Ep 83: Embryology and Embryo Grading with Christine Briton-Jones
Fertility Forward Episode 83:
When one starts IVF and fertility treatments, it can be a lot to take in. There’s tons of jargon to familiarize yourself with and seemingly endless academic articles on every topic imaginable. This can be especially overwhelming when you are presented with embryo options and you don’t know which one to choose, or whether the single option you’re being presented with is worth pursuing. Here to help us make sense of embryo grading and offer much-needed peace of mind is Christine Briton-Jones, a clinical embryologist and Director of Laboratory Services at Reproductive Medicine Associates of New York (RMA of New York). In our conversation with Christine, we discuss the intricacies of embryo grading and why it requires years of experience to fully grasp its nuances and the subjectivity involved. Tuning in you’ll hear Christine break down how the day of an embryo affects its grading, what each of the letters represents in embryo grading, and why a C grading is something to celebrate. Be sure to tune in to learn about the intricacies of embryo grading and why it merely serves as a snapshot of the process, and why that should make you feel hopeful.
Rena: Hi everyone. We're Rena and Dara, and welcome to Fertility Forward. We are part of the wellness team at RMA of New York, a fertility clinic affiliated with Mount Sinai Hospital in New York City. Our fertility forward podcast brings together advice from medical professionals, mental health specialists, wellness experts, and patients, because knowledge is power and you are your own best advocate. I am so excited to welcome to Fertility Forward, Christine Briton-Jones, who is the Director of Laboratory Services at RMA of New York. She wears many, many hats here and for the sake of this episode, we are going to specifically be talking about embryology and her work in the lab. I am so excited to have you on and talk about the question so many patients ask, so many patients go to the internet to try and find answers, but embryo grading. And what do the days, what do the letters, what does everything mean? Thank you so much for coming on and helping us break this down.
CBJ: Yes, sure. Thank you so much for inviting me. It's great to be able to talk about this. Cause I think it is really interesting because in fact it is quite nuanced. I think lots of people probably think that embryo grading is kind of black and white. It is or isn't, but in fact, it's actually quite subjective to start with. We certainly are entering an era where more and more we're using computer algorithms to help us compare between different characteristics of different morphologies that we look at, but it still is very largely subjective and on the embryologist, which is a part of why our training is so long, a lot of it really is kind of nuanced and based on experience.
Rena: So tell us, okay, so people, I think they hear, you know, you can have a day, that's a day three, day five, day seven embryo, and then that could have a letter grading. So AA, BB, BC, et cetera. Can you tell us what is the difference between days? And then we'll talk about the letters.
CBJ: So usually, and it sort of maybe might be good to just throw in a quick little historical sort of note. So that, and when I started, so I started back in the early nineties and the whole field was very new then and we used to actually transfer, do the embryo transfer on day two. What we would call day two. We expected the embryos to be at two cell or four cell on day two. And it seemed that we really hadn't worked out things in the lab, how to grow embryos any longer. So we kind of the thought was a strategy was let's put them back in the uterus as quickly as we can. And then as we developed and became better in the lab, giving the embryos what they need, keeping the conditions as close as possible to the human body, and in some respects with people that are having trouble getting pregnant on their own, the lab conditions actually may be more optimized than certain people's bodies with different things going on. As they got better, we realized that we can actually look more at the grading at different stages of embryo development. That's where the days come in. So on day two now very few people would look on day two anymore cause it really doesn't give us much prediction as to how, what is the implantation potential or the pregnancy potential of that embryo? We do look on day three. Day three is it's also almost like a misnomer when we say day three, because we actually do the egg retrieval on day zero. Fertilization check starts the embryo growth, the embryo journey. So that's day one is fertilization check the day after the egg retrieval. On day three, we really want to see that embryo that textbook would tell us eight cells. We know that anywhere from six cells through to even 12 cells is a healthy embryo. That's hitting the stages where we expect. And from there we look at characteristics like are the cells even? Are the cells the same size? Are there any extra cellular fragmentation? And so those things would bring us to have a lower grade. We start off by saying, okay, here’s grade A and at that stage on day three, you would only have one letter grade. So day three would be the number of cells, say six cell I, and in fact, we have stopped giving a letter grade on day 3, we just give the number of cells.
Rena: So day three, never has the letter grade. So it's just, so you never get a day three AA embryo. It would just be day 3?
CBJ: At day three, you have eight cell, six cell, four cell, something like that. So it's actually one way of doing blastocyst where you start to get your two letter grades. And the reason for that is that we have two cell types that we're grading the inner cell mass cells and the triphectoderm cells. The inner cell mass cells are the cells that will eventually become the fetus and hopefully the baby and the triphectoderm themselves are the ones that will become the placenta if the implantation occurs and progresses. And so that's why you've got two letter grades and the convention is to have what is the expansion of the blastocyst and the expansion so a clear distinct embryo or the cells are nestled next to each other. And blastocyst you have the inner cell mass will form, tight cell cell junction. So it's like a ball of cells that it's often hard to see the individual cells and then all around the outside is the triphectoderm cells and then you'll have a fluid filled cavity. So that's the blastocoel. And the expansion is graded on what is the percentage of the entire space of the embryo that, that blastocoel your cavity could be taken out of the entire embryo. And so that's where you'll hear like a blast 1, 2, 3, 4, 5, or six and six is where there's has completely hatched out of the zone of Palucida and it's a fully hatched blastocyst.
Rena: So would that be considered, you know, cause people always want to know what's the best. So is it day six, better than a day three?
CBJ: So it's that it's different. And you could say the fact that it has continued to grow to day six is better because we know that it's kind of like at each stage we’re seeing the potential more. So if an embryo, one of the things that we know was is the embryo to stop growing is aneuploidy. So where they don't have two copies of each chromosome, they might have one chromosome, that's got three copies or one copy. And if that's the case, we know that that's very likely just stopped growing. And so if something has reached a blastocyst, we know that it's got a higher chance to be euploid than if it stopped growing at like the eight cell stage. So in some ways, yes, it's better. But also if you were just comparing that same embryo on day three, to what it's like on day six, then it's sort of just a different thing rather than being better.
Rena: Okay. Cause I know this is going to be sort of the same question over and over, but it's just because I know what patients ask, you know, they come to you and they say, well, I have a day three, and then I have a day six, you know, which one is better, which one's a higher statistic of implantation and viable pregnancy? Which one would you choose? Like what would the lab choose if you had a day, three or day six?
CBJ: Yeah, we would probably choose. In fact we will, we would choose the day six because having grown out those extra days and having continued to grow is kind of proven itself. Whereas that day three, it might have the exact same implantation potential, but we just haven't seen it go through those extra steps yet.
Rena: OK and what about day 7?
CBJ: So day seven, I think again, if you were comparing it to a day three, a day seven, cause we wouldn't freeze the embryo if it wasn't what we can see clearly that there is an inner cell mass there that there are trophectoderm cells out there that's needed for implantation. So we would probably still choose that day seven blastocyst as the embryo to transfer first, over a day three in like to compare. And it's the same patient. Yeah. Just that it's proven itself to be able to form a blastocyst.
Rena: So does that mean unequivocally sort of the longer days it grows the better it is? So then a day seven would be better than day six?.
CBJ: No. So that's interesting. So what we do, we will freeze blastocyst on day five, six and seven. We ideally want to see them at a blastocyst stage on day five. And we've found that if we grow them to day six and when we do ourstatistics, so we're a very large program. We've got literally hundreds of thousands of embryo transfers, what we collect all that data. And so we're looking at really good numbers that show us good trends as to what's happening and how we can predict the pregnancy potential. And we have found that embryos that form a blastocyst on day five and day six, they have very, very similar pregnancy rates day five and day six, but because we are ideally, so again, we think about a textbook is telling us they can form a blastocyst on day 5, if they don't reach that stage until day seven, we still certainly have quite a lot of healthy babies, healthy pregnancies from day sevens, but it is a lower implantation rate. So lower pregnancy rate with the day sevens. So we believe that that could still be a healthy embryo that it's just, it's slower in reaching that stage of development
Rena: Because I know day seven, they're pretty controversial,
CBJ: Right. Correct. So some labs won't do a day seven and it's one of those things that's tough. I'm a really strong advocate for patient education and also to understand that when you've got a reduced chance of pregnancy, it's not zero chance. So if you're a patient that the embryo didn't reach day 7, we would only do it when we're doing a biopsy cause then we actually get the ploidy status. So it wasn't able to be biopsied on day six, but it grew that little bit more. We had enough cells that we could safely take, you know, three to five cells and get an, a diagnosis on that. Then we know that that probably has a lower pregnancy potential then, an embryo I'd say on day six, that would have been at the same stage, but it's not zero. So we're finding that it is approximately 30% implantation rate per transfer as compared to close to, to the high sixties, but it's not nothing. So again, that idea of patient education. So I find it hard when I have had other labs have different philosophies who said, we will not say transfer in and accept and do a day seven transfer because it's still a challenge of a live birth, even though it might be half that chance, but it's sort of not nothing. I think, I guess in some ways that's just sort of different cultures, different philosophies from the labs.
Rena: Well I think too if you’re a patient who maybe finances are an issue maybe you have a very hard time creating embryos, you know, to transfer it, to have a day seven to transfer is better than nothing, you know, a chance.
CBJ: Exactly. And while I would say, if there's an embryo that stopped growing, so there it is, it's still say eight cells all the way on day five. I am again like a strong advocate of saying, do not transfer that because what you don't want to have is that wasted time or you're going to continue taking progesterone. And when we know that that embryo essentially is non-viable, so it is one of those things where I definitely think that the day sevens they’re worth it, we've got quite a few healthy babies from it and hundreds from that. And so those, yeah, it's still kind of say, oh well, that's, it's a reduced chance. Let's not even bother. That's certainly not my philosophy.
Rena: Well, I mean, I think everyone should be so lucky to work with you because I think that makes so much sense. And I mean, you know, as much as I do how tough it is, and again, you know, for people where finance is an issue, maybe they can't afford to do more cycles, maybe they have a hard time creating embryos, you know, I think given the chance most people would choose the day seven because you have the hope you have something over nothing.
CBJ: For sure.
Rena: So let's okay. So now I think we have a good understanding of the days now. Let's can we break down the letter grading a little bit more? So I know you mentioned before, one of the letters is the fetus and one is the placenta.
CBJ: Hopefully we'll keep growing and form those.
Rena:Okay. So when you have, okay, so it goes a through c?
CBJ: We actually do go through D and D is what we determined is actually like a non-viable grade. So we may not see any cells in either the inner cell mass or the triphectoderm, or there will be very few cells in there looking what we call a degrading so they're kind of dying those cells. So that would be a day eight.
Rena: So would you not transfer an embryo that had a degrading?
Rena: Is it like, AD, you wouldn’t transfer??
CBJ: That's right.
Rena: OK so you need your embryos to have either an AB or C. Okay. So if, you're getting your results back and you find out you have a day six, which we know is very good now, but it's an AC. Should you be devastated by that? Should you be hopeful? What sort of statistic on that?
CBJ: Yes. And I think, you know, our patients are often they're successful in life and they're driven. And so they think that a C is a bad thing. It's not a bad thing. So while we find that there might be a slight reduction in pregnancy rates with a C grading, that is when it's in the inner cell mass. The triphectoderm has less sway over what we can predict well, compared to the inner cell mass. And so in fact, a day six say 4 AC is a very strong embryo. So we would be happy to see that.
Rena: Okay. To not be devastated if you have a C that's still okay.
CBJ: Yep. Yep. Yep.
Rena: Okay. Cause I know, I mean, as you said, so many of our patients are really, you know, driven, hardworking and used to getting A's or feel A is the standard. And I know a lot of patients get very upset when they have that C grade, but it doesn't mean that necessarily, that you have anything to fear.
CBJ: Yeah. It's still a strong embryo. So when we have say a four CC, that would be sort of the, what we consider the lower grade that we would be vitrifying or freezing. And again, there is a drop in the pregnancy rate, but it is a relatively small reduction. So it's still not something that you would say, oh, I've got no chance. They're not bad embryos. So they still got enough cells. And we certainly still get, you know, thousands of healthy babies from the say 4 CC.
Rena: Do you have any statistics, the rate of success from an A embryo versus a C?
CBJ: We actually do. And I know we've got them published as well. So that's something that one of our doctors, Dr. Taraneh Nazem and she, I think it was three years ago and it's just, I kind of the top of my head, I sort of don't want to give out the wrong numbers and I haven't got them with me, but we've certainly published on that. And I know that there is a reduction it's in the order of like five to 10%. So it's really not dramatic. So that's sort of the important thing to keep in, but they can look on few look, perhaps even look up Dr. Nazem Taraneh’s I think that will pull up.
Rena: Okay. Yeah. If anyone's interested to, if they want they can just DM us or shoot us an email too, and we'll, we'll get it to them.
CBJ: That would be awesome. Yeah.
Rena: So anything else, very pertinent you think we should share with our listeners about embryos and embryo grading?
CBJ: I think that something that's important to keep in mind too, is that when we do a grading of the embryo, we are just taking like a snapshot of the embryo at a certain time in its development. So we haven't seen just say a few minutes before, or just a few minutes after that. So it is a dynamic process and we're taking like a static testing or grading of that very dynamic process. And we know that things can change. So one extra day you can have a grading of say a 4CB. And in one extra day, the inner cell mass grows some more cells or the cells compat down together, you can get even an A grade in 24 hours. So I think that's something to really keep in mind too, is that any of the grading, it gives us something to go on, but it's not everything. It's not all of the puzzle. And it's something that actually is dynamic and can change too.
Rena: That's a great point. I love that you shared that. I think that's a super hopeful point too.
CBJ: Yeah. I think we really do get hung up on the grades. And I understand, I really absolutely understand that people want as much information as possible. And there still is so much that we don't know, but it's not everything it's truly, the grading is not all of the puzzle.
Rena: I love that. You said that. I think that will inspire hope in so many people, because, you know, with medicine, people want a tangible, right. And an embryo grade is a tangible statistic. And it’s something to hang on to and, you know, I see it inspire hope in people. And then I see it inspire fear and distress in people. So I think to know that, look, this is a snapshot, one moment in time to really file that away. If you're someone who, you know, maybe just got embryo results back and you're feeling really devastated by them, remember, you know, exactly that - it's just a snapshot. It's a moment in time.
CBJ: Yep. Definitely.
Rena: So anything else, any insight as to, you know, where the technology is going, obviously things change so quickly.
CBJ: They do, and we really are moving towards using sort of people love to talk about sort of artificial intelligence and I don't think we're there, but more like machine learning where we are. And you know, what's exciting, I think is that, you know, RMA of New York is we do have a large patient volume. So we're learning things very quickly because we're getting to see so many every week. And so we are looking at using the data. We're very careful to keep accurate records so that we can learn from our own experiences, what we can do to keep improving, even if it is getting more accurate with embryo grading, or maybe even becoming more robust, if we can start using computers to grade, maybe more so than the embryologist so that we're getting, if it is more accurate. So that type of thing. So I think that is still moving there because one thing that you'll often hear and I've certainly said it, and it's true, like it's not all the pieces of the puzzle. It still is one of the most important things that we do have up our sleeve. Now we do know certain characteristics of an embryo, probably more at the low end, the Ds. We sort of know that those embryos, we know aren't viable. Those are the ones that we know can't produce a baby. Not so much at the high end, it's harder to differentiate for sure. And C grade embryos are actually considered high end. They're not the low end. There's still a good quality embryo. But yeah. So I think it's in that part where differentiating, and maybe it's going to be computers can help us to do that.
Rena:That is fascinating. I love this field because things change so quickly and everything that's being developed is incredible.
CBJ: It is. Yeah. I agree.
Rena: Well, thank you so much for coming on today. I think that was such a great tutorial of embryos, embryo grading, and I think it will be helpful to so many people. So I'm really excited that you came on and shared that. And I learned a lot because I, you know, I love to just brush up on this.
CBJ: Yeah, absolutely. Well, thank you again.
Rena: So we like to end the podcast with a note of positivity, so each sharing a gratitude, so something, and it's so pertinent today because we're recording right before Thanksgiving. So something that you are grateful for.
CBJ: Oh my goodness. And it's almost like, you know what to choose. And I have, I would say it is the people that I work with. So yes, it is like the culture of the company itself. I believe that the company is unusual in that we kind of have almost like an old school university kind of culture, but we're lucky in that we are private practice that we can give our patients sort of the best, the latest, and what's going on there. So I love that. I love the embryologists that I work with who come to work each day, excited to do their best. They're kind of, each day is a challenge. And they work really well together. They have a good time. They work hard, they certainly work hard, but they are striving each time. And, you know, they get excited. Like they get beautiful embryos and then we find out that that's a baby and it's, yes, it's like a great success. So it's a great culture.
Rena: I love that. And I, the embryology team is fantastic and I know always, always pulling for the success stories. So it's a pleasure to work with you and everyone on the team. And you totally took my gratitude because I also was going to say, I'm just grateful for my job. You know, reflecting now, I think at times, patients, especially, have been a little bit more mindful of also kind of giving thanks, and which is nice because it's kind of few and far between, you know, I get that, it's always really nice and people remind me that I actually help them and make a difference. And it's just such an honor to be able to do that and work at such a fantastic place as RMA with everyone that cares so much about our patients. And so it's just, it's so wonderful to be here. So grateful for that too.
Rena: Well, thank you so much. If anyone has questions, comments, et cetera, you know, they know how to find us, reach out to us and we so appreciate you being on.
CBJ: Yes. Thank you so much. A lot of fun.
Dara: Thank you so much for listening today and always remember: practice gratitude, give a little love to someone else and yourself and remember - you are not alone. Find us on Instagram at fertility_forwarad and if you're looking for more support, visit us at www.rmany.com and tune in next week for more Fertility Forward.