Here we present the first series of webinars created to help educate the field about Preimplantation Genetics and how PerkinElmer’s products are being utilized in labs around the world. In this series, which was put together originally as part of a preconference course for a meeting in Germany earlier this year, covers preimplantation genetics from large mammal species like cows and pigs, non-invasive testing of human embryos for chromosome gains and losses, mosaicism and the impact of transferring embryos suspected of being mosaic and testing methodologies for combining preimplantation genetic testing for specific monogenic diseases with PGT-A to improve the health of families. We hope that you enjoy these webinars and look forward to producing more content so please stop back at our website frequently to see what is new.
The concepts of IVF and PGT will be familiar to this audience. What will perhaps be less familiar is how widespread it is in non-human species. For instance, in 2017 nearly one million cattle embryos were transferred worldwide. The reasons for cattle IVF/PGT are not for fertility treatment, but for improved food production. More correctly referred to is IVP (in-vitro production), there are a host of reasons for applying assisted reproduction technology to not human species. These include more rapid introduction of genetics, more environmentally friendly and biosecure transport and biobanking. Cattle as a model for human IVF and human as a model for cattle IVP has the potential to be a highly synergistic programme of studies, especially when developing novel technologies in animals such as pigs, where it is less well developed but nonetheless much needed. This talk will cover the need for cattle and pig IVP and our progress in getting this to work in pigs while, in cattle, implementing a programme of PGT-A.
Modern PGT-A technologies are capable of identifying embryos containing mixes of euploid and aneuploid cells. Several groups have shown that uterine transfer of such mosaic embryos can result in healthy pregnancies and births, albeit with decreased success rates compared to euploid embryos. A binary system of PGT-A classification (normal/abnormal) has therefore become obsolete. The new mosaic category can further be refined, as recent evidence discussed here shows that characteristics of mosaicism can influence clinical outcome in a significant way.
Preimplantation genetic testing for aneuploidy (PGT-A) aims to rank embryos for clinical transfer by their ploidy, and relies on evaluating the chromosomal content of a representative for the entire conceptus. Historically, that proxy has been a cellular biopsy, but its isolation by microsurgery is technically challenging and invasive to the embryo. An alternative method evaluates extruded cell-free DNA in the fluids surrounding the cultured embryo. Here we consider the current developments in minimally and non-invasive PGT-A for clinical use.
Preimplantation genetic testing for monogenic diseases (PGT-M) has been applied for many years and it can be performed for any genetic disease that can be diagnosed. With the development of Whole Genome Amplification (WGA) technologies, it has become possible to test monogenic diseases and select euploid embryos with 24 chromosomes screening simultaneously, which is designated as combined PGT (PGT-M and PGT-A). As a result of the widespread use of whole exome and whole genome sequencing technologies, the variety of single gene diseases referred for PGT-M application has started to increase thus leading to an considerable elevation in the number of setup studies conducted for very rare disease. In this context, a steady test setup and a uniform WGA which will not be affected by the Alel Drop Out (ADO) trap, has become a necessity. The purpose of this webinar is to demonstrate that we can reduce the ADO ratio for a wide range of PGT-M conditions using target sequence enrichment protocol during WGA of biopsed cells which also allows sequential aneuploidy screening.