This information letter is to update you on the current options available for pre- Implantation genetic screening (PGS). The use of PGS is in conjunction with in vitro Fertilization (IVF) to enable genetic testing of the Embryo.

The use of Assisted Reproductive Technology (ART) has revolutionized the treatment for male and female fertility. Since the first live birth of Louise Brown in 1978, millions of babies have been born using ART. The second major breakthrough in the field came with the discovery of ICSI or intracytoplasmic sperm injection. This technology allowed couples with severe Male Factor Infertility to conceive. The next largest breakthrough in the field was the technology associated with pre-implantation genetic testing. This allows for biopsy of the embryo and testing for either a single gene disorder, such as cystic fibrosis or sickle cell anemia, or Aneuploidy screening. It is this arena of ART that is rapidly expanding and uses cutting edge technology.

Blastomere biopsy from a day 3 embryo is one option for genetic screening. In most cases, a single blastomere is removed from an embryo containing at least 6 cells on day 3. The blastomeres are then tested concurrently while the embryo continues to grow and develop into a blastocyst. On day 5, only euploid embryos are transferred. Two things have to happen in order for an embryo transfer to occur. First, the biopsy has to return with normal results. Second, the embryo from which the cells were removed has to continue to grow and develop into a blastocyst. This is the traditional way that PGS has been performed. The technical aspects of embryo biopsy as well as optimal culture conditions to grow blastocysts are major impediments for many IVF programs in providing this technology. At FCI, we have experts in embryo biopsy and a lab that has an outstanding blastocyst culture medium placing our group in the forefront of medicine in offering this technology.

The actual methodology for chromosome testing for PGS is rapidly changing. The traditional method of screening chromosomes was through the use of Fluorescent In-Situ Hybridization (FISH). This technology relied on DNA probes that recognized the centromeres of a select number of chromosomes. One of the major criticisms of PGS with FISH was that it did not screen all 23 chromosomes and while embryos could be PGS normal, they may still be aneuploid. In addition, the technology relied on the ability to visualize the fluorescent probes and there are problems inherent in this visualization. As the field of genetics is rapidly expanding, much of the amazing technology is now able to be applied pre-implantation and used on blastomeres. One such test is microarray and we are now offering blastomere screening with the use of microarray platforms. The microarray chip enables testing of all 23 chromosomes with results in a timely fashion to allow for transfer on day 5. Day 3 testing, however, may not be as accurate as day 5 testing because of some characteristics inherent in day 3 embryos. For example, there is a significant percentage of mosaicism, or coexistence of separate cell lines, within a single day 3 embryo. If the aneuploid cell line is tested, the embryo may be misread as aneuploid and vice versa if the euploid cell line is tested the embryo may be misread as euploid. Mosaicism rates in day 3 embryos have been reported to be as high as 10%. In addition, it has been hypothesized that “self correction” occurs in day 3 embryos. In other words, the embryo may be aneuploid on day 3, but may self-correct to euploid discarding the aneuploid cells as growth continues. Therefore, we would be overcalling abnormals and discarding potentially euploid embryos.

To get around the inherent problems associated with day 3 embryo testing, one can biopsy the trophectoderm cells of a blastocyst. The rate of mosaicism and self-correction in blastocysts is markedly lower. In order for an IVF program to utilize this technology, the lab must have the ability to culture embryos to the blastocyst stage. The lab must also have personnel skilled in blastocyst biopsy. In addition, the lab must have the ability to freeze and thaw embryos without diminishing their implantation rate. Vitrification technology allows this to occur. FCI is a leader in the field of both blastocyst culture and vitrification, and thus, we are optimally positioned to move forward with this exciting technology.

Once the embryos are cultured to day 5, several trophectoderm cells are removed. Blastocysts are generally more resilient than day 3 embryos and are better able to tolerate biopsy. Furthermore, the cells destined to become theFetus (inner cells mass) are not disturbed. In addition, one can remove a greater number of trophectoderm cells and can obtain more DNA for more sophisticated testing methods.

The two new types of DNA testing that we are offering are microarray and comparative genomic hybridization (CGH). Both of these tests allow us to screen all 23 chromosomes. Microarray will be able to screen for single gene disorders in addition to aneuploidy.
The potential downside of this testing is that the embryo must be frozen while the testing is taking place. Currently, in 2010, the turnaround time for testing does not permit us same day or next day results. We therefore will biopsy the blastocyst then freeze it using vitrification technology. The patient then awaits results and once results return she would then undergo a frozen embryo transfer Cycle . It is therefore a two-step process. Preliminary data from the handful of centers that are currently offering this technology has shown that it is worth the wait with increased pregnancy rates and decreased Spontaneous Abortion rates.

As the field of genetics rapidly expands, and as we partner with our colleagues in the field, the options for pre-implantation genetic testing and screening will increase.

Should you have any further questions about ART or PGS please do not hesitate to contact me, or any Fertility Centers of Illinois physician, at any time. I hope this letter has helped to educate you on cutting edge technologies that we are using at FCI for pre-implantation genetic screening.