Welcome to Fertility and Sterility Roundtable. This podcast will delve into sections of the journal previously unexplored in the Fertility and Sterility podcast family. Articles that we would consider some of the most timely, cutting edge, thought provoking, and dare I say controversial.
We will be joined by a couple of the authors each month to explore the themes, debate the pros and cons, and generally expand our knowledge in a conversational format. I'm your host and FNS interactive associate, Dr. Emily Barnard. And I'm your co-host and producer, Dr. Ben Peipert.
We will be covering articles in the Fertile Battle and Views and Reviews portions of Fertility and Sterility. This podcast is brought to you by the Fertility and Sterility family of journals in conjunction with the American Society for Reproductive Medicine. Welcome everyone to Fertility and Sterility Roundtable.
I'm your host, Dr. Emily Barnard, and I'm joined by my producer and co-host, Dr. Ben Peipert. Today, we will be discussing the views and reviews from the May 2026 edition of Fertility and Sterility entitled Male Infertility and Immune Function. This views and reviews brought together experts, some of whom we will be interviewing today, who evaluated and summarized the evidence on how the immune system plays a role in male fertility and infertility in general.
We know that infertility is caused at least in part by a male component in up to 50% of cases. And we are so appreciative for our guests for joining us today. We encourage all of our listeners to read the full articles in the journal as we will not be able to cover all the content in depth in this episode.
I would like to start by introducing our guests. First, we have Dr. Michael Eisenberg. He is a professor of urology and obstetrics and gynecology at the Stanford University School of Medicine.
Dr. Eisenberg is also the director of men's health at Stanford, and he has an NIH funded laboratory which seeks to understand the association between a man's reproductive, sexual, and overall health. Welcome Dr. Eisenberg. Thank you very much.
We are also joined today by Dr. Marcelo Mass Lindenbaum. He is a clinical research fellow at the Cleveland Clinic Foundation, soon to be transitioning to his urology residency at Cleveland Clinic Akron General. His primary academic research focuses on male infertility and its relationship with the urologic microbiome and infection risks associated with prosthetic surgery.
Welcome Dr. Lindenbaum. Hi, thank you so much for the invitation. We are also fortunate to be joined by Dr. Scott Lundy, who is a staff urologist and surgeon scientist at the Cleveland Clinic Foundation.
Dr. Lundy specializes in male reproductive medicine, sexual dysfunction, and microsurgery. Beyond his clinical practice, Dr. Lundy leads significant research efforts, including establishing a multi-institutional consortium to advance the study and treatment of male infertility. Welcome Dr. Lundy.
Thanks for having me. I'd love to kick us off by just learning a little bit about what inspired you all to write this views and reviews. Well, you know, I think when we think about male fertility, probably about a third of the time, you know, we don't understand exactly why there's an issue.
You know, we do obviously evaluations looking at semen analyses, hormone function, physical examination. So we really do a deep dive into, you know, man's reproductive function, overall health. And a lot of times we are able to identify a likely causative agent, but many times we can't.
And I think there's emerging evidence that the immune system is involved. And, you know, we know like from the female side, like for example, endometriosis, there's probably some altered inflammatory immune pathways that play a role. And so I think it sort of stands to reason that there's likely a male component as well.
And I think we've seen lots of signals of this. And so I think based on that thought process, you know, the idea behind this views and reviews was essentially to assemble experts, you know, in this field to kind of take us deep into some of the research they're doing and kind of really the frontier of, you know, immune function as it relates to male fertility. You know, we know a lot of our listeners are likely trained in obstetrics and gynecology.
That's kind of their background. We were wondering if one of you would be willing to give us sort of a brief overview of spermatogenesis, just so we all have kind of that baseline understanding of how a sperm becomes a sperm, some of the important cell types involved that we might talk about as we're talking about the immune system and the testicle. Sure, I can give you a quick overview.
So making a sperm is a really difficult thing in a lot of ways. It takes the better part of two to three months to make a single sperm. But paradoxically, most healthy men make a thousand sperm every heartbeat, which is fairly mind-blowing when you think about it.
The general structure of how a sperm is made starts at the edge of a seminiferous tubule, which is a round structure, kind of like a donut. And then as that spermatogonial stem cell travels inwards towards the donut hole, it becomes a haploid cell, and then a spermatid, and then finally a spermatozoa, which is the typical shape that we're all familiar with. And this process is very tightly and closely regulated by a structure called the blood testis barrier, which separates those haploid cells via the sertoli cells from the immune system, because the immune system has never seen a haploid cell, and it appears foreign in the eyes of the immune surveillance cells, if you will.
And so this process is tightly regulated and requires lots of hormone input, requires hormones like FSH and high levels of testosterone. It requires a very careful coordination of many genes that don't have any other role beyond making sperm, because the process of meiosis is challenging and is unique in the body. And so that's how this process all comes together, and it sometimes goes awry, and that's part of the issues we're talking about today.
So one point I found really notable from the review by Dr. Babcock et al was that the blood testis barrier is not a fully impermeable barrier. There are immune cells that come into contact with germ cell antigens during the egress of germ cells into the interstitium. Could one of you talk a little bit about why this is important for immune tolerance and prevention of autoimmune reactions to sperm? We don't fully understand the blood testis barrier and its relationship with immune privilege and immune tolerance.
There have been some really provocative studies in this area that I found fascinating. If you take rodents and you rear them in a germ-free facility where there's no bacteria in their gut, they are far less fertile than animals reared in a normal wild-type environment with bacteria. And as soon as you introduce bacteria back, what you find is that the blood testis barrier heals itself, and that leaky blood testis barrier associated with the germ-free environment becomes tight again, and spermatogenesis rejuvenates itself.
And so I think this isn't necessarily the entire picture of the immunology of the reproductive tract, but it really speaks to the complexity of this system and the crosstalk between the gut and the immune organs associated with the gut, but as well the immune system within the testicle. And we know that there are immune cells within the testicle. We just don't always know what they're doing.
And in some cases, they may be protective. In some cases, they may be harmful. And to add one further layer of complexity, it's not just the testicle that matters, it's the epididymis too.
And the epididymis is sort of the unsung hero and villain in a lot of this, and perhaps a lot of the male factor infertility that we're discussing today, especially related to immunology, is really happening in the epididymis more than it's happening in the testicle. We just don't know because we don't have the data to support that yet. Yeah, I mean, I think just to add on to that, I think that we are continuing to learn new things about the role of the immune system within the testis.
I think to your point, I also found this review fascinating, and I was really delighted that Dr. Babcock, led by Dr. DeFore, put this together for us, because I think it really is a nice summary of current state-of-the-art understanding of the blood testis barrier. But the role of the immune system within that really is necessary for somatogenesis, right? I mean, I think we learned about how, as Dr. Lundy or Scott taught us how germ cells kind of progress down into the lumen, that transit really involves the immune system and kind of opening and closing some of these junctions, allowing this movement, and that is really overseen by cytokines that are involved in the system that we're talking about here. And so, I think without the immune system within the testicle, I don't think we would have somatogenesis, and I think, again, we learned sort of more and more about it, and that was sort of, again, the genesis of this article.
It's not something that we test for, it's not something we think about, but it's probably really crucial, and without it, I don't think that reproduction would be possible as we think about it. And so, I think, you know, hopefully it's incumbent upon all of us, all the listeners, to think more about it, think of novel ways we can test it, because it's likely that it is affecting some of our patients. We just don't know how or what to do about it.
We'd love to talk a little bit, since we have Dr. Lindenbaum on the call, about the article that was entitled, Anti-Sperm Antibodies and Autoimmunity in the Era of Assisted Reproduction. Dr. Lindenbaum, could you talk a little bit about what is an anti-sperm antibody, and how do they form, and kind of the negative impact they might have on fertility? Dr. Lindenbaum Sure. So, as we were talking before, the immune system is deeply intertwined with fertility.
As Dr. Lundy explained before, generally, the sperm is not exposed. I mean, it is, because we saw in this article of the blood testis barrier that it is a bit leaky, but generally, there is an immune tolerance towards sperm. But when we have an injury, let's say testicular trauma, all this tissue gets exposed to the immune system, and the immune system starts producing immunoglobulins, or antibodies.
These are proteins produced by B-type lymphocytes, and their main function is to attack the sperm. This is an autoimmune reaction. This is the body attacking the sperm, and we mainly have two types of immunoglobulins, IgG and IgA, immunoglobulin G or immunoglobulin A, and they impair fertility.
I mean, the main problem that they produce for us is that they impair fertility, mainly by two mechanisms. One is agglutination. They cause the sperm to clump together, and this kills the progressive motility.
And also, they produce a physical barrier for the sperm's ability to penetrate the cervical mucus and to bind to the egg's zona pellucida. That's mainly, in a nutshell, what ASA, or antisperm antibodies, are. I know in your article, you mentioned that these could form after a traumatic event, obstruction, inflammation, infection, including a lot of very common sexually transmitted infections.
I was just thinking about how many men probably have these risk factors, you know, that maybe I'm not even properly asking about when you think about just a guy playing sports growing up and having unprotected intercourse, potentially getting exposed to some of these things. So, this is really interesting to think about how this might have a negative impact on their fertility on the road. Yeah, the main examples, the main triggers are, like, trauma, obstruction, also vasectomy.
This is a classic cause of obstruction. And also, epidermal orchitis or severe prostatitis. All of these trigger an immune reaction in the testis that can eventually produce these antisperm antibodies.
And what we can tell the patients, we can start asking, have you ever had a testicular trauma? If they have a history of a vasectomy and they're coming for a vasectomy reversal, this is a discussion we have to have with the patients. And also, if they're not, if they're telling, Doc, I'm starting to play contact sports, well, it's our duty to tell them, wear a cup, right? These are small things we can do for our patients. I do want to point out something that I find very puzzling in all of this, and that's that antisperm antibodies exist.
We can quantify them. We can test for them. We know that they're highly prevalent in the infertile population, but simultaneously they're present in the vast majority of people who've had a vasectomy reversal, who've had disruption of the carefully constructed sperm flow pathway.
And these men are perfectly capable of causing pregnancies. And at a relatively high degree, we quote up to 50% within the year after their reversal, if there are no other risk factors. And so I think that underscores the complexity of this issue and the possibility that there could be physiologic or at least, you know, iatrogenic versus pathologic effects of these antibodies.
And perhaps it's more complex than just presence or absence, which I think may explain some of the discrepancies we see in the data when we talk about antisperm antibodies. Given the prevalence of antisperm antibodies in these men post vasectomy reversal, are you recommending any sort of screening or testing for antisperm antibodies in these patients? I do not because I presume that they're present. And if we jump ahead a bit to the treatment possibilities for men with antisperm antibodies, for couples who undergo a reversal, we're usually attempting to avoid assisted reproduction, if possible, they'd prefer a natural conception.
So we can sort of table the ART discussion until later. We then invoke the idea of steroids, and we have often used steroids as a rescue for patients who are stenosing their vasectomy reversal, keeping in mind the lumen of a vas is about 200 microns, so there's not much room to scar. Men who have high-dose routine steroids after a reversal have worse outcomes in terms of pregnancy than men who have no exposure or low-dose exposure.
And so it yet again muddies the waters, I would say, and I'm curious if Dr. Eisenberg routinely uses steroids in that case, or if he tests for this, because I don't. Yeah, no, it's something that I used to do, but I've stopped, I would say, over the last probably 10 years or so. And one of the reasons, I think, you know, from a clinical standpoint, I think it's kind of fallen out of favor, but also it's just become more challenging.
It used to be a very simple test, and there were many laboratories around the country that did it, and fewer and fewer do, and I think that's likely for a variety of reasons, but I think certainly, you know, the increase in utilization of IVF has been one of the strong drivers for that. I think that, you know, that's oftentimes a pathway that couples choose, I think, you know, regardless of whether there's, you know, a lot of anti-sperm antibodies or not, just because, you know, if they're not getting pregnant with, you know, treatment X, then, you know, IVF is certainly very effective in most cases. Yeah.
Dr. Lindbaum put together a really nice summary of some of the potential strategies that we'll talk about as far as treatment, with ART being certainly one on the list. If I put my high-complexity lab director hat on for a moment, we run two andrology labs in parallel with our REI facility here. We do continue to run anti-sperm antibody testing.
I will acknowledge that the frequency of testing has fallen, mainly because the indications are so narrow, and even when tested, I don't always know what to do with the results. I can give some hints or suggestions, but that's still not always rooted in high-quality evidence. We do offer it.
We try to make it financially feasible for patients where we do think it's necessary, and then we scratch our heads about what to do about it. Yeah, I had been telling Ben, I graduated my fellowship in 2017, and I recall that we would test for this. It wasn't routine, but fairly commonly, especially vasectomy, reversal, that kind of thing, and then I told him now that I've been at my current practice the past five and a half years, I have ordered it zero times, so it's interesting what Dr. Eisenberg was saying, maybe not a lot of labs are running it.
I know you mentioned trying to make it financially feasible. Is it a pretty expensive test? Is that another reason why it's not ordered much, aside from the ambiguity in the results? It's actually not. If you look up the HCPCS code for anti-sperm antibody testing, the reimbursement for it, at least according to CMS, is quite low.
It's about $194, and so it's less than most of the other testing we offer. Now, there is likely patients who don't have the ability to receive infertility testing under a state mandate, and I imagine labs who are charging cash pay for this would charge more, but at least the MAR test is not a particularly complex test to run. It's not labor or resource intensive, and one of the arguments against it is that if it doesn't change management, then why run it? And that's a very valid argument, but the counterpoint to that is that a lot of $200 tests can be run to equate one IVF cycle, and so you have to be mindful of that in terms of orders of magnitude, and if there are cases where it might provide you clinical insight to either have some confidence to go to IUI or to potentially try a couple of rounds of steroids, admittedly, the evidence behind that is weak, then I don't think it's wrong, but I will be the first to say that data supporting some of these interventions is very limited.
Just to build on that, I mean, I think from, again, from an efficacy standpoint, I think, you know, you certainly, I guess, could question it in some cases, but there are certainly many patients that are very, very averse to the idea of IVF. You know, they want to do anything possible to avoid that. Maybe they had a bad experience in the past, or they just, you know, kind of worry about it in general, and so I think those are the couples where it's nice to have, again, as many different options as we can to figure out what's going on and what we can do to try and optimize their situation.
I think just like in a varicocele, sometimes we do that. You know, I always tell couples there's many paths, you know, to get to a pregnancy, and some involve, you know, the man more, some involve the woman more, but, you know, again, for these cases where we identify a problem, it's nice that we do have some options both to identify the problem and then hopefully to fix the problem. I'd love to talk a little bit more about the clinical utility of antisperm antibody testing for patients who are attempting unassisted conception versus those who are already down the path of pursuing assisted reproductive technologies.
I think Marcelo can give a really nuanced answer to this, so I'll give him, I think, the floor in just a moment. I would philosophically state that we have a friendly banter between our REI physicians and our reproductive urologists where my goal is really, as a minimalist, to try to avoid ART when possible, and REIs are very comfortable using the very, very useful and very powerful hammer that is ART, and for many patients that is absolutely the right answer, and we send patients for IUIs and ICSI on a daily basis. In some cases where couples can't or won't pursue ART, we really do try to find every nook and cranny and explore it to find an opportunity to avoid having to pursue with those technologies or to proceed with IUI rather than IVF rather than ICSI, and so, you know, I think it's all a matter of perspective, and yes, if the antisperm antibody quantity is high, then ICSI is probably the right answer for many couples, but if that's not within their goals or their financial means and they don't have insurance coverage, then it is an opportunity for us to at least consider whether we can offer some degree of reassurance or treatment that might help them.
Okay, so I'm going to give a very nuanced answer. It's based on the review, and if you read the review, there's a pretty cool graph that we did. It's a proposed algorithm, and there you can see, of course, these are not guidelines.
Actually, if we read, I actually cite in the review three different guidelines. One is the AUA and ASRM guideline that actually says that it's the question who gets tested, right, because we as clinicians, and specifically in America, that's very guidelines-based. You know, all the professors ask, what do the guidelines say, right, in rounds and everything, and specifically in America, the AUA guidelines say or the joint AUA-ASRA guidelines say that clinicians should not perform ASA in an initial evaluation.
If a patient comes for infertility, we do not order ASA as an initial test, but if something in our workup warrants ASA, for example, as we were talking before, the patient has agglutination or low progressive motility or asthenospermia, which is something that is widely cited as something that we can use to start and trigger this ASA workflow, they do recognize that it is a valuable tool. The European urology guidelines say that specifically they do recognize it as a tool, but there is a pitfall. MAR and IBTs do not have gold standards in terms of numbers, right.
Each lab has to specify their own standards, and that is one very important limitation. And the European Society of Human Reproduction and Embryology, or the ESHRE, they actually say that if a patient has a normal semen analysis, it is completely contraindicated. Okay, so those are what the three guidelines say.
Now, if we do test it, the testing is indicated, we do the MAR or the IBT, depending on the lab, specifically here in America, we're probably going to do an MAR. And what we want to look at is the ASA binding percentage, right. That is a number we're going to get from this MAR.
If the binding is less than 50%, really what it is telling us is that the infertility, the probability of it being from an immune cause is low. So that's when we should do time intercourse, or if the patient is already coming here because they've tried the time intercourse, we can consider IUI. Okay, if you can see, if we look at the literature, they're going to say also a range from 50 to 80% of ASA binding, then we, this is like very practically, we should consider IUI as a first option.
And we should repeat it for three to four cycles. Also, if this fails, we should go directly to ICSI. And again, if when we go back to the percentage, if we have more than 80%, the odds of the infertility being from an immune cause is very high.
And then we go directly to ICSI, because we want to bypass this whole immune barrier that we're having for fertility. So that is like a very practical framework. It's not guidelines.
It's just a summary of what we found in the literature. That's a great point. And the only thing I wanted to add, because, you know, Marcelo made the good point that this is how we would assess sort of immune function or like immune abnormalities within the semen.
Even though, again, if you look at the, all the views and reviews, I think, again, there was a really nice paper by Dr. Robertson and Sharkey on, you know, cytokine profile of semen. And I think that's, again, this emerging way to look at it beyond just antibodies, but look at cytokine profile. And again, that's an emerging thing, you know, as they point out in their excellent review, and I would certainly encourage all the listeners to read that, because I think there's probably something for everybody in there.
You know, there's not really gold standard clinical testing for that yet. And we do know how important, you know, the cytokine profile is, you know, within the ejaculate in terms of, you know, setting up the sperm to fertilize, setting up the embryo for implantation. It sets up, you know, the endometrium.
It's, you know, very, very powerful, you know, what all these chemokines do. And so I think that's, it would be nice in the future if we could, you know, measure that clinically. But, you know, currently with current testing, certainly, in a sperm antibody is going to be the gold standard, or really the only clinical tests where we have that.
And keep in mind that all of this testing we're discussing is in the dish. It's artificial. It's the male side only.
We're not exploring the role of the female reproductive tract at all in any of this. And, you know, we did many tests back when they, tests like the cervical mucus testing was in favor. That was excluded from most guidelines because it doesn't offer much clinical utility.
This may fall into that realm, but it may be very well that the two put together are a totally different story and can explain a great deal of unexplained infertility if you simply look at both factors in the appropriate way, whether it's cytokines, as Dr. Eisenberg pointed out, or whether it's bacteria or whether it's antibodies. I mean, there's a hundred things that can go wrong when you have two patients that you're trying to treat simultaneously to achieve one goal. One of the populations that you identified in the review as being a good group to test for anti-sperm antibodies was patients with unexplained infertility.
Do we currently underutilize anti-sperm antibody testing in this population? And if so, why do you think that's the case? I think partially it's likely related to the ability to obtain the testing and to have validated quality control testing. You know, I think there's probably 30 labs in the country that run this on a regular basis, so it's not widely done. I think there's always a concern in the cost-conscious era of value-add.
I would counter that though, and I would say that there's been some really interesting recent literature that identifies the role of HPV in anti-sperm antibodies and how we're likely missing the boat, at least on some causal insults that create ASA, and, you know, maybe it'll become moot by treating HPV and vaccinating. Maybe this issue will go away. That would be a great thing, but, you know, I can't necessarily answer the question directly.
I can just say there's a lot of facets to it. Yeah, that caught my eye too. I mean, of course, the HPV vaccine has been just revolutionary, you know, for gynecology, but I noticed that as well, that that was one of the leading causes it seemed like in some of these papers.
So have you seen, I don't know if many of you see younger men, boys, teenagers, but do you feel like we are seeing a reasonable uptick in that? I know there's been some more vaccine hesitancy recently, but it really seems like this could help fertility actually for men in decreasing the risk of HPV and thus subsequently decreasing this anti-sperm antibody risk. Luckily, we have the world expert on young male preventative health and reproductive urology and overall lifestyle and morbidity and mortality on the call with this. So that being Dr. Eisenberg.
So I think he can probably speak about the importance of us as reproductive urologists examining patients holistically. Thank you very much. Yeah, I mean, I think hopefully we will see just, I think increasing attention on men's health, men's reproductive health, I think is going to be a good thing.
And I think there may be a lot of downstream benefits for, you know, vaccination for HPV. I think certainly it is, it seems to be, again, emerging evidence suggests that it's, you know, a cause of infertility. And I think, you know, even beyond that, I think, you know, a lot of times when men come in with, you know, abnormal semen analyses, they want to know why, right? They think they're the pictures of health.
They've never really touched the health care system before. And even if you don't have a treatment for it, I think they want to know that someone is looking. And I think they'd like to have, you know, a reason.
You know, obviously there's going to be many causes, genetic, anatomic, et cetera. But I think if you could sort of put your finger on a likely contributing factor, I think that does provide a lot of meaning for the man. I think that's important.
You know, going back earlier, why we're not doing antisperm antibody testing, especially in these idiopathic cases, I think it just goes down to treatment, right? And there are some treatments that are offered, I think, with mixed efficacy. But again, if, you know, on the other end we have IVF or IUI, these really powerful technologies that work well, I think, you know, when couples see male providers or male, you know, reproductive urologists, it's oftentimes somewhat late in the journey, right? They've been trying for six months, 12 months, 18 months. And so they don't necessarily want to wait for further testing, for further treatments that may or may not work.
They just want to move forward. They want to get pregnant. Now, you know, I always kind of try and do some of this stuff in parallel.
You know, we can fix your varicocele while you go through IVF, you know, and then maybe this will help with child number two. But I think the number one goal when they see us is really pregnancy. And it's hard to compete with IVF.
It's certainly very powerful, very effective. And so I think that does, you know, somewhat limit the testing that we offer. I think sort of just a story I always like to tell, and I'm sure a lot of the listeners know it, is, you know, the Reproductive Medicine Network was this kind of network of, you know, large reproductive centers around the U.S. a number of years ago tried to do a study on varicocele.
And I think, again, you know, hopefully everybody on this call knows that varicocele repair is effective. But they wanted to do this randomized trial to show that it, you know, leads to higher pregnancy rates. And so, you know, this was a multi-center study all over the country.
You know, there was lots of money, lots of effort dedicated to this. In over 18 months, they only recruited, I think, three couples. And, you know, afterwards, they did sort of a, you know, kind of like a post-analysis, right, to try and figure out what had happened.
You know, what went wrong? Why were they not able to do it? Because they had to, obviously, close the trial after that period of time with such poor accrual. And I think, you know, one of the reasons it was given is that, again, couples have been through this for a long time. And by the time they see a male reproductive specialist, you know, the idea of being randomized to a placebo was not very appealing.
But the idea of waiting for anything wasn't appealing, right? They don't want to get a varicocele repair and then wait three months for a cycle of traumatic genesis to see that improvement. They just want to get pregnant. So, I think, you know, again, we see that same thing.
You know, if couples come in, you know, after we do a sort of first round of testing, they do have questions. But ultimately, they want a pregnancy. And so, they don't necessarily want a second round of testing or kind of add-on tests.
You know, some of them do have that curiosity and sometimes we can add it on. But I think, really, the goal for these couples is going to be pregnancy. And so, I think that also does limit some of these, you know, additional testing that we can do on some of our patients.
I have two thoughts on that. I think that's absolutely on point. The first is that if we shift this in the broader framework and context of policy, California has an IVF mandate for coverage.
And this is, I think, highly beneficial to patients. And I wish this was more widespread in our current political landscape. Ohio is one of the rare states that has a diagnostic mandate only, meaning we can perform diagnostic testing but not therapeutic testing or therapeutic treatment, I should say.
And that likely changes the dynamic between providers and patients in our state a little bit because many of these couples drive a couple hours from, you know, rural Ohio to see me and IVF isn't really an option for them until they can find a part-time job that does offer IVF coverage. Thankfully, there are some. But it likely makes this discussion about the risks and benefits of delayed gratification from waiting for treatment and shifts the balance to the less cost-intensive treatments.
And there's no right or wrong for that other than to say that we should be more proactive in expanding coverage across the country. But it becomes a complicated geographic discussion as well as a treatment and therapeutic discussion. The second question I had is for Dr. Eisenberg directly.
You know, one of the potential treatments for ASA is steroids. And have you explored that with patients very often? Do you have any anecdotal or objective experience with that? Do you find that that works at all for these men? I haven't done it in a long time. I think I was underwhelmed when I tried it a few times, again, sort of anecdotally.
Some of them had some side effects, you know, from being on these tapers. So I stopped doing it. Yeah.
How about you? I rarely will treat these men. I have, ironically, had one pregnancy in a couple who struggled with antisperm antibodies and cyclic steroids. I've also had a patient develop an acute infection that, in my mind, was likely due to the steroids that I prescribed.
So, you know, it's a double-edged sword. And the limited data we have suggests that it's not terribly useful. But I also would counter that to say the data is not strong enough to preclude me from ever recommending it.
It's just that it has to be done in the appropriate counseling. Are there any other treatment strategies aside from IUI or IVF, you know, kind of the fertility strategies that we do to address the antisperm antibodies or not really? Marcelo, do you have any? In a clinical setting, not really. There have been, like, other immunosuppressing therapies described in the literature, but all the guidelines say they recommend against them.
So, in a clinical setting, we either do, you know, ART or, as Dr. Lundy said, like, you could do steroids, but it's completely up to you and the patient. And there is no formal contraindication, but you have to know that there are side effects. One aspect that just excites me about this field in general is that it seems like every month, you know, these new targeted therapeutics are being developed.
And obviously, they're for, you know, different autoimmune diseases or other specific targets. But, again, in my mind, it seems plausible that some of these may have other applications, and I think that as we learn more about it, it's possible that potentially reproduction could be, you know, another use case for some of these novel therapies that really seem like they kind of target just specific aspects of our immune system that we're learning about constantly. Yeah, I think it's a really interesting topic, because if we were still doing anti-sperm antibody testing on a routine basis, paradoxically, we would have a lot more data to explore the patients who are immunosuppressed because of a transplant or on immune modulators for their Crohn's or their UC, and we could assess whether those agents would have resolution of their ASA.
But because there was no use case for this routinely, we stopped doing it, and so we're sort of in a catch-22 there. I wish we could find better ways to study questions like that, but, you know, we're limited to doing what's right for the patient in front of us until we have the data that we don't have. Also, there is a small avenue of treatment that isn't either medications or ART that is washing the sperm.
It has been described, but really the data, it's not good enough for us to lean towards using it, because also washing the sperm does not remove the antibodies that are binded to the sperm itself. There is a small study that does describe using chemotrypsin, like enzymatic washing, but also, again, it's a very small study. We can't draw any clinical conclusions from it, but it is another avenue that could be studied for future research.
Yeah, it's really fascinating to me how much our discussion of anti-sperm antibodies and the immune environment around male infertility is so similar to the challenges we face on the female side. I think there's a lot of situations in which patients are concerned about inflammation or autoimmune conditions affecting their infertility, and we just really don't have a for some cases, especially for patients with recurrent implantation failure, but there really isn't the data to support it. I think we find ourselves in a very similar situation of wanting solutions, but not really having anything that we know is targeted enough in this really complex immunologic milieu to truly see an improvement in outcomes that we know makes any sort of biologic sense.
I would even take that a step further, and whether it's due to the relative lack of male infertility research funding on a national scale, or whether it's due to the smaller cohort of providers who focus on male infertility relative to REIs or to urologists, the quantity and quality of data in our field is well behind many other areas of medicine, and I think that's what drives me, and I'm sure it drives Dr. Eisenberg and Dr. Lindenbaum as well, that we feel tasked to gather this data and do better because there just needs to be more of it, and there's nothing worse than telling a couple that I can't explain to them why they're struggling and my toolbox is exhausted. It's really a pretty sad day when we have to do that. I think it's important to just, like, factually state that this is a really interesting cognitive discussion, and there is certainly a role for nuanced management in patients with antispermantibody indication for testing or for treatment, but at the end of the day, ICSI will fix this problem, and there is a high degree of confidence that if the problem is antispermantibodies, it'll go away with ICSI and with many other male factors as well, not all, but many, and so we're fortunate.
Had we been having this discussion 30 years ago, it would probably be a very different discussion, and so we're thankful that we have our REI colleagues to back us up in cases like this where we don't have the tools that we wish we had. Yeah, I think it's just great that we're having this discussion thinking about these sorts of things, I think kind of pushing the envelope a little bit about what we can offer our patients and potential new avenues we can explore. Fertility and Sterility Roundtable was developed by Fertility and Sterility and ASRM as an educational resource in service to its members, other practicing clinicians, and members of the public.
The opinions expressed are those of the discussants and do not reflect the views of Fertility and Sterility or ASRM.
