What is PGD and what does it test for?

Preimplantation genetic diagnosis (PGD) allows physicians to analyze an embryo formed outside the mother’s uterus for genetic defects that would prevent that embryo from implanting, produce a miscarriage or cause an inherited disease upon birth. Many genetic diseases are currently screened by this technology, including single gene defects such as Cystic Fibrosis, or chromosomal abnormalities like Down Syndrome.

How does PGD work?

PGD requires patients to use In Vitro Fertilization (IVF) to produce multiple eggs and embryos that will undergo biopsy and genetic testing. The biopsy of the embryos can be performed at different stages. The earliest way of testing the embryos is by studying the polar bodies (small cells consisting of a tiny bit of cytoplasm and a nucleus, formed during maturation of the egg). The polar bodies can be removed and studied to determine the maternal genetic contribution to the developing embryo. Another way of testing occurs three days after the egg has been fertilized in the lab. In this method, one cell from the eight-cell embryo is removed and its genetic material is tested to identify possible defects.

Regardless of the type of cell studied, there are two types of testing available. One technique, the polymerase chain reaction (PCR), produces thousands of copies of a specific DNA fragment. The size of the fragment distinguishes the normal from the abnormal gene. Another technique, fluorescent in situ hybridization (FISH), uses fluorescent dyes to visualize specific chromosomes. A cell with an abnormal chromosomal set will have a characteristic fluorescent pattern.

The results from the PCR and/or FISH tests are usually available within 24 hours. Once identified, a limited number of normal embryos are returned to the mother’s uterus to allow implantation and pregnancy to be established.

What are the indications for PGD?

PGD can be used for diagnosis of single-gene defects or chromosomal abnormalities. Single-gene defects are classified into two categories: autosomal recessive and autosomal dominant. Autosomal recessive disorders (i.e. Cystic Fibrosis, ß-thalassemia, Tay-Sachs Disease, Sickle Cell Anemia, etc.) require both partners to be carriers of the abnormal gene. These couples have a 25% risk of having a child affected by the disease. For autosomal dominant disorders (like Myotonic Dystrophy, Huntington’s disease, etc.) individuals carrying a single defective gene are affected.

Chromosomal aberrations that can be diagnosed by PGD include abnormal number of chromosomes (aneuploidy) and specific rearrangements of the chromosomes (translocations). While most embryos with abnormal chromosomes don’t survive, fetuses carrying an extra chromosome 13, 18 and 21 (Down Syndrome) can survive to term. There is extensive evidence that the higher infertility rates in older women are due to an increase in embryos with abnormal number of chromosomes. PGD could be used to decrease the risk of these women having a chromosomally abnormal fetus, reduce their risk of miscarriage, and possibly increase the embryo implantation rates.

Finally, couples in which one of the partners is a carrier of a chromosomal translocation are at risk for recurrent pregnancy loss as well as conceiving an abnormal fetus. PGD can be used to identify and transfer only the embryos with normal chromosomal patterns and thus reduce the couple’s risk of miscarriage.

Does PGD cause genetic damage or other damage to the embryos?

No. The polar bodies naturally dissolve at implantation and have no significance after fertilization. With embryo biopsy, the three-day old embryo is unaffected by the removal of one or two cells. Thus far, there has been no increase in the rate of congenital abnormalities or pregnancy complications in patients when embryo biopsy has been done.

Why is PGD important?

PGD is important because the technology holds the promise of reducing the incidence of genetic disease. To date, an increasing number of life threatening and debilitating genetic diseases may be screened before embryo transfer. It also changes reproductive options for families at risk.

Who should consider PGD testing?
There are several groups of patients that could benefit from PGD:

  • Genetic disorders: PGD testing can be performed for couples aware of genetic disorders through family history or based on carrier testing to help them conceive a healthy child. In genetic disorders where the genetic mutation is known, such as Cystic Fibrosis or Tay-Sachs disease, the actual genes of the embryo are examined for presence of the condition.
  • Advanced maternal age: Chromosomal abnormalities due to advancing maternal age are more likely to occur in women over the age of 35. PGD testing can determine the number of the chromosomes and help select the embryos most likely to result in a healthy pregnancy.
  • Recurrent miscarriages and repeated IVF failure: These two groups of couples have been found to produce a higher proportion of abnormal embryos. PGD testing can determine which embryos are the most likely to result in a healthy pregnancy.

What is the accuracy of PGD?

Overall PGD is able to diagnose genetic defects with approximately 98% accuracy. Even if a patient undergoes PGD, prenatal testing such as amniocentesis and chorionic villus sampling (CVS) is usually recommended to confirm the PGD diagnosis. Revealing genetic defects before pregnancy can significantly reduce the risk of a fetus being affected.

What ethical concerns does PGD technology present?

At present, nearly all-pregnant women are offered some form of prenatal screening and diagnosis. Since PGD allows for screening embryos before they are transferred, many believe that it spares some couples from the emotionally wrenching ordeal of having to decide about a second trimester pregnancy termination if their baby has a genetic disorder. PGD has been generally applied to identify genetically abnormal embryos known to cause significant health issues in the newborn. The Ethics Committee of the American Society of Reproductive Medicine (ASRM) has established ethical guidelines regarding sex selection and PGD. According to the Committee’s recommendations, PGD used for sex selection for non-medical reasons should not be encouraged. Moreover, the initiation of IVF with PGD solely for sex selection was strongly discouraged.

What is the future of PGD? What is yet to come?

PGD is rapidly advancing with improvements in accuracy and availability. More and more genetic disorders will be able to be diagnosed. New techniques are being developed that will allow all the chromosomes from the embryos to be checked, improving the success rates of IVF.

PGD is an exciting technology that offers couples at risk an alternative to pregnancy termination of an affected fetus. PGD of aneuploidy has the potential to decrease miscarriage rates and possibly increase implantation rates. Further studies are required to demonstrate whether or not patients with repeat IVF failures, recurrent pregnancy loss, and advanced maternal age could benefit from routine application of PGD. Finally, PGD offers the promise to become an important tool in clinical IVF to select for transfer a single embryo with the greatest potential for implantation, thereby maximizing pregnancy outcomes and at the same time reducing the risk of multiple births.