Preimplantation genetic diagnosis (PGD) is a treatment that allows for genetic testing of embryos prior to embryo transfer. Classically PGD is used for couples with a family or personal history of a genetic disorder, however, newer techniques referred to as preimplantation genetic screening (PGS) are available to assist chromosomally normal couples with embryo selection prior to embryo transfer.
In PGD and PGS, an embryologist removes one or two cells from each embryo created in the IVF cycle. These embryo biopsies are performed with a laser mounted in a microscope on day 5 or day 6 of embryo growth. The cells are tested for the number of chromosomes and for any abnormal genes. While we await genetic testing results, the embryos are cryopreserved. Selection of the embryo(s) to transfer into the uterus can be determined after the test results by knowing which embryo(s) are normal.
PGD was originally developed to help couples with a family history of genetic disease. As PGD has become more refined we have found that PGS is increasingly beneficial to couples with all forms of infertility including recurrent pregnancy loss and repeat IVF failure.
At its most basic level PGD and PGS are ways to select which embryos should be transferred back to the uterus in an IVF cycle. Over the last 30 years we have relied primarily on embryology labs to help determine which embryos to transfer based upon their cell number and developmental patterns. Over the last 30 years monitoring embryo growth with a microscope has proven to be successful in embryo selection and is the typical way IVF cycles are performed.
The new application of PGS allows us to biopsy all embryos that are growing normally to determine how many chromosomes they have. Studies have shown that up to 40% of all embryos that look normal under a microscope are in fact chromosomally abnormal and will result in a negative pregnancy test, early miscarriage or rarely, an abnormal baby. Accordingly the use of PGS in some patients appears to help with embryo selection and pregnancy rates.
The use of PGS in an IVF cycle is to enhance embryo selection in those patients who are likely to have a high number of embryos available for transfer. PGS also appears to help patients with a history of recurrent pregnancy loss, repeat IVF failure, or those patients above 40 years of age who are at increased risk of having abnormal embryos. In the right patient, the use of PGS increases pregnancy rates and lowers miscarriage rates.
PGS is invasive, adds cost, and is definitely not for everyone. PGS should be applied individually based on a couple’s risk factors. For patients who are younger and have a lower chance of having abnormal embryos there is not as much advantage to the use of PGS. It also may not be helpful in those couples who have a low number of eggs and embryos as conventional embryology techinques can help determine which embryos should be transferred.
At Coastal Fertility Specialists (CFS) we strongly feel that each patient is a unique individual and as a result deserves an individualized treatment plan. Part of that plan is to help determine if PGD or PGS will improve your success rate. Your CFS physician will make a recommendation and we will then allow you to make the decision that is right for you.
One of the biggest risks to PGD and PGS is damage to the embryo from the biopsies or embryo cryopreservation. PGD and PGS require the removal of one or two cells from each embryo. Coastal Fertility Specialists is using newer biopsy techniques which includes a biopsy of only the placental cells of the embryo with a laser on day 5 or day 6 of growth which results in significantly less embryo harm. The biopsied embryos are then cryopreserved with newer freezing techniques called vitrification and transferred back into the uterus two to three weeks later.
Another risk to PGD is incorrect results. Incorrect embryo results can occur in a small percentage of cases due to the very small amount of DNA being analyzed.
The first step is to speak with your doctor to determine whether PGD or PGS is appropriate for you. Just as in a normal IVF procedure, the next step is the administration of medications to create eggs followed by the retrieval of the eggs. The eggs are then fertilized with sperm and the embryos are allowed to grow for three days. At this time the embryos are typically six to eight cells.
The next step is the embryo biopsy. The embryologist on day 3 of embryo growth uses a laser that works through the microscope to make a small opening in the outer membrane of the embryo, the zona pellucida (see picture at right). This is a similar process to assisted hatching. The embryo is allowed to grow to the blastocyst stage (day 5 or day 6) at which time the embryologist gently removes one or two cells out of the embryo through the hole. These cells are then tested for genetic abnormalities. While we await results the embryos are cryopreserved with a new freezing process called vitrification and later transfered back into the uterus two to three weeks later.
In most cases, all the cells of an embryo will have the identical genetic makeup. Therefore, the tested cells will show the genetics of the remaining, viable embryo. The remaining cells of the embryo are young enough that they will form a complete, normal fetus.
Women over 40 are more likely to have eggs with an extra or missing chromosome (aneuploidy). In these cases, the laboratory will examine the cells to count the chromosomes that usually lead to severe birth defects.
Each human chromosome has 22 pairs of chromosomes, except the X and Y chromosomes that determine gender. In PGS the biologist uses a technique called DNA microarray technology to detect the presence of each of the 24 chromosomes within the cells to help ensure the embryo has the correct number of chromosomes. For couples with a family history of a disorder, the laboratory will test for the specific defect. The laboratory must first test cells from the parent who has the disorder or may be a carrier to determine the exact defect. The embryo cells are then tested in a process that uses PCR to see if they contain that exact defect. The test doesn’t reveal other genetic defects.
After the tests are completed the best embryos without the defect are transferred into the woman’s uterus as in a standard frozen embryo transfer cycle.