What is Preimplantation Genetic Diagnosis?
Preimplantation genetic diagnosis (PGD) is a reproductive technology used to identify genetic defects in embryos created through in vitro fertilization (IVF) cycles. The technique is used when one or both parents have a known genetic abnormality. Embryos are tested for a panel of the most common chromosome abnormalities so that only normal embryos can be used to create a pregnancy.
Today, a growing number of genetic disorders can be diagnosed with the use of PGD. However, not all genetic disorders can be identified in this way. Still, the ability to identify many genetic abnormalities prior to the embryo being implanted into the uterus prevents the dilemma many couples face with regard to terminating a pregnancy in the event of an unfavorable prenatal diagnosis.
PGD was developed in 1989 as an alternative to prenatal diagnosis and potential termination of pregnancy of a fetus affected by genetic disease.
What is the procedure for PGD?
The process of genetic testing with PGD is done in concert with IVF or ICSI. As with all IVF procedures, eggs are removed after ovarian stimulation and fertilized in a laboratory. About three days after fertilization, the embryo will have developed approximately eight cells. Typically, one to two cells are removed by biopsy and are tested for genetic abnormalities. In addition, a newer technique called comparative genomic hybridization (CGH) allows doctors to remove cells from the embryo at a later stage. At five days, the embryo has about 100 cells, and removing cells at this stage can cause less damage. In addition, it enables doctors to analyze more cells. This provides doctors with greater certainty about whether or not genetic abnormalities in the embryo exist.
PGD uses these techniques to analyze genetic material from the embryo:
- Fluorescence in situ hybridization analysis (FISH) – this technique uses fluorescent probes to determine genetic abnormalities. It is used for sex determination in diseases linked to gender and for numerical and structural chromosomal abnormalities.
- Polymerase chain reaction (PCR) – PCR is used to detect the mutation of a single gene.
- Haplotyping – this technique uses DNA fingerprinting to identify chromosomes carrying affected genes.
- DNA Chip or Gene Chip- this is a new technology which allows the DNA of the embryo to be compared to over 20,000 different genetic mutations.
The embryos determined to be healthy and which contain the genetic characteristics that are desired by the woman and/or the couple are transferred into a woman's uterus.
Who are candidates for PGD?
PGD is recommended for women or couples who are at risk of passing on a known genetic abnormality to their children. The process reduces the risk of a child inheriting a genetic disorder and minimizes the risk of late-term miscarriage and pregnancy termination by only implanting healthy and normal embryos into the mother's uterus.
In particular, candidates for PGD include:
- Couples with history of recurrent pregnancy loss due to genetic disorders
- Couples with repeated IVF failure
- Male partners with severe male factor infertility
- Couples with a child who has a genetic disease and are at high risk for having another
- Couples looking for a tissue match for a sick sibling who can be cured with transplanted cells
- Couples with a family history of X-linked disorders
- Couples with chromosome translocations (a condition in which a small piece of one chromosome switches places with a small piece of another chromosome), which can cause implantation failure, recurrent pregnancy loss, or mental or physical problems in offspring
- Carriers of autosomal recessive diseases, such as cystic fibrosis, sickle cell anemia and Tay Sachs disease
- Carriers of autosomal dominant diseases, including dwarfism and Huntington’s disease
Couples with genetic disorders should obtain adequate counseling before undergoing the PGD technique. Other options should be fully explored as well. These include: prenatal diagnosis, egg donation, sperm donation, and adoption. The risks associated with misdiagnosis should be fully addressed in counseling as well.
PGD is not recommended for older women and women with high FSH levels. Pregnancy rates are lower for this population, and they may not be able to produce enough embryos to undergo testing. Men also must have a normal to high sperm count for adequate testing to be done.
What is sex selection?
Gender selection is a reproductive technology that can increase a couple’s odds of having either a boy or a girl, depending on preference. There are a number of reasons couples may wish to do this: a desire to balance the gender of a family, to avoid genetic disorders that are more common in one sex or another, and sometimes, to accommodate cultural or social norms.
There are different types of procedures used for sex selection, most of which involve separating X and Y chromosomes from sperm or involve the selection of embryos with male or female DNA in order to produce a baby of the desired gender. PGD is one method used for this purpose. Once embryos have been analyzed for both cell structure and DNA, it is possible to determine their sex. Embryos of the desired gender will then be implanted into the mother’s uterus with the use of IVF procedures.
Sex selection can be controversial. Ethical concerns are particularly strong when the reasons for sex selection are social or emotional in nature, rather than for the purpose of avoiding a genetically based disorder. This procedure is available at some clinics throughout the United States, but is typically offered only to patients who have legitimate concern about genetic disorders or are dealing with family balancing.
What are the results?
While the long-term impact of this technique on the fetus is not known, there are no current reports of increased abnormalities following PGD. With PGD, there is a 98% chance that the implanted embryo will not carry the genetic abnormality. Also, the PGD method offers couples a 99 percent chance of having a child of the desired gender.
What are the risks?
There is the risk with PGD, as with all tests, of either false positive or false negative test results. This is because many embryos show chromosomal inconsistencies from cell to cell. As a result, the cell taken for biopsy may not represent the other cells of the embryo.
Because only one or two cells are available for genetic testing, inconclusive genetic test results can lead to an inaccurate diagnosis. Because misdiagnosis is possible, PGD often is confirmed by additional testing typically done in early pregnancy to identify certain problems. Such tests include chorionic villi sampling or amniocentesis.
What is the cost for PGD?
PGD can be an expensive procedure and is not covered by most insurance. Using PGD adds an average of $3,550 to the cost of IVF.