Creating a Family: Talk about Adoption & Foster Care

What Are Your Chances of Getting Pregnant With Unexplained Infertility

January 05, 2022 Creating a Family Season 16 Episode 1
Creating a Family: Talk about Adoption & Foster Care
What Are Your Chances of Getting Pregnant With Unexplained Infertility
Show Notes Transcript

If you have unexplained infertility, what are your chances of ultimately having a baby—either through infertility treatment or natural conception? We talk with Dr. Denis Vaughan, a board-certified Reproductive Endocrinologist at Boston IVF and a Clinical Instructor at Harvard Medical School. He was the principal investigator on the study "Long-term reproductive outcomes in patients with unexplained infertility".
In this episode, we cover:

  • What year was the original FASTT trial and what were the findings?
  • What is unexplained infertility and how common is it?
  • Did most of the women try to conceive after the original FASTT trial?
  • How did the women who agree to participate in this follow-up study compare to the original FASTT participants? Was there a difference between those who participated in the follow-up and those who did not?
  • What percentage of the women were successful at conception with IUI? IVF? Natural conception?
  • What percentage tried to conceive with donor egg?
  • What percentage adopted?
  • If the woman had conceived via fertility treatment in the original FASTT trial is she more likely to conceive successfully in the future?
  • Some speculate that a significant proportion of unexplained infertility is due to un-diagnosed endometriosis. Did this follow-up study shed light on that question?
  • Did many of the women after the original FASTT study receive a more definitive diagnosis of why they were not able to conceive?
  • What did the study show about patient satisfaction with their family building process and ultimate family size?
  • What did we learn about conception with unexplained infertility as a result of the follow-up to the FASTT study?

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Welcome to Creating a Family. Let's talk about infertility. I'm Dawn Davenport, your host and the director of creating a Today we're going to be talking about your chances of getting pregnant with unexplained infertility. We will be talking with Dr. Dennis Vaughan. He is a board certified reproductive endocrinologist at Boston IVF and a clinical instructor at Harvard Medical School. He was the principal investigator on the study long term reproductive outcomes of patients with unexplained infertility. Welcome, Dr. Vaughan to Creating a Family.

Thank you very happy to be here.

So this was the study that that long term reproductive outcomes in patients with unexplained infertility was a follow up to an earlier study that was called fast tracked and standard treatment trial, the acronym was US was fast FAS TT, and the fast study was a large federally funded randomized control trial that evaluated the optimal treatment courses for couples with unexplained infertility. What year was the original fast trial? And what were the principal findings.

So the first trial was conducted at Boston IVF, between 2001 2005 So almost 15 to 20 years ago now, depending on when the patients were enrolled. And the primary aim of that study was to evaluate how best to treat patients who present a clinic with unexplained infertility. And at that time, the treatment paradigm consisted of oral stimulation medication with IUI or intrauterine insemination. And if that wasn't successful, the patient will move on to injectable medications or gonadotropin IUI. And if that was not successful, a patient would move on to IVF. And it was quite a prolonged period of time patients were taking until they reached IVF. And a lot of patients ultimately needed IVF to succeed and conceive. And so the purpose of that trial was to evaluate whether the additional step of the injectable IUI was actually necessary. And so, patient for that study were randomized to either receiving oral agents have been successful going directly to IVF. Or the traditional paradigm, as I mentioned, oral agents, injectable medication IUI, followed by IVF. And what they found was that the addition of the injectable IUI component was not very helpful along there are very few additional patients who are pregnant from that. And so the conclusion was that the treatment really should be oral agents with IUI, followed by IVF and successful and the time to pregnancy, which is, you know, ultimately, our patients want to get pregnant as soon as possible, was much shorter in that patient group.

So what was the primary aim for the follow up study that you have recently published?

Yes. The question that we all get is reproductive endocrinologist in the office from our patients is if IVF, or even IUI is needed for the first conception for the first baby that this patient is having. Does that mean that the patient or the couple are infertile thereafter, will they always need assistance from us if through IUI, or IVF, in order to have subsequent troller. And so it was really to find out what happened to those patients following the trial, and to see whether these patients with unexplained infertility are indeed in fertile for life, or whether they can conceive by themselves subsequently.

So we're gonna come back to what you found. But before we do that, let's talk a little about unexplained infertility. So, it seems to be self evident from the tie from the name but let's what is unexplained infertility and how common is it?

So, unexplained infertility is an extremely frustrating diagnosis.

And it's certains.

Actually, you know, it's an interesting one, because what we'll often see is that if a couple for example, present for with infertility will have the male component, obviously the female component, and we do the evaluation for both male which consists, it's pretty crude, but it consists of just a semen analysis, and a basic history looking at some sperm parameters. And then on the female side, it's a little more involved with some hormonal testing for ovarian reserve is some anatomical evaluation, looking at the uterus uterine cavity in the fallopian tubes. And technically, in order to meet the unexplained infertility diagnosis, both the male evaluation and the female evaluation should return as within the normal reference ranges are within the normal limits and will sometimes see even patients that are designated as unexplained infertility. There'll be a subtle male factor and a subtle female factors that overlap and combine There's a couple of makes it more challenging for those patients to, to conceive. But True, true, unexplained infertility, shoot, everything should be completely normal with the testing, and therefore we don't know why those patients are not getting pregnant.

is the percentage of patients coming to you now, with that ultimately diagnosed with unexplained infertility? Is that has that decreased since the early 2000s, when the fast trial was first done?

That's a great question. And the answer is marginally. I will say marginally, you know, I think that our testing largely is very similar to what it was back then. The hormone testing is very similar, we have the addition of an another hormone test called anti mullerian hormone, which is produced by the granulosa cells in the follicles and that gives us is a sensitive indicator of how many eggs we're likely to get when we do an egg retrieval. That's new. But otherwise, the day three traditional day three testing of follicle stimulating hormone estradiol is similar. The evaluation of the uterus and the tubes is similar to evaluation. The semen analysis is similar, although they the reference ranges have changed slightly between the WH over that timeframe. So it's only really now the last 234 years. And it's only really in the research setting now that we're getting some more answers through genetic testing, but we're not quite that's not mainstream yet, and doesn't come through to the clinic just yet.

Okay, so basically, slight decrease, but for the most part about the same,

yes, very much, very much the same. And that was one of the the kind of secondary outcomes of this study was to see those patients who are diagnosed with unexplained infertility because that was the main inclusion for the trial, how many of those patients subsequently got an ulterior or another diagnosis that wasn't really unexplained that they found out subsequently, male factor had a surgery found in vitreolysis, etc?

Yeah, I was gonna I was going to talk about that later. But I'll jump into it now. I have certainly heard it speculated that, that some percentage and some would say a significant percentage of unexplained infertility is due to undiagnosed endometriosis. Did the follow up study shed light on that question?

Yeah, good question. There's been a number of studies because we used to do diagnostic laparoscopy as a routine part of an infertility evaluation. And a lot of the time we find in vitro some studies, quote up to 50% of patients who underwent a diagnostic, laparoscopy it probably not as high as that, but it's probably 20 to 30% of all patients with unexplained infertility have some degree of endometriosis. And when we when we did the study, the original fast trial, those patients who had a laparoscopy would have been excluded from the studies, but they weren't part of the study. But we were asking those patients subsequently if they had a surgery, it has to be a confirmed diagnosis, which is the gold standard for diagnosis and rejoices in surgery with a biopsy and pathological confirmation, rather than just symptomatic. But we found that overall, there were 20% of the patients that we contacted and spoke to received a subsequent diagnosis other than unexplained infertility, which you know, is still relatively low, the majority were still unexplained throughout the reproductive life. And of those endometriosis comprise about a quarter so about four to 5% of those 4.5% of our patients who had an unexplained diagnosis at the time of the trial, subsequently had surgery confirmed endometriosis.

So too, so you were following up? The original was what? 500?

Something? Three? Yeah, 503 couples.

Okay, so you had 503 couples, and your goal was to find out what happened. They were they were in treatment. They were then participate in this study, they were randomized to either a standard protocol or into the fast protocol, which meant skipping the injectables with an IUI. And some of the women got pregnant and some of the women did not get pregnant in that trial, and then the and then the fast trial was over. did most of the women try to conceive after the original fastball? I mean, I would assume some got pregnant and that was their ideal family size or some may have just given up because they just felt like they their body or their minds had gone through their emotions they gone through enough. So what percentage of the women continue to try to conceive?

So during the fast trial, about 65% was 64.3, I think was close to 65% of couples conceive during fast Have those 503. And then we managed to get in touch with 286 of the female partner in a couple of weeks were ones that we contacted. And almost 80% of them reported that they continue to try to conceive following the trial. And that actually didn't differ dramatically whether they had successfully had a live birth during the trial, or whether the different run successful during the trial, most people continued to try to have either a baby or another subsequent baby following the trial.

When we say try to conceive, they're different, different degrees. One is just not using birth control and hoping it happens. The other one is is actively trying naturally, and then it progresses all the way to continuing to go through infertility treatment and IVF. Did you what percentage of the women that when you contacted which was 200 some odd, how many of those actively sought fertility treatment versus just having timed intercourse?

Yeah, so I'm following the trials that one 80% continue to try and as you mentioned, varying degrees, 70% of those patients told us that they tried by themselves, and the patients because of the trial proportions and got pregnant with IUI, some of those patients went back and did another IUI, about 5% of the patients. And then the remaining ultimately ended up continuing on the IVF path or trying again, for baby number two with IVF. About 40% of those patients. So some of those overlap, because they might have tried for a period of time by themselves. After the trial. They weren't successful, then they went back and had IVF. You know, it's it's kind of a continuing to go back and forth between different methods of trying.

And how did was there a difference that you noticed between the women who participated in this follow up and those who did night? I mean, just tried to figure out there's a bias, and I'm sure you were looking for this as well, and who agreed to participate in the follow up?

It's a great question. Yeah, that's one of the biggest concerns with with survey studies in general is we tried to get as good a response rate as we can to have a representative sample, our response rate was 56%, in the study, which, you know, ideally, you'd be 60 to 70%. But these patients were in treatment almost 20 years ago, and so very, very difficult hit those numbers. And so we were happy with our with our response rate that we got, but we did compare patients that were unable to contact versus those who contacted and consented to participate in the study, just looking at, you know, age, enrollment or fast, which is similar between the groups, the only thing that we did notice, slightly different between the patients that participated in this study compared to the ones who didn't or weren't able to contacted, or that the patients who participate in the follow up study were slightly higher education status, at least at the time of enrollment to the fast trial. We don't know what happened subsequent, but higher proportion of patients participate in this study had higher level degrees, and had a higher mean household income and inclusion too fast. Interesting.

Okay. Any speculations on that as to? Or is that outside of your area of expertise? I'm just curious.

Question. I think some of it might be as simple as, you know, trying to find these patients. So we initially looked at our electronic medical record system, we had some, you know, addresses, cell phone numbers, very few emails that will say back then, but that was our first pass or reaching out at the patients. And if we were unsuccessful, then we went into publicly available databases, such as by pages, and to try and find these patients. And so some of the patients were easier to find, especially, you know, patients who are maybe professionals or they make sense. Yeah, so I think there's an element of that. And then I think, you know, perhaps, especially some of the patients who were involved in fast, who are in the medical field, I think, are open to research and want to participate in research. And so I think they were more willing to return Trump calls. I think, so probably multitude of factors involved in that.

Yeah, that makes sense. I was, in my mind speculating that people with more research or mean with more education may be more inclined to participate in research from either having benefited from it or understanding the importance of it or something along those lines.

Yeah, possibly. Yeah. I think that could be a factor for sure.

If you have enjoyed this, or any other of creating a podcast over the years, can you please do us a big favor? Go to this site, rate this Family and leave us a rating and review. This is a one stop shop that makes it simple to leave your review. And it's posted many places many of the podcast apps access this. It is simple, it is easy. It is fast, and it really helps us. It is rate this A family. Okay, well, so now let's, we've buried the lede long enough, let's go ahead. So what percentage of women were successful at conception? And I'm going to ask you with natural conception that with IUI. And then with IVF, after the fast trial, now, these were people who were keeping it just reminding everyone these were people who had been diagnosed with unexplained infertility, and then you followed up with them 15 to 20 years later. So what percentage of them were successful with natural conception? No, this

big, the biggest finding for us, I think, was that of those patients who reported that they tried to conceive by themselves following the trial. 64% of them had a spontaneous live birth, subsequently to trial. And so the majority of patients who tried to conceive by themselves, ultimately, we're successful, which leads us down the to that initial point that I made when patients ask us, you know, does this mean I need IVF? Forever? The answer clearly is no. And there are a significant number of patients who will conceive by themselves. So it's great. Now, one thing caveat I wanted to mention is that the demographic has changed slightly from when the first trial was conducted to the patients we see today. And there are geographical differences as well, for example, and enrollment too fast. The average age patient was 33, which is quite young. Yet now. Yeah. Now into in today's world, you know, my practice in Boston is in Chester new. And most of my patients are professionals who are and it's mostly delayed, childbearing spicy. And so the average age patient that I see my clinic, female side is 37.5, which is a different demographic, what was enrolled and fast. The other thing is that the BMI has changed, unfortunately, from 2001 2005, where most of these patients were average BMI between 20 and 25. Whereas now in our clinic, unfortunately, our mean BMI is in the overweight category at about 26 26.5. So things have changed slightly. And so the generalizability of of the data, you know, might not be applicable to all all groups, but certainly for the younger patients who are presenting with unexplained infertility, it's very reassuring in that regard.

Let me ask a question, would it in one way, I mean, the way you were phrasing it was that although they were infertile, that after treatment, they were eventually able to conceive with another way of looking at that be that even without treatment, if you have unexplained if you try long enough, that the chances are good that you would conceive naturally without treatment. The question

Ganser, we strongly believe is no. And the reason for that is because there have been studies from Europe, particularly in Italy, where they have governmental coverage for infertility treatment, then those patients. Similar to us, if the patient's older, they have been trying for six months about over the age of 35, they have been trying for 12 months under the age of 35, then those patients get put on a waitlist for infertility treatment. And they may remain on that waitlist sometimes for 12 to 18 months. And they've been studies looking at those patients, what happened to them in that interval. So technically, they met in fertility at diagnosis. And then there was a subsequent period of time before they started treatment, how many of those patients actually successfully conceived and the percentages were much, much lower, there was only about five to 10% of patients in those studies who conceive spontaneously in that interval, which is a lot lower than our 64%. So we think that there's something with the treatment, either ovarian stimulation, something something that's perhaps resetting the hypothalamic, pituitary ovarian axis, or pregnancy itself, that subsequently makes that patient more likely to conceive spontaneously compared to nothing at all. Interesting,

huh? Okay. Yeah, that's fascinating. So what about what percentage of the women were successful at conception with inner uterine insemination? IUI.

So the patients from the first trial who went down the IVF road, they were unsuccessful with oral agent IUI. Injectable IUI, then went to IVF. None of those patients that we spoke to went back to do IUI they either conceived by themselves or they had another baby with IVF down the line, whereas those patients who did get pregnant with IUI, the first time were more likely, as you might expect to go back and try IUI the second time. And of those patients, 22% of them had a baby the second time with IUI are the ones who tried.

And do you know what percentage were stimulated with oral meds, or which percentage were stimulated with Gananoque? Injectable gonadotropins.

So all of those, most of them were oral agents, very, very few actually received injectable medications. I think that was probably subsequent to the trial, the trial results came out and people started to move away from LightWave.

Yeah, that makes sense. Right. Okay. So what percentage of the women were successful at conceiving using after the after the first trial was over, using IVF.

So if they conceived with IVF, the first time of those patients, 57% of them had another baby with IVF. So of the patients who had a baby with IVF, first time, 57% of them had at least one more baby with IVF, again, of those patients who had a baby born by IVF, the first time 53% of them had a baby spontaneously. And as I said, none of them had IUI because it didn't go backwards DIY to the group that we were really interested in was the patients who were unsuccessful during the fast trial. Yeah, we our question was, are these the real infertile cohort of patients, they've been through IUI. They've had injectables that had oral agents, they've been through multiple cycles of IVF. And they haven't been successful, does that mean that their chances of getting pregnant are really, really low. And actually, we didn't find that at all, we found that 68% of those patients continued to do IVF, even after the trial, and had to be by IVF, for 68% of them. And even those patients, again, who didn't get pregnant with all that treatment, even those patients, 51% of them had a baby without any intervention, subsequently. So a large proportion of those patients even had babies spontaneously without any further treatment.

And again, your thinking is, again, I realized that your study was not designed to answer this question. But you're thinking is that there was something in the treatment itself, of course, they weren't pregnant, so that couldn't be in the pregnancy. But even though the treatment was not successful, at resulting in a pregnancy at the time, the thinking is that these people would not have gotten who would not have conceived naturally, but for having the treatment,

I think, a small proportion, if you know, again, we can only kind of extrapolate and hypothesize based on the previous studies that have been done, a small percentage would have, but certainly nowhere near the 50% Spontaneous low birth rates that we saw, though, that was very, very surprising to us. So either there's something about the treatment, or we have a unique patient group. But but it's very, it was very interesting, surprising finding to everybody.

Yeah, so it kind of begs the question, what would you recommend for somebody who came in had a either a successful with through treatment, who either was successful in treatment or not they have a diagnosis of unexplained infertility? What's the best recommendation? Should they just stop treatment continued to try naturally? And I realized that even asking this question that it's so much dependent on the person's age, but anyway, how does it shifted what you recommend for people, whether they are successful or unsuccessful?

You know, I think that if a patient is down going down the treatment paradigm, I think it makes sense to continue as much as they feel that they can, from an emotional and physical standpoint, achieve their first pregnancy, with assisted reproduction treatment. However, if they're successful and have a baby, and they're on the younger side, like you mentioned, there's actually no reason why they couldn't try for a period of time following the birth of their first child to see if they get pregnant by themselves the second time around, and if they don't, then they could come back to us again, for further assistance. But I think that's the big the big thing here is that there is hope for a spontaneously conceived baby after IVF treatment, you know, irrespective whether they were successful or not, but certainly for those who are successful, it's worth trying for a period of time by themselves following the birth of their child. Now very different, as you said, it's a 40 to 43 year old dismantled in his labor, it's extremely, extremely low. And so those patients should move to us a little bit sooner, but if they're young, healthy, they lose nothing by trying for

several months. So I would think that that some percentage of these patients went on to try donor eggs if they were not successful, and I would guess that if the average age was 33, there would have been a gap that they would have continued to try before they moved to donor egg. What did you find out about their success with donor egg and how many even saw it out that option?

You know, I think this is something that's changed even in the last five to 10 years. So very few of the patients in this study, in single digit percentage moved on to donor egg or adoption, there were very few, what we found in general, of all of the patients who participate in the study, only 6% of those patients never had a live birth. So 94%, almost of our patients had a live birth. And the vast majority of those were with their own eggs. Only single digit percent, I think was around 5% of our patients went on to use donor egg and have a low birth for donor egg. But again, these are younger patients in general, age 33, which has changed in the last last five to 10 years for the use of donor egg has become far far more common.

Well, and then I think that there are so many things that have shifted, and this in this interim of time with donor conception, you know, the the advent of donor banks versus a donor egg banks, versus having and that shifts the costs, it also shifts what you do with you know, so a lot has changed.

Exactly the availability of donor eggs is far greater now than it was we're not trying to find a specific donor anymore. Right? Rarely these days with use of donor egg, these things are just much more available accessible. And well, it's still expensive, relatively, the cost has come down.

So it just to go back. I think you've answered this. But if the woman had conceived the fertility treatment in the original fast trial, Is she more likely to conceive successfully in the future, regardless of what of whether it's natural or whether it's with IVF, in other words, was six set this success in pregnancy breeds success in it more likely to be successful in the future?

Slightly slightly, so patients who've gotten pregnant before were slightly more likely to get pregnant again, spontaneously, whereas more patients who didn't get pregnant during the trial had IVF, in order to conceive. And so there is something slightly different. But that being that the overwhelming majority of all patients, whether they were successful, were not successful, the first time ultimately had a live birth. And whether that was with assistance, or without assistances, and a great portion, or half of them how to baby's funding, see without any help at all.

So you've got this amazing cohort of couples, women or couples, and you have a lot of data on them from but starting in 2000 and early 2000s. And now in the you know, the I guess what this was actually done in 2022. Was Yeah, exactly. So 2020 years worth of data, what are the plans? Or do you have plans for other things to do to study this cohort since you have access to them?

Yeah. So you know, one of the big one, the couple of points that very jumped to that, that I wanted to make was that the one big part of what we want to do with this was to look and see how many of our patients were happy overall, with their outcomes, you know, whether it was IVF spontaneous, you can see donor eggs adoption. And what we found was, the overwhelming majority of patients were happy with their ultimate family size, about 65% of them reported that they were happy, and that was directly related to the number of babies that they had. And so the more know this is, there's a bias population, obviously, they came to us looking for babies, more babies, it doesn't always equal more happiness, but is patient population, having two or more children was associated with increased satisfaction around family size, and that moving to treatment sooner, and receiving assisted reproductive treatment ultimately allowed the patients to build their families and have an extra child, which again, allows more babies, which in our study, was associated with increased satisfaction. So so we think that moving to treatment, you know, at the appropriate times, should be encouraged, because ultimately that that maximizes your likelihood of having the family size that you want.

Did you again this was started at a time when multiple births were significantly a larger percentage of children being bored pregnancies resulting from IVF. So I'm wondering if and this may not have been something you've studied that from a satisfaction standpoint The whether or not there was a multiple births did that impact? It certainly impacted family size. But did it impact happiness or the patient's perception?

Yeah, so it's interesting, we did have multiple births in this group we had, I think, was close to 30 sets of twins, in the 286 patients that we spoke to. And actually, it although it was relatively small numbers didn't reach statistical significance. But more of those patients who had twins, you know, had more had a bigger family in general, which again, was more more likely to report satisfaction around family building size. So I don't know was the fact of having the twins but ultimately having more children was associated with with increased satisfaction. So so that was that was an interesting finding.

Yeah, if that's Yeah, cuz I could see that another thing, that it would be that if they had two sets of twins, that's maybe a plentiful blessing, maybe too much. And that that you would see a at some point, you would see the number of children would be reversing, but you did not find that.

We didn't find that we didn't find it now. But the most most children one patient had was five in our court. Interesting. Yeah. So we didn't see that. But yeah, like you said, potentially, if somebody was only trying for one and they got triplets, then that one might be might not be associated with the with the outcome they wanted.

Having. I have not read the original fast trout, but there weren't any triples. Were there. Or maybe I'm just not remembering.

Not in the original fastball. The word twin there were twins though. Yeah, yeah, I knew that. Yeah. And we, we had two sets of triplets, or at least patients older stage twos, two patients had a set of triplets in the reproductive lifetime of the 286 patients.

Really? Hmm. That they were they had them subsequent to that. Exactly, exactly. And well, we have to assume that that was part of the group that received treatment. So

exactly. I can, you know, that's one of the big reasons we moved away from gonadotropin IUI is, is that that has been associated with with increased risk of multiples. And it's just more difficult for us to control whereas when we're doing ovarian stimulation for IVF, obviously, we can get as many eggs as we want and ultimately transfer a single single embryo at a time, whereas we don't have that control with IUI cycles.

Yeah, the whole push to single embryo transfer has has dramatically shifted. The Er, yeah, absolutely has even though that wasn't what you were studying, it's not what's happening during that period of time.

Exactly. Exactly. Exactly. Right. Very different.

Yeah, totally. You said that. I think you said that. That a certain number. I think it was a relatively small percentage of the the 286 that you were studying had adopted? And that what you're saying is, I think what you said was their satisfaction with it, I think you were just studying family size was not different from whether or not they conceived in gay birth, or whether they adopted and form their family that way.

That's exactly what we had 21 patients adopted at least one child of the 286. And we didn't look specifically at that, at that group, we just asked them about the family building satisfaction and the size and how that pertains to satisfaction. But there was no clear indication that that detract from their satisfaction. So our ultimate conclusion was, it didn't really matter how that family was built. Ultimately, it was a numbers and numbers and a size effect. And the bigger the bigger the family in this group, the more happy the patient, the patients and the parents were, irrespective of how that company was built, which I think is an important take home message because we see patients all the time who go through treatment, and you know, sometimes are unsuccessful with their own eggs and need to go down the donor egg router need to go down the adoption route. And while it's not everybody's first preference, for clear reasons, ultimately, those patients are extremely happy that they've done that. And it leads to increased satisfaction, particularly around the family size and family.

I don't I can't recall. It studies and I'm sure there are some with donor egg. But I have read numerous studies with adoption. And that holds true from what we've seen in those studies as well, that it's ultimately the satisfaction and parent satisfaction and parenting satisfaction. Were how it all turned out seems to be the same regardless of whether they gave birth or not.

Exactly, exactly. And mean you form an unbreakable bond with a child and raise their child from from a young age? And so whether they're biologically related or not, does not seem to have any effect.

So let's go back to my question about I'm fascinated by that you have this, this cohort of people that you could continue to get information. It's so hard to find to do longitudinal research. And it's so important. It's, it's easier in other countries,

maybe, like Scandinavia, have databases that were ready itself? Yeah,

very envious. And so most of the longitudinal studies that we know will come from other countries, because they have national databases. And that's also because they also generally have nationalized insurance. Exactly. Yeah. So it's a two things going, however you still have, it may not be as large, but you do have a group of people. So do you have plans on any other studies of this group?

So this was kind of our first, or this is our primary aim. I will say that we, you know, we asked pretty five different questions during the survey. And one of the other things that we were exploring and we haven't published that data yet is we get questions from these patients. Are they more likely to go through menopause early, for example? That's an important question, are the more likely to have longer term poor health outcomes is, and we see this in the male. So there are multiple studies coming out now that males with poor sperm parameters that may be an early biomarker for poor long term health outcomes. And so some people have hypothesized the same thing in the female side, or these patients who are presenting with infertility is that an early marker for something to negatively impact the patient's life downstream, whether that is a malignancy, cardiovascular disease, mental health issues, etc. And so we collected a lot of data surrounding that patient's medical history, their surgical history, the medications they're taking, as a pre menopausal status. And that data is is is interesting, and we're in the process of analyzing that data and writing that data.

Will it be presented at ASRM 2022?

I think it hopefully will be published. I'm hoping it'll be published by the fall of 2022. So we will hopefully just get to get into into publication. We presented that we did present an abstract last year on on menopause.

Oh, did you? Well, you know, you're saying is the way I if I understood you correctly, that you're curious to know whether the underlying infertility is indicative of poor health of early menopause, our poor overall health outcomes, would you also be able to determine whether treatment itself exposure to either the oral meds are more likely to take Anana trogons? It has long term health consequences. I don't know if your cohorts large enough. But isn't that something

that's the thing, it's something we're all interested in, you know, the, in larger studies, the safety data is very reassuring in terms of gonadotropin exposure and ovarian stimulation, particularly as it pertains to malignancies downstream. But worse, that's something certainly that we're all interested in as well. I'm looking at breast cancer rates, ovarian cancer rates, etc. Because that's a common question we get from our patients but from from other larger studies, the data is reassuring. So we're hoping we're expecting that we won't find anything different than this smaller CT.

How will you tease out though, whether the health impacts are the result from the underlying the fact that they are in fertile and therefore the infertility itself has put them at greater risk versus being exposed to the ovarian stimulation?

Well, that's going to it's going to be impossible. Pretty much it'd be it'd be descriptive study. But the question is, you know, whether it's kind of a chicken and egg scenario, which which comes first? Yeah. Is there something underlying that's causing infertility? Or is there something with infertility that's affecting them longer term, and especially on the male side, we're seeing that they're having poor semen analysis. Why is that is something that's undiagnosed in the mail that subsequently comes to life? Downstream versus the converse? So it's a it's a challenge to tease apart the two things. But at least if you can, identify a link or association, that patient can be screened more often, you know, attend physician and hopefully be able to intervene on your sites ultimately optimize longer term

health. Yeah, exactly. This show as well as all the resources we provide here at creating a family would not happen without the support of our partners who believe in our mission of providing unbiased medically accurate information to the patient community, to such partners. Are Prayas international sperm and egg MC. They are dedicated to providing a wide selection of high quality extensively screened frozen donor sperm and eggs from all races, ethnicities and phenotypes for both home insemination as well as fertility treatment. Prayas International is the world's largest sperm bank and the first freestanding independent egg bank in the United States. Also, we have Reproductive Medicine Associates of New York, they are one of the largest fertility practices in the state of New York as well as one of the biggest in the country. By combining the latest innovations in reproductive sciences with compassionate and customized treatment plans, RMA of New York is able to provide the very best possible care. So after after having done this study, what what do you recommend to patients? I mean, how has this changed? What you tell patients? Obviously, this is just for unexplained infertility. So how does it shift the advice that that you are giving. So

overall, it's a very positive message for patients that the vast majority of patients who present with unexplained infertility, although it is a frustrating diagnosis, the vast majority of those patients ultimately will have a baby. And as I said, 90 94% 90, almost 96% of those patients had a had a live birth at some point in the reproductive journey. And the second thing is that, as mentioned, 64% of those patients had a spontaneous live birth without any assistance at all. Therefore, again, it's positive that the patients may not need assisted reproductive technologies for a subsequent life or so. So those two things, you know, the overwhelming positive message for patients that they will be successful, it's question of how we get them there. And then ultimately, that it's worth them trying by themselves, you know, following the first like birth, because a good proportion of those patients will, will have a second baby without our assistance. And, you know, we'll hear oops, babies quit stories, anecdotally all the time. But it's, but it's true, there is a good proportion of patients who will get pregnant.

And the challenges to weigh age and other risk factors, BMI being one of them, and how to? Yeah, that's the that's the that's the challenge.

And, you know, as I said, ultimately, we think that moving to treatment sooner allows them to have more babies, which is what these patients want, ultimately. And also, another important message is that we're able to do this in Massachusetts, because we're a mandated state. And so these patients, you know, we're fortunate, not everybody know, but a good proportion of our patients have some form of insurance coverage. And it removes that financial barrier to treatment, which, you know, a lot of patients unfortunately, across the country across the globe face every day.

I'm so glad you raised that. Because the reality is that the patients, the people who live in mandated mandated meaning that the insurance companies in that state are required to provide if they're covering other health conditions, they have to provide some degree of coverage for infertility. And because of that, the patients that you're treating have the option, and they don't have the financial imperative that says we can only do this once. And it also reduces the pressure of saying, I want you to transfer at least two embryos, because this is it. This is all I got, you know, and other places face that much more often. And one last question. I think I actually don't know the answer to it. Of those, it seems to me that it would make a difference on the ability to conceive through IVF. Afterwards, if there was if they were using embryos that were created through the fast trial, that in other words that were created, originally that they had embryos, frozen embryos leftover, this was pre vitrification, so there wasn't as good of a freezing technique. But was that teased out were they excluded if they were going through subsequently, not even that, you know, they were having to use a variant simulation, just a frozen embryo transfer.

Now wasn't teased out. So we everybody switched devitrification, at varying time points of Boston IVF, was exclusively vitrification in 2012, the end of 2012. So these patients were all slow freeze. But as we know, the age at which the embryos created, the age of the female at which the embryos created is the most important determinant of outcome. And so it doesn't matter if these embryos were in frozen for five years or 10 years. If they're created at age 33. Those majority of those embryos are going to be high quality embryos and those embryos still do very, very well, even though they were slow frozen, the survival and the tire survival transfer, unlike birth rates, were still very, very good for those patients. So we didn't look specifically about whether these embryos were created during the trial just was there an embryo transfer in order to have a live birth. But there were a good proportion of patients who had embryos frozen from the trial that came back and use them for a subsequent pregnancy. And we're seeing that more and more these days for family building patients, you know, sometimes you're allowed, insurances won't allow them to do it. But self pay patients who are older, who think that they will want to have to treat children will ultimately come to us and bank embryos, or freeze a quart of embryos, maybe do genetic testing on those embryos and have them frozen, and then transfer one at a time, tell them to build their family, because if somebody presents, you know, in their late 30s, maybe they get pregnant with the first cycle, but they carry a pregnancy for nine months. Maybe they breastfeed for a period of time, they come back to see us two years later, now they're 4142 minutes. It's a very different picture. So for those patients, if they are sure that they want to have multiple children that sometimes banking embryos or freezing embryos is the way to go. So there were definitely a portion of our patients who had embryos left over from the past trial.

That makes Yeah, that makes perfect sense. Thank you so much, Dr. Dennis bond for being with us today to talk about the research, which was the long term reproductive outcomes in patients with unexplained infertility, which was a follow up to the the fast trial that was done. Thank you so much for being here. I found the report absolutely fascinating. And I'm so thankful that we're doing some longitudinal work here and

in the US, that we went to the pleasure of being here,

and have everybody else join us next week. We've got more in store. Thanks.

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