The Odds are Even

I had a missed call on my phone while I was at work yesterday, which I frustratingly didn’t see until after the Fertility Associates clinic would have been closed for the day. The specialist left a message saying they had our results (already!), and after some back and forth I was finally able to speak to them this afternoon. Of the four embryos biopsied, two were affected by the SCA3 gene, and two were unaffected. A textbook 50% transmission rate! We are super happy that we have two healthy, unaffected embryos so that we can have one implanted and one in reserve. It’s also great that the results were clear and that none came back inconclusive, as that could have required further testing and more agonising waiting. Both of the unaffected embryos were ones that were graded AB, so are also two of the higher quality embryos.

Autosomal dominant conditions like SCA3 mean each embryo has a 50% chance of inheriting the gene.

So within the next couple of weeks, I am to arrange with my GP to have my IUCD taken out some time before my next cycle starts. We will be using a ‘manufactured cycle’ to prepare my body for implantation, which means I will be taking more hormone medications to simulate what my body would be doing naturally had we conceived the conventional way. I am to call the clinic on my day 1, and they will advise me to start taking Progynova (estradiol (E2)) tablets. E2 is the main estrogen hormone usually released by developing follicles, and one of its purposes is growing the endometrium (uterine lining), which is what I’ll be taking it for. Fertility Associates will also make me an appointment for approximately 10 days later for a scan and blood test in Nelson to check my body’s response to the Progynova. They will also dispense Utrogestan (progestone (P4)) vaginal pessaries. This is another hormone normally made by a follicle once it has secreted its egg, and maintains the endometrium so that the embryo can implant and cause a pregnancy. An appointment will be made for approximately six days after the scan and blood test at the Christchurch clinic for an embryo to be implanted. Two weeks later I will have a blood test to see if the implantation has successfully resulted in pregnancy. From there, if I’m pregnant the risk factors will be roughly the same as a naturally conceived pregnancy, and so hopefully everything will progress normally from there. 

This is all starting to feel very real!

Four on Ice

On Wednesday, the embryologist from Fertility Associates called with an update on our embryos. To be eligible to be biopsied (sampled) for PGD, they need to develop to the blastocyst stage of development. This generally occurs around day 5 or 6 of development, at which point the embryo is comprised of approximately 200 cells. They said that of our nine embryos, one was developed enough to biopsy for PGD so far, and so had been biopsied and would be frozen that day. Four more embryos were looking promising for biopsy the following day. The remaining four weren’t looking as good, and while it is likely they wouldn’t continue to develop, they would continue to monitor them and make a decision regarding their viability the following day. On Thursday, three more embryos had been biopsied and frozen, and one more was still ‘trying’, so the embryologist said they’d give it until Friday to see if it too reached the blastocyst stage, and would call then to let us know.

Development of a blastocyst embryo

Today, the embryologist called to say the final embryo didn’t make the cut, which leaves us with four embryos in total biopsied and frozen, a great result. For each embryo, there is a 50/50 chance that they do not have the gene for SCA3, and will be suitable for implantation. We are cautiously optimistic that four embryos gives us a reasonable chance of one with a clear result. They sent the samples to the lab today for the genetic testing, and advised us that the results will take between 2-6 weeks. 

Further information
Blastocyst embryos are graded A-C according to their appearance and rate of development. They contain two groups of cells, one that develops into the foetus (the inner cell mass), and one that develops into the placenta (the trophectoderm). Embryos are given one grade for each of the two groups of cells. I asked how ours were graded, and three of them are graded AB, which is very good, and one is BC which isn’t as good, but embryos with that grade can still develop normally. The trophectoderm is the part which is sampled for PGD.

Diagram showing biopsy of the blastocyst's trophectoderm for PGD

Harvest

At 10:30pm on Wednesday night I gave myself the Ovidrel trigger injection as instructed. I worked out this was the last of 41 injections I have administered to myself in total (Ovidrel was the 41^st) in the 29 days between 22^nd January and 19^th February. When I woke up on Friday morning I drank lots of water up until two hours before the procedure (8:30am) when I had to go nil by mouth. The exception to this was the three paracetamol I was instructed to take with a sip of water one hour before egg collection. We reported to the laboratory at Fertility Associates just before 10am, and delivered the semen sample Dave needed to provide. The embryologist was actually the one who received the sample from us, and once Dave had completed the submission forms for the sample they took us straight into the day clinic and got us set up in a small room with a big chair in the centre. Here they went over all our paperwork, re-confirming my details and the medical history I had previously provided. I was then instructed to change into a hospital gown, and shortly afterwards a nurse came to take my observations (check blood pressure, heart rate and dissolved oxygen). My doctor then inserted a cannula into my hand ready to receive intravenous medication. They explained that I would be given a cocktail of midazolam and fentanyl for the procedure.

Once I was all set up, they showed us through to the theatre, where a team of six staff comprised of nurses, doctors and the embryologist were busy preparing. I was seated on a big chair with stirrups and surgical drapes were placed over my legs and abdomen. Dave was seated in a chair slightly behind and to my left, able to watch the procedure. I was given a nasal cannula providing oxygen, a dissolved oxygen monitor was placed on one hand and a blood pressure cuff on the opposite arm. They then injected the sedative medications into the port in my hand. The doctor used an internal ultrasound probe to guide a needle which was used to collect the eggs from my ovaries, which took around ten minutes in total. While I felt really light-headed and woozy, I was surprised to find that I was fully conscious for the whole procedure, and I think I can remember most of it. The medications obviously did their job though as I felt no pain or discomfort throughout the egg collection. I recovered really quickly from the sedation. They provide tea and toast before you leave to aid recovery, so after this and two glasses of water I was a little light-headed but ready to go after half an hour. After lunch, I just went about my day as normal and felt no further discomfort than the same slight bloating I’ve had for the last week.

Diagram showing how egg collection is carried out

When they were finished the team were really pleased to announce we had collected ten eggs in total, which is a great result! They will fertilise them in the laboratory later today using the ICSI method, where an individual sperm cell is injected into each egg (https://www.fertilityassociates.co.nz/media/1699/updated-fertility-facts-icsi-and-ssr.pdf). While this method is often used where sperm motility is an issue, in our case it helps ensure no additional sperm adhere to the outside of the egg or zygote (fertilised egg), which could confound the results of the genetic testing later. After discussion with our specialist we had previously decided to pay an additional $975 to use Time-Lapse Morphometry Imaging (TiMi). For this the embryos are placed in a special type of incubator that photographs them every 10 minutes as they develop (instead of removing them from the incubator to track progress), which can help embryologists detect which ones are developing most normally and identify the highest quality embryos (https://www.fertilityassociates.co.nz/about-us/latest-technologies/time-lapse-morphometry-imaging-timi/). This will hopefully help ensure we have as many embryos as possible reach the point where genetic testing can be carried out.

The lab will call us early tomorrow morning to let us know how many of the eggs have successfully fertilised. On Wednesday and Thursday next week they will call us to update us on how many embryos are developing well enough to be biopsied for PGD. On day five of growth they will then perform the biopsies on any suitable embryos and freeze them while we await the results of the genetic testing.

22/2/20 Update:

The lab called this morning, of the ten eggs collected, they were able to inject sperm into nine of them. And all nine have fertilised! They will develop them all to Wednesday/Thursday next week and call us each of those days to update us on how many are developing as they should. We are feeling cautiously optimistic. 

Thinking Fecund Thoughts

I managed to get my Puregon doses from the pharmacy in Nelson during the 9am-10am window on Sunday without incident. From Sunday/Monday I’ve been feeling a bit uncomfortable and bloaty in my abdomen – like I’m tight/full from eating too much but in a slightly different place. This is a common side effect from the ovary stimulating medications. Yesterday I headed down to Christchurch in time to collect my next Puregon dose from St George’s Hospital (they are associated with Fertility Associates but are open a little later). They only dispense as much medication as you need as they cannot accept returns due to them being refrigerated products, and they are very pricey. A Puregon 900 injection pen (contains 900 units, my dose was 300 units so three injections for me) costs $1035. While it has been quite stressful trying to make sure I had each dose in time, at ~$345 per dose I can see why they only dispense what you need, as you need it!

An image from my scan today. This is one view of one ovary. The dark, round objects clumped together to the centre left are follicles, each which should contain an egg.

First thing this morning I had another blood sample taken, and an appointment for a scan at Fertility Associates in Christchurch. My scan showed several follicles in each ovary that were measured and met the size criteria to have egg collection this week, as well as a few smaller ones. From what I could tell, ideal size is 18mm or larger in diameter, and a few of mine were at least 20mm, some around 18mm, and a few around the 13-14mm mark, although several overlapped each other so were a little difficult to get an accurate measurement. All in all, they seemed very happy with what they saw, and there were enough suitably-sized follicles to go ahead with collection this Friday. In preparation for this, a nurse dispensed to me the trigger injection Ovidrel, which contains human Chorionic Gonadotrophin (hCG) and is used to trigger ovulation. They talked me through how to use it – it’s another injection pen similar to the Puregon. It’s pre-loaded with the medication vial ready to use, all you need to do is dial it to the 250iu dose. They advised me that Fertility Associates would phone me this afternoon when they had received the results from my blood test to advise me when our appointment on Friday will be, and when to administer the Ovidrel – it needs to be 36 hours before egg collection. In the meantime, I do not need to inject any more Buserelin or Puregon. 

The tools of the trade. From top: case with Puregon injection pen with vial and needles, Buserelin vial with syringe/needle, Ovidrel injection pen.

The nurse called at 3:30pm, and advised that I need to have my Ovidrel injection at 10:30pm sharp tonight, in preparation for egg collection at 10:30am Friday. I am not allowed to eat anything for six hours before the procedure, and can drink clear fluids for up until two hours prior. I am also instructed to take three paracetamol one hour before the appointment, and Dave must provide a fresh semen sample for the appointment on Friday too. Interestingly, we are not allowed to wear perfume or anything overly strong-scented (though deodorant is ok as long as not too strong) as the eggs and embryos are very sensitive to chemicals and strong odours.

In the meantime, I'll just keep thinking fecund thoughts as we hope for a successful collection procedure yielding a good number of healthy eggs on Friday.

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.