Preimplantation Genetic Diagnosis & Screening

Testing embryos in the IVF lab for genetic abnormalities before they are transferred back to the uterus (preimplantation) has been possible since 1989. Preimplantation genetic testing is a diagnostic test used in conjunction with in vitro fertilization (IVF) and is performed on embryos to assist detection of known genetic diseases or chromosomal abnormalities.

When the testing is searching for a specific genetic disease known to be present in a family, the test is called Preimplantation Genetic Diagnosis (PGD). When the testing is searching for a number of possible genetic problems that might be present, the test is called Preimplantation Genetic Screening (PGS).

For couples with a known genetic risk, PGD is a major medical breakthrough. This includes single gene disorders that are recessive in inheritance, in which 25 percent of the offspring could be born with a serious medical problem. It includes gene disorders that are dominant in inheritance, in which 50 percent of the offspring would be born with a serious problem.

It also applies to chromosomal abnormalities such as translocation, in which one parent has a rearrangement of chromosome such that 25 percent of the embryos could be abnormal.

Other important applications of PGD are screening for hereditary cancer disorders to for testing embryos for their tissue type so that cord blood from the newborn can be used to treat a medical problem of a sick sibling.

Published reports show PGD decreases the risk of conceiving a child with a genetic abnormality. The implantation rates for patients needing IVF with PGD may be slightly lower than those patients who need IVF but not PGD, yet the benefits of PGD in decreasing the risk of having an abnormal pregnancy are clearly established. It is still recommended that prenatal genetic testing, such as CVS or amniocentesis be performed to confirm the PGD results.

Pregnancy rates with PGD are mostly a function of the age of the woman and her FSH level. The pregnancy rates with PGD for single gene disorder are comparable to those of IVF in the same age group.

NOTE: PGD and PGS do not screen for all potential genetic diseases and cannot guarantee a healthy child.

Why PGD or PGS?

Overview

The basic concept of preimplantation genetic testing is simple. Each embryo is analyzed for a specific kind of abnormality through a specific genetic test. This information is used to identify embryos that are normal. Then the doctors select the healthiest embryos to be placed back in the uterus. By utilizing the normal embryos, the probability that couples will have a healthy child increases.

Steps for IVF and genetic testing of embryos

1. Medication is used to stimulate the production of multiple eggs.
2. Eggs are recovered through a minor operation performed under anesthesia using ultrasound guidance.
3. Eggs are fertilized with sperm in the IVF laboratory and allowed to grow. Most often, IntraCytoplasmic Sperm Injection (ICSI) is required.
4. Part of the genetic material of the egg or one to several cells from the embryo are removed and submitted to a specialty genetics lab for testing.
5. The test results can take anywhere from 36 hours to a few weeks.
6. Normal embryos are transferred to the woman’s uterus either a few days after the biopsy or in the next month in a new cycle if the testing requires a longer time.

While the concept seems straightforward, the application of this technology has been more complex and the benefits variable. When first introduced, Preimplantation Genetic testing was hoped to become a major advance in IVF. While Preimplantation Genetic Diagnosis has fulfilled the expectations to help reduce the risk of having a child born with a family-related genetic problem, Preimplantation Genetic Screening has not resulted in as great of benefits.

Preparing for PGD or PGS

1.  IVF consultation

The IVF process and its associated risks is reviewed. Several topics should be discussed including:

• What is the benefit of the genetic test?
• What are the risks of PGD or PGS specific to that individual and the genetic disorder?
• What specific test is to be performed?
• What percent of embryos are expected to be normal?
• Which embryos will be frozen and which will be discarded?
• What type of biopsy is appropriate?
• Is ICSI required?
• Will there be a fresh transfer or will cryopreservation followed by a frozen embryo transfer be done?

2.  Genetic Consultation

A genetic counselor, either affiliated with RSC or one affiliated with the genetics lab performing the test meets with the patient and her partner to review their individual histories. Sometimes additional testing is recommended.

3.  Appropriate Genetic Testing

• If PGS is being performed with either FISH or CGH, a karytotype on both partners is necessary to insure accurate interpretation of the test results.
• If PGS with SNP microarray is being performed through GSN, both partners need to be tested first as well. For single gene disorders, the genetic lab will require blood from both partners and time to run an internal test to be certain that appropriate linked markers can be identified and that the specific genetic mutation can be accurately detected.
• If PGS for a single gene disorder is being preformed, the genetics lab may need to do additional testing.

Limitations of Preimplantation Genetic Testing

• Risks associated with IVF: ovarian hyperstimulation syndrome, multiple pregnancy, increase risk of birth defects not related to the genetic test.
• Risk of harm to the embryo from the biopsy or from freezing.
• Possibility of a false result. This may mean the transfer of an abnormal embryo thought to be normal resulting in either miscarriage or facing the decision for termination of the pregnancy. Or it may mean discarding a normal embryo thought to be abnormal reducing the chance of a healthy pregnancy.
• Possibility that there may be no normal embryos to transfer.

Alternatives to PGD and PGS

Listed below are alternative options to PGD or PGS:

• Testing the fetus during pregnancy can diagnose whether or not the fetus has a genetic abnormality. Chorionic Villus Sampling is a procedure where a biopsy of the placenta is performed at 10-12 weeks into the pregnancy. Amniocentesis is a procedure where the amniotic fluid is removed for analysis. Amniocentesis is performed at 14-16 weeks. For either of these, PCR can be done for single gene disorders. FISH or CGH can be done for rapid analysis of the chromosome number but typically a more time-consuming test, called cytogenetics for chromosome analysis or karyotype, is done to obtain the most definitive answer. These tests take about one week for the results. If an abnormality is detected, the option would be to consider an abortion.
• Ultrasound with or without blood tests can be done during pregnancy. Typically the results of this type of testing are not specific. The ultrasound and blood tests may miss abnormalities. If abnormal results are obtained, CVS or amniocentesis may be recommended.
• Donor eggs or donor sperm can be used to avoid the risk of disease.
• There is also the option not to do prenatal testing and not to do IVF or genetic testing of embryos.