Sperm DNA Fragmentation Testing: The Latest Tests for Abnormal Sperm with guest Dr Ramy Ghayda
We all know that a healthy pregnancy requires one good egg and one good sperm, and while there are a lot of important things to discuss regarding that “one good egg,” I don’t think we talk nearly enough about the importance of sperm health.
Dr. Ramy Ghayda is returning to the show today to talk about sperm, the importance of sperm DNA fragmentation testing, how sperm abnormalities are diagnosed, how to improve sperm health, and new tests to consider.
Dr. Ghayda is an experienced urologist who has a long history of working in the higher education industry. His specialties include urology, andrology, and male infertility. He is currently an assistant professor at University Hospitals in Cleveland, Ohio and a chief medical officer at Legacy, a company that is literally revolutionizing how men and couples test and freeze sperm from home.
I’m delighted to have him back on the podcast today, and I know you’ll learn so much from this important conversation with Dr. Ghayda.
Dr. Aimee: I don’t feel like we talk about sperm enough. There’s no one better to talk about sperm than a reproductive urologist. Welcome back, Ramy.
Dr. Ramy Ghayda: Thank you. Thank you for having me. We’re 50% of the equation. I think we should be 50% of the discussion. Right? We know that we are responsible for about 50% of infertility cases. It’s always good being here, trying to shift the blame away from the female, and trying to have these discussions and conversations just to educate people and raise awareness about the role of the men and the sperm and the whole journey of fertility.
Dr. Aimee: Ramy, I think that your parents really meant to name you Amy. You should talk to them about it. I feel the same way. Especially as more and more people are freezing their eggs and then they’re going back to thaw their eggs, I’m like you have to do advanced sperm testing. You guys make it easy for them to do. You don’t want to learn the hard way after you “put your eggs all in one basket” and then did an egg thaw, or even did an egg retrieval, to find out that maybe you should have paid more attention to that 50%. So, I couldn’t agree more.
Dr. Ramy Ghayda: I think we live in a very exciting time. We have now more access that is way more affordable than before for reproductive care, for females and for males. It’s very important for people, patients, and society at large to know their options and to be educated about what they can do to improve, to test, and to make sure that the whole journey is the best possible leading to, hopefully, good outcomes.
Dr. Aimee: Let’s get right into that. Let’s talk about the different ways that sperm can be tested. Tell us about them.
Dr. Ramy Ghayda: Sperm is the smallest cell of the human body. The egg is the biggest cell. Let’s start there. You have a clear advantage over men. However, the main function of the sperm is to carry this genetic material that is encapsulated in the head of the sperm called DNA, and then try to go inside of the egg and release the DNA fragmentation for fertilization to happen.
Traditionally, for over 50 years, or 70 years, the main testing for sperm and male factor fertility was relying on the traditional semen parameters, meaning that the people and andrologists were only checking the quality and the quantity of the sperm, and that’s it. With the traditional semen analysis, you have the volume, how much sperm and semen fluid you have, you the concentration, the motility, how fast the sperm can swim, you have the morphology, so you can calculate something called the total motile sperm count, which has been correlated closely with success of fertility, whether natural conception or assisted reproductive techniques.
Nowadays, with all the medical advances and technological advances, we have more ways to test for sperm and male factor infertility, we have more data points. We have something called functional tests for the sperm. We try to assess the function of the sperm, is it able to penetrate the egg, is it able to fertilize it. However, these tests are expensive and they need very highly trained technicians, so they have fallen off in the labs nowadays.
The next new thing that’s on the market now is DNA fragmentation. Basically, DNA fragmentation looks at the integrity of DNA, so how good the DNA is inside of the sperm head. This has been correlated very closely to miscarriages, to very bad IVF outcomes, to very prolonged periods of natural conception. It’s very important to have this additional data point. Alongside the quality and the quantity, we need to know if this sperm is carrying good DNA to be able to fertilize the egg or not. This is one of the indicators.
Dr. Aimee: When do you think it should be checked, and why?
Dr. Ramy Ghayda: This is a very tricky question. Traditionally, in the guidelines, in the ADA guidelines, the ASM guidelines, all the European guidelines, we don’t have a clear timeline on when to check it.
However, it is more accessible and it’s cheaper. Some companies, like Legacy for example, are doing it from at home, it’s mail-in, you don’t have to pay a lot of money, so it’s more available and accessible to people.
Anyway, the rule is if you have recurrent miscarriages, if it’s taking you a lot of time to naturally conceive, or if you have bad outcomes from IVF, IUI, or ICSI, then you need to dig deeper into the DNA fragmentation of the sperm just to know if there is anything out there that you can fix.
Dr. Aimee: I would say, also if you’re trying to figure out what the best treatment type is for you, doing the test is something that I suggest to my patients. It is not mandatory to do, but it is part of my conversation with new patients if they haven’t done this testing before. Even if they’ve never had any of those worst case scenarios that you’ve talked about, I always say the more you know, the better things will go. There’s nothing wrong with having a guy eat healthy, sleep better, drink water, stop smoking, stop using THC. I appreciate you saying all of those things.
We’ll get into more about the Legacy test, too. Tell us more about how you actually do the test. How does the testing actually work?
Dr. Ramy Ghayda: We have different ways of testing DNA fragmentation. It all depends on the technique and the availability of the lab. At Legacy, we use a specific test called the SCD or the Halo test. Basically, we’re just checking how much dematuration there is in the head of the sperm. It’s a very technical term. However, we have so many other ways, a ton of testing, SCD, SCSA. These are all different labs who test the same thing.
The only caveat here is we don’t have one reference range. Because this test is relatively new, we’ve been using it over the last 10 years, we don’t have a cutoff or a reference range. Usually, people and scientists would say anything over 30%, meaning you have 30% of your total DNA that is fragmented, is not good. Anything more than 30% is considered positive for DNA fragmentation and might be correlated with poor outcome.
Dr. Aimee: I know a lot of people are wondering if you have that result, what does it actually mean clinically?
Dr. Ramy Ghayda: That’s a great question. This is a reflection that there’s something not right going on inside of the whole sperm formation. We divide these etiology, or reasons for high DNA fragmentation tests, into extrinsic and intrinsic.
Extrinsic meaning that the patient has the ability to control these symptoms. It’s all lifestyle, as you mentioned, alcohol, high BMI, smoking, exposure to pollution. Everything that is bad for your whole body, for your wellbeing, is bad for sperm. This is the golden rule I tell my patients. If something is good for you, it’s going to be good for sperm production. If you eat healthy, a lot of green stuff, no added sugar, no trans fat, if you sleep around 7 hours per night, if you exercise a couple of times per week, if you’re not super stressed, that is going to be good for sperm and for your overall wellbeing.
Anything that would increase the temperature of your testicle is bad. Naturally, the testicle would sit outside of the body for a specific reason, because they like cooler temperatures compared to the internal body temperature. For a patient to use a jacuzzi, sauna, or very tight underwear, for a patient who puts their laptop on their lap for an extended period of time, this is going to increase the temperature of the scrotum and might lead to increased DNA fragmentation. Finally, smoking and excessive alcohol consumption. Social alcohol is good. Moderate caffeine is good. Any marijuana or recreational drug is bad for sperm DNA fragmentation.
That’s the external factors. The internal factors could be a medical reason that is leading for the increase in DNA fragmentation. For example, varicocele, which is a very common condition in men, is basically the dilation of the veins around the testicle that increase the pressure on the sperm formation, increase the temperature and the blood flow. There are so many other conditions, like some genetic conditions.
This is why it’s very important for anyone with an abnormal semen DNA fragmentation test to go check with a urologist or a reproductive endocrinologist just to make sure that we’re not missing any organic or medical cause that can be corrected. Once we do some testing, like a physical exam, a scrotal ultrasound, some hormone testing, we might be able to figure out what the problem is, we might fix it, and then we expect the DNA fragmentation to go back to normal.
Dr. Aimee: What about low testosterone as a cause?
Dr. Ramy Ghayda: Low testosterone is one of the causes for abnormal sperm production and abnormal DNA fragmentation. This is a very important point, especially for people on testosterone replacement therapy. The most important hormone for sperm production and sperm health and DNA integrity is internal testosterone, it’s the testosterone that is secreted by the testicles themselves.
When people are taking external testosterone, like they’re injecting TRT or using the gel, or any other type of TRT, the body is going to perceive that it has a lot of circulating testosterone and shut down its own production of testosterone. When you shut down the natural production of testosterone, the sperm production is going to take a big hit, so you’re going to have a decrease in the semen parameter, the volume, the quality and the quantity, and the DNA fragmentation might also be affected.
So, it’s a very important topic. Any patient of reproductive age trying to conceive should have a really prolonged discussion with their healthcare provider regarding testosterone replacement therapy.
Dr. Aimee: I agree. I often suggest to patients to ask their reproductive urologist if there is a rule for other drugs, like maybe Clomiphene or Arimidex.
Dr. Ramy Ghayda: Absolutely. We have alternatives to boost the internal production of testosterone other than giving external testosterone, and these are usually safe for fertility. This is a great alternative.
Dr. Aimee: I have been using a sperm chip called the ZyMot Chip. I like to talk about stuff, but just because I talk about it doesn’t mean that your doctor has to use it. There are so many other ways of reducing sperm DNA fragmentation in the lab, for example, if you’re doing ICSI or going through IVF. Let’s talk about a few of those things, TESA, ZyMot, and PICSI. What do you think about a different approach in terms of what you do with the sperm on the day of your egg retrieval?
Dr. Ramy Ghayda: This is part of the exciting journey in andrology. We’re trying our best to find ways to mimic natural selection. We’re trying to optimize for the best sperm. How can we find the best sperm out there?
ZyMot is one of the ways. Just imagine it as a marathon of sperm. You’re putting all of these sperm together and you’re telling them to run, and whoever is faster you’re going to catch at the finish line, isolate it, and use it for ART, like ICSI for example. We’re trying to select the best, fastest sperm because the idea and the hypothesis is that the best sperm has the highest chance of fertilizing the egg. ZyMot is one way of doing it.
PICSI is another way. PICSI is when you put the sperm in hyaluronic acid. We know that sperm trying to fertilize the egg should penetrate the very thick capsule of the egg, and by doing this it should attach to the egg. We’re trying beforehand to preselect the sperm that has been able to do so with the best ability to penetrate this egg. What we do is we put the sperm in hyaluronic acid and we isolate the sperm that is linked together. The hypothesis is also this is the ultimate sperm that is the strongest and is going to be able to fertilize the egg.
TESA is a different story. We have some evidence saying that sperm will increase its DNA fragmentation along the way. When you have the factory itself, which is the testicle, you have the lowest DNA fragmentation index. The closer you are to the factory, the better sperm you’re going to have from a quality and quantity perspective. This is why rather than taking sperm from the ejaculate after they’ve traveled from the testicle to the epididymis, which is the small tube, to the outside, you’re just going directly to the factory itself and aspirating some sperm from there. The idea is you’re going to get the best quality sperm from the factory.
All of these factors are trying to decrease the subjectivity in selecting sperm. The technician out there is looking under the microscope and thinking, “What’s the best outcome I can have by selecting the best, fastest sperm that is able to connect to the egg,” and these are ways that can help. I think this is the beginning of a very exciting era in andrology and IVF. Ten years down the line, I think things will be even way better and more specific, so I’m very excited to be here.
Dr. Aimee: I’m excited to have you here, too, because I think we’re very like-minded. One of the things that I hear from other patients is that they bring these suggestions to their doctor, “I’d like to check my partner’s sperm DNA fragmentation,” and they say, “It doesn’t matter, just do IVF, I don’t believe in it.” You’re shaking your head, too. I’m like of course it matters.
Dr. Ramy Ghayda: This is another data point. The more the merrier. The more information you have, the better outcomes you’re going to get if you know exactly what you’re dealing with.
Sperm DNA fragmentation, semen analysis, everything that has to do with male factor infertility testing is relatively easy, accessible, and affordable, so this should be used in parallel for any testing for the female and should precede any final decision over IVF and ICSI because you don’t want to put the female through the whole IVF cycle if the problem was within the male. If you can fix the male factor infertility with either medication or surgery, what have you, then you can just fix the sperm, improve it, get it back to normal, and then you can attempt natural conception. If this is unsuccessful, then you go to the next level.
I think people are used to being overly aggressive and overly treating women for multicultural and social reasons. I think we need to change that. We need to change this conception around not only patients, but some physicians are very traditional in thinking let’s bypass everything that’s easy. I think these podcasts are very important in trying to change the whole discussion and conversation around male and female infertility.
Dr. Aimee: I agree, because then patients will bring these topics up with their doctors. Now you guys make it really easy to order the test for people. I always tell patients you can do this test yourself, you just go to the Legacy website and you can order a DNA fragmentation test, it’s as simple as that.
I want to talk a little bit about vitamins and supplements. If you were a guy that had an abnormal sperm DNA fragmentation test, what are the best things that you should be taking right now from a supplement standpoint?
Dr. Ramy Ghayda: That’s a loaded question. We don’t know. We have some evidence that using antioxidants is able to counteract the oxidative stress leading to high DNA fragmentation and decline in the quality and quantity of the sperm. We know that if a male patient is taking some antioxidants and vitamins, this might help ultimately improving the quality and the quantity of the sperm and getting the DNA fragmentation index back to normal.
The caveat here, and the problem, is we don’t have big randomized control trials on which is best. We know that multivitamins like Vitamin E, Vitamin C, Vitamin D, L-Carnitine, L-Arginine, and folic acid are all great, but we don’t know the exact dose. Any multivitamin should be good.
I would say one of my favorites is something called Co-Q-10. Co-Q-10 has the highest level of evidence that is showing people who took Co-Q-10 versus people who took a placebo showed an improvement in the semen parameter. I always tell my patients “take any multivitamins you want, just make sure that it includes Co-Q-10, 300 milligrams per day.”
This is the short answer. The long answer is we need a lot more studies to figure out which is the best antioxidant to use.
Dr. Aimee: What you say is exactly what I share as well. I say take something like ConceptionXR and add Co-Q-10. I also say fish oil and Vitamin D. Those are the things that I tell patients to take at their new patient appointment, from the very beginning, to improve things so that people have the best chance of getting pregnant without my help. And if they need a little bit of my help, hopefully they’ll be successful the first time, but I know that doesn’t always work.
Dr. Ramy Ghayda: The sperm cycle is 74 days, so any change that they make in their lifestyle, whether they’re taking a supplement, a vitamin, or doing any surgery, they have to wait a couple of sperm cycles to see any effects.
Let’s say they’re taking Co-Q-10. They should test in probably three to six months just to give time for the sperm cycle to recover, to have new mature sperm, and see if they had any improvement. This process will take so much time, so as you said, it should be one of the first things that people do is change their lifestyle because they have control over this. They can change their lifestyle, they can be more conscious about what they eat, their weight, their lifestyle, and they can start these vitamins while waiting for other more advanced testing.
Dr. Aimee: What I say is your children are not going to have children until you’re 50 years old, so if you take your age now, at 50, you need to live that long to see your grandchildren, so you need to start thinking about those things before you even get pregnant so that you can live as long as possible. We don’t want to leave our children behind. We want to be here to support them as long as we can. Most of my patients are over 40, so I’m like we have to start working on this lifestyle stuff now, it’s very important.
Dr. Ramy Ghayda: I agree. We have a trend of advanced paternal aging. We have people, more and more, wanting babies, natural conception or ART, after their 40s. This is a new trend. Traditionally, we had people in their 30s, the average was 33 or 34. Now the average is around 38. People are wanting more children when they’re a bit older, which is very important, going back to what you said about testing, about changing their lifestyle, and planning the whole journey. This is something that you need to put active energy into or it’s not going to happen. Most people it can happen naturally and very easily, but you need to be conscious about the whole journey.
Dr. Aimee: I don’t know if Legacy knows I sing as well. I will spare you my song, but if you guys want to pay me for the rights to the song, it’s called It’s Always Nice to Have Sperm on Ice, I’ll be happy to license it to you guys and sing it from the top of my lungs. I will be asking my sons to freeze their sperm in their 20s, just so that when they’re ready to have children in their late 30s, they have the opportunity to use younger sperm if they want.
Dr. Ramy Ghayda: I completely agree. The younger you are, the younger your sperm, the healthier, the better. You might not use them, but in case you need them. You don’t know what’s going to happen in your life. If there is going to be an accident, or chemotherapy, some major life event, you have an insurance policy that is affordable that is ready for you, that will give you so many other options. I am in 100% agreement there.
Dr. Aimee: Talk to me a little bit about how Legacy can help people with that, because they can help with sperm freezing as well.
Dr. Ramy Ghayda: Legacy is a digital fertility clinic. At this point, I think we’re testing and freezing more sperm than anyone in the nation. We have probably 25,000 samples so far. It’s an easy, affordable, accessible way of testing, freezing, and improving sperm.
We have multivitamins, we have an STI test, you have access to telehealth consultations where people can help explain the journey, the sperm cycle, any questions around sperm. We can provide that in a very accessible client-friendly way. I’m very excited to be working both in an academic setting, but also at the start of us trying to change the whole field. I think this is a revolution and we’re part of this driver to hopefully better outcomes, better success helping people conceive.
Dr. Aimee: Healthier families is the goal. Just teaching people what they can do from the beginning.
What’s next in the future? I imagine a little robot or some sort of thing that I can tie to a sperm cell and then take a robot, outside the body obviously, take that sperm cell and watch it inside of the fallopian tube, and then put the sperm in an egg.
Dr. Ramy Ghayda: There might be. I think the future is AI, artificial intelligence. At some point, we’re going to have an algorithm that will take all of this data we have, the semen quality, quantity, sperm DNA fragmentation, the PICSI, the ZyMot, all the information we have is going to feed into one algorithm, and hopefully we’re going to be able to select the real best sperm to use for ICSI to try to increase the chances of ART. I think we’re going to be able to be more specific and more accurate in the whole process.
I’m also very excited about all of the genetic testing and genetic therapies that are coming. More and more, I have more faith that we’re going to be able to treat so many people. Like people who don’t have any sperm because of some genetic mutation or a combination. I think the future is bright for these types of patients, because we will hopefully be able to change some genetic coding and get some sperm out of it.
It’s a very exciting time.
Dr. Aimee: Wow. I can just think of the families that would benefit from that technology. I hope you’re right. I really do. Thank you, Ramy, for coming on today.
Dr. Ramy Ghayda: Thank you for having me. It’s always a pleasure.
Dr. Aimee: Is there anything else that you want to add?
Dr. Ramy Ghayda: I’m available 24/7. Any question, any concern, they can reach me through my email, via Legacy. My passion is to raise awareness, educate people, and answer their questions, so I’ll be more than happy to answer anything.
Dr. Aimee: Thank you again. Thank you for doing that. Thank you for sharing your knowledge and wisdom with me today. For all of our listeners, I know they’re going to learn so much. Hopefully, they’ll get over to the Legacy site and see if there is a test or something that they might want to do before they start their journey to parenthood, or even if they’re already in IVF, maybe they’ll benefit from learning more. Thank you again.
Originally published at https://www.draimee.org.
