Our First Rollercoaster

It’s been a bit of an odd week. On Wednesday I had a blood test as scheduled to check my body’s response to starting the Puregon (FSH) injections the Friday before. I had my blood drawn first thing in the morning as instructed, and a Fertility Associates nurse called me just after 2pm that day. They let me know that my blood test suggested my ovaries weren’t really responding to the FSH injections, as my oestradiol level was only at 189, and they would hope it would be in the late hundreds or early thousands at this point. They said it’s looking likely that we wouldn’t achieve egg collection this time as the blood test indicated that I wasn’t producing or maturing any or many follicles, and we might need to try again with a different medication regime. She double-checked that I was administering the medications correctly (I was) and said to continue with the same doses and they would refer me for a scan and another blood test on Friday to see if anything had changed. Apparently, sometimes it can take the ovaries a little longer to respond to the FSH injections for patients on what they refer to as the ‘long cycle’, which is IVF treatment cycles like the one I’m on where they start with the Levlen (or equivalent) pill for several weeks before a few weeks of Buserelin.

We felt a bit deflated and disappointed, but not devastated. The injections haven’t been too taxing on me as I don’t mind self-administering them and I haven’t experienced any side-effects so far except for bruising on my poor stomach. This wouldn’t count as one of our two funded IVF cycles, as a cycle is only considered complete once an embryo has been implanted (unless they have to call the whole thing off for medical reasons). It was frustrating, but we started coming to terms with trying again next time.

A stock photo showing a follicle in an ovary. (I'll try to get photos of mine next time)

I had my blood test done Friday morning as instructed and had my scan (internal ultrasound) done later that morning. The technician measured my ovaries, and then measured and counted any follicles they found in each ovary. They found 3 larger follicles that they said ‘met the criteria’ in one ovary, plus several smaller, less developed ones. There was another larger follicle and a few small ones in the other ovary. The technician couldn’t tell me what this might mean for my treatment, so I had another long afternoon waiting to find out.

My stomach after 30-odd injections over the last few weeks (it doesn't feel as bad as it looks).

Finally a nurse from Fertility Associates called later Friday afternoon. They wanted to give my follicles a little more time to develop and wanted me to keep giving myself the injections. I am to travel to Christchurch in time for a blood test and scan there first thing Wednesday morning next week, with a view to egg collection on the Friday. We are relieved to hopefully still be on track after all. 

To add to the excitement, the pharmacy that Fertility Associates sent my Puregon prescription to (I need more to get through to the appointments and MUST inject it daily) is closed over the weekend. In desperation I approached a neighbouring pharmacy, which while they didn’t stock Puregon were able to tell me the other one is open for one hour 9:00am-10:00am on Sunday as a methadone clinic. The pharmacist even knew someone who worked there and was kind enough to call them for me and confirm that I’d be able to collect my prescription during that window.

It’s going to be a busy week.

Down-regulated

On the 22nd of January, in accordance with my treatment plan I started injecting myself with Buserelin. This, together with the Levlen ED pills I was taking, 'switches off' or down-regulates my ovaries by stopping the production of lutenising hormone (LH) and follicle stimulating hormone (FSH). These injections are self-administered into my stomach across a line in the area below my bellybutton, and must be done at the same time every evening. The needles are so small (29G, 12.7mm long) and the volume injected so small (0.4ml) that most of the time, I don't even feel it penetrate my skin, or the liquid inject. A few seconds after injection, the site does start to tingle, and it raises and looks and feels like a tiny insect bite for a few minutes before abating again. Sometimes there is a small pinprick mark or bruise visible the following day, but not always. On one occasion I must have accidentally nicked a tiny blood vessel, as a tiny drop of blood was visible when I took the needle out, and I had a larger bruise there for a about a week. I alternate between injecting on my left and right side to avoid accidentally using the same site two days in a row. Following my plan, I stopped taking Levlen on the 29th of January. With the exception of spotting and mild stomach cramps a couple of times a day the whole time I was taking Levlen, I thankfully have not experienced any of the more severe side effects from the Buserelin such as mood swings, and have felt and acted like myself the whole time.

Thankfully, the daily injections haven't been an issue for me so far.

On the 4th of February I had a blood test as scheduled, where they check if I have down-regulated by testing my levels of LH, Oestradiol, and Progesterone. As instructed I called Fertility Associates later that afternoon to obtain my results and further instructions. I spoke to a nurse who read my results from my file, and advised that my blood test indicated that I have down-regulated. For logistical reasons, the plan now showed that I am to start my Puregon (FSH) injections and lower my Buserelin dose from 40 to 20 units on Friday 7th February instead of Wednesday 5th as orginially planned. Dave and I are also both to take our doses of Azithromycin on Friday. This is a prophylactic antiobiotic against Ureaplasma, a bacteria known to increase the chance of miscarriage during IVF using ICSI (intracytoplasmic sperm injection). See https://www.fertilityassociates.co.nz/media/1712/updated-fertility-facts-ureaplasma-and-azithromycin-for-ivf.pdf for more information on Ureaplasma.

Following on from my updated plan, I am to take my next blood test on Wednesday 12th instead of Tuesday 11th February. They said it is likely that I will have a scan in Nelson on Thursday or Friday next week (to be confirmed following the blood test) followed by a second scan in Christchurch possibly the following Monday, but also still to be confirmed. From here they will give my Ovidrel (trigger injection) and advise me on when to administer it. I will travel to Christchurch again 36 hours after using the trigger injection for my egg collection procedure.

Starting Medications

When day one of my cycle arrived, I phoned Fertility Associates to let them know as instructed. The nurse I spoke to went through a list of questions, took some notes and then let me know that someone from my team would call me back. That afternoon they called back, and said they’d like to start me on Levlen ED, starting that night. They sent the prescription through to a pharmacy near me so I could collect it that same day.

Interestingly, Levlen is actually a commonly prescribed oral contraceptive pill, the same one in fact that I took for over ten years before deciding to try a copper IUCD instead. While seemingly counterintuitive to IVF, this is commonly used at the start of a treatment cycle. The low dose estrogen in the pill stops the release of Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH). This causes down-regulation or ‘switches off’ my ovaries, a step which actually increases the reliability of the treatment cycle in most women. They decided to start me on Levlen before I start injections because it starts the same process (down-regulation), but the first injection (Buserelin) can apparently make you feel pretty crappy (basically PMS), and starting the Levlen first will apparently help temper this effect.

Two and a half weeks later, Fertility Associates called to let me know that they were couriering my medications to me, and they arrived the next day. In the courier package were:

·        Medication vials of Buserelin and Puregon (with chilly pack as are refrigerated)

·        Syringes, needles and a Puregon injection pen

·        A sharps disposal container

·        A specimen container

·        A letter detailing my treatment plan with important dates as they currently stand

·        Information sheets on the various medications, protocols and contact information

·        Lab forms for the blood tests I will have in February

·        Prescriptions for Azithromycin for both Dave and I. This is an antibiotic that is used as a prophylactic against Ureaplasma, a bacteria commonly found in the reproductive tract that is hard to test for, but is known to increase the chance of miscarriage during IVF and ICSI.

The medication kit that arrived from Fertility Associates.

The current timeline:

20^th December: Start Levlen ED pills.
22^nd January: Start daily Buserelin injections.
29^th January: Stop Levlen ED pills.
4^th February: Blood test to check down-regulation.
5^th February: Start Puregon injections, continue Buserelin injections at lower dose. Start
      Azithromycin.
11^th February: Blood test to check response to Puregon.
17^th Feburary: Trigger injection (Ovidrel) and egg collection is expected this week, dependent on further scans and blood tests.

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.