PGD
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CGH - a basic overview.

 All couples want to have a healthy pregnancy and a healthy baby. In normal IVF the choice of which embryo to transfer is based on appearance, how the embryo ‘looks'. However we know that half of the early embryos that ‘look good' will have a genetic problem in their chromosomes. They will have more or less of some chromosomes or parts of chromosomes; resulting in no pregnancy, a miscarriage, or a baby born with a disorder.
We can do PGD; that is we can test the embryo before it goes into the mother's uterus, using a technique called CGH (Comparative Genome Hybridisation). 
We remove 1-5 cells from the early embryo and test all the chromosomes to make sure that the embryo we select for transfer to the mother's uterus has the right number of chromosomes and therefore the best possible chance of achieving a healthy pregnancy and a healthy birth.
Removing 1-5 cells from suitable early embryos does not damage the embryos.
We will compare the embryo's chromosomes (or DNA) to normal human male and normal human female DNA using CGH ‘chip' or ‘microarray' technology.
We can then identify gains or losses in the embryos chromosomes and select for transfer an embryo with the right number of chromosomes and therefore no apparent chromosome problems.

 

  

What is Aneuploidy?


 Normally most cells in the body have 23 pairs of chromosomes.
Aneuploidy describes chromosome problems caused by having extra or missing chromosomes. The most well-known example of aneuploidy is Down syndrome, which is caused by having an extra copy (or three copies) of chromosome 21.

 

Studies have shown that about 50% of early embryos have an aneuploidy problem, and that all chromosomes can be involved in aneuploidy in the early embryo


What is CGH?


CGH is a method that can detect imbalances of all chromosomes in the early embryo.
It helps us to understand the genetics of the embryo and improve aneuploidy detection by considering all 24   chromosomes.
It provides new opportunities for patients who may have experienced unsuccessful IVF attempts, miscarriage, or have a previous history of chromosome problems (eg,. translocations)


PGD-CGH for Chromosomal disorders


At Superior A.R.T. we use the BlueGnome 24Sure comparative  BAC CGH, a molecular technique which compares embryo DNA against control reference male and female genomic DNA using a microarray or ‘chip'.
Each Microarray contains several thousand probes equivalent to thousands of chromosome parts spread across all 24 chromosomes.
It identifies gains and losses in embryo DNAs (gains or losses of whole chromosomes or large parts of chromosomes).
CGH has many advantages over the outdated FISH technique - the main one being that it can accurately assess ALL of an embryo's chromosomes, rather than the 5-9 that FISH allowed.
Cells biopsied from the embryo undergo whole genome amplification (WGA), producing multiple copies of the sample DNA. The amplified sample DNA, and normal human reference DNAs, are fluorescently stained and added onto the microarray. Amplified stained DNA is allowed to stick to the probes. The microarray is washed, and a scanner reads the amount of colour at each point on the microarray. The amount of colour in the sample DNA and the reference DNAs are compared. Embryos found to have a normal chromosome complement can then be transferred or frozen. Two scientists read all results.

 

A result showing a female with a chromosomal abnormality of trisomy chromosome 16, that is three copies of chromosome 16 instead of the normal two.


What is Preimplantation genetic diagnosis (PGD)?


In a normal IVF cycle the embryologists choose the embryo for transfer to the uterus based on appearance and development. Preimplantation genetic diagnosis (PGD) gives us another factor on which to base our decision - the genetic health of the embryo, excluding embryos that contain an obvious genetic abnormality.

PGD involves carefully removing small number of cells from an embryo for analysis. From this tiny biopsy sample Superior A.R.T. can determine whether an embryo has Down syndrome, cystic fibrosis, Huntington's disease or any of a wide range of other genetic problems.


How is the PGD biopsy done?


At Day 3 a small hole is made in the outer layer of the embryo using a delicate laser beam. The embryo continues development until Day 5 or 6 when trophoblasts, the outer layer, are drawn out through the hole using a hollow biopsy pipette. The required cells are separated from the others using the laser and collected separately. The remaining cells quickly realign.

 

The analysis

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.
 
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.)
 
Superior A.R.T.  scientists use a number of different methods  to analyse the biopsied cells.
 
We use CGH to analyse all 24 chromosomes is one of them.
 
We also use a technique known as the polymerase chain reaction (PCR) to analyse for single gene disorders such as thalassemia. 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.
 
At Superior  A.R.T., we can also use PGD-PCR for HLA matching to produce an unaffected sibling who is an exact HLA match to an existing affected child, where the disorder is potentially treatable using stem cells harvested from the cord at birth.

Recent Advances

Improvements in the whole genome amplification stage of the CGH mean we can now offer PGD-PCR for single gene disorders and/or HLA matching in combination with CGH
The patient not only gets the results for the single gene disorder and/or HLA matching, but also gets CGH screening for all 24 chromosomes.

What are the Risks?
Risks of IVF


All medical treatments and surgical procedures carry a risk. The risks associated with IVF are described in the patient information 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 (a false positive result) or a normal result when there is really an abnormality (a false negative result).From published studies and from our own research we know that the chance of a false result from a CGH test is very small. We offer 95% reliability on all CGH tests to reflect a level of uncertainty associated with testing at such an early stage of development.
Your fetus or baby might also be at risk from other conditions not tested for; you should therefore discuss prenatal testing with your obstetrician.

Can all chromosomal problems be found using CGH?


Unfortunately there are a small number of small chromosomal errors which may not be detected using CGH. These are very low risk.

Will we always get a result?


Superior  A.R.T. achieves a result in more than 95% of embryos tested.


Will we always have an embryo for transfer?


Unfortunately not. At the end of a cycle, there may be no suitable embryo for transfer;  for example, all embryos tested may be abnormal.


Getting started on an IVF cycle for PGD


When you want to start treatment at Superior A.R.T. you can choose the pathway you prefer from amongst these options:
1.Be referred by your OB-GYN doctor to Superior A.R.T.
2.Be referred by a Genea clinic in Australia. You would be referred to do the key steps of the laboratory procedure at Superior A.R.T.  Your treatment would be coordinated between Genea and Superior A.R.T.
3.Contact us directly to arrange an appointment with a Superior A.R.T. allied clinician.
 
We recommend that all potential CGH patients have a karyotype; that is that the chromosomes in the patients themselves are checked. A karyotype can identify some chromosomal rearrangements (eg. translocation) and we may then use customized CGH to detect these rearrangements in embryos. It is compulsory for all high risk patients (eg. recurrent miscarriage) to have karyotypes done.

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