Pre-implantation genetic diagnosis (PGD) can evaluate the status of an embryo with regard to its chromosomal makeup. An abnormality in an embryo’s chromosomal configuration may cause a specific disease or syndrome to occur in the offspring or may cause the pregnancy to miscarry. PGD is 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 specific chromosomal abnormalities prior to transfer into the uterus (IVF-PGD). Since it is not possible to test all chromosomes, 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 problem which prevents them from having a healthy baby. Certain individuals may have a greater risk of a chromosomal abnormality (aneuploidy), which may arise in egg or early embryo development. This application may be appropriate for those at greater risk for aneuploidy, such as:

• Older IVF patients
• Individuals who carry a fragment of chromosomal material in an abnormal location (translocation carrier)
• Couples who have experienced repeated early pregnancy loss
• Couples who have had a previous pregnancy or baby with a chromosomal abnormality
• Couples with multiple previous unexplained IVF failures.

Gender selection of a female embryo through PGD is an appropriate 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 WAS IVF-PGD DEVELOPED?

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). Now scientists have the ability to create probes to find a chromosomal problem in as little as a single cell. This technology allows doctors to select embryos free of that specific chromosomal problem in order to create healthy babies.

Until recently, if a couple had an increased risk for aneuploidy, 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 chromosome 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 chromosomal problem and only embryos not affected with the condition in question are transferred into the mother. This prevents the disease caused by the chromosomal defect from being transmitted to their child.

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 embryos

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 chromosomes representing that embryo, is specially prepared and couriered to the genetics laboratory.

At a specialized genetics center, fluorescence in situ hybridization (FISH) is the technique used that allows direct visualization of specific chromosomes to determine the number or absence of chromosomes. This technique is most commonly used to screen for aneuploidy, gender determination, or to identify chromosomal translocations. However, FISH can currently detect abnormalities in only up to nine chromosomes including the sex chromosomes.

A newer technique for identifying chromosomal aberrations involves comparative genomic hybridization (CGH), in which pre-amplified DNA from a single test cell and a control sample are labeled with different dyes and then compared. CGH may have the advantage of being able to examine all chromosome pairs present in a single human cell. More rapid versions of CGH may allow its use in PGD in the near future.

It takes 24-48 hours to do PGD. Once this information is relayed to your physician, this allows for embryos free of the specific chromosomal abnormality, 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 the evaluation of nine (of 23) chromosomes in one cell of a six to eight cell embryo and the results are being interpreted very rapidly, the estimated misdiagnosis rates of about less than 10% for aneuploidy is remarkably low.

A misdiagnosis may occur if the cell removed 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".