I-36: Preimplantation Genetic Diagnosis - Where Have We Been and Where Are We Going

Preimplantation genetic diagnosis (PGD) is now considered routine in IVF laboratories with micromanipulation capability and access to genetic diagnostic services. The past two decades have witnessed a dramatic increase in the use of PGD, the number of cycles performed, and the indications for which PGD has been used. This increase has been mirrored by a slow, but steady, increase in the range of new technologies used to facilitate PGD. This lecture will focus on the evolution of these different techniques - focussing on those which have persisted (e.g. Fluorescence in situ hybridization and PCR) as well as the newer, more sophisticated tests (e.g. array CGH) which look set to replace them. Microarray based technologies are already in routine use in some laboratories and will likely become commonplace. From the IVF laboratory samples are simple to prepare and with the availability of centralized commercial testing laboratories, the clinical service is scalable. The use of genome wide SNP approaches has led to the possibility of a universal PGD test which can simultaneously diagnose any known genetic disease (for which a family history is present) and the presence (and, uniquely, the paternal origin of) chromosomal abnormalities. While these new tests are considerably more expensive than their predecessors they should come down in price with time, produce accurate reliable results, can reduce waiting times for test development considerably, and offer a wealth of potentially useful diagnostic information. As a consequence this raises the question: ‘How much information is too much information in the context of PGD?’ My objectives are to distinguish between different methods of preimplantation testing, compare the strengths and weaknesses of different laboratory methodologies used to perfrom preimplantation genetic diagnosis, describe the new technique of karyomapping which uses genomewide SNP analysis and its value in preimplantation testing for inherited disorders and aneuploidy. I will conclude by identifying ethical and practical problems associated with different forms of preimplantation testing.