Hutchison’s Huddle: Embryo Grading

When an embryo is created in the lab at RHC, they are assigned a grade. If you’ve gone through IVF, you’ve probably heard these grades, typically a number with 2 letters following. But just what do these grades mean? On this Hutchison’s Huddle, Dr. Scot Hutchison explained the different grades, what they mean, and even had photos of microscopic images of the different embryos.

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Hello this is Dr. Scot Hutchison here for another Hutchison’s Huddle. I guess we’ve done like 11 of these things now! And anyway, today’s is on Embryo Grading. And so welcome from sunny Tucson, Arizona, where today was about 94 or 5 and I’ll get down to about 63 degrees tonight. So if you all want to visit in June, it’s not not a super bad time to come. We’ll get hotter later on this weekend well over 100.

Anyway, years ago, the embryology folks figured out that people were getting pregnant with embryos that look different than other embryos. So pretty rapidly, there was an understanding that better looking embryos typically resulted in better pregnancy rates. 

So, anyway, there are different grading schemes out there. So for those of you who have done IVF, you will hear us talking about the grade of your embryos. But let me start out with kind of just some basic embryology stuff. So, I’m going to show you some pictures that one of our embryology staff, Eva Vega, so graciously made for us today of some good and bad quality embryos. So these are just fertilized eggs. These are what we call–so you can see the pronuclei for both the male and the female in here and then you’ll also see both extruded polar bodies. This one here did not fertilize it all. But the rest of these have fertilized normally. And believe it or not, we used to transfer embryos just like the day after this. And now we actually go to day five or six. And as you all are probably aware, we don’t do fresh transfers anymore because–unless they’re going from like a situation where you’re going from donor egg into another person, in which case that’s fine for that to be fresh–but fresh embryo transfers, as you probably recall me talking about, result in less good placenta formation, and that results in less good duration of the pregnancy and the babies tend to be born about two and a half, three weeks early. But at about the day four mark, an embryo will kind of look like this which is what’s called a morula, give or take this is the–morula is the Latin word for berry. And, you know, people kind of looked at that and said, you know, it kind of looks like a mulberry. Because the cells really don’t have a lot of them are not very discreet. Their cell membranes are kind of blobbed together and they’re sharing a lot of cellular information at that particular point.

Then, by about day five, you want to see this particular picture, which is what we call an early blastocyst. So, the outer cells out here–this cameras backwards–he outer cells along the rim in here, these are all the are what are called the trophectoderm cells. That’s what’s going to form the placenta and then the inner cell mass which is right here, this is going to form the baby. This cavity is actually a fluid filled space and that’s what blastocyst refers to, as you’re starting to see that fluid accumulation in the center part of the embryo. Then, hopefully, you go on by again, day five, day six, to see what we would call, you know, a really good quality blastocyst. So, and in this particular embryo, this is the inner cell mass–this part right in here–and these other cells are going to be the flank and kind of form the, the sphere of the embryo, these are going to be the trifecta germ cells that turn into the placenta. So this embryo is fully expanded, you can see that blastocyst cavity is much bigger now. And the outer rim of cells is even thinner walled. And then finally, you get to this particular point where the embryo is even bigger. Again, then you’ve got this nice inner cell mass right here. And then you’ve got a very nice group of trophectoderm cells. Again, this is a three dimensional structure, so really it’s a sphere. This outer layer which is called the zona pellucida, which you can barely see in here–actually, you can see it over on this side a little bit better–this area right into here. That will eventually break open and then the embryo will be able to hatch out. So in this case, the embryo is–you’re starting to see the embryo hatching out of zona pellucida. Now in modern IVF practice, most practices will do what’s called assisted hatching and certainly we do because it’s just sort of standard of care and you know. So you’re gonna make an opening in that zona pellucida because for some people, especially as we get older, the zona can get very, very stiff and it just won’t allow for better hatching. And so if you can open it up, it will really help the embryo be able to get out and implant. 

So when the embryo finally is completely free of the zona, then that’s a 6. So the embryo expand–the first like when we talk about a 4AA embryo, you’re talking about the number grade is how expanded the embryo is. So it’s 1 through 6, which is all the way hatched out. And then 5 is fully expanded less is or 4 is less. So and then 3 is kind of more early blastocyst stage. 

So let me show you. This is a group of embryos which is actually very good. So here’s a good group of embryos. So these are–you can see there’s a whole bunch of really good quality blastocysts in this particular frame. So you have ones like this one. And yeah, all of these are actually pretty good. These are nice looking blastocysts. You can see one that is sort of at the morula stage. This one down here is now going to be an early blastocyst. Here’s another group of nice looking embryos. Again, lots of nice looking trophectoderm cells, nice looking intercell mass. And this patient has–this couple has several of these that look really, really nice. 

What we don’t like to see is this sort of picture. And so these are–this may be this one down here may be a blastocyst, but not very many cells. Not a lot of, you know–there’s a lot of discrepancy among the sizes of the cells that you see, this one up here is not–very few cells, and they’re all different sizes. And same thing for this guy up here. So, you know, here’s another group of embryos that just really don’t look that great. And then a lot of cells are kind of dark as well. And then this is like a day 3 embryo that doesn’t look very good. You know, what you’re hoping for on day three is eight cells and you’d like all of these cells to have about the same size and to have very nice, uniform structure to them with very little of this sort of dark, granular fragmentation stuff on the inside. Here’s another kind of marginal-looking blastocyst and another embryo that just looks like it’s just not doing very well, it’s sort of that morula stage.

Here is an embryo that is completely hatched out. So nice looking blastocyst, free of its zona. And you know, the cells look nice and similar in size and a lot of them and nice inner cell mass. 

So that basically is it in a nutshell. So, the letter grade or the number is how expanded, the first letter grade is the quality of the inner cell mass and that is usually graded from–usually people will do A through C with A being the best. I’ve also seen when I’ve gotten records from other clinics, you know, one through three or one through five, whatever or even breaking it down even further into like, A through E, that kind of thing. 

But typically, what we would love to see is that by day five, even into day six that you have AA embryos. So it doesn’t really matter how expanded they are, but we would like to see AAs. Oddly enough, you know, most embryos you know, I would say, a good half of them are probably BBs and we get plenty of babies out of those because things have changed quite a bit, you can have an absolutely gorgeous embryo–like, for example, these two embryos right here, look just you know, they look perfect, but, you know, this one could be completely aneuploidy or chromosomally normal and then you know, the other is okay. So embryo screening has really kind of–especially for women over 35–has really made this whole process a whole lot better. So this grading of the embryos or timing to see how fast they develop or whatever, sometimes that you know, they can look great, and then you wind up with a genetically abnormal embryo. So, in the big picture, the embryo grading is I think important and certainly everybody loves to see more beautiful looking embryos. But if the embryos are genetically normal, and they have low mitochondrial DNA fragmentation scores, then that really is important. So even with those BB embryos, we tend to see about 50% of the people getting pregnant if they’ve done that embryo biopsy testing on them. 

So somebody asked in here, do you grade at day three? Well we do grade at day three, we look at them on day three, and what we are hoping to see again is a really good quality 8 cell embryo–and that grading is different on those eight cells–but we grade those on a scale of 1 to 5, with 5 being the best. And you always want to see a few of those grade five, eight cell embryos on day three, but we no longer transfer on day three. Because the, you know, pregnancy rates are lower and you want to be able to biopsy at day five or day six, when you’re taking out five or six cells out of a 200 cell embryo rather than taking out one whole cell out of an eight cell embryo which, you know, may decrease the development of that embryo a little bit more. 

So, around here, the best embryos are AAs, so really good quality inner cell mass and then really good quality outer cell mass. And then a poor quality embryo would be a CC. So in our practice, we don’t verify CCs because the pregnancy rates are just so low. And those embryos are usually aneuploidy, they are usually genetically abnormal. 

So, and then somebody asked if an embryo grades poorly, can you still use that for IVF? Meaning can you still transfer that and you can, but the chance of pregnancy with it is lower. But again, you know, we’ve all been there before the days of embryo biopsy, lots of times, you would just transfer the embryos that you had, even if they were really poor and people would get pregnant, not embryos that are in that CC category–I can’t remember one of those. You know, but we might have an embryo that had maybe one C letter grade and we were just going to go ahead and transfer it anyway and the people hadn’t had a nice normal baby.

And then somebody asked in here, does a grade of the embryo affect the likelihood of implantation? And this again gets kind of slippery because it depends on the grader and some graders are tougher than others. And again, if you can biopsy embryos now and know that they’re genetically normal, you’re going to get pregnancy rates, even with embryos that look lower quality like BBs that we typically used to get with AAs. So anyway, you know, I think that you have to just look at the whole picture. 

Certainly, for women who are younger, they’re poor quality or poorer quality embryos seem to do better with regard to implantation than women who are a lot older. And in which case, you know, if you get somebody in the early 40s, and you’re transferring even AAs embryos, I would bet on the 35 year old with a BB embryo on day six, you know, over even the AA from the 42 year old that got there on day five. But certainly, again, you know, being able to test the embryos has kind of made that a little bit more of a reasonable thing to do as far as chance of pregnancy. 

And so somebody else asked what are the grades that you use? So again, we go letter grade, we go first is the number is  the level of expansion. And that’s 1 through 6 which has been hatched out. And then the first letter grade is the quality of the inner cell mass, the second letter grade is the quality of the outer cell mass that’s going to form the placenta. And so, we go A through C. But again, other people, they may flip that around or they may do A through E whatever. 

So anyway, that is embryo grading. If anybody has any other questions about that, feel free to to holler at us. 

Somebody asked, Are we still doing telemedicine appointments? And yes, we are. I think that’s going to be the way of the future for the foreseeable future to minimize the risk of COVID for everybody. So the way we do things is we do most of the talking on the telemedicine or on the telephone. And then we do the exams and the procedures in the office here. But we try to do that with as little of talking as we can get by with. As you probably are aware, the transmission of COVID is primarily droplets, so, you know, trying to minimize–if you’re in a small enclosed space, trying to minimize, you know, coughing, singing, yelling, laughing, all of that is probably really good. And of course, everybody should be masked and I think that the CD, this week started recommending that practitioners start wearing face shields as well. And so, you know, that’s what we’re doing with it. But every practice is a little bit different. But what has seemed to be working for us with IVF to try and keep everybody safe, is we’re testing the staff and testing the anesthesia folks for COVID at the beginning of each IVF batch and the patients as well who are going through the IVF. Obviously if somebody shows up positive, it’s gonna throw a real wrench in things, but kind of the way it is. We try to have just one person in the office at a time. So like for us, you know, you come to the office you call, we let you in and then you know we do your exam or procedure and then you leave and the next person comes in. And so we’ve been able to do it that way. It has extended hours a little bit longer. And to me, it’s a lot less fun because there’s a lot less human interaction and the partners aren’t able to come in like they used to but definitely bring your phone so you can FaceTime with your partner during your exam or or ultrasound or whatever it is. 

So anyway, if you have other questions or anything, please feel free to give us a call.

And please look up our other Facebook Live things on polycystic ovary syndrome and nutrition and endometriosis and all that kind of stuff, because some of them are really quite helpful. And anyway, we will see you down the road and thanks for tuning in and have a great night wherever you are.