Add-ons in fertility treatment – What you need to ask

After thawing, we can see the quality of the cells. We do the thawing under light microscopy, and the cells have a certain appearance; when they are living, they have a certain contrast, a colour, and a shade of grey inside. An experienced embryologist can see in light microscopy if the cell is living or degenerating.

During the thawing process, it’s recommended to wait two hours between the thawing and the transfer. Sometimes, we see that some cells look unusual, while others look good. When we freeze embryos at the blastocyst stage, the embryo has around 150 cells in the embryoblast and 150 in the trophectoderm.

In this stage, if some cells don’t survive, it’s usually fine. For example, in PGT testing, we take some cells from the embryo and send them to the genetic lab, so the embryo doesn’t need all these cells. It’s generally okay if about 90% of the cells survive; the embryo can rebuild, divide more, and recover from small cell losses.

After thawing, if we’re unsure if the embryo will develop further or stop developing, we need these two hours to be certain. When, after two hours, we see the embryo start to re-expand and make developmental movements, we’re sure it’s living and suitable for transfer. However, if after two hours the embryo still looks poor and hasn’t changed, we don’t transfer it. Instead, we thaw another embryo or take other steps.

So, yes, we can see if the embryo has survived thawing.

This is a tricky question. In a 43-year-old, it’s harder to reach the blastocyst stage because there’s a higher chance that the oocyte will be aneuploid and won’t fertilize or develop into a blastocyst. Not every 43-year-old patient will produce blastocysts in each cycle, but once we reach the blastocyst stage and do PGT-A testing, it becomes more individual.

Statistically, for a 43-year-old, I’d estimate around 10-15% of blastocysts may be euploid. In younger patients, like those up to 32–35 years, the quality of oocytes remains fairly high, but as age increases, the likelihood of aneuploidy rises, and quality declines. Even in younger patients, about 50% of blastocysts may be abnormal, so in older patients, this percentage decreases further. For some 43-year-old patients, they may have three blastocysts with two being normal, while others may have 6 with none being viable.

It depends. PGT-A testing has its limitations. As I mentioned earlier, a blastocyst has around 150 trophectoderm cells and 150 embryoblast cells. We only biopsy trophectoderm cells since embryoblast cells are the future children, and we don’t know the effects of sampling these cells. There’s also the issue of mosaicism, where not every cell in a blastocyst has the same genetic profile. Sometimes, we may take trophectoderm cells with abnormal genetics, but the embryoblast, which is the future child, is normal.

We’ve encountered cases where an embryo tested as euploid based on trophectoderm cells, but the fetus later tested as abnormal, or vice versa. Additionally, blastocysts have self-repair mechanisms, as seen in research on animals like mice and rats. Even if an embryo has some genetic issues, it may still repair itself.

So, if a patient has only one embryo, I would recommend transferring it because the information from PGT-A might not be completely reliable. If a patient has two embryos, I might recommend PGT-A on the second embryo. If there are three embryos, we could test the two freezing embryos and use the one with the best information for transfer.

In general, whole-couple PGT-A testing isn’t something I strongly recommend unless there’s a clear reason. Usually, only clinics with in-house genetic labs may push for testing because of the financial aspect. We don’t have a genetic lab in our clinic, so we send samples to other labs and maybe offer more objective advice. We only recommend PGT-A testing when we feel it’s truly worthwhile.

In biology, nothing is ever 100% certain, but generally, up to the 3rd day of development—when the embryo reaches around 8-cell stage—it relies entirely on the resources from the oocyte. You can think of the oocyte as being packed with “bricks” needed for early growth. Since the oocyte is the largest cell in the human body, it’s full of these “bricks” to support the embryo up to this stage.

After 3 days, the embryo needs to start making its own “bricks” for further development, which means it begins to use its own DNA. Before this, the DNA came entirely from the oocyte, but now it combines the DNA from both the mother and father. If there’s an issue with the sperm’s DNA, it often won’t appear until this stage when the embryo starts relying on its own DNA. At this point, if there’s a mutation or some problem in the sperm DNA, the embryo may not be able to produce the necessary components and could stop developing.

So, if an embryo develops well up to the 3rd day but then stops, it can be an indication—though not a 100% guarantee—that the issue might be with the sperm. If, for example, you have a batch of embryos, say ten, and they all develop well until the third day and then suddenly stop, it could suggest a mutation affecting all the sperm since they’re behaving similarly.

However, sometimes an embryo stops developing not because of a sperm issue but due to an issue in the oocyte or a mutation affecting later stages of development. If the oocyte doesn’t fertilize or develops poorly from the start, it might indicate an issue in the oocyte itself. But if an embryo develops well until the third day and then begins to degenerate, it can suggest a possible issue with the sperm—though this isn’t certain. There’s no absolute evidence, just predictions.

You could do PGT-A testing on the embryo to see what went wrong, but this would mean discarding the embryo to examine it. This may reveal that the sperm had an issue, but as I mentioned before, we need viable sperm for fertilization, and there’s no way to know beforehand if the sperm is good or bad. So, ultimately, even if you find a problem, it might not help much in the next cycle.

ZyMot is a company specializing in microfluidic sperm sorting systems. It had different names over time, and then it was bought by Cooper Surgical, so it may even have a new name in the future.

For the first question, yes, ICSI can be done on frozen and fresh oocytes. At our clinic, in the last two years, we’ve been using frozen oocytes in about half of donor cycles, maybe more. The fertilization rate and blastocyst rate are the same for frozen and fresh oocytes. There’s a slightly higher rate of degeneration in the freezing and thawing process, but once they survive the thawing, their quality is comparable to fresh oocytes. So yes, ICSI can be done with frozen oocytes.

Regarding the second question, yes, there were some studies I read from large groups showing a small difference in the male-to-female birth ratio with ICSI—about 51% male and 49% female, not a significant difference like 60/40. There could be other factors involved, not just ICSI itself. Large statistical studies sometimes show this, but they’re not definitive. Some studies, published quite a while ago, stated this minor difference, though.

Yes, let me explain. In our clinic, we use time-lapse monitoring for PGT-A, and here’s why. To perform PGT-A as safely as possible, we need the embryo to exit the zona pellucida naturally. There are other ways to biopsy cells, such as cutting into the zona, but I’ve found that embryos respond best when we collect cells during their natural extrusion. When the embryo is moving out of the zona pellucida, we take trophectoderm cells from the extruding part, which minimizes impact—often the embryo doesn’t even react as if anything was done. It’s the safest approach, in my opinion.

To ensure the best timing, I use time-lapse monitoring, which allows me to check in from home. Living in Prague, I’m about 15 minutes from the clinic, so I can plan the biopsy precisely, even if it’s late at night or early morning. For a patient with several embryos, timing is manageable. However, for older patients with one embryo, where we’re trying to be as cautious as possible, biopsy timing becomes even more critical. Time-lapse lets me monitor the embryo in the incubator remotely, so if the timing is right, I can come to the clinic, even after putting my own kids to bed.

This is why we use time-lapse for PGT-A biopsies. Since time-lapse dishes and incubators cost significantly more than standard ones, we have to charge extra for this. If the patient only needs the PGT-A biopsy without any other selection methods, time-lapse is part of that service.

The worst-case scenario in morphology isn’t a specific Z1 or Z0 score—there’s a range, let’s say, from 0% to 100% quality, with 100% being best and 0% worst. Various irregularities can appear in oocytes: there can be debris in the perivitelline space (the space between the zona and the oocyte), shape irregularities, cytoplasmic granulation, vacuoles, or smooth endoplasmic reticulum (SER) clusters filled with fluid. Initially, when these SER clusters were discovered in oocytes, WHO recommended not fertilizing them. However, later studies showed healthy babies were born after ICSI with these oocytes, so now we proceed with fertilization if we have them. In donor oocyte cycles, we only use oocytes of good quality, discarding the rest. But in cycles with a patient’s own oocytes, we use every viable oocyte, including those with SER clusters, and sometimes even get blastocysts and transfer them if no better embryos are available.

I’m not entirely sure. I might know it by another name. This is an AI-based tool. As I mentioned earlier, AI is advancing in our field as well. In the Czech Republic, though, there’s a requirement that AI tools need CE Mark certification for medical devices, specifically class 2A, to be used here. Without this certification, we cannot implement them. I don’t know if Magenta has this certification. I know only the iDAScore from Vitrolife has it, but there are a few AIs with this level of medical device certification.

Also, I’m currently involved in a scientific project on AI in embryology, and we’re deep into research to see what is possible and reliable. I’ve tested some AIs in my lab, and some aren’t yet at a stage where I’d trust their results completely. I’d need to check Magenta specifically, but in the Czech market, it’s still challenging to use these technologies fully due to certification and reliability issues.

Yes, I’ve worked in 3 labs in the Czech Republic. One did egg collection on Sundays, but the other two—including the one I currently work at, Gynem—only do collections on Saturdays. The doctors can adjust stimulation to 1 day earlier or later, depending on the patient’s response. Sometimes, Sunday would be optimal for egg collection, but I’m not a gynaecologist, so I don’t do stimulations.

Generally, we have to balance scheduling. We also work Sundays for freezing and biopsies. During the week, we have 8 people in the Gynem lab; on weekends, just 2 or 3 depending on patient numbers, and usually 1 on Sunday. We work every Saturday and have staff for certain procedures on Sundays too.