Pre-Implantation Genetic Screening (PGS)

In Pre-Implantation Genetic Screening (PGS), the testing seeks to identify embryos with chromosomal abnormalities that sporadically occur in a proportion of all embryos. PGS is not based on a known genetic or chromosomal abnormality, but the fact that a certain proportion of embryos will form imperfectly—note that these imperfections most often will be lead to miscarriages—and are most frequently age-related in both men and women. In both Pre-Implantation Genetic Diagnosis (PGD) and PGS, the normal embryos are then selected for embryo transfer.

Age-Related Chromosomal Abnormalities in Women

In addition to a decline in the number of eggs, reproductive aging also results in a higher percentage of chromosomal abnormalities in the remaining eggs. These chromosomal abnormalities impact fertility by decreasing the overall chance for fertilization of the egg and increasing the chance for miscarriage if a pregnancy occurs. The following graph compares the 2007 national average for the percentage of miscarriages using fresh non-donor eggs in IVF to the percentage of chromosomal abnormalities found in eggs for one specific study with respect to the women’s ages. In both graphs, miscarriage and chromosomal abnormalities increase with age with an acceleration around age 35.

As a woman ages, the chance of conceiving a child with a survivable chromosomal abnormality increases. The following graph presents the risk of Down’s syndrome, the most common chromosomal abnormality, and the risk for all chromosomal abnormalities in newborns (live births). The graph shows that the risk of chromosomal abnormalities accelerates as the maternal age increases.

In fact, many obstetricians offer a variety of tests during pregnancy to assess for chromosomal abnormalities of the fetus. These tests may include amniocentesis, early blood screening, chorionic villus sampling, and ultrasound evaluations of the fetus for signs of abnormalities. Amniocentesis is the test in which the amniotic fluid surrounding a fetus is sampled and then tested for chromosomal abnormalities.

Pre-Implantation Genetic Screening (PGS)

There are currently three basic methods to perform genetic testing of an embryo: fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), and recently, microarray technology. In 2008, the ASRM Practice Committee opinion concluded that although current studies of PGS using FISH with IVF did not improve birth rates, improvements in the technology, such as the development of more accurate genetic technology, might yield a different result in the future.¹

Until 2009, PGS using FISH technology could test roughly half of the chromosomes for one cell. The untested chromosomes could be abnormal, however, thus limiting the accuracy of the tests. Recent advances called microarray have enabled testing of all 24 chromosomes. The microarray approach has led to an exciting advance in pre-implantation genetics called Parental Support™ technology, introduced by the Gene Security Network (GSN) in 2009. The power of this technology not only assesses the 24 chromosomes, but if there is an abnormality, the source can be attributed to the maternal or paternal contribution.

The first live birth with Parental Support™ technology occurred in 2009. A clinical trial was announced in February of 2010, seeking to validate that this technology increases IVF live birth rates. Our experience at FSMG supports the hypothesis that IVF with PGS using Parental Support™ technology improves pregnancy rates.

IVF with PGS

Couples who have an increased risk of chromosomally abnormal embryos as indicated by advanced maternal age, recurrent pregnancy loss, or repeated IVF failure may be recommended to pursue IVF with PGS. One of the predictors of success with this treatment is the number of embryos available to test with PGS. As maternal age increases, the number of embryos that are obtained from each IVF cycle decreases. Dr. Morales has developed a case rate that combines two IVF cycles with one genetic screening (PGS). The embryos made on the first IVF cycle are vitrified (rapidly frozen). During the second IVF cycle, those embryos from the first cycle are thawed and added to the fresh group of embryos in the second cycle. All of the embryos are then biopsied and sent for analysis (PGS). Chromosomally normal embryo(s) are selected for transfer. The remaining embryo(s), if any, are then vitrified for future use.

With a greater understanding of their genetic predisposition, couples now have the answers they need to decide whether to continue to pursue a genetic child, to pursue other reproductive options such as egg or sperm donation, or to obtain closure with respect to using their own sperm/eggs. Please schedule an appointment if you would like to meet with a physician to discuss this new technology with respect to your reproductive health and goals.

The PGS Process

PGS is performed on the third day after the egg retrieval, when the embryos are at the 6–10 cell stage of development. The procedure includes:

1. An opening is made on the outer covering of the embryo (zona pellucida), and then one or two cells of the embryo are removed using micromanipulation pipettes and gentle aspiration.
2. The cells are then sent to an outside laboratory that performs the analysis on the DNA (genetic material) of the cell, which usually takes one day.
3. The results are reviewed and then a transfer of non-affected embryos is performed on Day 5 or 6 (a blastocyst transfer).

The main advantage of PGS is that affected embryos are identified and only non-affected embryos are placed back in the uterus. PGS does not detect all genetic abnormalities, as stated above, and there are still genetic risks that may occur spontaneously (without known cause) during the course of your pregnancy. Performing PGS, therefore, cannot guarantee that your embryos are genetically normal. Prior to undergoing PGS, detailed counseling and informed consents are required if you want to use this form of technology.

References

¹ Pre-implantation genetic testing: a Practice Committee opinion, Fertil Steril 2008; 90:S136-43.