Treatment Protocol

Here is my treatment Protocol as I currently understand it:

1. Firstly, I’ll need to call the FA nurses on day 1 of my next period (which I have been doing anyway to track my cycles). The week following they will courier me the medications and paperwork that goes with them, including more specific instructions as to the timeline and what is to happen when.

2. Approximately 2-3 weeks later, I will start injecting myself with a drug called Buserelin, which is a Gonadotrophin Releasing Hormone (GnRH). This is a modified version of the hormone my body produces to stimulate the release of Follicle Stimulating Hormone (FSH) which stimulates the follicles in the ovary to grow. These follicles are what develop into eggs during ovulation. Injecting the Buserelin will cause my body to adapt and stop secreting it’s own GnRH, effectively ‘switching off’ my ovaries. This is called ‘down-regulation’, and stops my normal hormones from interfering with the IVF process.

3. Approximately two weeks after starting the Buserelin, I will be told to take a blood test to ensure it’s done the job, and that my ovaries are ‘switched off’. Assuming this is the case, I will be advised to now start another injection, Puregon, which is a Follicle Stimulating Hormone. This Follicle Stimulation Phase is to stimulate my ovaries to start producing follicles and keeps them growing in preparation for egg collection. During this time, I continue injecting the Buserelin as well, but at a lower dose than before.

Flow diagram from Fertility Associates' 'Pathway to a Child' booklet

4. Approximately a week after starting the Puregon, I will be advised to have a blood test and potentially a scan (vaginal ultrasound) to track how many follicles there are, and how they’re growing. This can be done in Nelson, and depending on what this shows, I may need a follow up scan and test 2-3 days later.

5. The last scan I will need to travel to Christchurch for, and they will give me a final injection to administer that night. This will be Ovidrel, which is a copy of human Chorionic Gonadtrophin (hCG) hormone which will trigger ovulation. At this point I will be advised to stop the other two injections, and will again insert a vial into an injection pen to administer it into my stomach.

6. 36 hours after administering the Ovidrel (trigger injection) I need to be back at the Christchurch clinic for egg collection. For this procedure I will receive a narcotic sedation, and cannot drive for 24 hours following. At this point Dave will also need to provide a semen sample, which they will use to fertilise any suitable mature eggs that are collected from me.

7. The day following, they will call us to tell us how many eggs have successfully fertilised, and so how many zygotes (early embryos) we have. These are then incubated until they are 5 days old.

8. At day 5, they will let us know how many high-quality (viable) embryos there are (it is expected that some will not make it to this stage). These will each have a tiny sample (10-20 cells) lasered off and sent to the lab for genetic testing. The embryos will then be frozen to await results.

9. FA will contact us after 2-3 when the results come back, and if there is a suitable, high-quality embryo that tested negative for SCA 3, they can replace (implant) the embryo.

10. Again, on day 1 of my cycle, I contact FA, and they will advise me to start taking Progynova tablets 3 times a day. This contains Estradiol (E2/estrogen) which will help growing and preparing the lining of my uterus (endometrium) for implantation.

11. After approximately 10-12 days, I will have a vaginal ultrasound.

12. At day 12-14, I will have a blood test to check my progesterone level. When this is at the right level, they will advise me to start using Utrogestan vaginal pessaries 3 times a day. These are Progesterone (P4), which maintains the lining of the uterus so that an embryo can implant and cause a pregnancy.

13. Five days after starting Utrogestan, they will thaw and replace (implant) the embryo.

14. Ten days after transferring the embryo, I will have a blood test to find out if I am pregnant.

There’s obviously a whole lot more from here, but that gets us to a potential pregnancy anyway.

All Systems Go

This week we had our first series of appointments at the Fertility Associates clinic in Christchurch, which they helpfully scheduled these all for one day knowing that we’d need to travel.

Semen analysis
We started with Dave submitting a semen sample for analysis – this was the first one done by Fertility Associates, the one from the start of the year was organised by our GP. This was booked for 10am, and we had the option of him utilising a room at the clinic to produce a sample, or collecting a pottle prior to the appointment and bringing the sample to the clinic within an hour of collection. They also provided a page of instructions including how long to abstain for prior to collection (which depends on what the sample is to be used/tested for), and how to exercise basic hygiene to minimise contamination of the sample. Dave opted to drop a sample off, to the disappointment of his friends who wanted to know what ‘material aids’ may have been supplied at the clinic. We were directed to their lab by the reception desk, dropped the sample off, filled in the brief submission form and returned to the waiting room for our next appointment – we’d receive the results later.

Counsellor
Our second appointment was with the FA counsellor. She explained that due to being referred to FA for PGD, we’d sort of landed straight into treatment compared to a couple who had been receiving fertility advice often for months or years before treatment. This appointment was for them to get to know us and to get a feel for what our understanding was of the IVF treatment process, how it works, and (reading between the lines) how we would cope. We explained what we knew of the process we were about to go through, and discussed SCA 3 and the effect it has in Dave’s family. She asked whether we are talking to anyone about what we’re going through, and we told her about our belief in how important it is to discuss these things. We said that we are being open with our family and friends about starting treatment, even to the extent that I am writing this blog. She seemed satisfied with our conversation, and after making sure we knew we could contact her or other members of the FA staff at any time should we have questions or need additional support, concluded our appointment. Though an hour had been allocated, this appointment only took around 30mins as I guess she learned all she needed to from us in that time. We had a couple of hours until our next appointment, so headed out and came back in the early afternoon.

Drug education
The third appointment was with one of the nurses, to go over the regime of medications I would need to take as part of the IVF treatment process. 

The medications are provided in either a vial where I will be drawing up a dose into a syringe for injection, or in smaller vials which are inserted into an injection pen, which you fit a needle to and have an adjustable dial that you use to set it to your dose. I will be injecting myself daily, and the injections must be done at the same time each day. They are administered into the flab in my stomach in a line below my belly button. The nurse showed me an example of the vial, the syringe and needle, and gave me the opportunity to practice inserting a needle into my stomach. I gave it a go (figured best to do any trouble-shooting while there!) and it was easy, the needle is so small I actually didn’t feel it at all. This is where I’m glad I have no problem with needles, and am not at all shy of medical procedures!

Drug taking 101

Appointment with the specialist
Our final appointment for the day was with the fertility specialist overseeing our treatment. First they gave me a vaginal ultrasound, viewing my uterus (with IUCD in place), and both ovaries. They commented that everything looks normal and is in a normal position, so it should be a routine enough egg collection when the time comes. In my right ovary we could see one large follicle and 2-3 smaller ones, indicating that I am likely to ovulate from this one this cycle. In my left there were 3-4 smaller follicles.

After the scan, they checked the results from Dave’s sperm analysis from that morning, which were perfectly normal. This was all very reassuring, knowing that there are no surprises so far with each of us that could affect treatment.

We then went over the consent forms for treatment, one for IVF in general, one for this specific cycle, one from FA for the PGD, and one from the lab for the PGD. During this they mentioned again that they will use Intracytoplasmic Sperm Injection (ICSI), injecting an individual sperm into an egg directly, rather than just adding semen to the eggs. In this case, this ensures there are no other sperm attached to the outside of the egg, which could affect the results of the genetic testing. I also enquired about Timelapse Imaging Incubation (TiMi) which I had read about. During this process, instead of removing the embryos briefly from the incubator to observe and photograph their progress every couple of days, daily images are taken without removing from the incubator. They can even make a video of the embryo development. The articles I read suggested that the daily monitoring of development can help them better select which are the highest quality embryos. I asked whether they thought this was worth doing, if it could be part of our treatment program, and if it cost extra. The specialist said it is worthwhile doing, but more as they felt the incubator was better and therefore any more sensitive embryos were more likely to thrive. It costs $975 extra if we wanted to opt for this, which we are leaning towards doing. 

So now we wait for my next cycle and go from there. I have made a summary of the next sequence of steps as far as I understand it, and will make this a separate post as I've included quite a lot of detail. 

The Saga Begins

Approximately four and half weeks after the blood samples were submitted for feasibility testing I emailed the embryologist to check in and see how things were going. They responded that the feasibility report had come through fine, and they were in the process of planning a cycle of IVF treatment for me. At this stage, they just needed to determine how it could work around the time they are shut down over Christmas and New Years, but they would be in touch very soon! I’m not sure if I was more shocked or excited that my treatment will be starting sooner than we had expected, but we’re keen to get started.

About a week later I had a call from one of the nurses at Fertility Associates in Christchurch. They were in the process of narrowing down dates to book in our initial appointments, they just needed to plan with respect to my menstrual cycle and the holidays. They ended up needing to call me back the following week to confirm dates, as there are a whole chain of appointments that need to be carefully scheduled in sequence, and some things just weren’t lining up. The outcome was that we are booked to go the Christchurch FA clinic for a day in early December for our initial appointment, with me likely starting medications/injections in early January, and egg collection in late January. My understanding is that the PGD testing takes approximately 4-6 weeks, so if all goes to plan and there is a viable, healthy embryo, it’ll be some time around February that it can be implanted.

During our initial visit to the clinic in December, we are scheduled for three appointments across the day. The first is to see their counsellor, as all couples undergoing fertility treatment including IVF are required (or at least strongly recommended) to do so. The second is to see the fertility specialist who is overseeing our treatment. During this appointment I will have a baseline ultrasound to check that everything looks normal, healthy and ready to go. Finally, we will see the nurses for our drug education, where they will discuss the medications I am to take, and how to administer them. At some point during the day, Dave will also submit a semen sample for testing. We will also need to take our consent forms for treatment with us to the clinic, where we will be talked through everything and they will witness us signing each page.

The information booklet published and distributed by Fertility Associates.

In the meantime, for some light reading they sent out their official information booklet (also available online, it’s called Pathway to a Child) and our consent forms for treatment, which we have received. There are three consent forms that we both have to sign, one to consent to IVF treatment overall, one for this particular cycle of IVF, and one to consent to embryo biopsy for PGD, totalling 20 pages in all. I have also been advised to start taking folic acid at this point (recommended for anyone intending to become pregnant, to be taken until the 12^th week of pregnancy). I have also started trying to take better care of myself by watching what I eat and drink, and increasing my exercising.

So things are getting very real.

Our current timeline as I understand it (all going well):

•  Early December – initial consultations with FA counsellor, fertility specialist, drug education
• Early January – begin IVF medications
• Early-mid January – blood tests and scans
• Late January – egg collection and fertilisation
• Late January/early February – embryos biopsied for genetic testing and then frozen
• Some time in February? –hopefully thawing and implantation of a healthy, unaffected embryo, followed by blood tests to detect pregnancy.

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.