PREIMPLANTATION GENETIC DIAGNOSIS (PGD) 

 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 they draw fluid from around the fetus [unborn baby] while the mother is pregnant and test the cell 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.

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 or lead to pregnancy loss or result in the birth of a child with physical and/or mental problems. PGD can help prevent these unfavorable outcomes by identifying embryos prior to transfer during IVF.

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). Aneuploidy occurs more frequently in eggs and embryos in women over 34 years of age. 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 9 chromosomes most commonly involved. These chromosomes are 13, 15, 16, 17, 18, 21, 22, X, Y. We do 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 type of problem that can be tested is a specific gene disorder. 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.

INDICATIONS for PGD include:

• Advanced maternal age (over 34 years).
• Advanced paternal age (over 39 years).
• Carriers of chromosome rearrangements, translocations, inversions or other chromosomal or genetic abnormalities.
• Recurrent pregnancy loss > 2 .
• Repeated IVF failure > 2 .
• Males with an abnormal Sperm Penetration Assay or Sperm Chromatin Structure Assay.

BENEFITS of PGD 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.
• Reduction in pregnancy loss (~1/2 of existing rate).
• Reduction in multiple birth (~1/2 of existing rate).
• Increase in implantation rate (~10% above existing rate).
• Increase in delivery rate (~15-20% above existing rate) .

 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 Program of Alabama. The genetic testing will be performed at a referred 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.

In conjunction with PGD, we recommend that these studies be performed based on specific criteria. The decision whether or not to proceed with testing and all financial obligations resulting from the tests are the sole responsibility of the patient. These tests are not 100% accurate. As with any pregnancy, regardless of whether IVF is used, there is no guarantee that an infant with some undetected physical or mental abnormality will not be born. Current data suggests there is no higher risk of abnormalities for IVF than if pregnancy occurs spontaneously.

If an abnormality is identified following testing, the couple and their obstetrician will discuss the options. If termination (abortion) is recommended, it is at the option of the patient and the patient is financially responsible for the termination. Should the pregnancy be continued the patient is responsible for any complications to the patient, fetus or baby and for all costs incurred.

Whether pregnancy is achieved through Assisted Reproductive Technology (ART) or natural conception methods, certain risks exist. During the course of pregnancy and childbirth, fetal abnormalities, ectopic pregnancies, spontaneous miscarriage, stillbirths, multiple births, and childbirth complications may develop.

If you are undergoing IVF treatment, you should be aware that infertility itself, age, multiple pregnancy, and possibly other unknown factors may put you at an increased risk of problems such as stillbirth and prematurity. Multiple pregnancy also increases the risk of premature labor and increases the risk of neurological problems such as cerebral palsy in surviving infants. Should you have a multiple gestation (twins, triplets, or quadruplets), you should obtain care from an experienced obstetrician who can provide referral to a medical facility that has an appropriate neonatal service, in the case it is needed. We recommend that you discuss all the above issues with your obstetrician.

Insurance coverage for any or all of the IVF procedures may not be available and you will personally be responsible for all costs for any related procedures.

Should you or any of your offspring require additional medical treatment as a result of any physical injury or additional procedure arising out of your participating in this IVF program, the financial responsibility for such care and treatment will by yours.

REVIEW OF THE PGD PROCESS

• Routine IVF procedures prior to and including retrieval of eggs (oocytes).

• Routine laboratory procedures necessary for the handling of any eggs (oocytes), sperm and embryos and micromanipulation procedures.

• Laboratory procedures including the biopsy of embryos (via chemical or laser method) followed by blastomere fixation on day 3 of culture.

• Shipment of the fixed blastomeres to the referral laboratory.

• Genetic testing of the fixed blastomeres by the referral laboratory followed by result reporting by day 5 of culture.

• Transfer of the embryos with normal testing on day 5 of culture at the blastocyst stage to the uterus.

• Routine IVF and cryopreservation procedures following embryo transfer.

• Routine pregnancy testing procedures approximately two weeks following egg retrieval.