Does Preimplantation Genetic Testing for Aneuploidy ...
Norway Grants Lecture
Does Preimplantation Genetic Testing for Aneuploidy Work? Negotiating the mosaic of science, regulation and egos
Darren Griffin, Ph.D
Professor of Genetics, University of Kent / Director, Centre for Interdisciplinary Studies of Reproduction (CSIoR)
Preimplantation Genetic Testing for Aneuploidy (PGT-A) formerly known as Preimplantation Genetic Screening (PGS) is an adjunct to regular IVF treatment. It was designed to improve IVF success rates, decrease time to first pregnancy, reduce the incidence of miscarriage and of affected live births. Aneuploidy is the leading cause of mental retardation, pregnancy loss and IVF failure in humans. It is also one of the leading causes of stillbirth and infertility. In its mosaic form (i.e. when there are both normal and aneuploid cells in a conceptus) it can lead to abnormally high and low birthweights, placental insufficiency and diseases such as Prader Willi and Angelman syndromes. Intuitively therefore there is general consensus in the scientific community that PGT-A has a robust and mechanistically-based rationale.
The referral categories for PGT-A are as follows
• Advanced maternal age (AMA) – older mothers are more likely to have chromosomally abnormal embryos
• Recurrent pregnancy loss (RPL) – chromosomal abnormalities are the leading cause of pregnancy loss in humans
• Recurrent implantation failure (RIF) – most chromosomally abnormal embryos do not implant
• Male factor infertility – men with severely compromised semen parameters (and hence treated by ICSI) frequently have sperm DNA damage including aneuploidy, and this can be reflected in the embryos themselves
• Some commentators have suggested it could be applied to all IVF cycles
Nonetheless, it is perhaps the most hotly debated areas of reproductive medicine with strong and vocal advocates and opponents. The nature of the controversy surrounding PGT-A is multi-faceted and, in effect, both sides of the argument have valid points. With 20+ years of ongoing controversy then neither side can possibly be completely right nor wrong. Breaking down the issue to individual components can however shed light on what is quite a complex problem. These are:
• How to interpret the existing data, including the Randomized Controlled Trials (RCTs)
• Mosaicism – when a result (following next generation sequencing (NGS) shows clear evidence of normal and abnormal cells
• Are there any deleterious effect of biopsying the embryo?
• Stubborn people who stick to their own point of view in spite of the evidence, and who are often the most vocal in the argument
• The attitude of the Human Fertilization and Embryology Authority (HFEA), the UK’s fertility regulator for PGT-A and its “traffic light system”
The talk will be a personal appraisal of the state of the ART for PGT-A with specific reference to my laboratory’s in-depth, independent assessment of the activities of varioius groups throughout the world.
Make sure you log in ahead of time, so that you catch the lecture start at 16:00 h sharp, and to keep your microphone muted unless requested otherwise or for critical comments and the final Q&A. As for all lectures in our lecture series, you are strongly encouraged to attend, join the discussion and find out what is going on in and around the CING.