Demystifying IVF and FET Protocols

Have you ever wondered why your REI made a certain choice for you on your IVF journey? Or why they kept the same protocol or chose a different protocol which none of your friends have tried? Or why different REI’s have different recommendations on protocol selection?

This is a question I get over and over, and I’m here to empower you with a deeper understanding of these protocol and the ability to feel confident in your treatment plan.

Also—please let me know what other science-based podcast topics you’d like to hear about.

The bottom line is that there are many right ways to do IVF, and a tailored approach is always the right answer.

As always, please keep in mind that this is my perspective and nothing in this podcast is medical advice.

If you found this conversation valuable, book a consult call with me using this link:

https://calendly.com/loveandsciencefertility/discovery-call

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Please don’t let infertility have the final word. We are here to take the burden from you so that you can achieve your goal of building your family with confidence and compassion. I’m rooting for you always.

In Gratitude,
Dr. Erica Bove

Transcript:

Hello, my loves and welcome back to the Love and Science podcast. As you guys know, this is love and science and you, my loves are asking for more science to help you navigate your journeys. This is so easy for me because I live and breathe in the REI clinical space.

As you know, I am a 0.6 FTE faculty member at the University of Vermont and IVF protocols are like the water that I swim in, the air that I breathe. It's easy for me to talk about and I know that these are some of the things that stress you out the most. I've gotten so many requests lately to talk about different protocols and so that's what we're going to do today. I was going to go through fresh IVF protocols and frozen IVF protocols and to maybe give you a glimpse into why your particular REI is choosing one protocol over the other. Again, always recommend a conversation with your own REI to understand their reasoning, but I think sometimes just having some context like a scaffolding can be helpful to understand.

I will tell you, I did not even understand these things at the end of my OB/GYN residency and that's with an interest in REI. These things really are fellowship level at the very least.

Let me empower you to be able to have a fluency in these things so that you can feel like you're not in some foreign country speaking some foreign language.

Let's talk about it. This is how I teach my fellows. IVF is basically the process of growing a cohort of eggs. If you think back to physiology, we have the dominant follicle, which is selected in a "natural cycle." It is selected because it's the one that's able to express the most FSH receptors, that's follicle stimulating hormone receptors. When it can hog more FSH, then it can suppress the others. That's the one where the dominant follicle is chosen and that's the egg that is ovulated that month under ideal circumstances.

We know that eggs like to be surrounded by other eggs and that's the whole point of the intrafollicle ultrasound is that we have a cohort of eggs. Say somebody who is 30 years old with that diminished ovarian reserve might have a follicle count of 20. That would be very typical to say she goes through 20 eggs in a given month, but one egg is the dominant follicle and all the others, their fate is that they're lost to atresia. If you remember reading that in our textbooks back in medical school, it really does make me sad every time I think about that, that the fate of every follicle is for atresia unless it's rescued.

That is what it is and if we do IVF, that doesn't have to be the case. In an IVF cycle, we use exhaustionist FSH to stimulate that cohort so that a single dominant follicle is not chosen and so we bring up the whole cohort as a cohort ideally to get as many eggs, many mature eggs as possible during that cycle. Now, like I just shared, we're not stealing those eggs from the future because those are part of the cohort that would have been lost that cycle either way. It's kind of like use or lose it. So IVF captures follicles that would have been lost otherwise, eggs that would have been lost otherwise and allows one dominant follicle with one mature egg, that cycle then turn into 5, 10, 15, 20 mature eggs in a cycle. I mean, 20, I'm always very lucky if I can ever get 20 eggs in a cycle because that means high egg reserve and good maturity, but the point is that we're going to these cohorts of eggs all the time and IVF captures those in a way that is hopefully safe and successful. So that is the point. Also, most things, reproductive endocrinology mimic the menstrual cycle and if you've ever tried to teach the menstrual cycle, you will learn how complicated it is. Like even as a new attending, and even still, I mean, if I read Spare Off, I learned something new every single time about the menstrual cycle, which is just amazing because it truly is a beautiful choreography. It's very complex, but what IVF and most things in REI are trying to do is simulate a menstrual cycle because that is how we're designed to reproduce. So let's just take sort of the general philosophy of IVF. So we're giving exogenous gonadotropins and we know that there's not just FSH, but there's LH as well. There's something called human menopausal gonadotropin or HMG, which is also called menopure and that is LH and FSH actually in concentrated form and those two hormones are injected to basically kick off the cycle. And so when the ovarian follicles see those hormones, they start to like perk up and then we know there's the two cell, two gonadotropin hypothesis and sort of reality, we know this is true. And so we have the LH, which basically sort of acts on the theca cells and we know there's the FSH that acts on the granulosa cells. The net result is that we get estradiol production and we see that estradiol number go up as the follicles are growing and the estradiol is being created by those cells. And so when we're doing IVF, we're doing ultrasound monitoring and blood work monitoring to look at the number of follicles that are growing in the cohort, the size of those follicles, because we know that anything that is about 14 to 15 millimeters in mean diameter that has the potential to have a mature egg inside. And so because immature eggs cannot be fertilized by sperm, we're really looking for mature eggs at this point.

We retrieve everything that's big and small, but we don't usually expect mature eggs from the small ones. So we are monitoring about every other day. We're looking at the follicles growing. We're looking at the estrogen levels. We're also often looking at the progesterone levels to make sure it's not rising prematurely. Many of us also track luteinizing hormone levels to make sure there's not a surge in the meantime, because IVF is like the gas pedals and the brakes, right? The gonadotropins are the gas pedals, but we have to stop premature ovulation somehow. And one of the ways that we do that is with our different protocols.

And I'll talk about that in a minute. So we're growing this cohort. We're looking for as many follicles between 15 and 22 millimeters as possible in a cohort size. And then when the time is right, we use a trigger shot, which basically mimics the trigger that we have inside our own body, the LH surge. Typically what's used is either HCG, which there's different versions of that, pregnant or avidrial, or maybe if you're in another country, you might hear other names as well. And then there's also a Lupron trigger actually, which can, that releases the body's own endogenous luteinizing hormone so that in an endogenous luteinizing hormone surge can happen. And there's different reasons to do that. If you can reference my OHSS podcast episode about how that can help reduce the risk of ovarian hyperstimulation syndrome. But we have lots of tools in the toolkit to cause that final maturation of the eggs in the hope that as many mature eggs are fertilized because they're mature in the first place. And so if you think about it, you can divide IVF into the different stages.

There's the getting ready for IVF stage and the prep work that's done, any sort of suppression that needs to happen in the meantime. And then the stimulation phase, most simulations are between eight and 14 days. You know, any shorter than that is really not a good sign any longer than that, also not a good sign. So that's typically how many days of stimulation meds people take coming in about every other day for ultrasounds of blood work. And then the trigger shot and then the retrieval happens on a very specific time interval. After that our office, we use 35 hours at my previous office, we use 36 hours. There is a slight range, but if you wait too long, then somebody ovulates all their eggs into their pelvis.

And I think of them like little clementines, like they're out of their packages at this point. And so unfortunately you can't retrieve the eggs. You can go into the cul-de-sac to retrieve the fluid, but it's usually not as fruitful as retrieving the egg from the follicle in the first place. So then, you know, we retrieve the eggs. And then at that point, your job as a patient is done other than following along. Most of the magic happens on the laboratory side. Then the fertilization happens. We watch the embryo development and then we either turn around and do a fresh embryo transfer on day three or day five, or we, and or, because you can do both in a cycle actually, we biopsy the embryos and freeze them and then send those cells off for genetic testing. The only caveat is that those, you know, it takes too long for those cells to come back in most labs. And so usually in those situations, we're talking about a freeze all cycle. So that's the whole point of like, you know, the stimulation and getting eggs. The question is why do different protocols exist? And so back in the day when there was basically no, like no suppression, about a quarter of patients would ovulate because if you remember, as the estrogen rises, that's what kickstarts that luteinizing hormone surge in the body. And so if, if say even after like an estradiol of like 250 sometimes or 500, like you can actually get an LH surge. And so like I said before, if you have that happen and all the eggs go into the pelvis, it's much harder to retrieve them at that point. Now, what I will say is that some of the smaller follicles, like under 14 millimeters, they may not even have a LH receptors, which is why we can quote unquote, get away with not doing suppressive medicines quite until the follicles are bigger, but especially in a woman with like diminished ovarian reserve, their thresholds seem to be a little different in terms of this, the surge. And so we watch people very closely always with the mindset of preventing a premature LH surge that would negatively affect the follicles that have receptors and then cause a premature ovulation event. So let's talk about the different protocols.

And I think thinking about the gas pedals and the brakes that kind of makes sense. And so, you know, the antagonist protocol, let's talk about that one first. And so that's actually a relatively newer protocol. It existed in my fellowship, but we didn't do it very often.

We sort of were doing it for like PCOS patients and older patients with DOR, but like everybody else got standard Lupron for the most part. That's another protocol to talk about. The beauty of the antagonist is it's not too suppressive, right? So you can kind of like let the follicles grow until about treatment day six, sometimes treatment day eight. And then as you start to see the estrogen rise and the follicles grow, then you can put the brakes on the system because then you're like, okay, well, we're going to put the antagonist on to try and stop premature ovulation. So that's a beautiful way to do it. I mean, it works if it works every now and again, we have somebody with a breakthrough ovulation event, which is obviously very devastating when that happens. But that's the reason that we chose to that protocol is because it's this nice balance of not overly suppressing, but then allowing the suppression when it matters the most. And there's other reasons to use the antagonist protocol. Another reason is because we can still use a Lupron trigger. If we use the other protocols, which are Lupron based using Lupron primarily as the suppression, then those receptors are internalized. And so you can't use a Lupron trigger. You can only use HGG. And especially for high responders, people can have a higher rate of ovarian hyperstimulation syndrome.

So that's another benefit. Now I will tell you, I'm old enough. I'm mid-career now. So I feel old sometimes that that's okay. It comes with wisdom and experience. And I remember back in the day when we really did give most people HGG triggers and probably like once a month in my fellowship, we were rounding on somebody in the hospital who had moderate to severe OHS. And it's always like, did they get a pigtail drain through IR? Do we do vaginal paracentesis to reduce some of the pressure? You can get plural effusions. People can get actually pretty sick from hyperstimulation. And not to mention, if you're a female physician trying to get back to your job, that kind of cramps your style to be kind of waddling and walking very slowly because you have all this extra third spacing and extra fluid that you're carrying. So even if it's quote unquote, just moderate hyperstimulation, it's not quite criteria for hospital admission. It can really affect how you feel and your return to normal activity as well. So there's that advantage of the antagonist protocol. Anything else to say about that? I think that's pretty much it. So that's the antagonist protocol in a nutshell. Now, the more historical protocol is the standard Lupron protocol, which is basically where you start Lupron even in advance of the cycle. Because we know, remember that like with Lupron, you can have a flare because it basically stimulates LH and FSH release and you don't want to do that. So there's different ways you can actually either have somebody on a birth control pill so their endogenous gonotropins are already low and then start the standard Lupron so there's no flare. Or you can actually start the Lupron in the previous luteal phase because that's when the endogenous gonotropins are also the lowest and then you can sort of glide on from there. So there's different ways to start it. But the point is that they call it the long Lupron protocol because it actually starts like weeks before you start your IVF medication so it can feel like more times of injections.

And I want to be clear, this is not like Lupron suppression for people with endometriosis.

This is just truly like one of our mainstays, one of our mainstay protocols for IVF. So say somebody's on a Lupron, it's suppressing their body's endogenous gonotropins, then you can give people FSH LH from the beginning. Some people even start with just FSH and then add an LH. You can even do an FSH only cycle too but most of us feel a little bit more comfortable using a little bit of HMG just given that there's some populations where there's some benefit. It seems to be there's some benefit. So we do the stimulation protocol, same thing, monitoring. But the nice thing is because the generator receptors are already internalized that there's not really that same fear that you're going to have somebody have an LH surge through the Lupron. So it's a little bit more suppressive. So yes, it can sometimes lead to sort of a more suppressed response and lower response. But especially if somebody has like a single dominant follicle in a previous cycle and you're really trying to get or maybe somebody has two cohorts in their previous IVF cycle and you're really trying to get a more unified cohort, the standard Lupron protocol is a very nice way to achieve that. And you don't know if you try and there's some biological variability, which is like the bane of our existence as REIs because we want to be able to control the things we can and sometimes the body doesn't act the same way from cycle to cycle. But I think it is a tried and true protocol. And the only caveat is you got to really be careful with the high responders because we can only use an HMG trigger in those situations with this protocol and that sometimes can lead to some OHSs in ways that the antagonist protocol doesn't always with the Lupron trigger. Okay, so that's standard Lupron in a nutshell. There's also and we're talking like, you know, 10 units, right? Like five units, 20 units, like small doses, not like this depot Lupron big slug of a shot that lasts for like a month or three months, but really like daily Lupron injections. An antagonist at the cetera tag get around. Those are also injections. There's this other protocol called microdose Lupron flare, which maybe you've heard of it before. And basically the idea is that we're giving like the teeniest dose of Lupron in a way where you actually start this, the IVF cycle by giving the microdose Lupron, which causes actually like a mini flare. So you're like flaring the pituitary to release the endogenous catatropins. So the cycle actually kick starts off with a release of endogenous FSH, which is great. Sometimes people also give comafine during a cycle for the same reason, because it stimulates the release of endogenous FSH.

And then we add in the catatropins from the outside world, the FSH, the exogenous, uh, the exogenous, uh, the FSH and the LH. And then sometimes that boost because you have endogenous and exogenous. Sometimes that gives you a leg up compared to the exogenous hormones alone. And so in the beginning, the microdose Lupron is actually flaring the pituitary and causing a little bit of stimulation. But then the magic is that about seven to 10 days in that my girdos Lupron actually then down regulates the receptors because that's what happens after you've been on Lupron for that long. And then your stimulation actually becomes your suppression. It's kind of brilliant actually, if you think about it. So, you know, the caveat is that, you know, you need an HGG trigger as well for this protocol. Um, oftentimes it is poor responders. Um, we try this protocol in, but I will tell you, I swear like I have had so many patients who did not respond favorably to the first two protocols and they cut to like an Eshin of over 5,000 with the microdose Lupron, Lupron flare. And that was the only protocol that gave them, um, you know, good embryos. And it's, it's fascinating because if you look at the data, like if you look at poor responders or you look at all comers, like one protocol does not seem to be sufficient than another, but that's like looking at large population data. I do think that we have to look at the individual and, you know, do some tailored tailored care here because there are some ways in which some people may respond better to something else. And we got to be mindful of that. Um, then, you know, you might sort of ask the question about, okay, well, what about like priming? So priming actually, like we've really only been doing that for within the last 10 years. I would say, at least from my experience, I, we didn't start priming until I was well into my fellowship, maybe barely as a new attending. And that concept is really, um, the thought that if we, some people do a birth control lead-in, which kind of is very effective for timing.

Most people do okay with that, except for people with, you know, bad diminutative, and reserves. Sometimes that can be like a little too suppressive. And so the nice thing about estrogen priming, especially for people who have like a mildly elevated FSH is that it allows for a little bit of suppression of the, a person's FSH in their luteal phase so that you don't get a premature rise of the FSH, which, you know, if you think about why do people have short cycles and recruit a dominant follicle too early, it's because the FSH is rising like in the luteal phase actually, and starting that, that process in the end of the luteal phase. But if you can cause that negative feedback by just a little bit of estrogen, either through a patch or a pill, sometimes that can allow the FSH to kind of stay at bay. And so when you give, when we give our exogenous FSH in L.H., you're actually starting at a true baseline. You're not fighting a dominant follicle that's already started and you can do estrogen priming. You can do that with, with microdose, the bond flare. You can also do it with the antagonist protocol. You can't really do it with a long loop run because you're already suppressing in the luteal phase with the kind of heavy hitter loop run. So that's like more suppression. Again, the estrogen priming is like a break, but like a soft break rather than like a hard break. If you think about it that way. And I will tell you when I froze my eggs, my REI and my FSH was over 10. My REI chose estrogen priming and I'm really glad she did because I think we got more eggs than we would have given my physiology at that point in time. So I do think it really works. Sometimes the timing is a little tricky. You got to track your ovulation and then the question is, well, what do you do if you don't obviously there's all these different sort of caveats, but I think the estrogen priming can be a nice adjunct, especially if you have diminished ovarian reserve. Now I get the question all the time, like what's the best protocol for people with diminished ovarian reserve? Now I will say that's a very individual question. You know, it depends on what you've tried. I always look at like how people responded to oral medications.

If they were on oral medications, people asking about mini-STEM IVF, like there's not one protocol that is the protocol for DOR. I will be very clear. I do think that estrogen priming can help. That can be a very nice way to help people with DOR. Like I said, I've also had some, I don't want to say luck because that sounds very unscientific, but like some good success stories with the microdoses loop run flare and select patients when they didn't have good responses to the other protocols as well. I think that, you know, typically I start with more traditional higher doses of gonadotropins to see like if somebody has an antral follicle count of six, I don't want to leave, you know, follicles on the table.

I want to get as close to six as possible. And we know that for more traditional IVF, we can get that number plus or minus two is often a good estimation. It doesn't always happen, but it's kind of the antral follicle count is a good estimation of the cohort size like we talked about in the beginning. So, you know, I think that the estrogen priming can be very helpful in that regard and also kind of being more bold with the IVF medications can be helpful. But I will say that like, you know, if somebody only has a follicle count of two or three and they're going to get the same response, whether you use 450 combined of gonadotropins versus say 225 or 300, like why would you give somebody extra gonadotropins? Doesn't make sense. Like it's going to be more expensive. It's going to be harder on the body. And sometimes we do actually see better responses when we go a little bit lower on the medications and maybe not even push people to such big follicle sizes. And so again, that's where the tailored approach happens. That's where, you know, a previous review of all previous treatment IVF and non IVF included is very helpful because, you know, this is a very nuanced conversation. And I think that we can really do well when we tailor the care. So like I said, there's not one protocol for diminished event reserve.

Sometimes we use microdose flares. Sometimes we use chlamyphine. Sometimes we use, you know, estrogen priming with antagonists. Like it really depends. But I think the whole point is to synchronize the cohort as much as possible to get as many eggs and as many high quality embryos as possible in the given cycle. So that's, you know, sort of the fresh IVF protocols and maybe we'll have more protocols as we move forward into the future. Maybe we'll have, you know, maybe we'll start using Orlyssa. I know some people have started using Provera as a sort of ovulation blocker, which in free cell cycles has been shown to be very effective and cost effective. And it's an oral medication instead of an injection. So I do think the jury is not out in terms of IVF protocols, although there's been, you know, relative stability over time, if you think about sort of what we're able to do with our toolkit. But let's now transition to talk about frozen embryo transfer protocols and the differences between those. So let's see. So frozen embryo transfer protocols.

Again, the whole point is to stimulate a menstrual cycle, right? Where we're in the first half of the cycle, there's the follicle. There doesn't always have to be a follicle in these cycles, but the estrogen needs to rise in some way that allows the endometrium to respond in kind because the whole point of the endometrium is to be receptive to the embryo. We know this happens in a 28 day cycle around day 21, right? So the embryo is actually created around like day 14, right? And then it spends seven days making its way down the fallopian tube and landing inside the uterine cavity. And then finally implants around like seven days after it's created, you know, and then after that, that's why we say an embryo should implant 24 to 48 hours after a rheoplasticis transfer, because that is actually the timing of what an embryo does inside the body. And then it's another week before we know if that embryo has taken. And so everything is based on a physiology of like a normal menstrual cycle. But a lot of the reason that many of us are, you know, in the IVF world is because that's not happening on its own and we need assistance or there's sperm issues or tube issues or whatever. So if we think about what a typical menstrual cycle is physiologically, I think a lot of these protocols make a lot more sense. So there's the typical like programmed cycle and that means that we're giving estrogen and then we're giving progesterone to kind of mimic a cycle. What we've found is that in a programmed cycle where the ovaries are completely kept quiet and all the hormones are coming from the outside of the world, there is a benefit. The ongoing pregnancy rate is higher when we use some progesterone in oil. And now there's lots of tips and tricks of how to make that more bearable. The oil can be very caustic to the skin. It can, you know, create hives even in some people, especially my lean patients have a really hard time with the injections. And so, you know, I do not see any harm in icing the area ahead of time. Some people have used M-law, you know, but it's a deeper injection. So I'm not really sure that helps entirely, but you know, try to change the spot around, see if you can find some more real estate, but you know, it is a long time on these injections, right? So it's basically from like the time that you've like six days or so before your embryo transfer and then you wait, you know, another nine days to see if you're pregnant. So that's roughly like two weeks. And then if you are pregnant, you're like four weeks pregnant. So then it's about another six weeks of daily injections. And so it can really be a lot, but I think because the success rates are so much higher in these program cycles, it really does make a difference to do them.

So, you know, estrogen pills or estrogen patches, sometimes even vaginal estrogen is really helpful because the absorption is so good. And then monitoring, looking at the lining, making sure it's trilaminar and thick. How thick is thick enough? I mean, this is a whole other episode, but I think most of us ideally would like to see seven millimeters or greater and trilaminar, although success rates are pretty equivalent in the six millimeter and above group two. So if yours is like 6.3 and beautiful, like I would not lose sleep over that. But if it's like super thin or heterogeneous, then I mean, there are maybe reasons to look into that more for sure. But the physiology is like estrogen, progesterone. And then because all the hormones are coming from the outside world, maintaining that until even a little bit beyond the luteal placental shift, which happens around seven to eight weeks. So most of us keep the hormones going until about 10 weeks or so. And then the placenta at that point confidently has taken over. There are people do these program cycles, some members with Lupron. That's how I started in my fellowship. I think we've found that we don't always have to give an ovulation blocker as long as our estrogen doses are high enough. So, you know, in my experience, I have had a people, a few people have breakthrough ovulation through cycles where the estrogen dose is on the lower side, like four milligrams a day for sure is kind of low. But once you start to get to six to eight milligrams a day of estradiol, oral estradiol, vaginal estradiol, that really is enough to create negative feedback such that you don't really need an antagonist or a Lupron, which is kind of nice because those are both injections. So that's a program cycle. Let's talk about natural cycles. So I love natural cycles. I mean, they're finicky and they are time consuming for patients. But I think that there are many people, many of my patients and my clients to this day, I don't think would be pregnant without a natural cycle. Some people just don't grow a good lining on a medicated cycle for some reason. And their body's own endogenous estrogen is really helpful to make that happen. So you can do a purely natural cycle where you truly just like if you're ovulating, you just watch the body and you see when the LH surges and then you time the embryo transfer to after that surge. Typically, it's about six days after the LH surge, although there are some different protocols. We look at the progesterone level and we look at when the progesterone crosses one and then we time the embryo transfer to when it would be like physiological. And so that's a purely natural cycle. I don't trust older ovaries, so I do not like purely natural cycles. To be clear, I'm very opinionate about this because you're trusting the corpus luteum to do what it's supposed to do. And most of my patients are having infertility in their hair for a reason. And so I don't tend to trust that function. I like to augment with a few hormones, but that's just me. I do know people who are pregnant today because of a purely natural cycle and good for them.

I said I was like good for them. Then there's like a modified natural cycle. And so that's basically where you can take like letrozole is kind of the most common one, letrozole for five days and then watch the follicular development. I personally love this protocol because some women are like mildly and ovulatory, even just like the effect of stress can throw off cycles. How many of you have been like, why isn't my period coming? It's probably because you had a wonky cycle maybe due to stress or maybe people are coming off the IVF hormones. We know that can affect the follicular development in the next cycle.

So it's kind of like a nice way to kickstart the cycle with some predictability that doesn't rely on the body's own ability to just reset itself after all these changes. So letrozole, you can do 2.55, 7.5. My typical protocol is to start with five unless I have data that somebody's responded better to a different dose. And then the thing is you just don't want to miss the ovulation event because you're timing the embryo transfer based on what ovulation happens. So I like to bring people in like day 11 or 12 of their cycle, see what's going on, check their LH, check their progesterone, check their estrogen. And then if say they have like a mid-sized follicle, like 15 millimeters or so, I might bring them back in a couple days to be like, okay, how's your lining? How are your labs? And then when we have a follicle of at least 18 millimeters and a lining that's at least seven millimeters ideally and a low LH and a low progesterone, still that's when we can do a trigger shot. And so you might say, well, why do you need a trigger shot? I mean, technically you don't, but it just aids in the timing of the transfer. So you could follow the LH surge like in the first example, but I kind of like that predictability and I like the timing because the surge if it starts at night and then sort of peaks sort of in the morning, like it's really, really hard to track a natural cycle and to get the timing right, especially in a lab that's not open like 24/7. And so I find that if we sort of trigger and then do the transfer seven days later, that that works out really well as long as the baseline hormones are low.

Now if the LH starts to surge or if the progesterone starts to rise, then we got to kind of do our best calculations of when the best time to transfer is, but that tends to work pretty well. And then, you know, augmenting with hormones in the luteal phase. I'm a big fan of that. Like, why would you not do that? The nice thing is you don't necessarily need progesterone and oil because you do have some corpus lydium function. You can truly supplement with vaginal progesterone. And especially for people who hate injections or who have a hard time tolerating them, this is a really nice protocol to use. Sometimes the lining just looks prettier with the letters all, sometimes it gets thicker, all sorts of different situations. Sometimes if you're having somebody who has a history of breast cancer or VTE and they want to keep their estrogen levels low, it's also a nice way to do that as well.

So I think there's many advantages to this, but again, you don't just start with a transfer date and work backwards like you do with the program cycle. You actually kind of march forward towards your ovulation and then, you know, have your transfer about a week later once you're ready. And so there is some more, like more lab monitoring and ultrasound monitoring for sure. And also it's a little bit less predictable in terms of the timeline. So especially a lot of my surgeons with OR dates and things have a hard time with this, but I always say that there's a, well, there's a way and this has to be the top priority. So we figured out a way to make it work. There's also a modified natural cycle with follicle stimulating hormone meaning good atropins. So I've had some people, especially who've had really tricky linings like thin lining, but you saw in their IVF cycle, they had a lining of like 6.5 millimeters and trilaminar. There is a way to do the same thing that we just talked about with the latrazol with FSH. Now, the only issue is that these are people who are actually at high risk of OHS because we're not retrieving any follicles, right? We're using the FSH to grow many follicles as if in an IVF cycle or using a trigger shot. Somebody may have 5, 6, 7, 8, 9, 10, corporal lutea that have not been retrieved. And then they have just like boatloads of estrogen, progesterone coming from those follicles. So I will tell you, I have patients who I've taken care of who I do not believe would have children right now if it weren't for this protocol. It takes a lot of monitoring. It's expensive, especially if insurances don't pay for it. But I do think that's a nice option to have in the toolkit.

And people absolutely need luteal support with hormones in these protocols because we know that gonadotropin cycles outside of IVF, actually patients have lower ongoing pregnancy rates if they don't take luteal support because of some suppression of the endogenous hormones.

And so if you're going to do an FSH stimulated, modified natural cycle, yes to the trigger shot, yes to the luteal support until about 10 weeks of pregnancy. And it can be very beautiful and just be prepared that, hey, what's worse, not getting pregnant at all, or maybe having a touch of OHS? I think you can make your best call there, but I have seen this work. It's never my first protocol that I use, but I think it can work.

Now there's a whole other field of sort of topics that I have not even broached on yet.

And that's adjuncts. I do actually have a recorded talk on IVF adjuncts that may be useful. Some people ask me about baby aspirin during frozen embryo transfer cycles. Some people ask me about, you know, Claritin and like antihistamines and other medications that can kind of calm the system down. You know, I don't know of any data that support their use, although I'm, I don't really know of any particular harm either. And so I would just say like, listen to your REI on these, like other than, you know, there's a whole talk on things like, you know, things that are truly not evidence-based and are super expensive and may actually have some harm. That's sort of where I'm like, okay, I would not offer that to my patient because, you know, if something is like $30,000 a pop and there's no data for it, I'm not going to just like recommend that to my patients. Also embryo glue, I get a lot of questions about that. It sounds really great. Like who doesn't want embryo glue? But I think that if you look at it, like it's just marketing, there's no evidence that it works any better and it's fairly expensive too. And so we say first you know, harm. We're used to paying a lot of money for those treatments, but I do think that there is financial harm to be, you know, paying for something that's not even necessary, in my opinion, and based on the data. Let's see. Is there anything else to talk about with transfer protocols? I mean, I think, you know, I do get some questions about endometriosis and like, what's the best way to deal with having an endometriosis and making a transfer as successful as possible. There is a study that looks at Lupron and Lettresol together, you know, for two months prior to an embryo transfer that the ongoing pregnancy rates were higher. And I've seen that, you know, I think that it's always that question when somebody has an endometriosis and that's part of why we're doing IVF is like, do we take a pause between the retrieval and the transfer and commiendo, comedy, I don't know that's present and then move forward. You know, I think it's a good option for many people.

Again, very individualized approach depends on how somebody's uterus actually looks, how their lining looks, what their history is before we make that decision. But I think it's a very tailored approach to that question, but I'm a big fan of suppression. I know it's controversial. I know not everybody would believe, would agree with me. I think that it's biologically plausible. And I do, again, I have many patients in my practice and many clients who I truly think that end of suppression, what was what finally got them to get pregnant and stay pregnant. So here ends my talk about different IVF protocols. If there's things I left out or if there's things you want to hear more about, please do ask me, this is love and science. I feel very passionate about the fact that my people, who's all of you have the knowledge and the tools that they need to make empowered choices. And so just having the lingo understanding the framework, I think that can be like invaluable. It's like if I, you know, when my mom was sick in the ICU after her aortic valve replacement, I was like, why did I not pay more attention? Like what's the, what's the map again? Like what are all these numbers? And I was just sort of like, oh my gosh, like I don't even know where to start. So my goal is to orient you to this whole field that is REI in a way that you can start to understand like why your REI is maybe choosing different things for you and just to help you even go to your REI and ask more empowered questions. Okay.

With that, you know, I love you and write to me. Let me know what else science topics you want to hear about because I'm here for you. Take care. Bye.