Sperm DNA Damage and Recurrent Miscarriage (Episode 638)

Full Transcript: Episode 638

This is the Fertility Friday Podcast, episode number 638.

Today’s episode is a bit of a follow-up to last week’s episode. In last week’s episode, we did a throwdown on the WHO guidelines for semen analysis, their most recent 2021 update. In today’s episode, we’re going to talk about some of the limitations of a traditional semen analysis and why we should be learning more about the impact of sperm DNA fragmentation, or sperm DNA damage, on pregnancy and fertility. That’s what we’re going to be talking about in today’s episode.

The paper we’re going to be going through specifically looked at not just the topic of DNA fragmentation, but went a little bit deeper and actually looked at different types of DNA damage and how they could impact your risk for miscarriage, or your client’s risk for miscarriage.

This is a really interesting paper with some really interesting findings. I think this is going to be an area that we see a lot more research in. I think we’re going to see a lot more discussion into it. And I do hope that at some point this will become more of a standardized testing practice.

A little bit about the study: the researchers looked at 100 men whose partners had at least two consecutive first trimester miscarriages. Couples who were conceiving naturally, but having at least two consecutive losses. They compared that to 81 proven fertile sperm donors with confirmed live births. For all of these men, they went through the semen analysis using the updated 2021 WHO 6th edition criteria. In order to be classified as normal, they would have to meet those standards.

They also specifically tested the sperm DNA damage, or the DNA fragmentation, using a variety of different methods. This gave us the opportunity to compare the semen analysis to the DNA damage report. The paper took this a step further because they were also measuring a specific type of DNA damage: double-stranded DNA breaks, which are the more severe type. They were looking at this more specifically because they wanted to see if the more severe type of sperm DNA damage is associated with recurrent miscarriage.

Let’s talk about some of the findings and points that stood out to me when going through this paper.

The first point is something the research has been showing for a while. If you already have a copy of Real Food for Fertility, you can take a look at the sperm chapter. There’s a whole section in there about sperm DNA damage. The research is extremely compelling because there is a very strong link between a high percentage of sperm DNA damage and how it affects fertility.

There is a certain point where, if the sperm DNA damage is high enough, pregnancies are not reported in studies. We do know that there is a link between the level of sperm DNA damage, or DNA fragmentation, which is just a synonym. Just saying the same thing in a different way, but I’ll use those terms interchangeably. It does show us that there is a specific link to fertility issues and the level of sperm DNA damage, independent of the semen analysis, which is an important point we’ll be getting to.

When they looked specifically at the 100 men whose partners had had two or more miscarriages following natural conception, 66 of them had semen analysis classified as normal per the WHO 2021 criteria. But of those 66 “normal” men, 61% had an elevated sperm DNA fragmentation result. And 52% had an elevated double-strand DNA fragmentation result. That double-stranded measure was something this paper looked at specifically because it’s the more severe form of sperm DNA damage.

Even though these men were being told that they were fine, because they met the WHO criteria, when they actually looked deeper at whether these men had evidence of sperm DNA fragmentation, they did. The couples had a median of four miscarriages. It was a minimum of two, but some of these couples had multiple miscarriages. It took, on average, about four miscarriages before the sperm DNA was even tested.

This further solidifies my point that men are often being overlooked, and we’re quick to say that they’re fine if they’re hitting these very low WHO criteria. But if we’re trying to determine what would be optimal for conception, we can’t really look toward those guidelines.

The paper also said that only about 25% of clinicians internationally are routinely ordering sperm DNA damage, or DNA fragmentation, testing. This isn’t surprising because, as I mentioned at the beginning of the episode, this is not part of the standard semen analysis. Often, couples who are being sent for DNA damage analysis are the ones seeking out assisted reproductive technology.

There are a lot of concerning pieces of this for couples who’ve experienced recurrent miscarriages. It’s standard practice for a couple to have to experience a minimum of three miscarriages before they’ll even look at additional tests. Typically, they’re testing the woman: uterine anatomy, clotting disorders, hormonal status, chromosomal issues. But for the man, they may simply do a semen analysis. It comes back above or meeting the WHO criteria, and that’s the extent of it. This paper is showing that there is a clear link between elevated levels of sperm DNA damage and miscarriage.

This is certainly an opportunity for clinicians to look deeper into the issue of recurrent miscarriages. What this piece of data is showing us is that the semen analysis is not sufficient to confirm whether or not the sperm is okay. Over 60% of the men who were fine based on these guidelines were clearly not fine when a deeper analysis was done as to the integrity of the sperm DNA.

Another key piece is that this study didn’t just look at sperm DNA damage overall. It separated out the type of DNA damage and specifically looked at the double-strand sperm DNA damage, or DNA fragmentation, because it is known to be more severe. This novel clinical distinction gives us even more information because there is a level of specificity that can be done when we’re looking at this specific link.

Not only does sperm DNA damage overall link with fertility issues, what they found in this paper is that when a man has an elevated level of the double-strand DNA specifically, it is more specifically linked to miscarriage. That means we actually have the capacity to test a man’s sperm beyond a semen analysis to look at who would be at greater risk of their partner having a miscarriage. In this case, the miscarriage risk is linked to his sperm. I don’t know many women who’ve had one or more miscarriages who even think it could be related to his sperm parameters, because that’s just not something that we’re taught. This is huge, and it’s why I wanted to talk about the paper today.

The researchers found that the double-stranded DNA damage was specifically linked to miscarriage, and the single-stranded DNA damage made it harder to conceive. The single-stranded DNA damage was more linked to infertility, just not conceiving, whereas the double-stranded DNA damage was specifically associated with miscarriages. Newer research that’s coming out often takes a while before it’s incorporated into day-to-day clinical practice.

To follow along with this line of research and evidence from the paper, the double-stranded DNA test dramatically outperformed the general sperm DNA damage testing at predicting miscarriage specifically. Compared to just looking at the percentage of DNA damage overall, distinguishing between these two certainly had a higher role. It shows us there’s so much more that we need to know.

There was something else interesting. One of the things I said in last week’s episode about the WHO guidelines is that generally speaking, the medical community’s proposed solution for male infertility is IVF, assisted reproductive technology. The specific type of procedure they tend to recommend in situations where we know the sperm parameters are poor is ICSI. If you’re not familiar with ICSI, you’ve probably seen images of it: an egg cell, and a tiny needle sticking the sperm in. That is what ICSI is. The medical professional looks at the sperm, chooses the ones that look best, and sticks it into the egg. That is their solution to male infertility.

What the researchers found with this paper, by dividing out the double-stranded DNA damage compared to the single-stranded, was that if the male partner has this elevated level of the more severe type of DNA damage, even if they’re trying to look at which sperm look best and stick it into the egg, that does not actually solve this problem, because they can’t tell which sperm have the damage by looking at them. The selection process in ICSI currently does not screen out this issue. That means that if your partner has this elevated level, assisted reproductive technology doesn’t just magically resolve the issue.

This is not surprising because in Real Food for Fertility, when I talked about this issue, there’s a whole section where I talk about ICSI. If you’re wanting to nerd out about it, grab the book and read through the chapter. Even when they do all of these things in the lab, the success rate is still fairly low. The conception rate is not 75% when they do these procedures. It’s typically closer to 30% overall. There’s a lot that they don’t know, even though they have all of these different procedures. This paper shows a specific piece of this that isn’t being looked at as specifically.

I think it’s so interesting that the medical community’s solution to male infertility is assisted reproductive technology, when there exists such an incredible opportunity to improve these situations. One thing I’ll always say about these conversations about sperm quality is that this is not a hopeless situation. Even if your partner did a sperm DNA analysis test and it came back that he had a high level of sperm DNA damage, that’s not the end of the story, because there are a lot of proven strategies, from dietary strategies to supplement strategies to just having a full evaluation and identifying if your partner has any risk factors. 35% of male infertility cases are related to infections. There are some specific physical issues that can impair sperm, some specific habits and lifestyle factors that can impact sperm, and certain medications that can have a negative impact on sperm.

This conversation is hopeful. That may not have come through at the beginning, but the crazy thing about male infertility is that there’s often ways to significantly improve it, even if the sperm DNA damage is really bad. If you know that, you can take the opportunity to start incorporating strategies to support sperm quality. After years of working with clients, if their partners are willing to make a few specific changes and incorporate a few evidence-based strategies to support sperm quality, within three to six to nine months, you can see a dramatic improvement in these parameters, and even in sperm DNA damage. As the paper shows us, assisted reproductive technology is not necessarily the solution in all cases, especially if the man has this elevated sperm DNA damage, particularly the double-strand DNA damage outlined in this paper.

The last point to bring it all together, which is fairly obvious by now, is that there’s a lot more that can be done to investigate the men. We have a history of all things fertility looking at the woman. I can remember working with clients who’ve been trying to conceive, and it’s not happening. They’re asking their doctor if their male partner can be tested, and the doctor is telling them there’s no need to do that. That’s not the case in all situations, but we do have this tendency to look to the woman and assume everything’s fine with the man, even though all of the research would tell us there’s a really big problem happening with men.

Over the past 50 to 70 years, sperm parameters have declined significantly. It’s outrageous. If these trends continue over the next 30 to 40 years, we’re going to have a really big problem, because if the sperm count, testosterone levels, and all of these things keep declining, we’re going to get to the point where the average man is in that subfertile range. That’s really scary. We should all be concerned about it. We should definitely not be pushing male fertility issues under the rug. We should be looking at it.

Within the context of charting, what I always say is that when you have couples who are having sex at the specific time of the cycle they’re supposed to be having sex, and we know so much about the menstrual cycle, so much about the role of cervical mucus, when you have a woman who is fairly healthy, whose cycles we can’t really detect huge problems with, she’s making mucus, we know she’s ovulating, and it’s just not happening cycle after cycle, this is when we have to look deeper. It shouldn’t take an average of four miscarriages before her male partner is given a test beyond the typical semen analysis to actually assess his DNA, especially when the research is quite clear that there’s a very specific link between recurrent miscarriage and this specific type of sperm DNA damage.

Whether you are a practitioner working with fertility clients, or whether you are trying to conceive and trying to get answers, and what they’re telling you is unexplained, there’s nothing else you can do, you’re not really sure where else to go, chances are they haven’t necessarily dug as deeply into this topic as they could have. Whether we like it or not, it’s often up to us to look deeper, to learn as much as we can, to increase our knowledge so that we can really advocate for ourselves and advocate for what we need.

If you don’t have your copy of Real Food for Fertility, you can head over to realfoodforfertility.com and grab the first chapter free. I spent a whole lot of time and effort in the sperm chapter, and we have over 250 citations just in that chapter alone. Not only do we talk about the WHO guidelines and some stats around how common male factor infertility is and how it can contribute to the time it takes to conceive, we also have a significant section with lifestyle, dietary, and supplemental strategies, all evidence-based, showing you what the studies are saying, what the research is saying, because this is an area where there’s a lot of hope.

I will continue to stand on this hill and go on and on about the importance of paying attention to your partner’s sperm analysis and semen analysis and overall results, and even taking it a step further when possible, seeing if your fertility specialist is willing to run a DNA analysis. If you’ve had multiple miscarriages, if the semen analysis looks okay but you’re still having some concerns, it is worthwhile to push for these things and to advocate for yourself. Because if you’re not going to do it, who will?

If you enjoyed today’s episode, if you can think of someone who would benefit from hearing it, then I highly encourage you to share it. If you’re listening on your favorite podcast player, there are always share links in there, and you can always head over to fertilityfriday.com for the link to share this episode.

One thing I haven’t mentioned for a while on the podcast is that literally word of mouth has probably been the most powerful way that my work has been shared around the world. I appreciate those of you who have been sharing the podcast, who’ve been sharing the Vital Sign and Real Food for Fertility, because ultimately it is word of mouth that has brought the vast majority of listeners to me. Thank you all for sharing.

I haven’t mentioned this for a while either, but if you’ve been enjoying the podcast and you’ve never left a review on Apple Podcasts, I would really appreciate that as well. I read every review. It helps listeners know what they are to expect when they hear the podcast. There are so many podcasts out now. When I first started the Fertility Friday Podcast back in 2011, there were zero fertility awareness podcasts and very few fertility podcasts. It’s crazy to think of how much has changed. Now there are definitely hundreds of podcasts in the genre, but back then there were none. Now, when people are looking for information, the reviews are really, really helpful. Anytime I’m shopping for anything, anytime I’m booking a vacation, anything I’m doing, I’m always looking at the reviews to see what people are saying. So if you’ve never left a review before, I would really appreciate it. It really helps to get the word out and helps listeners, or potential listeners, know what they’re getting into when they dive into this podcast.

So with that said, I hope you have a wonderful week, weekend, whenever you’re tuning into the show. And of course, as always, until next time, be well and happy charting.