Male Factor Infertility: Demystifying Sperm

For those of you who don't know , my father is a urologist and so I grew up with him wearing all sorts of ties with various urological themes and , needless to say , it was a very interesting childhood , including various Christmas emergencies that we lived through as a family .

So , you know , it's interesting that my father's father was an OBGYN and my father's urologist , and kind of the joke is that we keep it below the belt in terms of , you know , the problems that we we help , and I would like to say I'm very interested in the brain and how that , you know , influences fertility outcomes , et cetera .

But today I'd really like to talk about male factor infertility , which you know is basically half of the equation when you're talking about a heteronormative couple with sperm exposure , who , you know , wants to conceive , or sometimes even without sperm exposure , if you're talking about extracted sperm , and so I'd really love to shed some light on , you know , what is

male factor infertility ? What is a semen analysis ? What are some of the things that we think about when we're referring to a reproductive urologist , and also what are some of the newer technologies that may or may not be beneficial as pertains to helping out people who do have male factor infertility .

So you know , I think that , like we learned in medical school , a lot of this starts with a good history . I'm very fortunate in my office I have 45 minutes , you know , when I wear my doctor hat , to see a couple , and so I really get to take a pretty thorough history on the male , if there is a male involved in the equation .

We talk about health history , we talk about surgeries , we talk about medications , we talk about toxic exposures and all those things , because all those things really do matter in terms of lifestyle , like marijuana , chewing , tobacco , all of that stuff . It really does influence the quality and the quantity of sperm .

So you know , I go through that history and at the end of my first consult we usually talk about okay , you know , given your situation , this is what I recommend for you as a couple , and invariably I recommend a semen analysis for the husband if that's appropriate . And so you know it's interesting .

Most guys get a little bit shy when you ask them to produce sperm into a cup . Thankfully , in my office . I have printed instructions so it keeps it less awkward . I even now have an electronic file welcome to 2024 , that I can send over the portal so that people can kind of know what to do , what not to do . I give them a sterile cup to go home with .

It's interesting . Actually , before COVID we really were not offering at-home sperm collections just because it was like , yeah , you'll go to the office , you'll produce a sample . But that can be a very awkward experience .

I mean , hey , if you live two to three hours away from the clinic , that's one thing , but you know , if you really are close enough that you or your partner can produce a sperm sample at home and drive it in , I always say , hey , it's upstate New York , it's Vermont , be careful about the dashboard in the winter .

But really , the sperm they kind of come with their own sort of nutrients and supply and so they really can live for quite a while before they are analyzed . Usually the recommendation is within an hour . So what is a semen analysis ?

Semen analysis , basically , is a test that looks at various parameters of the semen , including the sperm , so that we can understand do we think that this couple is suffering from some element of male factor infertility or not . And I will say , you know , at least 40% of infertility has some combined male and female factors .

So this is not to point blame or to assign blame , it's more to say , you know , if I am trying to put my detective hat and figure out , you know , figure out where are things not connecting , a lot of the times there is a sperm component , even if it's not the only thing going on , and I really can't fully help a couple unless I understand all the things .

So it breaks my heart when I hear that somebody has been doing ovulation induction for polycystic ovarian syndrome for months and months , and months . And then finally the husband produces a sperm sample , whether it wasn't ordered in the first place or it was like , oh , just do a few cycles and then we'll see , you know .

And then , oh goodness , lo and behold this , you know , the sperm aren't that great . Like how much wasted time is that ? So I always say do as many things in parallel as possible . It's really not that onerous of a test .

Get it at the beginning , just because then that really does help with just , you know , framing what the diagnosis is moving forward and what interventions might work . So say there is .

You know , I think of sperm in three buckets , so I'll sort of go over this now I think of sperm that could help somebody conceive at home or wherever in a sort of outside of a clinical setting . That's their bucket number one . Bucket number two is intrauterine insemination range sperm .

So you know , maybe it's not the most beautiful sperm sample there ever was , but it's over than 5 million total modal count .

You know it's a decent sample where it's more likely to work when we put the sperm through the cervix into the uterus , compared to at home where the cervix is a big filter and most sperm are just not even going to make it inside the uterus where it can then swim up to they can then swim up to find the egg . So that's the IUI range sperm .

And then there's IVF range sperm and those are sperm where it's like okay , you know , less than 5 million total model count . Maybe there's incredibly poor morphology , which is the sperm shape . Basically , the sperm test looks at three main parameters .

There's a whole bunch of different parameters , you can see , but what we really care about for the WHO criteria are the numbers and the movement and the shape , and so you know it's all kind of an equation .

So you get the concentration of sperm and then you get the volume of sperm , and so then you can figure out like how many million sperm there are total , and then you can actually multiply that number by the percentage that are moving and then you get the total model count . So we like a total model count that is at least 20 million .

That's sort of a good number to have . The World Health Organization says that they like to see at least 39 million total sperm . But if only 10% of those are moving , then that is really sort of not so good . So you kind of have to think about that . And then in terms of the are moving , then that is really sort of not so good .

So you kind of have to think about that . And then , in terms of the sperm shape , the World Health Organization likes that number to be at least 4% normally shaped sperms . You might say , oh my goodness , that's terrible . Like all those other sperm are abnormally shaped .

But a typical semen analysis , of a normal semen analysis , is about 4% to 15% normally shaped sperm . So we get the report numbers , movement , shape kind of sort of categorize the sperm into one of those mental buckets , as we say , and you know , if there is an opportunity to move somebody from one bucket to another , that's fantastic .

You know , say somebody has IVF range sperm but you know they may be chewing tobacco or they may be smoking a lot of marijuana or maybe they have environmental exposures through their work , which I mean that can be hard to figure out because that's their livelihood , but things can be done .

So any meaningful change that you see in sperm is going to take about three months from the time you make that intervention . So say , somebody is on a medication that's not so great for sperm , et cetera .

Like you know , once you stop that , it's going to take three months for the sperm to actually be formed , to make their way down the male reproductive tract and then out the body . So you know it does take some patience , but the good news is that a lot of the time something can actually be done to improve the sperm quality and the sooner you know about .

So say , somebody has an abnormal semen analysis , right ? So what do you do then ? The most immediate important next thing to do is to repeat the semen analysis and I mean , hey , maybe they just had a really terrible virus and a fever and it kind of wiped out their sperm count . Maybe there's another explanation . Like you know , somebody missed the cup .

It actually happens more than you would really know if you didn't do this work . Um , but you get another semen analysis and if that one is abnormal , then that's two data points .

And then you start to say , okay , well , maybe there really is something going on here , and at that point I suggest getting some labs for the you know , the male um , getting them before 10 AM is preferred , usually testosterone , follicle stimulating hormone , estrogen luteinizing hormone , prolactin and a TSH .

Those are what I usually get If the sperm is really terrible . Sometimes we also get genetic studies like a karyotype and a Y chromosome , microdeletion . It just really depends . I mean , I think that , if you think about it , sometimes we even get a student analysis that has no sperm , and that's I mean azoospermia .

And if there's azoospermia times two and somebody hasn't had a vasectomy , then you start thinking about okay , does this person have undiagnosed cystic fibrosis ? Has there been scarring due to some infection ? You know what's going on , and so that's usually categorized into obstructive azoospermia and non-obstructive azoospermia . So that's kind of how people think about it .

And then if the FSH is super high , then that's a worrisome sign , just like it is for women . You can see my episode on female age and egg reserve markers is kind of analogous in the male and if the FSH is high it means the brain is working really hard to keep the testicular function going and you know , that's sort of a sign of testicular insufficiency .

So you know , just thinking about it , everything in REI does make sense , which is great . But in those situations we're usually talking about referring to a reproductive urologist , which is someone who's specifically trained in handling these sorts of problems .

And I mean , hey , I'm a gynecologist , so when I'm wearing my clinical hat I can do this , take this history and sort of know what the next steps are .

But I really do lean on my reproductive urology colleagues who can do a thorough physical exam , see if there's a varicocele present , you know , or any other physical issue that might be causing a sperm abnormality , and sometimes those can be surgically corrected as well .

So that's sort of how I think about the semen analysis and then , if it's abnormal , looking at lifestyle , looking at labs and really working together with reproductive urology to see what can be , you know , intervened upon . So , thinking about sperm , I think it's really important to understand that there is quantity and there's quality .

It's really important to understand if somebody's sperm has worked in the past , and so it's always a tricky conversation because sometimes people are in , you know , different relationships than they were before . Sometimes a pregnancy has been not disclosed to a current partner .

But all this is useful and important information to really understand you know what is the quality of this sperm Because the semen analysis can say okay . So you know , men on four different continents they looked at 95% confidence intervals . 95% of men who got people pregnant in the last year had , you know , ranges above these values . But it's not really .

I mean , there are people under those values who did get people pregnant . It's just they had to put the cutoff somewhere . So it's , it's a useful test . But the clinical history also matters because you know I've had couples before where the semen analysis looked terrible but somebody kept getting pregnant , right , the partner kept getting pregnant .

It was just a recurrent loss situation . So I think about that very differently than if there's not even enough sperm or the sperm aren't getting to the egg and there's not a conception happening at all . So they're kind of different situations . So you know what are some of the current controversies in male factor infertility . Well , there's a lot .

I just got back from the American society of reproductive medicine conference . There wasn't a ton on sperm research .

There is , there is some Um , but I think that it's really , really important to understand because if you're thinking about it like the whole male genome is compacted in one single sperm and so that attachment to the egg , that delivery of the DNA , the formation of the first pronucleus and the you know , from the male and the first pronucleus from the female , like

this is all very , very important in terms of early

embryo development . So one thing I get asked all the time in my clinical practice is like well , what about just this thing called isolated teratospermia ? And that is basically where the whole semen analysis looks normal but the sperm shape or the morphology is abnormal . Whole semen analysis looks normal but the sperm shape or the morphology is abnormal .

Now , that has always been thought to be inconsequential . However , if you think about it like , say , somebody has 3% normally shaped sperm and the sample is like 10 million , then that's going to be a much lower number compared to if somebody has 3% normally shaped sperm and the sperm sample has 150 million . So you have to sort of take it .

You know , use common sense and interpreting these values . And also , like I've definitely had couples before where there was isolated teratospermia and somebody's gotten pregnant before right or repeatedly just not stay pregnant . That's a different situation than if somebody has not gotten pregnant .

So , especially if somebody's thinking about doing in vitro fertilization and we're wondering if we should be doing what's called intracellular plasmic sperm injection , you know I at the very minimum do something called an ICSI split , so intracellular plasmic sperm injection slash IVF split , which means half the eggs get conventional insemination , half get the sperm injection

and then at least half the eggs have the chance to get the sperm delivered specifically right inside the egg , right , instead of bathing the two together like a recipe .

Now if the next day when we look at the eggs , like the conventional insemination group did just as well as the ICSI group , then we have our answer Like we don't necessarily need to go through that extra step in the future of putting the sperm directly inside the egg .

But what we're trying to avoid is the situation of what's called total fertilization failure , which is where we get eggs from the female and then the next day nothing fertilizes and gosh . That is a really , really awful situation to be in . It's estimated that perhaps 2% of IVF cycles have this particular problem . What do you do about it ?

There is this thing called rescue ICSI , which is where you can then , you know , the next day after conventional insemination , where nothing has fertilized , then physically put sperm inside the eggs . But the timing is really not quite right . You know , in my whole career I think I've had like one blast assist from this .

Uh , rescue XC technology and the live birth rates . You have to freeze all the embryos that you get , um , and the outcomes are very guarded . So it's it's always better to set this up for success from the beginning .

Um , and really just sort of , if there's any suspicion that the fertilization step is not going to go well in the setting of in vitro fertilization , definitely , you know , at least a good amount of the eggs should be subjected to ICSI , if not all of them .

I've had too many times where I had an intuition and you know it's like , oh no , let's keep things as quote unquote natural as possible . And you know , you see the eggs the next day that infertilize is like gosh , we're there , we're so close , like , why not just do it ? Um , and that's a whole .

Other conversation is the benefits and risks of XC , which I will not get into in this podcast , but I love to talk about those things and so , again , it's all risk benefit conversation and the whole point is to try to bring about um , you know fertilization .

So another thing that we talk about is these sperm sorting devices , and so when there's been a situation with poor fertilization , or if people are trying to optimize their fertilization in the setting of in vitro fertilization a few different things that people try biological , intracellular plasmic sperm injection , or basically the sperm that bind to high alluronic acid

those are seen to be the best ones and those are selected for fertilization . There's also something called Zymot People ask me about this all the time that uses microphoretics to select the sperm . I will say I think that sometimes , when we get to the gray zone of what we don't understand in fertility medicine , we grasp at straws .

We look at newer technologies , but based on my own experience , I do not believe these technologies have really . There's not enough data behind them for me to recommend them . Do they exist Absolutely ? If somebody's had a number of bad IVF cycles , is it unreasonable to try ? I guess it's not unreasonable .

I don't really know of any particular harm other than expense . But really these things are not standard of care and I just wanted to share that .

There's also a lot of controversy for DNA fragmentation testing and there's basically this thought that I mean we know that the male genome is not even turned on until the embryo is three days old , so the the eight cell stage , um .

So sometimes we see poor blastocyst progression , so the embryos are really struggling from day three to day five Um , and so in that situation sometimes it's possible to look and see if the DNA in the sperm are highly fragmented , and so it's another thing .

It's not all or none , you know , there are some DNA that are naturally fragmented , but when there's a high DNA fragmentation it's thought that those embryos have a harder time making blastocysts and being viable embryos .

And so if we're trying to making blastocysts and being viable embryos , and so if we're trying to improve not just egg quality but embryo quality overall , if the sperm contribution is there and this can be very tricky to tease out , because it's really hard to sort out egg and sperm issues as pertains to embryo development but that is one test that can be done .

It is a very specialized test and many places do not even offer this testing . Talk to people who've had this done . It's like a robot or rocket ship is sent to the house and then the sample is obtained and then sent off . So it's quite an interesting experience .

But I always was taught in medical school don't order a test if it's not going to change your management , right . So the question is what would be done with an abnormally high DNA fragmentation test ? And so the answer to that question is that you can use actually a different extraction method for the sperm .

So ejaculated sperm are thought to probably have the highest DNA fragmentation because they've been sitting so long in the male reproductive tract before they can make it out . But if you can extract , you know , sperm either from the testicle or from the epididymis , that's thought to have a lower DNA fragmentation , and so you can extract that and freeze it .

It to be clear that type of sperm uh , because the concentration is , um , you know , just , it's like a so low it's . It's a high concentration , but it's a . It's like a low number of sperm overall , um , and a lot of times it's non-modal , so that sperm can really only be used in an IVF setting .

It's not appropriate for an injury or insemination , but you know , it is something where you know , if those sperm are thought to have a lower DNA fragmentation , that that might be a possibility . Another possibility is also that you know somebody can say , okay , the DNA fragmentation is high . Let's look at lifestyle factors .

You know , three months without marijuana or you know whatever it is .

I mean , I will say most of my patients and my clients , they are already living very clean , pure lives , however not always , and so sometimes this can be a good opportunity to kick that habit or whatever it is , to finally really make all the vectors in line as best as is possible to bring about a successful outcome .

So I mean , those are kind of the controversies as I see them . You know it's always hard when we have an area of controversy or a data-free zone in medicine , because you know I want to help steer people with the right answers right , especially when I have my doctor hat on and I'm really truly giving medical advice .

But I think you know , just understanding the basics of the semen analysis , the numbers , the shape , the movement , understanding what we're looking for , understanding that sometimes the semen analysis really does need to be repeated if it's abnormal , to understand if that first one was just a fluke or whether that was truly a trend and there really is something deeper

going on . The labs can be very helpful , just as in the female , because they help us understand the communication between the brain and the testes , because that's its own access to right . The brain and the testes have their own access and they're always in conversation with each other . And then also , you know when to refer to a reproductive urologist .

Throughout the years , I have had the absolute pleasure of working with so many wonderful reproductive urologists and they just are so good at what they do and they just , you know , really care about helping people bring about their families , and so , um yeah , I think that if that's what's warranted , don't hesitate , just go for it again .

You know it's never um bad to get extra information that can help with decision-making et cetera . But just be wary of some of the newer technologies , because I think that a lot of it isn't entirely worked out and it is tempting to grasp at straws . But I think sticking to some of the evidence-based stuff is really kind of the tried and true way to proceed .

So I hope you found this helpful . I have been hearing that people love the sciency series , and so I will do my best to keep those up and to educate to the best of my ability . I love you .

May we all understand as much as possible about the male and the female sides of infertility and let's keep bringing beautiful children in the world , because knowledge is power . Okay , I'll talk to you soon . Bye .