Preimplantation Genetic Diagnosis - PGD

Preimplantation Genetic Diagnosis (PGD) is a recently introduced technique in Assisted Reproductive Technology and involves the biopsy of a single cell per embryo followed by its genetic diagnosis through different techniques such as Fluorescent in-situ Hybridization (FISH) , Polymerase Chain Reaction (PCR), or Comparative Genomic Hybridization (CGH). Subsequently, embryos classified by genetic diagnosis as normal are transferred to the IVF Patient.

Patients requesting PGD screening undergo in vitro fertilization to maximize the number of oocytes (eggs) to be retrieved and having an increased probability to identify unaffected healthy embryos prior to transfer to the mother's uterus.

The following people may benefit from preimplantation genetic diagnosis:

• Women who are over 35 years of age,
• women who experienced repeated spontaneous abortions,
• prior pregnancy with chromosome abnormality,
• couples who experienced several failed IVF cycles,
• women who have difficulty conceiving a pregnancy due to low sperm concentration,
• couples with a family history of Huntington disease,
• if the woman or her partner carry a recessive genetic disease such as cystic fibrosis,
• if the woman or her partner carry a balanced structural chromosome rearrangement,
• if a woman or her parnter carry an x-linked disease such as hemophilia or Duchene Muscular Dystrophy,and
• if the couple simply wants to balance the gender in their family.

Is PGD safe?

Yes. PGD is done before the embryo's genetic material becomes "active". Since it is done so early, the cells inside the embryo are still all identical and each cell is capable of becoming a baby. Removal of the cells of the early embryo does not alter the ability of that embryo to develop into a complete normal pregnancy. The micomanipulation technique used for blastomere biopsy is safe with little risk to the embryo. The risk of accidental damage during biopsies is less than 1%. There is no risk to the embryo following chromosomal of single gene defect analysis because the analyzed cells are not put back into the embryo. There may be slightly lower chance of implantation after embryo biopsy compared to an embryo not being biopsied.

Removal of the cells is performed on day 3 post IVF Retrieval. At this time the zona pellucida is cut open by using acidified culture medium that will dissolve the zona pellucida. The cut is usually made smaller than the cell itself and this help in the integrity of the embryo within the jelly coat during further development in the IVF Laboratory. The embryo during manipulation on the inverted microscope is held in a warm culture medium that helps allow the cell to be removed with minimum trauma to the overall embryo. All cells at this stage are known to be tot potent meaning, all are fully capable of directing further embryonic development. Once the blastomere is removed, the cell is either fixed on a glass slide for chromosomal analysis, or placed in a small tube of chemical buffer for single gene diagnosis. The cells are then analyzed using FISH of DNA analysis. During the genetic analysis which usually takes 24-48 hours, the embryos are further grown to the fifth day of development and at which time they may be at the blastocyst stage. Embryos found to be free of genetic abnormalities are then placed into the uterine cavity.

PGD for aneuploidy testing is done on chromosomes X,Y,13,15,16,17,18,21, and 22. This is based on trisomies arriving to term (XY,13,18,21), common in spontaneous abortions (16,22,15,21) and most common aneuploidies found in day 3 embryos (22,16,21,15,17) (Munne et al, Reprod Biomed online 2004:8:81-90). In PGD for translocations and other chromosome rearrangements, diagnosis is performed by PGD using FISH with custom made probe cocktails involving 3-4 custom probes. Before a PGD cycle can start, blood studies from the carrier as well as extensive preparation of the test is necessary and therefore these tests should be scheduled well in advance of the IVF procedures. These tests are coordinated through the genetic councilor and a deposit is required. PGD for translocations can be combined with PGD for aneuploidy, but priority will be given to obtaining translocation results. PGD for any genetic disease with an identified mutation is also available. As for translocations, before a PGD cycle can start blood studies from both parents as well as extensive preparation of the test is necessary and therefore these tests should be scheduled in advance of the IVF procedure. These tests are coordinated with the genetic councilor and a deposit is required.

 

Last updated: August 11, 2008
Reviewed by Dr. Rachel McConnell and her medical staff