Behind the Scenes in the IVF Lab

I have Dr. Carol Lynn Burton Curchoe on today’s egg whisperer show and we’re going to talk about everything related to embryo making. She is kind of a badass and I’m super excited to have her with me here today.

Let me just tell you guys a little bit about her. First of all. Hi Carol.

Dr. Carol Lynn Burton Curchoe, also known far and wide as Dr. Curly Queues, joins me during National Infertility Awareness Week. Dr. Curchoe is a Senior Clinical Embryologist and Founder of ART Compass IVF. We are talking to her about the latest cutting edge technology used in today’s IVF labs. We will also be talking about the ART Compass app, a mobile application platform for IVF cycle management, and how her technology has changed workflow and improved safety in labs everywhere. ⠀

Dr. Carol Lynn Burton Curchoe is a reproductive physiologist, her Ph.D. research focused on animal cloning and our postdoc fellowship focused on human embryonic STEM cell research.

Say that 10 times human embryonic STEM cell research. That’s amazing.

Her previous startup experience includes being the founder and CEO of 32 ATPs where she applied her knowledge of biochemistry and biotechnology to the field of renewable energy creating a patented biological supercapacitor. I mean there should be a show about you. I just want to follow you around with a GoPro. She’s the founder of ART Compass IVF. She’s going to tell us more about that. It’s a mobile application platform for IVF cycle management. Carol, how did you get to be so awesome?

Dr. Carol Lynn Burton Curchoe:

Well, I’ll tell you, it was a long winding path. My mom actually was a single mom that had five kids and I did not make it through high school. I have a GED, but I had some solid mentorship and went to a community college, got an associate’s degree in biology, transferred to the University of Connecticut, and had amazing teachers at both places.

I’m incredibly proud to be a Husky and to be a native of Connecticut and to have attended Manchester community college. They recently honored me with the “Alumni of the Year” award, which just blew me out of the water.

It was really just such a nice foundation from a state where girls are really expected to make something of themselves. So, even though my background was sort of inauspicious, you know, I come from a cattle town sometimes we say more cows than people, and I got to the University of Connecticut. I wanted to do high tech science, but I ended up right back with those cows in the biotech lab. I had just an amazing graduate advisor there. She was the person who got me into graduate school. I didn’t know anything about having a Ph.D. or a doctor or having an advanced degree at all. And, and so, yeah, it was just a series of very fortunate events for me.

Dr. Aimee:

So then how did you get from cows to humans? How did that transition happen?

Dr. Carol Lynn Burton Curchoe:

So after I did cattle cloning in my graduate work, I think when into the human embryonic STEM cell model. So a human embryonic STEM cell, comes from an embryo, and it’s a cell that can become anything in the body, as I’m sure you know, but maybe some of your listeners don’t.

So when you’re an embryo, all of your cells are exactly the same, but then as you grow and differentiate, you go on to have a heart and lungs and the liver. And so what we were doing is we were trying to create the nerves that go to your peripheral nervous system. So your sense of touch, taste, and smell. And that was kind of my first stop off after cloning, which is a form of reproduction. And to create those human cell lines. Then I went to the administration side of things where I was overseeing a department that had a lot of very high-tech labs, including viral repositories where they were freezing tissues.

And eventually, I took a detour into politics. I was actually the governor of Utah’s science advisor and they worked on a huge project there. It was a $10 million allocation from the Utah state legislature. This was in an effort to get the STEM action center up and running.

Following that is when I did my startup. I applied everything that I learned from the freezing of tissues and growing cells. And then doing science to trying to create this biological supercapacitor. So that was an energy device, kind of like a battery. That’s what a capacitor is. If you think of the old-style cameras, you used to hear a whirring as the flash charged up. That’s a super capacitor. So a whole, a lot of energy, but it releases it very quickly.

So what we were trying to do was do that in a green way that didn’t require the toxic components of batteries. So we wanted to make a super capacitor that was essentially a cell. We used sugars and enzymes just the same way your cells do to create energy. And we did that in an electrical device.

Dr. Aimee:

And this was while you were working for the government in Utah?

Dr. Carol Lynn Burton Curchoe:

No, that was after.

Dr. Aimee:

Got it. I was like, what are they doing? Dealing with supercapacitors as the government? Okay, got it. Got it.

Dr. Carol Lynn Burton Curchoe:

Utah had a whole bunch of programs that were aimed at clean energy and startups and entrepreneurs kind of got in through that channel. But basically what ended up happening was my supercapacitor project brought me back to San Diego where there was a clean energy cluster. And right as I was wrapping up that project, I became pregnant with my own miracle baby. I realized that I needed a career that I felt was worthy of me of missed time with my miracle baby. And I also wanted to apply all of the science that I acquired throughout the years to help women get the same love that I now had through a child.

I just knew that I had to go into embryology. So at the age of 37 with an eight-week-old baby, I basically started a brand new career.

The field of embryology has a very long, slow learning curve because it is so highly technical and it really depends on your technical skill. And so I was just at the bottom rung of the ladder as you know, a worker bee trying to learn the field of embryology. But I just knew that it was something that I had to do and I’m so glad I did it. I wish I’d done it earlier. I am in love with this as a career. It is just the best thing I’ve ever done.

Dr. Aimee:

Yeah. So I mean it sounds like it’s fun. It’s not working. When you love what you do, it’s, it’s really a joy to go to work every single day.

Dr. Carol Lynn Burton Curchoe:

Absolutely.

Really everything that I did in grad school relates to or ties to the field of human embryology. From the freezing of tissues to growing cells to working with eggs.

Dr. Aimee:

Yeah. You mentioned something, and if you don’t mind, I’d love to hear more. You mentioned something about your pregnancy and, and, and can you just share a little bit about your personal journey as well? You know, maybe someone who’s watching can learn from it.

Dr. Carol Lynn Burton Curchoe:

Yeah, I would love to. So like so many women nowadays, I waited until I felt like I was in a really good point in my career to have a baby. And it did become a little bit like, “okay, it’s now or never.”

You know, I was getting into my late thirties. My whole life I had been focused on preventing pregnancy. So for 15 years, I was on the birth control pill and a lot changed in my body over that time. When I went off that pill it took me years to get off that cycle.

I had something called mean phenotype, PCOS. So I had some kind of insulin metabolic processing problem that was causing me to not ovulate. In fact, I didn’t even get there yet. So I embarked on a plan of aggressive carb-cutting. I cut out all the wine, all the refined carbohydrates, really tried to get it down to that under one serving a day that they recommend.

I was actually very skinny at that point. My doctor wanted me to try Metformin. For some reason, at the time I didn’t want to do it. Now looking back on it, I wish that I had. I also did try some cycles with Clomid and I actually eventually gave up because my insurance didn’t cover IVF and it didn’t cover seeing the reproductive endocrinologist that I needed to see.

So I was really not under the care of a fertility specialist, but I maybe should have been for my lining. Because I wasn’t getting my period my lining wasn’t that thick. And so my, my daughter ended up having not a great placenta, not a good placental attachment. And her cord was very stiff. So the flow of blood through it was there was some resistance.

So she ended up having intrauterine growth restriction. And you know, possibly a factor of age, health, nutrition, all of those things. But really, you know, I, I do wish that I had been under the care because we ended up having to induce early.

I was so small. So all of those things that people are supposed to do like come up to you and say, ”Oh when are you due, and congratulations and all these things.” It was almost like you couldn’t even tell I was pregnant.

She ended up being just a smidge over five pounds, which was actually really good.

Dr. Aimee:

Good. Well, and how old is she now?

Dr. Carol Lynn Burton Curchoe:

She’s three now.

Dr. Aimee:

That’s an awesome age. So, so now I want to hear more about what you do now.

You’re a senior clinical embryologist. What does that look like for people who are listening? Like literally from the time you wake up until the time you leave work.

Dr. Carol Lynn Burton Curchoe:

Yeah. So usually the first thing I do when I get in in the morning is I do the quality check in the lab and make sure that all of the instruments are functioning within the correct parameters.

What we’re trying to do in the lab is replicate the fallopian tube. So literally a human organ. We are trying to replicate the environment of a human organ in the lab. So everything has to stay within a certain humidity, a certain pH, a certain temperature. We do this because that’s where the fertilization is going to take place — in the lab!

So I get it in the morning and I do all the quality control checks and make sure that the incubators are functioning properly. And then usually we, we launched straight away into egg retrievals. I love egg retrievals because that’s what starts it off for my patients on their journey.

And so after the egg retrievals are done, usually what happens is somebody else is thawing embryos in the lab and somebody else’s biopsying embryos at the same time. All of those things need to happen in the morning. And then usually the embryo transfers happen in the afternoon, the cells that got biopsied get packed up and shipped off in the afternoon. And then we are also taking those eggs that we collected in the morning. We’re also processing the sperm at the same time and they get creating the embryos later that day.

Dr. Aimee:

And which lab do you work in right now? Where are you located?

Dr. Carol Lynn Burton Curchoe:

Yeah, so right now and, and obviously what I do on my own time is not connected, but I’m at CCRM in Orange County.

Dr. Aimee:

Beautiful. What I’d love to do is ask you a series of questions related to embryology as I know patients would love to learn from you.

Okay. Here we go.

Does ICSI really cause birth defects? What do you think?

Dr. Carol Lynn Burton Curchoe:

Oh, so this is a good question. It’s a little bit esoteric and academic. So the question really comes down to this. Are people who are undergoing fertility treatment and need ICSI, are they healthy or are they passing something along that’s causing birth defects?

So far we haven’t had very good clinical studies to help us tease out those effects. But what we do know is that there is a small elevated percentage of maybe cardiac defects, maybe epigenetic defects and possibly some congenital defects. But we don’t know what is exactly causing that. We don’t know if it’s the culture environment or if it’s because somebody is being treated for infertility. So they are passing on a problem. We don’t know if it’s, you know, simply just from culturing embryos outside the body. We just don’t have enough information yet.

Dr. Aimee:

I’m glad you said you put it that way. That’s exactly what I tell my patients too. We don’t know if it’s the actual procedure itself or the fact that someone a genetic predisposition to have a slight, and we’re talking about a slight increased rate of birth defects.

What about assisted hatching? Does that harm embryos?

Dr. Carol Lynn Burton Curchoe:

There are two times we do assisted hatching in the lab. One is if on day three the embryo is made of cells that look to have a space in between the border. That’s where we take the laser and we have to write in that space in between the cells. We’re not hitting the cells at all.

Then the other time we do assisted hatching is usually after we thaw the embryo before transfer. And if an embryo is in its zona and the zona is thick and it’s in there all the way, we really do want to assist that embryo to help get it out of the zona because it needs to do that to implant in the uterus.

When we freeze the embryos it’s shrunken down and the zona, there’s a space between this membrane around the embryo and the embryo itself. As a result, we take the laser and we’d go over the zona and we’re not anywhere near the embryo itself. Unless you have somebody who’s not skilled at all using the micro manipulator will not be damaging embryos by doing assisted happening.

Dr. Aimee:

Beautiful explanation. I mean what I tell patients, it’s basically like if you need to have your appendix removed, you have to have the surgery part, right? I mean you can’t do assisted hatching or you can’t, let’s say biopsy and embryo without hatching it first. Would you agree? I mean it would be impossible.

Dr. Carol Lynn Burton Curchoe:

It would be impossible. It would be mainly because you know, a lot of the way people are being treated is because their embryos are slow-growing. So it is possible in a very young, healthy person with young, fast-growing eggs and embryos to have a fully hatched or hatching embryo on day five or six. We would likely see that in patients who maybe were using an egg donor or as they were, you know, they were doing X, Z, and IVF just for gender selection and family balancing. And they just wanted the PGT. But other than that they were young and healthy. But even, even then, the majority of embryos, are not going to be hatched on day five on their own.

Dr. Aimee:

Right. And do you do a lot of PGT in your lab?

Dr. Carol Lynn Burton Curchoe:

I can’t really answer questions about my lab specifically, but I can talk in general about the field.

Dr. Aimee:

Absolutely. I guess my question would be if it were you knowing everything that you know, would you feel that PGT is a safe procedure?

Dr. Carol Lynn Burton Curchoe:

Absolutely. So I would say that in 99.9% of cases PGT is absolutely safe. Now I think in the field we’re using it on 80–90% of IVF cases.

There is a ton of controversy around PGT. It’s benefits and it’s so clinic specific on whether it’s improving the rates. It’s really confounding the data when you start to put it all together from all these different clinics and trying to answer the question, “Is this good for any patient undergoing IVF?”.

So if I don’t know if anybody does have this question out there, but if they’re asking themselves, “should I do PGT?”. They really need to decide in conjunction with their clinic what pregnancy rates for people in their age group are with their indication. I encourage them to try to see if it’s helping the patients. The closer you get to forty the more embryos you have that are going to be chromosomally abnormal, right?

Dr. Aimee:

Yeah. I mean, the thing is they are discouraging you from doing it, there’s a reason why. They know what’s going on in their lab. Clinics who have the highest tech equipment and the best-trained embryologist, I think of embryologists as if they’re pediatric surgeons, right?

They have to have the skillset in order to do this procedure so that you’re not damaging embryos. And that’s really, really important.

So asking questions such as, Who is actually doing the biopsy on my embryos? What is their training? What is their background? How long have they been doing it? I think these are very fair questions to ask before you embark on an IVF cycle journey.

Dr. Carol Lynn Burton Curchoe:

Yeah, I was going to say, so embryology has this really, really long training period. That biopsy procedure is the last thing you learn. And it really does take years of clinical competencies building on each other to get to that point as an embryologist, because there’s so much more that goes into, you have to look at the embryo and which top of cells to surgically remove. And that judgment takes a long time. It’s not just, you know, can you remove a little clump of cells without damaging the embryo? And then there’s also this whole chain of custody that happens. So each chunk of cells has to stay with the number of that embryo because the embryo is going to be frozen away and put away and the chunk of cells needs to be sent off the genetic testing company and it has to correspond back.

So it’s, it definitely, you know, I think within the field of embryology, we have our own internal standards for training and it’s very, it’s really very strict and it’s very hierarchical.

Dr. Aimee:

Can you tell us about the ART Compass app that you have?

Dr. Carol Lynn Burton Curchoe:

Yeah. so when I first started in clinical embryology at 37 I was brand new. Yet I was highly educated, having a Ph.D., yet one of the things that were a bit frustrating to me was how to determine what clinical decision to make.

There was really was no good way to know except by sitting directly with an embryologist and trying to absorb their knowledge from 20 or 30 years in the field. And I felt like there had to be a better way to train the next generation.

The app has a patient portal and portal that’s for the administrators. They can see all of these statistics that are related to their practice for success rates. And you know, the doctors can have the cryo storage inventory in their app, and they can see exactly all the details of their patient’s cycles.

But it started off as one humble module for it, for embryologist competency training. And, it grew from there. As my own training increased and I saw all these different areas that could be digitized and then realized that MDs and patients want to have access to the same type of information throughout the journey.

So it’s very role-based. So you only see the information which is relevant to you. It’s very comprehensive for labs. There is a whole suite of quality control tools as well as delivering those PGT results and patients can see that images of their embryos, which they love.

Dr. Aimee:

They love it. Everyone asks me and I love to be able to give them images of their embryos.

So the next question I want to ask you, and for those of you who don’t know, there is something out there, it’s called noninvasive PGT and we’re going to be hearing more and more about that probably in the next year to five years.

Can you just tell our viewers what that is and what you think about it?

Dr. Carol Lynn Burton Curchoe:

Sure. So I just want to start by saying noninvasive means that the, you know, the conventional way to do PGT is that you’re plucking some of those cells of the embryo. What noninvasive means is that you’re not doing that. So there’s a couple of different techniques. The embryo is full of fluid and so in one of those text techniques, you’re actually taking some of the fluid itself from the embryo and you’re leaving the cells. And in the other one, you’re taking the culture media, which is all of the sugars and water and all of the foods that the embryo eats and you’re taking the culture media and analyzing it. So I think that these are technologies that are maturing and they definitely are going to impact the field at some point. Every embryologist I know loves PGT for the results that it gives, but we dislike plucking a few cells. Even though the cells are coming from the home around the embryo, which is the layer that will become the placenta and we know that it’s not damaging the embryo and all of those things. But it just doesn’t feel like amazing to do. It’s like pulling hairs out of a child. Who would enjoy doing that?

Dr. Aimee:

Yeah. I say a special prayer and do my little dance before every egg retrieval. It’s the same thing for you. I mean, I would love to be able to be like for what we do for men, for women. I’d love to give women a cup and instruct them to give me their eggs.

Dr. Carol Lynn Burton Curchoe:

It is. Like you were saying that we are just plucking a few cells so it doesn’t give us the full picture. And so as these technologies are maturing, I think what we’re hoping to see is that the technology of PGT and maybe some of the reason first this, all the discord in the field and disagreement about whether PGT is effective or not can kind of be solved by us getting more information from the whole embryo instead of those few cells from that perfected or minor.

Dr. Aimee:

And I think that actually that leads into my next question about mosaic embryos and how you would feel if you, I mean, I know I’m asking you very personal questions, so feel free to decline. If you only had one embryo and it was mosaic, let’s say for a high priority embryo to transfer, I won’t call out any chromosomes here. Would you feel comfortable transferring it with everything that you know?

Dr. Carol Lynn Burton Curchoe:

I would transfer it. Yeah. I agree. Yeah, I think that so. In the end, that mosaic embryo might actually be more normal than we know.

And we certainly do know that the human genome is not immutable. It changes. I think there’s a lot of evidence now from papers that have been published, but I’m showing the success rates of mosaic embryos. It can vary depending on the exact chromosomes that are mosaic for how many of the cells are mosaic. But you know, the way that I always tell my patients to think about it is an embryo is like the soccer ball. It has black spots and white spots, and when taking the biopsy, if we take it all from one color spot, that can generate a false positive, it can generate a false negative, or it can generate this result if we take it right from the border of a mosaic result.

So you’d have to also think we’re only taking five cells. If one cell is different, out of the five cells, that will be called a normal embryo, two cells out of the five cells are different. Or let’s say instead of a five cell biopsy, we took a four-cell biopsy and two of those cells are different. Suddenly that’s 50%. And your genetic testing lab might call that mosaic or it might call that abnormal. But if we had taken a bit bigger of a biopsy, let’s say we’d taken seven cells and two of them are abnormal, that would put your embryo back in that, in that normal territory or that low mosaic territory. So I think that the, you know, in terms of order up for ranking the embryos for transfer, what I want to do is get my patients pregnant quickly.

So I’m going to pick the best-looking embryo. That is the biggest because that gives us an indication of its metabolic health. So I’m going to pick the most expanded embryo that has the least amount of fragmentation and has a PGT score of being more. But I’m putting all that information together to take the embryo to transfer first. In the case where there are only one or a few embryos to transfer. So I’m always on air on the side of transfer as we’ve all seen embryos that we thought may not make it become babies.

Dr. Aimee:

Right, right. So basically what you’re saying is the embryo quality really does matter, but sometimes the ugliest embryos can turn into the most beautiful babies.

Dr. Carol Lynn Burton Curchoe:

That is so true. Yeah.

Dr. Aimee:

If you were a patient, what kind of things would you be looking for in an IVF lab to choose that lab?

Dr. Carol Lynn Burton Curchoe:

So I think one of the things I would like to know is what the overall level of experience of the staff is. Is there a lot of staff turnover? How long has the program been in existence? How long has the embryologist been working there? You know, and I actually say that as a new embryologist at my current practice, I’ve been there for less than a year, but I moved because the reputation of this practice is so good. It’s like those, those things do matter. But then if you were to look at me and you would say, okay, she’s only been there for a year. Right? But the other people that I work with have been there for a long time. We are always are trying to bring new embryologists into the fold and to train them.

You do want to train them in your specific way of doing things. So it is good to get them young and to train them. Prior to working with a lab, you want to know that their quality control procedures are really good. You want to know that they’ve passed inspections. So usually there’s going to be a certificate on the wall somewhere saying that this is a cap accredited lab or a joint commission accredited lab or so I think all those things are important. And then, I also want to know that the lab is using new technologies.

Dr. Aimee:

What kind of questions could we ask that could help us understand if a lab is using new technology?

Dr. Carol Lynn Burton Curchoe:

Well, I think one of the things that I would love to know is if the lab is doing a laser-assisted biopsy, and if so if they are doing it on day five, six, or seven.

Most places have stopped biopsying on day three. Lasers are expensive, but the best for cutting cells.

Dr. Aimee:

There’s a reason why lasers are very expensive. If people are not using the laser they haven’t invested in their lab. And if they haven’t invested in the laser, you can imagine they haven’t invested in the latest incubators or anything else that’s potentially important to the quality of the lab output.

Dr. Carol Lynn Burton Curchoe:

Yeah, it’s a little bit of a tough position because if the lab has, is a long-established lab that is running well and it’s getting patients pregnant and there are no problems with their rates, then it almost doesn’t matter what kind of culture systems they’re using if they’re producing beautiful for babies. Right. So it’s, it’s a little hard, but from your perspective, what do you think that patients could ask about the lab? Like what would you tell your patients if they were asking questions about the lab?

Dr. Aimee:

I mean, I know that in the Bay area and in California in general, people are just so lucky to have the access and so many options to different IVF centers and they’re really all top-notch.

So, you know, I don’t know that necessarily these questions are as useful, let’s say in the Bay area for example. But in other parts of this country and in California too, you know sometimes there still are centers who aren’t using a laser. They’re not, you know, they haven’t invested in the technology in the lab. But I mean for me it’s just one question is how many people work there?

I mean that’s a very simple question to ask because if it’s just one person, there might not be the checks and balances in place to make sure that you won’t have a wrong embryo transfer or a label issue. Or like you said, that chain of custody, the COC, it’s so important in the lab that might not be there if there’s just that one person.

Because how could you, if you don’t have that second person to double-check things and sometimes there are even three people in the lab for certain procedures that check everything, the labels, make sure you’re throwing the right embryo, make sure you’ve labeled the Petri dish correctly, for example.

Dr. Carol Lynn Burton Curchoe:

Sure. And so now there are also electronic witnessing systems because there are some technologies that are being developed for these smaller labs. And even for big labs, right, that we, we want to be sure that everything we’re using is barcoded to the patient. You can scan it in.

I would want to know that my embryos are the only embryos in that section of the incubator.

Dr. Aimee:

Right. You want to make sure that you’re not sharing an apartment or you’re not roomies with somebody else’s embryos.

Dr. Carol Lynn Burton Curchoe:

Absolutely. Yeah. And you know, the incubators these days, usually they have low oxygen tension. You know, usually the oil that the embryology lab is using is very clean and they’re buying commercial sources. But, and you know, another thing that patients might want to know is are they making reagents themselves or are they buying them from a commercial source? Again, along those lines. Now, I don’t know if the practice is necessarily going to tell people that, but it may be worth asking.

Dr. Aimee:

I mean I think it’s fair, these are very fair questions and I tell patients being in an IVF doctor is kind of like being in the restaurant business. You kind of know what’s going on in other people’s restaurants. Like I know who’s doing these things and who has this and who doesn’t.

But a patient wouldn’t know unless they asked. And you’re right, they might, you might not get access to the embryologist to ask these questions and that might be a red flag right there if people won’t, you know, I know the lab directors that I work with, they’re just so transparent. If a patient wants to ask these questions, I can do an email introduction with the lab director, and they will personally talk to the patient and answer their questions about all of these things. And a lot of these things are written up as protocols inside the lab and they’re also on the website sometimes, for example, the chain of custody and how that is taken care of behind the scenes.

Dr. Carol Lynn Burton Curchoe:

Yeah, very good points.

Dr. Aimee:

So let’s go back to our questions. I can never talk about this stuff enough. So thank you for your time. I know we’ve been talking for a while, but I can keep going. Is that okay with you? Okay. Here we go.

To freeze or not to freeze, that is the question. What do you think?

Dr. Carol Lynn Burton Curchoe:

Okay, so I, so a little outside of my area because now we’re bringing in the endometrium in the home that the, that the embryo is going into. So, you know, obviously, you know, to say it again, nothing I say here should be taken as medical advice.

Dr. Aimee:

We’re just here for educational purposes only. Just do people know what questions to ask their doctor. Of course. No one’s going to stay with us through our conversation.

Dr. Carol Lynn Burton Curchoe:

Well, so from what we have seen in studies is that when you take off these drugs to stimulate your ovaries, you know, the whole body is active in this process. And what seems to be the best way is to let the body come back down, prepare the endometrium separately, freeze all the embryos, and then transfer one single genetically normal embryo back at a later time. But there are certain patients where some practices are still doing, you know, a day three fresh transfer. So that would be a few days after the egg retrieval. Right. You know, there’s, I almost want to say that when you’re doing a fresh transfer like that, it’s almost kind of like a last-ditch effort. Like, like with an Olympic athlete, you’re shaving seconds off of your time. And sometimes that is the way that we’re practicing IVF and reproductive medicine is where like, it probably wouldn’t be good for the normal person to do an Olympic athlete does. But what do I need to do to get this patient to the finish line? So occasionally the thought is that in some, some cases, some certain cases age-related or related to the different why the person’s being treated for infertility. The embryo might be better off inside of them on day three than in the lab until they five.

Dr. Aimee:

Right. Or a fresh transfer on day five to based on their personal story. So what I’m hearing from you is basically freezing an embryo isn’t going to harm your chances of pregnancy if you’re in a top-notch lab.

Dr. Carol Lynn Burton Curchoe:

Sure. And they even look at freezing and thawing an embryo as a strategy for increasing pregnancy rates.

Dr. Aimee:

Freezing embryos have been improving pregnancy rates in several studies. That’s absolutely true. Okay. So with freezing embryos then you’re dealing with storage of embryos and we’ve all heard of a lot of these sad stories about storage issues with tanks and tank failures. And you know, I have patients that are very nervous about the tanks, not so much now in 2020, but for example, in 2018 there were storage issues.

And we don’t hear those questions as much, but have things changed as far as how people are taking care of embryos and tanks to make sure that those kinds of things don’t happen anymore?

Dr. Carol Lynn Burton Curchoe:

Well, so I should say that many, many years went by and there were never any tank failures or anything like this happen. There were two highly publicized events. They happen at good labs to good people. They could happen to anybody. It is really terrifying for all of us in the field who thinks that something like that could happen.

I don’t know specifics, but I do know that in one of the cases, it was a catastrophic failure of the device that nobody could have predicted. And I don’t know if a lot of people know this, but liquid nitrogen is minus 180 degrees. And as a gas, when you cool a gas off, you condense it. And when that gas warms up, it expands. So liquid nitrogen can expand to seven times the size. So if you were to the warm a bunch of liquid nitrogen, it actually created a missile out of your tank, a bullet, a bomb.

The explosion is significant and it’s, it’s one of the fears that everybody has because of a dewar, liquid nitrogen where the embryos are kept. Think of your thermos that you’ve put hot soup in. That thermos has a vacuum that’s keeping your soup pot. And the dewar is the exact same thing. It has a vacuum that’s keeping those extra freezing cold temperatures in there. And those freezing cold temperatures can break many, many things. In general, it’s very safe. We went 30 or 40 years without anything like that ever happening. So of course, you know, we worry about manufacturing defects, we worry about all of those things. In other cases, there are ways to fill the tank automatically with more liquid nitrogen.

And if those pieces malfunction, which you know, you’re dealing with ice crystals and again these freezing cold temperatures, they can break down the chemical components. So I think what everybody’s doing now is visually inspecting the tanks more than one time a day.

We’re also measuring the liquid nitrogen level itself with a long ruler. And so that would be for every tank — you’re recording it. Several times a week you have this schedule that you’re filling tanks on. There are alarm systems on every tank. And then there are some new technologies as well that are thermal imaging cameras where you can see your whole cryo storage inventory on your phone. You can visually see if a tank is about to fail with a thermal imaging camera. And then I think the other technology now that’s being developed is an actual weight system.

Like a scale, but for these, you know, heavy nitrogen dewars that are also very sensitive so that they can detect just a little bit of evaporation of liquid nitrogen.

We don’t want to rely on any one thing. There is human error, there is a failure of equipment. There’s, you know, there’s just a variety of things that can happen. And so you want to have multiple monitoring systems to catch any one of those things from happening.

Dr. Aimee:

So maybe one question someone can ask of their doctor, you know, to feel like they really feel like this is the right fit for them is what kind of monitoring systems do you have in place here at tanks? That’s a totally fair question.

I have just a few more questions.

So what do you see in the future of the IVF embryology world in five, ten, and fifteen years from now? What do we have to look forward to? And I know some of your research and some of the stuff that you’ve talked about is related to AI. So I’d love to hear what you think about what’s to come.

Dr. Carol Lynn Burton Curchoe:

Yeah, absolutely. So one of the things that it’s in development right now is being able to do fertility preservation by taking a slice of ovary itself, maybe with a lot of eggs in it that are immature and freezing that slice of ovary and then at some point in the future maturity of those eggs. So all, all, so those pieces, how do you freeze a slice of tissue? How do you, you know, can you graft it back onto the patient at a later date? How do you graph it? Can you mature the eggs in the lab?

Another big area of research is can we create embryos from two of the same gender people? Does the body contain any STEM cells that we can coax into becoming an egg or a sperm? Or can you use a patient’s skin cells and have them go backward to the embryonic STEM cells and then forward again instead of being skin, they become an egg cell or a sperm cell.

Dr. Aimee:

Do you see that happening next 20 years? I mean, do you think that that is, that’s something that could really happen? I mean, I think it would be great. I’d love to never have to freeze eggs for somebody and have them go through STEM and hormones. It’d be really cool. It’d be like, here come, you know, or go see the dermatologist for your, your skin biopsy.

Dr. Carol Lynn Burton Curchoe:

Yeah. It’s realistic right now in animal hospitals. And you know, it’s, it’s probably a long way off from happening in humans, maybe five or 10 years. But these, these fields move incredibly quickly. You never know what the next breakthrough is going to be that will enable that technology to suddenly be deployed on a mass scale.

So those are some of the things I think one of the hot areas of research is sperm fragmentation. And it’s something that is just, you know, coming more well-known and there are you know, I think a lot of times the men kind of get left out of the equation, but they’re 30% of the infertility, right.

Men are aging their sperm and is aging too. And the DNA inside of it is aging. And even sometimes in young men, we can see high DNA fragmentation and sperm due to lifestyle or environmental factors or possibly even things that we haven’t even begun to figure out yet.

Right. So that’s a really hot area, sperm processing. And you were mentioning artificial intelligence. So artificial intelligence is being applied all throughout our world now. Self-driving cars. You know, when your credit card pings you that there’s been some activity on it that is outside your normal spending. That’s artificial intelligence at work and it’s being applied to the medical field. A lot of the applications right now are in cancer. So being able to look through a lot of radio imaging to see is that a normal lump or is that cancer, which does it fit? And so the computer and artificial intelligence is uniquely good at solving problems like that because the human eye takes 20 or 30 years of training, whereas the computer might actually see something that is completely unknown to humans. But it has studied so many outcomes. Like did this turn into invasive cancer? So do we have time for an analogy?

Dr. Aimee:

Oh, please. I love analogies.

Dr. Carol Lynn Burton Curchoe:

Okay. So I like to describe artificial intelligence as taking two pieces of colored paper and crumpling them together. You have crumpled something into this very, very complex structure and you know that at one time it existed as two separate pieces of paper, but how do you uncrumple those papers? Great. So a live healthy birth, that is our crumpled ball of paper. What we want the computer to do is work backward through all of them. Those unfolding that crumple one layer at a time until we have the pieces of paper that make up our patient, our patient’s embryos, our patient's demographics, and fertility history and diagnosis. And we want to be able to put all of those together so that the computers can tell us something we don’t already know. So we are pretty good at getting patients pregnant, but there are still some cases that I’ve repeated failure implantation or where we’re just not making embryos. There’s the STEM needs to be, you know, tweaked a lot to get some good quality eggs to make some embryos. Or the embryos are not making it to blastocysts or we’re implanting them and the patients are not getting pregnant. There’s a whole bunch of different things and that we really would love to apply artificial intelligence to these big intractable problems in human embryology.

Dr. Aimee:

Do you think we’re ever going to get to a point where we’re going to be able to culture embryos past day seven?

Dr. Carol Lynn Burton Curchoe:

Yeah. So we can now, to day 14 in the lab, but we can’t culture embryos past day 14 and at some point the embryo needs to act like it has implanted in the endometrium. And so now it’s being done experimentally, to day 14 but due to international agreement and local laws, you’re not allowed to culture any embryo past day 14. So I think that the technology could get there, but right now legally the experiments can’t be done. But I definitely had patients ask, you know, why do I need a gestational carrier? Or why can’t you just grow the embryo in the lab?

Dr. Aimee:

Well. Again, thank you Carol for joining us.

For those of you who don’t know and didn’t hear her credentials, she is a senior clinical embryologist. She has her Ph.D., her research focus in animal cloning, and her postdoc fellowship in human embryonic STEM cell research. And we’ve had a great conversation today.

In Summary:

We talked about her career, her personal pregnancy journey. We talked about all the things that you as a patient could ask the clinic to feel empowered to know that your IVF lab is top-notch. We talked about lots of controversial questions in the embryology world. For example, does ICSI cause birth defects? Should we transfer mosaic embryos is fresh versus frozen better? What’s going on with PGT is noninvasive PGT in our future? I really appreciate you taking the time to talk to us about the future of embryology and what your predictions are for the future.

This conversation has been super informative. When something’s informative for me. I hope it doesn’t make those out there snoring cause I could literally talk about this all night long and I know we’re not going to, we’re going to end this show very soon, but I just wanted to say thank you for doing the work that you do. Thank you for being as passionate as I am. I’m like the most annoyingly positive person in the whole world. Like you don’t get more annoying than me. And to know that there’s someone like you, you’re not annoying, but you’re extremely passionate about what you do. You’re incredibly intelligent. So it just makes me so happy to know that there, there are people out there just like you and I know that others watching this show, you know, we should be excited about our future.

We shouldn’t let the pandemic take away our joy. We shouldn’t let the pandemic take away our fertility. And there’s always hope. There’s a future, you know, you and I have our boats, we’re all in this storm together and we’re throwing out our life vests to all those patients out there. And because of people like you and the research that you’re doing, there is a better future in the IVF lab and the IVF world. And I imagine you would agree that there are patients that you’ll be able to help in a year from now that maybe we couldn’t help five years ago.

Dr. Carol Lynn Burton Curchoe:

That is true. I also want to say we can’t wait to get back in the lab for our patients and also that they’re worth the wait, you know, they’re worth the wait for us to make sure that we’re all doing this safely for everybody’s best interests and we’re going to get back up and going again soon.

Dr. Aimee:

Yeah, and I mean that’s what I was going ask you to do is before we close the show. if you had fertility patients standing right in front of you right now and you had one thing to say to them, what would that be?

Dr. Carol Lynn Burton Curchoe:

Well you know, I think it would be just that, that your health is a top priority and your future family, keeping you healthy so that you can have that future family is my top priority.

I know there’s a lot of concerns about whether egg quality can change in just a few weeks. I’m not aware of any studies showing that egg quality can change in just one month or two months' time. I understand people might start getting a bit afraid of, you know, six months delay or a year delay, but we’re, you know, right now we’re still in that period where if they were on a treatment course before, you know we’re going to stay the course and egg quality can vary from cycle to cycle anyway.

There are so many things patients can be doing right now to prepare their body and health to make sure that they are in tip-top shape for when a retrieval can happen.

But I think now we’re starting to see practices are preparing to open back up. You have states that are now coming through and saying that you know, these procedures can start to move forward and all of our practices are looking about ways that we can open up safely.

We can distance our patients, distance the time in between procedures, and limit how many people are in the office on a certain day. We’re rotating embryology teams so that if anybody does get sick it doesn’t take down the whole team. But like you were saying, hopefully, there will never just be one person. You know, looking after the embryos. So and I know that now at this time we’re all antsy to get back to it and we want to start seeing patients again.

Dr. Aimee:

Absolutely. Well, thank you. Thank you. Those are great closing words. Thank you for joining us on the Egg Whisperer Show talking about the latest and greatest in the embryology lab and getting your input and all the stuff we talked about. Thank you for all you do and thank you to all the viewers. Hopefully, you’ll join us again next week for our next show and everyone have a great night

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