The Embryonic Olympics: Making Our Embryos for IVF
We have embryos! While my husband and I are thrilled to be at this stage in our fatherhood journey, it has not come without some unexpected ups and downs.
In this article, I want to describe the process of creating our embryos. This figure gives an overview of the steps and numerical results from each stage in the journey:
I will describe the process, challenges, and results from each of the following stages:
Egg retrieval
Fertilization
Development
Genetics
Embryos
Throughout this Embryonic Olympics - my new term for the process given the feats of strength that these clumps of cells have performed - we have three ‘medal-winning’ embryos. They are all gold medal winners to us, and this is the story of how they came to be.
Egg retrieval
I have previously written about my husband and my selection of our egg donor (https://www.babymoonfamily.com/original-articles/choosing-egg-donor) as well as the general medical procedure of egg donation (https://www.babymoonfamily.com/original-articles/egg-donation-procedure), so please read these for a bit of additional information about the process.
Our reproductive endocrinologist estimated that we should expect about 20 eggs from the retrieval, given our donor’s age, anti-mullerian hormone (AMH) level, and overall healthiness. However, two days before the retrieval, after she had already received the majority of her hormone stimulation cycle, she had an ultrasound at the IVF clinic. The clinic reported to us that they had observed only 7 oocytes.
We were crushed. Not only was this not what we had been told to expect, but we knew the calculations of embryo creation in that each stage results in significant decreases. So, starting out with 7 oocytes meant we should not expect more than 1 or 2 normal embryos.
While my husband and I are still undecided about a sibling journey, no one starts out this process expecting a single embryo. Yes, there are heterosexual couples who have medical infertility where 1 or 2 embryos would be amazing. However, we are medically optimized on our journey. We have a healthy, young egg donor, and our reproductive endocrinologist had set our expectations to a number almost three times the reality we were now confronted with.
We do have a ‘piece of mind’ program with our IVF clinic and agency, ensuring that we will have a child at the end of this journey. However, the thought of having to choose another egg donor and start the process over again - after taking over a year to get to this point - was extremely disheartening.
I couldn’t sleep the next two nights while we waited for the retrieval. As the stress and sleep deprivation were becoming almost unbearable, we received a secure health message from the IVF clinic. The retrieval had gone well and without complications (amazing), and they had retrieved 18 eggs!
It seems that the last two days of hormones had allowed our egg donor to more than double her oocyte count. It felt like we could breathe again for the first time in two days, and that night I slept like a baby. It seemed like everything was back on track.
Of the 18 eggs, the clinic stated that 14 were ‘mature’ and capable of undergoing fertilization. A ‘mature’ egg is one that has a structure called a ‘polar body,’ which indicates that the oocyte has reached nuclear maturation and is ready to be combined with sperm (1).
We were still thrilled with this result. 14 eggs was double our expectations after the pre-retrieval ultrasound. I also did some additional research, and it seems as though 15 oocytes is the ‘magic number’ when it comes to egg retrievals.
There have been two scientific studies in the last decade that analyzed hundreds of thousands of IVF cycles and pregnancies in the U.S. and U.K., and found that the likelihood of successful pregnancy rose with each additional egg retrieved, up to about 15 eggs. Outcomes leveled off when 15 to 20 eggs were retrieved, and then steadily declined beyond 20 eggs (2, 3).
These studies indicate that egg retrievals with more than 20 eggs likely result in a higher proportion of these eggs being immature or unable to successfully undergo fertilization and/or implantation. Knowing this, we were excited to continue the process with our 14 mature oocytes.
Fertilization
About 10 months ago, my husband and I flew to Los Angeles to undergo our medical evaluations and deposit our sperm, which you can read more about here (https://www.babymoonfamily.com/original-articles/clinic-masturbation).
Our IVF clinic’s protocol is to utilize intracytoplasmic sperm injection (ICSI) when fertilizing eggs with thawed sperm. I have previously written about ICSI and why it may be better for previously frozen sperm (https://www.babymoonfamily.com/original-articles/icsi).
So, our 14 mature oocytes were divided equally, and then 7 were fertilized with my sperm, and 7 were fertilized with my husband’s sperm.
ICSI, like all things in science, is not as perfect as we would like. From this procedure, 4 of the 7 eggs combined with my sperm were fertilized, and all 7 of the eggs that underwent ICSI with my husband’s sperm were successfully fertilized.
We now had 11 embryos ready to undergo development.
Development
The new embryos undergo 7 days of development in the lab before they are graded and genetically tested.
At this point, we were in the fortunate position of having 11 possible embryos. However, our contract only covered preimplantation genetic testing (PGT-A) for 8 embryos. Because there could be no delays in the testing of the developing embryos, we had to decide now if we wanted to biopsy and test all 11 or only the 8 that were covered. This would mean the untested embryos would go directly into cryopreservation.
This decision was not one we were prepared to make, but we quickly did some additional research on the impact of freeze-thaw cycles for embryos, knowing that if we needed the untested embryos, they would have to be thawed, tested, and then re-frozen before they could be used.
The other consideration was cost. Each additional embryo cost $350 to test. While an extra $1,050 is not a lot when you are already paying $225,000 for the journey, it is still more money and therefore warrants some evaluation.
One study from 2018 analyzed how multiple freeze-thaw cycles negatively impact pregnancy outcomes and found that embryos that underwent repeat freeze-thaw cycles resulted in lower pregnancy rates compared to control embryos. However, this result was only significant when the embryos that underwent the multiple freeze-thaw cycles had average or poor morphology (or cell structure) (4).
The science seemed to indicate that multiple freeze-thaw cycles could have some impact on the success of pregnancy, not to mention the possible damage that could result from the additional manipulation of the embryos through these procedures. Therefore, we decided to allow for all the embryos to be genetically tested before cryopreservation.
Genetics
Immediately before the biopsy, the 7 day old embryos were evaluated for successful development. As with each stage in this process, the numbers continued to decline. Of the 4 eggs fertilized with my sperm, only 2 had successfully developed and were biopsied. For my husband, who had 7 fertilized eggs, only 3 had developed normally over the week in the lab.
Given this, our previous concern on having more than 8 embryos to test was no longer applicable. So, our 5 embryos underwent biopsy and PGT-A testing, and then we waited an additional 2 weeks for the results.
Embryos
Finally, after about a month of waiting and communicating frequently with the clinic through secure health messaging, we had the results of our genetic testing and grading of our embryos.
Embryos fertilized with my sperm:
5AA with normal chromosomes
4CC with abnormal chromosomes
Embryos fertilized with my husband’s sperm:
4BC with normal chromosomes
4BC with normal chromosomes
4AB with low-level mosaic chromosomes
So what do these results mean?
To start with the embryo grade, this is composed of a number followed by two letters, and this grade encapsulates three elements: Blastocyst development, fetal cell quality, and placenta cell quality (5).
The blastocyst development is numbered from 1 to 6, with 6 being the most advanced and described as ‘hatched.’ However, anything at grade 3 or above is described as ‘full.’ For the first letter, this is the fetal cells or inner cell mass (ICM) quality. This group of cells will eventually become the fetus. The second letter is the placental cells or trophectoderm epithelium (TE) quality. This group of cells will eventually become the placenta. Both the ICM and TE are graded from A to C, with C being the fewest number and lowest quality of cells.
For the PGT-A results, normal means there are a normal number of chromosomes (46 or 23 pairs). For abnormal results, this means there are either missing or additional chromosomes, and these embryos would either not be viable or result in significant birth anomalies such as Down Syndrome. Embryos that are mosaic can have different proportions of normal and abnormal cells. A low-level mosaic embryo, such as one of ours, would have mostly normal cells and a lower percentage of abnormal cells.
Given these results, our total embryo count for implantation is three, with the grades being 5AA, 4BC, and 4BC.
Epilogue
If you had asked me at the beginning of this process how many embryos we would end up with, I would have guessed seven. Not only is it a good (and lucky) number in general, but given what I had read about retrievals from healthy egg donors and the reductions along the process, seven seemed a likely estimate.
Ending up with less than half of that and having struggled through some sleepless nights of anxiety, I am hard pressed to say we are ‘ecstatic’ at the results. However, we have genetically normal, higher grade embryos who have survived what I am now calling the Embryonic Olympics, in part because we have 3 embryos and also because we just recently came back from the Paris 2024 Summer Olympics.
We have excitedly chosen to not know the sex of any of the embryos, and we are also open to any embryo being implanted first. In a process that is so procedural and formulaic, having some elements of the unknown are a welcomed feature.
These are the three embryos that were meant to be for us at this time. While the chances of successful implantation are high (over 60% for the first attempt), it is not guaranteed. If we do not have a successful pregnancy from these embryos, we will take a deep breath and start again, possibly with a new egg donor.
However, at this time, we have our embryo champions on ice, and we await the next exciting stage in the journey: Meeting a gestational carrier.
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