
Transcript
This episode of the SART Fertility Experts podcast provides an in-depth discussion of the technologies used in in vitro fertilization (IVF) and advancements that enhance success rates and accessibility. Dr. Brooke Rossi and Dr. Lowell Ku cover topics such as the critical role of embryology labs, the specialized training of embryologists, the use of artificial intelligence for embryo selection, and the importance of technologies like vitrification and microfluidics in sperm selection. They also discuss the ethical and technical challenges these innovations present, emphasizing the balance between technology and humanity in patient care. Finally, they stress that these tools should complement, not replace, the expertise and compassion of medical professionals, always prioritizing the doctor-patient relationship.
Hello and welcome to the SART Fertility Experts podcast. My name is Dr. Brooke Rossi and I am a practicing reproductive endocrinology and infertility specialist in Columbus, Ohio. Today's episode will focus on technology and assisted reproductive technologies and IVF.
We have the pleasure of discussing this topic with Dr. Lowell Ku, a practicing REI in the Dallas, Texas area. He has had several roles in the American Society for Reproductive Medicine and the Society of Reproductive Endocrinology and Infertility. Dr. Ku has a special interest in technology and is the president of the ASRM Technology Committee.
Dr. Ku, thank you so much for joining the podcast today. Thank you, Brooke. Thank you so much for having me on the podcast.
It is an absolute pleasure and a privilege and an honor. I'm excited to be here and to talk to you today about all things technology and our field. Perfect.
So maybe it goes without saying that there's a lot of technology in the field of IVF. But one of the things I just wanted to bring up first, since this is a podcast geared towards patients, sometimes patients don't have a good sense of who's actually in the IVF lab. So, you know, we have an IVF lab director, we have embryologists.
Maybe you could tell us a little bit about those careers and the training that goes into being someone who works in the either in the andrology or the sperm lab or in the IVF lab. Absolutely. You know, it takes a village to really help a couple grow a family.
And the embryology lab is an absolute critical part of that. In the lab, at our lab, we have embryologists, as you were saying, and our HCLD lab director. And typically, in any day, we have three or four embryologists in our lab that are doing all their chores, which is the tasks.
Number one is quality control. Number two is checking on the day's embryos to make sure that they are progressing and noting it down for our charts and the progress for the patients. You know, the training isn't quite established really for embryology.
They do have courses that you can take. But typically, what we do is we start with our andrologists and our andrologists are in our sperm lab. And so they are spinning the sperm down for IUI and for semen analyses.
And then they can advance to the embryology lab where our senior embryologists will help guide them and teach them and basically educate them on how to be an embryologist. Yeah. And that may, I mean, that training from the time that someone starts as an andrologist to an embryologist to doing, you know, from the very beginning to doing the techniques with IVF.
I mean, that could take years. It takes a long time and it takes a lot of skill. And some people may not have that.
So it does, we have to find the right person. And so, but it does take a long time. Because in rightfully so, because we're working with very precious tissue and it's very important to be exact as possible.
Right. And the lab directors are often, they're doctors because they have PhDs, but they're not, you know, MDs like the clinicians. But they specialize in running the lab under, like you said, quality control and they have special certifications to make sure that the lab runs properly.
You know, and for the embryologist that is an HCLD, they do take a test and they have to pass a licensing exam and some sort of testing that certifies that they are now a high complexity lab director. And it's very vital that each lab has one of those. Correct.
Well, but one of the things I thought we could do today, since there is so, so much technology in IVF was to almost kind of go through step by step to remind patients, you know, how technology affects each step of the IVF process. And then we're going to speak more, you know, kind of more broadly about some emerging technologies and kind of even the good and bad things about the technologies that may be on the horizon. So even at the very beginning of IVF, we have patients taking medications and doing ultrasounds and doing blood work.
And, you know, the medications are somewhat old, but do you want to talk a little bit about the science of the medications that we use? Absolutely. You know, it is amazing though the science is, like you said, quite in the past, but it's still absolutely amazing how they came up with this process. So for example, there's a medication called Menopur.
And my patients like to call it the holy shot because originally they had menopausal nuns who, they distilled the urine from menopausal nuns and were able to extract out and purify the menotropins and that's Menopur. So the technology to do that is still amazing. And to purify, now they have highly purified menotropins.
So it's a very, very cool technology. Yeah. And so the medicines in general are used to, you know, to help the ovaries make several eggs at once, because without these medications, the ovaries only want to make one egg.
So all of the medications that patients are taking are kind of pulling and pushing the ovaries. Like we want them to take medicines to grow several eggs, but not ovulate before. And then, so then the trigger shots, tell us about the trigger shot.
Yeah. So the trigger shot is a medication that sort of tells the brain, hey, it's time to release the eggs or to loosen them up and have them ready for ovulation. So it's not exactly the exact hormone that the body uses, but it's something very similar.
So it's called ACG. And that tells the body, it's time to finish the maturation of the egg and get it ready for ovulation. And we go in after the egg before it comes out.
So a very interesting technology, very cool that, you know, I think it was originally ported over from the bovine and equine industry, and now it's being used in humans. And we've been using it for decades. It's a great, great technology.
Yeah. And so then, you know, the patients will take these medications and have bloodwork and ultrasound. Obviously the ultrasound technology has improved where we can look at the ovaries very well.
I've seen, you know, some different ideas to try to expand access to IVF where patients may even be doing home ultrasounds or salivary estradiol levels. They may all be things that we will use in the future to help patients make the IVF process more convenient and easier for them. Right, right.
You know, for those who don't quite know, like how does the sonogram work? The technology is really cool. So it's using sound waves really to bounce off of the tissue and they'll reverberate back. And the computer can analyze based on what the sound waves are when they come back and can tell you like, okay, is this going to be dense like a bone or this is empty like air? And so the sonograms, they've really increased in their ability to really refine and have a high definition look on the pelvis, especially the ovaries and the follicles.
It's really cool. I was just actually in the expo hall and now they have technology where you can press a button and it'll measure the follicle for you immediately. Yeah.
Totally cool. And of course there's like 3D imaging. So the technology is absolutely amazing.
It's really evolving nicely. That's great. So the patient will then go ahead and she has her egg retrieval and this is when the magic really happens, right? Because now we're in the IVF lab.
And you know, one of the most basic instruments we have on the lab that obviously is critically important is just a microscope because none of the things, I mean, we really need microscopes to do any kind of work with eggs and sperm. So why don't you talk a little bit about, you know, when we're doing the egg retrieval, how are the microscopes used to help us look at the eggs? And then are there any other new technologies that may be used to help assess egg quality or location of eggs, that sort of thing? Absolutely. The microscope is absolutely single-handedly the one tool that we absolutely cannot live without in the lab.
I'll give you an example. This is a great microscope where we can do our biopsies on and inject sperm in. And so basically it's on a table and it's an anti-vibration table.
And so they'll turn on a little canister of gas. And what it does is it causes the table to float on a bed of air. So it's nice and stable in case a car rolls by because you're dealing with such microscopic things.
And then you have these micro manipulators that can help basically make your movements very small and you can inject sperm in and make biopsies. Amazing technology. Really cool.
And speaking of being able to look at the embryo and eggs and decide, well, which ones are the best ones? For many, many years and still to this day, it's always been in the eye of the embryologist. And so the more advanced and experienced the embryologist, perhaps the better they were able to choose which embryo would turn into the kiddo. And so now they have AI.
So artificial intelligence is really coming along. And I think there is a place for it in our field, including the laboratory, where they have now trained AI to be able to identify which embryo has the highest chance of implanting and turning into a pregnancy and a baby. So absolutely fantastic and fascinating technologies coming on the forefront of the field.
I'm just going to elaborate a little bit on that. So one of the things that you're discussing is, you know, when we're trying to select the quote, best embryo, basically what we're trying to do is to pick the best, the embryo we think has the highest chance of implantation. And as you were saying, basically that's done by an embryologist looking and deciding what the cells look like with the embryo.
So now there's artificial intelligence or machine learning that has been built to sort of be able to, you can just put the embryo underneath a microscope and it assesses that. And then it somehow, and if you were to put whatever, six embryos underneath a microscope, it would be able to then assess the one that may have the best potential for implantation. Exactly right.
You know, the strength of AI is that as long as it's been trained properly by experienced embryologists, it will have the knowledge of the experienced embryologist so that it can make better decisions. That's the only thing about AI that hasn't come to maturation, which is really training AI to where it is a world-class embryologist. And it can, like I said, look at 20 embryos in a millisecond and tell you which one has the highest chance of implanting.
Even with collection of the eggs and, you know, when the eggs come out of the body, they have, you know, cells around them and the embryologist has to find the group of cells and take them off the egg and then put, you know, do all these different things with the egg. And I've seen technology where, and again, this may increase access for different patients to, you know, where they may be able to put the fluid into a device where it very gently kind of like moves the eggs along. It can even take the cells off of the eggs, the cumulonimbus cells off of the egg.
And, yeah, and it, you know, embryologists are very highly trained scientists and there's not that many of them and they do a lot of hard work. And as the volume of IVF goes up around the country, there may be little parts of this that can be more automated so that they can do, you know, almost like higher level things like select embryos and that sort of thing. Speaking of selecting embryos, one of the other aspects of AI is that there's something called an embryoscope, which is a little telescope that can look into the chamber where the embryo is culturing.
It's like a time, so it's like time-lapse photography or microscopy. Of the growth and culturing of the embryo. And you can see the embryo literally divide into two cells, four cells, etc.
And they call it morphokinetics where they can actually tell you, okay, this embryo is dividing properly and has a higher chance of implanting, whereas this one is dividing, yes, but it's dividing not at the proper rate or dividing asymmetrically. And these things can determine whether that embryo is chosen for transfer. Yeah.
And so I think that, you know, one of the things that AI can be used for would be embryo selection. I've even seen, you know, even before that in terms of creating protocol, medication protocols for patients, you know, if there was a way that we could insert different parameters about the patient, you know, their age, their anti-malarian hormone level, if they've done a cycle, if they have a child, and, you know, you may be able to have assistance with artificial intelligence to help you create a protocol for that patient. Yeah.
Imagine, imagine harnessing the knowledge of hundreds of, of, and even thousands of REs in training an AI system to be able to understand, okay, this type of patient with this type of presentation, these types of lab results, this is the protocol that's best for them that works best. That would be amazing. Yeah.
It's really interesting to think about. You know, one of the things I think that I don't know if patients know about, you can imagine it's very hard to grow a human embryo in the laboratory. And I don't know if they understand anything about the incubators that we have and how closely monitored they are.
Do you want to talk a little bit about the incubators in the lab? You know, the incubators really come a long way, but basically the incubators have to mimic the interior of the fallopian tube and the pelvis. And so there's certain percentages of gases that need to be mixed together to mimic the amount of gases that are in the fallopian tube. And so it's a mixture of the carbon dioxide and O2 and nitrogen.
And so it's very complex. And so, and, and these, these basically these incubators, they look like little tiny refrigerators. And so there's constant quality control to make sure that the gas combination and the percentages are all exactly the same.
And so if there, if there's any sort of aberration, it alarms the embryologist and they can come and fix it. But what's happening now, which is amazing, is that the, the, one of the Achilles heels of these larger incubators is that every time you open up the door, the environmental air would go in and it would take a longer time to recalibrate those gases. And we worry that that could expose the embryo unnecessarily to volatile organic compounds and things that could perhaps harm the growth of the embryo.
So now they're shrinking these incubators down and they're really small, whereas they're just one little compartment where you can put in one little tray with all of the embryos of this one patient and it equilibrates way faster. It's really neat. And we tend to just leave them alone.
Right. Exactly right. Right.
I mean, I think, you know, back whatever, 10 years ago, there was a lot more monitoring of the embryos. Even patients still want to know how their embryos are doing. And we have to tell them, we just put them in there and we let them grow because a lot of times we're not looking at them until day five after they've had their retrieval.
Yeah. If you don't mind, I bet patients would be interested to hear a little bit about embryo and egg freezing, specifically egg freezing, because that's changed over the years. And maybe you could mention a little bit about vitrification and how we're currently freezing eggs and embryos.
Right, right. So in the old days, we didn't have the ability to really freeze an egg fast enough to not allow any sort of crystallization of the water that's inside, because the egg is a single cell and has a lot of water in it. And so we were worried that we couldn't freeze it fast enough.
So now with the advent of something called vitrification, which is essentially means to make it in a glass-like state. And so it's flash freezing the embryo or the... Either. Right.
So I tell patients it's flash freezing it so that there's little to no time to really cause any harm to the DNA and the egg itself. So with the advent of vitrification, egg freezing has really taken off. Now we're able to freeze eggs and really to be able to ensure for the patient that they absolutely can freeze their fertility for a long term.
Yeah. And that's been a big, I mean, that was really what allowed us to start freezing eggs for patients and making it non-experimental anymore. Very cool.
And it's obviously it's helped our success rates with embryos as well. So that's been a big change in the last probably 10 or 20 years. Maybe you could talk a little bit because I know that patients are reading about different types of sperm selection.
So, you know, and this could be for a patient who's doing intracytoplasmic sperm injection or maybe just doing conventional IVF. Maybe you could talk a little bit about that type of sperm selection. There's all sorts of ways right now to really sperm select.
And we're not exactly sure which one is the best. There's all sorts of ongoing studies and we're still trying to figure it out. Traditionally, it's always the eye of the embryologist or andrologist to be able to identify which sperm is the best for, let's say, ICSI and inject the sperm in.
There are new methods out now. And that also goes along with the DNA fragmentation index and how that you can perhaps identify which sperm perhaps have higher DNA fragmentation versus those that don't. I'll give you one example.
It's called SCSA or S-C-S-A. And basically, it's a cell... So it's a test for the sperm. It's a test for the sperm.
Yeah. So basically, it tells us which sperm are good and which ones have the abnormal DNA. And there's all sorts of things like the microfluidic sperm sort where you let sperm swim down this channel and the ones that swim into a different channel are the ones that are good.
And so these technologies are absolutely really cool and they're definitely now here and available. We're just not sure which one is the very best one yet, but stay tuned because a lot more studies are coming out and one day we'll know which one's the best. Right.
And we're just trying to make sure that anytime there's... I mean, this is actually in general about technologies. We always want to be really thoughtful before we introduce a new technology that we have enough data to make sure that it is not only effective but not harmful and that it can also be cost-effective and that it's time-effective for everybody. And this is a big challenge in our field, mostly because we all are so thoughtful at trying to get people pregnant as fast as possible, but we really need to be patient and make sure that we have proper studies and good data to make these decisions for our patients.
Absolutely. Data-driven care is so important. And I get it.
There comes a point in time in a patient's care where something may not work. And now I get it. I mean, when my wife and I, we were struggling to conceive.
We were literally desperate for anything that could work. And patients will come to me and ask, well, what about this technology that I read on the internet? Correct. Yeah.
And it's always a technology that's great and it looks fantastic, but it just hasn't been proven yet. And so I don't know whether it's worth the money. I don't know if it's going to actually improve the outcome.
And I don't know if it's going to cause any harm. So unfortunately, sometimes I have to tell the patient, unfortunately, these are unknown technologies. We don't recommend them at this point in time until we know more about it.
Right. I think that's the safest thing. I wanted to talk a little bit more about a very common technology in our field that a lot of patients may be doing, and that's pre-implantation genetic testing.
Pre-implantation genetic testing is a procedure where we biopsy the embryo in its blastocyst stage, and we can then test those biopsy cells for several different genetic conditions. Sometimes we're doing PGT-A to look at aneuploidy to see if the embryo has the correct number of chromosomes. Sometimes we're looking for one specific disease that the patient or partner may carry.
And then sometimes we're treating patients who have a balanced translocation. Maybe you can talk a little bit about the technology behind PGT and the data and whatever we know about that. Absolutely.
Fantastic technology. Thank goodness we have this available. It really has really improved pregnancy rates in certain populations of our patients.
So basically, when you biopsy the embryo, we're removing about 6, 7, even up to 8, 9, 10 cells from the trophectoderm, which is the portion that turns into the placenta. And so we're biopsying these cells off, and we're going to send them off for analysis. We'll freeze the embryo and keep them safe in the office or in the laboratory.
And then the cells need to be evaluated. And so ideally, they run all cells. They test each cell that we send, and they should all say normal, normal, normal, normal, normal, or abnormal, abnormal, abnormal, abnormal.
And by normal, you mean right number of chromosomes or doesn't carry the disease. Exactly right. Exactly right.
Can be used. Yeah. Yeah.
And so what happens when perhaps 6 out of the 10 or 8 of the 10, that's where we get a little bit confused. We're not sure what to do. Is this embryo considered normal genetics or is it abnormal? That's one thing.
It's called mosaicism. So we're not sure what that means. But I tell patients, even if an embryo comes back as completely quote unquote normal with all the chromosomes and all the DNA it needs, unfortunately, it doesn't necessarily mean it's perfectly normal.
And the reason why is because the technology is good, but it basically is a high-resolution look at the DNA, but it's not checking every base pair. And there are technologies where it's checking every 20th base pair or every 10th base pair. But if it's every 10th base pair, there are 9 base pairs in between that are not checked.
So I tell patients, it's like you have... So base pairs, you mean like actually all the chromosomes? The chromosomes. Exactly right. So it's like if you have this book, PGT can tell you, okay, the chapter or all the pages are there, the chapters are there in the right order, and the paragraphs are there, but sometimes it'll not see a spelling error.
And that's the reason why sometimes an embryo that has been considered normal from PGT-A goes in and it doesn't implant or it miscarries. Yeah. Yeah.
That's one of the other things I think patients should be reminded of is often there's, you know, even though they've had embryo testing, they should have prenatal screening done as well. But that's a great technology that has really changed over the years. And it's one of, I think, the greatest parts of our field that we can help patients try to have a higher chance of having babies.
Well, I have a question for you, Dr. Ku. Yes, ma'am. All of these technologies seem great.
But what I'm wondering is if you see any limitations of these new technologies. I was talking with some colleagues before you and I met today, we were talking about patient experience. Like she was actually sharing a story where a patient was frustrated that all of her instructions went through her patient portal as opposed to a phone call.
So I'm wondering if you think that there's any limitations to this new technology and how does that affect the clinician or physician-patient relationship? Great question. I would say two things come to mind. Number one is like you were saying, I think that it perhaps takes away some of the personal touch of modern medicine and the art of medicine, whereas we're not as in tune with our patient because we're not seeing them.
We're just sending messages via the portal. I get that. And that absolutely is one problem that can occur with technologies that we're using it, but now we're removing some of the humanity from our care.
The second thing I see is it's very common. For example, if my computer crashes, I'm absolutely reliant on my computer. I am out of luck.
And so I think that there might come a point in time where we may be so reliant on the technology, but what happens if for some reason there's a glitch and we are absolutely helpless and we're dead in the water? So I worry about that. And I think that the other thing is we want to always be in control of our patient's care to help the patient and guide them. We don't want technology to be in control.
But I think these are tools, right? I was speaking with our embryologist, our lead embryologist today, kind of about this topic as well. And I could see her sort of thinking, you know, it's hard to let some of this stuff go and to think that maybe a computer or some program could do the work that you're currently doing. And I think the idea is that we're using these as tools to help us, but it wouldn't replace the human side of what we're doing.
It wouldn't replace a human brain or years of experience and that sort of thing. I mean, patients still need human embryologists and human providers to take care of them. But one of the things we know about our field is that we need to be helping more patients and we have to figure out a way we can make it more efficient and more effective.
So it may be that some of these technologies will continue to help us with that. I agree. I think that AI, for example, can be a tool to augment our brain power rather than replace our brain power and replace our humanity.
So I think that though these are great, strong and very powerful tools, we do need to make sure and keep them in check that the doctor-patient relationship is always first. Great. Well, Dr. Ku, thank you so much for talking to us with us today.
Again, this is Dr. Lowell Ku and he is talking to us, the SART Fertility Podcast series, about technologies and in vitro fertilization. Thank you so much. It's been a pleasure.
Thank you so much. The information and opinions expressed in this podcast do not necessarily reflect those of ASRM and its affiliates. These are provided as a source of general information and are not a substitute for consultation with a physician.
For more information about the Society for Assisted Reproductive Technology, visit our website at https://www.sart.org
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SART Fertility Experts Podcast
SART Fertility Experts is an educational project of the Society for Assisted Reproductive Technology, this series is designed to provide up to date information about a variety of topics related to fertility testing and treatment such as IVF.
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