Ep 346: Sperm DNA Fragmentation & Male Fertility: What Actually Matters for IVF?

0:00Dr. Carrie Bedient: You're listening to the Fertility Docs Uncensored Podcast, featuring insight on all things fertility from some of the top-rated doctors around America. Whether you're struggling to conceive or just planning for your future family, we're here to guide you every step of the way.

0:21Dr. Susan Hudson: This episode is brought to you by Receptiva DX. What if unexplained infertility isn't actually unexplained? For many women, hidden inflammation associated with endometriosis and other uterine conditions can go undetected for years, even when everything else appears normal. For more than a decade, Fertility specialists have trusted Receptiva DX to provide deeper insight into the uterine environment, helping women and their physicians uncover answers and make more informed treatment decisions. Hello, everyone. This is Dr. Susan Hedson from Texas Fertility Center with another episode of Fertility Docs Uncensored.

0:58Dr. Susan Hudson: I am here with my amazing, loving, audacious co-host, Dr. Keri Badient from Fertility Center Las Vegas.

1:07Dr. Carrie Bedient: Hello. How are you? I am good. What have you been up to? Well, in that instant, I was thinking how grateful I am that you didn't choose adjectives that started with you and go with uniquely unhinged co-host Dr. Gary P. as I am as I'm making faces at you before the recording turns on.

1:25Dr. Susan Hudson: You are not unhinged. You are very unique though but all the best of us are.

1:29Dr. Carrie Bedient: Yeah I will take that. I will totally take that. How how are you doing going into pumpkin spice season?

1:36Dr. Susan Hudson: I love the smell of pumpkin spice things but because of having to do gluten-free because of celiac for the most part. I don't usually get to partake in things like that just because it's so complicated finding out if X companies, whatever, doesn't have any gluten. And so I enjoy by proxy. When I come into my office in the morning and everybody has their pumpkin spice whatever's, I appreciate the smell. It does give me like the warm fuzzy, but I don't usually get to have it myself. What about you?

2:13Dr. Carrie Bedient: I wouldn't think that because pumpkin spice is just a series of cinnamon, nutmeg, cloves, whatever. I wouldn't think that that would be a super gluten-tastic.

2:24Dr. Susan Hudson: So I realize that anything like that is usually not as simple as just having those different spices that they have all kinds of other things added in and malt and barley are often added into those to accentuate the flavors and the richness, which is gluten in all of its beauty. Yeah, it's not a good day. Anything that's flavored, you just have to know what's in it. And there's not a lot of resources for those types of things, especially seasonal things. If you want to go down the rabbit hole of figuring out if something's gluten-free, if it's something you can get all year long. It's worth the effort.

3:07Dr. Susan Hudson: But finding out this year, does you no good next year because they may have changed their formulation and then you have to find out all over again. And for me, it's just not worth it. Got it.

3:16Dr. Carrie Bedient: I was at Target the other day and I normally buy the Tazo chai mix because never in my life have I ever had time or the desire really to sit at a coffee shop and wait for an order of whatever. And I don't like coffee as it is, but I bought the pumpkin spice chai whatever latte mix we'll see how it goes I always feel like the pumpkin spice things are heavy for the coffee drinks which is not my jam but I do like cooking with all the pumpkin things and from about mid-september to late december it's entirely acceptable and then after that I'm afraid we have to switch flavor profiles understand understand I have to say I

3:59Dr. Susan Hudson: I was on TikTok the other day and something from Trader Joe's came up with these gluten-free pumpkin spice donuts. And as getting gluten-free donuts that taste any good is pretty rare. I was like, hmm, I may swing by next time in San Antonio and see if they have any that are available. I think those types of things get snatched up pretty quick. So who knows? But maybe I'll get there right after a delivery truck gets there. Yeah.

4:26Dr. Carrie Bedient: Yeah. Hopefully between that and the ube pancake mix.

4:29Dr. Susan Hudson: exactly yes what's our question for today our question for today is i'm a 30 year old female husband is 31 all testing has been normal except morphology of two percent on my husband all other sperm counts were normal amh of four trying to conceive for two years started ivf in january of 26 did an egg retrieval and ended up with five pgta normal embryos and one inconclusive that's awesome. Did one medicated transfer in March with a euploid embryo, which failed to implant. Lining was 8.5. Did a mock transfer the next cycle with Emma Ellis ERA hysteroscopy and all came back normal. Did another transfer in June.

5:17Dr. Susan Hudson: And this time we did a natural modified with two PRP before transfer and autoimmune protocol for psoriasis. Lining was 7.2 this time around. still failed. What do you recommend next? Feeling defeated.

5:31Dr. Carrie Bedient: The biggest thing that I don't see that's been done is making sure that all of the antiphospholipid antibody tests have been done. They may have been because you mentioned an autoimmune protocol, but that's definitely one thing. The other thing that I would really focus on is how is the growth and expansion of the embryo when it thaws and making sure that it's really truly a good quality embryo that is being transferred and not just transferred because it derived the thaw, but you can't really say much else about it. It's interesting that they're focusing so much on the lining, especially when that first one was eight and a half, which most of us wouldn't fuss about.

6:12Dr. Carrie Bedient: And then they did a bunch of stuff and then the next one was only seven. That's interesting to me. You may say that you'd do better with a programmed cycle rather than the modified natural.

6:22Dr. Susan Hudson: I thought it was weird to do an ERA on a programmed cycle. I'm assuming you did it on a programmed cycle and it was normal and then turn around and change the protocol to a modified natural cycle. Maybe you did your ERA with a modified natural cycle. Then in that case, that would make a little more sense. But I agree that's a little bit unusual. The things that I would recommend is you've had two failed transfers. I would definitely recommend Receptiva. Receptiva is a test where you look at a chemical within the lining of the uterus called BCL-6. BCL-6 has a relationship with endometriosis, but not everybody with endometriosis has BCL-6 and not everybody with BCL-6 has endometriosis.

7:07Dr. Susan Hudson: But we know if it's present and not treated, that that can increase the chances of you not getting pregnant and it can increase the risk of miscarriage. And there's some pretty good, relatively non-invasive treatments, if that's present, that could have a positive impact. Additionally, there's a pretty good study that was probably done over 10 years ago now that looked at people who had had two embryo transfers. And actually in this study, it was untested embryos. So the fact that you've had two PGTA-tested embryos, I think makes it even stronger. That 30 % of people have something going on in the lining of the uterus that's only evident with hysteroscopy.

7:47Dr. Susan Hudson: So an outpatient procedure where we put a little telescope inside your uterus, make sure it's a perfect place for a baby, even with a prior saline ultrasound or HSG to evaluate the lining. And those are two things that I think could have potentially a very positive impact. But I agree with Carrie. If you had 8.5 the first time, I would go back to that program cycle.

8:09Dr. Carrie Bedient: Like I don't really understand why the PRP was done for the second cycle. That intervention doesn't make sense in that set of information with the information that we have. Well, good luck. I hope everything works out well. The fact that you got so many embryos out of a single cycle is an excellent start. And what we are talking about today may actually impact, heaven forbid, you go through and you don't get a baby out of the remaining two embryos. Our topic today may actually be impactful for you because we're talking about DNA fragmentation in sperm and how that impacts people's lives and cycles and all the rest of it.

8:46Dr. Carrie Bedient: Very good.

8:49Dr. Susan Hudson: Let's play a game. How many tabs do you have open right now about IVF? One says your chances are great. Another says they're terrible. Reddit has one opinion. TikTok has another. Facebook is full of horror stories. And somehow, after two hours of searching, you have more questions than answers. Sound familiar? That's exactly why we wrote the IVF blueprint. This isn't another fertility book filled with opinions or miracle cures. It's an evidence-based guide that walks you through every stage of IVF, from understanding your fertility evaluation and choosing a treatment plan, to medications, egg retrieval, embryos, genetic testing, transfers, and the two-week wait, and beyond.

9:33Dr. Susan Hudson: Because the last thing you need during IVF is more noise. Close the tabs, put down your phone, open the IVF blueprint instead. Available now wherever books are sold.

9:47Dr. Susan Hudson: Well, let's start off with the basics, Carrie. When we're talking about DNA fragmentation, what exactly is DNA fragmentation?

9:56Dr. Carrie Bedient: To back up a couple of steps, DNA is the genetic material that encodes all the instructions for every cell in our body. And every cell has it. And how that DNA is divided up in germ cells, so talking about eggs and sperm here, is unique from every other cell in the body. When we are working with germ cells, they only have 50 % of that genetic information. And the reason for that is because the other half is going to come from the opposite germ cells, so sperm and eggs, and that's how you end up with a complete packet of genetic information to make this new human being that is a mixture of two other human beings, which allows for genetic diversity and is all well-finding good.

10:43Dr. Carrie Bedient: When that DNA gets separated and distributed out, it has to go through a more complex process to do that. For eggs, it's part of the reason why women who are over the age of 35, 40, we start to worry about because their DNA doesn't get separated it out as cleanly. For men, it's different because men have sperm that is being generated all the time. Rather than having been created and placed before they were born, like eggs are for women, it is constantly being generated. So as a result, the way that that DNA is put together and what the integrity of it is, like how solid is it, how well put together is it, can vary over the course of time in a way that's a little bit different than how we think about women's DNA in eggs.

11:31Dr. Susan Hudson: So when somebody goes in for their basic fertility evaluation and the guy's getting his semen analysis, is there any information about this DNA fragmentation in that basic test?

11:43Dr. Carrie Bedient: The too-long-didn't-read answer? No. What information do we get from a semen analysis?

11:49Dr. Susan Hudson: So basically, the information you get from a semen analysis is we get count, how many sperm are there, we get to know some information about motility, how well they are moving or not moving, and we get some information on morphology or shape. And I'm going to add in here, there's a lot of people who really don't even know why we include shape. So it's definitely the weakest of all the parameters when we're talking about prognosis for fertility treatment.

12:20Dr. Carrie Bedient: And to bounce off of that, what is a normal parameter for shape? What's the percentage? Because people oftentimes hear this percentage in respect to their own testing and then they freak out. So normal is considered to be what and above?

12:32Dr. Susan Hudson: Normal is 4 % and above.

12:35Dr. Carrie Bedient: So that means 96 % can be abnormal, bad or otherwise, and we are totally good with that. That is absolutely true.

12:44Dr. Susan Hudson: I get a reason why most of us don't put a lot of stock into morphology. And it really is something. I mean, we were just at a meeting a month ago, and a board-certified fertility urologist is like, why are we still using morphology?

12:58Dr. Carrie Bedient: It causes so much angst, and it does not change a whole hell of a lot. It's kind of interesting to get the information of, all right, there may not be something that's completely normal here. But we kind of already knew that anyway, because you're already here in our office. Thank you for your no help. Absolutely.

13:13Dr. Susan Hudson: Additionally, in a semen analysis, we do look for white blood cells. So sometimes we can see that there is kind of a low-grade infection that's going on that's producing the little cells that fight off infection, and that can potentially decrease chances. So that is another beneficial part of the semen analysis. But in the basic semen analysis, there's no measure of DNA fragmentation. Carrie, who are people that you would recommend getting testing for DNA fragmentation?

13:45Dr. Carrie Bedient: DNA fragmentation is not a standard test that we order by default on every guy who's walking through the door. And typically, we are doing this test on someone where there's some other indication. The biggest one out of these is recurrent pregnancy loss, where there have been fertilizations, but not implantation that has continued on in a pregnancy. If we have IVF cycles where there's failed fertilization, we start to look into this more. If there have been multiple implantation failures after an IVF cycle, we start to look into it more. But it's something that is not typically recommended to be done at baseline testing for every couple that's coming through.

14:31Dr. Susan Hudson: And that's actually based on some recent guidelines. When I say recent, I think those guidelines came out within the last 12 months for sure, if not quite a bit shorter than that.

14:41Dr. Carrie Bedient: Yeah, I got interviewed for an article like a couple of weeks ago for it. It is relatively fresh off the press.

14:48Dr. Susan Hudson: Practically speaking, we all have the art of medicine. So not everything is done the same at every office, nor between even physicians within the same office. Who are guys that you would be more likely to say, hey, welcome to fertility care. In addition to the semen analysis, we're going to go ahead and check for DNA fragmentation.

15:11Dr. Carrie Bedient: Prior pregnancy losses coming in, I would tend to do it more on someone who's got major health conditions, whether that is prior cancer treatment and chemotherapy, whether that is autoimmune disease. If there is a lot of substance use and abuse, I think that that is more helpful. I've definitely had patients in the past who they were pretty healthy, but their sperm didn't look great. And it was related to substance use. And that was able to help quantify that for them, which was helpful. Those are the big people that we're going into it for. The other potential consideration that this is not an automatic, but at least flashes across my brain is if someone has sperm that doesn't look great and there's any question that we may have to do a testicular extraction for sperm, that's at least worth thinking about.

15:59Dr. Carrie Bedient: And most of the time, it doesn't automatically trigger ordering the test, but it's worth thinking about and occasionally talking about. Do you order for anybody else above and beyond that?

16:07Dr. Susan Hudson: Well, included in substance abuse, I do include my nicotine users. Nicotine's not good.

16:14Dr. Carrie Bedient: Nicotine's a substance. In our world, nicotine is absolutely a substance. That's worse in many cases.

16:20Dr. Susan Hudson: And I don't care if you're smoking, using Zen pouches, chewing gum. Nicotine's nicotine, and it's bad for sperm function. And I also tend to do it on my guys who are older than 40. Yeah. I think some of that goes along with the other chronic health things that start to happen as we get a little older. Although men can go on to father children for the rest of their lives, we are getting more and more evidence that age does matter. And it's not as blatant as it is in women, but in some ways it definitely is more insidious.

16:56Dr. Carrie Bedient: Absolutely. Absolutely. Because it doesn't show up on the easy, obvious tests and it's harder to pinpoint in many respects. Yeah.

17:03Dr. Susan Hudson: How do we test DNA fragmentation? How is that done? Is it a blood test? Is it a sperm test? How does that work?

17:09Dr. Carrie Bedient: Like all things that we do in the fertility office, he has to give us a sample in a cup. Now, this is done different places, different ways. There are some clinics where you have to go in to collect. There's others where they're able to send you to a lab. It just depends on the structure of your clinic, whether you have to collect there versus at home versus at a commercial laboratory. But two to five days abstinence and collect in a cup and send it off. And then we get results back usually a couple weeks later.

17:38Dr. Susan Hudson: Very good.

17:39Dr. Carrie Bedient: And what do we look at in those results? What kind of information are they giving us?

17:43Dr. Susan Hudson: They're giving us information within ranges. The company that I typically do my DNA fragmentation test, it essentially tells me if it's normal, if it's in a borderline zone, which means it's kind of no man's land. You can make a clinical decision based on what you think is the best thing. If it's abnormal, and at the very end, there's very abnormal. And I can say in my entire career that I've been doing this testing, I've had less than 10 people in that very abnormal. But I can tell you, having that piece of information, especially on those very abnormal guys, has made a difference because most of those guys are guys who've gone through IVF multiple times other places.

18:23And we've been able to institute some relatively non-invasive interventions, and we've had good success.

18:32Dr. Susan Hudson: Yes. So as we're talking about interventions, I'm going to preface this with this is definitely one of those things where if you have 10 doctors in a room, you're probably going to have 15 opinions.

18:44Dr. Carrie Bedient: Minimum. And some arguments to go with it.

18:47Dr. Susan Hudson: Exactly. If you add some fertility urologists in there, it's going to even add to the mix. So this is definitely part of the art of medicine. We are getting more and more evidence. And so if you listen to this podcast in two years from now, there may be updates. But right now, there's a lot of controversy, and a lot of us are dealing with this in multiple ways. What are some of the interventions that may be suggested by a reproductive endocrinologist if we have evidence of DNA fragmentation?

19:16Dr. Carrie Bedient: Vitamins and supplementation. As with every single qualifier about vitamins and supplementation, the data sucks. The industry standards and consistency from not just one brand to the next, but one bottle within the same brand has a potential to be all over the place. It is well worth it to make sure that one of the third party independent reviewing entities has evaluated the particular bottle of whatever it is you're buying.

19:44Dr. Susan Hudson: And we're talking about things like USP or NSF?

19:47Dr. Carrie Bedient: Yes, yes. That supplementation, there's a bunch of different things out there. In general, most of them contain some version of vitamin C, vitamin E, CoQ10, N-acetylcysteine, L-carnitine. Is there anything else I'm missing? Those are the big ones. Those are the big ones. But they will have some variation of those. A lot of antioxidants. A lot of antioxidants is what it boils down to. And those are supplements that you take every day. Typically, the recommendation is to take them for at least three months prior to needing that sperm again, because that will get the sperm that you will use during your IVF cycle to have the max benefit of its entire creation cycle.

20:28Dr. Carrie Bedient: You will have been on that support.

20:29Dr. Susan Hudson: All right.

20:30Dr. Carrie Bedient: What's another intervention?

20:32Dr. Susan Hudson: Stop doing the things you shouldn't be doing. Mostly, if you are using nicotine or drinking too much or you have obesity or you have uncontrolled health issues like blood pressure, diabetes, get those things under control. And we may not necessarily repeat the DNA fragmentation testing, but those lifestyle modifications can have more impact than you can even imagine. And it's really interesting. I've really started seeing over the last couple of years, almost like a cultural shift in who's willing to do interventions and who's not. And I do think it's a generational shift that I'm kind of excited about because in my practice, I have some 20-somethings who come in.

21:18Dr. Susan Hudson: I have a lot of 30-somethings and some 40-somethings and up and everything like that. But my 20-somethings are very, very motivated to make those changes. And I understand some of it's because time is not of as much essence as if we're in our 30s or 40s. But I've seen some huge, huge impact in this. And it's very motivating to me to at least be able to keep on counseling my patients that these are good things to do. Now, it's going to be up to you. No one's going to force your hand at making those changes, but know that when we're telling you that, hey, these things can have a big impact, it really is a real impact.

22:01Dr. Susan Hudson: What are some other things that we can do to potentially move the needle?

22:04Dr. Carrie Bedient: Testicular extraction of the sperm. This has varying data behind it and varying opinions. Again, you go back to that conference of 10 people, plus or minus a reproductive urologist, 15 opinions. Like Susan mentioned earlier, we were at a conference last month. So ask us how we know. It was a pretty heated debate here. There was some, not that we're ever nasty to each other, but it was hot for a little while, all about this specific topic. It was moderately uncomfortable. It didn't involve the two of us. I was sitting back eating popcorn and watching these two go at each other for things that there is no data for.

22:40Dr. Carrie Bedient: I mean, it is the art of medicine. You can make a good argument for it. You can make a good argument against it. But the beauty of that kind of argument is nobody's right. So doing testicular extraction, there are some urologists who really swear by it, some REIs who really swear by it, others who don't think it makes as much of a difference. But what it essentially means is going in and taking the sperm out directly from the testicles rather than have it going through all of the respective tubules that it needs to in order to reach the outside world on its own through masturbation. And the thought is that there's less opportunity for damage to the sperm when you do that.

23:14Dr. Carrie Bedient: That has been suggested, and there are certainly cases where, especially when we're dealing with a very high rate of fragmentation, very low sperm numbers where that may be more successful. Now, there's another really non-invasive technique, which is frequent sperm ejaculation, where you have somebody ejaculate very frequently leading up to the IVF cycle, including up to about 12 hours before the retrieval happens, and they're going to collect the specimen that is used. And the thought behind that is clear out everything old, clear out everything that has been sitting in the tubes that can be damaged by free radicals, get it all out.

23:53Dr. Carrie Bedient: And that way the specimen is actually used for insemination has the highest likelihood of no damage. And it's a technique that is not particularly helpful if you have really low sperm counts because the concern is, are we going to have anything there? But even for people who have low sperm counts, it can still be really effective because for an IVF cycle, we just need a small amount of sperm. We don't need billions of sperm. We just need one for every egg. So that's another intervention that doesn't require needles or anesthesia, but may have an impact. But again, there's not a whole lot of great data about any of this.

24:31Dr. Susan Hudson: And along that kind of theme, so there's also other sperm preparation techniques. So there's very simple, what we call swim up, where we have a way that we separate the sperm within the lab and it essentially swims in a certain direction. and the ones that swim up are the ones that are selected, obviously by the name swim up. And the other is by using a separation device. The one that I think is the most popular is probably the Zymot device. There may be other ones out there. And essentially it's a little maze that you put the sperm through and the sperm that come out to the other end have lesser degrees of fragmentation.

25:11Dr. Susan Hudson: and those are the ones that are ideally used either for insemination or for IVF. There are certain qualifications of how much you need to go through the little maze that can play into it. And again, there's people who are believers, there are people not believers, and they will go down fighting. Honestly, I don't think it's worth the fight. I think it's a very like, let's talk about pros and cons of different options and figure out what's going to be the best considering that the data behind DNA fragmentation is a little uncertain. I think the strongest data about DNA fragmentation right now is that relating to recurrent pregnancy loss, not necessarily fertilization, IVF success rates, and those types of things.

25:57Dr. Susan Hudson: I think there is a group of people that that absolutely impacts. I mean, I can think of one couple right now that I'm like, absolutely, their problem was DNA fragmentation. Once we identified it, we dealt with it, and we were successful, and we've had babies since. But this is definitely one of those, we really don't have randomized controlled trials where we have absolutely, this is better than this, or this causes this, but we know there are relationships. And just like a A lot of the things we do in fertility, there's a continuum. I mean, people who have PMOS, there are some people who have 50 follicles and there's people who have 20 follicles.

26:39Dr. Susan Hudson: Those are not the same people and we have to treat them differently. But it doesn't mean that there's not a problem. Exactly. Exactly. Okay. Well, I think we've had a lot to talk about today on DNA fragmentation. It's a little but big subject. And obviously, there's not a right or wrong answer. But again, I think that's just as important as anything else is understanding that this is definitely something that is emerging. We're getting more and more studies, but there isn't a concrete right or wrong when it comes to dealing with this specific part of the fertility testing and treatment world. Agree with above.

27:17Dr. Susan Hudson: Thank you for spending part of your day with us.

27:19Dr. Carrie Bedient: If you enjoyed this episode, subscribe, leave a review. Please, really, that's very helpful for us. And send us your questions at fertilitydocsuncensored.com.

27:27Dr. Susan Hudson: And if you want even more fertility information, including about DNA fragmentation, pick up a copy of the IVF Blueprint, our practical guide to understanding fertility treatment, IVF, and the decisions you'll face along the way.

27:38Dr. Carrie Bedient: Before we go, remember, this podcast is for education and entertainment only.

27:42Dr. Susan Hudson: While we are fertility doctors, we are not your fertility doctors.

27:46Dr. Carrie Bedient: Nothing we discuss should replace medical advice from your own physician who knows your individual history and circumstances.

27:51Dr. Susan Hudson: Thank you so much for listening. Bye. Bye. This podcast is sponsored by Receptiva DX. When fertility questions remain unanswered, Receptiva DX helps reveal why. Trusted by fertility specialists for over a decade, Receptiva DX identifies inflammatory changes in the uterine lining associated with endometriosis and other conditions that may interfere with implantation and pregnancy. From unexplained infertility, recurrent pregnancy loss, or simply undiagnosed pain, Receptiva DX helps women and their physicians make more informed treatment decisions and move forward with confidence.