PGD - PGD for Single Gene Defects


Pre-implantation genetic diagnosis (PGD) for genetic disease consists of evaluating the status of an embryo with regard to a known specific genetic abnormality carried by one or both parents. A genetic abnormality in the parents may cause a specific disease or syndrome to occur in their offspring or may cause the pregnancy to miscarry. PGD can be accomplished as part of the in vitro fertilization (IVF) process, commonly used to treat infertile couples. But, in this case, the embryos are tested for the presence or absence of the abnormality prior to transfer into the uterus (IVF-PGD).


Couples planning to have a child may be aware of a genetic problem which one or both of them carry. A large number of genetic diseases can be screened for with IVF-PGD. These include cystic fibrosis, Tay-Sachs, muscular dystrophy, Huntington's Disease and many hundreds more. The couple may be aware of the need for genetic diagnosis in one of several ways:

  • One of the couple or a family member may have a genetic disease and one or both of the couple have tested positive for the genetic abnormality.
  • One or both of the couple may have tested positive in a screening test done based on their ethnicity, such as cystic fibrosis in Caucasians or Tay-Sachs in Ashkenazi Jews or a comprehensive screening test.
  • The couple may have a child or other family member who needs compatible stem cells to save that family member's life. In this case, embryos that possess a desirable genetic trait, such as a tissue type that matches an ailing sibling or other family member can result in a child to provide cord blood stem cells.
  • The mother may be a known carrier of an X-linked disorder for which there is not yet a specific molecular diagnosis. In this scenario, PGD can be used for gender selection of a female embryo. Theoretically, half of male embryos would be affected, so that only female embryos will be utilized for the hoped for pregnancy.


Two sophisticated technologies are combined to help parents who carry a genetic defect prevent the passage of that defect to their offspring.

For almost four decades, infertile couples have taken advantage of in vitro fertilization (IVF) to help create their families. One of the latest advances in this reproductive technology is pre-implantation diagnosis (PGD). This technology allows doctors to select embryos free of a specific genetic problem in order to create healthy babies. This has evolved after complete mapping of the human genome identified the location of over 1,000 genetic diseases. Now scientists have the ability to create probes to find a specific genetic problem in as little as a single cell.

Until recently, if a couple was aware of a disease caused by a single gene defect in their family, all they could do to prevent the birth of an affected baby was prenatal diagnosis in the already pregnant woman with amniocentesis or chorionic villus sampling (CVS). These procedures can detect the presence of the abnormal gene in the fetus, but if present, the only alternative to having an abnormal child is to abort the pregnancy. Now with IVF and PGD, embryos can be screened in the laboratory for a specific genetic disease and only embryos not affected with the condition in question are transferred into the mother. This can prevent the disease caused by the genetic defect from being transmitted to their child.

What sort of genetic defects can be detected by IVF-PGD?

Inherited single gene defects fall into three general categories:

  • Autosomal recessive
  • Autosomal dominant
  • X-linked


The initial part of the IVF cycle is carried out in the same way as for infertility and consists of five basic steps:

  • Ripening of the eggs
  • Retrieval of the eggs
  • Fertilization of the eggs and growth of the resulting embryo(s)
  • Biopsy of the embryos and PCR to screen the embryos for the abnormal gene and CGH to determine its chromosome component
  • Freezing of the embryos to get the test results and transferring unaffected embryos in a frozen embryo cycle (FET).
    (In some cases it is possible to get the results quickly and transfer on Day 6 of the fresh cycle)

The most common PGD protocol used today is to biopsy the embryo on the fifth day (trophectoderm-precursor of the placenta biopsy) after the egg has been fertilized. Our embryologist removes a few cells from each multi-celled embryo (> 100 cells). The biopsied cells are specially prepared and couriered to the genetics laboratory.

The genetics laboratory amplifies the DNA so that the gene in question can be assessed. The error rate is very low but it is not zero, so amniocentesis is recommended. The error rate appears to be lower with day 5 (trophectoderm biopsy) because multiple cells are analyzed.

Because of the time it takes to do the analysis, this most often requires freezing of the embryos by vitrification and later transfer in a frozen embryo cycle. In some cases it is possible to get the results quickly and transfer on Day 6 of the fresh cycle.


Considering that the determination of the well-being of an embryo is being made on the basis of a tiny amount of DNA and the results are being interpreted very rapidly, the estimated misdiagnosis rate of about less than 1% for single gene defects is remarkably low.

A misdiagnosis may occur if the biopsied cells are not representative of the major cell line in that embryo. In other words, not all the cells in an early embryo may be identical. The medical term for this is mosaicism. Another obvious concern is the possibility of injury to an embryo during the biopsy procedure leading to decreased success rates, which should be much less likely with the Day 5 biopsy. Other concerns include unanswered long-term health consequences of IVF-PGD for the mothers and resulting children, as well as the risk of multiple pregnancies posing additional potential risks to the mother and offspring.


The alternative to IVF-PGD is for a couple to achieve a pregnancy naturally, or through conventional fertility treatment, and to rely on prenatal diagnosis through chorionic villus sampling (CVS) or amniocentesis using similar molecular diagnostic techniques. With these techniques, more material can be sampled from a pregnancy and more time taken for interpretation. Misdiagnosis may also occur, but less frequently than with PGD. However, the only options for the couple at this time are either giving birth to a child with the defect, or termination of the pregnancy.

In PGD cases, amniocentesis is recommended to confirm the accuracy of the PGD diagnosis.