Genetic testing of embryos is a state-of-the-art procedure, which enables us to screen embryos for genetic diseases before the embryos are transferred into the uterus. The purpose of this is to decrease the likelihood of finding chromosomal abnormalities, once the patient is pregnant, during prenatal diagnosis with tests such as chorionic villus sampling, amniocentesis or fetal blood cell testing. In order for PGD to be performed a patient must undergo IVF.
There are 2 types of genetic testing:
Preimplantation Genetic Diagnosis (PGD):
In this procedure the embryos are tested for a specific disease such as:
- Chromosomal translocations (where parts of the chromosomes have been rearranged).
- Single-gene disorders where there is a mutation in a single gene. There are over 4,000 single-gene disorders. The most common diseases tested for are Cystic Fibrosis, Fragile X, Thalassemia, Sickle cell, and Huntington’s disease.
- Inheritable cancers such as BRCA1, which would increase the chance of passing the disease to your child.
- Sex selection for inherited diseases that are sex linked.
Preimplantation Genetic Screening (PGS):
- PGS tests for the overall total number of chromosomes present in the embryo. In this procedure the embryos are screened for aneuploidy, which is testing for missing or additional chromosomes. An example of this would be Down’s syndrome which consists of an extra chromosome 21. As women age, the egg quality decreases and as a result the incidence of chromosomal abnormalities in the eggs increases. Embryos with missing or extra chromosomes generally result in either a miscarriage or a baby with chromosomal abnormalities. In the past, embryo selection for transfer was based on the “look” of the embryo. However we know that this can be misleading as even “good looking” embryos can be aneuploid or abnormal. PGS has revolutionized the field as we now have a powerful tool to select the normal embryos in order to increase implantation and pregnancy rates.
Some of the patients who would benefit from PGD include:
- Couples where one or both partners are carriers of an inherited genetic disorder.
- IVF patients over the age of 35.
- Patients with diminished ovarian reserve, regardless of their age.
- Patients who have had 2 or more failed IVF cycles.
- Patients with multiple miscarriages.
- Couples interested in gender of sex selection.
At Fertility Institute of San Diego, we use the latest cutting-edge modalities in an attempt to provide the best service for our patients. The PGD is comprised of 2 steps:
- The first step is the embryo biopsy. We usually perform the embryo biopsy at the blastocyst stage of development (day 5 embryo). A laser is used to make an opening in the shell of the embryo and a trophectoderm biopsy is performed in which a few placental cells are removed. This is a very delicate procedure that could damage the embryo.
- The second step is the genetic testing. The cells that are removed are sent to our reference cytogenetic lab. At the present time we use the services of Dr. Mark Hughes in Detroit, Michigan at Genesis Genetics. The tests typically performed on the biopsied cells are either
- Polymerase Chain Reaction (PCR) in cases where a single gene is being assessed, or
- Next Generation Sequencing (NGS) which uses the latest technological breakthrough in whole genome sequencing to study chromosomes at a level which had not been possible before providing the most comprehensive and accurate screening of all 24 chromosomes.
As it normally takes up to 48 hours to receive these results, after the embryo biopsy is performed, the embryo is immediately frozen at the blastocyst stage. The normal embryos are transferred back in a subsequent frozen embryo transfer.
Some of the important things to keep in mind are that:
- PGD cannot screen for all genetic diseases.
- Normal results do not completely eliminate the risk of genetic diseases.
- It is possible for all of your embryos to be abnormal in which case a transfer cannot be performed and the cycle is cancelled.
- There is a very small risk (0.1%) that the embryo may be damaged during the biopsy procedure.
- Misdiagnosis due to a phenomenon called mosaicism is possible. This is because not all of the cells in an embryo are the same. In the past the vast majority of patients had biopsies performed on day 3 embryos where only one cell was removed. If this cell was the only abnormal one in an otherwise normal embryo, then an otherwise normal embryo would have been discarded. Conversely, if the one cell biopsied was the only normal cell in an otherwise abnormal embryo, an abnormal embryo would have been inadvertently transferred. This is why at the Fertility Institute of San Diego, we primarily perform the embryo biopsy on day 5 as on this day the embryo has hundreds of cells and it is possible to remove 5-10 cells for testing thereby minimizing the problem of mosaicism.
- PGD is not considered a replacement for prenatal testing.
What to Expect?
PGD is an intricate process, which requires several weeks of preparation. The 6-step process can be summarized as follows:
1. Preparation for PGD
Once the decision has been made to proceed with PGD, it will be necessary to complete the routine evaluation for an IVF cycle including the testing of the couples’ ovarian reserve, uterine cavity and sperm parameters. In addition, there may be the need to draw blood in order to make DNA probes to be able to test for a specific genetic disease. You will be given the opportunity to speak with a genetic counselor to review your case. A calendar will be provided with the tentative dates of when your procedures will fall.
It is necessary to undergo an IVF cycle in order to perform PGD. You will undergo controlled ovarian stimulation and egg retrieval. Once the eggs are harvested, Intracytoplasmic sperm injection (ICSI) is performed in an effort to maximize the number of embryos. The embryos are then cultured to the blastocyst stage.
A laser is used to make an opening in the shell of the embryo and a few cells are removed. These cells are sent to our cytogenetic lab. Immediately following the biopsy, the embryo is cryopreserved or frozen for later transfer once the results are known.
Depending on the indication for the PGD either Polymerase Chain Reaction (PCR) or Comparative Genomic Hybridization (CGH) in which all 24 chromosomes are screened will be performed. The results are reported within 48 hours.
Once we know that there are normal embryos to be transferred back into the uterus, you will be prepared to undergo a frozen embryo transfer cycle (FET). This will necessitate taking medications so that we can control on which day the embryo transfer can take place.
The success rates are dependent on many factors including your age, ovarian reserve testing, the number of embryos produced and of course the number of normal embryos available for transfer.
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