Miscarriages and implantation failure with Dr. Niamh Tallon

Lorne Brown:

By listening to the Conscious Fertility Podcast, you agree to not use this podcast as medical advice to treat any medical condition in either yourself or others. Consult your own physician or healthcare provider for any medical issues that you may be having. This entire disclaimer also applies to any guest or contributors to the podcast. Welcome to Conscious Fertility, the show that listens to all of your fertility questions so that you can move from fear and suffering to peace of mind and joy. My name is Lorne Brown. I’m a doctor of traditional Chinese medicine and a clinical hypnotherapist. I’m on a mission to explore all the paths to peak fertility and joyful living. It’s time to learn how to be and receive so that you can create life on purpose.

Today on the Conscious Fertility Podcast, I have Dr. Niamh Tallon, and I know Niamh really well because she’s one of the reproductive endocrinologists over at Olive Fertility Center that we are integrated with at Acubalance. And today we’re going to talk about miscarriages and implantation failure. And I want to just give an introduction to NIV as well, so you know who you’re listening to. She actually grew up in Singapore and Dublin. She did her medical school training in Dublin and or in Ireland. And then she did her OB-GYN in Canada, I think it was over in Saskatchewan. And then she did her reproductive endocrinology and fertility here in Vancouver at UBC and is a big part of the Olive fertility clinic. She does teach, she’s an associate professor over at UBC as well, and she’s really well known I think now in our community around egg freezing. But today we are going to talk about miscarriages implantation failure. And something that I think is unique that a lot of people may not know about you is your mom was a really well-known Chinese medicine doctor in Ireland. Is that not true?

Niamh Tallon:

That is very true.

Lorne Brown:

So you’re kind of integrative in a sense through your bloodline, right? You grew up around Chinese medicine and then you trained and practices as a physician, a medical doctor.

Niamh Tallon:

Yeah. I’m very lucky that I’ve had the experience to see both in action and I think we’re very lucky to work closely with you too, Lorne and Acubalance, and all the practitioners that you bring to help our patients.

Lorne Brown:

Thanks. And let’s talk about something that’s really challenging. Infertility is challenging on its own, but when you go through infertility treatments like IVF, do some genetic screening and you have no implantation or you get pregnant and you lose that pregnancy, that’s both physically and emotionally so difficult. And so I wanted to provide our listeners with some more information so they can prepare themselves going into any fertility treatment, whether they’re trying to conceive naturally or through IVF. And I thought I would ask you, can you share what is the difference? Because I’ve heard the terms implantation failure and miscarriage. Can you just share a little bit about that?

Niamh Tallon:

Yeah, and it might even be worthwhile just to highlight the difference between infertility and those concepts too. For someone maybe hasn’t got the big picture, infertility is not getting pregnant in a reasonable period of time. And what’s reasonable depends on the age of the individual, but we usually say within a year of trying for people under the age of 35 and then recurrent miscarriage or having a miscarriage, is someone losing a pregnancy naturally less than 24 weeks in gestation and recurrent pregnancy loss being now the most applicable definition is two consecutive losses less than 24

Lorne Brown:

Weeks. Let’s highlight that because a lot of people, it used to be three, they had to wait until you had three losses, which was so difficult after somebody had two and they’re like, no, they won’t do a workup. I need to have one more, but I just wanted to clarify for our listeners, it’s not that way anymore. Now as of this recording, it’s two now.

Niamh Tallon:

So there’s a clinical diagnosis and there’s an epidemiological diagnosis. So if you’re going to do a study on a group of people and you truthfully want to work out what’s going on in them, you want a clean population. So you want those that really demonstrate a problem that you’re looking at like losses in a pregnancy. So the epidemiological diagnosis is three consecutive losses and that probably represents 1% of all patients, not a lot of people. Thankfully. Two clinical losses are used to work up clinically. Start an evaluation recognizing that you are still going to pick up a big yield of people that potentially have a problem. But when I say a big yield, it’s like 50% of that entire population. We find something in them when we do the workup. Other 50% we don’t find a reason, which I want to highlight as we go through this discussion.

We sometimes aren’t asking the right questions and maybe we don’t have the right tests as of now to necessarily answer some of those questions. But in terms of the frontier of where we are in testing and managing recurrent loss, we are pushing that border and getting a little closer to an understanding. And it is a little bit exciting because evidence is coming out for different treatments that we may be able to offer that makes a difference for these patients. But to go back to your point about recurrent pregnancy loss, that represents about 5% of all people and that could be they’re conceiving on their own naturally or they may be doing fertility treatments because of a history of infertility and now also are experiencing recurrent pregnancy loss as a consequence of getting pregnant with fertility treatments.

Lorne Brown:

So 5% of the population could have two or more pregnancy losses, and of that population, around 50% you’ll find a cause for it, which means 50% is kind of, you don’t have a cause unexplained. And I’m curious, and we’ll talk about this later, but I want to put it out there anecdotally, in my practice, we often and in Chinese medicine think the male contributes to unexplained infertility and miscarriages. And often when we’ve treated the man, when it’s unexplained in the woman, even though the semen analysis it looks normal, they go on to have babies. So I’m curious what you’re seeing in your practice as well on the male side. I wanted to go back to the workup I guess because a lot of women are probably wondering if I’ve had two miscarriages, who should I be getting referred to and what are some of the common workups that you guys would be recommending? And then we can talk about some of the treatments that you guys are using at your practice

Niamh Tallon:

For sure. So I mean in terms of who to access for workups, it’s usually an OB-GYN who’s interested in the area or a reproductive endocrinologist and fertility specialist. Some places may have recurrent pregnancy loss clinics that are dedicated to evaluating patients with this condition. So really any of those should really be able to offer you a thorough evaluation. And right now the evaluation really is for females, even though we know there is this association with the contribution of maybe damaged DNA from male sperm like you’re alluding to, we can talk about that a little more as to why necessarily that isn’t done upfront. Because it doesn’t necessarily for us in terms of what we’re offering, change the direction in which we may go. But like you said, in terms of diet, exercise, supplements, changing quality of life and improving overall, all those incremental little things you can do to try to improve the bigger picture I think is so important.

So I do talk to men even if their sperm looks normal about the potential quality factors. And we know from studies that DNA fragmentation, if it’s abnormal, so a marker of DNA damage and sperm is associated, you’re more likely to pick up that as a factor is associated with couples who have recurrent loss. So that’s an important piece. But the routine workup is more looking to ensure a couple, firstly doesn’t carry some inherent genetic problem, meaning one of them has a break or rearrangement in a chromosome that just occurred randomly or it could be running in their family and they don’t know about it until you evaluate them because they’ve made it to today and they have had no personal issues. So there’s no flag for them to recognize that they may be carrying what we call chromosomal translocation or rearrangement. So we do parental karyotypes, so a blood test on both parents coming to the table and we’re looking to see if either of them has a higher propensity to make abnormal sperm or eggs and then imbalance embryos that may result in a deemed miscarriage.

Like if you have a genetically abnormal embryo and it’s not capable of bringing a normal life birth. Amazingly, our system naturally can recognize that and it just is from the system just as easily if a man or woman has an imbalance chromosomally and they have made it to this point, if they pass that along in an embryo, that embryo is more likely to make it. So when we find something like that, our treatment is actually to try to create embryos often at IVF genetically screen for those imbalances and try to quickly get to the best one that may bring a pregnancy quickest.

Lorne Brown:

So if somebody has this genetic disorder, if you do IVF, that doesn’t mean that every embryo will have it, that you could find some embryos that don’t have it, which is why you do IVF. So you can look at all the different embryos that you get in that retrieval and determine if any of them, as you said, the best embryo that don’t have this disorder, you can test for that.

Niamh Tallon:

Correct. And also we can’t eliminate age, and that’s going to be a huge part of our discussion where when we talk about implantation failure as a distinct entity, you really are talking about having to remove the most obvious thing, which is aneuploidy. Aneuploidy being a chromosomal segregation error that we see as a consequence of women getting older and the machinery of their eggs not splitting genetic material as well. And every single woman is going to experience making some abnormal embryos even if they’re in their twenties. So it’s a reality of human reproduction that there is a lot of segregation errors. It just is that they become way more common and more of those errors happen the older we get. So that is there and is a thread throughout every way of getting pregnant. Naturally with fertility treatments at IVF, we’re not inherently able to change what’s brought to the table and we’re not able to ensure that someone makes genetically normal embryos. All we can do if we apply genetic testing to the embryos, we can screen for which is the best here, that it’s going to bring us the outcome that we want quicker.

Lorne Brown:

I want to just touch on that, the age part, and we talked earlier about integration. And so when you reach your later thirties or early forties, which is maternal age, as you said, you’re going to find usually more aneuploidy abnormal embryos. This is where we have to be more accountable, and responsible, and more work on ourselves. This is where the diet is more important, movement, sleep, and meditation. This is why we use acupuncture and low-level laser for blood flow because in your twenties it’s more forgiving because you’ve got youth on your side. So you can live a different sex drugs and rock and roll. Your body’s a little bit more resilient, but it does catch up to in your late thirties and forties, and this is where we have to do things to make us as biologically young as possible because chronologically we can’t change that.

So if you’re chronologically 40, but you could be biologically 50, so can we get back to biologically 40? And that’s where so much of the diet, lifestyle, movement, rest, and again, ratting supplements, acupuncture, and herbs leading into that retrieval to support that embryo quality. So I just wanted to put that out there for our listeners that, oh, if I’m 40 doesn’t mean I can’t do anything. There are things you can do to support your health and as we’re hearing, IVF is one of those tools that they can then test your embryos to see if they are abnormal or not.

Niamh Tallon:

And we call that pre-implantation genetic testing for ploidy when we’re looking for age-related abnormalities and immuno, we call it PGTA as in acronym, but really if we’re doing testing for those imbalances that someone inherently has, we call it PGT SSR for a structural rearrangement that we’re looking for. So now there is some evidence that people still can, if they’re getting pregnant and they have that kind of a break in a chromosome, ultimately if they’re willing to keep going, eventually they may get to a balanced embryo. But often these are people who have been pregnant six or seven times and miscarried every time. It’s really hard to live through an experience like that which can take years of your life and occupy a lot of time. And I feel like, and I used to work in a recurrent pregnancy loss clinic years ago, and I feel like I do that now as part of my infertility practice, but we would say really the journey is needing to have resilience to keep going in a lot of this, especially where we say ultimately someone has unexplained recurrent pregnancy loss.

There are a lot of things that can still be in your favor, but you have to stay in the game. And so this is where I feel like you got to address the stress. Look at Allied Healthcare who can support you with everything else that you can do because you want to be the best that you can be in managing stress and those other additive things from just the journey alone that may impair your success for having a successful future pregnancy. We know that acute stress can affect how our responses are like we make more adrenaline to deal with an acute stress response. Chronic stress is something that is probably more meaningful in terms of how it affects someone’s early pregnancy, but if you have both acute and chronic stress, there is thought to be an additive effect and you would see that more in an early pregnancy than maybe later on in a pregnancy. So this is where I feel like resilience, ensuring you’re doing mindfulness, yoga, whatever it is to address those underlying issues is super important when we go through the journey,

Lorne Brown:

Maybe don’t watch the news.

Niamh Tallon:

I know. Imagine, right? You’re living through those things.

Lorne Brown:

If you’re watching the news, you’re on social media, then we’re all having chronic stress, right? We can’t get away from it. So developing practices to find that balance, to find some pieces as you’re saying, it’s important. You mentioned the resilience, so the resilience is important. I just want to give a shout out to your colleague at Olive. Dr. Beth Taylor has an episode on the Conscious Fertility podcast called the Fertility Marathon, which is about that resilience. And then Alice Domar has a talk on stress and fertility also as an episode, so you can check that out as well if you guys want to hear more about that. So with the workup, you mentioned you’re an OB-GYN or a recurrent pregnancy loss clinic or a fertility clinic like yourselves can do this workup. I’m usually in favor of just getting to you guys right away because if you’re trying to have a baby, it’s just nice to, this is your expertise.

You’re looking at people who are trying to get pregnant, so you have the tools and the testing to check for any underlying fertility issues as well as the miscarriage issues because eventually, these other professionals are going to refer ’em to you anyhow. So if we can fast-track, especially as age is an issue, I would just tell our listeners, get referred to your local IVF clinic in Fear Vancouver. There’s all in their integrated well with Acubalance. What are the tests and, how invasive is it? You mentioned there’s some blood work. Is there any ultrasound? Would you, if somebody’s coming in with recurrent pregnancy loss, in your mind, what would be some of the things that you’d want to be testing and how invasive or noninvasive are these tests and how long does it take to get these results?

Niamh Tallon:

So let’s go through the causes and then how we test for them. So essentially a genetic test, a parental karyotype looks for someone what they’re bringing to the table in terms of their genetics, and that’s a blood test. The downside of that is it often takes a few months to get reported here in BC. So there are private options that are much quicker, but three months in the time of someone’s fertility journey can be a little challenging for them to wait for that result. We want to look at anatomic causes for a miscarriage. Now, when we talk about that, we’re talking about the uterus and its ability to house a pregnancy. And we know that every woman can be born with a slightly different shaped uterus. When we’re growing in utero, our uterus actually develops in two pieces or two halves, and it comes together and it’s got a wall in the middle that has to resorb to make a normal-shaped uterus.

And we know there can be residual defects of that wall. And so a large defect will be like a septum. A much smaller residual piece could be what’s called an arcuate uterus, and that’s really like a very mild heart-shaped uterus. Really considered part of the spectrum of normal. But we’re going to test a woman to determine if she has that. Now, the most obvious way to do that is with an HSG or hysterosalpingogram. A screening X-ray test is invasive in that it’s done in an X-ray clinic, the plasma catheter, some contrast dye that outlines the shape of the uterus and the imprint of that dye leaves us with a picture of what the uterus looks like. There are other ways of doing it. If that screening test shows up as highlighting maybe a problem, we’re going to do an MRI ultimately.

Or you could have surgery by looking at the bottom with a camera into the uterus and above from inside the belly to look at the outside of the uterus a laparoscopy, is less done that way because it requires operative time getting into the see a doctor. So MRIs are probably the better way to go if you screen positive. So that is an important piece. I got to say that is not very common to find that amongst the general population. We don’t actually know the true incidents of it because we don’t look for it unless there’s a problem amongst people with infertility, it’s not that common. It’s probably about 8% of patients and more common in those with recurrent loss. So you’re more likely to find it in recurrent loss patients. And we can intervene in those patients who have the residual piece of a wall, which is just not well vascularized.

It doesn’t allow a pregnancy to stick to it and have a good blood supply. So we can operate and cut those away and it kind of reverts them to being normal pain. So that would be the anatomic stuff. I would say a routine part of testing has become checking the uterine lining for signs of infection. So looking for what we call chronic endometritis. We think that it probably is more common in those who are experiencing chronic loss, the idea of background inflammation at the level of the lining. And so that can be done in an office situation, pass a little catheter, sample the lining, send it away, and they give us an idea as to whether or not that is looking overtly inflamed. And then often we treat with antibiotics. There are private tats of that. You’ve heard Lorne of Emma and Alice testing, Emma standing for looking for the microbiome, and Alice looking for chronic endometritis.

So good and bad bacteria certainly I feel like the yield of picking something up is much better with those tests, but they have a cost associated with them done in the same way as what’s offered to a pathology lab where they look under the microscope. But because it’s genetic testing of the sample, they’re really, really thorough and sensitive, and being able to identify bacteria, some controversy over whether or not detecting bacteria without background inflammation really matters. But in those where we’ve treated the finding, we do think that if you get pregnant from an overt-treated case of endometritis, your ongoing pregnancy rate is much better. This question is about though whether or not your implantation rate actually getting pregnant afterward has massively changed, but probably if you get pregnant, keeping it is of benefit. Okay, so we’ve talked about doing your genetics. We’ve talked about anatomic screening of the uterus, maybe a biopsy.

Now there’s also looking at from a history, the environmental stuff like diet. Are you smoking recreational drugs, like you mentioned caffeine in patients who have recurrent pregnancy loss? We really want to make sure that we’re addressing those lifestyle issues, stress everything else. So they’re part of the evaluation. It’s just a clinical evaluation from history. And then in terms of other potential things, well, theoretically you could have a clotting disorder where you actually in a pregnancy really need blood that flows clearly and thinly. You need to be able to have an embryo that can access the uterus and create a normal blood supply to create a placenta that’s going to support it for growth in a pregnancy. And the idea is if someone has a clotting disorder, maybe they develop really small microclots that prevent that vasculature from developing the most up-to-date and current recommendations are not to test anyone for thrombophilia, even recurrent loss patients that would be in every guideline that you would read.

And even in patients who go to see a very experienced reproductive immunology clinic, most of them would recommend, look, let’s do the testing because you can pay for it privately, but the yield is really low. And even if you find a hereditary, something you have that runs in your family is a clotting disorder and you were to get pregnant and treat that, they don’t really think that it massively makes a difference other than preventing you from having a big clot in terms of pregnancy outcomes, very controversial. So they just say, do not test for thrombophilias. So clotting disorders at all, unless someone has a family history and you don’t want them to have a big clot themselves like a clot in a leg or a lung that may affect their health. I do think it’s interesting that most of our patients who are doing IVF during that process are experiencing the most what we call thrombogenic environment they’ll ever have in their lives and that they have the peak level of estrogen from all their follicles growing. And that is a time where if you were going to throw a clot, it would be there if you had an inherited problem. And we don’t see that happening to everybody who is experiencing reproductive losses or failures. So it again highlights that. I don’t think that the piece that we’re missing, however, when we talk about treating someone with a recurrent loss or implantation failure, this will come up again as something that you could address

Lorne Brown:

Just putting on my Chinese medicine lens when you’re talking about clotting. And so the medicine developed well before we had conventional medicine where we could do these kinds of tests. And one of the things when it comes to reproductive health and health in general is the menstrual cycle. And the question is, is there lots of clots in your menstruation? Is it thick and clotty and painful? Well, that’s considered, it may be considered normal as in a lot of people have it, but it’s not considered healthy. And through acupuncture, herbs, and diet, we’re looking for the flow to become bright red, with no clots, no pain, and not thick. And so it’s just neat that in Chinese medicine that is one of the things they look at just the menstruation. And now today we can look at a microscopic level and really test for this kind, because all about circulation, right? Part of it in Chinese medicine, we’re looking for flow and circulation. And so that’s one of the things that we can visualize and understand if you have a good flow or not in that area, vascularization in the uterus. So we’re looking for that good microcirculation to create that uterine receptivity. Just when you were talking, that’s what made me think about that. So you guys aren’t, it’s not common then to do a lot of that kind of workup now the testing on the clotting factors, and that’s not something that is a common thing to test.

Niamh Tallon:

So not for inherited thrombophilias but acquired. Yes, we are. So routine testing includes a blood test for acquired clotting disorders. So really what we’re looking at is antiphospholipid antibody syndrome. Now the syndrome is clearly defined as having obstetrical issues. And so recurrent losses three in a row would fall into that or having a loss after 10 weeks in a pregnancy or a very preterm delivery. So to have antiphospholipid antibody syndrome, you have to experience those obstetrical outcomes and you also need to have abnormal labs. And the labs can’t really just be abnormal once they have to be persistently abnormal over three months. So this is again, part of the journey of these screen positive on something on the blood work for antiphospholipid antibody syndrome, we put a pin in it until we repeat that testing again 12 weeks later and we determine if it’s a real finding, like having an infection, a viral infection.

And of course, over COVID, we saw a lot of these initial first levels of tests being positive, but it was part of the immune response to being sick. So if you don’t really have the syndrome, that will resolve and go away over time. Okay, so we’re really looking for antiphospholipid antibody syndrome. We recently did a study, a very small study amongst patients who had implantation failure, which we can talk about in a bit. But the workup is very similar to recurrent loss. And interestingly in that patient subgroup, we found no systemic causes whatsoever over a year of testing, and all of our patients who had failures with genetically normal embryos. So saying not due to the genetics of the embryo, what else is going on? Are any of these other systemic things abnormal? And we didn’t find anything in the patients that were experiencing failures from embryos. So that also includes, and this would be a standard piece of the workup for return pregnancy loss as well, is the endocrine testing, do they have background issues with their hormones like prolactin being elevated or do they have bad sugar control? And we know both of those things can affect ongoing pregnancy. And so that would be another routine blood test and fasting for the sugars to make sure that they’re in the normal range.

Lorne Brown:

So you mentioned blood sugars. What was the other one you were checking?

Niamh Tallon:

Prolactin.

Lorne Brown:

Prolactin, blood sugars. And do you guys, because I think of our PCOS patients, you look at androgens, I always think of the high androgenic environment also is less receptive for implantation.

Niamh Tallon:

And so that’s kind of controversial in terms of how it’s evolved over the last few years. So the PCO population, I really believe their issue with implantation more relates to in a natural cycle if there’s ovulation dysfunction, your timing, you’ve asynchrony between the release of your egg, your embryo development, and your lining. And so often we’ll see that these patients get pregnant naturally, even in dysfunctional treatment cycles or dysfunctional natural cycles where everything doesn’t align perfectly, they get pregnant, but maybe they have a biochemical loss or a miscarriage. So I think it can relate more to the timing of the egg embryo and lining. The other pieces that patient population PCO group inherently have, and they are a much greater probability of having thyroid antibodies or thyroid dysfunction. And so that’s the other hormone we test is the TSH and checking to make sure that is balanced and normal for an ongoing pregnancy. So in the PCO group, they have a propensity for those kind of endocrine abnormalities and so they’re more likely to experience issues relating to that.

Lorne Brown:

Thank you for that. And we’ve also seen that correlation without research, just our PCO patients, vitamin D issues, and thyroid issues, there was a study using the low-level laser with PCOS, and the mechanism was how it regulates inflammation. So they were saying there’s even more of an inflammatory environment in some of these patients. The blood sugar thing I wanted to mention, I always want to share with the listeners what they can do. So blood sugar dysregulation, the comment went, oh, I got to eat better. And exercise can help with blood sugar, but poor sleep and stress can cause blood sugar dysregulation. That cortisol hormone that we were talking about earlier, when you don’t sleep well or when you’re chronically under stress, you have that increased chronic cortisol which can interfere with your blood sugar regulation. And that’s why stress and lifestyle are an important component and we’re happy to share as well in the IVF setting, they’ve shown how acupuncture helps with that anxiety going through the IVF and there are other studies with it, just using it for stress and depression. So finding ways to help yourself find that balance, that’s not easy, but just putting that out there it is something that we want to bring into our daily lives, not just a one time but a daily life to help us find peace. And more than ever, because the world, like we talked about earlier, getting rid of the news for a while, it’s hard. And prolactin sometimes can be high from stress. There’s other anatomical issues in the tumor and the pituitary, but stress also, right can impact your prolactin levels.

Niamh Tallon:

So I mean, it’s really hard to study in a really robust, very scientific way, the effects of stress because we don’t have really good clinical markers for it. Yes, cortisol can be used for a chronic stress response, but it is hard to study. Now that isn’t to say that it’s not an important issue. It is an important issue, but if you really break it down from an endocrine point of view, which is what I do every day is noradrenaline from an acute response or cortisol from a more chronic response. Both of those things we know will affect how your estrogen, progesterone, and pregnancy hormones develop. So if we look at how hormones develop in a body, there’s a precursor molecule, pregnenolone that is circulating, and then there’s different drives to make those different hormones at the right times. If you’re in a chronic state of stress, your body needs cortisol because your brain recognizes that you need some help.

And it signals from the hypothalamus to the pituitary to the adrenal gland and says, let’s make cortisol to help this person respond appropriately to these environmental triggers. But pregnenolone is also needed to make estrogen properly, progesterone properly, and pregnancy hormone. And if progesterone’s blocked, it’s not there to help with pregnancy hormone development. And so they’re very much intertwined. And if you’re pushing everything to cortisol, well the question is, are you putting those other hormones under stress for their required needs? So I do feel that managing stress is going to become a much bigger piece to all of this when we get really kind of acute or we get better studies looking at the acute on chronic effects. But right now it makes so much sense to me that we would just be doing what we know makes someone feel better. That’s what we should be looking at doing

Lorne Brown:

Because that’s the key, right? Feel better. It’s not like a downside. So if I develop a practice and I have more peace in my life, a child comes or not, I think people would be like, I’m happy I’m doing this right. We all want to be happy in the end. And so this is one of those things, it’s not another thing to put on your list I guess is what we’re both sharing. It’s not like, okay, now you got to be stress-free. Now you’re stressed out about being stress-free. It’s about developing practices so you have more flow in your life and more peace. And this will work towards your fertility.

Niamh Tallon:

Totally. And I do ask patients actually, do you feel another appointment addressing your stress is going to stress you out? And if they say yes, even coming to see you, I don’t have time in my week. I’ll be like, okay, well let’s the demands upon you because it is again, this resilience to keep going. If you can’t support the patient to keep going in their path, they’re just going to stop, which is really not what we want. I just wanted to mention vitamin D. We know that vitamin D can actually improve some of these stress-related effects. So when you read about it, it certainly is a value. And so we’re all probably vitamin D deficient anyway. So in the context of this, it probably makes a lot of sense for someone to be on vitamin D,

Lorne Brown:

Especially you and your friends from Ireland. Yeah,

Niamh Tallon:

Every day. So I guess big picture, I just want to make sure we haven’t missed anything. We’re talking about genetics, we’re talking about uterine abnormalities, checking for infection in the lining, looking at the hormonal stuff, prolactin, thyroid, making sure that you don’t have abnormalities of your milk hormone, the environment stuff, addressing lifestyle and stress, thrombophilias looking for the acquired antiphospholipid antibody syndrome. And then is there an immune component to recurrent pregnancy loss? So probably can we test for that routinely? No, we cannot test for that routinely. And the testing, it’s very controversial when we talk about testing for immune abnormalities. So this more becomes a conversation in the context of recurrent implantation failure, which we could maybe segue to after we talk about addressing treatments for recurrent loss. And I think we should keep it there. It’s probably talking about immune-related testing in that context. You okay with that?

Lorne Brown:

Agreed. So do you want to talk a little bit about the treatment then now for recurrent pregnancy loss? And tell us what you guys, and I’m curious because so many patients now ask about the screening, the chromosome screening, the PGTA, and now it’s kind of controversial, at least in the media. Is there a benefit to it? And I wanted to bring it to recurrent pregnancy loss because heard at your clinic before, this is where this can prevent some people that have from continuing to go through this putting in an abnormal embryo. So I’m just curious, what’s your thought on if somebody’s having multiple losses, is this something you would kind of want to go to screen the embryos to make sure that, to rule that out as the abnormal embryos? Or are you on the, because I’m not sure what you guys are doing at this point in time because there’s been a lot of media and research around this and I’m curious where you’re at today.

Niamh Tallon:

So I think what you’re alluding to more is controversy about screening embryos in the context of IVF for all comers is controversial. So let’s not get into that because it’s not really about recurrent loss, it’s more about infertility and how to manage

Lorne Brown:

Infertility. Agreed. Yeah. I want to talk about that tool for recurrent pregnancy loss.

Niamh Tallon:

So if I see someone who sent me, and I will always ask, how long did it take you to get pregnant? Your time to pregnancy? If it’s like two, or three months, that person is actually super fertile. They’re getting pregnant all the time. There are some people who get pregnant every time they try and they are just seeing early losses by chemical pregnancy losses again and again and again. We call that super fertility. Now that is different from someone who’s taking a really long time to get pregnant and it takes them a year to get pregnant and they have a miscarriage. And what happens is they’ll go, they forget about the fact they took a long time to get pregnant. They saw a benefit to them, which was we achieved a pregnancy and then they focus on the fact that they had a loss. In reality, if it took you longer than a year to get pregnant, you have infertility.

Your loss is one. We’re not so worried about one loss because that could just be bad luck relating to age. So the things we look at are how long did it take you to get pregnant? How old are you today? And what is the likelihood that if you get pregnant you’re going to have a miscarriage relating to age-related, those aneuploidies, those chromosomal segregation errors. So for all comers, you have to do a blanket sweep and peel away what is the probability that their experience relates to age. You have to do that as a first step. So for patients with recurrent implantation failure, that is also part of determining do they really have an underlying issue that is related to something else. Because again, we’re not meant to have abnormal embryo stick, our body is meant to stop them from implanting and they’re meant to pass as a way to safeguard for healthy pregnancy.

So that’s the first start. But there’s two scenarios where we’re going to go, look, you need to get pregnant more quickly. One is someone comes in and says, I’m getting pregnant all the time. I just cannot do this again without changing something. I cannot live through my age-related odds of a miscarriage, which may be at 40 years of age the age-related odds of a miscarriage is 25, 30% with every pregnancy. And they’re like, I’ve had two or three miscarriages. I can’t do the skin. And actually, that may represent two to three years of their life. We also know from a fertility perspective that your odds of getting pregnant at 40 on your own, even if you’re getting pregnant, is low, right? So we ask, what’s your ideal family size? You want two kids. If you want two kids at 40 without your first means, you’re very unlikely to have a second.

So we start talking about even if they’re getting pregnant, what’s your ideal family goal? Some really interesting research that came from the recurrent pregnancy loss clinic, Dr. Bedaiwy and Dr. Cho who both work at Olive as well, just presented this at A SRM and New Orleans where they looked at the length of time it took for someone who had recurrent pregnancy loss as a diagnosis to conceive their second child. And the average age of these patients is 28. They’re young and they’re having recurrent pregnancy loss. They may get pregnant with one, have a successful pregnancy, but how long is it likely that it will take them to have a second? And it was as high as seven years. So this patient group may have a propensity to inefficient reproduction and more reproductive losses, and we have to consider that if their family goal is more than one child.

So we start building into the discussion, if we’re going to achieve that, maybe we need to use fertility tools like IVF to get you pregnant more quickly. You can argue the pros and cons for that. At the end of the day, IVF is the quickest way to get pregnant for anyone, even with a low egg reserve. So it may not be the most reasonable option for a single individual given the cost and maybe other alternatives for them. But big picture, it is the quickest way to get pregnant for everyone. Now if you look at why IVF doesn’t work, and this is a really important thing to understand and make patients aware of upfront is again, we’re not changing what you bring to the table. If you’re bringing 40-year-old eggs, you’re going to have a 40-year-old outcome. In terms of embryos, we know one embryo’s probability of being genetically viable, having 46 chromosomes from mom and dad equally distributed is 35% at 38, 39, and 40 years of age at 41, it’s 20% of 42, it’s 13%.

So your benefit is ever declining with advancing age. And we need to build that into the discussion upfront. So I will say for someone who has recurrent loss and who’s older and who wants a bigger family size, listen, it may serve you best to do IVF younger, you get more embryos when you’re younger, you get better quality embryos in terms of their genetics. You’re more likely to have more embryos to use for a second baby, and you can apply genetic screening to those embryos and eliminate those that are overtly abnormal. And we’re not increasing the probability that we find normal embryos for a given individual. If we find them though and we identify that, remove all the other ones, that would’ve wasted time. That brings you your quickest way to having a baby.

Lorne Brown:

I love the math part of this, and I just want to summarize what you shared. So IVF becomes a strategy. So if you’re more of an advanced paternal age and you want more than one child, IVF becomes a strategy because it helps you get pregnant faster. And if you can test the embryos and you have more than one normal embryo, there’s a higher chance that later on you can use one of those normal embryos when you’re older to get pregnant again because they’re going to stay at that 40-year-old. Although you’re 44 when you’re trying again, the embryo was frozen at 40. And what you’ve shared here is you’re not increasing the odds of normal embryos, you’re just reducing the chance of putting in an abnormal one in a sense, not that you would put in an abnormal one, but every month that could be that abnormal egg turns into an embryo. So abnormal, abnormal, abnormal, and let’s just play a numbers game, you got seven embryos in your IVF. Let’s say out of the seven that you tested, tested only two were normal. Now you know can put in one of those two on the transfer and those other five wouldn’t turn into pregnancies or healthy children.

Niamh Tallon:

Yes. Now there’s some gray stuff in there that we talk about with patients just so they fully understand like the meaning of embryos that come back with maybe a tiny a few cells that are abnormal. We call those mosaic embryos, different potential from a fully euploid embryo with the full genetic complement and like you said, eliminating the completely abnormal embryos from use. I think it’s important to recognize that finding a genetically euploid embryo is not the end of the story. For some patients it is. And it is much more likely that a patient who experiences recurrent pregnancy loss that’s unexplained or has had age-related losses like they’re explained by Tri ME 21 or an imbalance of a chromosome that led to a loss, that we know the reason for that loss. That patient is going to do much better if they’re given the normal embryo, they’re more likely to find a direct route to success in patients with infertility and patients with implantation failure.

What we’ve learned is that not every genetically normal embryo is the same, and it takes up to about three genetically euploid embryos for 95% of all individuals coming to us to get a live birth. Now, many will find a pregnancy in their first transfer, many in their second transfer, but up to 95% in their third transfer with a genetically normal embryo without doing anything else. We’re just saying we’re going to fix embryo as the biggest problem here that affects whether you get pregnant, whether you miscarry, and then ultimately whether you find success with an ongoing pregnancy with untested embryos. So you have not tested an embryo at IVF, we just look at them in the microscope, we give them a grading system, we say they look like they’re really well cohesively stuck together, and the cells are really symmetrical and they look like the stage of development they should be even to achieve a 95% probability of a live birth, you would need seven untested embryos to be transferred.

That’s the most conservative estimate to achieve a live birth from untested embryos seven. And then if the patient has failed up to seven untested embryos and they failed three genetically tested embryos, we can identify 5% of people that really have an implantation problem. But until then it’s an embryo, right? So IV app is a way for that person who has emotional burden or baggage from their experience of losses and it allows them the opportunity to feel like they’re changing something and they’re more willing to give it a try. Recognizing age-related limitations. And then the other plates we’re really using PGTA is again the kind of idea of fertility preservation. Let’s get to freeze embryos for later before you get pregnant now so that we can achieve the goal of your family size.

Lorne Brown:

Excellent. Yeah, it’s great insurance. And I know the women that we see, they just have that peace of mind. They know they have the chance because they have some normal embryos stored for future use while they’re pregnant and they’re getting older. So yeah, it’s a great tool. It’s diagnostic as well. And so what are the other things? And I, I’ll ask you some of the things actually, because I often hear the kitchen sink approach and I’m seeing patients coming in on IVIG and lit heparin, all kinds of things that they’re doing where they’ve had repeated failures or repeated failures with genetically normal embryos. Is IVIG? It’s, I don’t think it’s something we’re doing in BC currently because they’re usually coming from the States or Toronto to get that therapy. But can you just briefly touch on some of these things because there are a lot of things that I’m seeing patients to help them carry full-term and have a live birth.

Niamh Tallon:

So it’s very controversial and there is not a lot of evidence out there for these kinds of interventions for all patients. They’ll just be upfront with that. There really isn’t great evidence, but we’re getting closer to it. And I think recognizing that probably we’ve done the wrong thing over the years by just throwing the kitchen sink at everyone upfront because it’s prevented us from really trying to go in a stepwise fashion and work out what has value for some people and what doesn’t like from a scientific endeavor. So the kitchen sink approach for recurrent loss is different from implantation failure. So from a very pragmatic approach for patients who have recurrent pregnancy loss, what they really need is emotional support and weekly scans usually starting early in a pregnancy. So that kind of treating the stress side, being a supportive care provider, there isn’t great evidence for progesterone anymore supplementation for those patients who get pregnant.

Actually a recurrent loss. Just to be clear, the really, really big studies addressing does progesterone supplementation make a difference? They’ve said no, there are huge studies on this promising trial, the PRISM trial. And so it’s probably not the answer yet. I don’t hold back on it if someone uses it, but obviously, you’re going to treat it if they’ve got it, is it going to treat those? You’re going to treat high prolactin levels and try to get them the best quality embryo. They’re kind of like the big-picture pieces. Manage any thyroid dysfunction if they truthfully have some empiric treatment for recurrent pregnancy loss includes aspirin use and fragment, which is a blood thinner. Again, trying to address potentially undisclosed antiphospholipid antibody syndrome or maybe some propensity to clotting in the background, but as an empiric use, meaning in just throwing it at someone not being guided by treatment. It’s a bit unclear as to whether or not that really carries an advantage for the entire recurrent pregnancy loss group. But we do that because we’re at a loss and we don’t really know what to do to help them other than maybe genetically screen embryos and get to the best embryo fastest. So now recurrent implantation failure is a different beast. Okay.

Lorne Brown:

Can you define it a bit? Is it a normal embryo that doesn’t implant or are you getting a biochemical, a chemical pregnancy? Can you give us the definition of what you’d call implantation failure please? I

Niamh Tallon:

Can give you my definition. So there are many, and again, that’s where the controversy comes from it’s evolved over time. But essentially you need to define someone whose young you believe has an issue beyond bad luck with genetically abnormal embryos from age. So you have to exclude that layer from things. Most people are just having bad luck and not having a successful implant from an embryo transfer, whether that’s fresh or frozen, mostly because of age-related abnormalities. So once you pull that back though, and you’re left with a group of people, a very small number of people we’re talking about, less than 5% of all of our IVF patients are experiencing failures of embryo transfers. And the most reasonable definition is three genetically tested embryos. That would definitely indicate to someone who truthfully has an implantation problem. And again, not very common or there are some definitions out there that they say for someone under 40, so again, that age shouldn’t be that big of an issue.

If they’ve transferred between fresh and frozen embryo transfers, four good quality embryos, they probably have an implantation issue. Okay, now I use three and I like to intervene. If someone has tested embryos and they failed to implant, I like to intervene with something before they end up on their third because I think it’s a lot to put them through without changing something before you get to the last embryo. I think it’s a lot. So ultimately, what are we testing for in this? It’s different from recurrent pregnancy loss because a lot of those patients are getting pregnant on their own. The question is, are they not seeing an implant because of the embryo? Are they not seeing an implant issue because of the uterus? Is that because again, you check the anatomy, is it because of something going on in their lining infection or is it because of receptivity?

So this is where we do an ERA endometrial receptivity array to determine are we putting that embryo at the right time for that person. We’ll also look for infection. So the Emma and Alice testing if they’re willing to pay for that private assessment or we just exclude overt huge inflammation with the pathology lab to rule out the endometritis as a factor. Now the thrombophilia workup, we won’t even get it if we order it here in BC, so forget about it. But usually, if I’m going to intervene with the kitchen sink approach after about two genetically tested embryos or untested about four to six, depending on what their other health is going on in their clinical history, you may start to offer adjuncts. So adjuncts, aspirin, and fragments we’re thought to be helping with a potential background thrombophilia issue. You may offer vitamin D, and vitamin E, I think they’re relatively innocuous.

I don’t think they should be held back. Why not? We do already for IVF, patients offer really high levels of hormone supplementation in terms of estrogen and progesterone like this benefits to those. And we use a combination of vaginal suppositories of progesterone and injectable progesterone. So they are in themselves supportive for implantation and ongoing pregnancy. And then you question if they’re not finding success with these things, and sometimes we’ll consider steroids or intralipid. If you look at the evidence for steroids from randomized controlled trials, they’re like, no benefit really. A SRM says no benefit. Then you may find the odd one that says there’s benefit to using 10 milligrams of prednisone through implantation to the first trimester. So 12 weeks of pregnancy for its ability to dampen immune responses. Everything that we use empirically that is meant to be affecting the immune system acts to dampen the immune response.

Okay, so we’re just throwing steroids at them. We’re going to maybe throw intralipid, which is a soybean fat emulsion infusion. We’re able to offer that at the clinic. It’s easy. It’s relatively cheap in the grand scheme of things. Some studies say no benefit and some say there is a benefit to its use. So why is there, I guess differing studies, and this is where the controversy comes from, is like why do some say there’s a benefit and others don’t? And the same goes for IVIG, Plaquenil Tacrolimus. Any medication you can prescribe for immunomodulation, okay, they’re all controversial. And the reason is we can’t identify what is really going on in these people. We don’t have the proper testing right now. I can send patients and I usually will recommend when I feel that they’re getting close to a definition of implantation failure, I will do the following.

I’ll say, I can offer you the kitchen sink. I can offer you a referral to a reproductive immunologist who will offer you blood testing in your blood to look for immune dysfunction. And some controversies around that, whether that really indicates to what’s going on at the level of the uterus, which is a different compartment to the bloodstream, right? So does it matter what you see as an abnormality in your blood or does it matter what you see at the level of the uterus? And should you be doing a uterine immune profile, which we can also offer here. So there’s some controversy about those two things. So do you want me to throw the kitchen sink, be guided by nothing, see if it works, see a reproductive immunologist, and do peripheral blood testing? Do you want me to do a uterine immune profile and see what I see at the level of the uterus?

And thankfully with that assessment, you can actually target with treatments that we’re able to provide for people. But what we’re getting at is should we be doing some other tests to define who will have benefit to these interventions. And if we better define them, these patients that really would benefit, well then we’re going to see evidence that comes out to say that these interventions make a difference. But if we keep throwing them at everyone, we’re not going to really see benefit for everyone. But I understand why patients want that. So without any other offerings to them, I say, I will give you all of these things that I know that may make a difference, but they could do some harm. And that is the biggest issue. And so this new task, the uterine immune profile, we should talk about this a bit because since I’ve read the literature around this, it’s given me some pause about the kitchen sink approach in the uterine immune profile.

Essentially you’re setting someone up for an embryo transfer cycle and it’s a mock cycle, but instead of putting the embryo in your sampling the lining like you would for Emma, ERA ALICE testing, it’s all defined to the window of implantation, which is very distinct to other times in the cycle. And we know that the immune system is very important in adapting and ensuring implantation takes place. And then it still needs to adapt and change to allow a pregnancy grow. And so the early implantation stage requires the immune system to be in what we call an actual pro-inflammatory state, which sounds counterintuitive, but the proin inflammation is actually, it mimics tissue injury and repair, which you need to have happen so that the embryo can stick. You need remodeling of the lining so that it can stick. And then there’s markers from the immune system that signal to bring that embryo into the uterine lining.

And then that embryo has to be capable of giving signals to modify the immune response. So this coughs talk between embryo and uterus and immune system in between trying to navigate that change. So the pro-inflammatory time, super important needs to be there. The anti-inflammatory transition needs to take place to allow that embryo that’s now expressing paternal antigens proteins on its surface. And the immune system needs to not attack that embryo and remove it as a foreign body. And so this transitioning between these two kinds of immune subtypes and anti-inflammatory is really important. And that’s what the UIN Pro is assessing.

Lorne Brown:

As you hear. I’m so interested because you talked about this. So there’s an inflammatory state around ovulation and around implantation. We need that and that’s why you counsel women not to be taking anti-inflammatory meds for pain when they’re trying to get pregnant around ovulation and around that implantation window. But I want to share with acupuncture and laser, I just got to bring in the integrative part, which I think can be part of that kitchen sink approach. It’s a regulatory because often we’ll say laser people say it’s anti-inflammatory, and the literature shows it regulates inflammation. So it’s certain pro-inflammatory cytokines and downregulating others. And so it’s mimicking helping the body do what it’s supposed to do rather than shutting something down. And so when we do, just from the pain study for back pain, when you give somebody NSAIDs, anti-inflammatories for back pain, you’re shutting down the healing response.

So they have this injury, you shut down the healing response. They have short-term relief, but they end up with chronic back pain. It never gets to have the full healing because you shut down that process of healing that micro-inflammation, when they used the laser, the laser reduced some of the inflammation, but it didn’t shut it down. It still allowed some of the inflammatory response necessary, which meant that there wasn’t chronic pain later. And that’s why I like it in the reproductive health. It is not anti-inflammatory. It is a regulating. And so it’s creating the environment for the body to do this. And they also talk about how it regulates immune responses and macrophages, neutrophils though it’s a regulator, and that’s what you’re talking about here, is you’re looking to regulate not shut something down. And

Niamh Tallon:

It is fascinating when you really start delving into this modulatory evidence that I could list you a whole bunch of things like everything from GCSF to PRP, just even HCG injections, everything that you could potentially offer someone. When you look at its proposed mechanism of action, it’s immunomodulation, IVIG is thought to remove autoantibodies, but it has three main mechanisms. So it’s like antibodies and then the immune modulating effects. And really you need natural killer cells. You need them to be mature and you need them to be less cytotoxic. And so all these things that we’re offering people, they all seem to have the same underlying benefit. So why are we not seeing that as a potential benefit for this group that are not getting pregnant? Why don’t we have the evidence for that? So my bias honestly is that I feel like they’re not all the same. And so Tim Pro was developed by a woman, Natalie Lid Day. She’s done amazing research over 10 years and has published a lot on intralipid and its role, different markers of the shift of balance between this pro-inflammatory and anti-inflammatory time. So there’s lots of evidence behind this uterine immune profile. If you look at their website, their website’s, Matrice lab or M-A-T-R-I-C-E, and they have an English version. They’re based in Paris and they have really amazing supportive evidence, but it comes from them. So it is fought to be a little controversial. Their proprietary test and

Lorne Brown:

Bias. There’s some bias there. Okay.

Niamh Tallon:

Yeah, a little bit of a bias. But what they’ve shown is that if you were to apply this biopsy to everyone that, and they do offer it for term pregnancy loss, there are kind of different subgroups of patients that come back. And so I’ve started offering this since January. And of all my patients, I probably have 35 people who have true implantation failure. And of all of them who’ve decided to do this test, they all come back. Abnormal bar one, I’ve had one come back normal. Otherwise, they identify there is a dysregulation and they put them into different categories. You’re either underactive, you’re a mixed immune profile or you’re overactive and they treat them differently. Now we’re really early in this, but your

Lorne Brown:

Mom would be very proud because Chinese medicine is about individualized care. So you got to diagnose and find out you don’t treat the disease, you treat their underlying pattern and that’s what you’re sharing. And that’s where western medicine is going through genetic testing and testing is even with the drugs. But what you’re sharing is individualized care because implantation failure is the disease, but you don’t treat the disease in Chinese medicine. What is the underlying cause of that implantation failure? And that’s what you’re suggesting. That’s why I said your mom would be very proud because that is individualized medicine and that’s the medicine that she practices. Great. Here’s the disease. Now why is this person manifesting it? And people may manifest the same implantation failure, but there may be five main reasons behind it really.

Niamh Tallon:

And to be honest with you, what I’m seeing, it’s a very frustrating test for patients, I got to say, and I can understand why patients don’t want to go ahead with it because it takes a full month to do it a full month to get the results back. And then they may say, we need a verification biopsy with everything we’re recommending in place, we want you to verify that biopsy and make sure that we’ve made enough changes. But in the patients that I’ve had to follow it through, not all of them do because of the timeline and it’s rough on them, but those have been committed. They can go from overactive now they say, put them on steroids and let’s have a look again. We do. And they go, actually, they’re now over. They’re a mixed immune response. It’s not suppressed enough. Now put them on intralipid and fragment with their prednisone. They’re like, oh no, we totally, we’ve made them underactive. You know what? We’re going to do a combination of intralipid and fragment and actually they need a scratch before their transfer. And you need to do intercourse on the day of an embryo transfer because sperm elicits an immune response from the uterus and demonstrates paternal antigens and acts to upregulate the immune response in the same person over its different cycles. With all these different interventions, you can change what they look like.

Lorne Brown:

And so again, it becomes individualized. It’s a lot of work on your part and a lot that the patient has to go through. And as you said, it’s difficult. They need the patients to do this, but it’s kind of like three steps backward, 10 steps forward because if you have the three months to figure things out, then within three to four months they are pregnant versus if you don’t, it could be ongoing implantation failure. So

Niamh Tallon:

I have to say though, honestly, I’m not there yet with what we’ve done here to be able to say that they’re all going to get pregnant, we’re right in the middle of where we are looking at this. I mean, I offer it to people because a test with some evidence that’s on the, they’re offering this routinely in Paris. It’s covered by their government and unfortunately patients have to pay for it here. What I’ve heard from the reproductive immunology group in Canada is they’re not really seeing a massive benefit, I don’t think, for patients with recurrent pregnancy loss, but they’re not doing verification biopsies and that’s yet to be published. So we’ll see that coming again, I think it’s probably a step in the right direction to try to determine what category do you fall in. And really my algorithm of care is if they don’t want to do kitchen sink or we’ve done it and it’s failed and they don’t want to do the uterine immune profile, this is really where I’m like, listen, I’ve kind of exhausted what I can offer you in terms of an infertility specialist here where I cannot access IVIG.

Now, I really believe there’s a role for IVIG anecdotally and in the evidence where they’ll say from big studies, there isn’t overwhelming support for using IVIG. But again, in that subgroup of patients where you can identify dysregulation, there is if you identify those people. So I mean in BC there’s a regulating body that just doesn’t allow us to access IVIG and they won’t until we have really clear evidence that it’s of benefit. There are suggestions for true recurrent loss patients. And a big study that came out last summer from Japan looking at people that had four embryonic demises and they were all genetically normal and those patients benefited from IVIG with improved life birth rates. But that’s a unique group. We don’t see a lot of people like that. We need the evidence to show that we know how to identify people that would benefit from IVIG and then I think we would be able to access it here in bc it’s expensive.

It’s like anywhere between five and $10,000 an infusion and you have to travel to get it because we can’t access it here. So in those patients who failed, either something we’ve done that we have been able to offer the kitchen sink approach or they don’t want to do YouTube Pro and they only have one embryo left and they just want to do IVIG, we can help guide them get to that place. Or they may seek just pure consultation with a reproductive immunology group like the Allen Bearer clinic or at Dr. K Kim in Chicago. And so through them, they get peripheral testing, which is thousands of dollars, and then they cite directly based on peripheral blood work, how best to treat them, but most get IVIG or LIT or some form of immunomodulatory treatment, ensuring that their sugars are good, ensuring that everything else is in order in terms of an ERA, no infection. So it’s just, I will say of all my patients who’ve had recurrent implantation failure of those that go to IVIG most get pregnant, not all of them do, but I have seen within one or two treatment cycles with IVIG so far in the small subset that I have anecdotally that they get pregnant with it. So I’m quite hopeful that we get more evidence to be able to make an argument for IVIG. But part of that is again, really working with these studies to try and identify the right people.

Lorne Brown:

That’s the key, finding the right people that will benefit. And I want to share, again, talking about the kitchen sink, and then we’ll wrap up. I know we’re going long here, but hopefully, our listeners are getting some good information that they can take to their practitioners. The acupuncture. I want to share with you that there was a meta-analysis published in July of 2023 where they looked at 4,700 participants and those that did acupuncture leading up to transfer and on transfer day had a 28% increase in pregnancy rates or implantation, sorry, 33% pregnancy rate, 33% live birth rate increase, and there was a decrease in biochemical pregnancies by 51%. So that’s another thing as part of the kitchen sink, we also use Chinese herbal medicine. I know in the west conventional, that’s still hard for people to get their heads around. There was a talk by Dr. Paul Elli who’s with Kind Body now at the Integrated Fertility Symposium, and he shared research out of Taiwan and Korea, China where they’re using herbal medicine and I VFS in those clinics and they were having higher pregnancy rates.

So something always to consider. A question I have for you, so this is something that I don’t know if you have evidence for, but it’s just something that I was thinking about when you’re talking about the ALICE test and the Emmett like looking at the ERA, I mean looking at endometritis, so inflammation and the microbiome, would it be beneficial then prophylactically just to give women an antibiotic and give women the probiotic because it’s not a high cost and it has low risk. And so have you ever thought of that just to give them just because we can’t always test or we don’t always find in the test and just give them that for a cycle or two? I’m curious just about your thoughts on that.

Niamh Tallon:

Yeah, I mean years ago we gave everyone doxycycline around the time of a transfer and that wasn’t shown to really be a benefit. And I think if we were to prescribe antibiotics for every patient, we’d see an emergence of resistant microbes that we would just have a really hard time treating ultimately with antibiotics and we’d never be able to eradicate them. We’ll just put pressure on them to evolve and develop resistance.

Lorne Brown:

So we’ll cut that one out. So don’t do that.

Niamh Tallon:

I used to prescribe a vaginal probiotic for everyone and then I would kind of wonder, it doesn’t seem very judicious when you’re doing an assessment like Emma or Alice and every single time it comes back showing you that the patient is low in their microbiome, good bacteria. And so I actually emailed the company and I said, why am I doing this test is if everybody has a low microbiome, why wouldn’t I just treat them all? And actually they gave me back their statistics for, I mean every clinic that feeds into them with biopsy results, we represented truthfully people who had implantation failure. And so they could show me because we have to fill out a form that says why we’re doing this. And they said, actually, you’re doing it in the right people, so you’re finding something in the right people.

Lorne Brown:

Well, the demographic you were testing

Niamh Tallon:

Was the right person to tap.

Lorne Brown:

Yeah, that’s why it was showing up low. Okay,

Niamh Tallon:

So no harm in treating them. I think that the issue is that real endometritis patients who truthfully have a deep NIUs of infection, you treat them, and it comes back again. You may have wiped out some of that bacterial infection, but now there’s an emergence of something else that’s taken over. You treat them with another antibiotic that should get them and then they come back again as positive. These people are different and thankfully not very common at all, not common, but their implantation rate, even when you fix ’em with antibiotics, their implantation rate is lower even after treating their infection. If they get pregnant, they’re less likely to miscarry though now there is emerging evidence on the role of the microbiome to actually support the health of an ongoing pregnancy. Most people would understand in the obstetrical world, we do screen sub-patients who experience preterm deliveries or very preterm delivery for certain bacteria that are associated with eliciting the pro-inflammatory response.

Again, pro-inflammatory in the second trimester after 13 weeks is not good for pregnancy and is associated with smaller babies. Placental dysfunction, having an earlier delivery or miscarriage before 24 weeks, that late miscarriage between 13 and 24 weeks. So the bad microbiome or bacteria can certainly elicit ongoing pro-inflammatory markers that then don’t support the normal growth of a pregnancy. So it’s going to become a much bigger piece I think of research and it’s going to direct I think more and more how we treat people earlier on, but right now we don’t have the evidence to do it for everyone.

Lorne Brown:

Just to relate it to the microbiome, just the gut microbiome, you’re talking about the uterine microbiome, but the naturopathic physicians, they’ve been looking at this for ages and how the microbiome often people think in the gut it’s got to be digestive stuff. So that is one of the signs. But skin-related stuff is affected immune now connected to there is some links to autism and depression. And so just addressing that gut microbiome is important. And so again, diet and lifestyle is a big part of that that can affect, that stress, can affect your microbiome, those stress hormones. And then I’m not sure if you’re aware, but I’m actually interviewing Ann Liebert next week to talk more about her Parkinson’s study because a link between the gut microbiome and its inflammation and Parkinson’s, they did a low-level laser study lasering the gut and the brain and they saw improvements in symptoms and they did also the DNA sequencing of the microbiome.

So they were able to see if it really did change, not just looking at the symptoms. And they did show a change. And again, kind of our kitchen sink approach at our clinic at Accu Balance when we use laser, we’ve combined many different approaches to help with blood flow, and regulate inflammation. And one of the things we’re doing is making sure we’re addressing the gut microbiome as well, just giving the body what it needs so it has that flow and receptivity so we can do what it’s supposed to do hopefully and create that balance. There’s a question about the intercourse, and then I wanted to, we’ll have to wrap up and we’re going to have to have a part two with you, but you said something about intercourse and it just reminded me of a colleague. So a Chinese medicine doctor colleague five years ago, I was at his talk and he talked about sperm and how it has that immune modulating impact on the woman. He was saying back then that he wanted his patients to have intercourse five days before they’re transferred leading up to it kind of when you’re starting to have intercourse leading up to ovulation, not just on, because transfer days is already five days past ovulation in theory. So he wants you to have sex five days before your transfer. And so when you said that, I was like, oh, interesting. Because when he said that, we’re like, eh, what’s he talking about? And now I’m like, interesting. No, I

Niamh Tallon:

Think it wouldn’t do harm if you are a normal person. It’s really this underactive group with the uterine immune profile that I find really interesting. The patients I’ve had, they have never had an implantation ever, no biochemical pregnancies. They’ve done loads of treatments, they’re using genetically normal embryos. And what you see is they come back often underactive, and you can do these things like a scratch to upregulate, like a scratch is a biopsy the week before a period and thought to cause tissue damage. And then you bring in the repair, which is the immune system is then coming influxing to try to help and repair and the eliciting of sperm for that same kind of immune response. But I don’t know what it would do to someone who’s overactive.

Lorne Brown:

Interesting

Niamh Tallon:

Because you’re eliciting more of an immune response in someone who you’re trying to dampen things down with. So I don’t know. It’s way more complicated than I think we’ve really had insight into. I think we’re beginning to recognize that not all patients are the same. Now, I would just want to add this, Lorne, I’m very hopeful for patients in general because I think what we’ve learned is real implantation failure is rare. It is not very common. And I hear from people all the time when they’ve not had success with fertility, they go to IVF, they do their first embryo transfer. It doesn’t work out that they’re like, I have an implantation problem. No, you don’t. You just feel like you have an implantation problem and we have to be able to support that kind of messaging. That really true implantation failure requires a lot of these aneuploid embryos to be removed, remove all the really big common things before we can really say you’re down to that tiny group of people who have a real issue.

Lorne Brown:

Thank you. And to kind of summarize this at the end, we shared a lot today, and for our listeners where they’re like maybe feeling, oh my God, what do I need to do? Here’s the good news, you don’t have to figure this out. You have the advice here is to see your local expert. And so here is a reproductive endocrinologist. So if you’re in BC, get yourself referred to Olive because they will figure that out for you. They’ll let you know what testing you need to have done and what treatment, so you don’t have to get too worried about that part. You just want to get yourself referred there. And then from the allied side, the Chinese medicine side, looking at your people that have autoimmune like symptoms, your gut health, your blood flow, your stress, looking at the vitamin Ds, herb supplements, again, we can help you with that.

The acupuncture, low-level laser therapy so you can get your team together and then they can support you on your journey so you have more peace on the journey and more confidence and resilience. So you can go through this because as Niamh shared at the beginning, it sometimes can take up to three transfers in an IVF to get that live birth. And the difficult part is the resilience. So if you have a good team around you, they can give you or support you with confidence and give you that resilience so you make it to that live birth. And so that’s kind of how I wanted to close. And I believe I’d love to have you have the closing statements. I just wanted to share that a lot of things that you’ve heard today could be this, could be that, could do this, could do that, and you don’t have to figure that out. You have experts like Niamh and the other docs at Olive and then the team at Acubalance, they can definitely support you on that. And do you have anything you want to share on this topic of miscarriage and implantation failure?

Niamh Tallon:

Everything you’ve said to wrap it up. I can’t highlight the importance of just ensuring you have a feeling that you have all your concerns addressed as you go through your journey. But I would say explained losses as much as they’re heartbreaking. It’s very reassuring when you find the results that says either in passage of tissue from a miscarriage or if we do genetic testing of embryos and we’re like, look, it’s abnormal. Don’t use that. It really can help with allowing you to move on to really determining where you’re going to get value from and making smart next steps. So you just want someone who’s looking at all of those pieces of your history, what you’ve gone through so far. And unfortunately, the embryo is a huge, huge part of this, and age is a huge part of this. So the sooner you are motivated to be seen and start your family journey or developing your family, that’s the best thing that you could do because really coming in older, everything is just so much more inefficient. So hence, I guess the great part of freezing your eggs when you’re younger, but we’re just not seeing as many women motivated to do that.

Lorne Brown:

Great. Thank you for that. And you talked about age as a factor. In the very beginning you mentioned that if you’re under 35, it takes up to a year to be diagnosed with infertility. You have to wait a year. And one thing I wanted to share is that, but if you’re under 35 and you’ve had two pregnancy losses, you do not need to wait a year. You can get yourself referred to a clinic like Olive because you’ve had those two losses.

Niamh Tallon:

Sure can. And I really feel like if you just want a bigger family size and you know that it’s taken you a long time and you’ve had a miscarriage that’s wasted your time, you want to get going with safeguarding a bigger family size, that in itself is an indication to be referred. You’re motivated to safeguard extra embryos for baby number two when you’re getting older. That in itself is meaningful.

Lorne Brown:

Great. Thank you very much ne for coming today on the Conscious Fertility Podcast and sharing this information.

Niamh Tallon:

Lorne, thanks for having me. And I think it’s amazing that you’re doing this and the people that you’ve had on amazing content.

Lorne Brown:

Thank you. You can go to olive fertility.com to check out Dr. Niamh Tallon and the team at Olive and it’s Acubalance.ca to check us out at Acubalance and wish you all resilience on your journey.

Speaker:

If you’re looking for support to grow your family contact Acubalance Wellness Center at Acubalance.ca, they help you reach your peak fertility potential through their integrative approach using low-level laser therapy for fertility, acupuncture, and naturopathic medicine. Download the Acubalance Fertility Diet and Dr. Brown’s video for mastering manifestation and clearing subconscious blocks. Go to Acubalance.ca. That’s Acubalance.ca,

Lorne Brown:

Thank you so much for tuning into another episode of Conscious Fertility, the show that helps you receive life on purpose. Please take a moment to subscribe to the show and join the community of women and men on their path to peak fertility and choosing to live consciously on purpose. I would love to continue this conversation with you, so please direct message me on Instagram at Lorne Brown official. That’s Instagram, Lorne Brown official, or you can visit my websites Lorne brown.com and Acubalance.ca. Until the next episode, stay curious, and for a few moments, bring your awareness to your heart center and breathe.