inform, discuss and consider many of the questions of our time in relation to genetics and the place of the new technologies in driving the future of medical practice in the field of human reproduction.

The Undersigned have issued the Statement below and welcome debate and comment in this forum.

CONSENSUS STATEMENT ON PGS

For all practitioners of IVF there is the clinical imperative to achieve the highest chance of a live birth per single attempt, reducing the time to delivery for each patient; to reduce the incidence of miscarriage; reduce the number of multiple pregnancies; decrease the number of non-viable embryo transfers ('unnecessary IVF transfer cycles'); eliminate the freezing of embryos that are chromosomally abnormal; to diagnose patients with no chance to deliver with IVF; and, given the high incidence of embryo aneuploidy in all IVF cycles, to minimise the chance of transferring an aneuploid embryo. The alternative to using PGS is to transfer embryos one by one, and studies have shown this can result in up to 50% patient drop out following a miscarriage.

To this aim, scientific endeavour in many laboratories and clinics worldwide has focused upon the development of methods to detect and screen out chromosome anomalies from human embryos using technologies to identify whole chromosome copy number. All IVF cycles have a significant risk of aneuploid embryos, from an average of around 30% in young female patients and also egg donors, up to 90% in women in their early 40s. Methods such as array CGH, qPCR and Next Generation Sequencing (NGS) are delivering high-fidelity information allowing for accurate assessment of chromosome copy number of embryos.

A wide-ranging expert critical evaluation of the new pre-implantation genetic screening (PGS) technologies, taking into consideration clinical data from the application of full chromosome copy number assessment including recent randomised controlled trials, concluded that there is strong evidence that PGS offers certain benefits to patients undergoing IVF. Evidence was provided indicating a significant increase in the chance of implantation per embryo transferred, as well as a reduction in the risk of miscarriage and an improved likelihood of live birth. By using PGS to screen the chromosome status of the embryo the chance of unnecessarily cryopreserving aneuploid embryos, and transferring aneuploid embryos that will lead to IVF failure or the risk of an abnormal birth is minimised. Additionally, by using such technologies, a high chance of live birth can be achieved by transferring only a single euploid embryo, and studies show singleton births results in an improved obstetric and neonatal outcome.

Whilst we recognize that as yet much of the published data do not meet the very highest level of medical analysis, there is now a significant, and increasing body of scientific literature supporting the recommendation of PGS to patients undergoing IVF, for the reasons stated above. Based on available data PGS should no longer be considered as an experimental procedure. We therefore believe that PGS should be part of the discussion with all patients considering/undergoing IVF treatment.

This Statement is a position on the current medical science, however we understand and appreciate that in several societies the offering of PGS is not permitted or available.

The scientific and clinical community remain committed to the further improvement of PGS for the benefit of patients; areas of enquiry include considering the origin of chromosome error (meiotic vs. mitotic), evaluating the level of mitochondrial activity, consideration of gene expression patterns and also of epigenetic processes. Finally, in addition to the focus on embryo genetics and other aspects of its viability, it is recognised that research into uterine receptivity and several other female factors are also of considerable importance to ensure the best and most efficient possible outcome for patients.

Summary:

Chromosome errors (aneuploidy) in human embryos are a major cause of IVF failure, miscarriage, obstetric complications, stillbirth, infertility, and can lead to the birth of affected children.
Accurate technology for detecting chromosomally-normal (euploid) embryos is now available.
Only technologies such as array CGH, qPCR, NGS that detect ALL chromosomes with high accuracy should be applied for use in PGS.
Such technologies should not be considered "experimental" and, where possible, should be made available for routine practice.
PGS can reduce the time to a live birth by selecting only euploid embryos.
PGS can reduce the incidence of miscarriage.
Transfer of single euploid embryos gives the maximum chance of a live birth whilst minimising the risk of a multiple pregnancy.
We believe it is good medical practice to avoid the transfer of aneuploid embryos.
Some patients may have no euploid embryos and therefore no transfers – but many patients prefer to know this at that stage and prepare for a further cycle, or move on rather than wait for failure or possible miscarriage, or the birth of an affected child

List of signatories:

Dr Francesco Fiorentino, President Genoma Group - Italy
Prof Simon Fishel, Founder and President, CARE Fertility, UK
Dr Jason Franasiak, Reproductive Medicine Associates of New Jersey; Rutgers, Robert Wood Johnson Medical School, USA
Prof Luca Gianaroli, Scientific Director of SISMER, Italy
Dr Tony Gordon, Managing Director, Genesis Genetics, USA - UK
Prof Darren Griffin, University of Kent, UK
Prof Jamie Grifo, Program Director NYU Fertility Center, USA
Prof Samir Hamamah, Medical school and University-hospital of Montpellier , France
Prof Alan Handyside, Bridge Centre, University of Kent, and Illumina, Cambridge, UK
Prof Ariel Horowitz, IVF unit, Sheba Medical Centre, Israel
Prof Mark Hughes, Founder & CEO, Genesis Genetics, USA
Dr Milton Leong, Medical Director, The IVF Clinic, Hong Kong
Dr Santiago Munne, President, Reprogenetics, USA
Dr László Nánássy, Laboratory Director, Versys Clinics Human Reproduction Institute Hungary
PD Dr. Andreas Schmutzler, IVF Center, Kiel University, and gyn-medicum IVF Center, Goettingen, Germany
Dr Richard Scott, Founder, Reproductive Medicine Associates of New Jersey and Robert Wood Johnson Medical School, USA
Prof Zeev Shoham, Director, Reproductive medicine and IVF Unit, Kaplan Medical Center, Israel
Prof Lee Shulman, Chief of Clinical Genetics, Northwestern University, USA
Dr Attila Vereczkey, ‎CEO and Medical Director, Versys Clinics Human Reproduction Institute, Hungary
Prof Ariel Weissman, IVF Unit, Edith Wolfson Medical Center, Holon, Sackler Faculty of Medicine, Tel Aviv University, Israel
Dr Dagan Wells. Nuffield Department of Obstetrics and Gynaecology, University of Oxford; Laboratory Director, Reprogenetics, UK
Prof Yuval Yaron, Director, Preimplantation Genetic Diagnosis Laboratory Sourasky Medical Center, Israel