Embryo freezing & IVF: What happens after the retrieval? A personal account (3/3).

This is part 3 of Ovally founder Kathy’s personal daily account of her embryo freezing journey to Spain. Read the previous two posts on the stimulation period and egg retrieval. This set of posts takes you from the egg fertilization through embryo development, genetic testing, and freezing. It doesn’t include the last IVF step of embryo transfer.

Day 13 – we’ve got some embryos!

This morning we got a message from the clinic’s lab – all 30 retrieved eggs were mature, and 21 of my 30 eggs were successfully fertilized. A fertilization rate of 70% is pretty typical (80% would be a great rate). Some of our 21 embryos will now continue to divide until tomorrow when we’ll have our next update; some will fail to develop further. The embryos are swimming in culture in an incubator called an “embryoscope” and are being videotaped to monitor the cell division.

I’m still doing well physically and haven’t taken any pain meds. I had no cramping for most of the day but am experiencing some tonight; I’ll probably take a hot bath soon. The most annoying part is still being bloated – even though the follicles are empty now, they’ll remain enlarged until my next period, which is supposed to start in 2-5 days. So for now I’m still sleeping on my side and wearing skirts.

We took the train to San Sebastian on the north coast of Spain in Basque country today and can’t wait for dinner – the food is supposed to be incredible here.

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Day 14 – yikes, our embryos are getting grades

We got our second embryo update from the lab today – 15 of our 21 embryos are still developing and received grades from the embryologist. We got a number and a letter for each embryo; the number refers to its size and the letter to its quality (A being the best). The number identifies how the embryo has grown so far – by day 2, embryos should have divided, or “cleaved”, into 4 cells that each have a nucleus. To monitor the division, the embryologist watched time-lapse videos of each embryo developing in the embryoscope, its incubator. Really fast or slow growth can apparently point to potential chromosomal problems.
The quality assessment likely involved several factors, including a) the timing and synchrony of the cell divisions, b) the extent to which the cells are of equal size, and c) the number of fragments left behind after a division (many fragments are bad news). This visual, non-invasive grading helps figure out which embryos are the most likely to implant and lead to a healthy baby. It’ll be repeated every day until the blastocyst stage on day 5.
I’m still fine with no pain meds and am now just bloated (and ready for that to go away!).
We had some delicious Basque tapas called pintxos and the famous Basque cheesecake today.

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Day 15 – more grading & impatience

We got another update from the embryologist today – 15 out of yesterday’s 15 embryos are still developing. However, 4 of them were downgraded in quality, meaning they might’ve been dividing unevenly or left behind a lot of fragments after dividing, and 11/14 are now in a low quality range. We’ll get our next update two days from now after the lab has performed the pre-implantation screening test, which identifies any embryos that don’t have the correct number of chromosomes.

The waiting game while the embryos are developing in the incubator has been unnerving. While it felt like I could contribute something during the follicle stimulation period (even if I had no conscious control over most of those steps), having no influence on the embryos’ development in the incubator feels disempowering. We know to expect a drastic drop-off in the number of embryos over 5 days, but I still find myself worrying if there’ll be 1-2 healthy embryos left two days from now.

I’ve been feeling less bloated today, which has been really nice. Tomorrow I’m going to try and wear pants again!

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Day 16 – pants all day!

No news from the embryos today, but just a quick update that the bloating has gotten much better and I finally wore pants today that fit like they used to. We also took the train to Barcelona, our last stop on our embryo freezing journey, and I’ve finally understood the otherworldly magic that is the Basilica de la Sagrada Familia.

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Day 17 – still waiting

We were supposed to get an update on our embryos today, but the embryologist delayed the pre-implantation genetic screening, which tests for the correct number of chromosomes, by a day. The reason for the delay is our participation in a research study that will have better results on day 6 vs. day 5 of embryo development. It tests whether the genetic screening test can be done using the culture the embryos are swimming in instead of a cell taken from each embryo through a biopsy. Apparently more pieces of DNA can be found in the culture if we wait another day, so we have to have some more patience for the next update.

I was admittedly really upset when we didn’t get an update on the embryos today – we weren’t told why, and I was worried it was simply because somebody didn’t come into the lab on the weekend. I experienced something akin to maternal rage – were our embryos ok, what was going on, why was nobody telling us?! Luckily, we did hear back that the delay was only due to our study participation, but it still wasn’t entirely satisfying. Was it good for the embryos to be developing 6 instead of 5 days? Why hadn’t we been told in advance that they’d be in culture longer? The powerlessness and lack of information and control continue to be challenging.

The good news is that my period kicked in today, which means my system is officially resetting itself, and the bloating is gone. Today is our last day in Barcelona.

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Day 18 – and then there were 6

We’re back home in California. Christmas came early for us yesterday when we got the news that six of our embryos have been frozen, so I’m really relieved. Of the 15 embryos that had developed until day 3, 6 made it until the final day of blastocyst development. 9 out of the 11 embryos with bad ratings did not make it until the final day of development, but 2 of them must have turned things around, leaving us with 6 embryos of good quality based on the embryologist’s ratings. As a final step of screening, we’ll receive the results of the chromosome test in about a week.

The 3-dimensional rating system the embryologist used for the 6-day-old blastocysts was different from the 2-dimensional system on day 3. For the blastocysts, the first rating referred to their level of development on a scale of 1-6. For instance, a blastocyst receives the highest rating if it’s “completely hatched”, meaning it has burst through its “zona pellucida”, the shell that surrounds the embryo. The second rating corresponds to the quality of the blastocyst’s “inner cell mass” – ideally it shows lots of cells that make up a cohesive layer. Similarly, the third and last rating refers to the quality of the “trophectoderm”, the blastocyst’s outermost cell layer that will eventually become the nutrition receptor in the uterus, which should ideally show many tightly packed cells.

While a number of studies show that these ratings are predictive of later implantation and pregnancy success, researchers have also found that the grading of the individual components of the blastocyst is subjective and prone to variability between graders. Some labs have very strict cutoffs for the quality level of the embryos they’ll freeze, but some researchers have argued that these restrictions should be loosened, as embryos that are deemed lower quality based on subjective visual evaluation often lead to healthy live births.

The bloating is still gone and I’m just bleeding heavily after the treatment. Now the waiting for the chromosome test begins, though we’re definitely relieved to have 6 embryos for now.

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Day 25 – our chromosomal screening results are in

We received our results from the pre-implantation screening for chromosomal abnormalities a few days ago, and I’m going to give you a bit more background on the test, the results to expect, and the implications. To perform this test, an embryologist takes a few cells from each embryo and does a biopsy – an assessment of the number of chromosomes in each removed cluster of cells. Each cell should have a total of 46 chromosomes – 23 that came from the sperm cell, and another 23 from the egg cell. If all 46 chromosomes are identified, an embryo is considered “euploid”. If there are more or fewer than 46 chromosomes or chromosome parts, the embryo is referred to as “aneuploid”. Most “aneuploid” embryos will not implant in the uterus or lead to miscarriages. If they survive, some of the most common syndromes resulting from chromosomal abnormality are Down’s Syndrome (additional chromosomal material) and Turner Syndrome (missing/damaged X chromosome).

Of our 6 remaining blastocysts (6-day-old embryos), 4 were assessed to be euploid, 1 aneuploid, and the embryologist unfortunately couldn’t get a reading on the 6th embryo. This means we have 4 frozen embryos that we could thaw and confidently implant  should we need to try and conceive through IVF. The lab has disposed of the aneuploid embryo and kept the embryo without screening results for a potential repeat test. In the case that we’ll have undergone 4 unsuccessful rounds of IVF with our euploid embryos, they’ll thaw this last unscreened embryo, biopsy another cell, re-freeze it, and re-thaw it to use if it turns out to be healthy.

We’re bummed to have lost at least 1 embryo, though I’m trying to remind myself that it’s not unexpected. In 5-10% of cases, a biopsy isn’t successful – for instance, an embryologist may extract too few cells, in which case they cannot get a confident read. I also looked into the likelihood of having chromosomally abnormal blastocysts, and the literature reports a wide range: In one study, 45% of blastocysts were chromosomally abnormal (women aged 27-35), in another 57% (most over 35), and in a third 71% (all women over 35). All of these studies were done on IVF patients.

Aneuploid embryos don’t just occur at the blastocyst stage, but the reason a high percentage of embryos stops developing before getting to be 5-6 days old is that they are chromosomally abnormal. This means that the majority of embryos obtained through IVF are typically abnormal, and the likelihood of aneuploid embryos increases with age. This increasing rate of aneuploid embryos is hypothesized to be the main reason why couples struggle more with fertility the older they get.

We’re comfortable with having 4-5 healthy embryos should we need to return for IVF at a later stage. Our doctor gave us a 70% chance of a healthy baby per frozen embryo. Even if our chances turn out to be in the lower range, our 4-5 embryos should allow us to get lucky at least once. We’re glad that were were able to travel over the holidays for this treatment and really relax while we were in Spain. Overall, we were surprised at how much traveling and sight-seeing we were able to do, and I might’ve been lucky with the relative lack of side effects.

 

 

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