Pre-implantation Genetic Diagnosis- PGD
Genetic Testing Yields Higher Success Rates
One of the most exciting innovations in the field of Reproductive Medicine is the ability to know the genetics of a fertilized human egg prior to conception. This technology is called Preimplantation Genetic Diagnosis, or PGD. This scientific breakthrough has allowed for improvement of pregnancy rates with In-Vitro Fertilization (IVF), a reduction in miscarriage and the preconceptual diagnosis of genetic disease. The result of this advanced fertility care is the improved chance of couples achieving a successful outcome in their journey to have a child and build a family.
When To Consider PGD
- Improving IVF outcome - IVF has emerged as the best treatment for the age-related decline in female fertility due to reduced egg number and quality as women age. Through an understanding of the genetic normalcy of the human fertilized egg, or embryo, we can achieve dramatically improved pregnancy and take- home baby rates by transferring back to the woman’s uterus a single normal embryo after genetic testing. This ability to transfer one embryo back after IVF and genetic testing has also dramatically reduced the rates of twins and higher levels of multiple births.
- Reduction in miscarriage - A reduction in spontaneous abortion, or miscarriage, especially in couples with a history of recurrent losses, is also an important and successful function of PGD. Given that chromosomal abnormalities are a major cause of both sporadic and recurrent miscarriage, we can reduce miscarriage by transferring back only chromosomally normal embryos. This is especially true when either the man or woman is a carrier for a genetic chromosomal abnormality such as a translocation (mismatched number of chromosomes), which is an additional risk factor for pregnancy loss. The embryo transfer of even a single normal embryo can reduce the chance of miscarriage and increase likelihood of take- home baby from the IVF treatment.
- Diagnosis of genetic disease - PGD can also be helpful to diagnose genetic disease in the situation where the man or woman is a carrier for a specific genetic disease. The most common situation is that of a person being a carrier for disease such as Cystic Fibrosis, a potentially life-altering and fatal disease for the child who born with this condition. In the situation where both parents are carriers of this type of genetic condition, called Autosomal Recessive Inheritance, there is a 25 % likelihood of the child having this condition. PGD can diagnose this condition prior to conception, with the goal to only transfer embryos that are genetically normal and therefore not produce a child that is affected with this disease. Likewise, PGD can help to prevent the delivery of a child with an age- related genetic disease, such as Trisomy 21, ( Down Syndrome), or even more serious chromosomal disease, with the transfer of only normal embryos to the woman’s uterus after genetic testing. A normal embryo produced as part of an IVF/ PGD cycle may also help to guide decision-making regarding whether to perform invasive pregnancy testing such as amniocentesis or Chorionic Villus Sampling (CVS). This type of PGD, for the diagnosis of genetic chromosomal abnormality, been recently re-termed Preimplantation Genetic Testing- Aneuploidy (PGT-A)
- Gender Selection - while not generally the primary indication for PGD, gender selection with current generation PGD technology is essentially 100 % accurate. Family Balancing, in which a couple has one gender at home and wants to achieve a specific gender, may be an important part of their clinical decision- making for their reproductive care. There may be cultural/social factors as well that prompt a couple to pursue gender selection.
Performing PGD with IVF
Prior to decision regarding proceeding with PGD as part of an IVF, the couple is counselled regarding the medical indications, logistics and financial aspects of this level of medical care. Each of these counseling steps is critical to the best standards for optimized medical care. The type of PGD is discussed, and the couple is given a full and complete disclosure regarding these issues. The PGD testing generally takes place on day 5 or day 6 of growth, or culture, of the fertilized embryos (Blastocyst), after fertilization in the Embryology laboratory. As part of the PGD, the Embryologist uses laser to open the human egg shell (Zona Pellucida), in order to sample a minute piece of tissue of the embryo. In experienced this does not harm the embryo and is a necessary part of the testing process. The tissues are then prepped and sent to an outside testing laboratory for analysis. Each of the embryos tested is then cryopreserved (frozen), pending the results of this analysis. Generally, it does take approximately 5-7 days after testing to get results back from the outside lab, at time a consultation is made with the couple regarding next steps. This consultation will review steps to either proceed with frozen embryo transfer, or to consider another IVF stimulation and retrieval. Some couples do decide to bank embryos as part of their reproductive journey or elect to proceed with another IVF stimulation if the PGD results are not favorable.
As PGD as evolved over the last 20 years, we are seeing tremendous improvement in reproductive outcomes. Prior high error rates with older technology (FISH- Fluorescent In-Situ Hybridization), has been replaced by much more accurate DNA- Based Technology. These new technologies, including array CGH (Comparative Genomic Hybridization), quantitative PCR (Polymerase Chain Reaction), SNP (Single Nucleotide Polymorphism), and the new technology of NGS (Next Generation Sequencing), have revolutionized the field, and offered low error rates, and high success for successful single conception and take- home baby rates. These technologies offer new hope for success for couples struggling with infertility. This is especially true with the recent reduction in cost of PGD, as this treatment becomes more available and part of standard medical care. Given the high rates of success, with low miscarriage risks, as well as affordability, PGD has become the new paradigm to help couples finally achieve their dream of having a child and building their family.