Implanted

Having travelled to Christchurch yesterday in preparation for our appointment, today we went to the Fertility Associates clinic. I was told to arrive with a full bladder, and was previously advised by the nurse that a good way to ensure this was to empty my bladder approximately one hour before my appointment, and then have two large glasses of water. A full bladder is easy to find via ultrasound, and helps position your uterus for viewing.

On arrival, the receptionist issued us each with a face mask (covid-19 level 2 precautions) and took us to the waiting area for the laboratory. After a couple of minutes the nurse called us through into a separate private room, went through the usual identity checks (full name, date of birth, address) and then gave us a run down on what we needed to know for the appointment, and for the days following. They said that of our two unaffected embryos, the five-day old one (the best one) had been thawed ready to be used. They also gave us a USB card with footage of the development of each of the two unaffected embryos from the TiMI (Time lapse Morphometry Imaging) incubator we used. They then gave us space for me to change into a gown, before we were taken through to the theatre whether another nurse and the specialist were waiting. One nurse was assisting the specialist, the other was on standby ready to pass the embryo from the lab, and Dave was seated next to me. They used an ultrasound probe (on my stomach this time) to try and visualise my bladder as a reference point, and then my uterus. Despite drinking water and feeling full, apparently my bladder was still so small it barely registered on the screen. They tried inserting the speculum, and tried threading the catheter through my cervix, which can sometimes help improve visibility and also help them 'feel' what they're doing. This felt a little uncomfortable, but not too bad. After a few minutes, the specialist decided they weren't confident enough they were in the right place, so they asked me to go back to the private room and drink some more water in the hope that a bigger bladder might improve visibility on the ultrasound.

The card given to us containing footage of our embryos. If you look closely, you can see embryonic development depicted on the card.

Around one litre of water and 10 minutes later, they took me back through to try again. My bladder was bigger, but my uterus still wasn't clearly visible, though the speculum and catheter showed up better on the ultrasound this time. The specialist explained that sometimes the position or the angle of the uterus can make it harder to see, or even some days it can be easier to see than others, depending on what your bowel and bladder are doing. They were satisfied that the catheter threaded through my cervix into the right place, and decided to implant the embryo 'by feel', which they explained was how they always used to do it before ultrasound technology was good enough to assist. They'd prefer to see via ultrasound as well, but it isn't imperative. The embryo was passed from the lab in a small (1ml) syringe that the specialist attached to the catheter, which was used to transfer and implant it into my endometrium (uterine lining). The nurse then double-checked the syringe to make sure the embryo had been transferred.

A stock photo of a blastocyst embyro similar to the one implanted in me today. For privacy reasons, we have decided not to post a picture of our actual embryos. You know, in case one of them is a person one day.

So now we wait. I am to have a blood test in approximately two weeks time to check to see if this implantation results in a pregnancy. In the meantime, I can go about my normal activities, though I will be making mindful choices about consuming pregnancy safe food and drink, just in case. Cautious optimism from here on.

T-minus 7 days and Counting...

On Thursday I had an early morning blood test and internal ultrasound to check whether my body was responding to the Progynova (estradiol) tablets that I am currently taking three times a day. The blood test measured my levels of LH (lutenising hormone) and progesterone to see if the levels in my body will help provide the right environment for an embryo transfer. The ultrasound examined and took measurements of my ovaries, cervix and endometrium (uterus lining).

At lunchtime, a nurse from Fertility Associates called and said my blood test results look good, and as of Thursday, my lining was 6mm thick, which is enough for the transfer to go ahead as planned next week (though I'm not sure what the reference range is). I'm to start taking the Utrogestan (progesterone) pessaries from Saturday, and continue the Progynova. I will also continue taking folic acid, and the oral probiotic supplement I have been taking aimed at supporting urogenital health through healthy flora (which I obviously cleared with my doctor prior to the start of my treatment cycle).

The current cocktail, since I'm off the booze.

We will drive to Christchurch next week for an appointment on Thursday to have one of our two frozen embryos thawed and implanted in to me. This is apparently very straightforward, and we should be in and out of the clinic in about half an hour. We are now at Covid-19 alert level 2, so Dave will be allowed into the clinic with me. Although this doesn't make as good a story as "Dad waited in the car outside while mum got pregnant", it does feel right to have both prospective parents in the same room at least when pregnancy hopefully begins.

Aaand we're back

At the start of this week, on April 28th 2020 New Zealand downgraded our Covid-19 alert from level 4 to level 3. This takes us out of complete lockdown, and allows more businesses to operate provided social distancing and appropriate non-contact measures can be taken. Fertility Associates sent an email and posted a general advisory on their website, which stated which treatments they are currently able to conduct. This includes manufactured embryo transfer cycles, which is the category that we fall into. 'Manufactured' refers to the process of using medications to generate an artificial menstrual cycle, ensuring my body provides the right environment for the transfer of embryos. I called to confirm our eligibility to continue treatment, and also to check this included permission to travel from Nelson to Christchurch. I was advised that we can go ahead, and that Fertility Associates are considered an essential service so we are permitted to travel there.

In preparation, I made an appointment and had my copper IUCD removed by my GP, since my previous appointment had to be cancelled as we started moving towards lockdown. I then called Fertility Associates on day 1 of my cycle, and after going over a checklist of questions with me, the nurse advised me to immediately start taking the Progynova (estradiol (E2)) tablets three times a day. I already had the prescription, but they will send another to make sure I have enough as I will need to be taking it for several weeks. As I mentioned in an earlier post, E2 is the main estrogen hormone usually released by developing follicles, and one of its purposes is growing the endometrium (uterine lining), which in this case will prepare my lining for the embryo implantation. 

The embryologist then called to go over the details of my plan for this cycle, which they emailed with a lab request form for a blood test, a letter declaring Fertility Associates to be an essential service (for when we travel), and a consent form for us to sign for this treatment cycle. I am to have a blood test and a scan (in Nelson) on May 14th to check how my body is responding to the Progynova. They will call with the results, but all going well, on May 16th I will start self-administering Utrogestan (progestone (P4)) vaginal pessaries. This is another hormone normally made by a follicle once it has secreted its egg, which maintains the endometrium so that the embryo can implant and cause a pregnancy. At this stage, the tentative date anticipated for embryo transfer at the Christchurch clinic is May 21st. Two weeks later I will have a blood test to see if the implantation has successfully resulted in pregnancy. 

Locked Down, but not Out

Since I've had a few people ask, I thought I'd let anyone wondering know that the next step in our IVF treatment will be postponed until the COVID-19 emergency is under control, and normal routines and services can resume. For those reading this overseas, as of 11:59pm tonight (Wednesday 25th March 2020) New Zealand is going into complete lockdown, with the exception only of essential services. For most people, this means remaining in their homes with the exception of trips to the supermarket/doctor/pharmacy if necessary, and we are allowed out to walk in our neighbourhoods for 'fresh air', provided we maintain social distancing from others of at least 2 metres.

Following the Prime Minister's announcement on Monday that we would be progressing to COVID-19 alert level 4: Lockdown within 48hours, a generic email was sent out from Fertility Associates. It provided a case-by-case list of what the plan would be for people depending on what stage of treatment they were at. As I have not yet started medications for my embryo transfer cycle, or been given a date for transfer, it will happen at a later time. We had figured over the last week or so that our cycle would likely be postponed, particularly since our next step, embryo implantion, would involve return travel from Nelson to Christchurch. We are feeling pretty relaxed about it, and feel fortunate that our cycle is at a good natural stopping point. As things stand, we have two healthy, unaffected embryos safely frozen, where they can stay for weeks, months, or even years if necessary. When society is able to return to normal, however long that takes, I can start the hormone medications in preparation and be implanted then. In the meantime, we will hunker down and wait this out with everyone else (from a socially distant proximity). I also figure now probably isn't the best time to get pregnant given the strain already placed on healthcare, and presumably maternity facilities will be extra busy in nine months time given the extra alone time many couples now have!

Stay safe out there everyone.

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.