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Preimplantation Genetic Diagnosis (PGD)Preimplantation Genetic Diagnosis (PGD) is a procedure used in conjunction with in vitro fertilization (IVF) to test early human embryos for serious inherited genetic conditions and chromosomal abnormalities before they are transferred to a woman's uterus. PGD was first carried out in 1990 for a couple at risk of having a child with cystic fibrosis. The procedure is sought by both fertile and infertile couples at high risk of having children with a serious genetic condition. It can also be used as a screening procedure to determine if an embryo is chromosomally normal prior to transfer. Before PGD the only testing option available to couples at risk of passing on a genetic disorder to their child is prenatal diagnosis. PGD offers another choice to carriers of serious genetic disorders and involves making decisions about the future of an affected embryo, rather than an affected fetus. PGD can be used to test for many disorders including things such as Hemophilia and Cystic Fibrosis Each cell of the body contains structures called chromosomes within their centers or nuclei. A human cell typically contains 46 individual chromosomes, grouped as 23 pairs. The embryo will get 23 chromosomes from the sperm and the other 23 which are obtained from the egg. These chromosomes are made up of genes, which are the blueprint that contains instructions as to how the cells within the body should function. It is very important, therefore that each cell contain a full complement of 23 pairs of chromosomes, as any imbalance in the number of chromosomal pairs (aneuploidy) can give rise to a failure of the embryo to implant, early pregnancy loss, or other conditions, such as Down’s syndrome. By analyzing the chromosomal content of early preimplantation embryos it is possible to determine which embryos are more likely to implant and create a normal ongoing pregnancy. In the case of testing for a genetic condition, a marker specific to the condition and the couple is developed prior to testing. This can then be used to specifically pinpoint any embryo that contains the gene disorder in question. In the case of a recessive condition, 2 copies of the gene disorder are required to exhibit the disease, and if only 1 is present then the embryo is considered to be a ‘carrier’. With dominant conditions, then the presence of just 1 copy will cause the disease to be exhibited. Therefore, a full genetic consultation is required prior to undergoing a single gene disorder PGD case. PGD involves several steps:
After removing a single cell from the embryo, the cell can be fixed onto a microscope slide and analyzed. This will then give us a picture of the chromosomal content of the embryo, and in conjunction with the embryo development score, the ability to predict more easily which embryos should be transferred during the cycle. Who may want to use PGD?PGD can be used by both fertile and infertile couples. Couples who are carriers of a familial single gene disorder may wish to access PGD to have children without the particular genetic disorder. PGD for aneuploidy screening can also be used for couples who are having trouble conceiving, and it is also useful for couples who have suffered from repeated miscarriages. It may also be recommended for older patients in whom we know that the aneuploidy rate can be increased. What are the potential benefits of PGD?It allows for the selection of embryos with a normal chromosomal content, although at this point in time there is a limit to the number of chromosomes that can be analyzed. PGD offers people at high risk of transmitting a serious genetic condition to their children an alternative to their existing options of:
For many people, termination following prenatal diagnosis is either unacceptable or less preferable because of:
What are the concerns associated with the use of PGD? PGD can only be used in conjunction with IVF. The live birth rate for PGD is similar to the live birth rate for conventional IVF. Despite the relatively wide acceptance of PGD in the clinical arena, it remains a technically demanding procedure. It is subject to a risk of contamination and misdiagnosis, particularly when it is used for single-gene disorders. PGD involves the use of highly technical molecular biology techniques, and the error rates can be anywhere from 5-22%. While PGD is diagnostically reliable, we still advise their patients to undergo prenatal diagnosis to ensure that the preimplantation diagnosis is accurate and to test for any abnormalities not screened for during PGD. Although many clinics in the US offer aneuploidy screening to couples having trouble conceiving or carrying a baby, no consistent evidence is available to show that aneuploidy screening improves the live birth rate for couples having fertility problems. What are the ethical issues associated with PGD?Discarding affected embryosPGD involves making a decision about the fate of affected embryos at a very early stage of development. This is in contrast to prenatal diagnosis, which requires a decision to be made about terminating an existing pregnancy at a much later stage. For many people, discarding embryos is likely to be ethically less problematic than terminating a fetus. For others, both abortion and PGD may be unacceptable. PGD for Human Leukocyte Antigen tissue typingHuman Leukocyte Antigen (HLA) tissue typing or tissue matching is an additional step to PGD to determine if an embryo could lead to the birth of a child who is a tissue match for an ill sibling. For some people, HLA tissue typing raises many ethical and social questions. One of the most significant issues is whether people should be able to select an embryo on the basis that the child born may be the source of life saving therapies for a sibling. Can PGD be used to select the sex of a baby?Yes. The use of PGD for sex selection is carried out for two major reasons. The first is to prevent transmission of sex-linked genetic conditions such as Hemophilia and Duchene’s muscular dystrophy, when a specific test for the condition is not available. This medically-based rationale is acceptable to most. The second reason, a social one, is to provide parents with a child of the preferred sex. Can PGD be used to ‘design’ babies? In principle, PGD can be used to select for or against any characteristic that has a genetic origin. Some contend that PGD could be used to select against homosexuality, obesity, or hyperactivity, or for intelligence, beauty, or athletic ability. However, the use of PGD for these purposes is not currently scientifically possible. Can PGD be used to ‘design’ babies?In principle, PGD can be used to select for or against any characteristic that has a genetic origin. Some contend that PGD could be used to select against homosexuality, obesity, or hyperactivity, or for intelligence, beauty, or athletic ability. However, the use of PGD for these purposes is not currently scientifically possible. For some, any selection of embryos is regarded as leading to designer babies. However, PGD does not allow people to determine the precise characteristics of embryos. In summary, with the advent of PGD, selection of chromosomally normal
embryos could increase implantation rates (pregnancy rates) in certain
high risk groups and, therefore, can prove to be of benefit.
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