Human preimplantation diagnosis: needs, efficiency and efficacy of genetic and chromosomal analysis

One of the limitations of existing assisted reproduction practices is that couples at genetic risk to their offspring have to face the abortion of an affected fetus following prenatal diagnosis. This is not acceptable as a measure to avoid a congenital disease in many communities or ethnic groups, where there is a great need for a method to diagnose and avoid the affected embryo before implantation and establishment of the pregnancy. In fact, preimplantation diagnosis is needed also for those who accept prenatal diagnosis as an option to avoid the birth of an affected child, because in most of the cases the couples are at high (25-50%) risk of having a child with a recessive or dominant disease, leading to their unfortunate experience of undergoing two or more abortions of wanted pregnancies. Two methods for preimplantation genetic diagnosis (PGD) have been recently developed and implemented in the framework of IVF. PGD can be performed by micromanipulation and biopsy of the first polar body before fertilization, or by blastomere biopsy before implantation of the pre-embryo. Another potentially realistic approach is blastocyst biopsy, which is still under development and has not yet been tested in clinical practice. Available data suggest that preimplantation diagnosis is safe, as no detrimental effects have been observed in studies on the viability of biopsied pre-embryos. Genetic analysis of biopsied gametes and blastomeres is now possible by DNA analysis, while enzyme analysis and preimplantation diagnosis of chromosomal disorders are still at the research stage. The accuracy of DNA analysis in preimplantation diagnosis is clear from available data on the outcome of preimplantation diagnosis: eight children free of genetic disease have been born following preimplantation diagnosis of cystic fibrosis, haemophilia A and other X-linked conditions. However, two misdiagnoses have been also described, showing the need for further development and improvement in the accuracy, efficiency and efficacy of DNA analysis in single cells. A particularly important implication for assisted reproduction practices can be expected from the further development and improvement of methods for preimplantation cytogenetic analysis. Although the efficiency and efficacy of these methods are not yet acceptable for application in clinical practice, considerable progress has been made, providing clear evidence for their feasibility in the near future. In spite of the high cost of the preimplantation diagnostic technique at present, its development is highly justified for high risk families as it provides a wider range of options for avoiding the risk of having an affected child.(ABSTRACT TRUNCATED AT 400 WORDS)