Preimplantation Genetic Diagnosis for Sex-linked Diseases and Sex-Selection for Non-Medical Reasons

• Fluorescence in situ hybridization (FISH) is the technique of choice to sex embryos. FISH provides a very robust test with a low risk of misdiagnosis; however, testing that only determines the sex of the embryos cannot discriminate between normal and affected male embryos or between normal and carrier female embryos, which is wasteful of male embryos and accepts a level of risk that carrier females may have clinical features of the trait. • PCR methodology has been used to develop direct tests for known mutations associated with a range of X-linked diseases. Protocols generally utilise a nested PCR approach, to include one, two or three microsatellite markers closely linked to the disease gene, in order to monitor contamination and allele drop-out, potential sources of misdiagnosis when using PCR-based testing. • Preimplantation genetic haplotyping (PGH) is a rapid way of developing indirect tests of X-linked disease. The same marker multiplex can be used for all families with the same disease, without the need for the development of family-specific mutation testing. PGH relies on the identification of the chromosome carrying the familial mutation by haplotype analysis of family members. The presence or absence of this chromosome in embryos can then be established by genotyping the biopsied cell. This approach has the added advantage of effectively “fingerprinting” each embryo, which obviates the need for washdrop blanks normally required to monitor contamination. • Testing for X-linked disease provides special ethical, counselling, and decision-making challenges beyond those posed by autosomal monogenic defects and chromosome rearrangements. • Many professionals involved in the PGD field take the view that sex selection for a non-medical reason is unacceptable. For others there are varying degrees of ethical risk and the balance between regulation and reproductive freedom is difficult to assess.