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Preimplantation Genetics Diagnosis for HD

What is Preimplantation Genetic Diagnosis (PGD)?

Preimplantation genetic diagnosis (PGD) is a method of prenatal testing for some genetic disorders, which has been developed over the past 12 years utilising in vitro fertilisation (IVF). The traditional methods of prenatal testing - chorion villus sampling (CVS) and amniocentesis - are performed during the first and second trimesters of pregnancy respectively. An abnormal result on CVS or amniocentesis presents couples with a potentially traumatic decision regarding pregnancy termination.  The advantage of PGD is that genetic testing can be performed almost immediately after in vitro fertilisation of the woman's eggs i.e. outside the body. Obtaining the results of embryo testing with PGD enables the couple to avoid this difficult decision, as there are usually embryos with a normal result that can be transferred back to the woman in an attempt to begin a pregnancy.

Conditions for which PGD is offered

PGD can be performed for most single gene disorders for which a specific gene fault (mutation) has been identified. These include conditions such as;
HD, myotonic dystrophy, cystic fibrosis, thalassaemia, and haemophilia. It can also be used to detect chromosome abnormalities such as Down syndrome.

What does PGD involve?

The initial consultation is usually with a clinical geneticist and/or genetic counsellor. The feasibility of the couple's request, including their level of fertility, is assessed and the PGD process is outlined (including its disadvantages). If PGD is possible for the couple, they are encouraged to take time to think about whether they wish to proceed. If they decide to go ahead, they embark on a strictly controlled process, referred to as a cycle, which involves manipulation of the woman's menstrual cycle, using hormonal medications, to stimulate ovulation of multiple eggs.  The eggs are retrieved using a surgical procedure, and fertilised with the male partner's sperm. When the embryos reach the 6-8 cell stage, one or two cells are removed from the embryos.  These cells are then tested for the specific single gene disorder or for a chromosome abnormality.  If there are one or more normal embryos, these are transferred back to the woman's uterus (usually no more than three). Hormone levels are then tested to determine whether a pregnancy is established. If successful, normal pregnancy management commences. As PGD is still a relatively new procedure, it is recommended that a chorion villus sampling procedure be performed at 12 weeks gestation, to check the accuracy of the PGD result. A recent survey of 21 centres worldwide found a misdiagnosis rate of 1.8%. If a pregnancy is not achieved, the couple must consider whether to proceed with another cycle.

Problems Encountered with PGD

In all centres, problems encountered include reduced fertility of one or both partners, retrieval of no or few eggs, failure of fertilisation, poor quality embryos, technical problems with embryo biopsy and/or with the testing process, most or all embryos being affected and implantation failure. For PGD couples lack of familiarity with IVF terminology and procedures may make the process even more confusing and traumatic. These couples do not just want a baby; they want a baby free of the condition they are at risk of transmitting.

PGD for Huntington's Disease

Couples in which one partner is at 50% risk or has tested positive for the HD mutation are becoming increasingly interested in PGD as a means of avoiding transmission of the mutation to their children, without having to confront the emotionally and ethically difficult issue of termination of pregnancy. In most centres where PGD is offered for HD, it is expected that the partner who has the family history of HD has already had a predictive (genetic) test and knows that he or she has the HD mutation. PGD therefore involves direct testing of the couple's embryos for the HD mutation. Statistically 50% of the embryos will have the mutation and the other 50% will have the normal gene.

Non-Disclosing PGD for Huntington's Disease

It is now well established that the majority of people at 50% risk for HD do not wish to have predictive testing to determine whether or not they have inherited the HD mutation. Some of these people nevertheless are concerned about the risk of passing the faulty gene on to their children, and they and their partners may seek a method of having children, which will ensure that the child does not carry the HD mutation.  One of the possible methods is non-disclosing PGD, in which the person at risk and the partner are not told whether any embryos were found to have the HD mutation.  They are only informed that an embryo (or embryos) with the normal copy of the gene was transferred to the uterus of the female partner.

Exclusion PGD for Huntington Disease

Another approach is technically possible for couples who do not wish to know the at risk partner's genetic status.  This approach, known as exclusion testing, utilises DNA linkage testing, which has been available since 1983, and was used for predictive testing prior to the discovery of the HD mutation in 1993. A blood sample is required from the HD parent of the at risk partner.
The main disadvantage of this approach is that it reduces the number of embryos available for transfer as, on average, 50% of the excluded embryos will not carry the mutation.  However the advantage is that it protects the couple's wish not to know the at risk partner's genetic status without any of the PGD team having that ethically challenging knowledge.

Cost of PGD

Check with Medicare and your Private Health Insurance about what costs they will cover.

More Info

IVF Australia

Centre for Genetic Education