Latest / Fertility Untamed / IVF Keeps Failing? What Fertility Specialists Want You to Know
Transcript
- 3 DOCTORS EP 5 HD V2: Alright, welcome back everyone to another episode of season two of Fertility Untamed. So I am Dr. Sylvia Ross and joined by my beautiful colleagues Dr. Devini Amaratanga and Dr. Rebecca Mackenzie Proctor. As you know, we are personal and professional experts in the area of fertility and women's health and we're hoping to increase people's knowledge in an evidence-based way to empower them with their own health decisions. So today we are talking about recurrent implantation failure, which is a an IVF specific term that we use when someone has had a number of embryos created in IVF, transferred into the uterus, but we have not had sustained implantation or clinical pregnancy. now it's it's interesting sort of diving into this because I would love to start this by saying this is the definition of recurrent implantation failure and this is what this means. But if you look at the literature, there are hundreds of definitions. So hard for exams, remember? How many did you memorize? Five. As an Ares or Ishra. And us. That's right. And so, you know, I think it's it's pretty well agreed, you know, amongst the fertility specialist space that you have to assess patients mm majority based on age, because that's going to tell us how many embryos we need to transfer for a good chance of pregnancy. And you know, looking at the Eshra guideline, which is the European guideline Which is quite recent, they actually suggested that a a a chance of clinical pregnancy of sixty percent and not achieving pregnancy should spark investigation. I can't say I totally agree with that because that's only one embryo transfer, right? So then you're actually going to recurrent, right? That's not recurrent. Even with that guideline, they do go into age and say when to investigate or not. And I think that's important because if you've had two transfers at the age of thirty we're a bit more concerned than if you've had two transfers at the age of forty purely because of the embryo factor. So I quite like using the eighty percent off and I and I've got some s numbers around that. And, you know, I always tell every patient, I'm sure you guys do as well, that any untested embryo has a less than fifty percent chance of giving you a baby. So what does that look like, you know, in terms of age? Age, yeah. And for anyone who's thirty four or under, that would be three embryo transfers before you have an eighty percent chance of of that Punical pregnancy. If you are 35 to 39, it's four. If you are forty, it's five. Forty-one is six, and forty-two is seven embryos. I mean, that is crazy, right? Because how many cycles would you need to do as a 40 plus year old to get seven embryos? And this is all untested embryos, okay? So when we look at pre implantation genetic testing, you know, essentially it would be two or three. Absolutely. But then once again, how many embryos are we gonna have to go through to get a normal embryo? So I mean you could you could do three six or seven IVF cycles and not get any normal embryos. And I think that's why RIF, we often call it RIF, repa recurrent implantation for that is so frustrating, right? It's so hard. And even when you put a normal embryo back in and you get an you get a miscarriage or you don't get a implantation result, it is very frustrating. Very frustrating. And it is hard to hold yourself back from going down this rabbit hole of Let's do this, this, this, this, this, this, and especially with AI and patients having much more information accessible to them, you know, which way we go investigating this. Yeah, they'll come to you and ask you to do everything under the sun and you're like, Well, actually, where is the evidence? Where does it actually lie and what shows us to have clinical meaningful outcomes? And I feel like no matter how Painfully realistically, I counsel patients. Even after the first embryo transfer, they often come to me and Well, what went wrong? Yeah. You know, expectations are always so much higher. And I've been there and I know that because you do that, like you do everything perfectly. And what do you mean? And especially a euploid embryo. You know, the embryo factor's already been taken care of. What do you mean it's only a fifty percent chance of it working or sixty percent chance or you know? Yeah. Right. And I think that's where the personalization comes in because I might have someone who's If you have someone who's forty two, you may not realistically get to seven embryos. Yeah, you know, i in a good time frame. And so you may offer them some investigation a bit earlier as well, because you don't really want to get to seven that have probably taken you many, many, many cycles to get, and then actually find out, they actually had this thing we could have fixed all along. And that's always the hard thing about any time infertility is that it's always that retrospective scope that we use to look back at things. That's right. And so it's hard when you're counseling a patient, you You know, you want to give them all the facts 'cause you want to minimize that risk of them having that problem later on, but also you don't want to overim over investigate. You don't want to cause a problem or put them at unnecessary risk when they're never gonna need it. And I feel like it's the same with lots of discussions we have about the investigations. Should you do that laparoscopy now, should you do that hysteroscopy now, or do you wait? And then when you have waited, they're like, Why didn't you do it sooner? Like, Well, because we didn't need to do it sooner, we didn't know. Yeah. And what happens if you did that investigation and it had a complication and you didn't need it in the first place? So I think that's really hard as clinicians to help people and that manage that and we and we do most of these investigations and a lot of things before we start treatment anyway. We've actually looked at a lot of general health areas first. And you one of the things which is recommended is checking thyroid function, but we often check that in in many patients anyway. We might have checked them for insulin resistance anyway, but if we haven't, we're gonna do it now. what other investigations, Dev, would you look at in someone who has this riff? Look, I I d I do like the Escher guidelines actually. I think they're quite reasonable. And so I generally do follow that. I start off with the global again, like you said, the diabetes and thyroid and then I do check caryotype routinely as well. and then somet I do actually check some of the thromophilias, so lupus anticoagulant beta two glycoprotein. And then I speak to patients about the you know, having a look at the uterus itself. And to me Yes, I get a very good tertiary ultrasound just because I live in a city that is easily accessible. but I do like looking at the endometrium if I can. So a hysteroscopy in RIF to me is quite useful and it certainly does you know, the patient's background gives me a bit more idea. So if they've had a cesarean section before, if they're a secondary infertility, or they've had a miscarriage before, or they've had chlamydia or gonorrhea, something where there's you know, potentially fine adhesions or not even fine, significant adhesions, or, you know, they might have some endometritis, you know, some chronic endometritis. You can kill a few birds with one stone by doing a hysteroscopy. So I actually quite like strengthen the S ray guidelines because you've got the recommended which is assessing endometrial thickness. Yeah. And then endometrium. And then you've also got three D Otrasound scanner hysteroscopy and chronic endometritis, which are your kind of good practice points. You cover you're covering three of the things that we would consider doing. So I think hystroscopy is a really good place. And I think that that and not to get it too ahead of ourselves, but that also goes in with the Emma and Alice you know, checking microbiomes and endometritis and actually cover that as well. Because if I see something that looks like endometriitis, I start treating at that point in time without having to go down the track of doing And it can be very obvious. I guess a And so what we're looking for for those that are interested is that we're looking for these things called micropolyps, these little tiny that usually they're millim not even millimetres in size. You might see a bit of sort of more red spots and things inside the uterus as well. And the other way the two main changes. Some and we do a blight we do a test and we look for plasma cells in the histology. So C D one thirty eight, yeah. Absolutely. So the other things that and if we see those any of those changes actually at the time of fistroscopy, if we start treatment, f two weeks later, you you know, you're good to go to having to see if you've actually reduced your chances of having chronic inmeteuritis return. So that would be those would be my main ones. look, Ashray talks about some other things to consider, vitamin D levels, you know They say don't do vitamin D yeah. And then yeah, and again ERA to consider. So do you Well I think I think there's actually been Some very interesting papers in recent years and a lot of things that we have been doing we're now starting to reconsider. So the first one is the paper that said actually don't do endometrial receptivity testing because so this is a this was a very commercial product that came out and sounded amazing and it was saying, you you've got this window of implantation within the uterus and if in the cycle prior you test it, we'll work out exactly what that window is and make sure that you're going to implant the embryo at the right time. And it didn't make quite biological No, I mean it can't be that hard, right? Or where would where would we all come from? But this paper was really interesting because not only did it show that this did not improve your outcomes, the people who had this test and changed their time of transfer based on that actually had a worse outcome. And that's why research is so important because we get these products and we want to help our patients so desperately. But if you jump into it without actually looking at the evidence, you might be doing harm. Yeah. And I think again, it's not that I I do do era sometimes because It's one of the last resort things that I can, you know, and we've counselled, we talked about everything and patients want to do it and I talk about it, you know. And sometimes for maybe for individuals like what you're talking about, in another episode, Beck, like these are population studies. There might be some individuals that give you a little bit of an idea. For example, I go in and in the luteal phase I take a biopsy and I see at and the histology comes back as doesn't fit in with time or I go, you what? I might do an era for you. Because that is the patient that maybe this is what it's for, right? So I think you do need to individualize it. And that's why again guidelines are guidelines and they're there for the bigger population. But when you've got people like we ourselves that have studied for over twenty years these topics, it gives us more flexibility to to look at the patient and say, Hey, well actually in this situation it'd be useful for you to try this test. And we're not saying that's There is lot of new data about microbiome. And so the other two aspects of that ERA tests that often go hand in hand is the microbiome and to also check for chronic endometritis. And I don't know, what do you guys talk about with microbiome? I'm a big big fan of me. So we go in the bags. Okay, it's okay. You know, and I I sometimes I even talk I talk to people also about the benefits of using empiric treatment anyway. I'm so I think everyone should to consider a vaginal probiotic or an oral probiotic vaginally but remembering if you take and I think we talked about this in the microbiome episode, that you're taking the probiotic orally it takes a long time to get through to the vagina. So putting it in the vagina just like a pissery would with the IBF can be quite helpful. Yeah. Yeah. I'm I'm a pro as well. I think it's a minimal harm thing. You know, often if a patient has chronic endometritis and you give them antibiotics you're gonna you're feeling disrupted there. microbiome anyway, what's the harm of just doing if you, you know, a course of vaginal. I use a lot for my B V patients as well. They have a current B V, I find it really helpful, or annoying discharge doesn't go away, or a current thrush. There's quite a few things you can use it for. something else which came up, we were at the Eshra conference a couple of years ago, Rebecca, you and I went to a whole day on platelet rich plasma and you know, that's another really interesting area if you could tell us about where that might be useful in this setting. So platelet rich plasma is where we take a sample of the patient's blood, we spin it down and we take out the platelets and we put you we use those to go back into the uterus. And the I idea is these cells have got a lot of growth factors, a lot of immune factors that can help kind of improve the the environment of the uterus. And the I I think of a bit like compost on the soil. It gives it's compost. Compost, like you know, like you know, like when you put compost on your soil, it helps the plants grow. Same idea, you've got all these wonderful factors that are helping your embryo grow, but like you with the plants. Yeah. So maybe it's yeah, yeah. So that that's sort of the idea of it for recurrent implantation failure. It's used for many other things in other areas. It's used in your, you know, vampire facials. It's we could you can use it st for studies around the ovarian PRP for ovarian aging. But in this case of recurrent implantation failure, it's a thought if it's sort of immunological or there's some other factors at the uterine e environment that we don't know about that actually putting PRP into the uterus has shown to improve outcomes on, you know, in w lots of studies these days. So it's something I do consider and I think that's still an area that we are looking more at. Yeah, and I think there's confounding with thin endometrium versus recurrent implantation failure. So once again it's an adjuvant, like Beck says, sh you talk to your patients about it. And I the other one that goes hand in hand with all of this is natural killer cells and what we do about that. I find NK cells really tricky as well. I I don't test for it personally. Patients often ask me and I give them the same spell, which is natural killer cells basically have a terrible name that make them sound evil. We need them for implantation. Certainly there's an idea that there might be some change in their function that that's affecting implantation, but the blood levels of natural killer cells don't correlate to the endometrial levels. The endometrial levels change over a cycle. We don't really know what's normal and what's very difficult to test. We don't have a treatment, so why are we testing for it? Yeah. Look, I'm also very I'm very conservative when it comes to NK cell testing and HLA DQ testing as well. But I'm also hoping that someone comes out with a really clear breakthrough because I would love to be able to treat recurrent implantation failure when, you know, we've put three, four Euploid embryos buck and we can't get patients pregnant. It's really tricky. The financial costs, the emotional costs and things. And I think that's when we're all wanting to practice the best evidence we can. But sometimes we do have to do things that might not be because with science and we're scientists. Science is only proven till it's not proven or we don't know about it till it is proven. So sometimes we do have to be at the frontier of things and try other things that might not be. I've chat to my patients about that. And sometimes I d you know, sometimes I do test it, sometimes I treat them in various ways. But I'm very clear that it's an adjuvant and I do discuss the pros and cons. And then what kind of immunological treatments? I mean, w in which settings would you consider using something immunological? I'm very conservative and I typically don't. I know Rebecca's slightly less conservative. What would you say about that? So would I use IV IG? probably very little. I mean I'm beginning to think that maybe I would like to use a bit more of it. It's sometimes it's hard to find the place that would do it safely, but there is if patients are needing it. intralipid. it's not really immunological, but it's more it's kind of supporting in a cycle. And I intralipid's a bit like having a a milkshake. It mops up some of it's it's giving a whole lot of fat into your body system, but it's thought to have some benefit. And I think it's got less risk compared to IV IG. but I think IVIG has got quite a significant side effect profile and I think you need to really counsel your patients quite quickly. clearly and before I'd be going to give them too much of that. I think one of the problems with the intralipid is that there were a couple of studies that showed there might be some benefit, but in recent times the studies have shown to potentially not have been done as they were reported. And there were some data integrity issues there, which puts me even more away from it. I look I use lower risk, well if you can call prednisolone and so forth lower risk, but that's an immunological agent as well and and blood thinners and so forth. in patients who are kind of immunogenic. You know, they've got a family history of having autoimmune type things. They may ha might have a high ANA that comes on testing. So I do tend to use those kind of things. I again would love to, you know, overseas, tachrolomus, they use all kinds of things, you know. Pequinel, and definitely increasing Absolutely, but we are conservative in in Australia. So and you know there are patients who have had good results with immune therapies. It's just very you know, a tight line between risk versus benefit and potential harm. That's right, that's right. And and I think one of the again, in recent times we've had some great research coming out and one of the papers that came out that had people where they just put back euploid embryo after euploid embryo. It's b basically everyone got pregnant after that. It ninety seven percent or something. So after two five of these are you after five. Yeah so they went from three to five They did the next the next lot, which is a hard study to do, you know? How many of your patients have that many embryos? Yeah, there was a cumulative pregnancy rate issue there. But but you're right, like you know the but I think it's reassuring. It is. And this is what we you know, patients patients always say, What are we doing different this time though? What are we doing differently? Different egg, different sperm, different embryo, you know? So we're the biggest thing is different every time we try. And we don't need to be buying everything you find online and Googling and and working out all of these things that may possibly cause you harm, even if just financial, but already doing something different. I think it's that sense of control that people really need. And as clinicians, we want the sense of control too. So not only are the patients suffering, the clinicians are suffering too, trying to figure it out 'cause of what we do what do we want more? Our baby women to get pregnant, our families to be built. And so and we're trying just as hard as the patients are, but we're not having to suffer that like the patients are. So we're really trying to reduce that by trying to find the best option for you. Yeah. and it's not always easy. Absolutely. But you know, it's really nice that I I think that we all agree for the most part on what things to investigate. We don't overdo it. I think there's a lot of tests that used to be done that now aren't recommended because one, lots of people in the general population may test positive. Two, we might not have a treatment for it. We're just adding stress. You know, it's nice to see that. We're all kind of doing very similar things. Yeah. It's not an easy thing to do to treat. One thing we haven't mentioned with the Ishra guidelines that can be considered an option. We'll be testing progesteroneables. So they do suggest that that is an option. So I think it's because most of us do that routinely. That's probably true. Without thinking about it. So yeah, so progesterone, of course, is is the hormone I always used to remember progestation, you know, it's this hormone that's going to help you maintain your pregnancy. And some people it can be harder to get them to have a a good blood level. And we, you know, we have to be realistic. It's not a steady state level and one point in time won't tell you exactly what's happening for this person. But there is some data to suggest that that, you know, if the blood level is Below a certain threshold, potentially supplementing with more luteal phase support and more medication can be helpful too. All right, great. Well, thanks so much, guys. I think you know that's a really important topic because it it does we do see it in our patients, and lots of people want to know what they should be doing, and and you know, we've got some investigations that we can do, we've got some treatments we can use, and if nothing else, we try a new embryo. All right, thanks for listening.