SHORT COURSE*
Monday, 13 April 2015 | 08:00 – 12:00
Preimplantation Genetic Diagnostics
In Vitro Fertilization (IVF) offers the opportunity for a range of genetic diagnostics to be carried out prior to the selection of fertilized eggs for implantation. In some cases a major reason for choosing the IVF route is because of the risk of serious recessive genetic disorders, which can be detected by targeted screening. Screening and de-selection of eggs with aneuploidies is also a way of improving the success rate of IVF. Experience with arrays and with next-generation sequencing will be discussed, as will recommendations for increasing the occurrence of singleton births.
Agenda
08:00 Registration and Coffee
08:45 Chair's Remarks
08:50 The Current Status of Preimplantation Genetic Diagnosis and Screening
Joyce Harper, FRCPath, Genetics, Embryology and IVF Group, Institute for Womens Health, University College London, United Kingdom
Preimplantation genetic diagnosis (PGD) was first performed in 1988 with the aim of offering couples a method of genetic diagnosis before implantation for those patients at high risk. In 1995, the methodology of PGD was applied to embryo screening for chromosome abnormalities for subfertile patients (preimplantation genetic screening). Advances in the methods used for genetic analysis in PGD and PGS has been moving fast and it is now possible to sequence a human embryo prior to implantation. In 1997, the ESHRE PGD Consortium was formed and annually reports on the worldwide status of PGD and PGS. An update of the current status of PGD/PGS and the Consortium data will be presented.
09:20 Single Cell Haplotyping as a Generic Tool for Preimplantation Genetic Diagnosis
Jorish Vermeesch, Ph.D., Department of Human Genetics, Catholic University of Leuvan, Belgium
Preimplantation genetic diagnosis (PGD) is the genetic testing of embryos prior to implantation to avoid the transmission of germline genetic disorders or of unbalanced chromosomal rearrangements when a parent is a balanced carrier. Current single-cell PCR or FISH PGD-assays require family-specific designs and labor-intensive workup. Genome wide SNP based typing is a generic method which enables not only the presence of Mendelian disorders genome wide, but also can identify chromosomal rearrangements and aneuploidies, including their parental origin as well as the meiotic or mitotic nature of chromosomal trisomies. The latest developments in this field will be presented.
09:50 Detecting Chromosomal Aberrations in Oocytes Using Microarray CGH
Karsten R. Held, M.D., Medical Director, Reprogenetics Germany GmbH, Germany
Polar body biopsy combined with array comparative genomic hybridization allows detection of maternal chromosomal aberrations. Although it has limitations, it can be seen as an alternative to blastomere and trophectoderm biopsy, especially in countries in which preimplantation genetic diagnostics is not permitted in embryos. Data from 451 cycles, comprising more than 2000 oocytes, will be presented, including 55 cycles from 32 translocation carriers. In addition data from a validation study comparing the new Oligonucleotide Array CytoSure Embryo Screen from Oxford Gene Technology with the BAC microarray 24sure (V3.0) from Illumina will be presented and the use of the two array types in the detection of aneuploidies as well as structural abnormalities will be discussed.
10:20 Refreshment Break
10:35 Preimplantation Genetic Screening in the Era of Next Generation Sequencing
Francesco Fiorentino, Ph.D., Chief Executive Officer, GENOMA Group, Italy
Chromosomal aneuploidy is recognized as a significant contributing factor in implantation failure and spontaneous miscarriage, and is likely to be responsible for the majority of IVF failure. Preimplantation Genetic Screening (PGS) has been proposed primarily as a method to improve embryo selection for patients with a poor prognosis for IVF success. Enhanced selection by PGS may provide a practical way to reduce substantially the risk of an adverse reproductive outcome related with the transfer of chromosomally abnormal embryos. The rapid development of next-generation sequencing (NGS) technologies has generated an increasing interest in determining whether NGS could be reliably applied for PGS purposes and if its use may offer any advantages current screening technologies. A comparison of NGS, both in its current form and potential advantages in the future, will be discussed.
11:05 The New Technologies Transforming Preimplantation Genetics in the Diagnostic Laboratory
Tony Gordon, Ph.D., Laboratory Director (UK) and Managing Director (USA), Genesis Genetics
New technologies are transforming pre-implantation genetics for single gene disorder (PGD) and preimplantation genetic screening for chromosomal aneuploidy (PGS). Genesis Genetics has moved from STR based PGD and now employs SNP based haplotyping (Karyomapping) to enable very rapid test development and highly accurate analysis of embryo inheritance, changing the process of PGD for patients from many months to a few weeks. Genesis Genetics has currently performed hundreds of such Karyomapping cycles. Next Generation Sequencing is now in routine use for PGS at Genesis Genetics, with the majority of PGS cycles using this technology. Moving from the 3-4000 data points of the existing arrayCGH technology to over a million NGS data points is enabling more sensitive, specific and accurate PGS thereby further improving the IVF patient’s chance of a successful pregnancy.
11:35 Panel Discussion
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