Preimplantation genetic diagnosis (PGD) involves screening 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 those interested in defining chromosomal normalcy prior to implantation, 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 normal embryos, so they can be transferred increasing the chance of pregnancy significantly.
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 can be applied to any blastocyst embryo produced during an IVF cycle. We anticipate 30% chance of all embryos in women less than 35 years will be chromosomally abnormal. PGS can define normal embryos, and thus, the patient does not need to undergo multiple embryo transfer cycles.
The accuracy, sensitivity and specificity for these techniques are nearly 98%. Currently, because there exists the possibility of error, PGD & PGS is not considered a replacement for prenatal testing.
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 obtaining a diagnosis on a biopsy also exists, although, at the Fertility Centers of New England this risk is less than 1%. Misdiagnosis is also a possible risk of PGD and PGS. Although unlikely, it is possible that one cell in the embryo may have different chromosome numbers than the other cells in the biopsy. 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) is required.
Representative cells removed from embryos at the blastocyst stage of development on day 5 (or day 6) of culture. Embryos that have not developed to the blastocyst stage of development can not be used for PGD. The biopsied cells are then transferred to a small tube for PGD analysis. Once the biopsy is performed, the embryos are vitrified (frozen) and stored in our facility 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. 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 and next generation sequencing to screen for all 22 pairs and the sex chromosomes. The results are reported back to us in approximately 10 days.
The physician and the embryologist review the PGD/PGS results with the patient. As these embryos are blastocysts (day 5 embryos), they will be transferred during a frozen embryo transfer cycle in a simulated cycle. The endometrium is prepared and monitored and most often progesterone is admistered for final preparation for implantation. The selected, cryopreserved embryo is thawed and assisted hatching is performed. Assisted hatching allows the embryo to free itself from the protective zona shell, which is necessary for implantation. The embryo is then guided into the uterine cavity via ultrasound to maximize implantation efficacy.
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.