Is Sperm DNA Damage the Missing Piece in Early Pregnancy Loss? (Episode 618)

Full Transcript: Episode 618

Lisa Hendrickson-Jack:

Miscarriage is a really difficult topic. It’s incredibly complex, and it’s so, so, so common. For those of you who have been listening to the podcast for some time, you may remember some of our previous episodes, which we’ve delved into miscarriage. We’ll link some of those to the show notes page. It is a really big topic. And as someone who has experienced an early miscarriage, one of the things that I often share is that until I had a miscarriage myself and shared about it, I didn’t even have any idea how many of my friends and other acquaintances had had a miscarriage as well.

It’s so, so, so common, but we don’t always open up about it and we don’t always share about it. We don’t always know if even one of our good friends or acquaintances have experienced a miscarriage. In my case, and I’ve spoken to many women who found something similar, it was only when they opened up about it that they really realized how common it was.

To put it into perspective and to share some stats, somewhere between 10 to 15 out of every 100 pregnancies ends in loss. And for many couples, it happens more than once. Certainly recurrent miscarriage is a lot more common than we would like it to be. And when miscarriage happens, we typically assume that it is the woman. As a woman, we’re the ones who carry the babies to term. We kind of assume if we’re miscarrying, there must be something wrong with our body. There must be something that we would have done. It must be related to egg quality. All those things theoretically could be true. But then the question is, could this also be related to the quality of his sperm? That’s what we’re going to be getting into today.

The paper that we’re delving into today — I always say the titles leave something to be desired — is called Sperm DNA Fragmentation is a Novel Biomarker for Early Pregnancy Loss. This is a fairly new paper, came out in 2021, and it really did have some interesting findings. Essentially what they did in this study is they looked at two different groups of men. They looked at 76 men who had recently, as they termed it, recently proven that they could father a child. Basically you have a group of men whose partners conceived within 12 months of trying and who also had a healthy birth. And they compared that to 217 men whose partner had just experienced a miscarriage within the past three months.

When we’re talking about testing, one of the very first steps that a couple should be looking into if they are trying to conceive, if they have some concerns, or if they’ve been trying for some time, is to do a sperm analysis. When they do the sperm analysis, they would be looking at the overall count and concentration. They look at the motility — if the sperm are moving, progressive motility, if they’re swimming forward — morphology, the actual shape of the sperm. And there are various other markers that they look at as well.

In this study, they went beyond that. They didn’t just look at the standard sperm analysis. They specifically examined the level of sperm DNA damage in these two groups. This type of testing is not necessarily as common, may not be as readily available, but it is something that you could talk to your fertility specialist about. And it is something that may be done more frequently in assisted reproductive technology situations.

What they did specifically is they tested for the level of sperm DNA damage. In order for a pregnancy to happen normally, the DNA does have to be intact. Chromosomal abnormalities increase the risk of a variety of different issues. One thing that you should know about sperm DNA damage, if you don’t know this already, is that a man can actually have a pretty normal semen analysis and still have a high level of sperm DNA damage. While the sperm analysis is important, and certainly it’s an important screening tool, it shouldn’t be overlooked — but it’s not the whole story.

Going back to these two groups, the average rate of sperm DNA damage in the fertile group of 76 men was 15%. However, in the miscarriage group, the average rate of sperm DNA damage was about 33%. Overall, the group of men whose partners had miscarried within the last three months had twice on average as much sperm DNA damage.

To put it another way, in fertile men, 9 out of 10 sperm, approximately, had good quality DNA. Out of every 10 sperm, 9 of them were pretty good to go. But in the miscarriage group, fewer than 5 out of 10 sperm had good quality DNA. The other half had medium to high levels of damage.

That’s certainly something to think about. When you think about fertility awareness at its most basic level, we are understanding a woman’s fertility to a deeper degree. A couple’s combined fertility basically would be her days of cervical fluid leading up to ovulation. If we look at the whole menstrual cycle, the fertile window from a scientific standpoint is typically the five days leading up to ovulation plus ovulation day. That is typically corresponding to her days of cervical fluid.

When you have a couple who is timing sex correctly, it means that they are having sex in the window. When we learn about cervical mucus, we learn that it screens out sperm of poor motility and morphology. It draws sperm into the cervical crypts rapidly, transporting them into the women’s reproductive tract. There’s all of these factors happening if sex is being timed correctly and it’s happening during that window that would really foster conception.

When I’m working with clients who are trying to avoid pregnancy, we are doing everything possible to identify that window and put some very specific evidence-based guideposts around her fertile window to prevent an unplanned pregnancy. If you have a couple who’s trying to conceive, they’re timing their fertile window correctly, they’re having sex in the window when she has her cervical mucus, and it’s not happening time after time after time — or it is happening, but she’s miscarrying and having early pregnancy loss — it does make logical sense to start to think, we should be looking at both parties here.

When the researchers looked at this information and discovered that the men whose partners had miscarried within the last three months had a significantly higher degree of sperm DNA damage, one of their conclusions is that instead of simply testing the sperm analysis and doing the kind of classical sperm testing, maybe we should be more specifically measuring the level of sperm DNA damage and using that as an even more sensitive marker of a man’s fertility.

The researchers did stress this point: they talked about how a man can have completely normal standard sperm tests and still have high levels of DNA damage. When a man has a semen analysis, if we analyze how they defined what a normal sperm test really looks like, we already know that just because his test falls into what they’ve defined as a normal range doesn’t mean his sperm is optimal for conception. There’s a big difference between normal and optimal.

If you’re listening to this and you found this specifically because you have experienced a miscarriage, or because you’ve been trying to conceive and it hasn’t been happening and you’ve been told that your partner’s sperm tests are totally normal — or you work in the field of women’s health and you work with clients who are trying to conceive — when you’re told that your partner’s sperm analysis is normal, that doesn’t tell us anything about the quality of the sperm DNA. That was something that the researchers wanted to stress.

When they’re looking at sperm count, motility, and morphology, it is telling us about how the sperm is moving, and it is telling us about what it looks like. In the research, total motile sperm count is the factor that is typically most highly related to the chances of having a successful pregnancy. We don’t want to throw out the baby with the bathwater. We don’t want to pretend like the semen analysis results don’t matter because they definitely do. But at the same time, even if the count, motility, and morphology look pretty good, it doesn’t actually tell us about whether or not the sperm DNA is intact and if it’s optimal.

Another troubling piece of information that the researchers shared is that even if a sperm has some level of DNA damage, it can still fertilize an egg. I had mentioned the cervical fluid and how it has the ability to screen out sperm of poor morphology and poor motility, but that doesn’t necessarily mean that it’s filtering out sperm with poor DNA, especially given what we saw in this study. They looked at over 200 men whose partners had conceived and miscarried within three months. That does mean that even when there’s sperm DNA damage present, that doesn’t prevent the sperm from being able to fertilize the egg. However, it can clearly prevent the baby from progressing to term.

This is important information. When we’re looking at fertility, it’s often thought of as just a woman’s issue — there’s just something wrong with her — when there’s certainly more to the story. This is not about blame. This is not about pointing a finger. Obviously, that’s not what we’re talking about. But we know that thorough screening is typically done for the woman’s side. Whether you’re looking at only conventional options or whether you’re looking at more functional options, we’re still typically heavily investigating the woman and kind of looking at her as the primary contributing factor.

When we just take a look at the stats, up to 30% of the time, male factor is solely responsible for infertility cases. And 50% of the time, it is a combination of both. Male factor is a contributing factor to infertility cases 50% of the time. It is high time that we are really looking at the male contribution and really taking seriously what it means, not just assuming that it’s only one-sided.

The egg actually has the capacity to repair a certain amount of sperm DNA damage. When you look into the research about the human egg cell, it really is fascinating. Our eggs do have the capacity to repair some degree of sperm DNA damage. However, the age of the egg is highly correlated to how much of an ability it has to repair. If you have a 25-year-old woman, her eggs would theoretically have higher capacity to repair some degree of sperm DNA damage. Whereas at 43, eggs may have less of that capacity. All this means, though, is that sperm DNA damage is a factor.

Potentially when we’re younger, or when we are really focused on supporting egg quality — and it’s not only about age — that may increase the egg’s ability to overcome some of these issues. But it would make a lot of sense, if we’re trying to increase overall fertility and improve a couple’s chance of conceiving, to look at his contribution and find out what we can do to improve the quality of his sperm and potentially reduce the level of sperm DNA damage.

The researchers outline some specific and practical things that men can do to reduce that DNA damage and improve the overall quality of the sperm. Interestingly, these things are not only going to improve the DNA damage — they will likely improve the other factors as well. When we look at the research on the typical sperm parameters that are tested, they also would improve when you do these things.

A few of the things that the researchers suggested: reducing or stopping alcohol, as alcohol is directly linked to higher oxidative stress in sperm, which is a contributing factor to sperm DNA damage. Quitting or reducing smoking — cigarettes or marijuana — as there’s a lot of research that shows that smoking significantly increases oxidative stress. Oxidative stress is a fancy way of saying damage due to oxygen. The easiest way to explain it: think of what happens if you cut open a banana and leave it sitting out — it turns brown. But if you dipped it in lemon juice, it wouldn’t turn brown for a while. Reducing oxidative stress is certainly a factor in reducing the level of sperm DNA damage.

A few other things that the researchers mentioned: avoiding protein supplements that contain anabolic steroids, as they identified that as a specific contributing factor. Losing excess weight, as obesity is independently associated with higher sperm DNA damage. And eating a diet high in antioxidants and whole unprocessed foods.

When researching for the sperm chapter in Real Food for Fertility, there are quite a few studies that talk specifically about high antioxidant foods. They talk about citrus fruits, green leafy vegetables. There were studies comparing organic green leafy vegetable consumption to non-organic, and of course the organic had better outcomes because of the reduced exposure to toxicity. In Real Food for Fertility, we talk about other nutrients that support sperm quality, other antioxidants — vitamin C, N-acetylcysteine, L-carnitine, supplements to support mitochondria, coenzyme Q10. There’s a lot of things that men can do to improve their sperm quality.

While at first it can sound very daunting to think, how could I possibly improve the quality of my partner’s sperm DNA, there are actually a lot of things that can be done. It takes a little bit of time. With sperm quality, it’s one of those factors when it comes to fertility that we can actually see. Men can actually give a sample and we can actually see numbers. If you make changes over time, you can actually see those improvements. And that can be very encouraging at a time when fertility challenges can just seem very hopeless because you’re not always seeing the fruits of your labor.

One other point that the researchers made that is worth mentioning is that up to 48% of men with fertility challenges have a condition called varicocele. That is related to enlarged veins in the scrotum that raise the temperature around the testes and damage sperm DNA. When we look at the research, there’s a reason that the testicles hang outside of the body — they’re supposed to be at least two degrees colder than the rest of the body. Research does show us that when the sperm is continually heated and not at that ideal temperature, it does reduce sperm parameters and increase sperm DNA damage.

This also indicates that instead of always looking at the woman as the only patient when it comes to infertility, or instead of just accepting a normal semen analysis result at face value, what the researchers suggest is that this makes a strong case for a referral to a urologist — a doctor who specializes in male reproductive health — when you suspect or are experiencing fertility challenges.

There’s certainly a lot to take away here. Let me summarize what we’ve talked about today. In this study, what the researchers found was that men whose partners miscarried had more than double the sperm DNA damage of fertile men. That is a huge takeaway.

The second takeaway: a standard semen analysis will not catch DNA damage. Having an analysis that falls into what your fertility specialist or doctor says is normal does not mean that the DNA is okay.

A third takeaway: the researchers showed that sperm DNA fragmentation testing did predict miscarriage with a high degree of diagnostic accuracy. There was a high correlation between sperm DNA fragmentation and an increased risk of miscarriage.

I always find the topic of miscarriage to be challenging because it is so common. Somewhere between one in five pregnancies ends in miscarriage. Sometimes it’s not uncommon for a woman to have a miscarriage and then go on to conceive and carry naturally. It doesn’t mean that we need to be alarmed beyond what makes sense. But for any couple who has experienced miscarriage, or who has experienced more than one miscarriage, and whose partner has not been tested or gone through sperm DNA fragmentation testing, it does add something that we could be looking at.

One of the most unfortunate aspects of the miscarriage conversation is that many women are not offered more of a workup to find out what’s going on until they’ve had three or more miscarriages. The doctors aren’t even really willing to look at it. This research would indicate that it does make sense to potentially screen for sperm DNA fragmentation, especially in couples who’ve experienced miscarriage, because it very well could be a contributing factor.

The fourth takeaway: the male contribution to the miscarriage conversation has been overlooked for way too long. That needs to change.

And finally, the hope in this conversation is that sperm DNA damage is something that can change. It’s not something that is a character trait. If you discover that your partner has a poor semen analysis or higher levels of sperm DNA damage, this is something that is typically fixable — whether through diet and lifestyle factors, which sperm is often very receptive to, or whether it prompts further investigation with a more specialized doctor to find if there is actually a physical issue like varicocele or a variety of other issues that may be contributing.