Frozen Embryo Transfers Demystified: Natural, Modified Natural, and Programmed Cycles

In this episode of Taco Bout Fertility Tuesday, Dr. Mark Amols dives deep into the world of frozen embryo transfers (FETs). If you’ve been through IVF, chances are you have frozen embryos ready for transfer—but how do you decide the best way to prepare your body for implantation?

Dr. Amols breaks down the three main approaches to FET cycles: natural, modified natural, and programmed cycles. You’ll learn:

• The key differences between these transfer techniques.
• The pros and cons of each approach, from medication use to cost and scheduling flexibility.
• How your medical history, lifestyle, and personal preferences play a role in choosing the best method for your transfer.
• Why success rates across these techniques are comparable when tailored to individual needs.

Dr. Amols also discusses common misconceptions, logistical considerations, and patient concerns like medication side effects, timing, and monitoring progesterone levels. Whether you’re looking for a natural approach, a controlled schedule, or something in between, this episode provides the clarity you need to make informed decisions.

Join us to demystify frozen embryo transfers and empower yourself on your fertility journey. Don’t forget to share this episode with others who may benefit and leave a review to help more listeners find Taco Bout Fertility Tuesday!

Thanks for tuning in to another episode of 'Taco Bout Fertility Tuesday' with Dr. Mark Amols. If you found this episode insightful, please share it with friends and family who might benefit from our discussion. Remember, your feedback is invaluable to us – leave us a review on Apple Podcasts, Spotify, or your preferred listening platform.

Stay connected with us for updates and fertility tips – follow us on Facebook. For more resources and information, visit our website at www.NewDirectionFertility.com.

Have a question or a topic you'd like us to cover? We'd love to hear from you! Reach out to us at TBFT@NewDirectionFertility.com.

Join us next Tuesday for more discussions on fertility, where we blend medical expertise with a touch of humor to make complex topics accessible and engaging. Until then, keep the conversation going and remember: understanding your fertility is a journey we're on together.

Transcript

0:00

Today we talk about different ways to prepare for a frozen embryo transfer. Natural, modified, and programmed. I'm, Dr. Mark Amels, and this is Taco about Fertility Tuesday. In today's episode, we're talking specifically about frozen embryo transfers. If you've been through ivf, there's a good chance you have frozen embryos and you're ready for a transfer. Whether it's the first, the second, maybe you're coming back for another child. There's a good chance your embryos are frozen. That's because overall, there has been a shift in the way we do frozen embryo transfers. In the past, we used to do fresh ones, but now we freeze most embryos and do the transfers later. It's not wrong to do fresh transfers, and some places still do them, but, most do frozen transfers. And so today we're going to talk about the different types of transfer processes, such as the natural, modified natural and program cycles. What I can tell you at first is almost all programs are going to be doing program cycles. That is going to be the norm. Additionally, they may have natural cycles as well as modified natural cycles. So in this episode, we're going to talk about these different techniques, we're going to talk about the pros and cons of each, and then we're going to talk about why is one chosen over the other and if maybe one might be better for you. So the first part is defining what is a frozen embryo transfer. Essentially, it means that you have an embryo that's frozen and now you are transferring it. So you're thawing it and then putting it back in the body, versus a fresh transfer where the embryo was growing in the petri dish and then was transferred fresh into the uterus without ever being frozen. The benefit of this is by freezing the embryo, if you were in a cycle with high estrogen levels, that could have caused progesterone levels to rise, affecting then the implantation. So by freezing it, we're able to give the endometrium the most optimized hormonal milieu for better receptivity and to achieve a successful pregnancy. In the past, we didn't do this because vitrification wasn't around. And so the freezing and thawing wasn't that good. And so it was scary to freeze embryos, but now there's a much higher success rate of thawing them. And for that reason, many programs have moved to frozen embryo transfers. The other benefit is it also reduces ovarian hyperstimulation, since you aren't creating hyperstimulation. And getting pregnant and causing it then to turn into secondary ovarian hyperstimulation. Now, a program cycle is a cycle where you are taking, like, estrogen, building up the lining, and checking with ultrasounds. And then eventually, once the lining is thick enough, then you start progesterone injections, and then you do an embryo transfer. Now, the estrogen you use can be different types. It can be pills, be patches, it can be injections. The point is, you're programming it from the standpoint of you're giving estrogen, you're watching the line grow, and you're controlling it. And then you can pick the data exactly when to start the progesterone before doing your transfer. Whereas in a natural cycle, what you are doing is you're just allowing the patient to develop a follicle on their own. And then some places will actually check for LH rises by checking ovulation kits. And then as soon as it's positive, then they perform the transfer approximately five days from ovulation. Now, in a modified natural cycle, we're not leaving it completely to chance. So sometimes the LH kits aren't perfect, you're not sure about the ovulation. So now what we do is we are watching natural ovulation. We might even give some medicine like letrozole to boost the stimulation a little bit. Then we watch those follicles grow, and then when it gets to the point, when it's ready, we then give a trigger shot. So that way we can time the transfer exactly where we want to, and then we do the transfer. So in the end, natural and modified natural cycles can technically use vaginal progesterone because you're making progesterone naturally through the ovulation, whereas with a programmed cycle, you're going to need to use some type of injectable progesterone. Now, some places may use injectable plus vaginal progesterone, but usually you will not use vaginal progesterone alone in a program cycle. So let's dive deeper into the differences of the pros and cons of each one. Let's start first with natural cycles. If you're someone who likes to do things very natural, in this situation, there are no medications, so you're using a natural hormonal environment of your body to build up the estrogen, to build up the lining. And so that also leads to things like lower cost, fewer side effects for medications. And as I mentioned prior, you can use vaginal progesterone. So if you don't Want to supplement with injectable, you can use vaginal. Now, there may be some places that don't use any progesterone, but I would not recommend that personally with an embryo transfer, because if there is any type of luteal phase defect and it's not recognized, you could have low progesterone levels. And that is known to reduce the success of an embryo transfer. Now, one of the cons of this approach is if you are someone who doesn't have a regular cycle, this is not possible. And it would actually be somewhat inappropriate to use in someone with irregular cycles, because now you don't know if the ovulation is correct or not. And that would be taking too much risk. And that's really one of the biggest things here, is that to be able to use this, you have to have basically pretty precise ovulation. And so if you're not very good at determining your ovulation, it can throw things off because there's some bit of unpredictability in this. And so you need someone who has very regular cycles to be able to do this. There's also a higher risk of cycle cancellation. Not every place is open every single day. And so if your ovulation falls in a time where your transfer should be, let's say, on a holiday like Thanksgiving coming up, you might have to get canceled by also having the unpredictability of the timing, it means you can't even plan ahead for the transfer. Now, once you ovulate, you'll know when your transfer is going to be. But up to that point, your schedule is kind of wide open waiting to when you're going to transfer. Now, with the modified natural FET cycle, it's going to be somewhat similar to the natural cycle. But now we're adding some medications, not excessive, but enough to help support the follicular growth to get a better ovulation and potentially a better corpus luteum to, help with those hormones. One of the nice things is because we're watching it with ultrasounds, the timing is controlled. So what that does is allows you to have a better idea of when your traffic is going to be, because we can see as the follicles are growing, when they're probably going to be ready. And we can maybe adjust it a little bit to help with scheduling conflicts. One of the benefits of a modified natural cycle over a natural cycle is it reduces the risk of premature ovulation because we're going to be using an HCG trigger versus just guesstimating where it is based off of the ovulation kit. In summary, some of the biggest benefits of a modified natural cycle is that you get to use fewer medications compared to a program cycle, but more than the natural cycle, and has a lower cancellation risk than the natural cycle, and yet still allows you to use vaginal progesterone versus injectable progesterone if you don't want to use injections. The benefit of program cycles is the predictability and very easy to schedule. Matter of fact, if you're out of state, such as at, our clinic, you now know exactly what day you need to show up to do your transfer. This allows families to be able to come together because they know the day that it's going to be. When it comes to natural cycles, we talked about how irregular cycles are very difficult to do and actually inappropriate to do in those situations. And in those situations, you should either be using a modified natural cycle or you could be using a program cycle because their irregular cycles doesn't matter anymore. One of the other benefits of a program cycle is you have complete control. If the lining is not ready, you can wait longer. If the lining is ready earlier, you can then start progesterone sooner and do the transfer sooner. You can't do that with a natural or a modified natural cycle, because once the body is ready to ovulate, that's the end. So the line's not thick enough or the line's not ready, you can't just wait. Now, the obvious downsides of a program cycle is it is the least natural when it comes to doing, an embryo transfer. Now, as I mentioned, that's not always a bad thing, because that allows things like predictability and people that full control. But there also is higher costs now because now you're taking daily medications. And so if you don't want to have to take medications every day, this can be a cycle that you may not like as much. And then there's also more side effects because you're taking more medications. And with this type of transfer, you do need to use injectable progesterone. This is because since you don't ovulate, you don't make a corpus luteum, which is what makes progesterone. And so if you don't make a corpus luteum, you have to get progesterone another way. And oral progesterone and vaginal progesterone are not sufficient enough with a frozen embryo transfer. Now, before I get into how I choose to do a transfer with someone or why I would recommend one over the other. I think it's first important to understand that when you look at the pregnancy rates between all these different types, they're about the same. There's definitely a caveat to this, which I'll get into, but overall, they're about the same. I do find that some papers have shown natural cycles do have a lower pregnancy rate than modified natural, but we don't know if it's because of the natural cycle or is it because maybe something got missed, such as the ovulation was incorrect. So you can't really say it doesn't work as well. We just know that there are more opportunities for error in those situations. So overall, I'm a big fan of program cycles. I think it allows you to have the most control, and that way I can adjust as needed. And I can also know exactly when the transfer is going to be, which helps the patient as well for planning purposes. As I mentioned, if you are a clinic who is doing, let's say, natural cycles and program cycles, then your menstrual regularity is going to affect what you can do. If you have very irregular cycles, you cannot do just a plain natural cycle. You would have to at least do a modified natural cycle or do a programmed cycle. This means women with polycystic ovarian syndrome would need to at least do a modified natural or programmed cycle. One of the other things I use when trying to determine what's best for a patient is looking at their comfort. There are some people that just cannot tolerate the injections, and maybe they've had a pregnancy before and they're like, I never want to do that again. Maybe they have a, complete fear of the needles. In that situation, I'm going to use a modified natural over a program because obviously I don't want to put them through something they don't want to go through if it's that severe of, a concern. The reason I like the program cycle more is because not only do I have the control, but I can check progesterone levels and know exactly where they're at. Whereas with a modified natural, the hormones are coming from naturally, but also the vaginal progesterone. And you can't measure the vaginal progesterone because it's not the local progesterone that you can measure. You can only measure the systemic, and there's not much systemic that's coming from the vaginal progesterone. Now, as I mentioned, at, my clinic, I usually use the program cycle, and I say over 90% of people use that. But one of the things I do is when a patient is going through the IVF cycle, you'll notice that even though we're checking the follicles, we keep doing a lining check. Now, part of that's because in the past, when we did natural transfers all the time, with fresh transfers, you would need to know that the lining looks good. So you knew when you're going to be putting the embryo back. It looked good to put the embryo back. But why do we keep doing frozen embryo transfers? I mean, it's not like we care what the lining looks like, because we're not going to transfer it into that lining. Well, for me, why I keep doing it, it's because it gives me a preview of what the endometrial line will look like when we're ready to do an embryo transfer. And so I look at that number, and if it's very low, then I know I need to be concerned. Eventually, when we get ready for the embryo transfer, I can preemptively start looking at things to figure out if there's other things we can do to help. On the same token, if it goes very well, but then we get ready for the program cycle, and now they're struggling to build the lining, then I can always say, hey, I remember when we did the natural cycle, meaning the IVF cycle, I saw her follicles growing, and once the estrogen level got to a certain point, her lining looked good. So then I can compare that estrogen level during the program cycle and say, does it look good then? And if it still doesn't look good, then I know for some reason her body isn't responding as well to those medications. And then I'll switch her over to a natural cycle, specifically at our clinic, a modified natural cycle. Now, there are some clinics who will just try different things. So if one doesn't work, they jump to another one. If that doesn't work, they jump to another one. Now, I personally don't think that's a good idea. I think that you should be looking at it from the standpoint of picking a method that works and then making adjustments based off the data, not just trying different things. So, for example, if I was using a program cycle and everything was going well, but it just didn't work in the transfer, I'm not concerned that the program cycle was the reason why, but I'm concerned about maybe timing issues. I might need to do things like doing the era, or I might be worried about the Receptiva test looking at the receptivity of the uterine lining, because maybe they have underlying endometriosis or inflammation. But the point is, I don't go just jumping to different protocols, because it's not the protocols that change things. The protocols are just for us to get to that lining to do the transfer. And as I mentioned, really one doesn't work better than another when it comes to pregnancy rates. Now, I mentioned that there really is no difference in the pregnancy rates. I mentioned about how I think modified natural is better than natural and have seen some papers that show there might be a slightly higher chance of a modified natural than the natural cycle. But I also want to be fair and explain that there is also some papers out there that say there might be trends of showing more miscarriages when you do a program, cycle versus a modified natural and natural cycle. Now, it's important to keep in mind this is not scientific evidence, just showing certain trends, and there needs to be a study done to actually determine if that is true. In summary, it's important to know that there are different ways to do embryo transfers. When you look at these different things, there's cost differences, there's logistical differences when it comes to timing, and there's also emotional and physical differences between them. Depending on your medical history, such as polycystic ovarian syndrome, you may not even be a candidate for things like natural cycles. And if you're someone who has maybe had concerns with miscarriages, you may want to use a programmed cycle. So now you can measure that progesterone. That way you can keep a close eye on it. Since we know lower progesterone levels can affect your chances as well as miscarriages. One of the coolest things about fertility is it's constantly changing. The science is amazing, and we're adding AI to everything. We are now doing much more studies than we ever have in the past of new techniques and new ways to analyze things. I wouldn't be surprised if in the future we start having measurements of uterine contractility and maybe even doing things like looking at the metabolomic milieu of the endometrium. Maybe someday there will even be a test for which type of embryo transfer we should do. But until then, I wanted to make sure at least you knew about these and not to be worried about using each of them and knowing which one kind of benefits more than others, so you can be a further advocate in your journey. As I always mentioned, it's never wrong for a doctor to do one of these. It's also not wrong if they don't do one of these. The reason they do it is because what they're good at and their pregnancy rates are because of doing what they're good at. I hope this episode was helpful to you. Maybe you know someone else who may be beneficial to you. If you do, let them know about it. And if you like this podcast, as I always say, please give us a five star review on your favorite medium and tell your friends about us. I want to make sure that everyone also knows about another show that I do with Dr. Wael Salem called Sperm Eats Egg, which is every other Wednesday. We've done 20 episodes so far this year and it's a great place for education and also for you to ask your questions directly live. While we're on air this week, we have an amazing guest with us, Allison Rogers, who is a great reproductive doctor in Chicago. I hope you should check out that episode. If I don't see you on Wednesday, then, I look forward to seeing you again next week. talk about fertility Tuesday.