Rescripted S02E08_When IVF Fails: Audio automatically transcribed by Sonix

Rescripted S02E08_When IVF Fails: this mp3 audio file was automatically transcribed by Sonix with the best speech-to-text algorithms. This transcript may contain errors.

Kristyn Hodgdon:
Hi! I'm Kristyn Hodgdon, an IVF mom, current IVF patient, and co-founder of Rescripted.

Lucky Sekhon:
And I'm Dr. Lucky Sekhon, a board-certified reproductive endocrinologist at RMA of New York.

Kristyn Hodgdon:
Welcome to Dear Infertility, the first-ever podcast that doubles as an advice column for the millions of people globally who have trouble conceiving.

Lucky Sekhon:
We're here to answer real questions from real fertility patients about what to expect during each stage of the fertility journey and to provide you with the patient-centric advice and guidance you need to be your own advocate when trying becomes trying.

Kristyn Hodgdon:
Now, let's dive in and help you feel more empowered during this overwhelming process.

Kristyn Hodgdon:
Hi, everyone. Welcome back to Dear Infertility. I'm your host, Kristyn, and I'm here with Dr. Lucky Sekhon. Hi, Lucky.

Lucky Sekhon:
Hi. How's it going?

Kristyn Hodgdon:
I'm doing well. I'm really excited to talk about what happens when IVF fails. You know, it's such a devastating time when you've put energy and money and your body through so much to go through IVF, and then you don't get the outcome you're hoping for. So today we're going to talk about some of the reasons why IVF might fail and then possible tests and treatment options.

Lucky Sekhon:
Yeah, so I'm so glad that we're talking about this. Obviously, this is such a challenging part of my job and my role in helping patients. Anyone going through IVF, whether it's their first step or they're coming off of IUI cycles that didn't work, and now they're moving on to IVF, I think you go into it with this bias that IVF has high success rates and this is going to be the magic bullet that fixes everything. So when you do encounter challenges along the way and we'll talk about all the different ways that you might not have a successful outcome because it can happen at different points in your treatment, it can really blindside patients and it can make them feel really hopeless. And so what I'm hoping that we get out of today's discussion is really illuminating what the different things that can happen are and the fact that there are often things you can try or potential solutions to discuss with your doctor. So even though we're talking about treatment failure, I hope that this has a really positive spin and gives a lot of people hope and information that they can arm themselves with.

Kristyn Hodgdon:
Yeah, I mean, so much of fertility treatments can feel like trial and error, but in a way that is a positive because there's always something to be learned and adjusted. So starting with ovarian stimulation, you know, you, you start IVF and you might be a low responder to, to the meds. Can you speak a little bit about that?

Lucky Sekhon:
Yeah. So the goal, first step in IVF is to stimulate the ovaries, to get as many of the eggs that are available to grow and mature so that we can extract them and fertilize them. And we're never completely surprised on a day of egg retrieval about how it went, because we're doing those check-in monitoring visits, usually 5 to 6 visits throughout the 8 to 10 days of injections where we're doing ultrasound and bloodwork so we can tell what your response is as you're going along. And we might use that information throughout the process to add or cut back medications. And for patients who tend to have a low ovarian reserve, they have a low AMH level or a low starting follicle count, oftentimes their reserve goes hand in hand with their response. And so we anticipate that it may take extra time, it may require maximal doses of medication. And even despite all of those things, you might still be seeing a low response where you're not getting the majority of the follicles that are there to grow, or there just isn't a lot to start with, and whatever is there isn't growing so well. Sometimes you can get a few of the follicles that kind of breakaway early and start to lead the way, and then the small to medium-sized ones aren't really progressing that much. So there's this idea of the cohort of eggs that was there to be stimulated, starts to kind of get split and there's this chasm between the smaller ones and the bigger ones. And that's always annoying when that happens because you feel like you're not getting as many of the eggs that you potentially could have had if the stimulation had gone differently. Another pitfall or negative thing that can happen during the ovarian stimulation process is ovulating through the medication. Now, that is very rare, I would say, because the protocols that we have in place do a good job of preventing ovulation, but you can have medication error. And some people, their biology just requires higher doses of that suppressive medication to prevent you from ovulating. So those are just a few examples of things that can go wrong during the ovarian stimulation part of the process. Now, the way I would address this, particularly the common issues of a low response or getting a wide disparity between the sizes of the follicles towards the end of the stimulation, I think that's where you would make a decision in a subsequent cycle if you were trying to improve upon what we learned, we would change the protocol and some protocols are better than others for certain individuals. In medicine, there's this concept of pharmacogenomics, which is this idea that we are all individuals with our own genetic signature and we're all unique, and part of that genetic signature is what determines how we respond to medications differently. And this is an area that's been studied in different fields of medicine, and it's been used to help come up with what dose of medication to give people, but we just don't have this information for fertility drugs yet. But it's not unheard of that some people will respond better to one set of drugs than another. And there are different protocols at our disposal, and we use different types of medication to prevent you from ovulating. So there are different sets of cocktails of drugs that we're using. And so if one particular protocol from a specific group did not work well, did not produce a good response, then it's logical to say in a subsequent attempt you could switch to a different group of medications that has a different mechanism of action and especially the way it's going to suppress you from ovulating. So I definitely think switching to a different family of medications could be helpful. The dosing, if you have room to go up, then maybe you would increase the dosing if you wanted a better response. But it's important to know that there's a certain level above which it doesn't make sense to keep increasing the dose because eventually the receptors on the follicles get saturated and you're just at that point wasting money and the patient's taking more medications than what's actually going to be useful to them. So it's always good to ask your doctor about what they view as a maximal dose and if there's room to go up on the dose. And then something that we talked about in the last episode was different supplements that can be taken. We've talked a little bit about acupuncture and adjuvant treatments. So these are all add-on things that you could talk about implementing before doing another cycle.

Kristyn Hodgdon:
Awesome. And in what cases would you actually cancel the retrieval versus moving forward with less than optimal results?

Lucky Sekhon:
It depends on the situation. But in general, I always say in a regular natural cycle, without medications, you're usually able to ovulate one egg. So ideally, if you're going to go through the whole trouble of an egg retrieval for the purpose of IVF, I think the minimum that I would feel comfortable going into a retrieval for is having two follicles that are measuring mature. If it's just one, it doesn't mean you can't have a retrieval, but I think it would make it far less efficient. The goal should always be two or more, just because not every follicle is guaranteed to yield a mature egg. We drain the follicle, which is essentially a bubble of fluid, hoping to pick up an egg. And when you go into a retrieval for just one follicle, there's a chance you might come out of that retrieval with no eggs or an egg that's not mature. So ideally, I think two or more, but again, it really just depends on the individual situation. I also think I've cancelled for patients that have even more than that because I thought they could do a lot better if their baseline count is 14 follicles, but only two, for some reason, grew ahead of the rest, and I'm worried about only getting two eggs when I think that they could potentially get more based on their AMH and their starting egg count, maybe that protocol just didn't suit the, maybe there's other things that we can do to improve their response, I'll talk to the patient and we'll come up with a decision together. Another thing that factors into the decision, as much as I hate to say it's not all about the medicine is also their benefit. Sometimes your insurance will count it as an entire cycle, even if you don't go through the retrieval, in which case it makes sense to just go through with the retrieval no matter what. A lot of times they won't. If you don't do the retrieval and you stop before that point, you'll be refunded the money that you didn't use yet because you didn't go through the whole process. And the most expensive part of IVF is everything that happens in the lab, right? So if you think you can do a lot better than getting just two or three eggs because you have a lot more eggs to work with, it might be worthwhile to stop the process, regroup and do things a bit differently in a subsequent cycle.

Kristyn Hodgdon:
That's really helpful. So what about post-egg retrieval? You go through the retrieval, but you kind of end up with less mature eggs than, than everyone was hoping.

Lucky Sekhon:
Yeah. So I always tell patients that I don't expect every single egg that's extracted to be mature because when we go in to do the retrieval, we're essentially draining those bubbles of fluid or follicles. And I'll drain any follicle that I see, right? Because these are all eggs that will be thrown away if they're not retrieved at the end of that cycle. So I'm going to drain even the smaller follicles and the size of a follicle tends to correlate with the chance of having the egg inside of it be mature or not. And so if you're draining smaller follicles, you are going to get some immature eggs, but my ideal proportion of mature eggs at time of retrieval is 80 to 90%. That to me is a successful outcome, it does not have to be 100%. If it's lower, like let's say only 50% of the eggs retrieved end up being mature, I think there's room for improvement. There's things that you could probably do better in a subsequent cycle in terms of timing when you do the trigger shot, perhaps that patient, even though on the day of trigger shot, their ultrasound looked like they had a decent number of mature follicles, perhaps they have a tendency towards egg immaturity and maybe they are a patient that needs extra time. So in a subsequent cycle, I would probably put a note to myself to say push an extra day. So even though they look, quote-unqu, s ready, give them an extra day of medication, because that might help kind of push those remaining eggs that are immature over the threshold where now they can be utilized and actually inseminated with sperm. We can't fertilize immature eggs. So that's the issue, right, is that they need to be at a certain stage of development in order to be utilized in the next stage of IVF.

Kristyn Hodgdon:
Yeah, absolutely. And then so then that brings us to sort of low fertilization rate. So if the egg isn't mature, we would, you wouldn't even try to fertilize it. But what happens when you do try to fertilize it or them and it doesn't really yield great results?

Lucky Sekhon:
Well, again, I don't expect 100% fertilization rates. What I think is the norm or average that, that we see at our center is 70 to 80% of eggs fertilizing successfully. So I think it's always important to interpret your results in the context of the averages and what we expect. So if you had only 40% or 20% fertilize, that's, that's lower and you would think about ways to do things differently to try to improve that outcome. You know, an extreme example is having none of the eggs fertilize. And that's always a very perplexing issue, especially if you already used ICSI as the method of fertilization where you're injecting sperm directly into each egg, that should theoretically overcome any sort of male factor issues, but sometimes it's not enough to do that. And when, when you have failed fertilization, where none of the eggs fertilize, some of that could be egg quality-related and some of it could be sperm quality-related, and some of it is a combination of both. So I think it's a frustrating problem because you don't always know, but you might have a clue based on the clinical history. Like if this is a couple where there is severe male factor fertility issues and you did the ICSI, but you still had failed fertilization, you would have a strong suspicion that this is coming from the male side. But if this is normal semen analysis and the patient is older and, you know, they're mid-forties or early forties, maybe it's an egg quality issue. What we can try to do and this is something that's, I wouldn't say it's controversial, but it's not something that's utilized across the board, but I've done this in the past where, in a subsequent cycle we'll tell the, the embryologist to try to activate the eggs with calcium ... for treatment and some cases that may help with any sort of fertilization defect because it's a pathway, it's a bunch of successive reactions that take place between the sperm and the egg. And so calcium is a major signaling mechanism for cells. And so at that early stage, activating the eggs with calcium can help to promote better fertilization. And then in cases where you really suspect that there might be a male-factor issue, I've had patients where they plan to inseminate half or all of their eggs with donor sperm in the next cycle. Half could be beneficial because that's going to also be diagnostic, right? If the half that are fertilized with donor sperm do so much better than the ones that were fertilized with the partner sperm, then, you know, you've really identified the cause of the problem. So it's a really difficult situation, but I've seen patients have really successful turnaround and better outcomes by making certain changes. And of course, if you're doing conventional insemination as your first step where you're just taking each egg retrieved at time of the egg retrieval and dumping 50,000 sperm onto each one and just letting them incubate and interact on their own, and that yields 0% fertilized or a very low proportion fertilized then, you know, in the next cycle to do ICSI, which involves injecting one sperm into each egg.

Kristyn Hodgdon:
Wow, that's really cool to be able to diagnose that way. Awesome. And then, this is something I'm really interested in learning more about, the, like when embryos arrest. Can you speak to that a little bit?

Lucky Sekhon:
Yeah. So embryos are fertilized eggs that have now grown and divided into several cells. An egg is a single cell, sperm is a single cell, they come together and form two cells and then keep growing and dividing, and that's embryo development. And we can see this happening in the lab. We grow embryos for up to one week and we typically see a lot of drop-off going from fertilized egg to a day five to day six, day seven embryo. Our average, I can speak to our statistics at RMA of New York, but the average rate of conversion of a fertilized egg to a blastocyst or day five embryo and beyond is about 60%. So we anticipate and we mentally prepare patients that you're going to see roughly half drop-off between those two points in time. And that is, I think one of the hardest parts about going through IVF is that waiting game to know how many eggs turned into embryos because especially if you've never done IVF before, it's really hard to know what to expect. And I'm anxious about that waiting game as well, because my hope is for everyone to have a really high conversion rate, so you have lots of embryos to work with. But a lot of embryos do arrest or stop growing along the way, and it's because of what the embryo is expected to do. It's a very intense process where in its stage from fertilization to day five to day seven, it's expected to get rid of all of the programs that it inherited from both the egg and the sperm and start turning on its own genes and a lot can go wrong in that process. So that, we know is a major contributing factor to why embryos do not continue to grow. And we know a lot of this can be driven by quality in general, and a lot of embryo quality is derived from the egg. And a lot of times when we see a sharp drop off, it might be something that we suspect that there could be an egg quality issue, but there is also a contribution of the sperm. And so something that's a newer idea is that sperm with lower amounts of DNA fragmentation might help promote that conversion of fertilized egg into an embryo, and some labs are utilizing technology to help sort the sperm. And by using sperm that can swim through this special membrane, you're selecting the healthier sperm that is going to have better integrity of its DNA. And it may help to contribute to more eggs that are fertilized turning into embryos. If you've done everything you can do and you're still having a lot of drop-off, the only other way around it is to try to do everything that you can possibly do to maximize the number of eggs retrieved that are mature and capable of being fertilized. Because if you have more to start with, even if there is a high level of attrition, it's going to improve your chance of ending up with an embryo at the end of the day.

Kristyn Hodgdon:
Absolutely. So I have a quick question, because I have heard some, I know a lot of clinics now, that sort of the standard of care, try to make as many day five blastocysts as possible and then send them off for PGT-A testing. But can you explain a little bit why a patient might not be able to make it to day five, but then all of a sudden does a fresh transfer and has success? Like I've seen that in a decent amount of cases and I, or just through the community and I'm just curious why that might be?

Lucky Sekhon:
Yeah. So before we really knew how to grow embryos out to day five and beyond, the mainstay of embryo transfer treatment was to transfer an embryo at day three of development. What we know now from decades of experience creating and growing embryos in the lab is that it doesn't take a lot to get to day three, it's almost like the embryo is on autopilot. It's still just following the directions or the GPS from what's inherited from the egg and the sperm, it's beyond day three that the embryo kind of has to sink or swim and turn on its own genes. So because it doesn't take much to get to day three, it's not hard to get a day three embryo and be eligible for a transfer. But a lot of that arrest that would have happened if that day three embryo was left in the lab is going to take place, but it's going to take place after the embryo is transferred. So day three transfers done right after the retrieval, you're not trying to freeze anything, do have lower success rates than day five day, six day, seven transfers, I would say definitely day five, day six transfers. And the reason for that is, is just the embryo that's being selected, the selection process is less stringent when it's in day three. To get to day five, you've weeded out a lot of those abnormal embryos that weren't destined to go anywhere. And now you're left with embryos that theoretically are more competent, and they were strong enough to get to that stage of development. So the majority of embryos that are rest would have been abnormal and probably not grown, or if they had grown and implanted, may have resulted in a miscarriage, right? But there's that small sliver that might just be slow growing, but not necessarily because they're missing or have extra added chromosomes or problems that would preclude them from turning into a healthy pregnancy, but maybe there's other issues that it can recover from. So that's kind of the secondary plan for especially centers that tend to do a lot of PGT, a lot of freezing of embryos, a lot of growing embryos to day five, if that's not a possibility for a patient and maybe we view that as the ideal situation where you have the most amount of control and ability to select the healthiest embryo. But not everyone's going to be able to meet that ideal goal of having embryos in that situation. And so I, in my own practice, have pivoted to doing things like a fresh transfer or just whatever's fastest growing on day five, let's put it back and hope for the best. Now, you're always by giving up the precision, the technology and the control, you're accepting certain risks. First off, in older patients who aren't doing PGT and we're just doing a fresh transfer to counteract the fact that we know a higher proportion of their embryos coming from their eggs at that age are going to be abnormal, it is a smart idea to put back more than one, right? And so there is a risk of twins which are higher risk pregnancies that come with their own risks, right? And also, if we don't know if these embryos are normal or not, so they might end up with an embryo that's missing or has extra DNA, and that could set them up for a miscarriage, which sometimes it takes until your eight weeks or nine weeks to go through that. So the earliest genetic testing that can be done during the prenatal stage is at the end of the first trimester. So it's always a little bit more tenuous, and overall the success rates are lower. But if that's their best opportunity or chance to have a transfer with IVF, then that's a reasonable thing to pivot to as long as they're counseled about the potential outcomes and, and complications. So, you know, I think it also depends on the center. Some centers are more comfortable with growing embryos to day five than others in different parts of the country. So I think it really just depends on what their practice pattern is and how much they've kind of evolved with the trends that are happening nowadays in IVF labs across the country.

Kristyn Hodgdon:
That's really helpful, thank you. So this is such a devastating experience when you get blastocysts and then you do PGT-A testing and none of them come back normal. What do you do in that case?

Lucky Sekhon:
I mean, I think you try again, right? You just happen to have a batch of eggs that turned into embryos that all had the errors, and this is the reason we did the testing. So, you know, I would not regret doing the testing. I would say, okay, great, we dodged a bullet, those are all embryos I could have been doing transfers back to back and not being successful or worse, having a miscarriage or even an unhealthy child like sometimes PGT reports come back, I remember one of my embryos came back, trisomy 21, and I was like, whoa, you know, it's just kind of that's, that's Down's syndrome. And that can be something that persists and you can diagnose it prenatally. But if you're not doing prenatal genetic testing for whatever reason, that, you could have a child with a chromosomal abnormality and they have significant medical problems. So it can really help to do PGT to rule out those things in advance. And when you get results back that are not ideal, where all of them or the majority of embryos come back abnormal, it's very frustrating, but it's still better to know than to not know in that type of scenario. And I think you could do another cycle. And the fact that you were able to get embryos, if you're able to get multiple embryos tested, that's a great sign, you try this again. Statistically, the odds are higher in a cumulative sense that you're going to eventually find a normal embryo. Of course, this depends on your age. If you're 38 years old, the statistics dictate that about 50% of embryos will be abnormal, 50% will be normal. And so if you end up having four PGT tested embryos and they all come back abnormal, I would say, well, that doesn't really fall in line with the 50% that I was expecting. And I'm sure statistically, if you were to do this again and we had another crop of embryos to test, it's likely that we could find a normal embryo. And it's definitely worth trying. Again, if you're doing this at 43, 44, where we tend to see rates of 90% or more of embryos being abnormal, I would counsel that patient look like you could do this again and end up with the exact same results, because these are the types of statistics that we expect. But it's really hard to predict, like, will you be that lucky patient that does this again? And one of the embryos out of four or five tested ends up coming back normal. So it really depends on what the situation is and the patient's age.

Kristyn Hodgdon:
And will you have the donor egg conversation at that point?

Lucky Sekhon:
Yeah, I think depending on the situation, if this is not their first time and they keep making abnormal embryos and we have tried all different ways of tweaking their protocol, of maximizing the number of eggs that we start with, to maximize the number of embryos sent off for testing, and they just keep coming back abnormal, and they're at an age where it's reasonable to expect this to keep repeating itself, 100%, you know, we would discuss donor egg, but it's it really, I think, depends on the patient's age. That is the number one determinant of whether an embryo will come back normal or not, the overall averages and rates tend to ring true for most patients.

Kristyn Hodgdon:
Okay, that makes sense. So moving on to embryo transfer, I used to think that stems and the retrieval were the hardest part of IVF, but now that I've been through several failed transfers, it's just so heartbreaking when you get to transfer, which can take a lot for some people, like they might have had to do multiple rounds of retrievals, you finally get to transfer and and it doesn't work. Can you go into some of the reasons, the underlying causes of implantation failure?

Lucky Sekhon:
Yeah, I think what you said is just so true that, you know, there's a series of challenges. And I think a lot of times when, especially when getting the normal embryo was a challenge in and of itself, it can be so disheartening, you know, after putting in all that work, and especially if it's a genetically normal embryo, we put a lot of stock into that and it almost like is this mentality of it's going to work, you know, it's 100%. But we know that that's not true. Even in the best case scenario where it's a beautiful day five, day six, which is faster growing than a day seven embryo. So they have the higher success rates with good quality grades like A's or B grades for the part of the embryo that becomes the baby, which is known to be the most predictive marker when it comes to grading in terms of chance of success, even in that type of setting, we're expecting 60 to 70% rate of live birth. And so it's not 100% and it's not like a small sliver of patients that sometimes require more than one transfer to be successful. And so it's important to go into it optimistic knowing you've done everything that you can, but also being realistic that it's not a 100% success rate and it might take more than one transfer, and that's why when planning this out, I always tell patients, if you want to have 1 to 2 children, it would be ideal to have three or four embryos to work with because it isn't 100%. And I think going into a transfer and having multiple embryos to work with is a different mental game than having all of the pressure on one single embryo. But obviously there's what's ideal and then there's what's practical and realistic for a certain individual patient. But, you know, the reason why embryos don't always implant, even in the best set up and the best situation where you have done PGT testing can be embryo-related or it could be other factors outside of the embryo. We've talked about this in a prior episode, but PGT isn't perfect, pre-implantation genetic testing is sampling a limited subset of the cells. An embryo, usually when it's getting biopsied, has about 100 to 200 cells in total, some of which become the placenta, which is what we're sampling and some of which becomes the baby, which we're not touching those cells. And so if you're testing just a few cells, like 4 to 10 cells of something that is 100 to 200 cells, it's possible that the cells you sent off for testing weren't entirely representative of what's going on with that embryo. We know in nature you can have different cell lines running through the same embryo, even in the same individual. It's also possible that there are errors in the cells that were sent off, but they're so small and tiny beyond the limit detection because PGT has limited resolution where it can't zoom in completely, you can zoom into like 5 million base pairs of DNA, but if there's a smaller section that's duplicated or missing and it involves, it happens to involve a gene that is essential for early growth and development, that might be the reason why that embryo actually wasn't a good embryo and didn't implant, right? So I think it's important to know PGT is a great technology. The error rate is low, it's less than 2%. But of course, an error could have also contributed, right? But even if it's accurate, it's not perfect in that you can't figure out every single thing that could be wrong with that embryo. So there's embryo-related issues. And then also beyond the amount of DNA, which is what we're testing with PGT, whether genes are being expressed appropriately or whether there's breakdowns in that process of a gene being expressed and dictating what proteins are developing like, there's other parts of the biology of the embryo that can be affected that's not what what's being tested with PGT. And then outside of the embryo, what's going on with the uterine cavity, right? You're just placing the embryo at the top of the uterus during an embryo transfer, we're not implanting it and putting it, we're just putting it in the region of where we think it should implant. And then whether it interacts appropriately with the lining is totally outside of our control. And so there could just be bad luck where it was placed there, and the signaling just didn't go the way it was supposed to go between the embryo and the lining, and that happens. And we don't know how often it happens, and it's really hard to know if that was a situation. There could also be lining related issues that you either know about or you have no idea about. You might know about having a history of fibroids, Maybe you had a surgery to remove the fibroids, but perhaps that cavity is just not perfect, and maybe it never will be, But all you can do is work towards optimizing it. Same with if you've had multiple DNC procedures or any type of procedure on the uterine cavity that's predispose you to scarring, scars reform. And so you may get a hysteroscopy done to remove that scar tissue, but it can come back, or sometimes it's impossible to restore the uterine cavity to its perfect state before it had those problems arise. So if you know that you have those issues, it's really important to advocate for yourself to get re imaging done, maybe even a histeroscopy, just to really look to see if there's anything that can be rectified or improved before your next attempt. Sometimes patients can have inflammation and dilation of their fallopian tubes that was previously undiagnosed. This is something that you can see on an HSG test, which is an X-ray of your pelvis after they put dye into the uterine cavity that spills out of either tube. And usually they say, if it's clinically relevant, you should be able to see that dilated tube on ultrasound. But if I've had a patient who hasn't gotten pregnant from embryos that are high quality, they've been tested, I will have a very low threshold to do an HSG just because if there's any sign of an inflamed tube, I might recommend that they actually undergo a minor surgery to have it disconnected or removed entirely because it's communicating with the uterine cavity and could be making the environment less than optimal for an embryo to implant. So those are some of the key things that I think about, other things that often are looked at as well. You know, doing a biopsy of the lining of the uterus to look for infection or inflammation that could be treated with antibiotics. If someone is suspecting that they have endometriosis based off of their painful periods, family history, things like that, you know, you could say, let's investigate that further, maybe you want to preemptively just give them Lupron for a month or two or a few weeks before their transfer to try to suppress any endometriosis that might be there. So these are all kind of things that I would think about testing wise and intervention wise before doing the next transfer.

Kristyn Hodgdon:
That's great advice. So we got this question from a community member, and I think it's something that I've wondered, too, why isn't any and all testing done before the first transfer? Why wait till you've had several failed transfers?

Lucky Sekhon:
So I get asked this all the time. As you can imagine, I'll have patients who know they're being smart and strategic. They'll ask me, Well, I'm doing my first transfer now, and can we just do everything you would do if this was my third? And, you know, it's a really smart way to think about it, because obviously no one wants to be a statistic and be in the situation where they've had multiple failed transfers, and only now are we thinking outside the box. But I think it's all about striking a balance, right? In theory, yes. You could do every single thing that I've talked about here beforehand. But in my experience, I think the most important thing that you can do preemptively in the lead up to your first transfer or any transfer, is a really thorough evaluation of the uterine cavity. And to make sure you're doing it close to the time of transfer, close to the time a transfer in my book is like within the 1 to 3 months before your transfer, because sometimes people will have an HSG that was done the year prior and they'll be like, yeah, they looked at my cavity and everything's fine, but things can change, right? Polyps, fibroids, scar tissue can reform, like all of these things should be looked at closer to the time of the transfer in my opinion. If you think about all the tests that I talked about, like endometrial biopsy, histeroscopy, laparoscopy, which is a surgery which you might be doing for diagnostic purposes just to look around, but these are all invasive, right? And any time you do these types of procedures, you're taking on potential risks. The risks aren't very high or likely, but you're putting a scope inside the uterus, there could be uterine perforation. Any time you're doing something invasive, there are risks of things like infection, bleeding, the risks of undergoing anesthesia. These risks are rare adverse outcomes but if you did this for every single person, it wouldn't be cost effective for them, it wouldn't be something that is patient friendly. I think it would really increase the burden of treatment and testing in general for all patients. And overall, you would have much higher numbers of patients who have complications from it, just because of the fact that they're rare in and of themselves, it doesn't mean it's not going to be a problem if you're applying it to everyone across the board. The vast majority of people don't need all this extra testing. You know, oftentimes even when I have patients doing this testing because they've had recurrent implantation failure, oftentimes the tests come back completely negative. So it's not something where we're doing these tests in patients that have a difficult time and we're very likely to find something and have a target to treat. But this is one of those attitudes of not wanting to leave any stone unturned and wanting to address every single possible scenario. But a very small minority of patients will fall into that situation, and that's why we don't apply this testing preemptively to every case. Does that make sense?

Kristyn Hodgdon:
Absolutely. And so what if you don't find anything? What's the appropriate next step?

Lucky Sekhon:
Well, remember, going back to the success rates, even in an ideal scenario, is like 60 to 70% chance of live birth. So I would say we've checked off all the boxes and it's time to put back another embryo.

Kristyn Hodgdon:
Absolutely. So hope is not lost just because you've had a couple of failed transfers, sometimes it takes.

Lucky Sekhon:
Yes, and it knocks your confidence for sure. But I will tell you that there is a good number of patients statistically that need more than one transfer to get there for whatever reason. And then I've had some really like they stick out in my mind type cases where and it's not the most common things, I don't want anyone listening right now to feel anxious that this could happen to them. But honestly, like a handful of cases of patients that I've treated where they did not get pregnant after three, four or five ..., meaning genetically normal embryo transfers. And it was a real mystery because all testing came back normal, some of them, some of them even tried experimental things outside of the scope of my practice. Like they went to go see a reproductive immunologist and did all of these treatments empirically that they're controversial because the data just isn't there to really support its use and there could be potential downsides. And even then in those cycles they weren't successful, but they just kept coming back. And thankfully the cases that I'm thinking of, they were able to make normal embryos and had the embryos to transfer. And I've seen patients where I just really didn't know what was going on. And they got pregnant on the sixth or seventh transfer and everything was fine and have since delivered live born baby. So I think while it's scary to think about that possibility and it's important to keep in mind that that's a very rare scenario. I think that the flip side of it is that it gives you a lot of hope that sometimes you do just need to put back another embryo and be persistent.

Kristyn Hodgdon:
Absolutely. So lastly, I just wanted to pose the question, when is it time to get a second opinion? Like you've either had a failed stem cycle or multiple or multiple failed transfers, is it just a personal decision or is, is there a certain point where even you as a fertility doctor would be like, okay, maybe, maybe someone else can better serve your case?

Lucky Sekhon:
Yeah, I mean, I think second opinions are great even if you don't get more information out of them and they just make you feel reassured that you're on the right track, right? I think it is a personal decision, it's never wrong to get a second opinion. In my opinion, it's never too early to get a second opinion. I think any time you have a difficult case where you feel like there's no other tests to do or that are recommended, and you just want to make sure that there's nothing that you could be missing or no additional perspectives that might be helpful at that point, having a second opinion doesn't mean you're leaving your clinic or that you're leaving your doctor. You're just gathering more information and getting more perspectives from an outside viewpoint. I often encourage my patients to seek a second opinion, especially when it's an objectively difficult case because they'll go talk to other people and either we'll all be on completely the same page, and that's very reassuring, you know, or they'll come back to me and we'll discuss some novel techniques or ideas that have been brought up. But it's a collaborative effort. It's not me against the doctor giving the second opinion, we're all on the same page, we all want you to succeed and we're working as a team towards the same outcome. I think if you're not having a good experience with your clinic or doctor and you feel like communication style doesn't suit you or there is a lack of communication, that's also another reason to go see someone else. So I think you have to go with your gut. And I think sometimes patients are so nice and over the top consider it, they don't want to hurt their doctor's feelings. But that's why I'm someone that typically brings up the idea of a second opinion, because if I feel like I'm helping this patient on their journey, they're having a difficult time. It's not clear exactly what's going on, and I can tell they're kind of hesitant, hesitant or just not feeling 100% confident about the plan, I will often bring up the idea of a second opinion because I think that it could help them to just get a sanity check and talk to someone else and then come back. Yeah. And then come back and talk to me about it. It's not like, you know, you have these dual perspectives and recommendations and that we're not going to talk to each other or collaborate. So I think it's just all in how you frame the perspective. And I think when doctors bring it up to their patients, it makes it way less awkward and it almost feels like they have the permission to do it and to speak openly about it.

Kristyn Hodgdon:
Definitely. I actually switched doctors within my clinic, so awkward. But.

Lucky Sekhon:
Yeah.

Kristyn Hodgdon:
It was fun. It worked out.

Lucky Sekhon:
Yeah. And you're advocating for yourself, so this is not a time to worry about hurting people's feelings. And trust me, like anyone who's in this field will understand and we wouldn't hold it against a patient. I think it's in your best interest, and it's just another way that you as a patient can advocate for yourself. And I would say there are certain things you can definitely do to get more out of a second opinion consult. So I think if you're doing it, make sure that you're getting your records. If you've done a ton of cycles and you have a really long, complicated history, something I always appreciate when I'm doing a second opinion consult is when patients will email the clinic, they'll send it to my assistant, they'll send it in advance of their visit, like just a quick summary or outline of what they've had done, even if they like jot down the protocol that was used, it's extra helpful if they can put details like this is how many eggs were retrieved, this is how many embryos I got, this is, and maybe you don't know all those details, but if you do have them kind of memorized or written down somewhere to just be able to put it down in a way that flows and is easy for us to follow because sometimes when we're getting a stack of records from the other clinic, it's like 200 pages and it's very hard to navigate, it might be handwritten, so if you can summarize it so that it's really clear and concise and even if you've done testing or surgeries, the date and just the timeline, because then we instead of spending the time piecing that all together with you, we can really focus on the actual recommendations that we want to give you and to answer any questions that you have and spend the time really focusing on the matters at hand, it really helps to streamline the conversation, and I think it's also helpful to get a recommendation for your second opinion in a way that's going to make you feel comfortable and confident. So getting a recommendation through word of mouth from a patient who had a good experience I think is helpful. You could use things like online reviews, but sometimes those are skewed and biased and because not every single patient writes a review. But I think going to a place that is reputable and is known to have good success rates is also important for your second opinion.

Kristyn Hodgdon:
Absolutely. Well, this this season has been all about learning to advocate for yourself when the journey gets hard. And I want to say thank you, because I thought I knew a lot, but I've learned so much, and I think this will give a lot of patients the tools they need to be able to go to their provider and ask the right questions or get a second opinion if they need to. So this has been so helpful.

Lucky Sekhon:
Yeah. And I feel like we could have kept talking every single episode, every topic. So yeah, I thought it was really helpful to be here and lend my expertise. But I think for anyone who's listening, if there are topics that we didn't cover, questions that we could have gone deeper into, I'd be more than happy to come back and expand on anything that might be helpful.

Kristyn Hodgdon:
Absolutely, awesome. Well, thank you, Doctor Sekhon, I always a pleasure chatting with you and that's a wrap on season two.

Lucky Sekhon:
Thank you so much. I hope everyone enjoyed this.

Kristyn Hodgdon:
Thank you for tuning into this episode of Dear Infertility. We hope it helps you feel more empowered to be your own advocate on your fertility journey. Whatever you're currently struggling with, Rescripted is here to hold your hand every step of the way. If you like today's episode and want to stay up to date on our podcast, don't forget to click Subscribe. To find this episode show notes resources and more, head to Rescripted.com and be sure to join our free fertility support community while you're there.

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