Feasibility Testing

Admin

Following our appointment with the Fertility Associates (FA) specialist, we needed to supply copies of our birth certificates or passports (including residency visas) to prove our eligibility for publicly funded treatment. The specialist then submitted a National Clinical Assessment Criteria (CPAC) for Treatment of Infertility form to the Ministry of Health on our behalf. For couples facing fertility problems, this form comprises a priority scoring system with criteria such as types of diagnosed fertility issues, age, time spent trying to conceive etc. where a score of at least 65/100 is required to be eligible for treatment. In cases like ours where hereditary disease is the concern, if there is a 25% or higher chance of passing on the disease, provided you are a non-smoker, have a BMI in the range of 18-32 and are under 39 years of age, then you qualify for treatment.

After a few emails back and forth with the FA administrator, (I wasn't taking any chances after the delays we had with Dave's results) I was told that the Ministry of Health coordinator meets with the embryology team from FA once a month to discuss ongoing cases. At this point a couple is required to undergo genetic counselling if they have not already, but the counselling we had around Dave’s testing and diagnosis proved sufficient in our case. 

Location of the ATXN 3 gene on chromosome 14:
Cytogenetic Location: 14q32.12, which is the long (q) arm of chromosome 14 at position 32.12

Feasibility

Four weeks after our initial appointment, the FA embryologist rang to let me know she was posting out the paperwork for our feasibility study, which is to be conducted by Canterbury Health Laboratories in Christchurch. Each of us and our parents were asked to have blood samples taken (which could be done at the local blood sample collection centres in Nelson) and to sign consent forms giving permission for the lab to store and test our DNA. She said that depending on how busy the lab is, the feasibility testing would probably take about a month.

The purpose of feasibility testing is to use our blood cells to conduct a trial run of the test they will hopefully eventually use on our embryos. The aim is to confirm that the mutation carried (in our case the repeating sequence in the ATXN3 gene) can be reliably detected in our embryos, and to develop the best strategy for embryo analysis. When PGD is carried out on an embryo, only a few cells are sampled for testing so the lab needs to ensure they can accurately ascertain the presence or absence of the SCA3 mutation using such a minuscule sample size.

Listed

We waited two weeks after being referred, and then upon following up discovered Fertility Associates had been provided incorrect contact details for us. Following this minor hiccup I managed to get in touch to make an appointment. We had the option of waiting until August for a publicly funded appointment available in Nelson in August, or travelling to Christchurch or paying privately to be seen sooner. We opted to go private to move things along again, and took an appointment in Nelson in early July at a cost of $285. Our thinking was that if eligible for treatment, we could perhaps get on the waiting list without further delay.

In preparation for our appointment, we were asked to fill out a registration form, a health questionnaire each, and were provided with laboratory order forms to get blood tests. I completely understand the reasoning, but found it funny that my test included 18 different parameters, while Dave’s covered only three. There was also an order form for a semen analysis for Dave, but as I alluded to in my first post, he actually had done one earlier in the year when we first saw our GP so wasn’t required to submit another at this stage.

Our first meeting with Fertility Associates

We weren’t entirely sure what to expect from our first meeting with the Fertility Associates specialist, but at the very least we were hoping to confirm our eligibility for publicly funded treatment, and have some idea of a timeline. We began with the specialist going over our medical and family histories and summarising the occurrence of SCA 3 in Dave’s family. She looked over our blood test results. One of the things I was tested for was Anti-Müllerian Hormone (AMH). This gives an estimate of your ovarian reserve (i.e. how many eggs you have), and can help predict how many you are likely to yield in an IVF cycle. Rather than an exact value, they graph the result against your age, to show how your egg reserve compares with that of other women of a similar age. This is genetically predetermined, so with the exception of smoking, which can reduce your reserve, there is nothing you can do to alter it. My result was in the 25^th centile, so in the specialist’s words is slightly below average for my age, but nothing to be too concerned about. The main thing to take from this is that we wouldn’t want to wait until I was 40 to try and conceive, but that is of course not ideal (and not the plan!) for many reasons. The specialist confirmed that we qualify for IVF and PGD through the public system, so we will go on the waiting list. She said the waiting time generally varies from 12-15 months, but that for those seeking genetic testing things can move a little quicker. 

PGD in a nutshell

Next up

The next step for us is a feasibility test. Sometime over the next few months, we will be contacted by the Canterbury Health Laboratory, who will eventually conduct the PGD. They will request a blood sample from each of us, and perform a trial test to check that they can accurately detect SCA 3 in our case. They need to do this trial run as when they eventually test any viable embryos, they only sample 5-10 cells from each one, so need to be able to accurately conduct the testing with a tiny sample size. The specialist was confident that accurate testing shouldn’t be an issue in our case, but can be more difficult in other cases where more than one gene can be responsible for a particular issue.

Some months following the feasibility test (depending on wait time), we will need to travel to Christchurch where Fertility Associates services for Nelson are based. Here we will have another consultation this time including another semen sample analysis for Dave, and a pelvic ultrasound for me. We will also sign the consent forms required for IVF treatment with Fertility Associates, and PGD with the Canterbury Health Laboratory. A nurse will show us how to administer the hormone injections I’ll need to have daily to begin the IVF process.

The specialist briefly outlined how our process will work, my understanding of which is as follows:

·         Feasibility testing (Nelson)

·         Pre-IVF consultation (Christchurch)

·         Begin hormone injections (Nelson)

·         Preliminary pelvic ultrasound (Nelson)

·         Egg collection following further blood tests and ultrasounds, fertilisation (Christchurch)

·         Embryos sampled at day 5 of growth, and then frozen. Samples sent for PGD testing (Christchurch)

·         PGD results back, all going well a suitable embryo is thawed and implanted (Christchurch)

Tails, We Lose

Diagnosis

Dave tested positive for SCA 3. He has the same number of CAG repeats in the ATXN 3 gene as his dad does (70) which thankfully means his symptoms should not onset any earlier than his dad’s did. This hopefully gives him until his late 40s (15+ years) before he starts to be affected by the disease. We can hope that perhaps by the time he develops symptoms treatment may be available, although we cannot depend on this. At Dave’s request the genetic counsellor is referring him to a neurologist, so that they can give him a check over to determine his baselines i.e. his ‘normal’ for a neural examination, and to discuss his diagnosis.

We were mentally prepared for this, at least as much as someone can be. Out of a sort of self-preservation Dave has always lived under the assumption he had the disease. We already had set up high mortgage repayments with a goal to pay off our mortgage sooner rather than later to secure our home. We found an insurance company that would provide life insurance without needing to rule out hereditary illness. As I pointed out to Dave before the results came through, the test was purely for logistical purposes. It doesn’t change anything, it just gives us the opportunity to be prepared mentally, physically and financially for if a treatment is not available by the time he experiences symptoms. It also of course will inform our decision on how to proceed with starting a family, knowing that we don’t want to pass the abnormal gene on.

There is a 50% chance of inheriting SCA3 from an affected parent.

Our options

The genetic counsellor explained the diagnosis, and answered the few questions we had before returning to the topic of our looking at starting a family. She revisited our options, though we had already made up our minds. I have laid out the options together with my own thoughts below:

1. Amniocentesis - getting pregnant and testing the foetus at 11 weeks by sampling the amniotic fluid. This leaves you in an awful position - what do you do with this information? Do you intend to terminate the pregnancy if the foetus tests positive? 11 weeks is a long time to carry a foetus anticipating such a decision and potential outcome. But is it ethical to have the child knowing that you are sentencing it and potentially subsequent generations to succumb to this disease if medicine hasn’t produced a cure by the time it experiences symptoms?
2. Pre-implantation genetic diagnosis (PGD) as part of in-vitro fertilisation (IVF). Firstly, it is important to clarify that no genetic manipulation/modification occurs as part of this process. The embryos that are produced from eggs harvested and fertilised during the IVF process are sampled and tested, and from among the viable embryos that do not carry the disease, one would be selected for implantation. Any other healthy embryos would be frozen for potential future use, while any that tested positive or were otherwise unviable would be discarded. There are strict criteria in New Zealand around eligibility for such testing, and also around public funding for IVF and PGD.
3. Conceive naturally without genetic testing. Is this ethical, knowing that there is a 50% chance of passing this disease on, and knowing that there are options to avoid this?
4. Opt not to have biological children. We could look at adoption, or foster a child. Or focus on our ‘fur family’ - our two very much loved rescue dogs.

Finally, is it ethical to test a foetus at all? Does screening for genetic conditions undermine the value and existence of people who have been and will be born into our communities with disabilities? As you know, for us there is no place for theology in this discussion.

Herein lie the ethical dilemmas of looking at starting a family in the face of hereditary genetic illness. Following much Googling and discussion, we had already made up our minds before this appointment. We asked for the genetic counsellor to refer us to Fertility Associates so that we could start the process in applying for PGD. There are strict eligibility criteria for IVF, PGD and public funding for these in New Zealand. Given Dave’s diagnosis for a hereditary disease that has a 50% chance of being passed on, we are optimistic that we will meet the criteria. In the meantime, we await contact from Fertility Associates to set up our initial appointment. We hope that we will find out sooner rather than later whether we are eligible, and how long the wait list is so that we can manage our expectations and plan.

A Coin Toss

Machado-Joseph Disease/SCA 3

Dave has always known he may possess the gene for Machado Joseph Disease (MJD), the same genetic disease that he has witnessed afflict his dad and paternal grandfather. Also known as spinocerebellar ataxia type 3 (SCA 3), it is a dominant hereditary disease that onsets in middle age. ‘Ataxia’ refers to a lack in muscle control or coordination. SCA 3 is caused by abnormally long repeats in a repeating sequence of DNA code in the ATXN 3 gene. In a normal sequence, the code ‘CAG’ repeats 12-44 times. In someone with SCA 3, this sequence is repeated more than 60 times.  This disease manifests as slow a decline in motor function, beginning with balance issues and slurred speech. Over years other symptoms develop, including impaired eye movements and vision, muscle spasms, and mobility declines until the affected individual becomes dependent on a wheelchair. In the case of Dave’s dad, symptoms onset at around age 47, and at 60 he is now wheelchair bound, and living full time in a care facility (though this is in part due to other associated health issues).  For more information detailing SCA 3, causation and symptoms please visit https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Machado-Joseph-Disease-Fact-Sheet for a more comprehensive overview.

There is no current treatment or cure for SCA 3, although recent breakthroughs in gene therapy for similar conditions such as Huntington’s offer hope that perhaps one will exist in the not too distant future.

Genetic testing exists for SCA 3, but Dave (now 32) had so far chosen not to get tested, as he didn’t welcome the idea of anticipating the symptoms. Understandably, he didn’t want to spend his life worrying each time he was clumsy whether ‘this was it’, if this was the onset of the disease. Of course, now that we are looking at having a kid, this changes things. As this is an autosomal dominant disease, a person is affected even if they inherit the abnormal gene from only one parent, and there is a 50% chance of the affected parent passing it on. There is also a possibility of the disease onset occurring earlier with each generation, with symptoms in some cases beginning during childhood. We felt it was important to make an informed decision when it came to the possibility of passing this disease on to future generations.

MJD/SCA3 TL;DR

The first step

We made an appointment to see our GP, to discuss our concerns together with other questions we had relating to thinking about having a baby. Understandably, they don’t just hand out tests for this sort of thing, so she referred Dave to a genetic counsellor, with a view to having a test conducted. This referral and the subsequent genetic testing could be funded under the public health system, with a potential wait time of 2-3 months for an appointment, and a further 2 months for testing as the genetic counsellors are based in Wellington, and only visit Nelson every couple of months. Now that the decision had been made however, Dave was anxious to get the test done. We opted to enquire about funding the consultation privately to try and move things along a bit faster. At a cost of $300 for an appointment for the genetic counsellor, and an additional $AU250 for the test, we decided it was worth pushing forward. The genetic counsellor contacted Dave and kindly agreed to have our consultation via video call, so that we didn’t have to travel or wait for her next visit to Nelson.

During the call, the genetic counsellor was informative, eloquent and thoughtful in forming our case and talking us through the testing process. She had access to Dave’s dad’s medical records including his test results, and asked Dave some questions relating to how the disease has affected his family members, particularly his father and grandfather. She also checked whether Dave was currently experiencing any symptoms himself (thankfully he isn’t). We discussed why Dave had decided to take the test, and what our options were should he test positive.

Testing

After discussing the disease, causation, family history and our motivations the genetic counsellor talked us through the testing process. She mailed out a test kit and paperwork with a courier pack pre-addressed for the referral genetic testing laboratory in Australia. The kit consisted of two sterile swabs (like cotton tips) with vials of solution to put them in when the samples were obtained. The sample collection itself was simple; first thing in the morning (so before consuming any food or water, or brushing his teeth which would contaminate/dilute the sample) Dave swabbed the inside of his cheek with each swab before sealing it into the vial of solution. (So not that other thing you were thinking, but there is a story about that for later).

We were initially told the testing would take 3-4 weeks, and when the results came in the genetic counsellor would contact Dave to set up another video call to discuss them with us. After a tense wait with no news Dave emailed on the fifth week, and the genetic counsellor cc’d us in with correspondence she had after following up with the lab. They explained that the scientist who had started the test earlier that week had gone on leave unexpectedly, but we could expect results the following week. We were frustrated that they seemingly hadn’t even started the test until we followed up on it, but at least it sounded like we’d have the results soon. The next email said the entire batch of tests (including ours) had failed. As they investigated why and started a new test, we were told it would be another week before we received our results. We were beyond frustrated at this point! Finally, Dave received an email that the results were finally in, almost eight weeks from when we submitted the sample for testing. We set up an appointment to talk to the genetic counsellor that night, who very kindly rearranged her evening to fit us in.