In 1992, Chloe O'Brien was the first baby to be born after being genetically screened as an embryo for the genetic defect, cystic fibrosis. Chloe was the first baby born as a product of PGD. What is PGD?PGD stands for preimplantation genetic diagnosis, or sometimes referred to simply as embryo screening. The genetic defects being screened for include Down syndrome, cystic fibrosis, Tay Sachs, muscular dystrophy and sickle cell anemia but are not limited to these defects.Technically speaking, PGD is a poorly chosen phrase because, in medicine, to "diagnose" means to identify an illness or determine its cause. An oocyte or early-stage embryo has no symptoms of disease. They are not ill. Rather, they may have a genetic condition that could lead to disease. Therefore it is probably more accurate to refer to preimplantation genetic screening because we are testing for a genetic condition when there is an absence of a symptom of a disease.PGD is a procedure that is performed on the embryo PRIOR to implantation. (Sometimes PGD can be performed on human eggs/oocytes prior to fertilization, but that is beyond the scope of this article.) The main advantage of PGD is that after PGD testing it is highly likely that the baby will be free of the disease it was tested for. PGD technology improves the likelihood of a successful pregnancy and birth for couples who are at risk for passing on inherited genetic disease to their offspring. If the parents are both carriers of the cystic fibrosis gene, then PGD offers them the opportunity to have a child that does not have the gene and is not a carrier for the gene. Without PGD these parents would need to undergo prenatal diagnosis to determine if their baby is a carrier of the disease or in fact has the disease and consequently most likely will face the decision of terminating their pregnancy.Who should consider PGD?There are two categories of patients that should consider PGD:1. Couples with a history of miscarriage or repeated unsuccessful IVF cycles. (From a statistical point of view, chromosome disorders occur in well over half of all first trimester pregnancy losses.) 2. Couples at risk for passing on a genetic disease to their baby.How is PGD performed?Eggs and sperm are placed in a Petri dish and left to fertilize and the resulting embryos are grown until they reach 4-12 cells. This typically takes three days. One or two cells are removed from each embryo through a procedure called embryo biopsy. These cells are analyzed in the PGD Laboratory to determine which embryos are free of genetic abnormalities. Every doctor's office has their own method of tracking the embryo to the one or two cells that was removed from it. Clearly each embryo biopsied and the removed cell(s) must be carefully tracked so that if a defect is detected the correct embryo is identified. Using PGD, embryos that are free of abnormalities are identified for implantation. The healthy embryos are usually implanted into the uterus 4-5 days following the egg retrieval.In routine genetic analysis there are usually hundreds of cells available for processing; however, with embryo biopsy only one or two cells are available. To enable testing to be done each cell must contain a nucleus with chromosomes present. The window of opportunity to biopsy an embryo is very narrow. By day 3 the embryo will be composed of between four and 12 cells that are still distinct from each other. After day 3 the embryo begins to compact. This means that the individual cells begin to lose their clear outline and therefore if biopsied harm could be done to the nearby cell. On Day 3 single cells can be individually removed without disrupting the adjacent cells in the embryo.Are there risks associated with PGD?The techniques used to biopsy are generally thought to be safe with little risk to the embryo. The risk of accidental damage to the embryo during biopsy is typically thought to be approximately 1%. (Some embryologists have stated that their risk factor is less than 1 %.) There is a slightly lower likelihood of implantation after embryo biopsy compared to an embryo not having been biopsied. (This remains debatable because so many factors need to be taken into consideration when identifying why an implanted embryos did not result in a pregnancy.) Since PGD is a relatively new technology other risks may become apparent over time, but to date appear quite limited and need to be weighed against the potential benefits for each couple. Think of it this way – identical twins means the embryos spit into two equal parts, in other words 50% of the embryo was lost! Finally with PGD there are certain to be some normal embryos that are incorrectly diagnosed as abnormal and discarded. Should I do PGD?You need to have this discussion with your physician who will take into consideration your age, fertility history and genetic history of your extended family. PGD is typically recommended most frequently for patients with a history of genetic disease, unexplained infertility, recurrent miscarriages, unsuccessful IVF cycles, advanced maternal age, or male factor infertility. The most likely cause for miscarriage or multiple failed IVF cycles is a chromosome abnormality. PGD can also vastly reduce the risk of a Down syndrome conception. In some cases where a couple has a large number of embryos they may consider PGD as a tool to deciding which embryos to implant. Finally, through PGD the sex will be identified so this procedure offers a couple the opportunity of family balancing. What disorder can be diagnosed with PGD?Most cells contain 23 pairs or 46 chromosomes. These include chromosomes 1 to 22 (the autosomes) and chromosomes X and Y (the sex chromosomes). Sperm and eggs only contain 23 single chromosomes (one from each chromosome pair). During fertilization, the embryo receives one chromosome of each pair from each parent resulting in a normal male (46, XY) or a normal female (46,XX). If the sperm or egg harbors a chromosome abnormality, this can be transmitted to the embryo resulting in a genetic disorder.Down syndrome is usually associated with advanced maternal age. Down syndrome is caused by having an extra #21 chromosome (3 instead of 2). It is also referred to as trisomy 21.Single gene disorders usually show a characteristic family history of a specific genetic disease. Gene mutations can alter the cells normal function due to a lack of a required protein. For example, Cystic Fibrosis (CF) is a common genetic disorder that primarily affects the lungs of CF patients. The CF mutation affects a protein within the cell that reduces the cells ability to function properly. This results in a build up of mucous within the lungs, lung dysfunction and possible death.Specific chromosomes are tested for specific disorders, including:Chromosome 13: Breast and ovarian cancers, deafness, Wilson Disease Chromosome 15: Marfan syndrome, Tay-Sach's Disease Chromosome 16: Polycystic kidney disease, Alpha thalassemia Chromosome 17: Charcot-Marie-Tooth Disease Chromosome 18: Niemann-Pick Disease, pancreatic cancer Chromosome 21: Down syndrome Chromosome X: Duchenne muscular dystrophy, Turner's syndrome, Fragile X Syndrome Chromosome Y: Acute myeloid leukemiaIf PGD can reduce the risk of having a child born with a genetic defect, what is the ethical concern regarding PGD?
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