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). Since it is not possible to test for all genetic defects, it might be technically more accurate to use the term pre-implantation genetic screening.

WHEN IS IVF-PGD APPROPRIATE?

Couples planning to have a child may be aware 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
• 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.

HOW WAS IVF-PGD DEVELOPED?

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

For over twenty-five years, infertile couples have taken advantage of in vitro fertilization (IVF) to help create their families. The latest advance 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 1000 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 prevents 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

When either the mother or father is a known carrier of a dominant or recessive genetic defect, they can undergo PGD to find embryos harboring the defective gene. While there is a growing list of single genetic defects for which molecular diagnosis is possible, common indications today include cystic fibrosis, Tay-Sachs, B- thalassemia, muscular dystrophy, and Huntington's disease.

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Gender selection of a female embryo is another strategy when the mother is a known carrier of an X-linked disorder for which there is not yet a specific molecular diagnosis. In this scenario, PGD is used to identify the male embryos, half of which would be affected, so that only female embryos will be utilized for the hoped for pregnancy.

HOW IS IVF-PGD PERFORMED?

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

• Ripening of the eggs
• Retrieval of the eggs
• Fertilization of the eggs and growth of the resulting embryo(s)

On the third day after the egg has been fertilized, our embryologist removes a single cell from each multi-celled embryo (6-8 cells). The biopsied cell, containing the DNA representing that embryo, is specially prepared and couriered to the genetics laboratory.

At a specialized genetics center, testing for single gene defect requires testing the cell’s DNA for the single gene mutation using uniquely designed genetic probes. For those with a sex-linked disorder for which there is not a specific probe, a technique called FISH (fluorescence in situ hybridization) is used to identify the presence of a Y or second X chromosome to determine the sex of the embryo.

It takes 24-48 hours to do PGD. Once this information is relayed to your physician, this allows for embryos free of the specific disease in question, or the desired sex, to be transferred into the female partner’s uterus on day 5. Other normal embryos, which reach appropriate maturity by day 5 or 6, can be frozen (cryopreserved) for future use.

HOW SAFE AND ACCURATE IS IVF-PGD?

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 cell is not representative of the major cell line in that embryo. In other words, not all the cells in an early embryo are identical. The medical term for this is mosaicism. Another obvious concern is the possibility of injury to an embryo during the biopsy procedure. 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.

WHAT IS THE ALTERNATIVE TO IVF-PGD?

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.

ABOUT REPRODUCTIVE PARTNERS

The physicians and staff at Reproductive Partners Medical Group, Inc. have been helping couples achieve their dream of completing their family for over 20 years and are responsible for thousands of births resulting from assisted reproductive technology. At Reproductive Partners, we offer comprehensive evaluation and practical treatment of all aspects of infertility care in five locations throughout Southern California .

Reproductive Partners is nationally recognized for their pioneering work in helping infertile couples. The physicians and our IVF Program are considered one of the best by publications such as PEOPLE Magazine, Redbook's "Outstanding Fertility Centers," Good Housekeeping's "Best Doctors for Women," Center for the Study of Services' "Guide To Top Doctors," and Castle Connolly's "America's Top Doctor's Guide".