You're listening to the fertility docs, uncensored podcast, featuring insight on all things, fertility from some of the top rated doctors around America, whether you're struggling to conceive or just planning for your future family, we're here to guide you every step of the way.
Speaker 2Hello, and welcome to fertility docs. Uncensored. I am Dr. Carrie BDN at the fertility center of Las Vegas, and I am here with Dr. Susan Hudson at Texas fertility center and Dr. Abby Evelyn at Nashville fertility center. And we are joined here by , uh , my partner, Dr. Bruce Shapiro, also from the fertility center of Las Vegas. And so I actually interact with Bruce all the time on zoom, especially now that we're all in, in isolation here and trying to keep everyone as separate as possible. Um, but it's kind of nice to have other people in on the call. Hello everybody. Hey guys. Hey, so how have you been , been keeping busy Bruce, since you've been, I mean, you've been locked up at home for weeks now. I haven't gotten to see your shiny face smiling at us in the office in a while.
Speaker 3Well, you've seen me by zoom, but I'm very busy here. I I'm been doing Skypes and , uh , zooms with patients , uh , with both consultations and new patients. And so I'm, I'm quite busy. There's lots of work to do lots of reading, catching up on journal articles, writing papers that we need to write that we are behind on because we were so busy. So I'm getting a chance to do lots of things. I didn't have the chance to do
Speaker 2Before. Or you getting cabin fever at all?
Speaker 3Uh , just a little bit, but at least I live in a neighborhood where I can still go for walks. So that helps a little bit
Speaker 4Self on the internet, looking at all these places around the world, trying to figure out where I want to go on my next vacation, just because I want to get out of places. What's your favorite vacation spot, Bruce ?
Speaker 3Well , you know, there, there are lots of places that I really like to go. Um, I love to go to national parks, so Yosemite or , um, uh , places like Yellowstone and, and those sorts of places where you can hike a lot. I love to hike. So that's, those are some of my favorite places to go, but I also enjoy going to the beach. So we're not too far from California here. So we go to the California beaches and we've even gone up to the Oregon beaches and , and it's great fun. We love to go hunting for all those things that wash up on the shore. You never know what you're going to see. Sometimes you see some strange animals. Sometimes you can roll over the seaweed and you can see some, all sorts of strange types of shells and sea creatures. It's , it's a great, it's a lot of fun.
Speaker 2I'm , I'm pretty sure I know the answer to this. When was the last time you went in the ocean water?
Speaker 3Well, I, I did go in , uh , just up to my ankles, but I'm not one of those that really enjoys swimming in the ocean, but that's okay.
Speaker 2What's the story behind that? Why
Speaker 3Don't you go on the ocean? Well, it, for me, it's a, it's a little bit disconcerting to know that there are about 10 million viruses per cubic centimeter of water,
Speaker 2But not the virus you're talking about, like a diverse , uh , diaspora of creatures, right ?
Speaker 3Yes. There are all sorts. They're , they're harmless to humans for the most part, but the idea of , uh , of doing that is a little bit disconcerting. And , and I don't know if you've ever looked at under the microscope at sea water . I mean, it's a veritable zoological garden. So I think it's good to have all those creatures in the ocean, but I don't really feel like drinking them when I'm swimming.
Speaker 5It's really a unique perspective because I think most people would be concerned about like, when I was talking to my ophthalmologist about a trip to the beach, he was talking about how he swims when he goes to Maui and the water. And he's worried about sharks. You're worried about viruses. I don't think I've ever heard anybody ever say they were scared to go on the ocean because of the viruses.
Speaker 3Well, it's not the same virus it's affecting us now, but , um , there's still, there's a lot of creatures per CC water. I'll let them on them . I'll let them remain where they are. I don't need to imbibe.
Speaker 2I say that I find myself becoming more and more of a germaphobe as the years go on.
Speaker 5Oh yeah, absolutely. You know, it's interesting. My teenage daughter just tell me the other day she goes, mom, you know, I don't think I'm ever going to be able to go, or at least not for the next few years to a concert again, with all those people and , and all those germs around me, I think it's really changed our society with virus.
Speaker 3It could be, it could be well, we're certainly going to be on the lookout for the next step pandemic once this one's over
Speaker 5This one first,
Speaker 2But that's an encouraging thing to hear. Um, uh, particularly given all the research that's going to come out of this. So one of, one of the reasons why I joined the fertility center of Las Vegas is that , um, Dr. Shapiro is a phenomenal researcher. I mean, we are very privileged to have our own statistician on staff. And the staff is oftentimes fussing at us as physicians because we need to be seeing patients and we're in Forrest or statisticians office talking about, well, what if we did this? And what if we did this? And what if we did this? And really some of the phenomenal research that has shaped our field has, has come out of those interactions, headed by Dr. Shapiro with frozen embryo transfers . So one of the things that, because we have you in a captive audience right now, and, and you're stuck at home, we get the pleasure of talking to you about this is how did that research come to pass? Like, what was it that made, made you say, you know, the standard is to do a fresh embryo transfer, but we really need to look into that and change that standard because we think we can do it better
Speaker 3Actually happened many years ago, back in the late eighties, we were doing IVF and we noticed that we had these extraordinarily high pregnancy rates in our egg population. So we were kept wondering, well, how come we're getting such high pregnancy rates in our donor egg population, when the same age group patients aren't getting pregnant when they use their own eggs and kind of scratched our heads. And I kept thinking about it . And I said, well, the main difference between just having young, healthy eggs and the rest of the population and having autologous, or , or patients that you know are using their own eggs, is that in the patients that are using their own eggs , um, their uterus, since we did all fresh transfers, their uterus was exposed to all the hormones that came with , um, developing those eggs. So there are high estrogen levels, progesterone levels, and progesterone levels would rise asynchronously asynchronously sometimes with the estrogen levels. So I thought, well, gosh, you know, maybe it would be a better idea to put these embryos into a pre-prepared endometrium that's devoid of all the hormone manipulations that occurred during the stimulation cycle when we're trying to get eggs. And so we tried that, but the problem was is that back in the late eighties, early nineties, our frozen techniques were our freezing techniques. Weren't very good. And so the survival rate for our embryos, wasn't sufficient to really be able to demonstrate any advantage to the process.
Speaker 2So to put that in perspective for people listening, who, you know, some are docs , so they know all about this, but when you say freezing embryos, are you talking about putting it in an ice cube tray and popping it in the freezer that we bought from home Depot? Can you tell us a little bit more about what that is so that we know really what it used to be and what it is now
Speaker 3We used to have when we started freezing embryos is we had controlled rate freezers and these were computer driven modules, machines that would freeze the embryo at a, at a controlled rate of decline of temperature. So it would lower the temperature as computer controlled intervals to try to avoid ice crystal formation inside the embryos, which is what actually does the men from the freezing process. And these were good, but they weren't great. And the loss from the freezing process outweighed any possibility of gain from the process of putting it back into a perfect endometrium. So we really couldn't get ahead of the game. So we kind of put that on the shelf and I didn't think about it again for about 22 years. And then 22 years later, I looked at our data. And by that time, our freezing technique had changed. We had different equipment to freeze the embryos, and I looked at our rates and I said, oh my goodness, here, our freezing rates, our rates with thought embryos are higher than our fresh ones. Maybe it's because our freezing rates have now gotten to the point where what we originally thought was going to be the case can now be proven. So what we did is we said, well, there's really only one way to find this out. What we're going to do is we're going to take half the patients and we'll say, look, we're going to go ahead and put your embryos back. Just like we always did. And in the other group, we said, well, what we're going to do is we're going to get your eggs, fertilized them, and freeze them. And then we'll put them back in another cycle that doesn't have all the hormones present from making the eggs in the first place. So we did that study and we set a limit. We have to, before you do a human study, you have to submit your plans to an institutional review board and the institutional review board. This is a board that makes sure that you're treating patients correctly, that you're not going to do anything on ethical. And just to make sure everything is , is done the way it should be in a scientific study. And what they said was, is, you know, we're really worried that you're going to do harm to the patients who are in the freezing arm, those patients who you're freezing and putting back later, we think that you might be doing harm to those cycles so that those patients may not get pregnant at the higher rate that we would expect in a fresh cycle. Even though we told them, we think the opposite is going to be true. We think that the frozen arm may do better than the fresh arm may say , well, nonetheless, we got to have a safety valve. So the safety valve was, is that after 100 patients , uh, we were going to stop the study just for a second and take a look. And we wanted to make sure that we weren't doing any harm to the freestyle arm of the study. So we did the study and we stopped at a hundred patients, just like we had planned to do. And we looked at it at the results and we said, oh my goodness, the freezing arm has done so much better than the fresh arm that we have to stop the study because it would be unethical to continue the study in the presence of such profound differences, because we actually would be harming the group that didn't freeze their embryos. So we stopped the study, we reported our results, and we actually had two studies going on. Simultaneously. One was for just regular responders. Those people that made , um , less 15 eggs or less. And the other one was for those that made a very large number of eggs. And so we did, we, we broke the code in the first study, the normal responders, the ones that made a normal amount of, and that's the one where we found this tremendous difference. And then we looked at our other arm and we had a different problem. We looked at that arm and we were getting too many twins in both arms of this study.
Speaker 2So when you say , when you were saying other arm, you mean the other arm of people who had really low or really high response. So it sounds like the first group was making about 15, which is about average. And , and I missed the, is the other arm, the really low responder group or the really high responder group of women who make a ton of
Speaker 3It, really high responded group, the ones that would make a large number of eggs. And we looked at that group and we had to stop the study because we were getting way too many twins. And it would have been unethical to continue that study because the twin rate was so high that we were putting too many patients at risk of all the complications associated with twin pregnancies. When we looked at that study more closely, we found that the embryos were implanting in the frozen arm, even if they weren't good quality embryos. So we still saw the same effect that we expected, which was that the lining of the uterus when it's made perfect can accept an embryo better than when it's the lining of a uterus. That's been subjected to all those hormones that we need to get patients and the responses to those hormones after stimulation for egg development and retrieval.
Speaker 2Was it hard to get patients to agree to this? Cause at the time, because this was in the early two thousands, I mean, freezing was popular and had been around for awhile , but, but like you said, calm and dogma was you don't freeze an embryo unless you absolutely have to. And you don't use a frozen embryo unless the better embryo that you transferred first and a fresh cycle didn't work. And so was it hard to get patients to agree to participate in this?
Speaker 3It wasn't. We explained the study to them and what we were trying to accomplish, and the patients were very excited to participate. So we were, we were quite surprised and , um, they, they studies and after, when we published this, they called back and wanted to know what happened with it. Uh , cause from , of course don't read the literature because it's, it's a literature that usually reproductive endocrinologists mostly read. And so we were happy to tell them that they had participated in this and many of them came back for another cycle for baby number two. And of course they had their frozen embryo stale and the majority of them got pregnant with baby number two,
Speaker 2What year was this published?
Speaker 3We published it in 2011. And we actually presented the studies a short time before , uh, at the European society of human reproduction in endocrinology. And just
Speaker 2To tell you a little personal story,
Speaker 4My , um, daughter was born through IVF and I was doing it across the country. And , um, she, she was born in 2010 and we were doing PDTA , which back then was PGS. And I remember I had one embryo to test and they were like, we don't want you to fly in w we just want to freeze the embryo. And I was like, this is like my one , like literally I'm flying across the country and then come, you know, come a year or two down the road. It'd be like, oh, well maybe, you know, fortunately I was successful, but I was so worried about doing the wrong thing when, what they were suggesting out of convenience, might've actually increased my odds.
Speaker 3Yeah. So, you know, now the way it's turned out is , uh, we, we challenged other people. We said, why don't you try it? Why don't you try it? And, and sure enough, slowly people started trying it. And they found out in their own labs, most of the time, it worked better than fresh transfers. And then it just caught on like wildfire. And now there are more frozen transfers done in the United States than there are fresh transfers . So kind of a , a little bit of a contribution we were able to make.
Speaker 2So whenever we go to conferences, I feel like you are almost always on the docket of speakers because the fresh versus frozen debate still still goes on today. And , and watching you with these, these other speakers debating fresh versus frozen is always really entertaining to me because granted, I hear a lot of it at home, but , um, but it's always interesting because you are always on the list of people talking about the merits of frozen transfer and how, how much more effective it is.
Speaker 3Yes, that's true. It's still a hot topic today. Um, not everybody accepts it, but the number of people that accept it are greater than the ones who don't and it's happening more and more throughout the world. So I hear from my colleagues all around the world that, you know , they go, Hey, Bruce, you know, we tried that and we want you to know it works.
Speaker 2And you being the polite soul that you are. I, I am sure I'm absolutely positive. Have never actually said, well, yeah, I told you so ago ,
Speaker 3You can't get your
Speaker 2Wonderful and you would never do that. Um, but there are some times that I think about it on your behalf when, when we're standing at meetings and talking to people about , well, yeah, didn't you read his research that was, you know, awesome outta here 8, 9, 10 years ago. So
Speaker 3Thanks so much, Gary .
Speaker 4I think it's definitely one of those things that , um, you know, there's somebody who starts doing it and then somebody else is like, oh, well, how are your success rates doing so well? And it's like, well, I started doing this and then they're like, boom. You know, it, it takes a little time for the dominoes to hit, but it's, it's slowly going everywhere.
Speaker 2Wonderful. Well, thank you so much. Is there anything else you want to add in about frozen embryo transfers or what you're looking to in the future to, to look at for how you're going to make the next big change and how we all do things
Speaker 3We're still not done yet. Um, now that we are putting in embryos , uh , into a uterus, that's going to give them the greatest chance of conception of getting pregnant. Now we have to work to make the other side better. So now we have to work on the uterus side and make that better and better so that our pregnancy rates can go up even higher. And that's what our current round of research is doing.
Speaker 2Excellent. And we're torturing our MAs and all of our coordinators on a daily basis saying, all right , enroll more into this study and let's do this and let's do that. And you can kind of see them roll their eyes every time we do it. And then as we get information and they're like, oh, this is great. So it's all worth it. It is definitely all worth it. Thank you for everything. Thank you so much for joining us, Bruce. I brought my pleasure and this has been fertility docs uncensored with Dr. Abby Ablin of Nashville fertility center, Dr. Susan Hudson of Texas for fertility center, our guests, Dr. Bruce Shapiro and myself, Dr. Carrie BDN of the fertility center of Las Vegas. So hope to hear you all see you all soon and have a wonderful day. Bye everybody.
Speaker 6[inaudible] .