Preimplantation Genetic Diagnosis

PREIMPLANTATION GENETIC DIAGNOSIS (PGD) is also known as genetic embryo screening. PGD is the testing of embryos using certain procedures prior to implantation within the uterus. PGD can also be performed on oocytes prior to fertilization. PGD is used as a testing option instead of prenatal genetic diagnosis that traditionally occurs after the fetus is in utero. PGD tests for genetic conditions that have the potential to cause the disease. The advantage of PGD is that the testing is performed prior to implantation. Embryos that are affected are identified and not implanted. PGD can only be used for women who are achieving pregnancy through in vitro fertilization (IVF). The main advantage is that it reduces selective termination of affected fetuses.

In PGD, polymerase chain reaction (PCR) is used to determine the sex of the embryo. This technology was first performed in 1967 by Dr. Robert Edwards who was able to determine the sex of rabbits. It would be decades later, in 1989, that Dr. Alan Handyside utilized PGD in couples who were carriers of the delta 508 gene in the cystic fibrosis transmembrane regulator gene. The couples had undergone IVF and the embryos were subsequently tested on the third day after fertilization. One woman had two embryos that were fertilized normally and were negative for the cystic fibrosis gene. That woman underwent an embryo transfer with the normal embryo and gave birth to a healthy female in 1990 who had no genetic (carrier or disease) abnormality. This early PGD proved that single—gene diseases could be identified prior to implantation, an important development for families with genetic abnormalities.

PGD can only be used for couples who are undergoing assisted reproductive technology (ART) and IVF. Proponents of PGD believe that PGD eliminates later elective terminations of pregnancies due to genetic conditions by eliminating the implantation of genetically mutated embryos. It can be used for couples who have a family history of a single gene monogenic disorder when the fetus will be at risk for inheriting a genetic disorder. The single—gene disorders include autosomal dominant, autosomal recessive, X—linked dominant traits, X—linked recessive traits, Y—linked, and mitochondrial disorders. Autosomal dominant, autosomal recessive, and X—linked abnormalities are commonly screened for with PGD.

PGD can also be utilized for screening for mitochondrial disorders, but this is rarely performed, although a few centers do perform the analysis. In these cases, PGD is used to test for reciprocal and Robertsonian translocations, or other abnormalities such as chromosomal inversions or deletions. The use of PGD has been used in detecting chromosomal translocations since 1996.

Autosomal dominant disorders involve the inheritance of only one mutated copy of the gene. Most individuals inherit the disorder from one parent and have a 50 percent risk of inheriting the gene. These disorders tend to have low penetrance, which means even if the gene is inherited, a small number will actually go on to develop the disease. Most people who inherit autosomal dominant diseases will not demonstrate symptoms until later in life. Examples of autosomal dominant diseases include Huntington's disease, neuroblastosis 1, Marian's syndrome, and hereditary nonpolyosis colorectal cancer. Achondro—plasia, the most common cause of dwarfism, is an autosomal dominant disorder. Multiple osteo—chondromatosis, on the other hand, is an autosomal dominant disorder with high penetrance that most commonly occurs in children.

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