PGS - PGS for Chromosomes

PREVENTING A CHROMOSOMAL PROBLEM IN YOUR BABY THROUGH PRE-IMPLANTATION GENETIC SCREENING

Pre-implantation genetic screening (PGS) 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 syndrome to occur in the offspring or may cause the pregnancy to miscarry. PGS 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-PGS). Since it is not possible to test all chromosomes, it is more accurate to use the term pre-implantation genetic screening rather then pre-implantation genetic diagnosis.

WHEN IS IVF-PGS APPROPRIATE?

There was a great deal of enthusiasm for PGS when it was first developed. Unfortunately it has not lived up to expectations and, in fact, leads to lower overall IVF success rates. Experience has shown that the value of PGS is very limited. According to guidelines from the American Society for Reproductive Medicine, available evidence does not support the use of PGS for the following indications:

  • To improve live birth rates in patients with advanced maternal age
  • To improve live birth rates in patients with previous implantation failure
  • To improve live birth rates in patients with recurrent pregnancy loss
  • To reduce miscarriage rates in patients with recurrent pregnancy loss related to chromosomal abnormalities (aneuploidy)

Gender selection of a female embryo through PGS is an appropriate strategy in the rare case 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, PGS can be 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-PGS DEVELOPED?

For almost three decades, infertile couples have taken advantage of in vitro fertilization (IVF) to help create their families. Now scientists have the ability to create probes to find a chromosomal problem in as little as a single cell. This technology has the potential for doctors to select embryos free of that specific chromosomal problem in order to create healthy babies.

If a couple has an increased risk for aneuploidy, all they can do to prevent the birth of an affected baby is 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. For those who would not consider pregnancy termination, PGS may be an acceptable alternative. Even though with IVF and PGS, 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, experience has shown that this does not improve live-birth rates.

HOW IS IVF-PGS 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 twelve 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 PGS in the near future.

It takes 24-48 hours to do PGS. 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-PGS?

Considering that the determination of the well-being of an embryo is being made on the basis of the evaluation of up to 12 (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 which leads to lower success rates in PGS cases. Other concerns include unanswered long-term health consequences of IVF-PGS 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-PGS?

The alternative to IVF-PGS 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 PGS. 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 PGS cases, amniocentesis is recommended to confirm the accuracy of the PGS diagnosis.