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Pre-implantation genetic diagnosis

WHAT IS PRE-IMPLANTATION GENETIC DIAGNOSIS? (PGD)

It is the genetic analysis of embryos created in vitro with the intention of transferring, to the patient’s uterus, a genetically healthy embryo: the goal being to maximise the chance of pregnancy and/or avoid the transmission of a known genetic illness.

PGD is carried out during an in vitro fertilisation cycle (IVF). Once fertilised, the eggs, now embryos are left in culture for 5 to 6 days until they reach the stage of blastocyst. At this embryonic development stage, 3 to 6 cells are removed from each good quality blastocyst. These blastocysts are then frozen in order to wait for the genetic analysis.

The cells that were removed from the embryos are sent to a specialised laboratory that performs the analysis to determine if those cells are carrying a genetic abnormality.
Healthy blastocysts are then transferred into the patient’s uterus during a frozen embryo transfer cycle.

There are two different types of PGD

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PGS

Pre-implantation genetic screening, most commonly called “PGS” is the complete analysis of the chromosome complement allowing for the detection of aneuploidy in the embryo. In humans there are 23 pairs of chromosomes, so a total of 46 chromosomes. A copy of each is inherited from the mother and one from the father. Aneuploidy is defined as the presence of an abnormal number of chromosomes, that’s to say the absence or surplus of chromosomes.

Aneuploidy is associated with a reduced chance of conception as well as an increased chance of miscarriage and in some cases an affected baby.

The aneuploidy most commonly seen in humans which is compatible with life is Down’s Syndrome (trisomy 21). Individuals with this syndrome have three copies of chromosome 21 instead of two. Research has shown that the percentage of genetically normal embryos in patients undergoing IVF drops with maternal age so that in patients under the age of 35 the rate of normal embryos is around 40% but this drops to only 20% in patients over 40 years of age. (1)

 

 

PGS

 

 

PGS allows us to select the genetically normal embryos and avoid transferring the aneuploid embryos. Aneuploid embryos have very little chance of giving a pregnancy and are responsible for an increased chance of miscarriage if there is an implantation in the uterus.

 

Patients with advanced maternal age, a history of miscarriages or failure to implant could benefit from the advantages of PGS. The use of PGS as a selection tool helps to increase the chance of pregnancy and reduce the chance of an abnormal pregnancy.

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PGD

Pre-implantation genetic diagnosis, usually known as “PGD” allows for the detection of a specific genetic anomaly (e.g. mutation) which is known in one of the parents and is responsible for a single gene disease.

 

One of the most commonly seen single gene diseases in the caucasian population is Cystic Fibrosis. It is caused by a mutation of the CFTR gene on chromosome 7. The mode of transmission of Cystic Fibrosis is autosomal recessive. That means to say that for an individual to be affected by the disease, he must have inherited a mutated gene from each parent.

Two parents who are both carriers of the CFTR mutation will have a 25% chance of having a child with two normal genes, a 50% chance of having a child with one normal and one abnormal gene and a 25% chance of having a child with two abnormal genes and therefore affected by the disease.

 

 

PGD

 

 

In combination with IVF, PGD allows us to avoid transferring an embryo which is carrying a specific genetic abnormality. The IVF procedures in the fertility clinic are the same whether a cycle of PGS or PGD is being carried out. Only the genetic analysis differs.

 

After having prescribed your IVF cycle, your physician will refer you to the PGD program coordinator who will be your resource person throughout the PGD/PGS cycle. The coordinator will give you all the information regarding the procedure to ensure that you can complete your file with the genetic analysis laboratory. This laboratory will need samples of DNA (e.g. buccal cells) from each potential parent in order to develop a specific test for the mutation in question. Once the test is developed and all the consents have been signed you will be able to start your IVF cycle.

REFERENCE

1) Munné et al. Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos. Reproductive BioMedicine Online. Vol 14. No.5. 2007. 628-634

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