Creating a Family: Talk about Adoption & Foster Care

Decisions To Be Made at Egg Retrieval

November 03, 2021 Creating a Family Season 15 Episode 45
Creating a Family: Talk about Adoption & Foster Care
Decisions To Be Made at Egg Retrieval
Show Notes Transcript

We talk with Corey Burke, an embryologist and Tissue Bank Director at Cryos International-USA and Dr. Mark Trolice, Reproductive Endocrinologist and Director of The IVF Center in Orlando and Professor of Obstetrics & Gynecology at the University of Central Florida College of Medicine, and author of The Fertility Doctor's Guide to Overcoming Infertility about decisions doctors and patient have to make concerning eggs or embryos after retrieval.

In this episode, we cover:

  • Overview of the IVF Process.
  • What determines how many eggs will be produced?
  • What number of eggs is ideal for an egg retrieval as part of IVF? Are more eggs always better?
  • Once eggs are retrieved, one of the choices a patient and doctor have to make is whether to freeze eggs vs. embryos.
  • Compare the challenges between freezing eggs vs freezing embryos.
  • How does vitrification differ from other methods of freezing?
  • What is the thaw rate success for frozen eggs compared to frozen embryos?
  • Why are eggs more difficult to vitrify than embryos?
  • Does the quality of the eggs retrieved factor into the decision?
  • What are the advantages to the patient of freezing eggs rather than embryos? 
  • What are the advantages to the patient of freezing embryos rather than eggs?
  • How many eggs is usually recommended for a woman to freeze to have a good chance of being able to create a viable embryo?
  • Can genetic testing be done on eggs?
  • How long can human eggs remain viable if frozen vs. the viability of frozen embryos?
  • If embryos are created, one of the choices a patient and doctor have to make is whether to transfer fresh or frozen embryos. 
  • How does genetic testing impact fresh vs frozen?
  • What are the advantages to the patient of transferring fresh embryos?
  • What are the advantages to the patient of transferring frozen embryos?

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Please pardon the errors, this is an automatic transcription.

0:00  
Welcome, everyone to Creating a Family talk about infertility. I'm Dawn Davenport, your host as well as the director of creating a family.org. You can find lots of great resources for your infertility journey on that website. Today we're going to be talking about choices at egg retrieval. We will be talking with Corey Burke. He is an embryologist and tissue bank director and executive vice president of operations at Cryos International USA. We will also be talking with Dr. Mark Trolice. He is the director of the IVF center in Orlando and Professor of Obstetrics and Gynecology at the University of Central Florida College of Medicine. He is double board certified in reproductive endocrinology and infertility and OB GYN, and he is the author of the fertility doctors guide to overcoming infertility. Welcome to you both to Creating a Family. We're so glad to have you. I should be here again with you Dawn. It's always wonderful, and kudos to you, and creating a family for all the wonderful education you're giving to a patient's Thank you. Thank you very much. Alright, I think that anytime we talk about choices, that egg retrieval, it really helps us to begin to understand the entire IVF cycle because egg retrieval is only a part. And to really understand egg retrieval, we really need to understand the entire cycle, the whole IVF in vitro fertilization process. So Dr. Trolice, can you walk us through the IVF process as it's typically done?

1:41  
Sure, it really hasn't changed much remarkably from the early 80s. When when this all started. It's it's stimulation, egg retrieval, fertilization, embryo development. So often patients are on the birth control pill for maybe about two weeks or so just to regulate the cycles if you do what's called batching. With with other groups of patients, or you can go right into stimulation, and these medications

2:11  
are the same hormones essentially that the brain makes. That sends signals to the ovaries to grow a eggs. Now every month, a woman who ovulates naturally has those hormone signals to the ovary, but only one follicle, one cyst. Within a call, the follicular cyst grows and the rest die off, we override those natural processes of feedback to stop just one follicle that's naturally but with IVF, we give continued stimulation to increase the number of follicles cysts that grow eggs. And after roughly about 10 days of those daily injectable medications, with intermittent monitoring with ultrasound and blood work, just to see how the woman's progressing and to adjust the medication as needed. We do an egg retrieval. And that's typically done in an outpatient setting, used to be hospitals, but really, that's pretty rare. Now we do them all in the office based surgery centers. And under conscious sedation through an IV, we just put a needle to the back of the vagina and vacuum out each of the follicle cysts, it takes about maybe 15 minutes, 20 minutes at the most to get all the eggs.

3:27  
woman goes home within the hour. So we call them the next day with fertilization after the sperm are added. And then embryos develop for either a fresh embryo transfer. Usually on day five. Now, transit has been much more toward blastocyst development. But sometimes we'll do a day three fresh embryo transfer, or if they're a freeze thaw cycle. And those cycles are typically for patients who are hyper responders which do better. In a frozen embryo replacement cycle, the lining is not as receptive in a fresh, or we are doing chromosome testing pre Implantation Genetic testing, where we biopsy the embryos and freeze them all. And then the subsequent cycle, then we do an embryo transfer after we've been on natural hormones. So that's basically the IVF cycle. And a nutshell, okay, so what determines how many eggs will be produced? We generally say we, you know, well, we're going to talk about the ideal number, but what determines how many eggs a woman is going to produce in any one IVF cycle? Well, that's a great question Don, and it comes to the point of ovarian aging. And with that, it's two factors, quality and quantity. So we know a woman is born with all the eggs they're ever going to have one to 2 million at birth, about 242,000 left at puberty, hundreds get used every month. That's whether she's on birth control pills, whether she's pregnant

5:00  
or any other process at age 37, about 10,000, near near menopause, which is age 51, year about 1000 or so. So, as a woman ages, quantity and quality go down, quality quality is driven by their birthday. Okay? The older a woman is, the lower the quality and vice versa. Quantity is measured by two tests that we perform one is called anti mullerian hormone, it's a blood test Hmh Okay, and the lower that Hmh level is the lower the numbers of eggs. Hmh is a hormone produced in the cells supporting and nurturing the A called the granulosa cells.

5:47  
The other factor is ultrasound to measure tiny little cysts around the ovary or in the ovary, that represent eggs. Now, women always get nervous when I talk about cysts. But these are little cysts in the two millimeter to nine millimeter range. And the number of them give you an indication about how many eggs so quantity is Hmh blood test and ultrasound for antral follicles and we call it the antral follicle count AFC. Those two together, we look at age antral, follicle count and Hmh level that tells us how to stimulate a woman to get appropriate numbers of eggs for IVF. And of course, body mass index is also an important factor, the higher a woman's body weight, the more medications she will need. We can't always say how many they're going to get roughly 10 to 15 eggs is what we typically would see on average, but there's hyper responders that you can get 2030 or more. And there are poor responders that were lucky that we get three to five, as we used to say, you know, the idea is to get as many as you can, because it's the the hassle and expense and, and the wear and tear on a woman's body to have to do to stimulate and have to go through a retrieval. But is more eggs always better? Wow, that's a that's a pretty, pretty powerful question. And I am not of the school that you need as many eggs as a woman can can produce. I think less is more. And there is some evidence that high dose of drug means it's controversial is mixed studies on that but high dose of children's might be detrimental to the ache. And so we always have to be aware that stimulating a patient excessively and which is by definition what we're doing, we're doing control to burn hyperstimulation but excessive stimulation beyond which is reasonable can place a woman at risk for ovarian hyperstimulation syndrome. Now we've switched from the older days of giving patients HCG, which is the homeowner pregnancy by the way, HCG mimics the body's own LH surge from the pituitary to trigger ovulation. And we give HCG injection, but that has been very well described to be associated with a risk of ovarian hyperstimulation syndrome, particularly in hyper responding patients. So with the advent of the GnRH antagonist, where we stimulate where we suppress a woman's ovulation right in the middle of a cycle, we can now use a medication called a GnRH agonist. Leuprolide acetate brand name is commonly as Lupron but that can trigger the maturation of the egg so we can go in and retrieve eggs. Not ideal for a fresh embryo transfer after they've had Lupron. But why I'm mentioning Lupron is because that significantly reduces the risk of ovarian hyperstimulation syndrome. Needless to say, it can still happen. So we don't push a woman to excessive stimulation. I think once again, you're dealing with 10 to 15 or so maybe a little bit more, which is considered the sweet spot in medical study recently, that is ideal and excessive numbers of probably not in the best interest of the patient, physically, but also for outcome. Okay, so once eggs are retrieved one of the choices that patient and a doctor have to make is whether to freeze eggs versus embryos. Cory compare the challenges between freezing eggs versus embryos fertilized eggs where the egg has been fertilized with sperm and and it's beginning to develop. So what are the different challenges between egg freezing and embryo freezing?

9:50  
Awesome. Thank you for having me. Again, Don. This is a pleasure to be here. So we're talking about eggs and embryos. We're really talking about two totally different animals.

10:00  
so to speak. The challenge with eggs is, in my opinion a little bit more difficult to vitrify and freezing the egg portion of eggs are one cell. Most embryos are multiple cells up any embryos, multiple cells after fertilization. So it's a little easier to freeze the embryos, you have one cell. And one of the biggest issues with eggs being one cell is that if you damage the one cell, you've killed the one cell. And that is our biggest challenge with electrifying eggs. You only have the one go at it. When you're when you're petrifying embryos, you have multiple cells and blastocyst has anywhere from 60 cells up. So you know, a few of those cells happen to die in the process. It's not ideal, but it doesn't have much effect on the embryo. You know, if 10% of the cells die, they usually regenerate. It's not a problem. So the challenge between eggs and embryos is certainly the single cell issue.

10:59  
And eggs are made primarily, they there's a tremendous amount of the percentage of the egg that is water or liquid is high. Absolutely. That is that I mean, the egg is essentially all water or fluid inside. And that also makes it a bigger challenge because you know, we're talking about freezing. When you talk freezing versus vitrification, which we'll talk about a little bit later. Freezing implies that ice crystals are forming, you know, we're making ice and if you look at ICE and they're in your freezer, and you look at an ice cube, it's usually white color. And that's because all the crystals at four minute. vitrification is a little different method it it quickly, very rapidly freezes the cell and it doesn't have time for the ice crystals to form. But that is the big challenge with eggs especially is that since they're about 90% fluid, they're they're very difficult to freeze because the ice crystals form they poke through the membranes and actually cause death to sell. So I talked with an embryologist once and he said he goes freezing is never vitrification freezing is never the problem. It's thawing. That's the problem. So

12:00  
yeah, what is the fall rate success for frozen eggs versus compared to frozen embryos? Meaning that when you get ready to utilize either the eggs or the embryos, what is your chance of of having a viable egg or an embryo? Well, that's that's a great question. Again, eggs or embryos are always easier to thaw and the

12:23  
the success rate with embryos it's hard to compare the two because you have an egg that's not an embryo. It's an it's a gamete. It's just an embryo. It's an egg versus an embryo which is already an embryo. So it's hard to compare the two so I can't really say I think you know most places have very good success rates with with warming and transferring embryos Pregnancy is a different issue because we can't really discuss pregnancy pregnancy is independent of warming and having a surviving embryo to transfer. You know, it depends on the woman's health and a lot of other factors outside of just the warming of the embryo to get pregnant. So when we're talking about the success rates, I think the success rates may be overall are higher with embryos because they are already embryos. But it is about is something that we we challenge that we face all the time as an egg bank is the fact that warming eggs is difficult for most people it's a it's a very difficult procedure and you have to the timing and the temperatures have to be exactly right and have to be done at the exact right times. So warming eggs is it's just such a it's such a task that you know we train everybody cryo has changed since embryologists out to train a clinics embryologist in how to warm our eggs. And we feel it's that important that because there's so many different ways that you can you know, it seems like like forming something is a standard thing. You have one way of doing it but that's not the case. You know, every every vitrification procedure has a specific warming procedure to go along with it. And it one doesn't necessarily work on the other some do, but some don't. So, you know, it's just very, very difficult to warm an egg. So I would say truly, if you wanted to compare success rates between an embryo and an egg, you would have to give it to the embryo itself.

14:11  
So does the quality of the egg retrieved. factor into the difficulty or the success rate of ultimately what we want is a it's a baby so we want an egg to be frozen. We want it to be able to be thawed. We want it to be able to be fertilized with a sperm and we want that, that that embryo to grow and then we want it to implant so put we're expecting a lot. So does the quality of the egg retrieved. impact the success of freezing and thawing Dr. troughs?

14:46  
Well, certainly, you know the egg quality is a major factor in the outcome of an IVF cycle. Now we know that sperm are contributing as well.

15:00  
men above age 40 to 45 have higher rates of infertility, miscarriage, even pregnancy outcomes are affected preterm labor, autism, schizophrenia and birth defects Believe it or not, the the man with testicular sperm more challenging with fertilization and pregnancy rates are a little bit lower. Men who have severe male factor that even just use Etsy. Now Etsy is a great equalizer when you have male factor. XC outcomes are probably similar to standard IVF for male factor but but the more damage the sperm is in terms of, say DNA fragmentation, where there's compromise of sperm, there is the potential lower success rate. There is some concern that there may be even issues of chromosome abnormalities of the embryo with severe male factor, but tried and true we've always been. Our understanding is that the woman's age is the major impact of the outcome of IVF, not ovarian age per se. In other words, if we have a patient with a very low AMA's talked about earlier Hmh levels, that's a whole other conversation. But let me just suffice it to say, well, we have your listeners is that Hmh does not predict natural fertility.

16:25  
There was a study by Anne Steiner in the journal American Medical Association that looked at women with severe low Hmh and normally MH, and their pregnancy outcomes, and they had the same success rate to age per age. So natural fertility is not affected by Hmh. with in vitro fertilization, the younger the patient, the better the success rate, even Hmh levels that are lower. Now, it may be a little bit of a lower success rate, but nothing to the degree, as when a woman is older, was particularly with a low Hmh level. So a quality, major contributor to embryo quality and development and, of course, the woman's age as an indicator of implantation success.

17:09  
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17:31  
So, Dr. ciallis, what are the advantages to a patient of freezing eggs after retrieval, rather than freezing embryos after retrieval? So we've got that this point, we have done the egg retrieval, we currently have eggs. Now the patient and the doctor and the doctor be advising the patient, the patient has to decide, what am I going to do? Do I want to freeze my eggs? Or do I want to create embryos? And then we'll talk about some of the different options there. So let's first talk about should they freeze eggs versus embryos at this stage? What are the advantages for the patient? Or what should the patient consider when deciding? Well, I you know, I thought about that question that when we started talking about this podcast and I think we're putting the cart before the horse there. The decision about egg freezing is way in advance. Patient comes for planned OSI crop preservation or what's called Social egg freezing, right? That's a big trend. Now it's increasing. The American Society for Reproductive Medicine had released the experimental label in 2013 on egg freezing and that really opened the door not just for the cancer patients that we froze eggs before they got a harmful chemotherapy that could impair their fertility or even cause sterility from ovarian failure. But then social egg freezing, okay, so we get consults. CO of course for patients who are usually in their 30s don't have a partner don't have pregnancy plan but are getting nervous so they want to go through an egg retrieval and freeze their eggs that's completely planned in advance. There is no specific number of eggs that is able to predict the outcome there are calculating models to look at age of the woman how many mature eggs are retrieved to give an idea about success rate. But clearly the most recent ASM practice committee opinion bulletin that came out showed that obviously the younger the woman who freezes their eggs, the better the outcome. The only time that I can imagine dawn that the decision to freeze a eggs has to be made at the time of the egg retrieval is when there's a sperm problem. In other words, if unfortunately, the man is unable to collect to produce sperm for fertilization

20:00  
and there's no sperm on backup. If he cannot ejaculate, then we have to freeze the eggs. Otherwise we would lose any chance for of subsequent fertilization. Or if we have frozen testicular sperm. And when we thought the vials we do not have any viable sperm to inseminate. But other than that, it is not common to make that decision on game day, as I call it for the egg retrieval. Well, let's let's talk about whether it has to be at the moment of retrieval. When I'm trying to get as what are some of the what are some factors that a patient would want to consider in saying, Do I want to freeze eggs or do a one or freeze my embryos, certainly one that we hear is they don't have a partner to provide the sperm or they don't want to be limited to that partner for their future parenting. So that's certainly something that we hear that that, okay, I'm going to freeze my eggs because I would at this point that makes, I don't know who I want to be the father. So that's one, that's one consideration. And another one that we hear that I don't know if the medical professionals hear as much, but if they have a fair number of eggs, and they have good quality, and their concern is that they don't want to create a lot of excess embryos because of their religious beliefs or their philosophical beliefs, of not knowing what they would do with the they only want to create the number of embryos if they would be comfortable parenting. So we do hear people say, I'm going to freeze eggs because of that, because of that factor. Those are the things that I would that I primarily hear. Those are discussions prior to the IVF cycle start. The first one that you mentioned was was social egg freezing. The second one is a unique circumstance where they are concerned over how many embryos would be created. But those are conversations that we do have prior, though not common. Okay. Okay, so Cory, what are the Why would a patient think in terms of rather than freeze my eggs, I think I'm going to freeze my embryos, what would be some factors that a patient would want to think about when making that decision when deciding perhaps embryo freezing is better for them? Well, I think I think we are covered a little bit of that. I think if you have a partner, I think that's the first and foremost thing, if you don't have a partner, you could do have the option of doing donor sperm, perhaps. But I think that's the I think that's the big selling point. So from my perspective, if you're collecting eggs to store social for social freezing, and you have a partner, you're probably better off making embryos, embryos freeze better, embryos are easier to warm and transfer, eggs are always a chance that you're taking. So if you freeze, you know, eight eggs, you may not end up with eight embryos. But if you make eight embryos, and then freeze eight embryos, you're probably going to end up with seven or eight embryos. So obviously, I think if you have a partner, and that is something as a partner that you know, you're going to go forward with probably freezing embryos is a better solution than freezing eggs. And you do have, as you mentioned, you do have the, the option if you are if you're worried about that, for whatever reason, you don't want to do more than one cycle, or whatever, you do have the option of using donor sperm. But that's something that that I'd we do here women consider at least Okay, and we I have I have run into the same circumstance you spoke of earlier about people for religious reasons not wanting to create more embryos than there are out there that they already have. So, you know, in that case, it would also be beneficial probably to do eggs versus embryos. But that would be the only other solution. Other situation I can think of where you probably wouldn't want to make embryos out of your eggs if you had a partner.

23:57  
So Cory, how many eggs is usually recommended for a woman to freeze to have a good chance of a viable embryo that I keep seeing different? That seems to be a moving figure. And this would be for either social or for a woman who is under going to be going through some medical procedure that would impact her fertility. So how many eggs should she ate? That is a fantastic question. And one that's really difficult to answer. It all goes back to age, health, BMI, all of that sort of thing. You know, a 32 year old woman would need to freeze more than a 23 year old woman, a 37 year old woman had to freeze a lot more than a 27 or 30 year old. So it's really difficult to say that, you know, because there's also the genetic aspect of the eggs. As you age your eggs get more, I don't say more genetically abnormal, but you're more likely to have an unemployed embryo. So you know, as you age, you get above 35. You would need more eggs than you'd need if you were 2729 or something like

25:00  
So it's a very difficult question to answer in terms of exactly how many eggs a woman would need to freeze to produce a pregnancy. Mark, you have any you have any insight on that? Anything, anything.

25:11  
Any thoughts on that? Well, I share with them modeling studies that have been performed, in general, when you're less than 35. And, for example, if you get, say, 15, eggs that are mature, now I want to make the distinction that the numbers of eggs that we get at the time of the egg retrieval are not always mature, in average, 60 to 80% are mature. And then on average, 70 to 80%. fertilized, that number is an average we sometimes get less than, and, of course, sometimes more. So if a woman gets 15, mature eggs, and she's less than 35, you're modeling studies saying that you're dealing with eventually, probably about 70 75% chance of a live birth, using all of those eggs eventually, okay, and the more eggs that you get, the more chance to have potential for a second child or a third child from that one, egg retrieval. You know, the Society for assisted reproductive technology looks at the statistics now as one cycle of IVF being one egg retrieval, and all of the embryo transfers emanating from that one cycle. And that's the pregnancy rate that is measured. Okay? years ago, we just looked at per embryo transfer, essentially. But now one cycle per egg retrieval. So this is your chance for one, egg retrieval and chance of pregnancy.

26:47  
Let's pick 10. So women less than 35, they get 10, mature age, you know, down to maybe around 60%. Whereas a woman above age 40. If you get 10 mature eggs, which is which is not common. Success rates could be around 20%. Okay, the American Society for Reproductive Medicine really does not advise above 38 to freeze a eggs because of the lower success rate. You know, and interesting. There was a study to look at sort of the most cost effective aids to electively freeze your eggs, and it was found to be around 37. He said, Oh, my gosh, I mean, 37, that's a little bit late to do something like that. Well, why would that be the case, less than 37, it's unlikely that they're going to use the eggs that they froze, they're probably going to have conceived on their own above age 37 is unlikely that egg freezing is going to be as successful. So when patients come to me and talk about electively freezing their eggs, I go through the entire gamut of this may not work. You may never use these eggs, or you use them and they may not work or your partner that you eventually meet may not want to use frozen eggs, a variety of factors. So it's very, very important to have informed consent to empower women to make this decision. Fortunately, egg retrievals and ovarian simulation do not have long term health consequences, like losing your eggs faster or going into menopause, because you're going to lose these eggs anyway. Remember, we talked earlier that hundreds of eggs are getting ready to ovulate every month on the one next to ovulation. The rest die off. So we're pushing the eggs that were going to die off that cycle. So it's it's been around for guys the first pregnancy in this country, was it Eastern Virginia Medical School Norfolk the Johnsons do 1981. So we've really gone through 40 years of in vitro fertilization in the United States 1978 When it started in the UK, but those were natural cycles stimulating throughout the 80s and beyond. And now it's standard, stimulating patients. So simulate egg retrieval, fertilization, embryo development. And I think to add to that, Dr. Travis, you know, one of the things we initially we used to see a lot of people 37 up wanting to freeze their eggs, initially weren't seeing many young people wanting to do it. And I think that's changing a little bit now. But

29:29  
37 is a tough age to freeze your eggs. So interesting stat that 37 is the ideal time, but it isn't isn't. It's hard because you've got a 34 year old woman, she is still thinking that she's going to meet Mr. Right and that she wants to have a be a parenting partner, and that she's still waiting for that. That's what her expectation is. And it's it. As a woman gets older she starts thinking well if I want to be a parent

30:00  
I mean, I may still meet Mr. Right, but I don't want to wait for Mr. Right in order to become a parent. So it's a, you know, it's an unfair thing. One thing I thought about, Cory, can we you know that as a woman ages her chance of having a genetically abnormal egg increases. And of course, a genetically abnormal egg is less likely to fertilize and less likely to become a viable embryo less likely to implant and less likely to make it to full term birth and, and more likely, if it does to have genetic Gatlin abnormalities at birth or birth defects. So having said all that, is it possible to do genetic testing on eggs? So if a woman gets at 37, she has 15 eggs? Is it possible and she's going to want to freeze? And can she determine whether what percentage of those eggs are genetically normal? So that's a that's a good question. But it's also a little loaded question. So we can we can test eggs genetically, but it's, it's a very difficult procedure, we actually need to do a second polar body biopsy to do the eggs. So it's, it's not really feasible, a better way to do it is just make embryos, we can biopsy the embryos do do analysis on the embryos themselves. It can be done on eggs, but it's not totally reliable. And it's certainly not an easy task. And the other thing to add on, if you don't mind is that excuse me. Now, if you did have a genetically normal a by sampling the, the material that's extruded from the egg or the Polo body, if that's normal, it does not preclude the embryo being abnormal once it's fertilized, because it goes through a biologic process of meiosis and the addition of sperm

31:48  
to facilitate that, so it's not really cost effective to do a test genetically, because it still has to go through the major process of fertilization and embryo development. So that's another factor. As an egg bank, we've looked into that previously. It's just it's, again, it's not cost effective. And it doesn't it's not really conclusive evidence that you will have a normal egg. Gotcha. So if that is a concern for a patient, and is another factor to for her to weigh to make the decision on whether or not to create embryos in freeze or whether to freeze eggs. Cory one other question, how long can human eggs remain viable, if frozen, versus how long? Can frozen embryos remain viable? Well, that's an easy question to answer, Don, that's, we don't know. As long as we've been raising them, they are still thawing and embryos. In particular, I know that I personally have done a 13 year old embryo that survived and actually achieved a pregnancy. Eggs, we don't know, since they since they became approved. It's only been about eight years now. So we don't have a long term data on it. But we don't feel there's anything that stands in the way of that that would affect eggs, or embryos in terms of frozen storage, they should be viable for almost ever, you know, once they're frozen, they're in suspended animation, they're just there and nothing is happening too little background radiation that we're all getting anyways. So really, there's nothing to say that there's any time limit on eggs or embryos at this point in time, we may find that down the line, but it just we just don't have enough. You know, even with as, as long as we're freezing embryos, we still don't just have enough time to know, as long as we've been freezing them, we've been able to follow them and produce good healthy embryos from them. Just kind of amazing. If you think about it, isn't it? Alright, so a another choice, that parent that that patients may make may have to make is after egg retrieval, if they do create embryos, they they in their doctor have to decide whether to transfer fresh or frozen, whether to freeze the embryos and wait for a later time to transfer them or to transfer fresh. Dr. trollocs. I think there is the use to be the perception that you would have a greater success rate with fresh transfers. Is that Is that true?

34:19  
Well, I my credo in our programming in my life is that always and never should not be used. So practices that just always only transfer blastocyst, always or use freeze all cycles. That's really not individualized personalized care. The patients are unique and and we have a patient centered practice. So if we follow the literature, and patients that benefit from a freeze thaw cycle or hyper responders, these are patients that are not necessarily doing pre emptive

35:00  
inject testing or PGT. This is just the fact that high levels of estradiol from an oval responding patient is not as receptive to a fresh embryo transfer on the lining of the uterus called the endometrium. So we freeze them. And this was an article in the Journal of Medicine. And PCOS patients are pretty classic for this kind of a scenario of polycystic ovary syndrome, the most common hormone problem and women, they are hyper responders, and they do much better in a freeze thaw cycle. So that has to do with with freezing. Now in patients who have an average, or a poor response, no reason to do a frozen embryo transfer cycle on them, because it's more expensive. And it's equally been shown to be effective. Fresh, you know, when we were raised in this field, frozen was a consolation prize, everything was fresh. And then in time, fresh and frozen became equal. Okay, both pregnancy rates increase, but fresh and frozen, became equal, and then frozen now exceeds fresh in that specific scenario. What has facilitated all of this is the concurrent breakthrough technology of the advanced freezing method of vitrification. And that's what allowed eight freezing to come into vogue, the older method of slowly freezing the egg. Because the egg has a high water content, it caused ice crystal formation and damage the eggs. But now it's instantaneous freezing of the egg and the embryo. So less damage minimal to the egg and the embryo and much better survivable eggs and embryos to be able to do what we do. So that was key to have this whole discussion of what's better the freeze.

36:58  
Makes sense. And you also mentioned that if Lupron was one of the medications using I thought you mentioned that if you promise us that would be counter intercut indicate if to do a fresh transfer. Did I hear you correctly, it's not as successful. There was a paper out of Connecticut that looked at high dose support of the lining of the uterus after Leuprolide acetate. Lupron was administered for final egg maturation. They felt that, at least in that study that was effective at rescuing the cycle and a fresh cycle. But I think the most programs in the country, if they give a Lupron trigger, they will freeze the embryos because of the the inability to adequately mimic the support of the lining of the uterus that would have occurred if you gave HCG and the natural hormone production of the ovary, as well as the HCG effect on the on the lining of the uterus. So I think that really is best to freeze the embryos after a Lupron trigger. And so the the medications that are used to stimulate the ovaries to produce more than one egg, do they impact the quality of the endometrial lining, which would then the receptivity of the lining for an embryo to implant?

38:28  
I didn't understand completely what you're saying is you mean the HCG sugar versus Lupron? No, I just meant the medications that gonadotropin and others that are used to stimulate more than one egg to produce. Do any of those. Is there any evidence that any of those medications impact the receptivity of the endometrial lining? So witness in other words decrease the chances of an embryo implanting? Well, we know that an excessive response of the patient with high estradiol levels seems to impair the endometrium, for implantation. With fresh and frozen embryo transfer success rates being equivalent for average and poor responders. I don't think that there is really enough information to argue that point that that unnatural program cycle is better than a simulated cycle. I mean, there's some mixed studies that will go either way. But in general, stimulated fresh embryo transfer cycles have been used for decades, and an average support responders, there is no advantage of a frozen cycle in those circumstances. Okay. And as you point out, we have many decades of experience with it now. So, especially with fresh transfers.

39:47  
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40:25  
So Cory, how does genetic testing embryonic genetic testing impact the decision on whether to chance for fresh or frozen and it's, uh, how long does it take to do the genetic testing? How long can we keep embryos viable in petri dishes? So how does genetic testing influence patients or doctors decision, genetic testing, usually, in most, most places that run the genetic testing on the embryos for us usually take at least a day or two to get back with the results. So it kind of precludes a day five transfer, we have to do the biopsy on day five, or day six or later. And that's generally our normal transfer date, day five, or day six is the standard time that we make the transfer. So in most cases, it it results in a freeze freeze thaw cycle, and then we do the transfers later. There are a few places or a few a few clinics that even have their own genetics lab in house and they do the testing on site, they can still do a fresh transfer. But I think we still get back to the same question is a fresh versus a frozen transfer better. And it all depends on the stimulation that was given everything else involved with it as well. But I think I want to say probably 90%, or more of the genetic cycle, or genetic testing cycles that we do, are turned out to be frozen transfers because of the timing factor involved with it. We could I mean, it's not so much a problem to grow the embryo out a little bit more. It's more uterus, uterus being ready to have the transfer done. It gets passed in that time. How long can we now successfully grow embryos outside in the petri dish? Is there a limit? Yeah, I mean, that's a big question. People. People are growing them longer these days. But I mean, standard practice for IVF is five to seven days. So generally, there people are culturing to this day seven now and freezing. People can grow on longer. They can and we've I'm not sure exactly what the limits are. Maybe Dr. Charles can comment what ASRM limits are I think they raised it up to they extended it just recently. I don't know how long it is. But we can grow on longer than than we need to. That's not a problem. But five to seven days is pretty standard and IVF.

42:46  
Dr. Charles, any any recent doctor tell us any recent research that you've read on that it's a it's a curious thing?

42:54  
Well, I've thought that there might be a moratorium on the days of embryo development. I don't recall the actual days, but growing today, seven has been performed in centers. And when you reach these seven, you are going to have a lower implantation rate, unfortunately, So traditionally, they five with a six. Interestingly, they five is fresh, they six may be equivalent, but when you do a frozen embryo transfer, they five and six seem to be equivalent. I don't remember the numbers of days, but I do. I do recall that there is a limit to how many days in embryo can be grown in this country. Yeah, I want to say 14 days. Yeah, I think it is 14 days. And they changed it recently. But I think it's around 14 days, nobody's growing them to 14 days other than research people in scientist but IVF practices seven days is probably the max people go to I do talk to a lot of clinics that do go to day seven with with eggs, and most of them are saying they have about a 15 to 20% success rate with those embryos. That's that's considerably lower than you get on day five or day six. But for people who don't have embryos or run out, you know, have only a couple of day five or more day six, you know, it gives them another chance anyway. 20% is better than zero. Why would you wait? If you if you could transfer it day five, what would be the factors that would indicate that you would want to wait to six or seven? Or particularly seven since it since you said that the success rates for implantation are less? Well, again that with frozen transfer? I'll let you answer it mark. But that'd be frozen transfer for day seven. So it wouldn't be a fresh transfer on day seven. So we'd freeze them and then transfer them in the normal sequence may not be developing on the blastocyst stage by day five or six. Gotcha. Five is a perfect day to get blastocyst but we know lots of times embryos are slower. They developed a blast to Sunday six and a few actually goes through today. Set

45:00  
And I'll tell you most of the day seven embryos that I've seen that make blastocyst are not great quality blast, but occasionally you'll see a good one. And if that's all you have, obviously, if you have day five, beautiful

45:14  
blastocyst, and that's what you would use. But if you don't have that, then you know, then you might want to 10% odds are better than nothing. Yeah. And you know, the whole IVF practices is a numbers game, you start with X number of eggs. So so many of those fertilized so many developed, so many developed well, and you know, if you got a woman who only has a handful of eggs to begin with, you know, they may need to go to day seven to get something, you know, a good blastocyst to freeze and transfer eventually. Yeah, well, you I'm so glad you mentioned that. Cory, I think Don, your listeners would benefit on understanding the attrition that occurs with an IVF cycle. In other words, not all of the follicles that are measured, are going to yield a eggs. And not all of those eggs in the petri dish are going to be mature. Not all of them fertilized and not all of them grow today, five. So as I mentioned, 60 to 80%, mature 78% of the eggs, 78% fertilize, and about 50% or so maybe up to 60% will make it today five. So there isn't a nutrition that it's important that patients are counseled about that so they're not disappointed and that they have realistic expectations. And I don't even add to that I could try less Yes, quality eggs. We talked about that in the beginning, but not every mature egg is good quality eggs. So you know as mature eggs that are normal, some of them are I shouldn't say normal out of the mature egg. Some of them are not quite normal and don't really make good embryos. Do you mean just genetically are for other reasons structurally and other reasons? I would assume it's mostly genetic because that's what that's what makes an egg an egg but you know, we'll get it we'll get eggs it'll be oval shaped instead of round. I will say from a from a embryologist perspective, I've made beautiful babies out of oval shaped eggs but not always, you know, sometimes they just won't develop into good embryos.

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You know, it really is an attrition game isn't it is a numbers game and it's it's a process of attrition, which is is hard for patients to hear, but important for them to hear. Well, thank you both so much, Corey Burke and Dr. Mark trawls for talking to us today about choices at egg retrieval, important information and we are so thankful to have you with us to talk about this, this topic. And to our listeners. Let me remind you that we will be here next week. So I look forward to talking with you then as well.

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