When to Hit the Panic Button Series: Patience vs. Proactivity - Navigating Next Steps After a Failed Embryo Transfer

In this episode of Taco Bout Fertility Tuesday, Dr. Mark Amols explores the delicate balance of patience versus proactivity following a failed embryo transfer. When should you hold steady, and when is it time to take action with further testing? Dr. Amols breaks down the odds, shares insights on additional evaluations, and guides listeners through making informed, proactive decisions to maximize future transfer success. Tune in to better understand when to wait and when to move forward confidently.

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Transcript

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Today we talk about when to hit the panic button when it comes to embryo transfer failures. I'm Dr. Mark Amels, and this is Taco about Fertility Tuesday. In this current series, when to hit the pack button. I'm trying to go over topics of when do you need to be nervous? And one of those topics that comes up, very common is when an embryo transfer doesn't work. And when it doesn't work, there is this fear that it's never going to work. And we all want to hit that panic button on the very first time. But the question is, do you need to hit it right away? And if you don't, when should you hit that pack button? It is absolutely true that, there are things out there that can make transfers not work. But the question is, there is also things out there that can make a transfer not work that are unavoidable, meaning there is already an inherent chance that it may not work. It is not 100%. And so before we get into what to do next and when to hit that pack button, we have to start first with understanding what is the natural odds of it even working in the first place. I think the best place to start here is let's use a euploid embryo, because a euploid embryo means the embryo is genetically normal, and that means we have a better idea of what the statistical chances are going to be. We'll get into scenarios later about other situations, but let's just start first with this. So with a euploid embryo, there's around a 60% chance of a live birth and around a 75% chance of a positive HCG test, meaning implantation, but not ending in the baby. That means that 25% of people who put back a euploid embryo will have no HCG, which means no implantation. And 40% of those people are going to, even if they have a positive hcg, will not have a live birth. And we all know what 40% means, but when we really look at it, that's a very big number. That's close to 50%. And honestly, that's astonishing. I mean, when you think about it, a euploid embryo, no genetic problems, and it doesn't implant. Now, it's important to understand that we are talking about basic baseline testing has been done and that everything is normal, meaning the lining built up, all the hormones are normal, and there is nothing there that we would anticipate that would affect the implantation not to occur. We are purely talking about the situation where when even things are perfect, there is a 40% chance that you will not end up with a live birth. So it sounds like we shouldn't hit the pancake button then. Well, that's true if you have a lot of embryos, but we're going to get into a scenario where you might need to hit the Panc button after one. But let's assume there's multiple embryos we have, and now we do another transfer. We're not panicked yet, and we do this second transfer. Now, what most people would think is, okay, well, you do another transfer, 60% plus 60%, that's 120% pregnancy rate, I'm going to get pregnant. I should definitely freak out after the second failed transfer. But unfortunately math doesn't work that way. You can't add the percentages together. You can only get another 60% of what's left over. Meaning if you have 100% and the first transfer had 60%, then there's only 40% left. Now, your chances would be around 85% chance that you should have had a live birth after two transfers of one embryo and over a 90% chance of a least implantation, meaning a positive HCG test. Now, 40% is a pretty easy thing to understand. If someone told you at a 40% chance of dying if you left your house that day, you're not going to leave the house and you're going to watch a bunch of Netflix. But what about a, 15% chance of failure due to just random chance? That's a little harder to kind of wrap your head around. It comes out to about one of every seven. So that means if seven people did a transfer, there would be one person that would not have a live birth. Out of those seven who all had one embryo put back the first time and didn't work, and then when they put the second embryo back, still didn't work, this is when the heart starts beating a little bit more because, yes, that is a pretty low number. Now, if you have a bunch of embryos, I wouldn't hit the panic button at this point, but it truly is a point where you need to start doing more testing. Statistically speaking, the tests that we do, such as an ERA and endometrial receptivity assessment tests occur around 10 to 15%. So we're right at that point where if it is something wrong, it would fit up perfectly with this current failure rate. And to bring things in perspective, I know one out of seven seemed very low, but what things do have a one in seven chance. For example, if you randomly pick a date, you have a 1 in 7 chance of it being a weekend, although not exactly 1 in 7. If you roll the dice, you have a 1 in 6 chance of landing on a certain number. So although it seems small, it's not as small of an odd as we think. So then what do we do? At this point, we've had now two transfers, both failed. Well, at this point, you start doing testing. The type of testing you're looking at is you're verifying things again, making sure the baseline things you did, such as checking hormones are still true, that your thyroid's normal, prolactin levels are normal, your vitamin D levels are normal. Maybe on the Sono histogram you did, there were some quality issues. Maybe doing a hysteroscopy now to look inside the uterus. But there are also some other tests you can do, such as an ERA and then the mutual receptivity assessment test. They can find out the timing may be off and there is about 10 to 15% of that occurring. So again, very reasonable test to do at that time. Additionally, there are some more tests out there like Receptiva, which can look to find out if there might be conditions that create inflammation, such as endometriosis, that could be affecting implantation. You can even go a step further and you can look at things like infections that could be going inside the uterus. Receptiva tests is that if you do the pathology portion, and there's also tests that can be added on to the ERA to determine if there might be bacteria there that's affecting things. I tend to look at it from the situation is, is there implantation as if there's no implantation? If there's some implantation, I tend to think whatever is going on is a major thing, such as the, ER being very far off or something like an implantation failure with a receptiva test being helpful. When I see implantation, but it's just not continuing, then I start thinking of other things like, you know, could it be something where there's a pulp in there, or could there be something where an infectious cause is causing issues with it continuing on? Now, it's important to remember we're still talking about Euploid embryos. We're going to get into the situation where we're not using Euploid embryos later. I do believe there is a difference, though, between having two transfers with no implantation versus two transfers not ending in a live birth. If, two transfers occur, but there was at least implantation being an HCG seen one time, that makes Me feel a little bit better and I'm less panicky, versus if I see absolutely zero implantation both times, then I'm a little bit more concerned. And then I start really thinking about things like an ERA or receptiva test. And if the ERA came back and it was off, then at least it makes some sense to me. However, having two embryos being transferred over time and not having a single one have a positive hcg, even low HCG does worry me more, and my hand is on that panic button a little bit. Now, if my results come back from the ERA showing there's something off, I'm less panicky because I found the problem. Same thing with the receptiva. But, what if you don't find anything? You don't have to technically panic. There are other things that can be done, and that's when you have to go and look through everything again and go, how did my lining build up? Should I maybe do a hysteroscopy now? Should I think about using things like embryo glue now, since I've had two failed implantations, Should I be considering a natural fat or maybe even doing something like a PRP wash? The goal of this episode is not to go over those treatments right now. But the point is, at this point, if you've had two transfers with absolutely no hcg, we really need to start looking elsewhere. If it had at least an hcg, there's some promise there. That's implanting. But there might be another issue going on, and that's where the testing comes in. Now, if you do the testing and you find something wrong, and that something wrong is something that could have prevented implantation, then in some ways you're starting back over again. Meaning if the next transfer occurs, and now let's say it's a chemical pregnancy, I wouldn't be as worried because now I fixed everything. I'm starting from day one, and as I mentioned, the one transfer not working isn't time to hit the panic button. Even though it's technically been three, it technically is only one since you corrected known issues. Now, if you do not find anything and you make those changes to have a third transfer and still did not have implantation, it is very fair to hit the pack button, because statistically now you are well above 90% that should have had a live birth by now, especially implantation. And at that point, it might be worth getting a second opinion. But what if you don't have Euploid embryos? What if you didn't do PGT testing? Then what do you do in that situation? Well, let's start with the first situation where you're 35 or less. And we know statistically the chances are very good. But even at 35 or less, we know that the chances of a live birth, even with putting two embryos back at the same time, is only about 60 to 70% chance of a live birth. That means there's a 30 to 40% chance that you would not come away with a live birth even after putting back two embryos that are untested and you're under 35. If you did it again, then you would be at the point where everyone was with the euploid embryos after putting back two embryos. And so what I would say is if you don't do testing on embryos, you're really looking around three embryos of untested embryos to start doing some of that further testing. It's not unreasonable to do it before then. But technically you won't be at that same statistical chance as someone with upload embryos until at least the third or fourth transfer. Now, the problem is, as you get older, if you're not doing PGT testing, then there's a higher chance that the embryos are genetically abnormal and the chances of success are even lower. So, for example, even just by age 38, it's only a, ah, 40% chance of a live birth per embryo. And so now, even after putting back three embryos, you're still well below that 85% chance of a live birth. And if we're talking about someone who is 42, each transfer is less than a 10% chance of live birth with embryos past 42. And so you can see that untested embryos are a little bit different. And you can't hit that panic button as soon. It doesn't mean you can't worry. But the point is, statistically, your odds aren't even that high. And so hitting the panic button doesn't make as much sense because the chances of it, not working were higher than the chances of it working. One of the difficult things without doing PGT testing is that you don't know if the embryos are normal or not. This is why I truly believe there's some benefit for everyone, because if a transfer doesn't work, at least you don't have to worry about the embryo being abnormal. So like I said, even under 35, I don't really get too worried if we put back two embryos and it doesn't work, because I know there was a 30 to 40% chance of not coming away with a live birth. Whereas if that patient did PGT testing and I put back two embryos and didn't work, I'm definitely concerned in doing more testing because I know there was an 85% chance of a live birth at that point. This doesn't mean you need to do pgt, but just keep that in mind that if you look at, let's say, one person who does PGT and puts back two embryos and their doctor is doing a bunch of testing, why is your doctor not doing that testing? Well, maybe because you're 40 years of age and you put back two embryos that weren't, tested at that point, they realized statistically the chances were actually higher that it didn't work than work. So clearly it does depend what the chances are. So if you're at, Bob's backyard IVF and they only have a 30% chance of live birth, you may not need to hit that pancake button as soon because their pregnancy rates are lower. But if you're at a clinic that has a 70% live birth rate for each transfer, then by the second one, you might need to be worried a little bit more because statistically your chances were higher of being pregnant than not. But when do you worry earlier? Meaning if we're not supposed to worry until at least the second embryo would euplate embryos, when would we worry if there was only one transfer that failed? Well, that would come in the situation where potentially you didn't have a lot of embryos and you have no way to get more embryos. So this would be the situation where, let's say someone can't get more embryos and they only have two. Or the situation where someone has a history of failed transfers in a prior place and then has failed transfers at your place in that situation, you don't have to keep waiting. Right? If you have two embryos and you want one child and you put one back and didn't work, it's not unreasonable to hit that pack button a little bit early and do some of that testing because you don't have multiple tries. Matter of fact, it wouldn't even be unreasonable to preemptively do some of that testing and go a little bit further because you've known you only have those two tries. The same thing is if you have a historical history of having failed transfers, then you don't have to wait again to have multiple transfers before you hit that pack button. So, for example, let's say someone was 32 and they did three transfers, meaning three embryos. Didn't have a live birth. Again, I wouldn't hit the pack button yet. I'd definitely be nervous, definitely do testing. But then if they did a euploid transfer at another clinic and didn't work, yes, I'm concerned now because now that's three euploid potential embryos, even though we don't know it, but one for sure euploid. By then we're well above that. 60% were close to probably 80 plus percent chance of live birth. And now I'm a little bit more panicky. Now, what I do in this situation might be different than other doctors, but I basically look at the patient again as if they're a brand new patient. I go back through all the charts again, I go through all the ultrasounds, I look at every little thing. How did they build up their lining during the stimulation cycle if they ever did have a pregnancy? What was unique about that? If they ever had a positive transfer? When was that transfer time? How did it change? Did I, When I look at the images, do I notice anything unusual? I basically look back at the patient as a brand new patient to see if I can find anything. Sometimes you don't. And unfortunately, sometimes you have to just do things trial and error, which sucks. But the point is, the goal of this podcast was to let you know, when is it a normal time to hit that pack button? And I mean, essentially, it's always normal. If that's when you need to hit it, that's when you need to hit it. But objectively, I wanted you to at least have a point in time when even I myself, as the doctor who sees these not work sometimes, and then the next month work when I start to hover my hand above that panic button. And truly, if I did three transfers with no implantation three times, and I knew that the timing was correct, I knew that the receptiva was normal. I know that we've tried the emblue, I've looked over the charts, I know the uterus is normal. At that point, I too am hitting the panic button. The one last thing I want to bring up before we end this is don't think of hitting the panic button as giving up hitting the panic button. It means being proactive and using all available tools to increase the chances of success in the future transfers. I wish I could tell you it's definitely going to work, but no one can. But what I can tell you is, most of the time in these scenarios, if you do the testing, get that second opinion or find what's wrong, you can end up having success. Hopefully this was a helpful episode to you. Maybe you know someone who's going through transfers and has a failed transfer may need this to help them know that hey, it's okay not to panic yet. This could be normal. As I always say. If you like this podcast, please let us know. You can send us an email@tbftirectionfertility.com you can also give us a five star review on your favorite medium. But most of all, keep coming back and listening to Talk About Fertility Tuesday.