Preimplantation Genetic Diagnosis (PGD)

Preimplantation genetic testing is a technique used to identify chromosomal disorders such as Down syndrome, or single gene genetic defects such as cystic fibrosis in embryos created through in vitro fertilization (IVF) before pregnancy. PGD can also be used to select the sex of an embryo. In the lab, the embryologist removes one or two cells from a day-3 or day-5 embryo and usually sends it off to a lab for analysis. Preimplantation genetic diagnosis (PGD) refers specifically to when one or both genetic parents has a known genetic abnormality and testing is performed on an embryo to see if it also carries a genetic abnormality. In contrast, preimplantation genetic screening (PGS) refers to techniques where embryos from presumed chromosomally normal genetic parents are screened for aneuploidy.

PGD can’t put to rest all fears of heritable problems: There are a certain number of tests we can do right now, ranging from 9 to 13 chromosome pairs, a relatively small percentage of an embryo’s total of 23 pairs. We can’t say that there aren’t problems in the chromosomes we can’t test for, but the odds of the non-tested chromosomes having an error are lower than the tested ones. Mutations on the chromosomes that can be tested with PGD account for about 85 percent of all abnormalities seen in fetuses or babies. The risk of damage to the embryo is small, with over 98 percent surviving the process.

Many patients first talk about PGD with a genetic counselor, especially if they have a family history of cystic fibrosis, Tay-Sachs, hemophilia, sickle cell anemia, or another genetic disorder, or if the woman is older. Multiple rounds of failed IVF may be another reason to investigate embryo quality with PGD, too. Indications for Preimplantation Genetic Diagnosis

Preimplantation genetic diagnosis (PGD) is recommended when couples are at risk of transmitting a known genetic abnormality to their children. Only healthy and normal embryos are transferred into the mother's uterus, thus diminishing the risk of inheriting a genetic abnormality and decreasing the risk for adverse outcomes such as early and late miscarriage and late pregnancy termination (after positive prenatal diagnosis).

Primary candidates for PGD include the following:

  • Couples with a family history of X-linked disorders (Couples with a family history of X-linked disease have a 25% risk of having an affected embryo [half of male embryos].)
  • Couples with chromosome translocations, which can cause implantation failure, recurrent mental or physical problems in offspring
  • Carriers of autosomal recessive diseases (For carriers of autosomal recessive diseases, the risk an embryo may be affected is 25%.)
  • Carriers of autosomal dominant diseases (For carriers of autosomal dominant disease, the risk an embryo may be affected is 50%.)

Conditions Diagnosed Using PGD

PGD is offered for 3 major groups of disease:
  1. sex-linked disorders
  2. single gene defects
  3. chromosomal disorders.

Sex-Linked Disorders

X-linked diseases are passed to the child through a mother who is a carrier. They are passed by an abnormal X chromosome and manifest in sons, who do not inherit the normal X chromosome from the father. Because the X chromosome is transmitted to offspring/embryos through the mother, affected fathers have sons who are not affected, but their daughters have a 50% risk of being carriers if the mother is healthy. Sex-linked recessive disorders include hemophilia, fragile X syndrome, most neuromuscular dystrophies (currently, >900 neuromuscular dystrophies are known), and hundreds of other diseases. Sex-linked dominant disorders include Rett syndrome, incontinentia pigmenti, pseudohyperparathyroidism, and vitamin D–resistant rickets.

Single Gene Defects

PGD is used to identify single gene defects such as cystic fibrosis, Tay-Sachs disease, sickle cell anemia, and Huntington disease. In such diseases, the abnormality is detectable with molecular techniques using polymerase chain reaction (PCR) amplification of DNA from a single cell. Although progress has been made, some single gene defects, such as cystic fibrosis, have multiple known mutations. In cystic fibrosis, only 25 mutations are currently routinely tested. Because most of these rare mutations are not routinely tested, a parent without any clinical manifestations of cystic fibrosis could still be a carrier. This allows the possibility for a parent carrying a rare mutation gene to be tested as negative but still have the ability to pass on the mutant cystic fibrosis gene.

PGD can also be used to identify genetic mutations like BRCA -1, which does not cause a specific disease but increases the risk of a set of diseases.

Chromosomal Disorders

The last group includes chromosomal disorders in which a variety of chromosomal rearrangements, including translocations, inversions, and deletions, can be detected using fluorescent in situ hybridization (FISH). FISH uses telomeric probes specific to the loci site of interest. Some parents may have never achieved a viable pregnancy without using PGD because previous conceptions resulted in chromosomally unbalanced embryos and were spontaneously miscarried.