PGD or preimplantation genetic diagnosis is sometimes also referred to as preimplantation testing. This is probably a more accurate description since we do many other types of testing besides genetic testing.  Recently the Society for Assisted Reproductive Technologies and the American Society for Reproductive Medicine recommended the use of the following terms:

Preimplantation testing:

A general term which describes the removal of cells from an egg or embryo and subsequent testing.

Preimplantation genetic diagnosis: 

This term applies when one or both genetic parents carry a gene mutation or a balanced chromosomal rearrangement and testing is performed to determine whether that specific mutation or an unbalanced chromosome has been transmitted to the oocyte or embryo.

 

Preimplantation screening:

This term applies when the genetic parents are known or presumed to be chromosomally normal and their embryos are screened for aneuploidy (having too many or too few chromosomes).

 

 

PGD is made possible through the use of IVF (in vitro fertilization). In short, a woman is first given fertility drugs to stimulate the development of multiple eggs in her ovaries. She is monitored during this time with blood tests and ultrasounds. At the appropriate time, the eggs are removed in a process known as an (oocyte) egg retrieval. Once the eggs are removed, they are inspected under the microscope to determine which eggs are mature and normal appearing. Each of these eggs will then have a single sperm injected into them. This process is called ICSI (intracytoplasmic sperm injection)

The day after the ICSI is performed; the injected eggs are inspected under the microscope to determine which have fertilized. We look for two features: two pronuclei and two polar bodies. The polar bodies contain chromosomes that the egg got rid of. At this time we can perform a polar body biopsy. The fertilized eggs are then placed back into the incubator and allowed to develop. Two days later, the embryos are removed and inspected. We hope to see embryos have reached the 8 cell stage. These cells are called blastomeres. Each one contains identical chromosomal information. The next phase of the preimplantation genetic diagnosis process is called a blastomere biopsy.

During this time, the cells that were removed from the developing embryo and specifically the genetic material inside of the cells can be tested for various abnormalities or characteristics. This information can be used to select which embryos to place into the uterus.

The most common type of preimplantation testing we do is to look at the number of each type of chromosome present. This is called aneuploidy testing. Any couple that is having in vitro fertilization is a potential candidate for aneuploidy testing. In all women, some percentages of the embryos are going to be abnormal. We can improve the chance for pregnancy and reduce the risk for miscarriage with this type of preimplantation testing.

A small percentage of couples who have a problem with recurrent miscarriage may themselves have a chromosome abnormality known as a translocation. This is a structural abnormality that occurs between two chromosomes. Preimplantation testing can also be used to identify embryos with translocations.

There are other types of problems that can be detected in embryos also. We can perform true preimplantation genetic diagnosis. That is, identify embryos with certain genes or genetic mutations.

One of the more controversial procedures we have performed is testing embryos to determine whether they are tissue matched to siblings that may be suffering from diseases that could be cured with a bone marrow or stem cell transplant. Another controversial procedure is testing embryos to determine their gender so that a couple can have a child of a particular sex. This is known as gender selection.

Frequently Asked Questions About PGD

Q) Does performing an embryo biopsy for PGD damage an embryo?

A) No. We have now studied thousands of embryos. Compared to IVF without PGD, embryos that have a polar body biopsy or embryo biopsy develop in a similar way. For example, when we compare the percentage of eggs that achieve normal fertilization, the PGD embryos which had a polar body biopsy had a normal fertilization rate of 78%. The eggs that did not have a PGD biopsy had a normal fertilization rate of 76%. Cleavage rate is a measure of the percentage of fertilized eggs that go on to start dividing. PGD embryos have a cleavage rate of 96%, compared to embryos without PGD which divide 95% of the time.

A very important quality measure is how often a fertilized egg will become a blastocyst. PGD embryos will develop into blastocysts about 40% of the time. Non-PGD embryos become blastocysts slightly more often at 47%, a difference that is not statistically different.

Rarely, an embryo can be damaged by the biopsy procedure itself. If this occurs, it can be identified right away by viewing it under a microscope.

Q) I'm under age 35, so my embryos won't have chromosome abnormalities, right?

A) Wrong. We have studied women of different age groups and have found that even younger women have abnormal embryos. We recently looked at women under age 35 and performed PGD for 5 chromosomes. We looked at chromosomes 13, 16, 18, 21 and 22. Abnormalities in the number of copies of these five chromosomes account for the majority of chromosome abnormalities found in embryos. We could identify that in women under 35, 40% of the embryos tested were abnormal for one of these five chromosomes. This does not mean that all women will have 40% of their embryos abnormal. Some might have a higher abnormality rate and some lower. Overall, it averages out to 40% at that age. We have seen some younger women with recurrent IVF failure have abnormality rates over 90%

Q) What are the chances that an abnormal embryo is going to be missed by PGD?

A) Remember that an embryo can have many different types of abnormalities. Preimplantation genetic diagnosis is only going to test for a specific type of abnormality. For instance, testing to determine if an embryo will produce a baby with Down's syndrome (caused by three copies of chromosome 21) will not rule out the possibility that the embryo also has a gene mutation that would cause the baby to have cystic fibrosis.

Furthermore, when we do chromosome testing, we can only look at a maximum of nine chromosomes. Since an embryo has 23 pairs of chromosomes, it means that we won't be testing the remaining 14. We choose the nine that we do test very carefully, however. We believe that we can identify about 85-90% of the numeric chromosome abnormalities by testing the nine. In other words, we expect to miss a chromosome abnormality about 10-15% of the time.

Q) What are the chances that an embryo will be diagnosed as abnormal when it is really ok?

A)When an embryo starts dividing, each of the daughter cells is supposed to be identical to the parent cell. Sometimes, however, the embryo can make a mistake. One cell from an eight cell embryo may be slightly different than the remaining seven cells. This is called mosaicism. Mosaicism can affect the results of PGD when blastomere biopsy is performed.

Remember, during a blastomere biopsy, one cell in an eight cell embryo is removed and tested. It is assumed that this cell is going to be representative of the entire embryo. If it is not, then a misdiagnosis can result. For this reason, PGD for chromosome abnormalities should always be performed using both polar body biopsy and blastomere biopsy. This will reduce the chances of an error due to mosaicism.

Q) Will PGD increase my chances of having a baby?

A) In many cases, the answer is yes. Preimplantation genetic diagnosis has been shown in our studies and in studies from other medical groups to increase the chance for pregnancy and reduce the risk of miscarriage in women who are 37 or older. Ordinarily, older women have a lower pregnancy rate and a higher miscarriage rate. This is true even when performing fertility treatments such as IVF. With each year, the pregnancy rate declines and miscarriage rate rises. Both problems are primarily due to the higher rate of abnormal embryos that occur in older women. By finding and placing the normal embryos into the uterus, the chances are better that a delivery will occur.

It is possible that younger women may also benefit from PGD but since they have a lower percentage of abnormal embryos, the benefit is likely to be smaller. Therefore, a much larger number of women need to be studied in order to statistically prove an effect. A recent PGD study conducted in the Netherlands actually found a lower live birth rate in women who underwent IVF with PGD compared to those with IVF alone. This study included women who were as young as 35 years old.

 

This also does not mean that every older women will benefit. In many cases, older women are found to have all of their embryos abnormal and therefore they do not have an embryo transfer and thus no opportunity for pregnancy on that particular IVF cycle.

Q) Is it likely that my insurance will cover the cost of PGD?

A) It is very unlikely that PGD will be covered by your insurance. Most insurance companies still consider PGD to be experimental even though we have been doing PGD for more than ten years.

Don't look for this to change any time soon. Although we have a law in Illinois which requires most employers to cover infertility, it took a great deal of effort to get that law passed. Even then, it was passed with some major loopholes that allow some employers to deny coverage to infertile couples.

PGD is a much more controversial technology than IVF. It can be used for things such as gender selection and selection of embryos for tissue typing. Many people do not believe that these technologies should be allowed. Because of this, there are not likely to be politicians that are going to be willing to back a measure that will require employers to cover PGD.