SART Fertility Experts - IVF Add-Ons Explained: Do They Improve Fertility Success or Just Add Cost?

IVF add-ons have become a growing part of fertility treatment, but do they actually improve success rates? In this expert-led SART podcast episode , reproductive specialists explore the evidence behind common IVF add-ons and whether they truly benefit patients.

Procedures like the Endometrial Receptivity Assay (ERA), routine ICSI, assisted hatching, and time-lapse embryo imaging are often offered with promising theories. However, research shows many of these add-ons may not improve live birth rates and can increase costs, treatment time, and potential risks.

The discussion highlights the importance of evidence-based medicine in a field that rapidly adopts new technology. Patients are encouraged to ask critical questions about effectiveness, risks, alternatives, and clinic-specific outcomes before choosing additional treatments.

Ethical considerations and informed consent are central to making confident fertility decisions. Whether you are starting IVF or reviewing your options, understanding the role of add-ons can help you choose the best path forward.

Hi everyone, welcome to another SART podcast. I'm Mark Trolice, a Reproductive Endocrinologist and Infertility Specialist in Orlando, Florida. I am here with Micah Hill, who is a Reproductive Endocrinology and Infertility Specialist in Maryland at Shady Grove Fertility.

I would give you a bio on Dr. Hill, but it would take the entire length of this podcast. He is involved in every aspect of our society, the American Society for Reproductive Medicine. He is a role model for education and mentoring younger physicians, as well as educating patients.

I'm delighted to have Micah here with us today. Welcome, my friend. It is a pleasure to be here, Mark.

Thank you for inviting me. My pleasure, indeed. We are recording live at the American Society for Reproductive Medicine annual meeting here in San Antonio.

The enthusiasm is infectious. I wish you all could be able to see us live when we are recording this. Today's topic is one that is of importance to academicians and those that practice evidence-based medicine.

It's called IVF add-ons. Our field has traditionally been one that advances technology, sometimes putting the cart before the horse. Micah, could you tell us what your understanding of it is for the patients to know what IVF add-ons really mean? I think the very nature of the word add-ons is pejorative.

By definition, it means we don't have evidence for it. The things that we have evidence for are by definition no longer an add-on. They are a necessary treatment.

The fact that we even have to have this discussion about add-ons and that ESHRA has developed this whole guideline to evaluate these add-ons does give us a bit of a view of the state of affairs of how we practice IVF. I think it's inherent to the type of physicians that are attracted to our field. Our field is very young.

We are very cutting-edge. We are innovating. We are learning and advancing new science all the time.

By definition, we are attracted to this because we want to push the boundaries to help people get pregnant. That can also be a negative when we adopt things too early, when we add things like the ERA before we have trial evidence that shows that it works. Then we wait until there are hundreds of thousands of those that have been done.

Then we say, now we have the studies that say we don't have it. The risk of being an early adapter, which I think is a field is what we are prone to do, is that we end up giving things to our patients that aren't to their benefit. There could be some harms in doing that.

There is not always no harm. Well said. There are financial concerns.

There are actual risks of procedures. Then there is also the ethical concern. Is it appropriate to be offering non-evidence based medicine to patients without certainly their knowledge of the fact that it is somewhat experimental if it is not standard of care? Let's define some of these.

Before we go too far into that, let's define some of these. You mentioned ERA. Let's be more specific for our patients.

What are some examples of these add-ons that are not yet proven enough to be standard of care? Sure. I think the Endometrial Receptivity Assay was certainly one of those. That is where they do a throw-mock frozen embryo transfer cycle.

Instead of transferring the embryo, on that day they do a biopsy. They look for the expression of certain genes in the endometrium at that time that are known to be important for implantation. If there are either too much of that or too little of that, you can adjust your progesterone exposure.

In theory, and based on some of the preliminary evidence, fascinating, wonderful idea, but in practice it didn't really bear out. Another example that can sometimes be an add-on and sometimes not is ICSI, Intracytoplasmic Sperm Injection. That's where they take a single sperm and inject it into an egg.

We have pretty good data that for patients, especially those with severe male factor, that's beneficial. For guys where the sperm has issue with motility, for swimming and finding the sperm, being able to bind to the sperm and penetrate it, helping the two DNA packets, so to speak, get to each other can help for fertilization to occur. We've taken that to the other extreme and say, let's just do it for everybody then.

If it's good for some, it could be good for others. And that's been shown to not be effective. That has been quite clearly shown to not be effective.

There's a couple clinical trials now that show no benefit. The observational data sets are huge, tens of thousands to hundreds of thousands of people showing no benefit. And some of those data sets, they actually show harm.

And there may be some advantage to that natural selection. Maybe we were designed this way or evolved this way, depending on your perspective, so that the best sperm finds it and gets there and fertilizes it. Maybe we're disrupting the cytoplasm of the egg or the spindle, the meiotic spindle, by putting that needle into it.

We could potentially be doing harm. So in theory, there are reasons that we could be doing harm. So I think those are a couple recent examples of these add-ons.

And as you say, there's cost. And certainly, when cost is such a barrier to care for our patients, adding cost is bad. In the case of the ERA, you can be adding a couple months of time.

And time is really important. For David Sable, it's one of his three pillars of how we improve IVF is time to pregnancy and cost for pregnancy. Some of these add-ons can violate both of those things, as well as what you said, the potential ethics of how we do this.

Yeah, another one that has been hanging around our field for a long time is assisted hatching, where you can make a little incision around the shell of the embryo intuitively. And I think some of these were spurred on by intuitive hope, essentially, that we're going to get better outcomes. But making that little incision has not been shown to improve outcome.

Let's switch over to AI. There's so much that's being explored now in that field. And while there's tremendous enthusiasm, we're not really clear that it's going to improve outcome.

Like, for example, time-lapse embryo imaging. Tell us a little bit about that. So time-lapse imaging is where they put a camera inside the incubator, and they actually take images of the embryos more frequently.

So historically, we've taken the embryos out sometimes every day at the start of it. Some of us now only take the embryos out the day of fertilization and not until the day of blastulation. So we only take the embryos out twice.

But the time-lapse, in theory, leaves it in there and gets us a whole bunch more pictures of what that embryo does. And this should give us some promise that maybe we'll learn some things from how that embryo grows that would then help us predict the best embryo to transfer. So rather than one image on day five, what if we have a thousand images over five days? And what if that helps us predict which embryo to transfer? It sounds like another wonderful idea, just like the ERA.

But again, unfortunately, the studies have shown us that has not improved the best embryo to transfer for the patient. And you don't have to take the embryos out. Like I said, in my practice, we only take them out on that day of blastulation.

So the theory that leaving it in undisrupted culture, you can do that without time-lapse imaging. Now, the question, can AI maybe figure out something that we haven't? That's potential there. Like what AI is really good at doing is pattern recognition.

So in things like radiology, where you're looking at a million x-rays, can it detect a pattern for lung cancer, early lung cancer, that we might miss as the radiologists? Maybe there's something that we as the embryologists looking at these thousands of time-lapse images have missed that AI can detect. Maybe, but maybe not. And so the AI question is interesting.

I think there's a lot of promise there. I have yet to see it move the needle practically in any of the studies that have come out. When you look at a technology that could make sense to employing, we really have to hold ourselves to the standard that we have to prove that.

And unfortunately, if we can't prove that, at least much more informed consent as opposed to just trying it. And I think the financial risk is that if the clinics invest in significant technology, then there's going to be, who's going to pay for that, right? So that could be passed over to the patient, yet we don't have the evidence that it's going to improve outcome. Yeah.

You know, in the UK, these add-ons are advertised, they looked at time-lapse, 67% of websites were advertising time-lapse, 47% PGT, which we haven't gotten into too much, and that's a bag of worms right there, and then assisted hashing about 28%. So I did bring it up. Would we consider PGT an add-on? Yeah, I think if you're saying what should be standard of care for all patients, yes, I would consider PGT an add-on because I don't think we have the evidence that it should be standard of care for all patients.

And I just want to step back because I think you touched on something that's really important. When clinics invest in these technologies, when we don't have evidence that it's going to improve patient outcomes, to me, that is on the clinic to bear that cost while they're doing the research to prove that it's going to improve the patient care. To spend money on more expensive incubators and then raise your IVF cycle fees and put that on the patient when you don't know that it's going to be helpful, to me, would not be ethical medicine.

Now, some embryologists will argue that it improves their embryology workflow, but to me, that still should go on the clinic because you're trying to save embryologist times. You have fewer embryologists who have more time to do other labor-intensive tasks that an embryologist needs to do. But again, in that scenario, it should not be passed on to the patient.

So I think you touched on what's really key with these add-ons. If you're going to be doing them, I think the clinic bears the responsibility. If you are going to be offering them to patients, I think you need to have a long conversation about it.

I was just talking to someone. I don't steer my patient consult. Ten minutes of that is spent on PGT-A.

That's a lot. That's one-sixth of the time. But it's such a complex thing.

I don't think I can share the pros and cons of it to them, and I don't steer my patients in one direction or another. We have some known benefits to it, but there are some known risks to it or some potential or theoretical risks to it. I think patients need to be well-informed of what those risks are, and sometimes I'm surprised with the decisions patients make.

Some, I thought, would not want PGT at all. They hear the chat, and they're like, yeah, okay, now I would really like to do it. Others hear it, and they're like, I'd much rather spend my money towards a future frozen embryo transfer cycle rather than doing PGT now.

The latest guidance from ASRM is that we still don't have definitive evidence that it's going to improve live birth per cycle. I've always felt that it's a robust technology that's still looking for the absolute perfect indication to apply. It remains to be seen.

It's one of those things where it's intuitive that we have an embryo. We don't know if it's normal. Let's test to see if it's normal, and that's going to improve outcome.

The premise is probably good intention, but it is a costly technology, and patients need to be aware. I think whatever that we're doing, of course, whether it is definitively proven or not, informed consent is vital for the patient to be able to make that decision of whether they want to proceed with that or not. Absolutely.

I was in a meeting the other day here where, unfortunately, I heard a physician say for PGT-A, it's only opt-out and only if the patient brings it up. To me, that would not be the way that we should be practicing. Unfortunately, for some clinics, that is the way.

That's not the approach that I think you or I take with our patients, not just for PGT-A, but for any of these. We only have so much time, and so we have to choose what topics we can afford to spend that amount of time on, but I completely agree with what you said. Yeah.

Add-ons, probably in my experience, and I'd love to know yours, but in my experience, when you have a patient that's gone through multiple cycles, the desperation can sometimes compel the healthcare provider from wanting to do things that are not standard, but they have tried everything else, and I think that's the slippery slope. Yeah, that is. We've had a couple of nice papers that have come out recently looking at three consecutive transfers, then five consecutive.

We have an abstract looking at six consecutive, and these are euploid, so you're ruling out other causes of embryo failure, so it's not genetic and euploidy. The pregnancy rates after five are 97, 98%. After six, it's even higher, and so I've had patients say, well, Einstein said the definition of insanity is doing the same thing, and I say, that's not true.

When a couple has sex, and they're 25 and just married, and they have sex one month, and they come and say, I didn't get pregnant, what are you going to say? Keep trying again and come back and see me. Sometimes what is the right thing to do is doing another transfer. Now, of course, we want to have looked, as the physician, at their cycles, at their uterine lining, at all the things that we know that can cause implantation failure that we have good evidence for.

We want to make sure we haven't ignored those things, but sometimes it is just a matter of the number of attempts that patients have had. For us as a field, to me, this is one of the areas that we really need to explore. Why is it that with euploid embryos we get 60% live births at best on the other side of it? We're missing something on the embryo and something on the endometrium.

That's actually exciting because we've come a long way over your illustrious long career, Mark, but I think we still, this next generation, has a lot of boundaries that they get to push forward to figure this stuff out. I would be interested to know if in states that don't mandate IVF, are physicians more compelled to try non-standard of care? We look at the studies that show three to six cycles of euploid chromosomally normal embryos having very, very high success, but that comes at a dramatic cost when it's not mandated, and that makes it a little bit more difficult. That's a good point.

I wanted to sort of summarize in terms of the unanswered questions about IVF add-ons, is that the questions for patients to be able to ask and how would you be able to provide our audience as to what they need to know before what they think is not standard of care, if they're going to use that, what kind of questions do they want to ask their provider? Yeah, if I was going to ask my doctor about things that I've maybe read on a website or on a blog that the patients are saying they're doing, the first thing I want to know is does it actually improve my chances, and how good is that evidence? Because a lot of these things just lack quality evidence, and your physician should be able to understand that. Not everything is risk-free, and sometimes the risks are cost, sometimes the risks are time, but some of these things where we're intervening in the embryo may actually have the risk of harming the embryo. Our embryologists are really good, but when they're doing biopsies and hatching, they're doing microsurgery on a tiny organism.

Maybe there's some small risks. How much is it going to cost me, and what are the alternatives to doing this? I think coming to a shared decision with your physician once they share that information to them is important, and asking how those things perform in their clinic, what their internal data is on that. I think all those are good approaches to your physician.

Excellent points, Micah, and for our listeners out there, when you're searching for clinics, you really want that clinic to buy into your problem. If you have a clinic that can answer your questions, to have a true dialogue discussion, so that you feel fully informed and empowered in being able to make this decision, then you have the right clinic. Yeah, absolutely, and this is the SART podcast, and I'm the outgoing president of SART, and Mark's been a leader on the SART board of directors, and so we would just say, look for that SART membership when you're choosing a clinic and start there.

That'll get you to the highest quality clinics to start asking these questions with. Thank you, Micah. Everyone, thank you so much for your attention.

It's been my pleasure to have Dr. Micah Hill joining us today to talk about IVF add-ons. Until next time, this is Dr. Mark Trolice. Take care.