Preimplantation Genetic Diagnosis (PGD) was developed in the late 1980s as an early form of testing of an embryo to aid couples that are at risk of giving an inherited disease to their child. Prior to PGD, the only option available for these couples was testing by amniocentesis (a test where fluid is drawn from around the fetus [unborn baby]) or chorionic villi biopsy (a test that removes a biopsy of placenta tissue at 11-13 weeks gestation while the mother is pregnant). The cells and tissues are tested to see if the fetus has the disease. The main drawback of this is if the fetus has a disease, the couple has to decide whether they wish to stop the pregnancy or continue the pregnancy knowing that their child is going to have the disease. PGD offers some of these couples a choice. The test is performed during an in vitro fertilization (IVF) cycle on the embryo prior to transfer to the uterus. Only unaffected embryos are transferred to the patient after the test. The pregnancy is started knowing that the fetus is free from the genetic disease. Unused embryos can be cryopreserved at the couple’s request.
Patients requiring PGD may be candidates for the Shared Risk Refund Plan for their IVF services.
PGD may be used in certain situations where there is an increased chance that embryos will be affected by certain chromosomal conditions. These conditions can decrease the chance the embryo implants (attaches) in the uterus, potentially leading to pregnancy loss or resulting in the birth of a child with physical and/or mental problems.
Not all genetic errors can be determined through PGD. Those that can include changes in chromosome numbers, or aneuploidy (having an abnormal number of chromosomes), and changes in chromosome appearance. Aneuploid, or abnormal, embryos are those with either a missing chromosome (monosomy) or an extra chromosome (trisomy). Missing or extra chromosomes can result in a child with physical or mental problems or miscarriage. All humans have 23 pairs of chromosomes. We will screen for the nine chromosomes most commonly involved. These chromosomes are 13, 15, 16, 17, 18, 21, 22, X, Y. The laboratory who performs our studies does not screen for all 23 chromosomes at this time.
Changes in chromosome appearance include translocations, a cause of recurrent pregnancy loss. Couples in whom one or both partners have a known translocation can benefit from PGD. In these couples, there is a higher rate of translocation that has only part of the chromosomes required (unbalanced). An unbalanced translocation is an abnormal amount of chromosome material and can lead to children with physical and/or mental problems. This testing requires preparation of a specific stain to check for the translocation that the parent carries.
Another category of genetic disorders that can be detected with PGD are single-gene disorders. These genes would be evaluated because the parents are known to carry the gene. It often takes two genes to create the problem for the baby, or one gene if it is on the X chromosome and the baby is a boy. The testing checks for the specific gene that the couple carries. Examples include cystic fibrosis – a lung disorder, Tay Sachs disease, hemophilia B or sickle cell disease. The parents will have been tested to see if they carry the gene because they may be at risk for carrying it due to familial factors. This screening is done during pre-conception genetic counseling before they begin IVF.
The American Society for Reproductive Medicine (ASRM) issued practice guidelines in December 2007 stating:
PGD is not a recommended test for:
Advanced maternal age.
Male factor infertility.
Recurrent pregnancy loss.
Repetitive implantation failure.
The current scientific literature demonstrates that live birth rates are not improved for couples using PGD for the above indications. Currently, the only proven benefits of PGD are for cases of single-gene disorders and chromosomal translocations. Other applications of PGD must be considered on a case-by-case basis in the context of the couple’s clinical situation.
INDICATIONS for PGD may include:
Screening for single-gene disorders.
Carriers of chromosome rearrangements, translocations, inversions or other chromosomal or genetic abnormalities.
BENEFITS of PGD may include:
Selection and replacement of only those embryos that do not have certain chromosomal abnormalities.
Reduction in delivery of a child with certain genetic abnormalities.
RISKS of PGD include:
Incidental damage to the embryo (< 1%).
Misdiagnosis (up to 10%).
3.5% chance that an affected embryo is diagnosed as unaffected.
10.0% chance that an unaffected embryo is diagnosed as affected.
No transfer due to PGD resulting in all embryos affected (up to 20%).
PGD is used in combination with standard in vitro fertilization (IVF) procedures. PGD involves the removal of one to two cells from an embryo (providing a combination of the mother and father’s genes). This is followed by genetic testing through fluorescent in situ hybridization (FISH) for aneuploidy, translocations and other structural abnormalities. A second type of test is called polymerase chain reaction (PCR). It looks for specific gene disorders. PGD involves two stages: (1) embryo biopsy with blastomere fixation and (2) genetic testing. The biopsy and fixation procedures will be performed at the ART Fertility Program of Alabama. The genetic testing will be performed at a specialty laboratory shown to have expertise in genetic testing (FISH and/or PCR techniques).
Diagnostic tests are available once pregnancy has begun to test whether development is proceeding normally. Amniocentesis or chorionic villi biopsy (removal of a sample of fluid or tissue surrounding the baby) can identify certain abnormalities. Amniotic fluid studies and ultrasound may detect certain abnormalities of the central nervous system or other body parts. Patients should discuss these tests with their obstetrician.