Navigating Fresh and Frozen Embryo Transfers
Choosing between a Fresh and a Frozen Embryo Transfer (FET)?
Join us as we explore the history, current success rates, and the specific clinical and practical reasons why one approach might be better for your unique situation.
Topics Covered:
The evolution of IVF success rates and the role of freezing technology
Clinical indications for a Freeze All/FET
Practical factors like cost savings and streamlined timing/efficiency
Natural, Modified Natural, and Fully Medicated Cycles
As research continues to push the boundaries of reproductive medicine, I keep watching how these protocols evolve to offer insights on the best possible chance at building families.
As always, please keep in mind that this is my perspective and nothing in this podcast is medical advice.
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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.
I get a lot of questions every day actually about the difference between fresh and frozen embryo transfers. And whether one is better for certain situations, for what different protocols look like. And I wanted to spend a few minutes talking about how I think about who should get a fresh versus a frozen embryo transfer. And maybe this will shed some light on your situation. So what I wanted to say is historically, fresh embryo transfers used to be all that there were, right? So people would undergo an egg retrieval, those eggs would be fertilized by sperm, those embryos would grow in a laboratory setting. And then the lab person would, in the REI would put in several embryos with the hope that at least one would take and success rates back in the day were in the single digit percentages. And so, when I talked to my embryologist who is sort of a seasoned embryologist and has been here since the very beginning, he said, if you had told him way back when that we would have a 65 to 70% chance per you put embryo that nobody would have believed that's possible. And so just for some perspective, people would put in what there was, there really weren't even supernumerary embryos in the beginning. And if it worked, it worked. And if it didn't, maybe people did another cycle.
But then there was the ability to freeze embryos and our technologies keep getting better and better. Success rates for IVF keep getting better and better. And so that does afford the opportunity either to freeze embryos at the outset or to go back to the tank and take embryos out in the context of a frozen embryo transfer cycle if the fresh transfer doesn't work. So let's start with frozen embryo transfers in 2025. Who are frozen embryo transfers really meant for? Well, first of all, if you are undergoing IVF for any genetic reason, for in most settings, we cannot really have the turnaround of biopsying an embryo and then doing an embryo transfer in that same cycle.
And so if anybody is doing, you know, PGT for monogenetic disorders or PGT a really those those cycles are freeze all by definition, because we are taking the eggs fertilizing them, growing them out in a lab, biopsying them and freezing them and then waiting to get the genetic data before returning to do a frozen embryo transfer. Now there are people who have said, well, I'm preparing my uterus and I know I'm doing a PGT cycle, but I have this Eupoid embryo in the freezer. Can I transfer it? Yes, you can absolutely do that. But I will say that in my experience, sometimes we do more aggressive simulations for people undergoing IVF for genetic reasons, because we know we are freezing all because we know that our goal really is embryo generation. So we're trying to get as many eggs as possible as is safe for the person.
Sometimes we allow the progesterone to rise a little bit in that context. And so, you know, even though we can do it, everything really has to be, you know, perfect slash ideal to be willing to thaw a very precious embryo and put it into a stimulated environment. I will say that.
So anybody who's doing IVF for genetic reasons really will need a frozen embryo transfer cycle.
What else? If anybody has like a risk for OHS or ovarian hyperstimulation syndrome, that is another reason why we might consider doing a freeze all. You know, there's some data that suggests that for PCOS patients that frozen embryo transfers actually have higher success rates. And maybe that's because the estrogen levels can get over 4,000 or sometimes the progesterone levels start to rise a little bit. But, you know, not for everybody with PCOS, because all PCOS is not the same, but there are some PCOS patients for whom it may make sense to do a cycle, get as many embryos as possible, like Lupron trigger and freeze all those, you know, embryos once they're there, you know, of freeze maturity of, you know, sort of quality to freeze and then return in a different cycle under very controlled circumstances to do a frozen embryo transfer. Also, endometriosis, you know, we know that endometriosis has estrogen receptors and sometimes, you know, doing a stimulation cycle can cause like almost like a mini flare. Some people actually have significant pelvic pain during their IVF cycles if they have endometriosis. And so sometimes it's beneficial to actually do the retrieval, generate the embryos, freeze them all, give somebody Lupron suppression for two to three months to calm the endometriosis down and then to return back and do a frozen embryo transfer, you know, under very controlled circumstances.
And there's also times where people want to embryo bank. So say somebody sees me for the first time at 39 and they want three children. Most people are not going to have three children from one IVF cycle. So, you know, if somebody gets pregnant, they're kind of out and they can't do another retrieval cycle. So embryo banking is a reason to do freeze all until somebody has a sort of sufficient, which is a tricky word to use, but a sort of a number they feel comfortable with in terms of embryos in the freezer, and then move forward with a transfer once that's done. And then also if some pathology is found during the stimulation cycle itself. So, you know, most of us are pretty meticulous about an up-to-date cavity evaluation, but for people who maybe it's been a year-ish and then we might see a polyp on their ultrasounds, you know, sometimes the most prudent thing to do is actually to freeze all in that situation, even though it wasn't recommended and then move forward with a transfer after the pathology is removed. Also, you know, in the context of an IVF cycle, if the progesterone starts to rise, that's a situation where a fresh transfer is likely to be less successful. So we might freeze all in that situation, like unexpectedly, right? But then in the sort of in the name of having a more successful transfer when the labs are looking better. So those are reasons why we might think about doing, you know, a frozen embryo transfer sort of as the first line. Now, why might we do a fresh transfer as the first line, right? I think we've all gotten very, I would even dare to say, obsessed with genetic testing of embryos. I think maybe the pendulum has swung a little bit too far, especially with everything we know now about mosaicism. I think that especially for younger women, PGT outcomes are actually worse when you look at, you know, PGT versus untested embryos. So I think we really do need to be cautious when we're thinking about PGTA. But you know, there are some people who really have a hard time making blastocysts and most labs, I mean, I think my lab at University of Vermont is an exception because our lab directors are very experienced at day three, you know, freeze thaws. However, many, many labs will actually, you know, not freeze at day three embryo just because their outcomes are not as good. And so if somebody, you know, decides to do a transfer on day three, while at least that embryo is inside of their body and has the chance to keep developing in their body, and studies are ongoing, this is a question we really haven't sorted in our field yet. But there are some people where, you know, I truly do think that they have a day three transfer, maybe that embryo would have been barely a morilla in our lab, right, which is not even fully a blastocyst, but it continues to divide inside the body and implants and then it makes the baby. So there are embryos that would not meet freeze quality on day five, day six, but are able to be transferred either on day three or day five, day, you know, day five, really, either of those two, and they actually do make babies. So I want to mention that, you know, being a fertility specialist wanting wanting to give everybody the best shot they can have at having a family, we never want to be discarding normal embryos or embryos that are potentially viable. That's like really not favored upon. But I do think that if we enforce this like strict freeze all criteria on everybody, we probably are doing that. So just to keep an open mind about that. You know, I think that there's like this thing that we can do kind of in a hybrid circumstance where say somebody's like 37, 38, they want a fresh transfer, but they also want to know what's frozen.
You know, if they're not pregnant with that, you know, cycle or say they do get pregnant, they still want to know what's, you know, sort of there with more detail. And so I don't recommend this in young patients, but if somebody's like 37, 38, 39, they want to do a fresh embryo transfer, and then do PGT of the rest, that can be kind of a nice way to blend the two of like, getting a fresh transfer in, which of course is better for timing. But then also, you know, having the data of the PGT, especially if people are like 38 plus, and that data is important to them. Again, it's not a perfect technology. But you know, the data are definitely more encouraging and older women as compared to younger women. So that's a possibility as well. And then I think about factors that are very practical, like cost and timing. And so, you know, at my center, where there's, you know, a decent wait list for IVF, if somebody has a fresh embryo transfer, that's going to be a lot more efficient from a timing perspective. And if somebody has a freezal cycle, and then has to wait, you know, to have a cycle subsequently, and you know, I will say, we have a process for this, so people aren't, you know, sort of at the back of the waiting list. But timing really can be a factor. And especially when sometimes it can feel like so many delays, and it already takes so long to get to IVF in the first place, many people want to try as efficiently as possible. And, you know, as long as it clinically makes sense to do so, the most efficient way to do that is to put the embryo in when the uterine lining is already ready and primed. Also cost, you know, I don't think we talk about costs enough. But the last time I checked doing a frozen transfer sort of in addition to doing a regular stimulation cycle was about an extra $2,000 in medications if people pay entirely out of pocket. And so if you think about it, like, you know, the uterus is already primed in a fresh cycle. So you don't need to like spend money on estrogen, spend money on progesterone. Progesterone can actually be quite expensive. But if you are, you know, thinking about it, and you are able to save that money, for many people, that might be like a vacation or money and investments, or, you know, thinking about all the different ways we can spend $2,000 wisely and judiciously, you know, and for other people, that's a deal breaker, many people aren't able to afford an extra $2,000. And that weighs on their decision process. So I guess in summary, what I would say is, fresh versus frozen, you know, somebody, you know, is poor prognosis, and really, we have a track record of not making blastocysts, then I think a day three, fresh transfer is very reasonable, maybe even a day five, as long as sort of, there's that thought to put the embryo in, but I always say, you know, where's the best place for an embryo and a reputable lab, it shouldn't matter. But there are some people who do get pregnant with day three transfers, and I don't want to, you know, sort of discard that data. So again, we need the study to show what is optimal, especially in poor prognosis patients, poor responders, but in my practice, you know, I always like to put the embryo in on the sooner side, especially if somebody has few embryos, and I'm worried about their ability to make blastocysts, also practical factors like cost and timing for fresh transfer. And then for frozen, you know, if we really need the genetic information for any reason, then it's going to be a freezall. Sometimes with endometriosis, in terms of PCOS, there are some nuances that push us towards frozen. Now, let's talk about frozen embryo transfer protocols for a second, you know, there's a couple of different ways to do it.
There's a fully medicated cycle, which is where we keep the ovaries in the brain out of it, and we focus on the endometrium, we give estrogen, either, you know, sort of pills orally or vaginally, there's also patches that we can give, and then some sort of progesterone, the data suggests that in a completely medicated cycle, some sort of progesterone injections, either every day or every third day, are going to be superior than vaginal progesterone alone. So that's been a shift we've made in the last five to 10 years, based on data. And so fully medicated cycle, estrogen, then progesterone transfer, and then those hormones are continued until about 10 weeks, usually, there's some practice variation, but till about 10 weeks until the placenta is sort of comfortably taking over at that point. And now there's the pen this rise in natural cycles and modified natural cycles. And there's as many protocols, it seems as there are people, I think what's important to remember is that these protocols are based on a typical menstrual cycle.
And there's different ways to do it. You know, some people do like follow somebody's menstrual cycle, if they happen to ovulate every month, and then they put the embryo in at the right time, and give no supplemental hormones. You know, I'm not so trusting of the ovaries. So I don't typically do that unless somebody is like, very, very crunchy granola, and they really want nothing else than that. I always meet people where they are. But my preference is to use a little bit of sort of support. And so I often will use Letrasol, which is a rheumatase inhibitor that helps to stimulate ovulation, we track ovulation. And then, you know, once we see a nice follicle of sufficient size and a thick lining, and a low progesterone, then we use the trigger shot usually, to then cause ovulation. And so then those ovarian hormones are starting. And then we can even give supplemental luteal hormone support to augment that. So that's sort of my protocol of choice for natural cycle FPT. There's also some women for whom the way that they make their best lining is gonadotropins. So the gonadotropins act on the ovaries, the ovaries make multiple follicles, kind of like an IVF. The downside of these sorts of cycles is that there's no retrieval at the end of the day. So like, if you do a fresh embryo transfer, at least you've taken out a lot of those granulosa cells. Although, you know, when you are doing a gonadotropin FPT, all those follicles are still intact. And so you can get hyperstimulation syndrome from this, I want to be very mindful about that. But if there's no other way that somebody is making an adequate lining, or that's where their lining looks the best, then I will often do that, obviously with caution.
And so those are basically the different protocols, you know, if somebody has a history of chronic hypertension or preeclampsia, there are some data that the maternal outcomes in this way are actually better when you look at sort of lower rates of preeclampsia and such with natural cycles compared to fully medicated cycles. And so we do look at that data. Also, if somebody has a very restricted schedule, the fully medicated cycle is going to be better because you start with a transfer date and then you work backwards versus the modified natural, it often can lead to like multiple monitoring appointments at the very end. And then, you know, finally, when it's like ready for a trigger, then somebody comes back roughly a week later for their transfer. So sometimes it's like three daily appointments in a row. And you know, most people who are working full time jobs, that can be hard to negotiate, even though I always advocate negotiating for these sorts of things.
You know, I've had like surgeons and other sort of really busy physicians who have a hard time making all those back to back appointments. And some people take a leave and they make it work.
But I will say the sort of the least amount of disruption to the schedule is going to be with the fully medicated cycle under most circumstances. So I hope that was helpful. You know, I think as we go on with time, we may even be seeing more protocols and different variations and novel therapies, especially as pertains to like thin lining and intrauterine injections, maybe PRP.
You know, this is such an exciting time in terms of reproductive research. I just returned from ASRM conference and I just I feel so inspired by how much groundbreaking research is still happening, even despite the cuts in funding to women's health research. You know, there's so much inspiring research going on, looking at all the different things you would think about in the different areas of reproductive medicine. So I do think this is one of them. I think we're going to continue to see advances with time. And I don't think the story is over. So just as the IVF success rates have gotten so much better in the last 40 years, I think those rates are going to continue to improve, especially with the research that's ongoing. So I hope this is clarifying. I hope you understand this topic a little bit better. And like I said, I'm always up for new suggestions in terms of more science topics to talk about. And you know how much I love you. Until the next time. Bye.
