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Up to 40 percent of infertility cases involve combined male and female factors, but the male partner is often skipped. Erica Bove, a reproductive endocrinology and infertility specialist, returns to discuss why that gap exists and what can be done about it. This episode is based on her article “What is often overlooked about male factor infertility,” published on KevinMD. You will hear how prescribed testosterone for low energy and low sex drive can wipe out sperm production, sometimes irreversibly, and why men taking it for low T frequently have no idea their fertility is at stake. You will learn what a basic semen analysis screens for and what a full male evaluation adds, including hormonal testing and a reproductive urologist exam. You will hear how varicocele surgery alone can resolve a couple’s infertility, why marijuana and tobacco are unusually bad for sperm, and why every change shows up three months later. Press play to find out which male factor causes are most often missed, and which are most often reversible.

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Transcript

Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast. Today, we welcome back Erica Bove. She’s a reproductive endocrinology and infertility specialist. Today’s KevinMD article is What Is Often Overlooked About Male Factor Infertility. Erica, welcome back to the show.

Erica Bove: Thanks so much, Dr. Kevin. It’s so great to be here.

Kevin Pho: All right. So tell us what your latest article is about.

Erica Bove: Sure. So I’m a reproductive endocrinologist, and that means I see couples with infertility all the time. Usually, it’s the woman who comes in. In a heterosexual relationship, she may or may not be with her husband if she has one, and the common trope is, “I just want to focus on myself, you know. We’ll deal with my husband later. He really doesn’t want to do the sperm test. It’s kind of awkward. Let’s just get my testing done, and then we’ll go from there.”

But what that misses is the fact that up to 40 percent of infertility is combined male and female factors. And so if we’re only focusing on the female partner, we’re missing a huge part of what might be going on under the surface.

Kevin Pho: All right. So tell us some of the initial steps that you would take, the questions you would ask to kind of suss out whether there’s a male factor involved with the infertility.

Erica Bove: Yes. We actually have a zillion questions that we ask in terms of the male component. So typically, we ask pretty basic history questions about any medical problems, any surgeries, any medications, any allergies, family history, those sorts of things.

But the fertility history is really important. I want to know, has that man ever conceived a pregnancy before? And sometimes it drums up older stuff that is a little sensitive to talk about, but we have to talk about it because I want to know, has your sperm ever worked in any relationship over the course of time, because that tells me a lot, right?

There are times when the male partner has been in a few different relationships and tried to conceive, and he’s the common denominator, right? It’s like, “OK, so I got divorced, and then my former spouse, she conceived right away with her new husband.” Those are sensitive things, of course, to talk about, but I need to understand those details to understand the full picture, right?

And so we talk about the reproductive history specifically. We also talk about things that may not come up on a typical PCP history questionnaire, such as toxic exposures, such as exogenous testosterone use. That is a huge killer of sperm that people don’t know about. We talk about marijuana and alcohol and smoking. Tobacco and marijuana are really, really bad for sperm. I call these my below-the-belt questions, right? Have you ever had any significant trauma? Have you had any surgeries? Have you had any infections, even sexually transmitted infections? I really need to know those details to understand what might be going on.

And so it is a pretty detailed round of questions, but I say, “You know, I know these are personal, but I need to understand so I can help you.”

Kevin Pho: So you said that there is a significant proportion of women that you see in your practice whose partner doesn’t come in. Do you insist eventually they come in so you can ask them these questions? Because it sounds like it’s a pretty significant potential cause of the infertility.

Erica Bove: Yes, and it’s interesting. I mean, I think the women will often sort of know their partner’s general history, but a lot of these more detailed questions, and I mean especially about previous pregnancy history, these things may not have even come up.

So what I like to do at the very first visit is say, “OK, can you get your partner on the phone?” The nice thing, sometimes we have video visits too, is that people can remote in from wherever they’re at, even if they’re at their jobs. And so I really want to hear from the male partner himself what has been his experience.

Or maybe this whole testosterone thing, I want to scream it from the rooftops that when men take testosterone because they have low energy and low muscle mass and low sex drive, when men take that testosterone, it will literally wipe out the entire sperm count. And so probably once a week I see a couple where nobody knows this man is taking testosterone. Maybe his PCP’s prescribed it. And the good news is that if I stop it, a lot of times the sperm will come back after three months, but sometimes it doesn’t and it’s irreversible, and so these are the details I need to know.

So yes, absolutely. And the other thing too is I will say fertility is a joint venture here. And so every now and again I’ll find couples that are not on the same page about having a child, and that’s also something that I need to know about because if I’m going to help a couple bring a child into the world, I really need to know that the social situation is something where I can move forward as well.

Kevin Pho: So let’s go a little bit more granular in the exogenous testosterone, because men of reproductive age, a lot of them, you see billboards, right? Low T and testosterone is being peddled in mainstream media. Just go into more detail in terms of the impact it has on fertility. You literally said it would wipe out all the sperm, but how permanent is it? You said after three months. Just give us some potential long-lasting implications of exogenous testosterone.

Erica Bove: Sure, absolutely. So it’s actually really bad. And in thinking about the physiology, the brain and the testes are always in this communication loop. And the brain is monitoring, OK, are the testes making testosterone? If they are, they send a message back to the brain, and they’re in this happy conversation. But if men are taking testosterone, injectable testosterone from the outside world, that tells the brain, “OK, we’ve got testosterone around,” and the brain truly shuts down, and the testes themselves don’t make their own testosterone.

And so what happens is, sometimes when we stop the exogenous testosterone, the damage has been done, and the communication doesn’t wake up, and it can be really, really hard. And so I’d say in the vast majority of cases, we can recover sperm again once the man stops. Sometimes not to the full potential, but at least enough to do some reproductive treatments.

But when I see this, it usually is azoospermia. You see the man on the call. He’s kind of bulky and looks like a bodybuilder. Maybe he’s even in a gym. That’s sort of the typical kind of clue. I ask everybody what their story is. And I will say a lot of men are really hesitant to go off of the testosterone because they feel so good on it.

So sometimes we even get in the situation where I’m like, “OK, you have to trust me here. Let’s stop the testosterone for three months. We’ll freeze a bunch of sperm if it comes back, and then we’ll get you right back on your testosterone.” So we’re really talking about multidisciplinary care here because men do get used to feeling so much better on testosterone if they have low testosterone to start with, and it can be kind of not as straightforward as it might seem.

Kevin Pho: So we talked about some of the external causes, like the testosterone. You mentioned marijuana and smoking as well. How about diseases? Any diseases that you typically see that are associated with male factor infertility?

Erica Bove: Absolutely. So chronic disease can always have an effect on the reproductive system.

So the first screening test, and we haven’t talked about this yet, is a semen analysis. And so there is a certain amount of abstinence and instructions. And thankfully, since COVID, most of us will now allow sperm collections at home if they live within an hour of the clinic. And so men will produce a sperm sample. They’ll bring it into the office. The andrology team will look at it under the microscope. They’ll look at numbers. They’ll look at shape. They’ll look at movement. Some other parameters, too, but those are the most important ones.

And then if that’s normal, fantastic. It’s a pretty good screening test. They look at 95 percent confidence intervals. But if that is abnormal, then we repeat the semen analysis again. And if that’s abnormal times two, then that’s a pretty good tip-off that there’s something going on on the male side of things. And so when that happens, then I start my evaluation.

So I’m going to do a hormonal evaluation. I’m going to get serum. And these have to be done before 10:00 a.m. just because of the diurnal variation. We get a testosterone, luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, and a TSH. And I can’t tell you how many men had no idea that their sperm counts were low because of hypothyroidism, for example, or also maybe a prolactinoma in the brain that’s secreting prolactin and suppressing the body’s testosterone.

I’ve also seen other chronic diseases such as really bad type 2 or type 1 diabetes that can have an effect. Even obesity, actually. I know it’s a controversial topic, but even obesity can have a significant effect on sperm counts and motility and such. And so really that’s why we really take a good history to understand the medical problems, the surgical problems, back surgery, spine surgery, right? All those nerves go down the spine and then into the groin region as well, and so we also have to understand what that history is so that we can then involve a reproductive urologist if we need a male exam, for instance, to look for a varicocele or maybe to do some of our more nuanced ways to extract sperm if the nervous system is involved as well.

Kevin Pho: So we’ve talked about, of course, so many causes that could affect male factor infertility. I guess in general, and you could go into the various causes, how reversible and how fixable is this if you do find whatever reasons causing the male to be infertile?

Erica Bove: That’s a great question. And so I don’t know how reversible it is. It is usually treatable. And let me give you my framework for how I think about sperm. I think about sperm in three different buckets. The first bucket is semen analysis completely normal, likely to conceive at home. The second bucket is intrauterine insemination may work for this couple. So again, total motile count is probably under 20 million. Maybe there’s abnormal sperm morphology, but if we can get the sperm beyond the cervix into the uterus, there’s a good chance that we’re going to be able to overcome that male factor. And then the last category is what I consider IVF-range sperm, which means that the total motile count is under five million.

Maybe the sperm morphology is bad. They’ve done three IUIs, it’s not working. My goal is always to move people from one bucket to another, right? Say I see a couple and I see IVF-range sperm, I want to work with the lifestyle factors. I want a reproductive urologist involved because if we can move that couple from an IVF-range sperm parameter to an IUI-range sperm parameter, the intrauterine insemination, that’s a lot less invasive. It’s a lot more money. And sometimes even a varicocele surgery is all people need to then get them to conceive at home.

The tricky part is it’s often multifactorial. So when we look at it, it’s not usually one giant thing that’s causing infertility. It’s usually a little bit of this and a little bit of that, and that’s why it’s really important to understand the female side as well because if we’re also dealing with ovulatory dysfunction, if we’re also dealing with endometriosis or diminished ovarian reserve, each couple really needs to be looked at and tailoring the care.

So I would say a lot of times we can’t fix the sperm entirely. Over half of sperm problems are idiopathic, which means we don’t exactly know why. But if we see a varicocele, that can be fixed surgically. If we see low testosterone, we don’t give exogenous testosterone. We actually give clomiphene or an aromatase inhibitor to help the body’s own axis wake up and do a little bit better.

And so it is very treatable, reversible. Really, the only reversible male factor, completely reversible, seems to be with lifestyle factors. If a man will completely give up smoking or completely give up marijuana. Now, keep in mind, any change that a man is going to make for his health is not going to be seen in the semen analysis for another three months because that is the life cycle of the sperm. It takes that long to be created and then make it through the male genital tract and then out to the outside world. So take some patience, but I will say there are many success stories, especially if we can look at the lifestyle stuff and make gains on that front.

Kevin Pho: So speaking of success stories, that actually would lead to my next question because we’ve talked about so many different potential scenarios. I would say can you share some of the most common ones that you see, where you identified a reason of male factor infertility, you addressed the cause, and then the couple was successfully able to conceive after your intervention? What would be, say, a common success story that you would see?

Erica Bove: Sure. I think varicocele is the biggest one. And so what is a varicocele? It’s basically like a varicose vein around the testicle. They’re very common. There are different grading scales, et cetera.

But I remember this physician patient I had when I was a fellow, and I saw her. She had a little bit of diminished ovarian reserve, and then we discovered that her husband had a varicocele. And typically the counseling is, “Well, you know, it could take at least three months, but maybe even six to 12 months to see an effect.” And I remember we sent her, him really, to a reproductive urologist. He did the varicocele surgery. Six months, six weeks, excuse me. Six weeks later, she called me with a positive pregnancy test. And so that was all they needed to get them over the threshold to be fertile, and that was all she needed. So that was very satisfying because if, say, we had just focused on her and we had ignored that piece of things, then that would’ve gone completely undiagnosed.

So that was very satisfying. I can think of another couple where the man had very poorly controlled type 1 diabetes, and we worked with his endocrinologist and really got his A1C down. We saw a corresponding improvement in sperm parameters, and that’s all they needed as well.

And, as an aside, my father’s a urologist, and we both practice in Vermont, and so we do share a lot of couples together. We recently had a combined case where the woman had PCOS and the man had male factor. They tried IUIs. They weren’t working, and then we did IVF for that couple actually. Again, sometimes it’s not always reversing it, but it’s finding the right treatment. We did IVF for that couple. She did well, and her first embryo transfer was successful, and they’re currently pregnant.

Those are the types of things. Sometimes we have to get it at the root cause. Sometimes we have to say, “You know what? We’ve done due diligence. We can’t figure out exactly why, but we’re going to go with our more involved therapies.” But I would say most male factor is able to be overcome.

Now, if there’s no sperm in the ejaculate whatsoever, that can be more tricky. Usually then we have to look and say, “OK, is it obstructive?” Meaning the sperm just are there, but they can’t get out, or are there very few or no sperm at all? And, I mean, that’s a whole other conversation, but I would say our advanced reproductive technology is usually best in those situations to do a testicular extraction, see how many sperm we’re dealing with, and then usually do in vitro fertilization to help people in that scenario.

Kevin Pho: Now, in your article, you also talk about some of the newer tools, like DNA fragmentation testing. So talk to us about how that fits into the diagnostic spectrum.

Erica Bove: Yeah, absolutely. So we know that as the sperm goes through the male reproductive tract that it is exposed to DNA damage and free radical formation. And so we all learn that superoxide pathway in medical school. And if we can extract the sperm earlier in the process, it has been shown that there is lower DNA fragmentation if you can do, say, a testicular or epididymal aspiration as compared to ejaculated sperm.

And so when we see perhaps that maybe a couple has unexplained recurrent pregnancy loss and even IVF isn’t making a difference, or say the day three to day five embryo progression is poor, again, the female genome is responsible for the first three days, and then the male genome turns on at three days. And so if you can see really rockstar embryos on day three, but then they really tail off from day three to day five, those are situations where we may send off the sperm for additional testing to look at DNA fragmentation to see, is it high? If it’s high, the first thing we do is look at lifestyle modifications, because a lot of times that will solve the problem in and of itself.

But if really the lifestyle has been optimized, then often we’ll work with urology to get a testicular aspiration to then get sperm that maybe don’t have such high DNA fragmentation, and that is sometimes what people need to get them through. And so that’s very nuanced. There are other technologies that people talk about. I think in fertility medicine we want to help people so desperately, and sometimes we grasp for tools that maybe aren’t the most evidence-based. And so there are other things like sperm-sorting techniques, or other things that people have tried to really try to get at the best sperm. As of right now, really none of those are evidence-based. But DNA fragmentation I think in certain populations can have a beneficial role, especially when there’s poor embryo progression from day three to day five.

Kevin Pho: So to sum up, from the male perspective, I know we’ve talked about this earlier, but why don’t you summarize for us what are some lifestyle things that they could do to maximize their fertility potential?

Erica Bove: Absolutely. So the biggest thing is what people put inside their bodies. I will say smoking, chewing tobacco, really, really bad for sperm. Same thing with marijuana. So much marijuana use out there. So really, working with the PCP, finding other ways to treat anxiety if that’s part of what’s going on, and to really wean off those substances is probably the most powerful thing that people can do.

Looking at the deeper health just to make sure that all the rest of the health is optimized. Sometimes I work with people who have toxic exposures in their job, like firefighters or welders or basic scientists even, or farmers. And so if there is a component, it’s really hard to change your job, but I have worked with couples before where they talked to their bosses and looked at OSHA regulations and were able to get better PPE to be able to reduce some of those exposures as well.

And I think really getting a thorough evaluation, the two semen analyses, if the first one’s abnormal, getting the hormonal evaluation, the deeper testing, and then also an exam with a reproductive urologist can be really, really helpful to understand what do we think is going on here, and where can we try to reverse the underlying cause? And if not, what treatment avenue is going to be the most successful, either intrauterine insemination or in vitro fertilization. Only in rare cases do we discuss donor sperm, if the couple’s open to that. But I would say the good news is that most male factor is treatable.

We just need to test for it early so that we don’t waste time treating the female partner, not knowing what’s going on with the sperm situation. And also weight loss. I mean, I think we don’t talk about that enough, but there is a good amount of data that male obesity can have a detrimental effect on sperm as well.

People have talked about supplements. I’d say coenzyme Q10 is probably the only one that’s shown modest benefit. Everything else really has weak or no data. So if people ask me what to do, I say, “Eat a balanced diet, get sleep, get exercise, cut out your toxic exposures,” because the female partner’s usually doing these things as well. And then let’s test the semen analysis in another three months and see if we can see some of the benefits of those changes.

Kevin Pho: We’re talking to Erica Bove. She’s a reproductive endocrinology and fertility specialist. Today’s KevinMD article is What Is Often Overlooked About Male Factor Infertility. Erica, let’s have some take-home messages that you want to leave with the KevinMD audience.

Erica Bove: Sure. So I would say if you are in a relationship where you’re trying to have a kid and things are not connecting, see a reproductive endocrinologist on the sooner side. So the general recommendation is, under 35, trying for a year, or over 35 or above, trying for six months, go see a reproductive endocrinologist. However, if you are in a relationship where, say, you’re listening to this and you’re a male partner and you’ve been the common denominator, you’ve tried over multiple relationships and haven’t been able to conceive, but your partners have in other relationships, really it’s not just a blanket recommendation for everybody.

We have to look at the whole picture. So a semen analysis, I know it’s kind of awkward, but really most people can collect a sample at home. Really, really important data to understand what might be going on and what can we do about it. And so I always think the female partner is getting poked and prodded and all these invasive tests. This is not really that invasive. So really, go with the flow, get the test done. If you need a second one, get it done because understanding the sperm side of things can really make a whole host of a difference. And also, if you do need in vitro fertilization, look into your insurance coverage early.

If you’re nearing open enrollment, look and see if there is a better plan that might cover IVF. If you’re in a mandated state, know about that. If you’re not in a mandated state, look at what groups are doing advocacy work as well, because I think there are access issues as well. But the more access you have to all the different fertility treatments, the better this is likely to go for you and the least amount of money out-of-pocket spent possible.

Kevin Pho: Erica, thank you so much for sharing your perspective and insight. Thanks again for coming back on the show.