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Double board-certified obstetrician-gynecologist and reproductive endocrinology and infertility specialist Erica Bove discusses her article “A clinician’s guide to embryo grading in IVF.” Erica breaks down the complex metrics used to evaluate embryo quality, a subject often reserved for subspecialty fellowship training. The conversation guides listeners through the critical developmental milestones from fertilization to the blastocyst stage. Erica demystifies the alphanumeric grading system used by embryologists to assess viability and explains why a “perfect” grade does not always guarantee a healthy pregnancy. The discussion also weighs the nuances of genetic testing (PGT-A), clarifying when it offers a true benefit versus when it might add unnecessary risk to the embryo. Discover how to interpret these technical reports to manage expectations and make informed choices during the IVF process.
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Transcript
Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast. Today we welcome back Erica Bove, obstetrician-gynecologist and reproductive endocrinology and infertility specialist. Today’s KevinMD article is “A clinician’s guide to embryo grading in IVF.” Erica, welcome back to the show.
Erica Bove: Thanks so much, Kevin. It is great to be here.
Kevin Pho: All right. What led you to write this article, and tell us what this article is about?
Erica Bove: Absolutely. So I am a reproductive endocrinologist, which means that day in and day out, I help people understand IVF and the results. Part of that is understanding the quality of the embryos. What I am finding is that people come to me with their heads spinning. They just do not understand. They might think: “OK, I have five embryos. How does the lab know which one to transfer? How did they rate them? Does day five versus day six matter?” People are really anxious about understanding what I call the alphabet soup of embryo grading. So I really wanted to make that more accessible to people as they are undergoing the IVF process.
Kevin Pho: All right. I am excited to relearn about this too because the last time I learned about this was probably all the way back in medical school, like 30 years ago. So give us a primer in terms of the basics for those who are new to this area.
Erica Bove: Absolutely. So one of the big assets of IVF is that we can use the embryos sort of against each other for embryo selection. When I think about it, it is kind of like asking which is going to win the race in terms of giving the best chance of a person getting pregnant with that embryo. We have different methods to look at. We have an egg and a sperm that come together. We retrieve the eggs through a transvaginal egg retrieval, and the lab then sorts through that fluid and picks out the eggs.
Then there are two different ways to fertilize those eggs. One is conventional insemination, which is like a recipe mixing the eggs and sperm together. The second way is called intracytoplasmic sperm injection, or ICSI for short. That involves physically injecting one good sperm into one good egg. Those are the different ways. The next day after the egg retrieval, the lab looks at what is in the lab and can really see which of those eggs has fertilized at that point. It goes from two independent cells, ideally to an organism that has two pronuclei, one from the egg and one from the sperm, in terms of the DNA contributions. Those two pronuclei embryos mean that they are normally fertilized eggs with a diploid set of chromosomes. From that point, that is the denominator to look at embryo development.
In our field, we can either do two types of transfers: a day three transfer or a day five transfer. When we are talking about a fresh IVF cycle, day three means that the embryos have divided to the point where they are around eight cells each. So we can look at the number of cells on that day, and we can also look at the grading of the cells to see how those cells look under the microscope. Then we make our best determination. An 8A is like the best that we can get on those days. Although anything with six cells or 10 cells can certainly make a baby. We like to see As and Bs in the grade because that sort of helps us understand that the embryos are meeting their milestones and the cells look healthy.
On day five, it is actually very different. By that point, thinking of exponential cell growth, the embryos should really be blastocysts. This means they have an outer rim of cells, the part that becomes the placenta, and then this inner cluster of cells, the part that hopefully becomes the baby, with fluid in between. That is called a blastocyst. When you look at those gradings, it is actually a much different scale or language. I am happy to go into that as well.
Kevin Pho: So when you are looking at these cells underneath the microscope, tell us some of the things that you are looking for. Is the grading subjective, or are there objective measures? What are you looking at under the microscope?
Erica Bove: Absolutely. It is interesting because you can’t see all the cells in one plane. I don’t know if you use a microscope on a day-to-day basis. I don’t typically, unless I am in the lab. You kind of zoom in and out to look at the different cells. You can count the number of cells in this day three embryo, and ideally you want to see eight cells because the embryo goes from two cells. Then there are mitotic divisions leading to four cells, and then eight cells. Those are very symmetric cell divisions and even numbers, which we like to see.
So you can look and truly count the number of cells. Then from the qualitative appearance of the cells, you want to see cells that are whole, circular, and not fragmented. Sometimes you can see these little granules where it almost looks like the cells are degenerating. You want to see these nice, crisp, round structures that are the cells. As we know, these cells then end up differentiating. A very nice structure is ideally eight cells without cell fragmentation, where each cell looks very cohesive and there are nice even numbers.
To your point about the subjectivity, I would say it is a lot easier to grade a day three embryo with less subjectivity compared to day five because there are fewer parameters. In general, nobody is going to argue with the number of cells that are counted for the most part. But regarding cellular fragmentation, determining whether it is an A or a B involves subjectivity. I will tell you, in my lab we have even more distinctions. That is where that subjectivity comes in. There is an 8B+, which is almost an 8A, but not quite an 8A. We have an 8B-. When you get into Cs and Ds, that is when we are talking about a lot less cell cohesion and more fragmentation.
Kevin Pho: What are some of the variables that affect the viability or grade of an embryo?
Erica Bove: Absolutely. Maternal age still seems to be the most important predictor of egg quality. It is super fascinating. If you look at a 40-year-old woman and she makes five or six blastocysts, we know that about 80 percent of those blastocysts will be abnormal. But if you look at somebody who is 32, roughly about half or maybe even up to 60 percent of those blastocysts will be normal on the chromosomal level. Certainly egg quality, which is related to age, is the most important predictor of that.
Sperm quality is also interesting. If there is a sperm issue, we will often see good day three quality because the male genome is not even turned on until day three. So you might see poor day three to day five progression, which suggests more of a male etiology, but it can be really hard to tell. Other variables can affect egg quality. Endometriosis does seem to play a role in egg quality, where even younger women can have worse egg quality. The same thing applies to polycystic ovarian syndrome, which can really have an effect on egg quality. Even obesity is controversial, but there is some data indicating that women who have a higher BMI do have worse egg quality, and that can impair embryo progression.
Kevin Pho: Now, how do you transmit all this information about the egg quality to the patient?
Erica Bove: That is a great question. When I see a patient, first of all, we decide if a patient wants a fresh transfer. There are some people who actually want a frozen embryo transfer, and typically we are talking about a blastocyst that is frozen. If we are talking about a fresh embryo transfer, I will look and see how many eggs fertilized and I will look at their age and say: “OK, are we more likely to do a day three embryo transfer or a day five embryo transfer?”
On day three, what I will say is that if there are one or two embryos that are really clearly ahead of the rest in the pack and the others look like they are of much worse quality, then we are going to be able to choose which embryos to put in. The American Society for Reproductive Medicine does have a very clear guideline on how many embryos to put in under different circumstances. We are doing a lot more single embryo transfers because if we put in two and they both take, the risk of twin pregnancies is higher.
So really I say: “This is how many eggs you had. This is how many fertilized.” I go through the number grades and the letter grades. I tell them this is how we would rank their embryos. Based on their age of 39 and their diagnosis, we might recommend putting in two day three embryos. I ask if everybody is in agreement with that. I go through the success rates for them, their age, and their diagnosis. I explain the twin rate if we put in two. There is always a very, very small chance that one of those embryos will split.
If everybody is in agreement, then we move forward. Now there are patients who say their worst nightmare is twins for various reasons. Maybe they already have children at home or they are a single parent. Everyone’s situation is different. We look at the recommendations and then we tailor our recommendation based on their situation and their desires.
Kevin Pho: Oh, so it is very number-based, obviously. So what would be a common scenario just to kind of bring these numbers to life?
Erica Bove: Oh yeah, absolutely. OK, so say there is a 36-year-old woman with male factor infertility, and we get 15 eggs from her on the day of the egg retrieval. I always say that not every egg is mature, and only mature eggs can be fertilized by sperm. So say we get 15 eggs, 12 are mature, and 10 fertilize with the ICSI technique that we talked about. I would say we can expect probably anywhere between three and five blastocysts from that cycle.
Somebody who has a good prognosis like that, who is still relatively young and facing male factor infertility, can use IVF to bypass the traversing of the sperm up into the reproductive tract. That person has a pretty good prognosis. I would typically recommend looking at the day three embryos, but if they were all kind of neck and neck for the most part, then we would grow those embryos out to day five or day six. Then I would say: “OK, this is what you have got.” We typically will do a transfer on day five.
Just to share a little bit about the grading, it is a much different scale by this point. You can actually see the embryos in the dish with the naked eye. They are very small, but you can see a little speck. They have 80 to 100 cells. Obviously, those exponential cell divisions have taken hold. Typically we grade the embryos from stage one through stage six. Stages one and two are very early, small blastocysts. You can’t really distinguish that outer rim of cells called the trophectoderm, the placental layer, from the inner cell mass, which is that cluster of cells that hopefully becomes the baby. So stage one and stage two are still very early blastocysts, although we can transfer them sometimes with good rates.
Stages three, four, five, and six mean that the blastocyst is in various stages of expansion. As I like to say to patients, blastocysts are really looking for a home. They are trying to find the uterine wall, the endometrium, and invade into the maternal vasculature because that is how they will continue to get the nutrients for their continued development. Stage three is still kind of compact, but you can see those layers. Stage four is where you can see the blastocyst starting to expand. Stage five is hatching, where you can really start to see the embryo itself hatching out of that outer layer. Stage six is fully hatched.
One is not necessarily better than another, but I like to help my patients understand where we are at. Say we get to day five, and this woman that we talked about has a 4AA embryo, and say she has maybe three or four other really strong candidates as well. A 4AA is a gorgeous embryo. It means that the first letter represents the inner cell mass, which is hopefully the baby part, so that is an A. Say the outer rim of cells, the part that becomes a placenta, is an A. That is a beautiful embryo for transfer.
Now we might then freeze three or four high-quality embryos after transferring the one, hoping she gets pregnant with that embryo. All those other embryos that are frozen have about a 50 percent chance each of success. The tricky part is you can go through a whole cycle where you get 15 eggs. Not every egg is mature. Not every mature egg fertilizes, and about 70 to 80 percent is typical. Even in young patients with a good prognosis, a 50 percent blastocyst conversion rate from the 2PN stage to the blastocyst is a good conversion. In older women, it can be even lower.
I try to say that obviously I only want my patients to have one egg retrieval if possible, but we want to maximize what we can. For that 36-year-old, she probably has a couple of kids possible in that cycle, but maybe not. If they wanted a third kid, they might need to go back to the drawing board and do another cycle. Is that helpful?
Kevin Pho: So it sounds like an overwhelming amount of information. I could only imagine for the patients and their families as well. How do you guide them through that? Because these are obviously life-altering decisions with a lot of numbers and a lot of layers of grading. How do you guide patients through that decision-making?
Erica Bove: Sure. I think one of the biggest things is you have to know the patient and you have to know their history. It is a little tricky because sometimes I am doing a transfer for my partner’s patient and I may not know them intimately in terms of knowing their values, goals, and desires. I make sure I always read the chart thoroughly ahead of time so I really understand. Do they have a unicornuate uterus? Should we really only be thinking about one transfer? Do they have a history of preterm delivery? I am definitely less likely to put in more embryos.
For me as the clinician, I really want to have a good understanding of that patient going in. Then I explain to them the embryo grading, either day three or day five, and say: “This is what you have.” This is how I break it down, Kevin. I say: “If you were my sister, this is what I would recommend.”
I find that we have sort of gone away from some of the paternalism in medicine, but I almost think we have swung in the other direction in terms of saying: “Choose anything. It is all going to be OK.” I find that patients want some direction. So I might say: “Hey, if you were my sister, I would really think about putting in two embryos. Maybe the quality isn’t so great, so I think the risk of twins in your situation is going to be less than 10 percent. But if that is your worst nightmare, then let’s only consider one.” We have that conversation in real time.
Sometimes I even take a step back and go back into the fishbowl, as I call it, where I sit and do my charting. Then I come back after the couple has had a chance to really talk among themselves about their goals, their values, and everything. Cost comes into play too. It is a lot less expensive to put in two embryos than to keep paying for storage and all those things. But again, we really want to minimize the risk of a twin and triplet gestation, which can certainly happen the more embryos we put in. So it is a very nuanced conversation and I think we have to sort of take everything into consideration.
Kevin Pho: Simplifying it down, is there an overall correlation rate? I know this is really reductionist. Is there a correlation between the quality of embryos and the success of having a baby? Yes. So what are some context numbers in terms of what that correlation is in terms of percentages?
Erica Bove: Yeah, absolutely. Say you have an 8A embryo and it is a good prognosis patient. That embryo can have a 40 to 50 percent chance of taking because it is a high-quality embryo. But if you are looking at a 6B embryo, for example, and I am throwing out numbers because I need to see the chart, it has roughly a 20 to 25 percent chance of taking because it is lower quality.
You can also look at what happens if we put in two embryos at once. What is your chance of a successful outcome going to be? Roughly speaking with high-quality embryos, if you put two in at once, it gives about a 10 percent increased advantage to the success of that transfer. So maybe it goes from 40 to 50 percent or something like that, but you also have to say that there is a 25 percent chance of having twins.
If we were to put in one embryo, keep that other embryo frozen, and return it in a different cycle, you would probably have an even higher cumulative pregnancy rate after two transfers. So I go through the numbers and say: “OK, your highest chance of one healthy baby at a time is to do this, whatever it is.” It may be one embryo or it may be two embryos, but we really look at the quality and the numbers.
Blastocysts are a little bit easier. I think that blastocysts are at a much farther stage of development. Really, a lot of milestones have to be reached between day three and day five so that the blastocyst success rates are a lot higher. If you have a blastocyst, now we are talking about a frozen embryo transfer. But say we have tested the chromosomes, that embryo can have a 65 to 70 percent chance of taking, which is far higher than anything outside of natural conception. We really only put in one tested embryo at a time when we have that information.
I think about this as having a lot of tools at our disposal. Making it accessible for patients involves placing it in the context of their situation. We use the ASRM guidance, but I think at the end of the day, it really is a nuanced conversation between the patient and the doctor.
Kevin Pho: We are talking to Erica Bove, obstetrician-gynecologist and reproductive endocrinology and infertility specialist. Today’s KevinMD article is “A clinician’s guide to embryo grading in IVF.” Erica, as always, let’s end with take-home messages that you want to leave with the KevinMD audience.
Erica Bove: Sure. So one thing I would say is some people go from clinic to clinic. Say things don’t pan out at one clinic. They still have embryos frozen and they go to a different clinic. Not all the grading is the same clinic to clinic and every clinic has its own success rate. So it is a really important question to ask.
Some clinics rate embryos a grade D. I was always used to that in my career. Then I went to a place where the lowest grade they gave was a C. So then I had to readjust my brain to be like: “OK, well, a C in this system is actually a D in my previous system.” Some clinics have different standards. I wish there was one true standard, but there is not.
Really understanding clinic-specific success rates, whether it is day five versus day six, are really important questions to ask your REI and your lab staff for your own clinic. But especially if you change clinics and are used to a different system, if you are switching clinics and you are used to something else, make sure that you are really comparing apples to apples.
I would always say that as patients, we really do want to empower ourselves with information. I really trust my embryology team, even as a physician, to help me make these decisions. Sometimes you have two 4AAs that are graded that way, but maybe the lab sees something different. Maybe one is expanding versus not having as rapid expansion. These are dynamic processes. So really trusting the lab staff because that is what they do is key. They are embryologists and that is what they are trained to do.
Sometimes they will grab me and say: “Hey, look under the microscope. Do you see this?” But really leaning on your clinic to help you understand which embryos to transfer and in which order can be really helpful.
Now, there are tools out there called embryoscopes. I want to just give a brief word on that. That is where you have 24/7 capturing of the data, where you watch the cells divide in real time. It is obviously a slow process, but you can sort of see if there are chaotic divisions and all those things. Those all sound really great on paper, but they have not been shown to improve outcomes and they are really expensive. They add cost to patient care. So I would love to put stock in those and to say that this technology is going to help us. I don’t think we are really there yet. As of right now, in 2026, it really involves trusting your lab, looking at their individual success rates, and then leaning on your team to help you decide how best to move forward.
Kevin Pho: Erica, thank you so much for sharing your perspective and insight. Thanks again for coming back on the show.
Erica Bove: Thanks, Kevin. I appreciate you.
