Ep 101: Fresh versus Frozen: How This Impacts the Creation of Genetically Normal Embryos, with Dr. Chelsea Canon
Fertility Forward Episode 101:
Today we are joined by Dr. Chelsea Canon to discuss her latest abstract entitled “Reproductive Outcomes in Single Euploid Embryo Transfer Cycles is Independent of Whether the Embryo Originated From a Fresh or Cryopreserved Oocyte”. Dr. Canon will be presenting this research at the upcoming American Society for Reproductive Medicine Expo but feels it is important to share it with patients too. Our guest is a third-year fellow in reproductive endocrinology and infertility at the Icahn School of Medicine at Mount Sinai in New York City and Reproductive Medicine Associates in New York. As more and more women are using eggs that were previously frozen, this has enabled the collection of data that we can use to help people make more informed decisions when deciding on how to preserve fertility. In this episode, Dr. Canon explains the difference between freezing eggs and freezing embryos and whether or not it matters if you use frozen or fresh eggs when creating embryos. If you have questions when it comes to fresh versus frozen, tune in today!
Rena: Hi everyone. We are 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 for medical professionals, mental health specialists, wellness experts, and patients because knowledge is power and you are your own best advocate.
Dara: Today we have Dr. Chelsea Canon to discuss her latest abstract which she will be presenting at the upcoming American Society for Reproductive Medicine Expo at the end of the month. Dr. Chelsea Canon is a third year fellow in reproductive endocrinology and infertility at the Icahn School of Medicine at Mount Sinai, New York City and Reproductive Medicine Associates of New York. Dr. Canon earned her Bachelor of Arts in Biology and Classical Civilization from New York University where she graduated Cum Laude with Honors. She completed her medical school education at Wake Forest School of Medicine of Wake Forest Baptist Medical Center in North Carolina, and her residency in Obstetrics and Gynecology at New York Presbyterian Weill Cornell. Dr. Canon, thanks so much for, for being on today. I'm very excited to hear what you have created over the last number of months.
Canon: Thank you so much for having me. I think it's always good to be able to present our data to the patients, you know, not just to the expo and to people at ASRM, but to our patients who this is actually affecting. So thank you for having me.
Rena: Yeah, and I think this one is especially pertinent. You know, I get a lot of questions from patients a lot of times about fresh vs frozen, so I think this is gonna be such a wonderful episode for people to listen to, to answer a lot of their questions…
Dara: So the title, you have, the title for this abstract is Reproductive Outcomes in Single Euploid Embryo Transfer Cycles is Independent of Whether the Embryo originated from a Fresh or Cryopreserved Oocyte. So that's very interesting, which I didn't realize that that wasn't something that's really been looked at thus far.
Canon: Yeah, it's, it's interesting because oocyte cryopreservation and now oocyte thaw cycles have been increasing over time. They, there's finally an oocyte thaw outcome paper published last year that kind of showed the trend over time. There's more women doing egg freezing and now more women actually coming back and using those eggs that were frozen. Previously, people started doing egg freezing and just the eggs were frozen. Now we're like, what should we do with those frozen eggs when people do need to use them? So it is something that's I think coming up more and more in these years of how should we use these eggs and are these eggs equal to doing a fresh IVF cycle?
Rena: So what have you found, and I guess first let's define for anyone that doesn't know an oocyte - what is that exactly?
Canon: Sure. So I know that our title is very scientific sounding, but really what we're talking about is whether when you do IVF, when you make an embryo, you can do a fresh IVF cycle where you go through the process, you immediately fertilize it, create an embryo, or if you had frozen eggs previously, the egg was frozen by itself. So an oocyte is just an egg cell that is not fertilized. You can freeze your eggs and then when you come back to use them you have to thaw the eggs, then fertilize them to create an embryo. So our question is, does it matter if the egg was frozen or is it okay these are frozen or fresh eggs when creating embryos?
Dara: And this is a big thing because as you said, you know, women have been freezing their eggs for quite some time, but now we're seeing people actually thawing them and using them to create an embryo.
Canon: Right, exactly. And you know, there is some research obviously into this. There's lots of groups that are trying to figure out what's the best way to use this. What we wanted to do in this study was trying to look at a very special population, so a population that makes embryos and they test the embryos. So some of the patients in other data sets have looked at just embryos that were created and not tested. So if we test the embryo so we know it's a good quality embryo, we know that genetics are normal, is there a difference if the egg was frozen previously or not? So we're trying to eliminate all of the biases and giving an embryo that's genetically normal.
Dara: This is a silly question. Is it tested? Is this the embryo that's being tested or is it the egg being tested?
Canon: I think that's a great question and the question we get from our patients all the time when they're talking to us about egg freezing. We can't test the egg itself. So when you go through an egg freezing process, the egg is just one cell. So you can't test just the egg. We freeze the egg and we hope that when we thaw them we can create embryos that are genetically normal. Once you create embryos, then we can take a few of the cells that would become the placenta and that's what we can test to see if it's normal. So a lot of patients going through egg freezing, we try to freeze X number of eggs in order to hope that you can get a genetically normal embryo or just an embryo at all. But we don't know that at the time of egg freezing.
Rena: So I get, you know, a lot of patients will say, is it better to freeze eggs or embryos? You know, maybe they're in a relationship, maybe they're not. What would you advise a patient with that question?
Canon: You know, that's, that's a great question and it's a very personal decision to be honest. I think over time we've gotten much better at egg freezing so our egg freezing and egg thaw success rates are better now than they used to be looking at our current data. But we don't know whether those eggs will make embryos and whether they'll make embryos that are genetically normal. The only way to know that, so if you wanted to say, plan your family ahead of time, you had a partner and you just weren't sure when you wanted to have kids, it's better to freeze embryos with that partner. You can genetically test them. You can say I have five embryos frozen that are genetically normal and have potential for pregnancy. But if you don't have a partner you should freeze eggs. Right? You don't have somebody to fertilize the eggs, you can freeze eggs by themselves. You just, it's not a guarantee for sure that you'll have a pregnancy from those eggs. You know, I think a lot of women go in thinking, I'm gonna freeze my eggs. I’ll for sure be able to have a baby later. It's not a guarantee, but that's what we counsel patients about in terms of their age, how many eggs they should have to give them the best chance of success later.
Rena: I would say, you know, and egg freezing is the most medically advanced option we have for women that are trying to preserve fertility.
Canon: Absolutely. Exactly. Single women or women who are unpartnered or who are, you know, dating somebody but aren't ready to make embryos with somebody is, egg is a great option.
Rena: Another thing people ask me, they'll say, Well, can I freeze eggs and embryos from the same retrieval cycle?
Canon: That's a good question. And I think that is really based on a practice, what their rules are in terms of whether you can split a cycle or not. Typically we would say, one cycle should be either egg freezing or embryo freezing. We wanna give you the best chance at one cycle to either make as many eggs as possible or make as many embryos as possible. When you split them in one cycle, you don't know whether those eggs will go on to become embryos or whether they'll be good eggs later. We really try to separate the cycles to give you the best chance per cycle for what your goal is. So if your goal is egg freezing, freeze eggs.
Dara: I never even would've thought of that. That's an interesting question, Rena.
Rena: Yeah, exactly. I’ve gotten that a lot recently. I think, you know, mostly from patients who are kind of in a relationship but not super solid in it. And so they're just trying to figure out how to set themselves up for success.
Canon: And I think some of that also has to do with insurance. So you know, the thing we don't like to talk about is money and insurance when it comes to these things, but it's billed very differently. Your insurance might cover one thing and not the other. So it's hard to kind of separate those out unless you do separate cycles.
Dara: So let's talk back about the study. You looked at fresh versus frozen. What was the difference in terms of how many in the fresh versus the frozen and what did you end up finding?
Canon: Sure. So you know, to our knowledge, no one has been able to compare pregnancy outcomes in euploid-tested embryos derived from either fresh or frozen oocytes. So what we did was we looked back at our data for the past like six years and we grouped people based on whether their embryo was created with their fresh oocyte and a fresh IVF cycle versus a cryopreserved or frozen oocyte from an egg, previous egg freezing cycle. So we compared the two groups, which were very similar, but we had 7,674 IVF cycles. So we do a lot of, we do a lot of IVF, we do a lot of PGT tested embryos that made up one group and in the same time period, so in about these six years there were about 136 oocyte thaw cycles where we created embryos that were genetically tested in order to have an embryo transfer. So that's an important thing to know is that these are patients who thawed their eggs, made embryos and were planning to to test their embryos and had an embryo that was tested that was genetically normal in order to transfer. So this isn't every single patient that did an oocyte thaw in this study period, but we wanted the patients who thawed them, tested them, and then transferred them later on in order to create the two groups so that you know, the age of the embryo, the age of the ocyte at the time it was frozen or used for IVF were similar amongst the groups. The age of embryo transfer was higher in the group that used frozen eggs, which makes sense. They froze at a younger age, came back and used them later. But the embryo itself was a similar age amongst the two groups.
Dara: I saw that - approximately 35.
Canon: Yeah, about 35 years old for the embryo creation age. And then what we looked at also were embryology characteristics. So amongst the two, these two groups, the number of eggs that were retrieved in the cycle were similar. The number of mature eggs retrieved were similar and the number of blastocysts created, so blastocyst is an embryo that we can actually genetically test and that was less in the cryopreserved oocyte group. So if you froze your eggs, thawed them and made embryos, there were less actual embryos to biopsy compared to the group who did a fresh IVF cycle. So that is one difference between the groups and the embryos that were created and biopsied were a little bit better quality if you used the fresh oocyte. So those are all looking retrospectively at the cycle. Then once you have an embryo that's genetically normal, we wanted to see what are the pregnancy outcomes? So if I use a genetically normal embryo from a frozen egg or a fresh egg, they had very similar pregnancy rates. So first we look at just the data as raw data, so just the number of pregnancies. And then we look at what we call multi-variate analysis. It's just a fancy word to say we want to make sure that our results are unbiased. So we wanna take into account things that could be different amongst the groups. So like we said, the patient age at transfer was different amongst the groups. We looked at the BMI that could be diff, that was different amongst the groups. Endometrial thickness is important in terms of whether an embryo will implant or not. So things that would affect your outcomes, we wanted to take that into consideration and then look at the results. And when you look at those, again, the primary outcome, which was ongoing pregnancy or live birth rate, was similar amongst both groups. Meaning that no matter if you used an embryo that was created with a fresh oocyte versus a frozen oocyte, the embryo had an equal chance of having an ongoing pregnancy or live birth rate.
Dara: That's pretty reassuring.
Canon: I think it's great data for our egg freezers, you know, especially people who are just starting the egg freezing process now, you know, they're going in and they're thinking, what's gonna happen in 5, 10 years if I wanna come back and use these? Now you know that if you get a genetically normal embryo, it's the same thing as if you had done a fresh IVF cycle 10 years prior. So especially thinking of those women who are asking you, Should I make embryos now or, or not? You know, you can tell them - if you get enough eggs to create embryos or to freeze in order to create embryos later, once you have that genetically normal embryo, it's the same thing as if you had made it fresh.
Rena: That's amazing, especially for people that also, you know, financially maybe they, they did an egg freezing cycle and maybe it's a financial hardship to do another retrieval or it's, you know, it's physically taxing to do that, to feel that they're making the right choice to, to use frozen eggs.
Canon: Yeah, absolutely. Cause they will come back, you know, maybe 5, 10 years later and say, Should I do a fresh IVF cycle? You know, I tried to get pregnant after I found my partner. I'm still not getting pregnant and now I have infertility. Right? Before they didn't have infertility, they just froze their eggs. Now I have infertility. Should I use my frozen eggs or should I go forward with an IVF cycle? And I think that's a decision you have to make with your team. There's lots of counseling and different things that may affect that for you personally, but they may say, let's, let's thaw your eggs. You made them 10 years ago and you have much better chance of having a genetically normal embryo from a 32 year old egg than from a 42 year old egg. You may not be able to go through IVF at age 42, right? So you might have to use your frozen eggs. But I think this data is reassuring for our patients.
Dara: Yeah, yeah. And especially, it's fascinating to hear that, I think you said with the frozen eggs that the quality may not have been as great relative to the fresh, however the outcomes were still reassuringly similar. So that's another thing to note.
Canon: As long as we, you know, when we genetically test them, which I think is a technology that's growing and growing and used more frequently now than it was in the past, now that we know the genetics are normal, it just, that doesn't matter as much. So I think that is reassuring for our patients.
Rena: I think it's also really interesting that it, it sounds like your sample size had very similar statistics in terms of number and blast and and all that. Did you, were you looking for something specific when you chose to use people for the sample for the data collection?
Canon: We tried to make the group similar, at least tried to have them be groups that would make sense to compare. Right? I think that, you know, when you look at the number of oocytes retrieved and the number of mature oocytes, it is interesting that these are equal amongst our patients and that's I think has a lot to do with our large sample size. So if you had, you know, a lot of the older data has like 40 patients in their sample size. We have thousands and I think that makes a big difference. So everyone regresses to the mean at some point and are similar if you have enough patients. So using a large sample size really helps us with this.
Rena: So is this one of the, yeah, your sample size is huge. Is that the difference that the, the studies on this prior were just much smaller data sets?
Canon: There are definitely studies with much smaller data sets and honestly a lot of our data has not had PGT tested embryos. So some patients will freeze their eggs, they come back to thaw their eggs and they want to either transfer embryo right away. So a fresh embryo from that oocyte thaw. They don't want to wait to see if they make a blastocyst. If they genetically test it, they want an embryo right away. So there's fresh embryo transfers, there's people who just don't want to genetically test their embryos, right, across the country. Not everybody is testing embryos. So this is a very select patient population that wants the genetic testing. And I think it's more common now, but it's not something that across the board, across the country, everybody is doing all the time's. You know, it's a big decision when you're your eggs, whether you test them, the embryos or not.
Dara: I think just the fact that there's an option to test and that it's much more common now compared to even when I was a patient years back. It's amazing how far we've come in such a short period of time.
Canon: Absolutely. The technology just continues to improve and it's just, I think it's a nice thing that we can offer to patients. And now it's nice to actually see the data, you know, to us it makes sense if you have a genetically normal embryo, which should be the same whether it was a fresh or frozen oocyte, but you don't know that until you actually look at the data and actually compare it. So I think, you know, making assumptions is one thing, but actually doing the research and doing the, showing the data, we can actually show this to patients.
Dara: For sure. Do you have any, is there any hopes to continue this research and to build upon that as more patients are coming in at the office?
Canon: Absolutely. You know, the number of cycles that we could use in this were of course smaller in the oocyte, the frozen oocyte group. So I think as in year after year, it's more and more patients coming back that can only help further this study and have, you know, strengthen the study so that we have more patients in that second group to compare.
Dara: Yeah. And especially now that there, there is some data to, to show them that there, there's hope and hopefully a little bit less fear with the frozen eggs. I think that in itself can hopefully propel people and make people more open to doing it in the first place.
Canon: Absolutely. Absolutely. I think fertility preservation is such an important topic, especially for single women that want to preserve their fertility for the future. I think it's just so important to have data for what happens after. I think more and more people are doing it, but without knowing how you're gonna use these, it's a lot of money to spend if you don't know it's going to be useful. So I think it's important research.
Rena: Absolutely. Well, we're so glad that you did this. I think this is gonna be very reassuring to, to many, many women. So, so happy that you came on and you researched this and we can present this to everybody.
Canon: Absolutely. Thank you guys for having me. I appreciate it.
Dara: Of course. So how we like to end our discussion is on gratitude. So Dr. Chelsea, what are you grateful for at this very moment?
Canon: At this very moment as I'm preparing for ASRM, I have to be grateful to my research team and everyone who helped me with all of the studies. I think it's, as the first author, you get all the glory of presenting, but there's so many people that help you, whether that's the statisticians, our research team that helps us pull the data, all the embryologists that day in and day out or create these embryos for our patients. So everybody that was involved, I think very grateful to them for helping me perform this research.
Dara: How beautiful. I'm sure they're grateful for you too. Rena?
Rena: I guess I'll piggyback on that and say, you know, I'm so grateful for, you know, the continued work and development in this field. You know, Dara, as you touched upon, for both you and I, the, the data and the technology has changed so much since we went through the process and it's really incredible and to be able to bring this back to our own patients and give them some reassurance and, you know, know that we have teams such as ours at RMA working so hard to help people family-build is something I'm, I'm so grateful for.
Dara: I totally agree. I'm, I'm grateful. I'm grateful for our group, our team. I'm grateful for, for people who are doing research in this field. I think it's, it's great to help patients day to day and I think it's great to reflect and really continue doing research to help further advance this field and help men and women who are trying to conceive. And also very grateful for my family and the RMA family and also my personal family. Lots to be grateful for.
Rena: That’s so beautiful.
Dara: Well, we're so excited for you, Dr. Chelsea. We’re wishing you only the best at the upcoming conference and what's ahead for you. Very excited.
Canon: Thank you so much.
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 @fertility_forward and if you're looking for more support, visit us at www.rmany.com and tune in next week for more Fertility Forward.