FFPLP_4. Root Cause: Audio automatically transcribed by Sonix

FFPLP_4. Root Cause: 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, proud women's health advocate, and co-founder of Rescripted. Welcome to From First Period to Last Period, a science-backed health and wellness podcast dedicated to shining a light on all of the women's health topics that have long been considered taboo. From UTIs to endometriosis, we're amplifying women's needs and voices because we know there's so much more to the female experience than what happens at the doctor's office. With From First Period to Last Period, we're doing the legwork on your whole body so you can be the expert in you. Now, let's dive in.

Kristyn Hodgdon:
Hi everyone, and welcome back to From First Period to Last Period. I'm thrilled to have Doctor Jason Kofinas back on the podcast. This time, we are going to talk all about why it's so important to find a fertility clinic that is willing to get to the root cause of your infertility. So welcome back, Doctor Kofinas.

Jason Kofinas:
Thank you, Kristyn. It's great to be back, and I'm excited. This is one of my favorite topics.

Kristyn Hodgdon:
Absolutely. Doctor Kofinas is a reproductive endocrinologist and infertility specialist, in case you missed the last episode, at the Kofinas Fertility Group in New York City. And what I love about Kofinas is just how you guys really try to get to the bottom of the issue and really have individualized care for each patient. First things first like, why do you think it's essential for a fertility clinic to identify that root cause?

Jason Kofinas:
I think it's important to make the point that not everybody necessarily needs an in-depth evaluation, right? A lot of patients, literally, they'll do an IUI, they'll get pregnant, they'll be on their way, but unfortunately, that doesn't work for everyone. And it is our philosophy to not get into a situation where we go through the steps, we increase the intensity of the treatments, and then you get to the point where you've done IVF, and you've done genetic testing on the embryo. You do a transfer, and the transfer fails, or even worse, you have a miscarriage or a biochemical pregnancy. Then you're saying, well, now we have to go backwards. And,

Kristyn Hodgdon:
Yes.

Jason Kofinas:
I think the most common frustration that I see in patients who come to see me, who have failed multiple transfers of genetically normal embryos, is why wasn't that looked at yet? Or why did I use all these embryos and do the same thing over and over again? And I see that quite frequently. And it did help guide a little bit of our philosophy as a clinic, although we've been around since 1987, and we've been doing a lot of what we'll talk about, I'm sure, for a very long time. But I think the importance of when you first meet a patient understanding what could be happening based on their medical history, and then formulating the workup and the diagnostic testing from there to figure out what could be potential pitfalls before they happen is really important.

Kristyn Hodgdon:
Yeah, definitely. And so, what are some of the diagnostic tests that are non-negotiables for you?

Jason Kofinas:
A basic fertility workup, which is not unique to us by any stretch of the imagination, is ovarian reserve testing your general kind of health, thyroid health, blood counts, electrolyte testing, infectious disease testing in terms of what you're immune to, I think genetic testing is essential, and I haven't really had any patients in the last few years that have refused to do that, which is good. And then if you're just coming in, you've been, you're young, you've been trying, but you haven't really had any testing done, really, the first question is, is the sperm okay? Are the tubes open? Are there any lesions in the uterus that might be getting in the way? And are you ovulating, and are there enough eggs, right? That's really the basic workup.

Kristyn Hodgdon:
Yeah.

Jason Kofinas:
So you do all that. But then one of the things that we like to do at the beginning is we like to look for things like polyps. So, we'll do a saline sonogram. We like to look for things like endometritis, which is inflammation of the uterus. That can be done at the same time as the saline sonogram. And if you do have the risk, there is that you'll either you're not going to get pregnant or you're going to have pregnancy loss. And it's so easily treatable that it's really, I don't personally understand why that's not part of the initial workup. A lot of places, a lot of clinics will look for that after you've failed an embryo transfer. That's something that we focus on. And then from there, those are the basic things. Now, for a very long time, we have been focused on blood clotting disorders. We believe, as a clinic, that initial connection between the embryo and the uterus. The better the connection, the healthier the pregnancy, the bigger the chance the pregnancy will go to full term, the smaller the chance that the things like preeclampsia or third-trimester complications will occur.

Kristyn Hodgdon:
Do you mean like initial hCG numbers?

Jason Kofinas:
Not just numbers, but just that initial process of the implantation, the process of implantation. You want that to be optimized, right? We believe that all those little blood vessels in the developing placenta, there really should be as much of you should really be focusing on keeping those blood vessels from clotting and allowing the proper kind of exchange of nutrients between the growing fetus and the mother. And getting a healthy placenta in the first trimester sets the pregnancy up for progressing in a not complicated way, and we believe that. So that's why we look at these blood clotting disorders as well in our patients, because a lot of times, we'll identify some very common ones that are very easily treatable and can prevent pregnancy loss and can prevent late third trimester complications.

Kristyn Hodgdon:
Yeah, it seems so obvious, but I have heard a lot of stories, actually, about endometritis being discovered later. And it's like, why?

Jason Kofinas:
Exactly. Because it's such an easy test. So you have experience. Good. Okay. So you know what I'm talking about them.

Kristyn Hodgdon:
Yes. And the saline sonogram, in my experience, at least, was pretty straightforward and not painful or anything. So that wasn't for anyone who might be nervous about it.

Jason Kofinas:
Yeah, it can be a little crampy, and people have different thresholds, but it's not a dangerous test, and it's a very valuable test, so it's worth going through.

Kristyn Hodgdon:
Yeah, absolutely. So what about unexplained infertility? Because that's such a frustrating diagnosis both at the outset and also like you've had failed implantation, and you don't know why.

Jason Kofinas:
Yeah, unexplained infertility is one of the most frustrating things that patients can hear. And the statistic is that if you have been diagnosed with unexplained infertility, most likely 50% of those patients have endometriosis.

Kristyn Hodgdon:
You know, that is so crazy. I actually know someone who just had a hysterectomy, and she's in her 50s, and she has had like painful periods her whole life, and it wasn't until she literally was getting a hysterectomy that they found that she has and she had really bad endometriosis.

Jason Kofinas:
Yeah.

Kristyn Hodgdon:
And I know that it takes 7 to 10 years on average to get diagnosed. So what do you typically do to diagnose endo? Do you do like those tests? Any testing off the bat in unexplained patients?

Jason Kofinas:
It's the gold standard of diagnosis, unfortunately, is a laparoscopy.

Kristyn Hodgdon:
Yeah.

Jason Kofinas:
So it's a surgical procedure. You have to go to sleep, and the camera goes to the belly button, and it's direct visualization. There are many attempts. Whether they're successful or not is another issue to get less invasive diagnostic methods. The first step is always an ultrasound. If you see a cyst on the ovary that is very clearly as the features of an endometriosis cyst or endometrioma, then that's a pretty easy stage three or stage four diagnosis to make. Sometimes, if the lesions are big enough, you won't see them on ultrasound, but you can see them on MRI. But a lot of times, the MRI can say, oh, there's no evidence, but in fact, if you go in laparoscopically, you'll find that the endometriosis. So you really have to look at the patient's history and the patient as a whole to understand who you're going to be a little bit more aggressive with. If somebody has significant pain with their periods, painful intercourse, and infertility, they have an over 80% chance of having endometriosis. Forget about all the testing and all that. That is a statistic that is very clear. If somebody doesn't have any symptoms, so that's silent endometriosis. That's a very difficult diagnosis to make. And it takes a little bit of a leap of faith from both the physician and the patient, in the sense that if I see someone who has had, you know, multiple failed transfers or is young and is not getting good results from their trials, there is a possibility that endometriosis has been missed. And in those cases, even if symptoms are not there, I will very often recommend doing a diagnostic laparoscopy at that point. Obviously, the important thing is that when we do a diagnostic laparoscopy, we find it. We are able to treat it right then and there, and it turns into an operative laparoscopy. But I think clinical suspicion is still the best kind of tool that we have. Tests like Receptiva, for example, that are basically an endometrial biopsy, and they look for a specific marker. I've had patients that the test was negative, but I suspected it enough that I went in, and sure enough, they had it. And I've had patients that were positive who did not have endometriosis, so it's not a perfect test. And it's appealing because it's not surgery, but at the same time, it's really not as accurate as we would like it to be. Also, the treatment modalities that the test recommends might not necessarily be some that I agree with. I find that endometriosis has multiple camps, and I'm in the camp that you really need to resect all the lesions and get rid of the disease in order to have optimal treatment.

Kristyn Hodgdon:
Versus Depo Lupron?

Jason Kofinas:
Correct.

Kristyn Hodgdon:
Yeah. And you guys have your own minimally invasive gynecological surgery center, right?

Jason Kofinas:
Oh, yeah. So we have basically, it's Article 28, which is a specific type of license in New York in order to run a surgery center that can do more complex cases. And we actually built that center with ovarian tissue cryopreservation in mind. So, it is built for that purpose, but we also do all our stage four endometriosis cases there. We do all of our myomectomies, many myomectomies that we do that would really typically be done in the hospital. And I find that our patients see the experience is more pleasant and the healing process a little bit better than staying in the hospital for two, three days. Yeah, we have this center. We definitely utilize it and we do focus a lot on this particular kind of surgical concept of treating infertility patients. And it served us well because a lot of patients who, even patients who had failed IVF multiple times in other centers, there are cases that we have been able to operate on them, and they get pregnant naturally.

Kristyn Hodgdon:
Yeah, that's amazing.

Jason Kofinas:
Yeah.

Kristyn Hodgdon:
How common is it to have PCOS and endometriosis?

Jason Kofinas:
Yeah, there is an association between PCOS and endometriosis. I don't know why, but I've noticed it looking at charts from other doctors who've seen patients. A lot of doctors that do endometriosis surgery have noticed that the literature has mentioned it. And definitely, if there's PCOS and pelvic pain, you have to consider it. You cannot ignore it.

Kristyn Hodgdon:
What about without pelvic pain?

Jason Kofinas:
That's a tougher one, right? Because one of the features of PCOS is that the quality of the eggs sometimes is not so good, right? And we think maybe it has something to do with insulin, or maybe it has something to do with the hormonal milieu within the follicles. But also, if there is underlying endometriosis that's not being diagnosed, perhaps it has something to do with that. Yeah, and if you have a PCOS patient that you tried everything and you're not getting good quality embryos or you're not getting plantation and they have no endometriosis symptoms, at that point, what else are you going to do except look for that one factor that you haven't really looked for?

Kristyn Hodgdon:
Yeah, it's definitely nerve-wracking thinking about a laparoscopy when you don't have any symptoms, but the only way you can really know is if you go in there, right?

Jason Kofinas:
That's right. It's a very hard thing to swallow if you're a patient, and especially if you're a patient who's nervous about anesthesia or surgery in general. But I think whenever a decision is made to undergo something as drastic as a surgical procedure just for diagnosis, you really have to look at the benefit-risk ratio. What are the actual risks to the patient from the most severe risks, but permanent damage to organs versus like just the risk to the ovarian reserve? And then you have to compare that to if you find this condition and you treat it and you get them to their end goal, that's obviously a tremendous benefit. So, that balancing act is a tough one, and I deal with that every day, right? So it's not easy, even from my point of view. I struggle sometimes to figure out what is the right thing to do? What do we, as a clinic and under the direction of Doctor George Kofinas, who's been doing this a long time, we have all managed to almost form this second sense where we're able to really understand who needs this.

Kristyn Hodgdon:
Yeah, absolutely. I wanted to talk a little bit about reproductive immunology too, just because I feel like immune, A, autoimmune diseases are on the rise among women, and I have Hashimoto's, which is a thyroid disease. And I just think there's not enough research out there yet, but it has to impact fertility somehow.

Jason Kofinas:
Okay. So, let's talk about the immune system. So essentially, you need the immune system to have an attachment and to get pregnant. And you can't, if you had a completely suppressed immune system, you will have a difficult time getting pregnant. If you have an overactive immune system and now you have all this kind of inflammation and the byproducts of inflammation, now you're at risk of rejecting a pregnancy. So there is a fine line, a balance between over-immune, activity, and under that is this sweet spot where the immune system's working for you versus the gets you. We know and understand this right. So, the natural killer cell, for example, is a very important reproductive cell that helps to remodel the lining and allow implantation to occur. If you have too much of that cell, that's where kind of biochemicals come from, for example, or even first-trimester pregnancy loss. So controlling the percentage of these cells that are active has been a way that we, as a clinic, have been able to help patients with recurrent pregnancy loss or even these recurrent biochemical pregnancies, which are difficult to explain. So, yes, we strongly believe that the immune system plays a major role. To your point, the research is lacking, right? And it is getting better. And I think it's becoming more accepted. A lot of what we do doesn't have robust randomized controlled trials at all, and we have a lot of internal data that we are collecting and trying to put together into a paper published. But we have a lot of internal data that shows if somebody has an elevated immune response, specifically a reproductive response in their blood. So we'll do a blood test. It doesn't necessarily mean that they're going to have that same response in the uterus at the time of implantation.

Kristyn Hodgdon:
And what blood test is that?

Jason Kofinas:
It's basically, you're testing for natural killer cells, so that you're testing for cytokines which come from T cells, and it's basically called a reproductive immunophenotype, essentially. So we used to do that pretty much exclusively without any further testing because that's really all we've had. And as things have progressed, they were understanding what's going on in the uterus and how implantation is a unique kind of time period, and what happens after implantation has its own kind of parameters and what that looks like. We started to understand that if just because the blood is showing suppression, i.e. we need to suppress, you can over-suppress and keep people from implanting. So you need to be very careful when you're doing immune therapy, or you're looking at the immune system that you focus your therapies on two time intervals around implantation. And then what happens after implantation?

Kristyn Hodgdon:
Okay. And that treatment, what does that look like?

Jason Kofinas:
Which one? The for the over immune activity?

Kristyn Hodgdon:
Yes.

Jason Kofinas:
It depends, right? So, if you have elevations in certain cell types, one of the very common therapies that we'll use is a medication called tacrolimus. And tacrolimus, a lot of endometriosis patients have elevations in their cytokines. And tacrolimus is being used to treat those and treat T cell reactivity. And just as a kind of a point of reference, tacrolimus is used in kidney transplant patients who prevent rejection of the kidney, and of course, they use it at a much higher dose. And you're going to say that can't be safe in pregnancy. And if I told you that some of the most robust, pregnancy-safe data exists on tacrolimus because these patients get pregnant and they can't stop the medication. So we have a lot of data. So it is, in fact, a very safe medication in pregnancy. And it's really used to prevent pregnancy loss secondary to excessive inflammation. So that's one another big one that everyone talks about is intralipids.

Kristyn Hodgdon:
Yeah.

Jason Kofinas:
You've heard of it. Intralipids, the're infusions. They're soy-based batting falsified. The point is that in vitro, they were shown to decrease natural killer cell percentages. So you could actually send your blood, and if you have an elevated natural killer cell percentage, they treat it with insulin, and they see how much drops. So, you know, if the treatment's that good, right? So that if you have elevated natural killer cells, then you would use the Intralipids to decrease those natural killer cells to a more acceptable level.

Kristyn Hodgdon:
Okay.

Jason Kofinas:
So that's another one. And then a very common treatment is steroids, right? So, prednisone is an extremely robust suppressor of natural killer cell activity. I have noticed that prednisone, if you have, if you're using it around the time of the plantation and you don't have an obvious need for suppression at the time of implantation, you can ... the implantation process by overusing the prednisone. So, the timing of the prednisone is really important as well.

Kristyn Hodgdon:
Interesting. That's very interesting. So much of this is so outside of the box. And in the best way possible, it, when you have all the information, you can actually ask your healthcare team and try to make. And then once you have all the information, you can make the best educated decision for yourself. But if you don't know about any of this, it's really hard to know what you don't know, like we said before. For the NK cells or like autoimmune tests, like to ask for that, would someone just, it was just a blood test?

Jason Kofinas:
Like cautioning people, you're a run-of-the-mill kind of fertility center that doesn't deal with this. They're either going to dismiss you or if you get the blood test, they'll probably order the wrong one, and if the result comes back, they won't know what to do with it.

Kristyn Hodgdon:
Okay.

Jason Kofinas:
So if they're, and unfortunately, discussing this with your fertility doctor is not going to get anywhere, then you go on the internet, which is not exactly the best thing in the world either. And you start to get all these kinds of different things, and you can go down this rabbit hole, which is not necessarily where you want to be if there's a concern, right, so concerns for immune issues would be something like recurrent implantation failure, multiple biochemicals with genetically tested embryos or pregnancy loss of genetically normal either pregnancies or embryos. In that case, you seek out care from a doctor who either deals with this and understands it. The field of reproductive immunology has also expanded. There are doctors who literally only do reproductive immunology.

Kristyn Hodgdon:
Yeah.

Jason Kofinas:
They are trained in a specific kind of unofficial fellowship. And then, they consult with the fertility doctors. And of course, your fertility doctor needs to be willing to listen to this individual and or incorporate the treatments that they're recommending.

Kristyn Hodgdon:
And I think. A lot of people just knowing that cost is such a barrier to care for so many people, like adding on the reproductive immunology is definitely daunting. So the fact that if a clinic is willing to do it in house, it's such it's so appealing.

Jason Kofinas:
Oh yeah, I've heard some incredibly high consultation fees just to get on the books for Reproductive Immunologist, and we're doing it every day for our patients just to increase their chances and increase the successes, obviously. So that, I found very interesting, and I'm sure this is experimental. So insurance is not going to cover it, so it's all out of pocket and it could be thousands of dollars.

Kristyn Hodgdon:
Yeah. So I guess, it's just like how do you even I don't know, as someone who's gone through field implantation, it's just so tough to know. Is it the embryos? Is it my body? Is, do I go down that route? Has it just been bad luck? It's, especially when you've had a successful pregnancy in the past, all you can do is check the boxes and.

Jason Kofinas:
My recommendation for someone like you, or someone who might be going through what you're going through, is to organize your thoughts, and your, and the direction that you're going in. And to your point, check off the boxes, but make sure that the correct boxes are being checked off and have a strategy with your doctor that makes sense.

Kristyn Hodgdon:
Yeah.

Jason Kofinas:
A strategy that I want you to come up with it, you then have a roadmap, and you do all the testing that's required, and you don't go off on tangents or start going backwards. So again, this goes back to the root cause issue. Know kind of which direction you're going in and keep moving forward, so that way you're not in a situation where you find yourself throwing your hands up in the air and saying, I think I've done everything or have I? Then we go searching for all these random things, right? So I think that's really a good point that you make. And I think that because it's so frustrating what you're going through and what many others are going through because it's not normal to fail that many transfers, right? Something is going on, and you do need a methodology to follow that's going to at least attempt to give you that answer.

Kristyn Hodgdon:
Exactly. And it can be easy to say, want to get to the finish line and be rushing the process. And I don't know if I want to repeat those tests, but in a way it's you're better off doing it beforehand because you don't want to wish that you had.

Jason Kofinas:
Yeah. That's correct. That is correct.

Kristyn Hodgdon:
Exactly. As a sort of last question, I always like to ask, what would you rescript about the way people think about their infertility, their clinic, and whether they're asking the right questions or their clinic is asking the right questions of them?

Jason Kofinas:
Oh, that's a that's a great question. For some reason and I'm not the only one who has noticed this, we all talk amongst ourselves. For some reason, the amount of transfers or amount of retrievals that it takes to reach a live birth, it's not going in the right direction. In fact, people are requiring quite a few more transfers than you would think.

Kristyn Hodgdon:
As opposed to a few years ago or?

Jason Kofinas:
Yeah, we even we'd have noticed that our kind of what could also be patient population. But we have noticed that it takes a little bit, maybe two transfers or three transfers, especially as you're getting older. And in those cases, I'll see patients, they had a failed transfer one transfer, and they'll come to see me, and I'll put you're starting over here one failed transfer, okay? If you have 5 or 4, I understand, but give your clinic a chance because it's not easy to move your embryos. It's not easy to go through everything again. And so that would be one of my main comments to patients would be, okay, if you're not feeling that your clinic is offering you reason or really paying attention and just doing the same thing over and over again, maybe it's time for a change. But if the clinic is being proactive, is trying different things, it really can become a little bit daunting to move clinics as well. So just understand that everyone's feeling the same thing, every clinic is having the same experience. The amount of transfers, and the amount of retrievals, it's changed a little bit from a few years ago, and you would think, how does that make any sense? We're supposed to be doing better and better, right? And my answer to that is the medicine and the science in our field has stagnated. We don't have major developments like we did a few years ago, for example, genetic testing of embryos. That was huge. Or when we started culturing embryos to blastocyst and not using all weekday three embryos. That was a major advancement when we were vitrifying our flash freezing versus slow freezing major advancement. There haven't been any like that in years. And sure, there's the artificial intelligence movement. And what does that mean for embryo selection? And sure, there are genetic screening methods of embryos that could potentially offer a little more insight into the whole genome of the embryo. But those are not ready yet. And again, it's been years since significant achievements have been made. So I think that's part of it.

Kristyn Hodgdon:
Yeah, I hope the next one is more people adopting the immunology approach, just knowing that so many women struggle with autoimmune issues. And it is, if it is taking more time to get to a positive pregnancy test, it just feels like it needs to be looked into more.

Jason Kofinas:
I agree, and I hope so. I'm rooting for that, absolutely.

Kristyn Hodgdon:
This was wonderful, Dr. Kofinas. I think, I am so in awe of how thorough you are at the Kofinas Fertility Group, and I've been taking notes over here. I appreciate your time as always, and talk to you soon. Thank you so much.

Jason Kofinas:
Thank you, Kristyn, for your time. I enjoyed our conversation and hope to talk to you soon.

Kristyn Hodgdon:
If this podcast means something to you, be sure to hit follow or subscribe. This helps you because you'll never miss an episode, and it helps us because you'll never miss an episode. For science-backed women's health content that meets you exactly where you are, head to Rescripted.com or follow us on social @HelloRescripted.

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