Primed and Ready: Choosing the Right IVF Prep for Your Body

Are all IVF cycles created equal? Not even close. In this episode of Taco Bout Fertility Tuesday, Dr. Mark Amols dives deep into the science of IVF priming—covering everything from birth control pills, estrogen, progesterone, and Lupron to the emerging role of androgen priming with DHEA and testosterone. Learn how synchronization, FSH receptor upregulation, and strategic suppression can make or break your cycle success. Whether you're a poor responder, have PCOS, elevated FSH, or premature ovarian failure, this episode will help you understand which IVF priming protocol may be right for your body. It’s time to move beyond cookie-cutter fertility care and personalize your path to pregnancy.

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Transcript

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Today we talk about IVF priming. A deeper dive into this topic. I'm Dr. Mark Amols and this is Taco about Fertility Tuesday. Back In December of 2024, I did an episode on priming for IVF. It was titled Balancing Synchronization and Suppression. But today we're graduating from priming 101 and going to priming 201. Because when it comes to IV of success, the devils in the details, and trust me, the devils love to mess with eggs. Ever heard the devil eggs? So, as we discussed the prior podcast, priming before IVF is often misunderstood. You might think of it as just taking birth control, but it's much more nuanced than that. Today we're not going to cover the basics. We've done that before. But in this episode, I want you to understand how we choose the right priming strategy for each person and why it's not a one size fits all type of situation. We're diving into real strategy, research and results. Think of this as, a kind of behind the scenes director's gut of your IVF cycle. The first question is, what is priming? Well, as you would see in my last episode, priming is the pre treatment before ovarian stimulation. Its goals are going to be synchronizing the follicles, preventing cyst formation, modulating the FSH and LH levels, improving the follicular response, upregulating, the FSH receptors to enhance stimulation. And sometimes it's just used to figure out how to put you in the cycle. And yes, it can absolutely backfire if done wrong. So as you can see, although a lot of people think of priming with birth control as just being a way for the clinic to schedule your cycle, there is more benefit. Synchronizing eggs is important. Stopping you from getting cyst is important, allows you to go on with your ivhip cycle. Increasing FSH receptors, but through up regulation is going to increase your stimulation efficiency. But with too much depression, you may lose some eggs. With too little suppression, you may get a leaf follicle that ruins your cycle that needs to be canceled. This is where the balancing comes in. So when it comes to synchronization, the way I like to think of this is if runners are going to be in a race, if you don't put everyone on the starting line, then they're going to just start whenever they want. And sometimes one of those runners are going to be halfway down the track before the others start. So synchronization gets all of the runners to start the starting line that's going to give us a better chance of synchronization. But why does it matter? Obviously, if you have a lead f call situation, the follicles can be so far ahead it may ruin your cycle. Now you have to let some eggs get too big. That can lead to post maturity, and then you have to try to get the other eggs to grow behind those. If you have 16 eggs, but then taking a birth control makes you only get 15 eggs, that's not a big deal. But if you only have three follicles, even one being suppressed is already too much. But it's not just about synchronization. As I mentioned, this also helps with recruitment of follicles because it upregulates deficits receptors. Some types of prime is going to actually prevent ovulation. So for example, if you start with a lubron priming, you're going to continue it through the cycle, which also then prevents you from ovulating. Now, it's important to understand you don't have the prime to do IVF. You think about it, when you do things like IUIs, you don't prime first. It doesn't mean you can't. But it's not very common. And that's because you're just trying to get a few eggs. So it's not a big deal of maybe they're not completely synchronized. It's like walking with three kids. It's okay if they're not synchronized because you can see them all. But you take 20 kids and now you put them in the line because you need to see them all at the same time there. Time synchronization is good. There's time that's not needed. So when you don't do any type of synchronization, we kind of call that a cold start, where you just start simimulation on the second or third day of your natural period. And many people do very well with this. The challenge is, identifying who benefits. And for most people, you don't want to learn through trial and error that that didn't work for you. So instead of guessing which patients will do better with cold starts, most clinics will just do some type of priming. But at that point, that's where we go into our toolbox to determine what type of priming is best for you. So let's define the different types of priming. There's going to be the cold start, which again is just starting on the second or third day of your period. Then there's the classical OCPs, birth control pills, Then there is estrogen priming, progesterone priming is the next. Then there's Lupron priming and there's even androgen priming. Now what's interesting is when you start some of those primings, some of them can be started at the beginning of the period, some of them can be started in the luteal phase after you oulate. A newer protocol now is using stimulation in the luteal phase. This would be very similar to, what people call duostim, where they go through a retrieval and then as soon as they retrieve their eggs, they start again. That way they're stimulating in the luteal phase. So let's talk about the pros and cons of all these different ones. So the pros of a cold start is that there's no suppression. It's good for people with regular predictable cycles. But the risk is there's going to be very little synchronization. You can't really plan around it because you don't know when your period is going to start. And potentially you could have a cyst before you start the process, throwing off the whole cycle. Whereas with birth control, you can be suppressed with the birth control so you won't develop a cyst. So that way you can start on the day you want to. Birth control is going to give you great synchronization. It's going to help prevent things like early recruitment and prevent cysts from forming. However, for some people, it may not be good people who it's going to overupprress. Women with diminish ovarian reserve, and that is significant. Dimenish ovarian reserve may not benefit from birth control. It's not a rule. There are times they do benefit from it. Some women with polycystic ovarian syndrome don't benefit as well from birth control. Some do. And then the type of birth control you use matters as well. When you're talking about taking birth control for preventing pregnancy, we usually like to use low dose birth controls. But when you're talking about for priming, you usually want to use something with a little bit of a stronger progestin component and will have at least a little bit higher estrogen component. Now it's not wrong to use a different birth control. It's just that if it's not strong enough, you can then ovulate past it, which again will cause your cycle to be canceled. When, when it comes to estrogen priming, there are definitely two ways to do this. You can start the estrogen at the Beginning of your cycle, like on day two, or you can start in the luteal phase. For me, I like to use it in the luteal phase, especially for people who have early recruitment, because I can then stop them from developing follicles very early versus if I start on day two of their cycle, theirby has already recruited the follicles that may ovulate past it. The people best for estrogen priming are going to be people who really don't have high FSH levels, and then you can just start them on the estrogen on the second day of their period. This is actually very similar to when you're doing a embryo transfer. You'll start the medicine on day two because it will be good enough to suppress you. But for people who have high FSH levels or known early recruitment, which usually means you have a high cycle day three, estrogen level, you're going to want to start that estrogen in the luteal phase. Otherwise it may be too late. By starting on day two, the benefit of estrogen priming is that you're able to get some mild synchronization. You also are going to have less suppression. But the con is the synchronization is going to be okay, and it's not very suppressive. Many people will ovulate past estzrogen priming, especially if it's started at the start of a menstrual cycle. The most significant type of priming is going to be Lupron. This is what's called a gna agonist, and this is very powerful. It actually suppresses the pituitary gland, putting you in like an, early menopause. The benefit of it is it takes your body completely out of it. There is no way you're going to need to develop a follicle on this. There is no way you're going to have early recruitment because your body can't do anything. It's basically paralyzed. All of the growth is going to come from the medications that we give it. As you can imagine, in today's world where we have antagonists now to prevent ovulation, we don't have to use GRNH agonist, and so we don't have to over suppress people. But there still is a time that's beneficial sometimes for people who ovulate past everything you do, you can use a GRNH agonist as long as they have good ovarian reserve. Now, the other group that may benefit from this are women with endometriosis, especially if you're going to do a transfer While being on lowbrn. Now you can start it as a priming agent, go through the ivf, keep them on the Loupron and then go into the transfer. Now, this does not mean every person with endometriosis should be on the gener H agonist Lupron protocol. This protocol is a very old protocol that everyone used to use, but we don't use as much. But in the right conditions, it may be worthwhile for most people with endometriosis. You're just going to do a standard antagonist protocol. They may even put Femaar on to lower your estrogen levels during the stimulation. But if you have good ovarian reserve and you respond well, a long Lupron gener agonist protocol is not always a bad thing. Another type of priming is progesterone priming. There's a couple ways to do this. You can do just a weak progesterone like northingro acetate or meddroxy progesterone, and you can start that on the second day of their period and use that kind of like a birth control. You can also start it in the luteal phase as well. If you want to suppress someone. This is a little stronger than estrogen, so you're going to get better synchronization. It's going to be a little bit more suppressive than estrogen, but it's still not as suppressive as birth control or even close to a Lupron cycle. However, there is another form of progesterone priming and that is where you actually continue it into the cycle. Here you start someone on the progesterone primum, keeping them on it, and then just start the stimulation and never come off of it. The purpose is it works almost like an antagonist. It's going to suppress the lh, which is sometimes great for people with polycystic ovarian syndrome. And the chances of ovulation during the cycle are very low. Now, there are some downsides of this. One of them is you can get some irregular bleeding. The other thing is you can't do a fresh transfer if your clin is doing fresh transfers. But if you're doing freezoles, it's actually a very valid beth the priming and can also be used as your antagonist to prevent ovulation during the stimulation. There are actually some studies out there that show that there's some non inferiority of using this type of progesteroin priming compared to antagonal cycles. The last type of priming that I did not go over in the prior podcast is androgen priming. Now a lot of the patients will take DHEA because we know that that will help a quality and sometimes help even poor responders. But you have to take it for a very long time and evidence out there is a little bit mixed. Some studies have shown a lot of benefit, some have shown not much benefit, but again you need to take it for about three months. The other option is theres some promising data showing that testosterone for six to eight weeks may help poor responders and improve egg quality. Now kind of like dhea, the studies are not very affirming. Some studies show theres some benefit, other studies show there isnt t. But overall there appears to be some potential benefit. Now unlike the other priming methods, in this situation it is not the only agent for priming. Sometimes people will use this with other priming agents or they will use it alone. I personally don't use this. However I'm aware of it and looking at it and seeing if it's a valid option in the future. So as you can see, choosing a primary method isn't just any meany miny mo. It's like cooking an egg. Whether you scramble it, poach it sun side up, cook it all the way through, each method can work but each method can also be disastrous depending on your taste and in this situation your biology. So what does the research show? Well, the research is not going to be as beneficial as you would like. Basically it's kind of all over the place. Research has shown that when using priming you do increase FSH receptor UP regulation which does improve the response. Research has shown that with andron priming there is some improvement in poor responders and that with DHEA it's not as convincing. However, no one has ever come up with a nomogram. There is no absolute way to know who needs what. This is where your doctor takes the information about you and then determines what's the best option. Sometimes it's not right. Maybe they start with estrogen priming and then you ovulate past it and have to cancel a cycle and then they go okay that didn't work, let's try something different. And that's because there is no research showing which protocol is best for each person. We just know that sometimes it can be better. So it's never wrong. It's kind of like an educated guess when they're picking that priming protocol. What we do know is that cold starting everyone is not always good. That can be very bad for some people. Just like Putting everyone on birth control would never be good. And that's really what the research says. If you're taking everyone as a whole, there doesn't seem to be much benefit. So whether you're doing cold start birth control, estrogen priming or even progesterone priming, there really isn't that much difference. However, that isn't true when you start looking at tailored special populations. In that situation, there is some benefit. When you look at poor responders, there is a wide spectrum of poor responders. A poor responder can be someone who has, let's say, young but just doesn't have a lot of eggs. A poor responder can be someone who's 44 and doesn't make a lot of eggs. But there's a difference there. If you take that first group who are young, have a decent ovarian reserve, but are poor responder, what we find is OCPs, which are birth control actually helped them versus if you gave that birth control to someone who is older, who has fewer eggs, it will likely hurt them. Polycyst ovarian syndrome is another area. Osops in some situations, such as a fresh transfer is not good to do. It would be better to give them something like Proera to induce a period and just start them or use one of those progestin protocols we talked about. However, if you're doing a frozen transfer, it's not going to matter as much. Someone with a high, let's say baseline FSH level has diminished ovarian reserve and they don't fall into that first group of young with a good reserve but poor response. So for them you don't want to give them birth control. You would want to give them something like estrogen or one of those progestne protocols which will prevent early recruitment and get better synchronization. Whereas if they did a cold start, they would likely get early recruitment and have to cancel their cycle. We talked about people with endometriosis. They could benefit from a lot of suppression by suppressing their endometriosis. Another group which you would never believe are people with severe din ovarian reserves such as premature ovarian failure. These are women who have actually gone into early menopause. And whats weird is they get them to ovulate, you actually have to give them a high suppression of birth control, sometimes double dose and then with that a severe suppression, you then hit them with an aggressive stimulation and they can yield eggs. Sometimes that's completely counterintuitive to the other situation where someone has dimin ovarian reserve. The point is, there isn't one best protocol. It has to be tailored to the person. The point is, it's all about strategy. Priming isn't about doing more, it's about doing what's right for your biology. Whether you're using estrogen to block early recruitment or testosterone to wake up sleepy ovaries, the key is individualization. So when you're getting frustrated by switching priming protocols or getting canceled cycles, know that it's not trial and error out of guesswork. It's about dialing in what works for you. IVF is chess. It is not checkers. Hopefully today's episode helped you see the thought process behind priming and why your cycle might look different than someone else is. If you found this episode valuable, please give us a five star review on your favorite medium and share it with someone else in their IVF journey. The idea for this episode was brought to us by Caitlylin, who is going through her own IVF journey and recommended this episode topic. If you're interested in sending me a topic that you'd like me to do, send it to TBFT for Taco Bell fertility Tuesday at newdirectionfertility.com and I'll definitely put it on my list. Hope to see you again next week. on Taco Bo Fertility Tuesday.