Euploid, But Not Equal: Why “Perfect” Embryos Have Different Odds

Why can two embryos both be genetically normal, both be labeled AA, and even be tested by the same genetics company… yet still have very different chances of leading to pregnancy?

In this episode of Taco Bout Fertility Tuesday, Dr. Mark Amols breaks down one of the biggest misunderstandings in IVF: the idea that “normal” means “equal.” He explains what PGT-A really tells us, why embryo grading is useful but limited, and how two embryos with the same label can still have very different biologic potential. He also dives into why IVF lab quality matters so much — from culture conditions and air handling to biopsy skill, freezing, thawing, and transfer technique.

If you have ever wondered why one euploid embryo works while another does not, or why some clinics may have better outcomes than others, this episode helps make sense of it all in a clear, patient-friendly way. 

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Transcript

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Today we talk about why two embryos can both look perfect on paper and yet still have very different chances of making a baby. I'm Dr. Mark Amols, and this is Taco about Fertility Tuesday. Let's talk about one of the most frustrating things in ivf. As a patient, you hear that an embryo is genetically normal. Maybe they hear it's Euploid. Maybe they hear it's an AA embryo. They might even hear that both embryos were tested by the same genetic company. And naturally, they would think, okay, so these embryos should pretty much have the same chances, right? And the answer is wrong. Not even close sometimes. And that's because one of the biggest misunderstandings in fertility is that normal means equal, and it doesn't. This means that two embryos can be called Euploid and still have different pregnancy potential. This means that two embryos can both be labeled AA embryos and still not be biologically the same. And that is why two clinics can both say they transfer Euploid embryos that are both AA from the same genetic company testing and have completely different success rates. So in today's podcast episode, I want to break down why that happens, what actually makes one lab better than another, and why two embryos with the same label can behave very differently in the exact same person. I think the easiest way to understand this is to realize that IVF patients are often given labels, and then those labels start to sound way more precise than they really are. Let's take the word Euploid. When we say an embryo is Euploid, what we're basically saying is that the sampled cells appear to have the right number of chromosomes. And that's important. It's actually very important. But what it doesn't mean is that this embryo is the same as every other Euploid embryo. What it doesn't mean is that this embryo is guaranteed the implant, or that this embryo is equally strong as the next one, or that this embryo is automatically the best embryo. It just means that it passed one major test, and that's a good thing. But passing one major test is not the same thing as winning the whole competition. Think of it like two houses being listed on Zillow. Three bedrooms, two bathroom, excellent condition. Okay, that sounds useful, but are those two homes actually the same? Of course not. One might have a stronger foundation. One might have been built better than the other one. One may have hidden issues that weren't apparent, and one may be just falling apart. The point is, same headline, but different reality. And that's what happens with embryos. Euploid is a headline, AA is a headline, but the biology underneath it, well, that headline can be very different. So let's talk about grading, because people love grades. And honestly, I get it. Grades feel really comfortable. When you hear aa, that sounds amazing. It's like your kid already got a great report card. So when you hear things like AA or ab, day five, day six, it feels neat. But embryo grading is still a simplified visual system. It's useful, but it's not perfect. When an embryologist is grading an embryo, what they look at is how it expanded, how the inner cell mass looks, how the trophectoderm looks. They look at things like how many cells are there, how compact it is, how symmetrical it is. Now, these things matter. But let's not pretend it's some kind of divine barcode system that's going to make the embryo do well. It's still a human visual assessment of a biological process. And that means if you have two embryos, both called aa, that does not mean they are equal. And if you use the Gardner system, which only uses abc, can you imagine greeting every human on earth with just three letters? Could you truly say that two people that are both labeled A are the same? And then imagine the people grading are, going to be different. Right. Some people may give an AA to everyone, others may be very difficult on grading and give everyone lower grades. And that's because it's subjective. It's not as objective as you would think. So how can two embryos both be aa, both be euploid, and still have different odds? Well, it comes back to that point that embryos are more than just their label. For example, if you look at embryos and how fast they develop into a blastocyst, that matters. Some have a stronger trophectoderm. Maybe one was more difficult to biopsy and they had a harder time on it. Maybe one embryo froze better and thought better, and things we can't see, such as biologically competent, can't be seen. And maybe one's better than the other than that. And that's the key point. There are things that matter about an embryo that are not completely captured by grading. And that's also true when it comes to chromosomal results. Euploid does not mean guaranteed to work. It just means in this embryo, the chromosome numbers is normal. So when the patient asks, but how can these both be AA euploid embryos and still have different success rates, the answer is simple, because the label is not the whole story. Well, now we get to the really important part. Why can one clinic get better results than another clinic, even when both are transferring normal embryos? And as we discussed, those are just labels, but how the embryo was created, how it was handled, how it was biopsied, frozen and thawed, and even how they were transferred, well, it makes a difference. And that's where the lab comes in. A really good IVF lab is not just a room with incubators and people in scrubs who look stressed and very expensive, by the way. A really good lab has very tight quality control. They have things like stable culture conditions, excellent temperature and ph management, and very good air handling. The air system and the incubators alone can make huge differences in the success rate. Also, the quality of the embryologists make a big difference. If an embryologist is not skilled in biopsies, that can hurt the embryo. If an embryologist is making too large of a drop on the straw, that's going to be frozen, that can prevent it from thawing later. And that's because embryos are very fragile. So a clinic who's constantly opening up their incubators, they're going to have lower rates because those embryos are going to be exposed to temperature fluctuations more often. A, clinic that's right next to, let's say, a diesel station and doesn't have a good air system is going to have lower rates. Embryos are just doing their best to try to stay alive and not get annoyed. And in ivf, sometimes even small annoyances can matter and can affect those cells, leading to lower pregnancy rates. So when you see one clinic with stronger outcomes than another clinic, it doesn't automatically mean the other clinic is bad, but it may mean one lab is simply more consistent. Culture systems, air systems, if they're better, it makes a difference. If one's biopsy technique is gentler, again, makes a difference. These small details matter. And, this is one of the hardest things to explain to a patient because from the outside, clicks kind of all look the same. And if they're using the same grading system and the same genetic testing company, well, you would think the results would be similar. And I can say they all do care. They all use things like advanced and cutting edge. And that's because it is cutting edge. But these differences, they do matter. And so, unfortunately, these are the questions you have to ask. Do you have individual incubators? What is your error system? How long has your embryologist been there for? Then you can turn to the CDC and find out, hey, is their pregnancy rates as good as the other place? Now, Keep in mind you can't really compare things directly. A, 64 is not better than a 62, but a 62 is definitely better than 32. That you can say no clinic can cherry pick patients and be that much better by 30%. So it's important that when you look at it, keep in mind that, yeah, 5, 10% may not be that big of a difference, but a 10, 20%, that is something of a difference and they're probably doing something a little bit better. But the other thing to look at too is look at the number of cycles they do. Someone shooting a basket four times and getting four in a row, yeah, that's possible. Someone shooting a basket and getting 100 in a row, that's very unlikely. And so a clinic that has more transfers and more retrievals, those numbers are going to be more accurate than the clinic that ends up having only 20 cycles. But the clinic that's doing only 20 cycles, you can't really extrapolate that and say this is how they are because there's not enough cycles to be able to truly know if those results are going to be valid. Another area that patients may get hung up on is this. Both embryo's were tested at the same genetic company. So shouldn't they basically be the same quality? Again, no. Yes, that one part may be valid and that company may do very well. So you can say both companies have the same confidence in the results. But it doesn't mean the embryos are the same because again, they weren't grown in the same lab, they weren't biopsied by the same team, or even frozen by the same team. And here's what, really messes with people's head. Even in the same patient with the same uterus, in what seems like the same situation, two embryos that have basically identical grading can still have completely different possibilities when it comes to success. Yes, the uterus matters, and if someone's failing multiple times, there could be a uterine problem. But the point is, the embryo still matters. And because we can't identify every factor that affects implantation, one embryo may be stronger and we have no clue of that. Unfortunately, we're not there yet. And, both embryos may look good and from our standpoint they do, but clearly they're not, because some embryos work and some don't when they look exactly the same. So what should you take away from this episode? Well, first, a, euploid embryo is good news and it's worth being very happy about. But it's not a promise. The second thing is the grade. Sure, AA is fantastic, but keep in mind that the lab still matters a lot, and so that AA grade just says that in their opinion it looks really good. But when you're comparing clinics, don't just ask whether they use pgt, don't just ask whether they transfer Euploids, ask how the whole system is. Ask about the experience level and the quality of lab. Because IVF success is not just about the labels that are put on the embryos, it's about the entire system. And that's the reason why two genetically normal embryos that have the same grade can have different pregnancy rates. Because normal M does not mean equal in ivf. Yes, the label does tell you something, it just doesn't tell you everything. And that's why one euploid embryo can work, another may not, and why one lab may consistently do better than another lab. They both have the same headline, but the labs are still different. It's just not as obvious. Hopefully this podcast was helpful for you. Maybe these questions have popped in your head and you thought the same thing of why did that work and this one didn't. More important, hopefully this gave you the tools to be able to ask your clinic and help you decide between clinics by knowing these different things. To ask if you know someone who's maybe going through IVF or trying to pick clinics, let them know about this podcast episode. It might help them. As always, I greatly appreciate everyone that listens to this podcast. I appreciate all the people who send me ideas to tbftewdirectionfertility.com and if you like this podcast, tell your friends about it. Give us a five star review on your favorite medium. But most of all, keep coming back. I look forward to talking to you again next week on Taco Belt Fertility Tuesday.