Preimplantation Genetic Diagnosis (PGD)

Find out more about PGD at Genea or call us on 1300 361 795

What is preimplantation genetic diagnosis (PGD)?

In a normal IVF cycle, your embryologist chooses which embryo (or embryos) will be transferred to the uterus based on visual observation of the embryos as they develop. Preimplantation genetic diagnosis (PGD) allows the scientist to base their choice on the results of detailed genetic tests on the embryos, excluding those embryos that contain an obvious genetic abnormality.

For example, when two cystic fibrosis carriers conceive a child, there is a 25% chance that the baby will have cystic fibrosis, a 50% chance that the baby will be a carrier and a 25% chance that the baby will be unaffected. IVF with PGD allows the couple to produce a number of embryos, but to transfer only those that are either unaffected or carriers.

Genea is one of the very few centres in Australia that successfully has the combination of IVF and genetics facilities to perform these sophisticated tests.

Types of genetic disease

There are four kinds of genetic diseases.

1. Chromosome errors e.g. Down syndrome, translocations
2. Errors within a gene. e.g. cystic fibrosis, myotonic dystrophy
3. Errors within the mitochondria
4. Errors in more than one gene

How is PGD done?

You will need to have an IVF cycle to create embryos, just like couples with infertility undergoing an IVF cycle. PGD requires the biopsy (or removal) of cells from each embryo for analysis. If the biopsy is done at Day 3 of the embryos’ development, when they consist of six to eight cells, just a single cell is removed. At Genea, our
advanced embryo culture techniques allow us to wait until the embryos have reached their fifth day of development (known as ‘blastocyst’ stage) when they can have a hundred or more cells, and remove three to four. At Day 3 of the embryo’s development, a small hole is made in the outer layer of the embryo (the ‘zona pellucida’) using a
delicate laser beam.

The embryo continues development until Day 5 or 6 when it trophoblasts becomes a blastocyst, characterised by the separation of cells into trophoblasts (which go on to become the placenta) and the inner cell mass (which go on to become the fetus).

The removed cells have not yet differentiated into the specific tissues of the body. Every one of an embryo’s cells has a full complement of the embryos genetic information, this is important for two reasons:

1. Cells can be removed from an embryo and the embryo can still continue to develop normally. (A small proportion do not survive the biopsy.)
2. Cells removed for analysis are usually representative of all the cells in the embryo. i.e. if the cell’s genetic material is abnormal, the embryo is abnormal. (There is a condition called ‘mosaicism’ where this is not the case.)

Genea scientists use a number of different methods to analyse the biopsied cells. The most common are fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR).

FISH

FISH is used to count the number of chromosomes and to observe their arrangement. Fluorescent ‘probes’, which adhere to a particular chromosome, are used. Each of these probes has a different colour. When viewed under a UV light, the probes appear as coloured dots on the cell nucleus. By counting the dots, we can tell how many of each chromosome are present. Trophoblasts are drawn out through the hole using a hollow suction tube called a biopsy pipette. The required cells are separated from the others using the laser and collected separately. The remaining cells quickly realign and the embryo goes on developing. As an example of how this works, we know that Down syndrome is caused by the body’s cells having an extra copy of chromosome 21. A FISH analysis would show an affected embryo’s cells with three glowing dots in the colour corresponding with chromosome 21.

PCR

If the problem is at a gene level, rather than chromosome, it is more common to use PCR. PCR makes millions of copies of a part of the DNA code, enabling us to see whether this part of the DNA in the sample is normal. For example, if cystic fibrosis (which is caused by a mutation of a particular gene) were suspected, PCR would show us whether that gene was normal or mutated.

Who can benefit from PGD?

If you have or carry a diagnosed genetic problem, you can discuss whether PGD is applicable with your geneticist or physician, or by calling Genea.

Other PGD procedures

New methods of PGD are constantly emerging and in the future, as well as to prevent transmission of genetic disease, it is likely that genetic testing of embryos will be used more routinely to improve IVF success rates generally. With the transfer of embryos with no identified abnormality, a higher rate of implantation and a reduced rate of
miscarriage can be expected.

What are the risks?

All medical treatments and surgical procedures carry a risk. The risks associated with IVF are described in the Patient Journal you have received or will receive. However, preimplantation genetic diagnosis carries additional risks. Risks of embryo biopsy The removal of a cell (sometimes two cells) from a Day 3 (usually 8-cell) embryo can possibly stop the development of the embryo, before or after it is transferred. This seems to be less likely with Day 5 or Day 6 (blastocyst-stage) biopsies. So far, there is no evidence to suggest that embryo biopsies cause birth defects.

Is the result always correct?

For most scientific and medical tests there is a small risk of an abnormal result when there is no abnormality (false positive) or a normal result when there is really an abnormality (false negative). From published studies and our own research, we know that the chance of a false result for FISH is 5%. A chance of a false result for a PCR
test is usually less than 1%, but varies for each family.

Can all genetic problems be found using PGD?

Unfortunately not. In many cases of genetic mutation the exact structure and location on a particular gene is not known. However, new information is always being obtained on gene mutations. Also, whilst we can use FISH to determine the presence or absence of chromosomes, Genea is currently looking at seven chromosomes for
testing on any single embryo cell (chromosomes X & Y, 13, 16, 18, 21 and 22). New tests are being developed at Genea to allow counting of all of the chromosomes in a single embryo.