Controlling misdiagnosis errors in preimplantation genetic diagnosis: a comprehensive model encompassing extrinsic and intrinsic sources of error

We have developed a mathematical model to explore accuracy of preimplantati on genetic diagnosis (PGD) using Single cell polymerase chain reaction (PCR ). The model encompasses both extrinsic technical errors and intrinsic erro rs related to nuclear and chromosomal abnormalities. Using estimates for th ese errors, we have calculated the probability of a serious error (affected embryo diagnosed as unaffected) using a variety of strategies designed to increase the accuracy of PGD, Additional information from genotyping a link ed marker or a second biopsied cell reduces the probability of replacing an affected embryo, while ensuring that sufficient unaffected embryos can be replaced. For a recessive disease, two genotypes are required to ensure a l ow probability of replacing an affected embryo (<1%) with a high proportion of unaffected embryos eligible for replacement (68%), These genotypes may be from a single cell with linked marker, or disease genotypes from two cel ls. PGD of a dominant disease is more difficult, as it relies on the amplif ication of a single copy of the mutation. Genotypes from two biopsied cells are required to ensure that a high proportion of unaffected embryos are el igible for replacement, This model can be used as a clinical tool to priori tize embryos for transfer in a PGD cycle.