Preimplantation Genetic Diagnosis (PGD)

Although Rotunda does not presently offer any PGD services, I thought it worthwhile to educate our patients & readers about Preimplantation Genetic Diagnosis. Couples with a family history of a genetic disorder and older mothers are relatively more likely to have a baby with genetic birth defects. Preimplantation genetic testing and diagnosis (PGD) can help these parents dramatically improve their odds of giving birth to a healthy child. Embryos that have certain genetic defects develop improperly. Used with in vitro fertilization (IVF), PGD can help us select the best embryos and avoid specific birth defects.
In PGD, a embryologist removes one or two cells from each embryo created in the IVF cycle(see picture). The cells are tested for abnormal genes. Only the embryos that have normal cells are transferred into the woman. Since PGD is not 100% reliable and only tests for specific defects, parents should presently still use other prenatal genetic tests, such as amniocentesis or chorionic villus sampling. PGD is expensive and still considered an experimental procedure by the majority of IVF laboratories.
Presently, only couples with family history of genetic disease and women over age 35 are advised PGD. PGD can detect genetic disorders when the defect is understood. As we learn more about genes and gene defects, PGD will become useful for more patients. PGD can tell whether an embryo will become a boy or girl, and reveal certain genetic conditions, including Cystic fibrosis, Down Syndrome, Duchenne muscular dystrophy, Hemophilia A, Tay-Sachs disease, and Turner Syndrome.
Prior to PGD, many couples with a family history of severe genetic disorder may have decided against having children. PGD dramatically improves the odds of having a baby without the disorder. In some cases, biologists can see whether the embryo has the defect. Some disorders only affect male offspring, so that female embryos may be selected to avoid the condition even if the exact defect isn't understood.
PGD helps prevent the stress and trauma after an abnormal result from an amniocentesis or chorionic villus sampling. These prenatal genetic tests can only be performed after 10-12 weeks into the pregnancy. Patients who use PGD should follow up with one of these tests, but the odds of an abnormal result will be dramatically reduced.
PGD requires the removal of one or two cells from each embryo. The embryo development is slowed slightly, but is otherwise normal. Most embryos are not adversely affected by the procedure. Some embryos may be damaged during the removal. An embryo that the PGD detects as abnormal may be normal in a small percentage of cases. This embryo would not be transferred, even though it could have become a healthy baby. An embryo that the PGD detects as normal may be abnormal similarly. This embryo would be transferred, and would result in a miscarriage or child with birth defects. Because of this risk, other genetic tests, amniocentesis or chorionic villus sampling, should be performed. To decrease the false positive & false negative results, some IVF teams employ a combination of tests using more than one cell biopsies. Since PGD is performed using embryos from an IVF cycle, the patient should be aware of the risks of IVF. There may be too few or no embryos without the defect. The embryos may not implant and develop even if they do not have the defect. If you decide to pursue PGD, you will prepare for an IVF procedure. The woman will take hormones to stimulate the ovaries to produce many eggs. Just as in a normal IVF procedure, the doctor retrieves the mature eggs from the woman. The eggs are fertilized with sperm. After two days, the embryos grow to four to six cells. The biologist forms a small opening in the outer membrane of the embryo, the zona pellucida. This is a similar process to assisted hatching. The technician gently sucks one or two cells out of the embryo through the hole. These cells are then tested for genetic abnormalities. In most cases, all the cells of an embryo will have the identical genetic makeup. Therefore, the tested cells will show the genetics of the remaining, viable embryo. The remaining cells of the embryo are young enough that they will form a complete, normal fetus. The test itself is a standard genetic test. It takes less than 24 hours to perform, so that the patient follows essentially the same schedule as a standard IVF cycle.
Women over 35 are more likely to have eggs with an extra or missing chromosome (aneuploidy). In these cases, the laboratory will examine the cells to count the chromosomes that usually lead to severe birth defects. Each human chromosome has a number, except the X and Y chromosomes that determine gender. The biologist uses a technique called fluorescence in- situ hybridization (FISH) to attach a particular color to each 13, 16, 18, 21, X, and Y chromosome. The biologist counts the spots of each color for each cell (see picture). Normal cells will have two of each color for the numbered chromosomes, as well as two X chromosomes (female cells) or an X and a Y chromosome (male cells). For a family history of a disorder, the laboratory will test for the specific defect. The laboratory must first test cells from the parent who has the disorder or may be a carrier to determine the exact defect. The embryo cells are then tested in a process that uses FISH to see if they contain that exact defect. The test doesn't reveal other genetic defects. After the tests are completed, the best embryos without the defect are transferred into the woman's uterus as in a standard IVF cycle. Follow the recovery procedures for an IVF cycle. If you become pregnant, be sure to follow up the PGD with another prenatal genetic test.