Priming for IVF: Balancing Synchronization and Suppression

Today, we dive into the world of IVF priming and uncover the delicate balance between synchronization and suppression. Learn how different priming methods like combined oral contraceptives, estrogen-only, progesterone-only, and cold starts play a pivotal role in setting the stage for successful outcomes. Whether you’re curious about the science behind follicular development, concerned about over-suppression, or just looking for a deeper understanding of why your protocol was chosen, this episode has you covered. Join Dr. Mark Amols as he demystifies the strategies behind priming and helps you navigate this crucial step in your IVF journey.

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Transcript

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Today we talk about priming, balancing, synchronization and suppression to optimize your IVF outcome. I'm, Dr. Mark Amols and this is Taco about Fertility Tuesday. Not all IVF cycles begin the same way. And thats for good reason. Today I want to uncover how priming strategies set the stage for success and why choosing the right one can make all the difference. I feel like priming has been misunderstood. I see lots of posts out there where people will talk about priming or even when patients come in and will say theyre worried about overupressing their eggs and they should be worried because there is some truth to that. But the question is there's this balance. And this balance is, yes, you don't want to overupprress, but you also want to have synchronization. And depending on the person, the right treatment is going to be different for everyone. And so I want to talk about that balance today and then also want to talk about what the studies say and whether there's even any truth to all of this. So let's first start by introducing what are the types of IVF priming? What does that mean? Priming means to get the ovaries synchronized so they have better development. But there's also other purposes for priming. Priming could be used to prevents from developing while you're waiting to go through. IVF priming can be used to synchronize you with a cycle. Let's say if everyone's going to be starting in a few weeks, it gets everyone on the same schedule. Priming can also help get a better response. And one of the ways it does that is by suppressing FSH levels. It causes upgulation of receptors and then your body may respond better to the medications when you come off of the priming. So in essence, it can be used for timing, synchronization, modulation of FSH levels and upre regulation of FSH receptors. Now, there's going to be a few priming methods. Now they may be called something different, but they are generally going to be very similar to these. The first is can be combined oral contraceptives. This is your estrogen progesterone combination that makes up most birth controls. This can either be in pill form, this could be in patches, and theoretically could even be in the vaginal ring. Now when it comes to the combined contraception, that is going to be your strongest priming agent. That is the one that's going to prevent you from making cyst. That is the one that's going to Reduce your FSSH levels the best. And that's also the one that is the most commonly used. It's also the one that can suppress you the most. Now, after using a combined contraception, then you get into the single hmum, contraception priming agents such as progesterone and estrogen. Progesterone is going to be stronger than estrogen, but it's much weaker than the combined. It will also help synchronize follicles. It will also help with reducing FSH levels and increasing FSH receptors. But it will have, less suppression than using the combined contraception. And estrogen is even weaker than progesterone. When you take estrogen, you will get some of the similar effects, but you will have less suppression. And then the very last method is going to be what's called a cold start. And that is basically where you're allowing your body to have a period and your starting stimulation on the third day of your cycle or second day with your natural ovulatory process, as you would imagine, you're going to have almost no synchronization with a cold start being in the natural cycle, you're also going to have more chances of having a cyst present and you will have no regulation of your FSH receptors and levels. This also means that you don't know when you're going to start your IVF process until your period comes. And so this clin is probably just running IVF all the time. Now, I can tell you all these methods are used. I know some clinics that only do cold starts and they just run all the time, and they just start people when they get their periods. Most clin, as I mentioned, will do combined contraception, and then most will use some type of combination of using estrogen only or progesterone only. Now, you can start those at different times. You can start them in the beginning of the cycle, you can start them after ovulation. So there are many ways to do this, but I want to focus on these different types of priming. Now that we've discussed the different types, the question, as I said, is if we put them in order of suppressiveness, combined is going to be the highest, then the next suppressive is going to be progesterone. Being less, then less than that is estrogen priming and the least is nothing. And then in reverse, that's exactly the way it is for synchronization of the follicles. The cold start is going to have the lowest synchronization, followed by the estrogen followed by the progesterone. With the most synchronization occurring through the combined contraception. So what's the big deal? So what if it suppresses you a little bit? Well, you're right. If you'got 16 follicles and you get put on contraception and maybe you would have made all 16 follicles grow, but with overupession you only made 14 follicles grow. Or maybe it made your cycles grow a little bit longer. That can feel like that's a big drop. But the thing is that there is this synchronization occurs where the follicles group together and grow as a group. And so let's take that scenario where you have 16 follicles and they're all growing, but they're spread out a bunch and you get all 16 but the zone of maturity, and we're just going to use this number, 15 to 20 is where they're going to be mature. Above that there's a potential be post mature. Below that they could be immature. Well, what if only nine of those follicles fell between them? All 16 grew, but because they were spread out, only nine fell in that zone. And then you take the other scenario, you say, well, if I took the contraception that was combined and I got better synchronization, only 14 follicles were going to grow. But of those 14, 12 of them were in that zone, maybe all 14 there. You can see how even though we accept some of the mild suppression, the synchronization actually makes up for it and we actually get a better group of eggs that are going to be mature. Now that's just one sample. Whether, if we're talking about someone who only makes three follicles. Well, if you only make three follicles and you're over suppessed, you only make two. That's a really big drop. And so in that situation you might want to have less suppression. So you can try to get all three of those follicles versus only getting two, because then you would be losing 33% of your eggs. Now, even if they spread out a little bit, there's only three follicles. So statistically both two of them are going to be in the same maturity zone. So you're still at the same number. So you don't really lose much in that situation. So seems simple. If you have fewer eggs, less suppression. If you have more follicles, more suppression, right? Nope, that's wrong. So then there's another thing you have to think about, which is early recruitment and People who have higher FSH levels are going to have early recruitment, meaning their body starts releasing FSH earlier than everybody else's. Most people, their max FSH levels can be around cycle day two or three. But people who have early recruitment might be having the highest FSH levels release, let's say cycle day one or even before the cycle starts. And what that does is it causes the follicles to start to grow a little bit earlier. And so in that situation, not using a priming agent could potentially lead to a lead follicle every time. And so if you're doing a cold start or an estrogen only type of priming, you can end up running into the situation where you have a lead follicle. And that's frustrating because now there one follicle is ahead of all the other follicles and you get this kind of cohort that's ahead and a court that's behind. And that can affect how early you have to start things like GAN relics, how early you have to potentially even trigger. So early recruitment is part of what we use to determine what type of priming we're going to use. But the other thing you have to look at, as I mentioned, was FSH levels. If those are high, the priming agents not going to suppress them. And if it doesn't suppress them, you can also develop follles past them. So for example, let's say you're going to be priming someone for two or three weeks. If you put them on the combined contraception, the chances that they're going to develop a follicle when you're ready to start is very low. But if you have them only on estrogen only then they may develop a falicle and now the cycle gets canceled. And so you have to utilize those things such as high FSH levels, such as let's say 18 or 20, they are not going to say suppressed with just estrogen. So you might have to put them on progesterone only in the luteal phase to stop them from developing that follicle. We see this all the time when it comes to frozen embryo transfers. Most clin don't use Lupron. What we do is when someone gets their menses, we put them on estrogen, build the lining up of their uterus and then we put the embryo back. But there are s some women who ovulate past that estrogen and that's because their FSH levels are so high that they're able to ovulate past the estron. That's why you don't really have an estrogen only birth control pill because it doesn't work very well. The same thing is you don't see progesterone only pills that prevent ovulation. Those usually just prevent pregnancy. The best way to prevent ovulation is going to be with a combined contraception. Now there are some unique situations. For example, some people have, lets s say have had GI surgeries and let's say they'absorb things as well. They may need to go on patches because the pills won't be absorbed well enough. Another unique situation is people who have blood clotting disorders. If they have blood clotting disorders, you really don't want to put them on birth control, even if it's for a short time, if they're a high risk. In that situation, we're going to use the progesterone only priming method to reduce the risk of, blood clotting. Another benefit prior to frozen embro transfers is if you were doing a fresh transfer and you weren't really sure if you were getting a period or with just a, uterine bleed, such as people with polycystic ovarian syndrome. One of the best things about birth control is you knew you were shedding your lining that way. When you were putting an embryo back, you knew you shed your lining completely and that way you were putting it back with a new lining versus someone who bled, thought they had their period and then you were building up the lining on old tissue and then doing a transfer. That's not that common anymore since most people are doing frozen embryo transfers. But if you are doing a fresh transfer, it is important to know that that period was really a period. And that's part of the decision making when you're looking at priming. If you have someone who doesn't get a period or you question whether they get a period every month, that may affect how you use the priming protocols such as putting you on contraception combined or esture and progesterone only if you were some with pcos you really couldn't do a cold start because you don't actually get your natural period. And so at that point you would either need to go on contraception or progesterone to induce a period. Now one really unique situation is people have very severe dimeinsional ovarium reserve called premature ovarian failure are also called ovarian insufficiency syndrome. In this situation, women are either near peramont menopause or are in menopause completely and they don't even ovulate anymore. And then you would think you would want to use almost no suppression. But interesting enough, if you give a very high suppression and you get their FSSH levels that go down for a long period of time, let's say like a month, then you stop the birth control and you start high stimulation, you can sometimes get them to ovulate. And so we call those premature overarian failure protocols called POF protocols. So before we get into the balancing of trying to balance the suppression versus the synchronization, let's take a deep dive into each priming method again. So when it comes to the combined contraception, the vanances are it's going to be effective in synchronizing follicles and preventing cyst formation. It may up regulate FSH receptors in patients with severe door or with premature ovarian failure, improving the ovarian response in that situation. The disadvantage is it has a risk for overuppression, especially with prolonged use. N may require longer stimulation or higher doses canadropins because of the suppression. Ideal for patients with irregular cycles who form cyst or who require some type of scheduling. Now, when it comes to progesterone only priming, the advantages are it's going to prevent CST formation with minimal ovarian suppression. The disadvantages are it has limited synchronizations compared to the combined contraception. This is going to be ideal for patients at risk for overstimulation or suppression issues. When it comes to the estrogen only priming, it may improve some minor follicular synchronization. But without almost any suppression, the major disadvantage is that you're not going to get the synchronization and you have the risk of forming cyst. When it comes to the cold start, the biggest advantage is natural without any suppression. The disadvantages completely the opposite. High risk of assistst formation, high risk of not having synchronization. But this can be used in people with very predictable cycles who don't have, let's say severe diminished ovarian reserve or who are able to get cycles. This is why it's so difficult when you're trying to pick a priming method because there's this balance. And as you deal with not trying to suppress someone, they start developing cyst and then you try to stop the cyst and then you could overupress. And so it could be somewhat frustrating because sometimes you have to do it more than once because there can be just things that you can't control. Like for example, if you develop a cyst, your doctor can stop the cyst from coming, but now you're going to be oversupprressed. And so there's that balance. But that means every month you have to keep waiting to try again. And that can be very frustrating. So it's important to understand that in that balance that yes, I know you want to move forward, but if I'm too aggressive, I overupress. And if I'm not aggressive enough, then you make a assist. If you're a patient who has s been through this and had to deal with this, you know what the frustration is like. I think the main takeaway is to understand the importance of individualizing priming protocols and understanding that there is not one right way for everyone and that if your doctor is picking one method, it doesn't mean that they don't care about overupressing you. But in your situation, they're bouncing that synchronization compared to overuppression. And now if you're one who has enough eggs, they're willing to take a small risk of some suppression if it means they get better synchronization. Hopefully this may address your concerns about why a specific protocol was chosen for you or what happens if you over underprime in that situation. In the end, priming for IVF is more than just preparation. It's about setting the perfect stage for your journey to parenthood. Hopefully this episode was helpful for you. Maybe this has been a frustrating part for you when you have to keep trying different primings and get it right. Maybe you just wanted to know about this or maybe you have a friend who's going through this and might be frustrating. You want to let them know about it. As always, if you like this podcast, I greatly appreciate if you can give us a five star review on your favorite medium. Tell your friends about us and get the word out about the podcast. I tried to give a little more in depth science than some of the other podcasts out there. That way I'm not just superficientially telling you stuff, but really giving you what the reasoning is in our heads as fertility doctors. I'm sorry I didn't have the episode last week. I actually was quite sick as you probably heard in the episode prior. Wasn't able to, do one. But I definitely will try to be here again every week and I look forward to talking to you next week on Talk about Fertility Tuesday.