PGD – Pre Genetic Diagnosis

Pre genetic diagnosis or preimplantation genetic diagnosis (PGD) allows the screening of embryos for specific genetic diseases or chromosomes before the embryos are placed in the uterus. PGD is primarily used to evaluate known carriers of specific single gene defects. Gene defects such as cystic fibrosis, or specific chromosomal abnormalities like trisomy 21 / Down Syndrome, Turner’s Syndrome, and specific unbalanced translocations. Transferring the screened embryos with the lacking genetic defect makes it extremely unlikely that the disease could be passed to the child.

PGD also is used to evaluate the embryo cells for abnormal numbers of specific chromosomes (aneuploidy). A normal embryonic cell has 23 chromosomes from the mother and 23 chromosomes from the father, thus totalling 46. Sometimes the dividing cells do not equally distribute their chromosomal complement. This occurs more often as the mother ages and is one of the reasons why fertility declines with increasing female age.

Due to the advances made in IVF, pre genetic diagnosis is possible.

The eggs are retrieved and fertilized with the partner’s sperm, often utilizing intracytoplasmic sperm injection (ICSI). Once the embryo reaches the 6 to 8 cell stage, 1 or 2 cells are removed (biopsied). For single gene defects, the DNA is analyzed by making multiple copies of the suspected gene. A technique known as the polymerase chain reaction (PCR) is used. Unaffected embryos are selected to be transferred to the uterus.

Chromosomes most commonly involved in miscarriages or live birth abnormalities can be counted. These could be chromosomes 13, 21, 18, X and Y. Currently, technology makes it difficult to screen all the chromosomes in a cell removed from the embryo. But the Jones Institute has and will continue to investigate other methods that will make complete chromosome screening possible in the future.

The FISH technique can be used to screen up to nine chromosomes in a cell from the developing embryo. This encompasses approximately 85% of the chromosomal abnormalities seen. The FISH technique also can be used to evaluate specific chromosome structural rearrangements known as translocations. When a person carries a balanced translocation, the offspring are at risk of having an unbalanced translocation. This results in either extra or missing pieces of the involved chromosomes. Many times, this could result in multiple implantation failures, miscarriages, or severe abnormalities at birth.

One of our first PGD successes was Brittany Abshire, who was the first child in the world born after PGD to rule out Tay – Sachs disease. This procedure was performed at the Jones Institute.

Patients who might benefit from pre genetic diagnosis include:

  • Carriers of known genetic diseases
  • Women over 38 years
  • Women who have had recurrent miscarriages
  • Couples who have had previous aneuploid conceptions
  • Couples who have had more than three IVF failures

Culturing embryos to the blastocyst stage may significantly decrease the number of abnormal embryos. A blastocyst is an embryo that has developed for five days after fertilization and has divided into two different cell types. A healthy blastocyst should hatch from its “shell” (zona pellucida) by the end of 6 days, and within 24 hours after hatching. It should begin to implant within the lining of the uterus. In recent studies embryos that do not survive to the blastocyst stage have a high incidence of abnormal chromosome numbers.

The transfer of high grade blastocysts has resulted in implantation rates between 30% – 40% in selected populations. With the transfer of only two blastocyst embryos, pregnancy rates as high as 50% – 60% per cycle have resulted. These high implantation and pregnancy rates are due in large part to selection of those embryos that have the highest chances of producing a pregnancy.