Ep 170: Inside the Embryology Lab with Rick Slifkin
Fertility Forward Episode 170:
The embryology lab is often a mystery to patients, but it plays a critical role in every IVF journey. In this episode, we’re joined by Rick Slifkin, Embryology Associate Laboratory Director at RMA of New York, for a rare behind-the-scenes look at what happens after egg retrieval. With nearly two decades of experience, Rick walks us through each step of the process, from fertilization and embryo development to genetic testing and cryopreservation. He explains what makes a lab truly high-performing, how strict protocols minimize stress on eggs and embryos, and why innovations in freezing and thawing are making a meaningful difference. Rick also shares the latest research on abnormal fertilization and embryo viability, offering a window into how science and data are improving outcomes. Whether you're navigating treatment or simply curious about the process, this episode offers clarity and reassurance from someone who has seen it all. Join us for a deep dive into the lab work that makes modern fertility care possible!
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 from medical professionals, mental health specialists, wellness experts, and patients, because knowledge is power, and you are your own best advocate.
Dara: Today on our podcast, we have Rick Slifkin, who I just found out has been a part of RMA for 19 years now and has worked in many capacities and currently serves as the Clinical Embryology Associate Laboratory Director here in New York City, but he oversees the Manhattan and Brooklyn embryology laboratories. So I'm so excited to have you today. Like Rick, I feel like I've seen you off and on over the years at RMA, but we really haven't spoken all too much and would love to hear how your time here at RMA has evolved and also kind of giving us a behind-the-scenes of what exactly you do, the other staff around you, what they do and kind of what happens post egg retrieval and beyond.
Rick: Awesome. Yeah, well, thanks for having me. So I guess I started here 19 years ago, and I started as an embryology lab assistant. So the lab assistants are kind of the backbone that allows everything to run in the lab. What the lab assistants do is they prepare all of our paperwork, they do our data entry, they keep the lab stocked, they make sure that we have everything we need as embryologists to get our job done. So that was my first role here before I was promoted into an embryologist position. And then I started training and you start as a junior embryologist, we have levels one, two, and three. And a level one embryologist starts with some of the more basic procedures: sperm processing, fertilization assessments. We move on to retrievals, and I'll get into what all those mean at some point. And then as your skills develop and your knowledge of the field grows, you also start performing more procedures. And a lot of that is hands-on training. So, anyone who donates embryos or gametes to research, we really appreciate it because we can use that to help our embryologists train and grow. And we can have the embryologists practice on materials. So that's what we do with some of our QC and research donated materials. And the embryologists then, once they demonstrate proficiency with mock cycles, with mock things, so we don't actually move a patient's samples until you've already practiced on something. So you could practice just moving media around with our different types of instruments or whatnot. And once you're proficient in that, then we continue our training where you will do a limited subset of actual clinical cases with a supervisor or senior embryologist. And then that embryologist will keep training and do more and more, and they demonstrate proficiency at each step of the way. So we make sure that their rates are in line with all of the rest of the lab rates. Going kind of back to my evolution, after I grew through level three embryologist, I became a supervisor, and where I am now as associate director, one of my main roles is to make sure that the embryology lab is performing as optimally as it can, which means that we want to make sure that we get the best possible fertilization rates, the best possible usable blast rates, and the best possible pregnancy rates. So I take all that data that we have from the lab and I look at it and I see if there's any areas for improvement, any areas for optimization, and make sure that all of the staff are performing to the best of their abilities and make sure that there's no outliers. One of the things that I love that we do is we'll take someone who's performing the best and we'll use that person as the trainer for the next kind of generation or for the next annual procedure review. So multiple times a year, we also sit down even with trained staff and we make sure that they're doing everything exactly by the protocol, exactly the way we want it done. Sometimes in any field, there could be drift and we have a big team here and one of the things we pride ourselves on is minimizing that drift and making sure that everyone's doing everything the exact same way so we have basically optimal outcomes. So when we do those reviews, we'll take the best people to watch everyone else and make sure that they're doing it the right way and the best way.
Dara: That's great. So it sounds like there's a big process from starting out, observing, to various levels. Is there an educational component outside of the practical lab or is it predominantly, I'm sure hands-on is probably the best, but is there also something that needs to be required outside of the lab?
Rick: Yeah. So we do, a lot of the junior embryologists will come in with at least a bachelor's degree in a physical science. So we all have the same kind of background biology knowledge. But then as you grow in the field, you're required to know more. And most of that is for troubleshooting and helping to develop new techniques and helping to understand ways that we can optimize. So we run a monthly lab lecture series that I'm really proud of, where one of our own embryologists will either present on a topic that they're currently researching on, they might present on a paper they read that's really interesting, or we occasionally will have outside people come in and present on something, but it really helps ‘round out our knowledge. Then as you grow in the field, you can also get your embryology lab certifications and you can get a technical supervisor certification. And then they have high complexity lab director certifications. And those come with years in the field, number of procedures, experience and degrees. We also, something that I really appreciate about U.S. Fertility is we have tuition reimbursement. So we try to get as many of our embryologists to go back and go back to school and get a Master's or a PhD in reproductive science and that really helps round out their knowledge as well. So we have a lot of staff who have Master's, PhDs. We have an MD in the embryology department as well. And yeah, that's really great. So our lab lectures, our education, and then we have a whole bunch of conferences each year and a number of embryologists go to those conferences and they come back and they bring back what they learned and share it with the team. And then we have journals that we read.
Rena: Amazing. So tell us also in our field, people often look to clinics and say, oh, this place has a good lab or this place has a bad lab. How do you make that decision or how do you know if a clinic has what would be classified as a good lab or a bad lab?
Rick: I think probably the easiest way for somebody who doesn't have friends in every lab the way that we do is to look at the national reporting rate. So SART publishes pregnancy rates and outcome rates from every SART-reporting lab. Every lab is required to report to the CDC. Most of them report to SART and, in the US at least, and you can look and compare labs head to head and see what the outcome rates are from labs. That's a good indicator of the physician and the laboratory and the whole support team. In terms of the actual lab, kind of what makes one lab better than the rest, I'm a little biased because we're fairly large labs, but I think having that large lab level of experience between the team that we have here, over 30 embryologists, I don't want to say we've seen it all because everyone still gets surprised sometimes, but we know how to handle kind of everything that comes at us. And when you're from a smaller lab, and some of those smaller labs really are great, but you just have less breadth of experience than the bigger labs do. And I think that's one thing that we really have going for us is we have so much data that we can pivot based on anything we've seen and we can learn and grow from that. And we have such a knowledge base from the team of embryologists we have here that we all help and support each other and make sure that we're really providing optimal care and performing procedures the best possible way in the industry, not just kind of the best way that one person knows how to do or a couple people know how to do it.
Rena: So does it have to do more with people or the technology in the lab that would make it good or bad?
Rick: It's a little bit of both. It's definitely possible for a lab to fall behind technology-wise. So you need to make sure that the clinic is investing in the lab and you have optimal equipment. For us, I mean, the basics is we need to make sure that our incubators where we hold the eggs and embryos are at the right gas levels, the right temperatures, everything that minimizes stress. That's really what we're looking to do in the lab is minimize stress on eggs and embryos because everything we do outside of the body can potentially introduce stress and inhibit growth. And we want to make sure that we're providing just an optimal environment for those eggs and embryos to grow in culture. All of our surfaces are temperature controlled. So if you touch basically any surface that we work on in the lab, whether it's a laminar flow hood or a microscope, they're all at body temperature. And we minimize the number of times we need to move dishes out of the incubator and where we need to lift them, because every time we lift that dish, we're altering the temperature of it and we're potentially altering the gas concentrations in there, which affects the pH and can induce stress. So we have protocols optimized to limit that and to really minimize stress, make sure that all of our equipment is performing optimally. We also, one of, I guess I didn't mention this, but one of the assistants, the lab assistants jobs is to, we call it QC quality control, every piece of equipment we have every single morning. So we have 40-some-odd incubators in our Manhattan lab, and they run gas analyzers on every one that independently checks the gas levels. We have independent thermometers in each one that verifies against what the equipment thinks it's reading and we analyze these against calibrated controls that actually tell us the real levels. We put thermometers on every single surface in the lab, and we just make sure that everything is at the perfect levels to minimize stress and optimize growth.
Dara: These are things that I never would have thought about. Do all fertility clinics have labs, or do sometimes they send things out to a lab outside of their clinic? How does that typically work? My assumption would be that every clinic would have a lab, but I don't think that's the case?
Rick: Yeah, so... I think there are a lot of fertility centers that have either centralized labs or they have monitoring locations, but even within the RMA network, we have multiple centers and they don't all have labs. So we have a laboratory in Brooklyn, Manhattan, Westchester, and Long Island, but we have more centers than that where patients can go and have their blood drawn or have ultrasounds done. It's kind of important to make sure that I would say not kind of attaching a lab to every center because there is that, like we talked about before, that strength in volume. And if you're running a laboratory for a few cases a year, you're really not going to be able to optimize your techniques the way we can, where we have a bigger volume and we can really monitor development. Every patient's samples are different. Every patient's gametes are different. And it's possible that one patient may have a better outcome than another. And we need to know, is that due to patient differences or is that due to the lab over-underperforming? And we can very quickly identify that when we have volume.
Dara: Wow.
Rena: So I guess tell us a little bit about even egg retrieval. And then they go off to the lab, the sort of big, dark land of the lab. And then patients, you know, that's when whether you're making embryos or freezing eggs, that's when they, you know, start to sort of get in their heads. What's happening? What's going on? Am I getting a call? They made it to blast? Are they getting graded? Like tell us, so what happens once the lab receives the eggs?
Rick: Yeah, everything starts actually a day ahead of time because we need to prepare for those eggs to be ready in the lab, which means we need to have dishes that are ready for the eggs. And that means they need overnight at least to equilibrate. So the media we use, not to get too technical, but it's bicarbonate buffered media that has an optimal pH at a elevated CO2 level. So our incubators are gassed at between 6% and 7% CO2. It kind of depends on the pH of the media once they're in the incubators and we'll equilibrate them overnight. We make sure that they're at the proper pH, the right temperature, everything. So then the next morning when the patient comes in for an egg retrieval, we'll take those eggs and we'll put them into this dish that's ready for them and that's at optimal temperature, optimal pH. The actual retrieval procedure is where we'll take the follicular fluid from the physician. We dump it out into a dish and it comes in a tube. So it's in a 14 milliliter conical tube. And there's going to be many of them, typically one per every follicle or two follicles a patient has. So if you have 20 follicles, we may get 15 tubes of fluid and they come about every 30, 45 seconds or so. So we take that tube and we pour it out into a dish and we search through that dish and it's something that takes a whole lot of training. We'll have embryologists sit next to trained embryologists for on average, probably three or 400 cases before we sign them off to perform a retrieval on their own where they're the only one searching for the eggs. Because it can be difficult to find the eggs depending on what's in that tube. It's not only follicular fluid in eggs. There's also other tissue that's in there. There's sometimes bubbles in there. Sometimes the tubes are a little more yellow or a little more red tinged with the amount of blood or media that's in there. So it's definitely a challenge, but we make sure that we're not missing any eggs and it takes, like I said, hundreds of cases before we're confident that embryologists have that proficiency. So we search through, like I said, every 30 to 45 seconds, we have another tube that we're searching through. It's very quick. And part of this is to make sure that the patient's not under anesthesia too long. And part of it is also, we want to get those eggs in the incubator as quickly as possible. Like I said before, anything we could do to minimize stress. So we have a very quick turnaround time from one patient to the next. And in one case, we work as quickly as we can. We find those eggs. We isolate them with a glass pipette. It's a nine-inch Pasteur pipette we use. And we pull those eggs out of the search dish. We put it into a holding dish. And we repeat that process until the physician finished aspirating all the eggs. We then will trim some of the excess supporting cells off called the cumulus corona complex. We trim some of those off with needles. That makes it a little easier to handle and we're also able to isolate away any blood or anything that may impair development. from the egg when we do this trimming, and then we wash them into the dish. At each step, every time we move from one type of dish to another, we also have a second embryologist come over and witness it, or we have a digital witnessing system. So either way, nothing gets moved without some type of secondary verification to make sure that it's moving from one dish into the patient's the appropriate patient's dish. That's something that's fairly standard across most labs. I wish it was completely standardized across every lab, but it's not. But most labs have a similar protocol where there's a witnessing step as well. After that, those eggs, there could be, you know, it depends on the patients. Some patients get one or two eggs. Some patients will get 20 or 30 eggs. And we're prepared for that. We have different dishes, different numbers of dishes based on what we're expecting from the patient the next day, based on the ultrasounds, all those times the patients go in and have an ultrasound and take their bloods drawn. We use all of that data to help prepare in the lab as well. So we're all prepared. Those dishes go in the incubator and they'll sit there for somewhere between one and three hours where we kind of give them a little bit of time to relax and de-stress. And then for the most part, we will strip off, it's called denuding, the cumulus cells from the eggs. So we do this for patients who are going to have egg freezing or ICSI. If there's going to be a conventional enzyme, we don't denude them. We combine the sperm with the cumulus cells still on. But otherwise, when we pull those supportive cells off, it allows us to assess maturity and handle the eggs a little bit easier. So what we're looking for after we strip those cells off is we're looking to assess the stage of maturity of the egg. And I think when patients get their fertilization reports, they may hear you had X many mature, X many fertilize. Maturity is what we're assessing at this point. So your eggs could be in any of three stages of maturity, germinal, vesicle, in meiosis one or in meiosis two. And for anyone who hasn't taken a biology class in a while, meiosis two is the stage, metaphase two of meiosis two is the stage where they're actually ready to be inseminated. So there's physical markers that we could see in the eggs that help identify this. When it extrudes that first polar body, we know that it's ready for vitrification. We know that it's ready to be frozen. So that's what we're looking for at that point. We sort them by maturity, and then they're ready for the next step. And if they're going to be frozen, they'll be frozen by an hour later. And we vitrify them, which means we take one or two eggs, we put it on this. Patients are typically fascinated when I've shown them what we freeze them on. It's this very, very flimsy, tiny piece of microscopic plastic. And we put the eggs on them. And after we equilibrate them in media, of course, it's a more complicated process than that. But we equilibrate them through media. We put them in very minute volumes of media on these flimsy pieces of plastic and we plunge it directly into liquid nitrogen. And the reason the device is kind of so funny, this little very flimsy piece of plastic is because it's all about the thermal rate of freezing. So we want to get those eggs from room temperature to -196 Celsius as quickly as possible. And the bigger the device, the slower the rate of thermal change. There's going to be more thermal resistance. So we use these devices and they're, of course, purpose-built for it. You know, we buy them from commercial companies, but it's kind of funny to see. And now we've vitrified tens of thousands, probably hundreds of thousands of eggs and embryos on these devices. And we love them, but they're funny devices. And then they'll sit, after we plunge them in liquid nitrogen, they sit in storage doers until a patient's ready to use them. When they're going to be ICS’D, I guess I can branch and talk off about that side of things too. When they're ready to be ICS’D, that usually happens an hour or two after we denude them. And that's when we take the processed sperm sample, and I kind of skipped over sperm processing a little bit, but we isolate the motile faction of sperm from the immodal and we wash out the semen. So we have this nice, you know, 98 to 100% motility of sperm in media. And we'll take some of that, we'll put in a dish, we'll put some eggs in a dish. We pick up individual sperm with this very small needle. It's about maybe like a three to five micron opening, very, very small. And we pick up the sperm. We will then move over into a different drop of media that has the eggs in it. We'll hold an egg on a 30 micron needle and we'll stab the egg with the needle that has the sperm in it and we push the sperm into the egg, into the ooplasm. So we have to get through two barriers with this needle. The egg has a shell around it called the zona pellucida, and then the actual membrane of the egg itself is called the oolema, and we break through the zona pellucida with the needle, and then we continue to break through until we get past that oolema into the ooplasm, and then we can deposit the sperm directly into kind of a little bit left of center of the egg. And the egg membrane will reconstitute within a minute or two. And it has a phospholipid bilayer, for anyone who remembers that from basic bio class, and it'll reorganize itself. And it holds the sperm in there. And we'll check the next day, somewhere between 15 and 18 hours later, and we'll look for signs of fertilization. It's possible that when you put the needle in, the egg breaks or it doesn't necessarily fertilize properly. There's some things that could go wrong. So on average, we're looking for about an 80% fertilization rate from this process. We're 80% fertilized normally, but there are 20% that either for some reason or another, the egg didn't activate or the sperm didn't activate properly, or the egg maybe didn't handle the needle introduction very well in that process, membrane didn't reform and the egg degenerates at that point. So those are kind of the possible problems with ICSI. But in general, we have about an 80% fertilization rate with ICSI, which is good. So then the next day, that's our fertilization check. And what we're looking for is we're looking for genetic material from the egg and from the sperm that form pronuclei. So one kind of this round mass looks like nuclei - a round mass from the sperm and one from the egg. And we're looking for two of those. And sometimes a patient may get a report that says you had some abnormally fertilized eggs. And that's when there are two, that's when there's maybe one or three. And there are so many different reasons why that could happen. I don't think I could really explain all of them. One, if we see one, it's possible that the zygote's a little fast and the two actually already went through syngamy and started forming a complete set of genetic material as opposed to half a set from the sperm half a set from the egg they already combined into one set if we see three it's possible that maybe one of the nuclei fragmented a little bit and some of these still could be normal or it's possible that the egg may have failed to release its other half of genetic material so you know an egg should have half of your genetic material sperm should have half of your genetic material and I'm trying not to overly complicate it, but basically they go through these processes where the sperm goes from kind of one cell into four. So it divides and then it divides again, and that's how it gets its half set. And the egg kicks out half sets of genetic material twice after it does a replication cycle internally. So it's possible that it doesn't kick out that other kind of half set of genetic material. And you could have an abnormally fertilized zygote that has three pronuclei. One of the, I think, get on a little bit of a tangent here, but one of the cool studies we've been doing is looking at these abnormally fertilized zygotes and seeing when and how often they actually develop into usable blasts and normal euploid embryos. And we've actually been able to, I'll call it rescue, a number of zygotes that I think a number of labs, probably most labs out there, would discard. Were keeping them doing genetic analysis on it and seeing that some of these actually are euploid and just because morphologically we saw something that doesn't look right doesn't necessarily mean that it's an unusable zygote or won't develop into a normal blastocyst.
Dara: Wow. I was going to ask that. I'm like, can they still be potentially viable down the road? And wow, the answer is yes.
Rick: And we have, yeah, babies born from these and normal from everything that we can see.
Dara: Wild.
Rena: I think you kind of touched upon this, but for my patients that have, you know, they're super psyched. Oh, I had a great egg retrieval. I had 10 sent out. Then they get devastated because none come back. What might be some of the reasons for that? And then I guess, is there a message of hope you can give someone if that happens? If you try again, that maybe you'll... Sometimes they say, oh, it's just a bad batch, right?
Rick: I think for the most part, especially with advanced maternal age, it's a numbers game. And when you get kind of past a certain age, the majority of your eggs are going to be abnormal. And that's just basic biology and there's really nothing we can do about that. So the more you have, the more likely of a chance you'll have to have at least one euploid embryo. Cycling again, there's kind of like, I think some patients get this thought where, well, if everything was abnormal this time, you know, I don't have any chance. And that's not really the case. Every egg has potential, but the older a patient, the older a female patient is, the less likely that each egg will be normal. So up to, you know, When a patient's over 40 some odd years old, 80, 90% of them are going to be abnormal. So, you know, if you have a cohort of 10 that were sent out and all were abnormal, that's just unfortunately really bad luck. We would expect out of 10, at least one of them to be normal from just about any patient age range. But I think if you cycle again, there's a very good chance that we're going to get a usable embryo out of the next batch if it's a similar cycle. There is also just attrition. So even though there's 80% fertilization rate, only about 50% of those make it to a usable, so a blastocyst, a day five, six, or seven embryo that's appropriately developed for us to biopsy, to actually test genetically. And I say only 50% because I think some patients think everything I have is its potential, 50% is actually a very good number. When you look industry wide, I think most labs are happy with 30%. We're happy with 50% or above. So that's kind of our threshold. But there is definitely that attrition. Not every embryo will continue developing. And even the ones that do won't develop to a proper stage for us to biopsy. And that means they have enough cells. They've developed a separate inner cell mass, which forms a fetus from a trifectaderm, which forms a placenta. We need to see a certain stage of development in order to actually biopsy it.
Dara: But you've seen a big evolution over the years. I know even myself, when I started 15 years ago, day three was much more common and it's unbelievable to see how we have been able to push it, which, as you said, allows for a lot more testing to be done.
Rick: Yeah, I think that there's a few reasons. big advantages with culturing to blastocyst stage, which is day five, six, or seven. One of them is any of that attrition that we would have had from day three to blast stage, we see in vitro and you don't need to see due to a negative pregnancy test. So we'll know that ahead of time. We'll only transfer the embryos that really have the highest potential. On day three, we used to actually biopsy them and we would, sometimes, we would take one cell out of a six to eight cell embryo. You're taking a very large proportion of that embryo's mass. And we're also only getting the genetic information from one cell. As much as we think and we've heard, you know, in biology classes, every cell in your body is identical DNA…that's not the case with embryos. Embryos can have cells that have errors in mitosis and lead to something called mosaicism. And one cell doesn't necessarily match the rest of the cells. When we do a trifectaderm biopsy, so we biopsy on day five, six, or seven, we pull about five different cells and we can look and see, are all of these cells normal? Are they all abnormal? Or do we have some normal and some abnormal? And then we have different protocols for each of that. So if they're all normal, that means we have a euploid embryo. We have a very good reason to believe that entire embryo is completely euploid, which means it has the right number of chromosomes. If they're all abnormal, we're very likely, 98, 99% likely to believe that the entire embryo is abnormal. When we have that mix of cells, that's when it gets into a bit of a gray zone and the patient's almost certainly going to see a genetic counselor to talk about potentially using that embryo because it does have potential, but it's reduced implantation potential. So you definitely need to talk to a genetic counselor if you have a mosaic embryo, which means some normal, some abnormal cells, and you want to use that for transfer.
Dara: You explained it so well, Rick, because I mean, I've heard in passing, but to actually hear all the stages, the process, I'm amazed at how controlled every step along the way is which is great. I mean, it's great for our patients. It's great for our clinic. And I realized there was a lot of controls, but I didn't realize how many.
Rick: Oh everything.
Rena: Can you tell our patients of the lab closures twice a year that really, you know, put people into a tizzy sometimes what, what happens in these lab closures? What are they doing?
Rick: So we have two maintenance periods per year, and there's a lot that we get done during the maintenance periods. And I'd need my 10-page list of chores if I were to list everything we do. The big ones are everything gets deep cleaned. So we mop. Of course, we mop and vacuum the lab on a regular basis every day. But we mop the ceilings and the walls twice a year. I mean, we really get in depth. Every surface gets touched and cleaned and we deep clean all of our equipment. So everything gets shut down and fully sterilized. That's also the time where, because the lab's non-operation, we can have technicians come in from the various companies, the different vendors, and they do all their maintenance on the equipment. So we work on a lot of different types of microscopes and they come in and they do a deep cleaning of the objectives and of the contrast and of the different parts of the microscope. They calibrate everything. We have hood technicians come in. We work in laminar flow hoods which make sure that there's sterilized air going over the dishes when we're working on them. And they come in and they test it and test the efficacy and they test the airflow in the hoods. They make sure that the HEPA filters are still putting out cleaned air. We change all the pre-filters. It's also a time where we can do projects in the lab. So say we need a new piece of equipment. We can't just drop a new piece of equipment in when we're in operation because a new piece of equipment has a whole lot of things that we need to both do to validate, we need to clean it. I think a lot of people don't realize how much of an enemy VOCs are, volatile organic compounds, to the laboratory. So we'll ask patients, please don't wear perfumes. Anytime we get a new piece of equipment, you know that new car smell, new equipment has that too and we need to get that out of a new piece of equipment before it could ever come into the lab. So say we need to do something as simple as like patch a hole and repaint, we can't do that during series when it's going to off gas and give those smells because that will actually get into the dishes, get into the media and inhibit embryo growth. So we need those times where we could actually do kind of any project from fixing the flooring to put a new piece of equipment in to run a new line, to something. So we really do a lot of cleaning, a lot of calibration, a lot of validation. All of our instruments that we use to verify temperatures and gases and everything, those all get sent out to the manufacturers and they get recertified either once or twice a year to make sure that our standard is actually appropriate. We test every thermometer we test, basically, you name it, we test it, clean it, or calibrate it.
Dara: Wow. So there's a good reason for twice a year, because people do ask often and they don't fully understand. I didn't even understand before. I thought it was like a great time for everyone to take vacation to clear their mind. But there's so much more to it.
Rick: There are a lot of projects to do. Absolutely.
Dara: Speaking of that - research, I know, Rick, you're very involved with research here at RMA, very involved at ASRM. Are there any a), recent research that you've done that you would like that you're interested in sharing and or b), new research that you really are interested in looking into?
Rick: Sure. So one of the things that I think I was just talking about was the abnormal FERT. And that's something that we actually haven't written up yet. So I'm hoping to write that up and either present that or publish it fairly soon. But we have a probably one of the best data sets out there of any of the labs in the world on these abnormal FERTs. And I'm really excited to share that with the industry because one of the great things about embryology is we're such a close-knit community, even though we're competing labs, a lot of the embryologists are friends with each other and we learn from each other. So when we go to these conferences and present our work or publish it in journals, we'll see that and we'll, we'll trial what other labs have done. And we love to share and try and just try to make the whole field better. That's kind of our goal, not just make our lab better, but improve the whole field. So the abnormal fertilization, I think is a big one that I'm excited about and really being able to make sure that we capture as many eggs as possible for a patient to really give them the best chance of having euploid embryos and the best chance of having a baby. So, you know, we don't want to accidentally, not accidentally. We don't want to discard anything that we think could have potential. So we're very careful in how we approach that. And I think looking at it genetically as opposed to morphologically, just under the scope, it's kind of the next evolution and how we're going to be doing these FERT checks. And that's what we've been doing for a while now here. Another one that we recently published, I think just this month we published how many oocytes are needed to thaw to have at least three euploid blasts for patients under 38. Some patients will come in and they'll say, do I need to thaw my entire cohort of eggs? You know, maybe I froze 40 of them. And for one reason or another, you just don't want to thaw everything now. Maybe you're using donor sperm and you think that down the line you might want to use a different donor sperm or have a different partner or whatever the reason. And we just published that thawing 12 to 16 oocytes oocytes, if you're under 38 years old, gives you a great chance of having three euploid blasts, which is enough for the majority of patients to have a baby. So that's something that it's just a statistical analysis, but it really helps clinical decision making. We looked recently at late M2s. So when I was telling you earlier about the different maturities, the germinal vesicle M1 or M2, what we can do is we can let the eggs sit in culture for a little bit. So even if they're immature, we could let them sit in culture for four hours or 24 hours even, and see if they mature in culture. And if they do, what's the potential of those eggs? Are they as good as eggs that came out of the body mature? The answer, we do have an answer on that and we're in the process of publishing that now. And the answer is no, they're not as good, but they still do have potential. So for our egg freezing patients, especially the ones that have low yield or the ones who may not have another opportunity to come cycle again, the patients who are undergoing certain treatments may not be able to cycle a second time, we'll culture everything to the next day and try to freeze those as well if they mature. And the answer is, yes, they have lower potential, but we still have seen blast development in normal embryos and babies from those late maturing eggs. So that's, I think, another neat one.
Dara: Those are great. Yeah. Interesting.
Rick: We're looking at different methods of freezing and warming embryos specifically. And this has been kind of a big mix up in the, a big shake up in the industry over the past year where a lot of the labs are going to these faster equilibration methods of freezing embryos. And basically the way a lot of systems work is they'll go through when you warm embryos, you warm them through different dilutions of media. So it's actually sugar, it's sucrose, just kind of like any sugar plus some other compounds in there. But the sugar in the media controls the rate of water diffusion when you're thawing embryos. And for the longest time for decades now, we've thought that the water diffusion had to be very, very slow. So it was a slow process. And when I say slow, I mean seven minutes. So not terribly slow, but the slow process of slowly diluting out the amount of sucrose so you could control this water diffusion. And there have been a number of pioneers in the field who have tried on these research embryos and said, hey, it looks like we actually have better development, better survival if we do this whole thing faster with fewer dilution steps. And there's a lot of compelling science behind it, which is, you know, it's less exposure time to basically just think of it as out of the incubator. You know, it's more stressed exposure time. So if we could minimize that without harming the embryo due to this water diffusion rate, let's do it. So there's been a whole lot published on and people who have labs who have trialed this on thousands and thousands of embryos and seen great results. rate. So we did our own internal trial on research material as well. We saw the exact same thing and we shifted to that method of the quicker thaw method. We also did the same thing with freezing. We looked at freezing in two different ways, whether we basically just drop the embryo on the device or whether we put a little puddle of media on this freezing, this little plastic flimsy device, and then aspirate the media off. And we saw that just kind of dropping the embryo on device performed better. And this is, you know, so there's all these little trials and these things that most people wouldn't even really think about. They were always trying to optimize.
Dara: What about even like, this is where I'm going. I'm like, even the environment that you guys create. So it sounds, you know, there's, there's so many controls along the way. Do you listen to specific type of music when you're in the lab? And does, I'm curious, like happy music does that work? I think it's a silly thing to think about, but I would think, you know, a happy environment really can allow for, I don't know.
Rick: I think we almost always do have music on in the lab. So we turn it down during transfer time. So patients probably don't get the opportunity to hear our music, but we have music on and we have Sonos systems in Brooklyn. We have a big speaker system built into the lab in Manhattan. And, I think it's the first person to sit down chooses the playlist. You know, we have a whole bunch of playlists, just online streaming radio, and we play it. I think you kind of hit on an important point, which is a good environment and it's probably a little less for the embryos and a little more for the embryologists. But it's just like any workplace, as much as we're scientists, as much as we're rigorous, we still have feelings and thoughts and good days and bad days. And anything we can do to maximize those good days, I think, is going to ultimately positively impact the outcome. And that's another big part of my job and the whole supervisor team we have here is to try to make sure everyone in the lab is as happy as possible. We work essentially shoulder to shoulder with 20 of us in a windowless room. and just staring into scopes all day, it's important that we do things to minimize our own stress and to make sure that we could provide the optimal care to the patients, to the eggs, to the sperm, to the embryos. And yeah, music is definitely a part of it, but also just having really good coworkers, everyone who has the same goal, the same mission to optimize and to kind of make each other's lives better really helps out.
Dara: Yeah, I think about Rena. I'm like, what Rena does to help support patients, but I do think that the notion of the staff, if there's so many, again, like in terms of quality control, it's so important and, you know, making sure that they're focused, not thinking about what's going on outside in their life. So even like clearing before work day, I would think would be so important for your role so you can provide the best care.
Rick: We've had Dr. Witkin provide us with de-stressing techniques. We've done that multiple times where, you know, we made a group with her and she shows us teamwork techniques. She shows us de-stressing techniques and basically, you know, she has this great method of it takes 10 seconds how to, you know, if you're feeling stressed, basically how to sit there quietly, de-stress and then let you refocus on what you're doing with full attention. And I love that.
Rena: So I guess anything else about the lab, any future changes or implications, anything you see the lab undergoing in the next year?
RIck: I don't know about in the next year. I mean, we didn't talk about biopsy much at all. We kind of touched on the subject, but that's after a FERT check, that's the next major stage when it gets to day five, six, or seven, we look at development and we biopsy it. And that's something that over the last decade has been a really big improvement, I think, in what we used to do in like the early 2000s or early 2010s. We didn't biopsy as much. And we're biopsying now more, which trapectoderm biopsy is where we're taking off those five cells or so from the part that forms the placenta, the triphectoderm. We send it off for genetic analysis, and we're getting back the chromosomal results, whether it's euploid or aneuploid, the right number of chromosomes or wrong number of chromosomes. That process on the reference lab's end, so when we send those off, it's kind of a black box to most of us, but that undergoes genetic analysis in different methods. And over the years that's evolved. So they used to run fluorescent in situ hybridization where they could look at six chromosomes or 10 chromosomes. Then they did CGH where they could look at all of the chromosomes, but it's just kind of not a very deep look at it. And now they do next generation sequencing, NGS, where they can get a really deep, like millions and millions of different reads across different points in the chromosomes. And now what we're doing on top of that is we're running single nucleotide polymorphism, so SNPs, on top of NGS, which lets us do that genetic FERT check that I was kind of talking about, where we can look and not not only make sure it has the right number of chromosomes, but also check that you have kind of one set from the egg, one set from the sperm appropriately. And there's evolutions, I think, on the horizon, on the genetic side, when it comes to looking at whole genome sequencing, that could be something that we see in the kind of near future where we're amplifying and looking at the entire genome and not just a few million points across it. I think that we are also really still working on optimizing everything we do. I mean, our embryo thaw survival rate is 99 plus percent. Let's get it to 100. Our egg thaw survival rate is about 90% or so. Let's get that up. So anything we do, and we're looking at these kind of minuscule changes of how long does it sit in this type of meteor? How do we load a device? Or what do we touch it with? What size device do we use? I mean, We have all these different tools in the lab and all these different types of devices and size devices, and we just try all different ones to optimize it. And I think that's really kind of the next step. And there's a lot of talk in the field also about automation and about Basically, not necessarily eliminating the role of the embryologist, but automating a lot of what we do. And I think that that's something that I'll probably see in my lifetime. I don't think that's in the next year. There is this automated system that in Mexico, it's in operation. It's under trial right now. I think that's going to be great to help more patients. I don't think that's really going to replace embryologists in at least my career. I've got hopefully another 20 some odd years left here, but I think that it's hopefully going to provide more access to care. We'll be able to treat more patients and have a higher throughput in the same lab, as opposed to what we can do now. Right now we're very, you know, we're limited on what we can do with the number of embryologists we have. So if we can double that in the same footprint, in the same space, and treat more patients, I think that would be great.
Dara: There's lots on the horizon.
Rena: Yeah. Well, this was super informative and really inspiring. I think it's going to be great for our listeners to really get such an inside look into the mysterious lab.
Dara: Less mysterious now!
Rick: I think we're always happy to talk about what we do. They just don't let us out of the lab all that much.
Dara: So Rick, how we end our podcast is with words of gratitude. So Rick, what are you grateful for today?
Rick: Geez, I'm grateful for so much. I think I'm grateful at the moment, the thing I'm most grateful for is my team. We have a fully staffed lab of embryologists who all come in and work on a shared goal. And we're all trying to do the same thing. We're all rowing the boat in the same direction. And we're all there to support each other. And across various jobs I've had, across various teams I've worked with, that's not always been the case. And to have that now, and especially to be somebody who's helping oversee this team is really gratifying, really satisfying, something I'm very thankful for.
Rena: Beautiful. What about you, Dara?
Dara: I'm grateful for chatting with you, Rick, today. I love meeting people, not only learning. I think a big part of my gratitude is being part of this podcast and learning, learning something new each time, but also seeing people in fields that they're meant to be in. I see the passion that you have for what you do, and it only helps inspire me to continue following my passions in my field and beyond. So thanks for that, Rick. What about you, Rena?
Rena: I would say the same, in similar vein, people that are really following their passions and doing what they love, not just because it's a job, but it's a career. And I think our field, our industry, we're really working with people, family-building, helping people create children. It's a huge responsibility and honor. And to be able to work with people that really genuinely care. You know, you're not just punching in and out and really helping people at such a pivotal point of life is such a gift.
Dara: Beautifully said. Well, Rick, we would love to have you on again down the road when there's more research and more evolution and changes in the field, but we are so appreciative of you being on today. Thanks so much.
Rick: All right. Well, thank you.
Rena: Thanks 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.