Preimplantation Genetic Diagnosis ( PGD )

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

PGD is possible because of the advances made in IVF. The eggs are retrieved and fertilized with the partner’s sperm, often utilizing intracytoplasmic sperm injection ( ICSI ). Once the embryo reaches the six to eight cell stage, one or two cells are removed ( biopsied ). For single gene defects, the DNA is analyzed by making multiple copies of the suspected gene by a technique known as the polymerase chain reaction ( PCR ). Unaffected embryos are selected to be transferred to the uterus.

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 yielding 46. Sometimes the dividing cells do not equally distribute their chromosomal complement. This occurs more often as the age of the mother increases and is one of the reasons why fertility declines with increasing female age.

Chromosomes most commonly involved in miscarriages or live birth abnormalities (such as chromosomes 13, 21, 18, X and Y ) can be counted. In the photomicrograph shown, you can see the nucleus of a biopsied cell ( blue “globe” ) with the fluorescent red, green, and yellow spots within the nucleus demonstrating chromosomes 13 / 21 ( red ), 18 ( aqua ), X ( green ) and or & Y ( yellow ).

The technique utilized in this example and process is fluorescent in situ hybridization or FISH. FISH 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. 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 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 resulting 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 PGD include:

  • Carriers of known genetic diseases,
  • Women over the age of 38,
  • Women who have had recurrent miscarriages,
  • Couples who have had previous aneuploid conceptions, or
  • Couples who have had more than three IVF failures.

Blastocyst Culture

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 six days, and within 24 hours after hatching, should begin to implant within the lining of the uterus. Recent studies have demonstrated that embryos that do not survive to the blastocyst stage have a high incidence of abnormal chromosome numbers.

Thus, culturing embryos to the blastocyst stage may significantly decrease the number of abnormal embryos. 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.