Preimplantation Diagnosis for Monogenic Disorders

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1 Preimplantation Diagnosis for Monogenic Disorders

2 Many serious genetic diseases are caused by an error, or mutation, in a precise location in a particular gene. Preimplantation Genetic Diagnosis (PGD) is a treatment option for couples who know that one or both of them is a carrier of a genetic disease, sometimes called a monogenic disorder. PGD allows these couples to reduce the chance of passing that disorder on to their children. This is achieved by creating embryos through IVF, removing one or a few cells from each embryo and testing those cells for the disease that the parents carry. In this way embryos that are predicted to be unaffected with the disease can be selected for transfer back to the woman with the intention of achieving a healthy pregnancy. A genetic pedigree.

3 How is the PGD performed? At Melbourne IVF we use a technique called Karyomapping for most of our monogenic disorder testing. DNA samples are collected, usually via a simple blood or saliva test, from the couple and other family members whose genetic status for the disease is known. Preliminary testing of these samples using Karyomapping allows a DNA fingerprint in the region of the faulty gene to be determined. Following this, as part of an IVF cycle, embryos are formed from the couple s eggs and sperm and a few cells removed from each embryo for DNA fingerprint analysis. By comparing the DNA fingerprint of the embryos to that of the family members we are able to determine, with approximately 98% accuracy, which embryos have inherited the disease and which are free of it. How is Karyomapping different to other test methods? Melbourne IVF has offered PGD for monogenic disorders for more than a decade. This has been achieved using a technique called multiplex PCR which is a very accurate and reliable test method but is expensive and timeconsuming. Feasibility testing is required during which a special individualised PGD test is developed for each couple and this can take several months. In contrast, Karyomapping has a rapid turnaround time, significantly reducing the wait before treatment can commence. What is aneuploidy and can Karyomapping detect it? Our genetic material, or DNA, is tightly coiled into structures called chromosomes. Every cell in an embryo should have 46 chromosomes, arranged in 23 pairs. An extra or missing chromosome is called aneuploidy and includes conditions like Down syndrome, an extra copy of chromosome 21. Aneuploidies can affect up to 70% of early human embryos, and most cause the embryo to die early in development resulting in failure to become pregnant or miscarriage. Karyomapping, unlike multiplex PCR, will be able to detect many aneuploidies. Whether an aneuploidy can be detected is related to how and when the aneuploidy occurred, not which chromosome is involved. Monosomies, or missing chromosomes, will be detected. Trisomies, or extra chromosomes, that have occurred either in the egg or the sperm are likely to be detected. Trisomies that have occurred during the first few days of development of the embryo are unlikely to be detected. We estimate that approximately 70% of aneuploid embryos will be identified during Karyomapping for monogenic disorders thereby reducing the likelihood of pregnancy loss or implantation failure due to aneuploidy.

4 When will my embryos be tested? For karyomapping, approximately 3 5 cells will be gently removed, or biopsied, from blastocyst stage embryos on day 5 or 6 of development. After biopsy, embryos will be frozen until the karyomapping test results are available. You can then discuss these results, available within two weeks, with your fertility specialist, before commencing a thaw cycle for transfer of a genetically suitable embryo. What are the advantages of Karyomapping? Whilst multiplex PCR remains an accurate and effective methodology, there are significant advantages when using Karyomapping; No lengthy feasibility testing is required which significantly reduces the time before treatment can commence. Likely to increase the live birth rate through the identification of many aneuploidies. Will Karyomapping be suitable for me? All couples who are at risk of passing a monogenic disorder to their children are potentially suitable for Karyomapping. We estimate that approximately 90% of couples with a monogenic disorder will be able to have PGD with Karyomapping. We will do an early assessment to determine if Karyomapping is suitable for you. This will involve an appointment with our clinical genetics team, including our clinical geneticist, as well as a review of your genetic history with our laboratory genetics team. Following this, we will need to collect a DNA sample from you and specific family members, to perform a Karyomapping Evaluation which will take 2 4 weeks and will establish whether Karyomapping is appropriate. If this is the case, your IVF treatment can commence. Lower in cost than multiplex PCR.

5 What if Karyomapping is not suitable for me? Patients for whom Karyomapping is not suitable will most likely be able to undergo PGD for their monogenic disorder using the multiplex PCR method. Melbourne IVF will continue to offer the PCR method specifically for these couples. Multiplex PCR is still a very accurate and effective method but will require a feasibility test which may take several months to complete before treatment can commence. You will be notified as early as possible if karyomapping is not suitable for you. What do I do now if I wish to proceed? After you have seen our clinical geneticist as part of our genetic clinic, and seen a Melbourne IVF fertility specialist who will care for you during your IVF cycle, you will be ready to proceed with the Karyomapping evaluation. For this you will have an appointment with a senior PGD scientist to discuss the Karyomapping evaluation and collect the necessary DNA samples. There is a fee for the Karyomapping evaluation that is payable shortly after the evaluation commences. Following this, there will be an additional four appointments required before the first treatment cycle can commence. These appointments will be made for you by a Melbourne IVF Patient Liaison Administrator (PLA). You will be guided by the PGD team as to when you should contact the PLA to arrange the following appointments: 1. Patient Liaison Administrator (PLA) to discuss the legislative requirements for having IVF treatment in Victoria, cycle administration and fees associated with the PGD and IVF. 2. PGD nurse to discuss steps in your treatment cycle and medications used. 3. IVF Counsellor mandatory session for anyone having IVF treatment in Victoria. 4. Genetic Counsellor to discuss your test and sign a consent form for the embryo biopsy and PGD test.

6 More information Melbourne IVF can provide you with general information via phone or through our website. Talk to our Community Liaison Administrator about making an appointment with a Melbourne IVF fertility specialist, by calling PI-COM APRIL2016 mivf.com.au