Preimplantation genetic diagnosis (PGD) involves screening single cells from embryos for genetic diseases and chromosomal disorders. This testing is performed with in-vitro fertilization (IVF) and occurs prior to embryo transfer, before a pregnancy is established. PGD offers at-risk couples the opportunity to select embryos for transfer based on their genetic and chromosomal status. The goal of PGD is to identify abnormal embryos so they will not be transferred, leaving unaffected embryos to be selected for transfer that are more likely to make healthy, disease-free babies.
PGD can identify the presence of chromosomal translocations (rearrangements of parts of chromosomes) and single-gene disorders (genetic diseases that are the result of a single mutated gene). There are over 4,000 single-gene disorders. The most common diseases tested for are Cystic Fibrosis, Tay Sachs, Fragile X, Myotonic Dystrophy and Thalassemia.
PGD technology can also be used to determine the sex of the embryo prior to the transfer into the uterus. Sex selection is offered to couples interested in family balancing who already have at least one child.
What is Preimplantation Genetic Screening (PGS)?
For those people with recurrent pregnancy loss or infertility, PGS applies the technology from PGD to improve their chances for a successful pregnancy. Embryos are screened for aneuploidy (missing or additional numbers of chromosomes), which is a leading cause of miscarriage and implantation failure (failure of the embryo to implant into the uterus). The goal of PGS is to identify chromosomally abnormal embryos, so they will not be transferred leaving the chromosomally normal embryos to be transferred in the attempt to achieve a successful pregnancy.
Who should have PGD and PGS?
PGD is an extremely useful tool for couples in which one or both of the partners are carriers of an inherited genetic disorder. Depending on the inheritance pattern of the disease, the risk of creating an affected child can be as high as 50%. PGD significantly reduces this risk.
PGS, on the other hand, may only be beneficial for a specific population of patients. This includes patients of advanced maternal age and women with a history of recurrent pregnancy loss. Patients must have a large number of good quality embryos in order for PGS to improve their outcome.
What are the risks of PGD?
The largest risk of PGD is not having embryos available for transfer and/or a negative pregnancy test. The results of the PGD procedure may show that all of the embryos are abnormal. In these circumstances, no embryos are transferred and the cycle is cancelled.
There is a small (0.1%) risk that the embryo may be damaged during the biopsy procedure. The risk of not getting any diagnosis on a biopsied cell also exists, although, at the Fertility Centers of New England this risk is less than 1%. Misdiagnosis is also a possible risk of PGD. Although rare, it is possible that one cell in the embryo may have different chromosome numbers than the other cells. This is referred to as mosaicism and will result in a misdiagnosis due to the fact that the information from the biopsied cell is not reflective of the entire embryo. Because PGD is the diagnosis or screening of an embryo based on the results from a single cell, there are limitations involved in using this technology, and PGD is not considered a replacement for prenatal testing.
The PGD Process
If PGD is recommended and you decide to proceed with PGD, you will work closely with our Fertility Centers of New England PGD coordinator. You will need to have the same lab work and tests performed as required for an IVF cycle. You and your partner may also need to have your blood drawn in order to make DNA probes from which to test the cells. A genetic counselor from one of our referring centers will meet with you to answer all your questions and discuss your specific case, the PGD procedure, and your options. A representative from our insurance department will also work with you in order to determine if PGD is a covered benefit under your insurance policy.
PGD is performed in conjunction with IVF. Patients will undergo ovarian hyperstimulation, oocyte retrieval and IVF in order to produce the maximum number of embryos that can be evaluated. Intra-cytoplasmic sperm injection (ICSI) may also be required.
A single cell is removed from embryos at the 6-8 cell stage on day 3 of culture. Embryos that have not developed to the 6-8 cell stage on day 3 do not continue to grow after having a cell removed and are therefore not used for PGD. The biopsied cell is then either fixed to a slide or transferred to a small tube for PGD analysis. In some cases, embryo biopsy may not be performed until Day 5 following fertilization. If Day 5 biopsy is performed, then the embryos may be frozen for later transfer once the results of the biopsy are known.
The biopsied cells are sent to one of our referring cytogenetic laboratories to be analyzed. Florescent in-situ hybridization (FISH) is used for PGD for translocations, sex selection and some types of aneuploidy screening. FISH uses fluorescent markers that are able to locate and evaluate the chromosomes from the biopsied cell. Polymerase Chain Reaction (PCR) is used to identify single gene disorders. PCR is used to amplify the DNA from the single biopsied cell to identify the mutant gene sequence. PGS will be performed for some patients using new emerging techniques such as CGH or microarray analysis to screen for all 24 chromosomes. The results are reported back to us within 48 hours.
The physician and the embryologist review the PGD/PGS results with the patient. The embryo or embryos are then selected and prepared for transfer. Embryo transfers for PGD/PGS patients always occur on Day 5 of culture to allow time for the screening process. In cases where embryo biopsy occurred on Day 5 following fertilization, the embryos may be frozen for later transfer once results are known.
Many factors go into making a successful pregnancy. Your chance of a successful pregnancy will depend upon your age, the number and quality of your embryos, the results of the biopsies, and other fertility-related factors based on your individual situation. While pregnancy success cannot be guaranteed, in general, a 30% to 70% success rate may be expected (depending on your individual circumstances) related to having PGD/PGS.