Why IUIs Fail 2.0: Bad Luck, Wrong Treatment, or Hidden Problem?

Why do IUIs fail, even when everything seems to be done right? In this updated episode of Taco Bout Fertility Tuesday, Dr. Mark Amols breaks down what a failed IUI actually means. He explains the three biggest reasons IUIs fail: sometimes it is just bad luck, sometimes IUI is the wrong treatment for the biology, and sometimes there is a hidden problem that routine fertility testing cannot detect. This episode also covers newer data on IUI success rates, the role of male factor infertility, how age and time trying should affect treatment decisions, when it makes sense to keep trying IUI, and when it may be smarter to move on to IVF. If you have ever wondered whether a failed IUI means something is wrong or whether IVF is the next step, this episode will help you think about it more clearly. 

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Transcript

0:01

Today we talk about why IUIs fail, but this is not the 2021 version. This is the updated version. Because the better question isn't just, why didn't my IUI work. The better question is, what does a failed IUI actually mean? I'm, Dr. Marc Emils, and this is Taco about fertility. If you have ever gone through an iui, you know how frustrating they are. On paper, it sounds great. You help make eggs, you wash the sperm, you place it right into the uterus and you expect it should work. And why wouldn't you just push the sperm all the way in the uterus? And yet it fails. And at that point you start spiraling because you start thinking, do we miss something? Did you do something wrong? Does this mean IVF won't work either? Well, the simple answer is no. Usually a failed IUI means one of three things. Number one, it was just bad luck. Number two, it might be the wrong treatment for the current biology you have. And number three, there could be some hidden problem that the routine testing we did simply does not detect. And that's what we're going to break down today. IUI is not a bad treatment. It's just not magic. One of the biggest mistakes people make is assuming that because an IUI is a fertility treatment, it should have a high odd every single time. But it doesn't. And that's not because it's a bad treatment. It's because it's a limited treatment. A large ASRM sized study looked at 14,000 IUI cycles in couples with unexplained infertility. And what they found is that the live birth rate, meaning having a baby in your arms, was about 6.2% with natural cycles, 8.9% with, Clomid IUI cycles, 9.4% with letrozole IUI cycles, and 9.5% with gonadotropin IUI cycles. So what does this mean? It means right out of the gate, this tells you something really important. Most individuals doing IUIs are going to fail. And that's just math. Now, yeah, the math may be rude, but it's honest. And then you could think, well, is it even worth doing if most people are going to fail? And that's a fair question. Now, back when I did this topic the first time, the main point was that IUI doesn't fix every fertility problem. And that's still true. That hasn't changed. But the newer conversation now is going to shift a little. Now the question is, is IUI good or bad? And even more, which couples are good candidates for iui and when should they move on? If you look at ESRA guidelines, which is kind of like the ASRM in Europe, they recommend IUI with ovarian stimulation as a first line treatment for couples with unexplained infertility. It also says IVF is probably not recommended over IUI with ovarian stimulation for most of these couples, and that the decision to move to IVF should be individualized based on things like age, duration of infertility, prior treatment, and prior pregnancy history. The guideline's practical framing Is that stimulated IUIs for about three to six cycles is viewed as first line treatment. Now, I realize that's not a black and white answer, and I know it'd be nice to just be just skip IUI and do ivf, but it's a little bit more complicated than that. Let's start with bucket number one. Sometimes it's just bad luck. If you think about it, even when M people try on their own, there's only about 50% people who are pregnant after three months without infertility, and then by six months, 70%. So even naturally, it takes some time. And sometimes a failed IUI means absolutely nothing. Except that low probability treatments sometimes fail. In a major randomized trial in unexplained infertility, they compared gonadotropins, clomiphene and letrozole up to four cycles. Live birth occurred in about 32.2% of the women in the gonadropin group, 23.3% in the clomiphene group, and 18.7% in the letrozole group. So even after multiple cycles, a lot of appropriate patients will still not get pregnant. Now, remember earlier I gave some numbers as well. That was the per cycle rate. This is the cumulative rate after several cycles. And this can create some stress, because if an IUI fails, does that mean you automatically earn the wrong treatment and that you shouldn't do it anymore? Maybe it just means that they were on the wrong side of the odds that month. The point is, a 10 or 15% chance is still mostly a chance of not winning that current round of iui. And it matters. And it matters emotionally. Many times after a failed IUI cycle, patients think they did something wrong. They think, well, I lifted something, or maybe I was walking too much, or maybe I stressed too much. And as I talked about in a previous podcast, stress could not cause that. Most of the time, the negative test is because chance and not because you sneezed on the wrong day. Bucket number two sometimes is the wrong treatment for the biology. So what do I mean by this? Well, sometimes an IUI fails because it is simply the wrong tool for the actual problem. IUI mainly helps with getting sperm closer to the egg and by bypassing the cervix. This can be very useful, especially if there is a vaginal milieu that's causing some problems. Think of like a hostile environment. But the real problem is that the sperm still cannot do the job. If there is something wrong with the sperm getting in the eggs, or if the tubes are not open or not functioning well, the sperm and egg will never meet up. Even at the level of the fertilization process. If there is something going wrong, it will not fix it. And this is very relevant when we're talking about male factor. The current AUA ASRM guidelines for male infertility say that men with a post wash total modal count under 5 million, have limited chances of contributing to pregnancy through IUI. Now, that doesn't mean zero. There's actually been several studies that show even with 1 million sperm, there's decent chances. I tend to use 3 million, and if it's below 3 million, I know the chances start to drop significantly, but it's not unreasonable. If you're not getting to that 5 million and this is something you're paying out of pocket, it may make sense to move on to something else. And this is a really important part to understand. Not every failed IUI is random. Sometimes it's the reproductive system telling you this treatment is not adequately bypassing the real problem. So even if IUI worked in the past, and this time the sperm counts a little bit lower, it just may not work because it wasn't the right treatment, even though it was in the past. And this is why some people move on to ivf. And IVF is not just a stronger iui. It is a different treatment entirely. It bypasses tubal pickup issues. It allows fertilization to be observed, or even using ICSI can inject the sperm into the eggs. The important part to understand is that a failed IUI does not predict a failed ivf. It makes sense why you would think that, because you think, well, if I failed this, why will I do better the next? But they're not even in the same league. Bucket three. The hidden problem. Now, this is the part that drives everybody crazy. Unexplained infertility. Again, I've said this before, doesn't mean that the doctor doesn't know what's going on. It's just we don't have a way to test for everything. And it doesn't mean there's nothing wrong. There is something wrong, it's just that we can't find it with routine testing. This is actually where IVF comes in and allows us to see things we couldn't see in the regular testing. For example, sperm may look great on paper, but we never actually put the sperm through an obstacle course. We don't know if the sperm's actually getting to the egg. We don't know if the sperm is actually even fertilizing the egg. So we have to make an assumption that that's working. When we do IUIs, the same thing comes with fallopian tubes. We can say the fallopian tubes are open, but we can't say that they're actually working. There are little fimbriae on the ends of them are pulling the egg towards the opening, and then the sperm and egg get together. That's impossible to know because we're just verifying if they're open or not. The point is, it's very frustrating when the workup says, yep, looks okay, but in real life it's apparently not okay. And this is the really important part. If you have unexplained infertility, listen up now, because this prognosis based way of thinking reflects kind of a newer way to review things. Instead of looking at all unexplained infertility as one uniform diagnosis with one universal answer, instead we should be looking at based on things like age, duration of infertility and overall likelihood of success with the treatment we're thinking about using. The point is, not everyone with unexplained infertility should do IUIs, even though some of the guidelines say that should be first line therapy. There is clearly a difference between two women who have, unexplained infertility. But one has it for 15 years trying to get pregnant and one has it for one year of trying to get pregnant. The one doing 15 years should not be doing IUIs. The same thing goes of age. If you're 24 years old, sure, try a couple IUIs, but if you're 40, don't waste your time. We talked about this in the 4T trial in one of the podcast episodes in that study it talked about when women are 40, they should just move on to IVF because the time doing IUI can waste time. Another important update to this conversation is that not all stimulated IUI cycles are equal. In that same major trial ganatropins had the highest live birth rate, but they also came with the highest multiple risk. If you were using gonadotropins, you had a 32% chance of having multiples versus a, 9% or 13% with Clomid or Letrozole, respectively. And because of that, many clinics won't even use ganatropins. So that means your chances of coming away successful with IUI even gets lower. That doesn't make them bad clinics. There's risk. And as a matter of fact, insurance companies are making it harder because they're denying the use of ganatropins. So it may not even be your clinic's position. It might be what they're forced to do. So unfortunately, we're not seeing as many pregnancies with IUIs because we're not being as aggressive. Several times I have wanted to use gonadotropins and I couldn't because insurance wouldn't allow me to. They would deny the patient it and wouldn't pay for their treatment if we used it. And at that point, it may be even worth talking to your doctor and saying, hey, if we can't use the treatment you're recommending, should we just move on to IVF and not waste time? I think that's a fair conversation. So here's the million dollar question. Should everyone just skip IUI and go straight to ivf? Well, this isn't easy to answer again, because obviously if everything was free, I think, yeah, pretty much everyone can go straight to ivf because it's not even about getting pregnant faster. It's even about understanding what's going on and you can see things and make adjustments faster. But a 2024 individual participant data meta analysis found that there was actually no significant difference between IVF and IUI when it came to ovarian stimulation in couples with unexplained infertility in terms of cumulative live birth rate or multiple pregnancies. So what that means is, is that if you did, let's say, an IVF cycle and you did six IUI cycles, in the end, they were very close. So cumulatively, you'll eventually get there if you are going to get pregnant. But as you've heard me say in previous podcasts, there was a study that showed that if it doesn't work in the first three cycles, it's probably not going to work, because 90% of people that are going to get pregnant with IUI are going to get pregnant in the first three cycles and only 10% after that. That doesn't mean you won't get pregnant with iui. It just means that protocol is in the protocol you should keep using. So both are viable options. And so no one's going to say yes. Everyone should Skip straight to IVF. Now, that does change again if you're 40, because the 4T trials showed that you should go straight to IVF. So the question then, in today's world, where everything is not free, everything is not easy, and you have to take time off work to do certain things, is IVF the right answer for everyone? No, it's not the right answer for everyone right now. But as I mentioned, if you've been trying to for multiple years, IUI probably isn't worthwhile. My cutoff is three years. If anyone has unexplained infertility and has been trying for three years and has no other problems, I recommend going straight to IVF. We will try IUIs if they want, but I don't recommend it. Even by two years in an active couple, I may even still recommend ivf. And I tell them, I can't promise you you won't get pregnant with iui. I'm just telling you, historically, I find the chances are lower. And we already know IUI chances are low to begin with. So where do we go from here? Well, if you did one IUI cycle and it failed, it means nothing. Don't get stressed, don't start going down the rabbit hole. Basically, statistics just did what it does. It was statistics. And the chances weren't that high to begin with. If you're a good candidate, especially in younger people who are good prognosis, it's not unreasonable to even do up to six cycles. But as we discussed, after three, you should at least be changing the protocol or doing something a little bit different because of previous studies. But in the situation where it's been two or three years of unexplained infertility with no success, or if the female partner is older, time matters more, especially if they're 40 and in that situation, they should go straight to IVF. If they're in the 38 to 40 range, it's not unreasonable to try one or two. As long as the post wash count is around 5 million or higher, I would say anyone 38 or above should not be doing more than three cycles of IUI. And really, even at 35, if you're wanting multiple kids, that's one of the important things. When I talk to my patients, I don't just talk about getting pregnant. I, talk about them building their family. If you want a lot of kids, then sometimes IVF is needed just to preserve your fertility. So if I had to leave you with one message, it would be this. A, failed IUI does not automatically mean anything is terribly wrong. Sometimes it's just bad luck, sometimes it's the wrong tool. And sometimes it's a hidden problem we cannot fully see with routine testing. But the answer isn't to panic after one cycle or to just jump straight to ivf. The answer is to ask, is IUI a useful treatment for you? Based off of those factors we talked about earlier, make sure to ask those questions. Was this bad luck? Is it the wrong treatment? Or is there a problem we're not realizing? And that's where good fertility care actually starts. I hope you enjoyed this episode. As always, if you have questions, you can always send them to tbftewdirectionfertility.com and if you really like this, tell a friend about it. Give us a five star review on your favorite medium. But most of all, keep coming back. I look forward to talking again next week on Taco Belt Fertility Tuesday.