Melanie Cole, MS (Host): Today, we're giving insights on the 2024 American Urological Association and the American Society for Reproductive Medicine's guideline amendment for male infertility. Welcome to Better Edge, a Northwestern Medicine podcast for physicians.

I'm Melanie Cole. And joining me is Dr. Robert Brannigan. He's the Vice Chair of Clinical Urology, the Chief of Male Reproductive Medicine and Men's Health and a professor of Urology at Northwestern Medicine. Dr. Brannigan, it's a pleasure to have you join us today. I'd like you to start by giving us a bit of an overview of the male infertility guideline and its significance in the field of Urology.

Dr. Robert Brannigan: Well, Melanie, first of all, let me just thank you for the invitation to join you today and to share information from this guideline, which I think will help not only urologists, but many other physician groups who help provide care for men who are not only trying to have children, but also thinking about future fertility down the road.

So, now, I think that this guideline amendment is important. The original guideline was published in 2019 and covered literature spanning from 2000 to 2019. This amendment covers literature that was published between 2019 and the middle of 2023, so four and a half years of data. And in that short period of time, there were a lot of new developments that led us to publish this update.

Melanie Cole, MS: Well, thank you for letting us know about that. So, let's get into this. Give us an explanation of the amendments recently added to the guideline in 2024 and the rationale behind their inclusion. Tell us what changed.

Dr. Robert Brannigan: So, I think a few of the big things that changed, one is the change in the indications for testing for a genetic cause of male infertility, and that specifically is Y chromosome microdeletion testing. So as many of your listeners will know, the long arm of the Y chromosome houses genes that code for sperm production. And in some men, some of those genes will be missing and that can cause an impairment in sperm production or outright absence of sperm production. So previously, the level of sperm concentration that would be an indication to pursue Y chromosome testing was 5 million sperm per milliliter or less. And now, we know from literature published since 2019 that really this testing is low yield if the concentration is above a million. So now, the guideline statement has been reworked and now we would only be ordering this testing if the sperm concentration is one million or less. So, that's one change.

We also have updated information about testing for suspected ejaculatory duct obstruction. We've added information about pursuing a non-invasive approach to clarifying this diagnosis, namely by using pelvic MRI imaging. And then, finally, there's another highlight of this amendment is the opportunity or the possibility to go to the testicle to extract sperm and use this sperm in in vitro fertilization for men who have elevated levels of sperm DNA fragmentation.

Melanie Cole, MS: Wow. Those are some interesting amendments. So, tell us a little bit about the most significant changes as you're telling us those amendments. Tell us where they fit in to practice for urologists.

Dr. Robert Brannigan: Yeah. So with the genetics testing, you know, 1-2% of men overall have azoospermia or no sperm in ejaculate. And an additional cohort of men have lower sperm counts. And pinpointing the cause of this azoospermia or severe oligospermia is important not only to let the patient know what the cause of their fertility issues is, but also there's an informed consent aspect to this for patients to understand, if they have a certain genetic abnormality that that could be passed on to offspring. So, that is why I think crystallizing, clarifying the cut point for the Y chromosome microdeletion testing is important.

Secondly, with the imaging of the prostate gland with an MRI in the setting of suspected ejaculatory duct obstruction, this is really important because prior approaches involved transrectal ultrasound imaging and possibly seminal vesicle aspiration, which while it's an office-based procedure, it's invasive and has certain inherent risks associated with it, including a risk of infection. And now, we know that pelvic MRI imaging is easy, it's non-invasive and, quite honestly, gives really invaluable anatomical information that can help guide care very, very effectively in the setting of suspected ejaculatory duct obstruction.

And then, this idea of going to the testicle for sperm in men who have elevated sperm DNA fragmentation, this is an important concept. I think the literature in this area has crystallized recently, and it seems that a sperm transitor make their way through the epididymis and the vas deferens. That journey carries with it a risk of increasing oxidative stress for the sperm, hence sperm DNA damage. And we know that that can affect fertility and reproductive outcomes for men and their partners.

So, that's why these amendments are important. There's a lot here, and it's just very important, I think, for urologists and others helping to provide care for or counsel men with reproductive issues to know what the state-of-the-art is to provide the best level of evidence to our patients as they're making decisions.

Melanie Cole, MS: Well, there is a lot, and we're going to be discussing as much as we can get through today, but if you were to say how this amendment enhances the ability of urologists to provide that optimal care for infertile males, take us from bench to bedside, what's your favorite part about it?

Dr. Robert Brannigan: Now, I think my favorite part is just providing increased clarity for urologists. And a lot of this gets to the level of evidence that is assigned to each statement within the guidelines. So, not every guideline statement is black and white, there are certain levels of evidence in the literature that are used to support making a statement in the guidelines. And I think with this update to the guidelines, with this amendment, I think there's just greater clarity with the strength of recommendation of every statement, based on the increase in literature and increase in evidence, that's been published since the prior version.

So, I guess at the end of the day, what I'm trying to say is that there's more evidence for clinicians to more confidently counsel their patients about how to handle their fertility, how to go through a workup, and what treatment steps to pursue. Greater confidence there for the clinicians and patients.

Melanie Cole, MS: Well, that makes a lot of sense, Dr. Brannigan. So now, can you elaborate on the updates involving the use of imaging modalities? You mentioned a little bit about MRI and pelvic MRI when evaluating patients. Give us some of the implications of those updates.

Dr. Robert Brannigan: Yeah. So, I think on one hand, when it comes to imaging, what we want to get away from is routine imaging with either ultrasound or MRI for all patients coming through the door who have infertility, even if they have azoospermia. We know that the yield on this, on indiscriminate imaging, is really low and in fact can adversely affect patient outcomes. Sometimes Incidental lesions are picked up with this imaging that may not be malignant, but may be there nonetheless. It may cause a patient to have to go through a series of additional steps or even procedures to figure out the diagnosis. So, sometimes patients will have a Leydig cell hyperplasia when they have infertility. We'll see this condition not uncommonly in men, and that may show up with radiographic changes on ultrasound imaging that may cause a patient and clinician alike concern, cause again further diagnostics when this really is not needed and wouldn't have been picked up in the first case if indiscriminate ultrasound imaging had not been pursued.

On the other side of the equation, again, I did briefly mention the use of pelvic MRI in men with suspected ejaculatory duct obstruction. And I think that's a real win for both the clinician and the patient. On the clinician side, the anatomical information from a pelvic MRI, including a good look at the ejaculatory duct and seminal vesicles is really helpful for understanding what's going on in perhaps even surgical planning. And for the patient, it's a big one because it's non-invasive, again, a transrectal ultrasound and possible needle aspiration of the seminal vesicles. All that is invasive and has with it associated risks, including the risk of infection.

Melanie Cole, MS: Well then, let's break down some of these updates made to the recommendations. Tell us a little bit about the update made to the recommendation on evaluating azoospermic patients and how that impacts the diagnostic process.

Dr. Robert Brannigan: So, the evaluation of azoospermic males has really evolved over the years. When I was in training, it was the standard to take the patient to the OR or to a procedure room when the diagnosis of azoospermia came back and do a biopsy. And the biopsy would tell us if it was an obstructive phenomenon or if the patient had non-obstructive azoospermia. And now we know, based on some important work done by, actually, a former resident here at Northwestern, a doctor named Richard Schoor, is in New York now, and Craig Niederberger, who's also here in Chicago. We know that using FSH levels and a polar length of the testicle can help us to differentiate obstructive from non-obstructive azoospermia, again, avoiding the need to take the patient to the operating room to figure out if they have a blockage pattern or not. And this approach has a very high level of success for predicting obstructive versus non-obstructive azoospermia. So, this guideline statement really underscores this notion that we should be diagnosing obstructive from non-obstructive azoospermia, really predominantly in a non-invasive fashion.

Melanie Cole, MS: Now, tell us about the key changes in the recommendations on karyotype testing and how that contributes to the evaluation of male infertility.

Dr. Robert Brannigan: So, we took a look back at the eukaryotype testing, and while we found that the threshold for Y chromosome testing, which we often check in the same patients would be more appropriately reset to 1 million sperm per milliliter, really, there's not been any change in evidence for karyotype testing. And so, for any man who's got a sperm concentration 5 million or less, those patients should undergo karyotype testing. And as I think most of your listeners know, both the Y chromosome testing and the karyotype testing are blood tests that are very easily obtained.

The most common abnormality that's going to be found on karyotype testing is Klinefelter syndrome, and I would just encourage listeners to be mindful of the fact that the karyotype abnormalities in Klinefelter syndrome, the phenotype is commonly not present in all patients. So, there's a common karyotype of men having visceral fat and tall stature, sometimes gynecomastia. And very often these patients do not have any of those findings on physical exam.

Melanie Cole, MS: Dr. Brannigan, the guideline amendment introduces a new recommendation on the utilization of testicular sperm in non-azoospermia patients. Tell us a little bit about the rationale behind that recommendation and its benefits.

Dr. Robert Brannigan: Melanie, this is an important point, I think one of the really novel aspects of this particular guideline statement. So, we know that when men have elevated sperm, DNA damage levels elevated, what we call DNA fragmentation indices. This can, in many men, lead to impairment in fertility, either with efforts to conceive at home, and it can even affect results with IUI or in vitro fertilization. And just as a brief review, the way these elevated DNA fragmentation levels come about is, we think, through oxidative stress. And so, oxidative stress comes when there is an excess level of free radicals. These are molecules that have an extra electron present in them. And these free radicals can damage the sperm directly. They can damage the sperm membrane. They can also damage the sperm DNA within. And so, what we found is, in taking a good look back at the literature, we found that since the time of the publication of the original guidelines, there's really been novel and well-grounded evidence that testicular sperm can provide enhanced outcomes over ejaculated sperm for men who have elevated levels of sperm DNA damage or elevated levels of DNA fragmentation. And so, what we're offering these patients now is the opportunity to go to the testicle and extract sperm and use that sperm in in vitro fertilization. So, there's a good amount of literature now showing that this can enhance reproductive outcomes for couples.

So, the good news is when we tend to think about a microTESE procedure, this can be a, fairly invasive procedure with an extended recovery. The good news is for these patients with elevated DNA fragmentation levels is that it's a pretty straightforward procedure. We know they've got sperm production present and we're simply going in and quickly and easily removing a piece of testicular tissue and then using that for IVF. There is some new literature not commented on in the guidelines, but I think it's important to note some work really coming out of New York, Dr. Schlegel and his group, looking at increased frequency of ejaculation, in other words, really kind of purging the system, having a number of ejaculations in a short period of time.

And the notion there is that we're decreasing the transit time in the excurrent ductal system. And that has, based on some literature, been associated with a decrease in DNA fragmentation levels. And so, the jury's still out on that one in terms of having really firm evidence, but that's going to be another issue that will certainly be looked at another approach. That'll be looked at carefully as time marches forward. But for right now, there's certainly good evidence to support the option of going to the testicle for sperm in this setting.

Melanie Cole, MS: Doctor, how do the updated World Health Organization reference ranges for human semen characteristics affect the diagnosis and management of male infertility, and does this have global implications?

Dr. Robert Brannigan: The World Health Organization is the organization that oversees the performance of semen testing, and they also are the organization that dictates the reference ranges for semen parameters. So, semen analysis reports in Europe and Asia, North America, South America, look very similar because they have the same standards, which is so important within our field to have standardized reference ranges. So, since the time of the publication of the last Infertilities Guidelines, since that time, a new edition of the World Health Organization Laboratory Manual on the examination and processing of the human semen has been published. So, this is the 6th edition. So, I would say that there really are not earth-shattering changes in this 6th edition by the WHO, but we thought it was important to reflect the current reference ranges in our guidelines amendment. And that's what we did throughout the guidelines document, we did update those.

Melanie Cole, MS: Tell us a little bit about male infertility globally, Dr. Brannigan, and why this is so important. I mean, we're having this discussion today, but this is really of global importance when we're looking at these recommendations.

Dr. Robert Brannigan: So, I'm glad we're taking a step back here because this is so important. So if we look at couples, about 15% of couples will have difficulty achieving a pregnancy. And I'm sure many of your listeners, those who may not be taking care of reproductive patients directly will know someone in their personal lives who either are or have grappled with this issue.

And so, if we look at the causes of infertility, we find that about half of couples have a male factor involved. Unfortunately, historically, and even to this day, the onus for the evaluation and treatment throughout the world has really fallen on the female partner and there are a lot of reasons for that. But it's unfortunate because, again, the burden for diagnostics and treatments have often fallen to the female partner. What I think is so important about these guidelines is that they point out how many opportunities there are in the male partner to treat him and very often improve or correct his fertility.

Why is that important? Well, very often improving the male partner's situation may reduce the level of invasiveness in either testing or treatments that the female partner needs to go through. So for example, if we can take a man who's got very low sperm counts and say correct a varicocele or medically optimize him and get enough improvement in his sperm numbers, then maybe they're going to be eligible for insemination, which is a lot less invasive than IVF or maybe they'll even be eligible or have greater success with conception by natural means. So again, I think that the idea that the male partner is a true partner in reproductive efforts just cannot be stressed enough.

There's one other important point about these guidelines and about male infertility overall, and that's this. The male infertility might be the only sign or symptom in a patient who has more substantial underlying medical issues that are causing that male infertility. We see so many patients who come through with a variety of underlying genetic issues, anatomical issues, behavior, or lifestyle issues, hormonal imbalances, or even cancer, where the infertility is this sole sign or symptom. So, the idea is that fertility could be a window into a man's health or barometer for his overall health. And so, there's an abundance of literature supporting this, and that's why it's not good enough for the wife's OB-GYN doctor to give the patient a cup and say, "Your evaluation is going to be semen analysis. And if there's any sperm at all, we're good, we can use it for IVF." That is completely inadequate. The patient needs to be treated like a patient and undergo full history, physical exam, hormone testing, and semen testing. And only then will we have a comprehensive look at the male partner and have the chance to see if there's any underlying medical issues causing their male infertility.

Melanie Cole, MS: As long as we're jumping back a bit and head back to our medical terminology days, Dr. Brannigan, the amendment includes a new table defining common terms in semen analysis. How does this table aid healthcare providers in interpreting and communicating semen analysis results effectively?

Dr. Robert Brannigan: A lot of this is common sense and just trying to standardize the language of the guidelines document with the published literature and trying to be inclusive with language, with our medical literature, not excluding folks. So, sometimes I think we as clinicians trip over ourselves and stumble to find the right words, I won't go through the full table, but I think that the point is that the terminology needs to accurately reflect what's going on medically. And it needs to be inclusive, and it needs to be consistent across the literature, especially as we're communicating our recommendations to patients. So, that's why we included this table in the guidelines document. It's not commonly done, but we felt that given the heterogeneity of terminology and phrases used in our field to describe various conditions, consolidating everything and using the state-of-the-art terms is really important.

Melanie Cole, MS: Dr. Brannigan, we've worked on this with other team members from other hospitals, yes?

Dr. Robert Brannigan: Yes, this amendment, there is actually one other urologist. It was a relatively small panel, so the way that these amendments are done is it's a more focused group, I think, in order to enable us to be nimble. So, the other physician that was involved is Cori Tanrikut, and she works for a group called Shady Grove. They're a fertility group that really has offices across the country. And so, she was my partner or colleague in this, and other associates or colleagues included Senate Kim and Aaron Kirkby with the American Urological Association, and then also colleagues from a group called ECRI, and ECRI is a group, ECRI stands for the Evidence-Based Practice Center Team or the Emergency Care Research Institute. And they're a group that helps to perform the PubMed search and gathering all the data that we use to publish the guidelines statement. So, those were the folks involved. And of course, it's important to point out that this amendment builds on the work of the original guidelines panel that was led by Dr. Schlegel and other colleagues back when that was initially published.

Melanie Cole, MS: One thing I think we've learned over the years is that male infertility is said to provide insights into male general health. How do you feel, in your opinion, these guidelines can contribute to improving men's general health beyond reproductive potential?

Dr. Robert Brannigan: This is so important, Melanie. Again, while female partners, I think very many women routinely go to their OB-GYN doctor annually, it's just something that they do. I think culturally, very often we see males just don't have a doctor. They don't have a primary care doctor, and they're not seeing a physician unless, you know, very often they really have substantial issues going on.

And so for the male coming in for a fertility workup, this might be their only touch point with a physician. That's why it's so important for us as urologists taking care of these patients to really do a thoughtful workup. And that includes listening to their concerns, their complaints, doing a good physical examination on them, and of course doing the hormone and semen testing, and not stopping there. If something is off or abnormal, we need to follow up. So, for example, the guidelines state that if a patient has low testosterone, you're going to want to consider going the next step and ordering an LH level. And if that's low ordering, prolactin. So by this pathway, we might diagnose pituitary abnormalities that could be representative of either hypogonadotropic hypogonadism, like Kallmann syndrome, or a prolactinoma with prolactin excess, which can certainly be a significant medical issue, a serious medical issue.

And so, I think the point is that, do the fertility workup, but we need to be doctors as well, and keep in mind, A, that these patients very often are not seeing doctors often, and this exam and this patient encounter may be the only one that they have for years. And be recognized again that fertility may just be the tip of the iceberg medically for these folks.

Melanie Cole, MS: What a great point that you made about men not really going into their doctors. So, this is a reason that they go in as the couple is trying to reproduce. And so, this could be the start of something or clinical findings. I mean, it is such an important point that you make. In what ways, Dr. Brannigan, do these guidelines promote the evidence based care? As we just said, that is not subjective really, but men getting in, getting their overall health checked. But here, this is evidence-based care you're talking about in these amendments, ensuring the best possible outcomes for infertile males. So, how do you feel that these will tie all together?

Dr. Robert Brannigan: It is so important when you say there, Melanie, that you put the emphasis on the evidence-based guidelines. And people talk about medicine as being part science, part art, and that's true. But I worry clinically when people treat it more like an art than a science and kind of wing it. And when we find that the approach to patient care is not rooted in evidence, very often things are missed. And important opportunities for optimizing health can be missed, and important medical diagnosis can be missed. And so, that's why I think really being familiar with the guidelines and using them as a road map to help in patient care is imperative.

And I think the guidelines are important. You know, this is not a black and white issue. These guidelines statements, this guideline document is not a black and white document. Of course, there's room for judgment and for the physician to discern his patient situation and how a particular statement might pertain to it. But I think that guidelines are really a relief for physicians, again, getting back to what I said earlier, providing solid ground for a physician to look at his patient, or her patient, or their patient, and realize, A, what's going on and, B, providing a very logical step forward that's grounded in evidence. And we want to be confident as physicians that we're steering our patients correctly. And there's a lot of painstaking work that goes into putting together a guidelines document like this. And that work is looking at the worldwide literature, discerning what is good evidence or what is strong evidence, and then formulating these recommendations from that.

And that, as you mentioned earlier, what about the bedside? That goes right to the bedside and that steers the direction of treatment for a particular patient. There's no question that I think since this original guidelines document was published about five years ago, we're seeing an enhancement in patient care, because physicians are not struggling with the basics of how to approach their patients. There's a very clear roadmap, and that provides consistent high level care for patients, not only here in the United States, but around the world. Globally, people look at and use these guidelines. I got a message from a colleague in Brazil last week, and a colleague in Australia the week before last, just about these guidelines and how grateful they were to have them as a reference point.

Melanie Cole, MS: That's very cool to hear. And I think one of the most important points that we can make today in this podcast, as you're talking about them being guidelines, and as you say, they can take these guidelines, and it really helps to standardize that assessment and that care. So, how can healthcare providers use these, implement these guidelines into their practices for optimization of evaluation and management of male infertility? Tell them how they can take these guidelines and put them into practice.

Dr. Robert Brannigan: I think right off the bat, when we're looking at applying these guidelines or where does the rubber hit the road, I think certainly the very first part of the guidelines document, just talking about the assessment, it used to be that we would wait until the female partner had been worked up and maybe that the couple had been trying for a period of time before we would do the work up on the male. No, now we know the guidelines clearly state, statement one, the evaluation of the couple should be concurrent. If we don't do a concurrent workup, we're going to waste time for the couple. And as we know, time is often of the essence, especially on the female side of the equation. So, that is just statement number one. I think the rest of the statements that follow the other 50 plus statements that follow the guidelines really help to provide that kind of clarity.

Also, I think another statement to point out or to counsel the patient on is that, when a patient does have abnormal semen testing, we need to let the patient know there may be other things going on, that's statement number five, and that we need to take a more close look at the patient to see if there's an underlying medical issue or condition causing the impaired sperm production. I think very often guys just want to get in and get out and do a semen test and bolt and not follow up, but we need to plainly tell them, "Look, there may be more going on causing the low sperm production. So, bear with me. This workup is not going to be painstaking, but I need to approach you as a patient like I would with any other condition."

Melanie Cole, MS: What are some future directions or areas of research that the Male Infertility Guideline amendments aim to address as you would give us a blueprint and look forward to the future? And you mentioned urologists all over the world. What do you think are some of the most important points that this aims to hit at, but also that you would like to see happen?

Dr. Robert Brannigan: So, first of all is the issue of really being able to provide more clear diagnostic information for the patient. Very often we don't know what is causing the lower sperm counts or the impaired fertility in men or women. We suspect for many patients with "unknown infertility", unknown cause of infertility, that there's probably an underlying genetic root cause. As time goes on and the years march on, there's more and more research identifying very specific genetic issues or changes that can cause male infertility, and that's helpful. But I think being able to provide more solid specifics for our patients will be a big advance. And so, ongoing genetic studies are happening, and that will help us be more specific with patients.

Another area of research that is really interesting is the following, Dr. Jason Hedges is a urologist in Oregon, Oregon Health and Sciences University, and he's an MD PhD who's doing primate research on marijuana and cannabis. So many of our patients are recreationally using marijuana and cannabis products. And there's really been a limited amount of literature to this point in time looking at what effect does it have on health? What effect does it have on reproductive health? Dr. Hedges is showing very interesting work in primates, so as close as you can get to humans in terms of research, showing an adverse effect of cannabis and marijuana products on fertility in both male and female primates. And we do think this information translates to the human experience.

So, this is something that we really counsel patients carefully. And I think a lot of patients figure, well, if it's legal, it must not be harmful. And it seems that that couldn't be further from the truth. Now, we do know it's not just smoked or inhaled marijuana, but also edible products that can have an adverse effect on fertility. And one other thing that I think really, really we need to look at is vaping. Vaping is so prevalent, but there's really limited information about how that affects fertility.

So, there's a lot of areas in which we can do research and advance our field. There's research underway looking at each of these issues. And our patients want answers, and it's our job, I think, to go out there and get answers to a lot of these questions so we can provide them more effective counseling on what is causing their infertility.

Melanie Cole, MS: Dr. Brannigan, what an enlightening discussion we've been having today. As we get ready to wrap up, you mentioned lifestyle, and we haven't even really talked about that. We've been talking about diagnostic criteria and assessment and possibilities for other conditions going on, but we really haven't discussed lifestyle and the assessment there. You mentioned vaping and cannabis, but there's smoking, there's alcohol, there's stress, there's exercise and obesity. I mean, there's a lot that goes into male infertility, right? So as we wrap up, I'd like you to speak to other providers. Put this all together for us, what they should consider in the evaluation and management of male infertility. Put it all together with us, how you approach patients and why these amendments were so important.

Dr. Robert Brannigan: Great, Melanie. I appreciate the opportunity to do this. So, just to my colleagues out there, be they urologists or others, you know, Internal Medicine, Family Practice, endocrine physicians, whoever, and you have a patient who comes to you asking for a fertility workup. I think that standard approach is really a good reproductive history. You want to ask them how long have they been trying to conceive. Have they had any prior pregnancies? Have they achieved any prior pregnancies? Do they have any children? And something that's often overlooked is sexual health. The stress of trying to conceive causes erectile dysfunction issues in about 15-20% of men. This often goes unspoken. So, asking the patient about that, explaining that it's common, and treating the situational ED if they have it is important.

Moving on from the history, the next step would be a physical exam, and it's just looking for things that can affect fertility. Varicoceles are prevalent. About 20 percent of men have them, and we know they can impact fertility in a lot of guys. Also, looking for evidence of perhaps absence of the vas deferens, or epididymal inflammation or obstruction. These are things that can sometimes be picked up on physical examination. The blood work, the hormonal assessment's really easy. Typically, it would involve a testosterone and FSH level and sometimes adding in prolactin and estradiol levels, and LH levels as well.

And finally, the last part of the testing, semen testing. And so, the good news is that this evaluation is actually really straightforward, and we're seeing many couples where they realize the male factor evaluation is very quick and easy, and they come to us first to see what's going on in the male side before even pursuing a female workup.

So, I think, again, history, exam, blood work, semen testing are really the basic building blocks. And from there, based on what you find, that's when you turn to the guidelines and figure out what the next steps are for a particular patient.

Just a brief word, I talk to all my patients about lifestyle optimization. Patients are super motivated. They want to know what they can do. So for our patients, I actually give them a document. It's a medical publication published in Fertility and Sterility called Optimizing Natural Fertility. The first part talks about the steps couples can take to optimize their chances for conceiving at home naturally, talks about the timing and mechanics of intercourse, and also the use of ovulation detection kits. And then, the second part talks about behavior and lifestyle issues for both the male and female that can help optimize their fertility. We see so many couples where there may be issues with patients being overweight or obese. We know that can have a real strong adverse effect on fertility. The increased fat mass can lead to conversion of testosterone to estradiol, that can lower testosterone and that can suppress sperm production. So, optimizing diet, optimizing exercise can have very real effects on the hormonal panel and in turn, by optimizing testosterone levels, can help further optimize sperm production. So, we know that these hormonal effects through increased diet and exercise are very real. These have been pointed out in the testosterone deficiency guidelines and other guidelines documents. So, taking a few minutes at the end of the visit and providing the patient with that encouragement to take control and optimize lifestyle can also have a real positive benefit for them.

Melanie Cole, MS: What a great conversation that we've had today, Dr. Brannigan. You are an excellent guest. Thank you so much for joining us. To refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/urology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole.