There are two types of genetic testing that can now be performed on embryos prior to an embryo transfer into the uterus. An embryo is what is formed after the sperm fertilizes the egg. The first type of testing is termed pre-implantation genetic screening (PGS) and is performed on a number cells obtained from an embryo. When the biopsy is performed on day five of embryonic life anywhere from five to ten cells are removed. The goal of this testing is to identify a chromosomally abnormal embryo in couples known or presumed to have normal chromosomes. This allows for the selection of only those embryos with normal chromosome numbers for embryo transfer. Usually there are 46 chromosomes in an embryo. There are two sets of chromosomes one through twenty-two and then either two X chromosomes (a female) or one X and one Y chromosome (a male). For example, if an embryo had three chromosome twenty-ones as opposed to two, the embryos would have what we call trisomy 21 or Downs Syndrome. Theoretically, avoiding transfer of chromosomally abnormal embryos, like an embryo with trisomy 21, will reduce the risk of pregnancy failure and improve the probability of conceiving a normal pregnancy. The primary patients for whom this approach is considered are women with the highest risk of having embryos that are not chromosomally normal, such as women over age 35 or those who have had multiple in vitro fertilization (IVF) failures or recurrent pregnancy losses. However, PGS has also been promoted to help with embryo selection in general. The second type of genetic testing performed on the embryos prior to an embryo transfer into the uterus is termed pre-implantation genetic diagnosis (PGD) and is performed on a number of cells obtained from an embryo. The goal is to establish a pregnancy that is unaffected by a specific genetic defect, such as a condition with a known genetic mutation (e.g., Cystic Fibrosis) or chromosomal abnormality (e.g., translocations) carried by one or both biological parents. It is also used to select embryos for transfers that have specific characteristics, such as a particular gender. When pre-implantation genetic testing is planned, assisted reproductive technology (ART) must be used for conception even if infertility is not an issue for the couple. ART is expensive, invasive, and associated with risks, such as ovarian hyperstimulation syndrome, multiple gestations and risks to singleton gestations that occur more often than in natural conceptions.
When the plan is for PGS, taking a biopsy of more than one cell from a day five embryo is the technique that is used. We are performing day five biopsies in our laboratory and we either send these cells to a specialized genetic laboratory for testing using comparative genomic hybridization (CGH) or perform it in our laboratory. CGH examines all 24 chromosomes, the 22 non-sex chromosomes and the two sex chromosomes X and Y. This technology uses what is called a microarray to compare DNA in the embryo to a known normal control using tens of thousands of genetic markers throughout the human genome. The results are in the format of a computer generated chromosome map for each embryo that is ready for the physician prior to the embryo transfer. There is now a newer technique, in lieu of CGH, that has been recently validated that is termed next generation sequencing (NGS). If you are moving forward with this testing, or with testing for a specific genetic defect, PGD, the cells that are biopsied are sent out to a specialized genetic laboratory for testing. Without using these technologies, we choose embryos based on how they look to the embryologist as opposed to a formal genetic analysis. There are disadvantages as well to genetic testing of the embryos in that it cannot detect all abnormalities in the chromosomes. Therefore we do still recommend testing in pregnancy like a chorionic villus sampling (CVS) or amniocentesis to confirm the results. Even though this technology is still in its earlier stages, it holds a lot of promise to be a tool to help select the best embryos for transfer into a woman’s uterus and is available now here at our center!