Embryo quality: is the best looking embryo always the best choice for transfer?

Dr Daniel Hlinka, Clayo Clinic, Czechia: I’ve been an embryologist for a very long time, more than 35 years. I’m still an active embryologist, doing basic embryological work such as ICSI and biopsies. What I’m aiming for now is a connection between gynaecology and embryology.

The story of the embryo starts from the oocytes, and the oocyte develops in your ovaries. Your ovaries are in your body, and your body has been living for some time. So it is a very age-dependent quality of the oocyte, which starts in you, and we have to create a healthy embryo after a very long time of it being in your ovaries.

All these aspects of creating viable embryos must be considered before we start treatment. So, my function is not only to teach my new embryologists, because I’m a bridge between old-time embryology and the new, very cut-down embryology, which is shortened just to five-day blastocyst culture supported by some PGT testing. I also introduce the older parts of embryology that are still useful today in some specific cases.

As the owner and CEO at our clinic, I devote a lot of time to speaking with patients before they start treatment, to help them set realistic expectations.

Dr Vladimiro Silva, PharmD, Ferticentro & Procriar, Portugal: I’ve worked in the fertility industry since 2003 for 22 years now. I used to be the lab director at a Portuguese clinic called Ferticentro. Then I was one of the founders of Procriar in 2019, a clinic in Porto. We created a group called Assisted Reproduction Alliance and joined a clinic in Lisbon. Now we have 4 more clinics in our group, in Denmark with the Maigaard group, and in Greece with the New Life group.

I started by doing a bit of what you both are doing—talking to patients a lot. Then I moved into being more of a lab rat, and now I’m back outside of the lab. I still speak directly to patients daily, and I do a lot of conferences and interventions with patients. Nowadays, I’m a bit more distant from real lab practice, but I speak with lab directors and embryologists in our group daily. We’re always reviewing scientific information.

It’s a pleasure to be here. I’ll try my best to answer the questions. Just a little comment on the title of this webinar: “Is the best-looking embryo always the best choice?” It’s kind of a reminder that we actually don’t know exactly what we’re doing, because we don’t know the answer to that question.

Dr Daniel Hlinka, Clayo Clinic, Czechia: Basically, you have to understand the process of embryo selection. First, before we answer this question, we should go back to the previous topic—whether the best-looking embryo is the best choice.

We must clarify that in embryology, we are facing millions of years of evolution. Our goal is not to evaluate embryos like a Miss Universe contest. It is not about selecting the most beautiful ones. During my long career, I have seen many cute babies born from totally ugly embryos—and vice versa. For example, tripolar cleavages, when an embryo cleaves from one to three cells immediately—so-called direct cleavage—can look very advanced and beautiful. Embryologists who are not skilled might select them, but those embryos are totally abnormal.

Now, step by step, I will go to the differences between day 5 and day 6 embryos. First, we must understand what we are evaluating in embryos. There are two basic properties:

1. Viability – the chance to develop to blastocyst stage after 5 or 6 days from fertilization.

2. Genetic constitution.

These two properties are not correlated. Many embryos can look viable but are genetically abnormal. For example, embryos with Down syndrome, Klinefelter, Turner, Patau, or Edwards syndrome can develop nicely and implant, but they are genetically abnormal. We are looking for embryos that can produce a healthy child—not just establish a pregnancy. Pregnancies from abnormal embryos may result in miscarriage or fetal abnormalities.

There are three main sources of genetic abnormalities:

• Inherited

• Meiotic (arising from oocytes or sperm, especially in older women)

• Mitotic (arising during early embryo cleavage)

The first two types cannot be recognized by microscope or time-lapse systems. Only mitotic errors, like abnormal cleavages, can be recognized visually. So to fully evaluate embryos, we must combine time-lapse systems, grading systems, and PGT testing.

Older women have more meiotic abnormalities. These embryos may not develop to blastocyst stage. Sometimes, we must decide whether to wait for a blastocyst or transfer earlier embryos (like day 3) and rely on prenatal diagnosis if pregnancy occurs.

The difference between day 5 and day 6 embryos reflects oocyte competency. Competent oocytes produce embryos that cleave on time, and reach the blastocyst stage on day 5. These are the better embryos. Embryos from poor responders or older women may lack mitochondria, which delays development. These may reach blastocyst on day 6. If these are just delayed and not compromised, they can still lead to viable pregnancies. However, some day 6 blastocysts are the result of abnormal cleavage and cell loss. These are compromised. So yes, I prefer day 5 blastocysts when possible.

Dr Vladimiro Silva, PharmD: Ferticentro & Procriar, Portugal: I think Daniel pretty much covered all of our intricacies. One thing we all need to bear in mind is that humans generate abnormal embryos all the time. Even when we are at the top of our fertility, for example, a 25-year-old woman and a 25-year-old man doing things naturally on the right day, without any fertility problems on either side, still only have a 25–30% success rate. Why is that? Because of random variability in human cells, sperm and eggs.

The older a woman gets, the less likely the embryo is to be normal. In fertility labs and clinics, we have been trying to assess embryo quality for quite a long time. When I started 22 years ago, we were looking at embryo morphology, and what are we doing now? We are still looking at embryo morphology. Of course, now we do it in a very different way. Nowadays, the norm is blastocyst culture. When I started, it was day 2, day 3. Rarely did we go to day 5, and even less to day 6. That was not considered. But it has now become more common. In the United States, they often go to day 7.

We still base our assessment on embryo morphology and use classification systems. For example, in Portugal and Spain, we prefer to work with the ASEBIR classification—the Spanish association of embryologists. In Portugal, we follow their indications closely. In other places, it’s the Gardner classification. There are many systems worldwide, and they are all good. Some are more informative than others. Nowadays, we are in the era of artificial intelligence. There are systems using algorithms that value parameters not understandable to the human eye. It’s very complex.

Putting it all together, I would say this: a disclosure of interest, I am very much in favour of preimplantation genetic testing. When someone is in favour of something, they tend to see only the positive aspects of that theory or technology. It is normal human behaviour.

Now, I will justify why I am in favour. It all goes down to the genetic quality of the embryo—that’s the most important factor. We look at morphology, but I’m sure you’ll agree that if you compare a very good-looking embryo from a 44-year-old woman with a less good-looking embryo from a 29-year-old woman, the chances of implantation are always higher with the embryo from the younger patient. It’s statistics.

Embryo development depends on many factors. Some are caused by us in the lab through our manipulation, CO₂ pressure, pH level, temperature control, quality of incubators, and the quality of our culture media. These factors do affect embryos.

Whether it’s ICSI or conventional IVF, the timing between stripping and placing the embryo in culture, the type of manipulation—all these affect development. Even the culture media matters. In some media, embryos go faster than in others. The difference between day five and day six sometimes depends on what time your embryology lab closes. If a blastocyst is just starting to expand, you may decide to leave it for tomorrow. But if the lab stays open two more hours, you may freeze it on day five instead of day six. Many such aspects play a role.

Again, I will repeat: it all goes down to the genetic quality of the embryo. That depends on many factors. The most important one is whether the embryo has a normal chromosomal constitution, which depends heavily on the age of the female patient.

I once heard a geneticist say that 70% of the likelihood of an embryo being genetically normal depends on the egg, and the other 30% depends on the sperm. We know the egg has some ability to repair DNA damage in the sperm.

Dr Daniel Hlinka, Clayo Clinic, Czechia: That’s a tricky one. Short answer—yes.

We have to understand that the embryo is influenced by three factors: the oocyte, spermatozoon, and in vitro conditions. Everybody must consider that in vitro conditions are not the same as healthy in vivo conditions, meaning in your body. Embryos from different people are differently resistant to in vitro conditions.

If we are going to state a strategy for embryo evaluation and transfer, we start by evaluating the previous history of the patient. If they are coming to us at 45 or 46 years old, not accepting donation, and have failed to produce embryos to the blastocyst stage, there is a usual assumption—this is natural selection of embryos, and those not able to develop to the blastocyst stage by day five would die even after transfer. But that is absolutely not true. We have many patients, and as I said, I am a bridge between the old approach and the current day five transfer approach. If I see sensitive cases, based on previous history or diminished ovarian reserve, where we can expect less resistant embryos, I always start with a day three embryo transfer.

There are many successful results. You must understand that statistics offered by clinics (e.g., 55% pregnancy rate after day five transfer) do not speak about cancellation or cycle rates. This means that out of 100 patients, only 70% had a transfer. The other 30% had no transfer at all. They do not mention cumulative pregnancy chances.

If you have just one embryo and we evaluate treatment success by cumulative chances, what are your chances of pregnancy after transferring all embryos from one stimulation? Then the more embryos we have, the higher the cumulative chances. If we rely only on day five or day six transfers, we may shorten the number of embryos transferred and ignore cancelled cycles with no transfer.

If we aim for personalised medicine, we must evaluate case by case: the patient’s history, age, and what is happening in our laboratory. The final decision I make is based on evaluating embryos in our time-lapse system with our own selection and grading, not Gardner’s, because we do not evaluate just one picture or basic morphology. That would be too late to properly evaluate the embryos.

Dr Vladimiro Silva, PharmD, Ferticentro & Procriar, Portugal: It can happen, obviously. What is the difference between fresh and frozen eggs? That’s important. For a long time, egg freezing was not done because the results weren’t good. When we started using vitrification, the whole fertility industry—the results become very good. The main suppliers of vitrification methods now claim and show consistent success rates above 90%. We can have very good survival rates after vitrification. But one thing is looking at 1,000 eggs, and another is your specific case.

If the vitrification process is successful, then the results we get from frozen eggs should be the same as from fresh eggs. We know that embryo survival after vitrification is 98–99%, but egg survival is a little lower, around 90–92%, because eggs are more delicate. They have more water inside; it’s a more delicate process. The lab must be optimised, and the person doing vitrification should be doing it daily. There’s a learning curve. When someone returns from holiday, they need to re-practice to get their hands back in sync before working on real samples.

It’s a manual technique. Some automated systems exist, but are not as good as manual ones. In that case, we don’t know what happened. Maybe the donor eggs were not of good quality to begin with. Maybe there was a male factor. But 90% of the time, results should be the same. 10% of the time, they are worse.

Dr Daniel Hlinka, Clayo Clinic, Czechia: Just a comment about the difference between fresh and frozen embryo transfer. I get this question very often from clients and patients. Many demand frozen embryo transfers because, in their experience, everyone around them got pregnant from frozen transfers. This is just a statistic.

Fresh embryo transfers often represent the first cycle. Those who don’t get pregnant go on to frozen transfers. So, among 100 women, if 20% get pregnant after the first fresh transfer, and 60% achieve pregnancy in subsequent frozen cycles, it creates the illusion that frozen transfers are better.

But IVF is invasive. I always say, “100 times nothing wouldn’t kill an elephant.” So if we don’t need to do something, let’s avoid it—same goes for biopsies. If there’s no risk of ovarian hyperstimulation or high progesterone (which could prematurely mature the endometrium), then we should perform a fresh embryo transfer. Otherwise, of course, we avoid it. But when possible, I prefer fresh. There is no real advantage to frozen over fresh embryo transfer. What matters most is a viable embryo and a receptive endometrium. This is the key to pregnancy.

Dr Vladimiro Silva, PharmD: Ferticentro & Procriar, Portugal: I think this is one of those cases where my answer will really depend on PGT—pre-implantation genetic testing. Just explaining to the public what PGT is: we create the embryos, we take the embryos until day 5 or 6, and then we do a hole in the embryo, we retrieve some cells—5 to 10 cells—and we send those cells to a genetics lab.

When we retrieve those cells, the embryo has more than 100 cells. These cells are taken from a part of the embryo called the trophectoderm, which is considered to be representative of the total genetic constitution of the embryo. Theoretically, the analysis of these 5 to 10 cells will tell us whether the embryo is viable or not.

Why am I advising this to this patient? This will not increase her chances of having a baby, but it will change the type of information that she has. With the quality of our embryologists and the quality of our laser systems, the chances of the embryo being damaged by a biopsy, being frozen, vitrified, and then thawed for a subsequent frozen embryo transfer are very low. This is true in good quality clinics with good quality embryologists.

That will mean the world to this patient because if we get to a moment where we just don’t have blastocysts—which seems to be the case—or if we have blastocysts but they are not viable, and that happens one, two, three, four, five times, then it’s a personal decision—the moment you decide to go to egg donation.

We know the statistics: at the age of 46, we’re looking at maybe less than 1% chance of having a viable embryo. Having said this, probably all of us have seen patients having babies older than 46, but those are very rare cases. In my 22 years of activity, I saw a 51-year-old patient getting pregnant naturally after getting pregnant with egg donation. At 49, at 51, she got pregnant naturally. I’ve seen IVF patients; the oldest I’ve seen was exactly 46 with their own eggs. After the age of 46, I never had a case. If you go to the statistics, there are cases reported. It’s a question of chance. These things are so rare that this is the reason why we don’t see them all the time.

It’s a very personal decision. If you feel like you want to have your baby and move on with your family as soon as possible, I would strongly advise you to go through egg donation. If you feel you are still not ready to make that move, you are producing eggs, obviously 4 eggs if you feel strong enough, also financially strong enough to try two or three more times, it’s medically acceptable.

We can try. I would definitely advise you to test your embryos to help you decide. Testing the embryos will not improve their quality. If they’re bad, they will remain bad. If they’re good, they will remain good. But it will help you make a decision. If you’re not changing your mind because of that decision, then you don’t do PGT-A. You can say, “I want to transfer my embryos no matter what.” Then it makes no sense to do the PGT.

PGT is for people who are hesitating between using their own eggs or moving to egg donation. It is something we really need to analyse, discuss with the patient—talk about money, talk about physical effort, talk about chances, and also what it means in terms of her family, the relationship with her partner, if she has a partner.

It’s a very personal discussion that involves physical, technical, medical, psychological, and economic aspects. It’s a complex decision. But in these patients, all patients above 37, I recommend PGT-A. In a case such as this, I would for sure recommend it.

Dr Daniel Hlinka, Clayo Clinic, Czechia:  Try to imagine: what are the biggest advances in IVF? Hormonal stimulation, ICSI procedure, and vitrification. Without these three steps, IVF would never be in the situation it is today.

Frequently, it is very common that some women are afraid of stimulation because of cancer. There is a very big belief about the risks of stimulation. My question is: why are patients undergoing hormonal stimulation for therapy if it would be a risk? I don’t want to comment more on that.

Let’s speak about chances in natural cycles. After normal hormonal stimulation, we can collect, for example, 10–12 oocytes. Ten would be fertilised, and from these 10 fertilised, we can have four to five viable embryos. So in such a case, we can have cumulative chances. If the pregnancy chances after one embryo are around 30%, and we have five or six embryos, the cumulative chance to be pregnant from this one cycle is around 95–98%. Usually, these women are pregnant after 2 or 3 embryo transfers. Now let’s calculate 12 oocytes and speak about it in natural cycles. Natural cycles do not mean 12 mature oocytes in 12 months. One month will finish with no follicles. Or the oocyte wasn’t retrieved. Or the oocyte wasn’t mature. If it was mature, it wasn’t fertilised. If it was fertilised, the embryo development wasn’t correct.

So it doesn’t mean 12 months equals 12 oocytes. If someone wants to suffer every month from unsuccessful natural cycles, let them undergo it. From my experience, after 3 to 4 months, everybody is totally spoiled from it.

I don’t mind natural cycles if they are waiting for agreement from insurance companies. Until they get approval, they can come for natural cycles. If God wants, it can happen. But from my experience, the chances for pregnancy in natural cycles are around 1–2% maximum. As a couple, you would be totally destroyed. I would never recommend anybody to undergo a natural cycle for IVF treatment. This is my opinion.

Dr Vladimiro Silva, PharmD, Ferticentro & Procriar, Portugal: Unfortunately, there’s no way to do this. When a chromosomal translocation happens, a part of a chromosome is placed in another chromosome, and a part of the other chromosome is placed on the initial chromosome. So, the amount of DNA in that person is the correct amount. They have all the genes they need to be normally functioning persons.

However, when their gametes are formed, in this case, when the sperm is formed, the DNA is split in half. An adult has 46 chromosomes, 23 pairs. When we produce sperm and eggs, we only share 23 of our 46 chromosomes. However, if we share the chromosome that has an extra bit or a missing bit, we will be sharing the wrong amount of DNA to form the sperm or the egg. In that situation, the embryo almost certainly will not be viable.

There is no known method to ensure that only the right chromosome is shared. These persons, for every affected pair, have a 50% chance of sharing a good chromosome or a bad chromosome. That means the chances of having a normal embryo are always lower. It’s not exactly 50% lower, because it’s more complex than that, but yes, they are lower.

What we can do is create the embryos and then check them and see what happened. I’ve seen cases where all the embryos were affected. I’ve also seen cases where none of the embryos were affected. It varies, sometimes 1 in 5, 2 in 5, etc. It’s a question of luck. There’s nothing medicine can do to help. We can only check the final result. If the embryo has the correct number of chromosomes, we can transfer it. If it doesn’t, we should not transfer it. The only solution is to try again or use donor cells.

Dr Daniel Hlinka, Clayo Clinic, Czechia: This is a situation I mentioned at the beginning when the embryo can be compromised in development. If there are some abnormal cleavages, the embryo has several rescue mechanisms. We are facing millions of years of the evolution of embryos.

The embryo can save some normal cells. Until blastulation, the embryo sequestrates these abnormal cells under the zona pellucida. These cells are considered fragments. At this stage, to speak your language, these embryos are very ugly because they do not resemble those which we can see in books and literature. There are a lot of fragments, but under these fragments, there can be a healthy nucleus. Several cells can be uploaded, and from these two or three or four cells, they continue their development even though they were compromised by the number of cells.

Finally, on day 5, you can see the growth of these embryos. Their separated cells are squeezed under the zona, and finally, you can see very expanded blastocysts. Usually, those embryos are a little bit slower than those which are healthy because they have fewer cells. So usually on day 5, they are early blastocysts. If somebody wants to use them for a biopsy, they wait until day 6 to have more cells to perform a healthy or safe biopsy.

This is the discrepancy between ugly embryos having a lot of fragments and, on day 5, a nice blastocyst. Finally, you have to decide because embryo scoring is always performed between the embryos of the couple, not between embryos of different couples. If it is the only embryo developing to blast, it would be transferred, of course.

Dr Vladimiro Silva, PharmD, Ferticentro & Procriar, Portugal: There are two sides to this question: the technical side and the legal side. If I were making the laws, I would say yes. That would be my choice. I would do PGT-A always if I could. However, it is not legal, at least in Portugal. In some countries like Spain, you can do PGT-A whenever you want. In other countries, there are age cut-offs, female age cut-offs, regarding when you’re allowed to do PGT-A.

Why are there those cut-offs? Because the chances of having an abnormal embryo are very low with egg donors, supposedly the lowest possible. Just so the patients listening to us understand: when we are looking at PGT-A, we are looking at chromosomal abnormalities that are very likely to originate from the egg. So they are very related to the age of the eggs and the quality of the eggs.

This being said, it’s true that when we are using donor eggs, we are at the lowest possible probability of having a genetic abnormality. In Portugal, the cut-off is at age 37. For those 37 and up, we can do PGT-A. Egg donors are younger than 35, so we cannot. In certain cases, we can ask for permission to do PGT-A on egg donation cases.

For example, let’s say we have 10 blastocysts. We transfer one and get a negative result. We transfer two, then three, and everything else is okay. Furthermore, we test the endometrium, the microbiota for immune diseases, thrombophilia, and malformations—we do a hysteroscopy. This changes from patient to patient. But if we don’t see any other reason why the embryo isn’t implanting, it makes sense to test the other embryos. The IVF authorities, the regulator in Portugal, authorise it. We need to submit a request, and most of the time they accept it, although sometimes they reject it.

It’s also important and fair to say that ESHRE, the European Society of Human Reproduction and Embryology, still considers that we shouldn’t do PGT-A in all cases. It comes down to personal beliefs and expectations.

Like I said before, PGT-A will not increase the chances of a pregnancy. It tells us whether that embryo is viable or not. But the cumulative pregnancy rate, like Daniel was saying, will always be the same. If you’re okay transferring 10 embryos across 10 embryo transfers, we know that at the end, if only one embryo is viable, after 10 transfers, we will get one baby. If we can know which embryo is viable and transfer just that one, we’ll be saving the patient nine potentially failed embryo transfers. This is why I’m in favour of PGT-A. If it saves just one failed attempt, then it pays off.

Of course, there’s money involved. There are countries where PGT-A is very expensive, almost impossible to afford, while in other countries, it is state-funded or insurance covers it. So the financial reality also plays a role. My opinion on this is: if I were the regulator, yes, I would advise it. Since I’m not, it depends on where you do your treatment.

When regulators set those guidelines, it’s because when you do IVF with donor eggs, you get 65% pregnancy rates. These are general results all over the world. And if you do IVF with PGT-A-tested embryos, you also get 65–70% pregnancy rates. So the chances are more or less the same.

This is why they say that, since PGT-A doesn’t improve the pregnancy rate, they don’t recommend it. I don’t think they are seeing the problem from the right angle. It’s not about improving pregnancy rates. We know it won’t do that. It’s about reducing the time to pregnancy, the number of attempts, the psychological and emotional burden of the treatment, even the financial burden of repeated treatments, and the stress on the couple. It also depends on how much value you place on that.

Dr Daniel Hlinka, Clayo Clinic, Czechia: We do not perform conventional fertilisation due to different reasons, mainly because of a lack of fertilisation even in men with normal sperm. We are protecting women from repeated stimulation. We want to be on the safe side and ensure fertilisation. I started IVF with conventional fertilisation and saw many failed cycles for different reasons. Many times, we had contamination due to contaminated sperm and a lack of fertilisation, even in normal sperm men. Now, we perform only ICSI.

Now, regarding DNA fragmentation, this is a frequently discussed problem in men. Everybody must understand that DNA fragmentation can occur as a result of improper in vivo conditions and also in vitro conditions. Even in laboratories, we can have the release of free oxygen radicals that can damage DNA. For example, in our laboratories, we don’t use any kind of centrifugation, which can increase DNA fragmentation. We use simple micro-separation methods based on sperm motility.

Let’s go back to in vivo conditions. DNA fragmentation is often increased by a prolonged state of ejaculation in the epididymis. In many centres, they ask you to keep sexual abstinence for 3, 5, or even 7 days before providing a specimen. We do the opposite. We want to have a fresh sample. So, we require our patients to have 6, 12, or a maximum of 24 hours of sexual abstinence. If we still see high DNA fragmentation, we ask them to repeat and provide another specimen after 2 hours.

If even in such cases, there is still very high DNA fragmentation, we perform tests, and if needed, we consider surgical retrieval of sperm. But of course, this is very rare. Usually, low abstinence is enough to bring fragmentation under 10%. When combined with very gentle manipulation in IVF, it’s enough.

Dr Vladimiro Silva, PharmD, Ferticentro & Procriar, Portugal: I’ve never seen that shown in a convincing way in research papers. I think that’s the short answer. We’ve always postulated it, but I don’t think anyone has been able to demonstrate it. So, I would say no. The problems probably arise later, with a higher miscarriage rate or lower implantation rates. Those associations are well documented. But here’s one important note: most DNA fragmentation studies have technical problems.

There are different methods on the market, TUNEL, COMET, and Halo Sperm, and not all methods are equally effective in identifying DNA fragmentation. The DNA fragmentation test is done with one sperm sample, and the treatment is done with another. These are subject to different types of lab manipulation, exposure, etc., so this is extraordinarily difficult to assess.

I believe DNA fragmentation has a role. I’m not saying it doesn’t have an impact. What I’m saying is that, when you look at the scientific quality of the published studies, the lack of uniformity in methods makes it very difficult to reach conclusions. Recently, I was at a congress, the Best of ASRM. There were many talks on this topic, people in favour, people against. Some of the biggest specialists in the world reviewed all the studies, pointing out which ones were good and why.

The reality, as Daniel was saying, is that we don’t know. The best solution is to try to have more sperm collections, less time of abstinence, and work under the best possible lab conditions. Apparently, doing ICSI is more favourable, but I’ve also seen studies showing otherwise. Using ZyMot could be a solution. There are other things on the market, but the truth is, we don’t know.

Dr Daniel Hlinka, Clayo Clinic, Czechia: Just a final sentence on this topic. If we compare how the egg influences embryo development versus how sperm and DNA fragmentation do, I consider DNA fragmentation to have minimal effect on embryo development. The focus should be on oocyte quality, stimulation, and the overall health of the patient. There is no need to overestimate DNA fragmentation. That’s why we simply shorten sexual abstinence, and that’s enough.

Dr Vladimiro Silva, PharmD, Ferticentro & Procriar, Portugal: You’re already saying half of the answer. It depends. In the first 3 days, I would say it’s the egg. From day 3 to the blastocyst stage, well, that’s when the sperm takes action.

I wouldn’t say it depends more on the sperm or the egg. If there are problems with the sperm, they’ll be more visible after day 3. I recall one conference at the ESHRE, where a genetics specialist explained everything with basic science. 70% comes from the egg and 30% from the sperm. I don’t know how he arrived at that percentage, but intuitively, it sounds plausible.

Dr Daniel Hlinka, Clayo Clinic, Czechia: Again, it is case by case. This becomes a problem in particular situations. If we are speaking about sperm-related fertilisation failures, yes. It is rare when sperm is unable to activate the oocyte. That means it lacks the phospholipase enzyme that initiates fertilisation. In my career, I’ve seen five such cases.

Compare that to failed fertilisation due to oocyte issues. There’s another very important part of sperm, the centrosome. It is inherited and contains centrioles, which are lost during oocyte development. The oocyte brings mitochondria, but the centrosome comes from the sperm. It’s located in the sperm tail.

In very severe cases, oligoasthenospermia, cryptospermia, or azoospermia, with poor testicular sperm, we can see abnormal sperm tail behaviour. In such cases, the centrosome is also abnormal. If such sperm fertilises an egg, we can see abnormal cleavage because the centriole is responsible for the spindle formation, which directs embryo cleavage. In such severe cases, sperm can cause abnormal embryo cleavage. In such situations, since you can’t pre-select viable sperm with progressive motility, it’s better to use donor sperm. Otherwise, the woman might suffer repeated stimulation.