ABSTRACT
For couples at risk of transmitting a genetic disease, preimplantation genetic diagnosis (PGD) and transfer of disease-free embryos offers an alternative to prenatal diagnosis by chorionic villus sampling (CVS) or amniocentesis, followed by therapeutic abortion of affected fetuses. Molecular PGD was initially employed for embryo sexing in couples at risk for X-linked diseases. The technique used the polymerase chain reaction (PCR) to amplify Y chromosome-specific sequences, and only embryos determined to be females were transferred.1 During the past decade, the range of genetic abnormalities that can be detected by PGD has dramatically increased (Table 29.1). Moreover, it is now possible to perform combined PGD and human leukocyte antigen (HLA) typing. This may prove beneficial in cases where a child is affected with a genetic disease amenable to bone marrow transplantation. In this
approach, future siblings are not only free of the disease, but may also be suitable donors for the affected sibling. This approach has been successfully employed for Fanconi’s anemia.3 However, the use of PGD for HLA-typing, particularly in the absence of a genetic disease, and its use in screening embryos for susceptibility to cancer and late-onset diseases as well as for gender selection, raise important ethical concerns. Despite its promise, PGD is still limited by technical difficulties due to the minute amount of genetic material, and the inherent pitfalls of the polymerase chain reaction, such as amplification failure, allele dropout (ADO), and foreign DNA contamination. There is also a rather narrow window of opportunity to perform diagnosis within hours, to enable embryo transfer without jeopardizing pregnancy rates. This chapter reviews the various aspects of the genetic analysis of preimplantation embryos. Chromosomal analysis of the embryo is discussed in a separate chapter.
