Inside the ZyMōt Chip: How Microfluidics Picks Better Sperm

In this episode of Taco Bout Fertility Tuesday, Dr. Mark Amols takes a deep dive into the ZyMōt microfluidic sperm chip — a device designed to mimic nature’s way of selecting the healthiest sperm.

We explore:

• Why sperm DNA fragmentation matters for fertilization, embryo quality, and miscarriage risk.
• How the ZyMōt chip works compared to traditional methods like swim-up and density gradient centrifugation.
• What the science really shows — from lab data to clinical trials — including studies where the chip nearly doubled live birth rates in male-factor infertility, and others where it made little difference in unselected IVF populations.
• Which patients benefit the most: men with high DNA fragmentation, couples with male-factor infertility, and those with failed fertilization or poor embryos in past cycles.
• Practical considerations — cost, limitations, and why some clinics use it for everyone while others use it selectively.

Is it a true game changer, or just another lab gadget? Tune in to find out.

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Transcript

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Today we talk about the Zymot chip. Is it a game changer for sperm selection in IVF or ici? Or is it just hype? Does the science actually back it up? Well, lets talk about it. Im Dr. Mark Amols and this is Taco about Fertility Tuesday. So why does sperm selection matter? Well it has to come down to sperm DNA integrity because it influences things like fertilization, embryo development and miscarriage risk. We all know sperm is not created equal. Clearly I dont have as good a sperm as Brad Pitt. Some sperm may swim really good, but they carry damaged DNA. Others look great, like maybe from Brad Pitt, but they cant fertilize an egg. And heres the kicker. Sperm with DNA fragmentation are linked to lower fertilization, poore embryo development and even miscarriages. Now its important to understand. Traditionally the way we separate the sperm is through a process called a swim up. The other method is through density gradient centrifugusion and this is the way its'been done for decades. But they involve spinning sperm at high speeds. And the problem with this is it can create oxidativeative stress and it doesn't always filter out. The sperm with the DNA breaks and this is where the Zymot chip comes in. Now before we can go in depth into what the Zymod chip does, you need to understand what does it mean by sperm DNA fragmentation? Does that mean DNA is missing? No, it means there's actually breaks in the DNA itself. If you remember, DNA is a double helix. If a piece of DNA was missing that would cause a problem. But when it's broken, it can actually stop the transcription completely of the DNA. Imagine missing DNA would be like having a book and pages being removed. But when it's fragmented, it's more like the pages are torn or crumbled in such a way that's not readable anymore. Now when these bricks are in the exon regions of the DNA, that is the portion, that is the codating that tells it what to do. If it's in the intron area of the DNA, that doesn't code for anything or empty areas and so it wouldn't affect the sperm. Now at the heart of the problem is all sperm may have some DNA fragmentation. Its because things arent perfect. But at some point when that sperm enters the egg, it has to undergo things like DNA polymerase or ribosomes to create proteins or to replicate the DNA. Now like usual, women have to do everything. And in the eggs the same thing happens. The egg is the natural repair mechanism for the Sperm. And the thing is, if there is mild DNA fragmentation, it can repair it. But if it is significant, the egg does not have enough ability to repair all the problems. And if the damage cannot be fully repaired, it can lead to things like developmental problems in the embryo and can also trigger the embryo to stop developing altogether, leading to a miscarriage. So prior to the Zymod chip and other microfluidic devices, the only thing you could do were the swim up or the centrifuge method. But this would still create oxidative stress. But the microfluid M device called Zymot, this did something a little bit different. This mimicked the natural tubes of the flopian tubes. So when sperm is deposited vaginally, of that sperm, only maybe 100,000 sperm get in the uterus. And from there, only about 50 sperm ever get to the egg. So essentially, the chip becomes like a mini obstacle course. And whats s important about this is that when you put the sperm on one end and you have it swim through a series of tiny microchannels, then only the most healthiest sperm will make it to the other side. And because theres no harsh spinning like a centrifuge, the sperm comes out on the other side tend to have better motility, intact DNA and less oxidative damage. As you can see, this was a game changer. Prior to this, if you had severe DNA fragmentation, other than going and doing a testsse, there wasnt many ways to get sperm not fragmented. Now, if you asked me how it works, clearly its magic. But the way it actually works, as I mentioned, is you put the sperm in an inlet chamber, then the sperm will swim through the micro channels on under laminar flow, thats smooth and gentle flow with very little turbulence. And then along the way, the sperm will essentially get weeded out. So only the best of the best sperm and the strongest sperm will make it to the collection chamber. Think of it as the survival of the fittest. And because the sperm are actively swimming, not being forced by a centrifuge, the ones that make it through are more likely to have good DNA integrity. So its settled. The Zymod chip is great and everyone should use it. Well, not so fast. Lets look at the science. Well, inside the lab, what we see with the Zymod chip is that the sperm consistently shows lower DNA fragmentation compared to both raw samples and standard preps. In fact, in, one blind study, DNA fragmentation dropped to almost zero percent in most samples after the microfluidic sorting. And thats quite impressive. They also showed Better motility, higher vitality and even more normal morphologic appearance compared to the centrifuge sperm. Basically, the chip seems to select the sperm that are both healthier and genetically cleaner. And this is rather fascinating because when you think about it, sperm usually just brings the DNA to the egg. So you would think that it wouldnt matter what the DNA is like, it should be able to swim there, because how it runs shouldn't matter what the DNA is inside it, because that DNA isn't the DNA that made the motility. But what this told us was something different. It said no, that DNA inside of the head may be still being used in small portions to run things. And the ones that have more DNA fragmentation wont do as well as the ones that have less. This basically goes against all prior thinking when it came to sperm. So again, clearly everyone should do the Zymod chip, right? Well, again, not so fast. Heres where it gets a little interesting because patients always want to know, does this actually help me get pregnant? So lets start first with unexplained infertility. Well, if you look at unexplained infertility, what the randomized control childial showed was more top quality embryos were obtained when using Zymon, but the pregnancy rates were about the same. So better embryos but not a guaranteed higher chance that the cycle is going to work. Now, what about millt factor infertile couples? Well, in a randomized control trial, they found that when using the microfluidic sperm sorting device, it nearly doubled the live birth rate, about 47% with the chip versus 25% with conventional prep. And thats a pretty big difference matter. In fact, when they looked at patients with high sperm DNA fragmentation, a large cohort study showed that Zymot dropped fragmentation by almost half. And these couples went on to have respectable live birth rates. Around 29% for the first transfer and over 40% cumulative across a few transfers. And thats fairly remarkable for a very tough group. But on the flip side, some large randomized control trials and unselected IVF groups being not selecting out maleactor or some specific part, found that Zaymont didnt really become superior and it really didnt improve embryo quality. It didnt improve implantation or pregnancy rates compared to the standard prep. So whats the takeaway? Well, the takeaway is kind of like the era. Youll hear people all the time say, well, the ERA shouldnt be used for everyone and it doesnt work. Not true at all. It just means it shouldn't be used for everyone. Because when you use it for everyone, you really don't see a benefit. And that's kind of the point with the Zymon chip right now. If you unselectively give it to everyone, you probably aren't going to help everyone. Now, you will help some people, but the people that appear to be helped the most are going to be the ones with mal factor infertility and people with high DNA fragmentation. And the patients that dont have that, they may have better embryos, but it doesn't mean they'going to have higher pregnancy rates. Now, you can look at this in two ways. You can say, well should and I then test everyone for sperm DNA fragmentation. So I know which ones to use the Zimot chip for. The answer is, yeah, that's pretty reasonable. But it can also be expensive. If it costs $500 to do a DNA sperm fragmentation test. With only $1 one to do the Zymot chip, it might make more sense just to preemptively give the Zymont chip. And thats actually what we do at our clinic. Everyone gets a Zymod chip that can technically use it. Now, there is a point. Not everyone can use the Zymot chip. If your sperm count is significantly low, you cannot use a Zimot chip. You need a certain amount of sperm to make it work. So people with very severe counts in their sperm will not be able to use the chip. Other groups that may benefit are going to be patients who have had failed fertilization or maybe poor embryo development in past cycles. And although not our research, anecdotally, I've noticed that when patients have struggled in other cycles and we change it, they tend to do better. And again, the other two groups that are always going to do beneficial are going to be men with high DNA fragmentation and couples with mal factor infertility. Now, just like the era, it never hurts to do it. Its safe. It wont hurt your chances. It may even give you a few good embryos. But in the end, it doesnt statistically give you a higher chance of a live birth, at least in an unselected group. But in a selected group, it absolutely can benefit you. So the bottom line, the Zymod chip is a clever way of letting sperm prove themselves just like they would in nature. The science shows us that sperm with less DNA fragmentation and better motility do better. And for certain couples, especially those with sperm quality issues, it might make a difference between the failed cycle and the healthy pregnancy. By using these microfluidic devices. Now, it'important to know there are now other devices. CYOT was one of the first, but there are others. And if youre going through fertility treatment, ask your clinic whether they offer Zmon and if it might be the right situation for you. Because when youre trying to make a baby, every detail counts. So in the end, do microfluidic devices help? The answer is yes. But in targeted groups in a general population, you might get better embryos, but youre not going to get consistent jump in euloid status or live birth rates. Now, like everything in medicine and science, this is just the first chapter in this story. Over time, these may get better and we may learn which patients are the best to use microfluidic devices for. Maybe in the future we might be able to use these to channel sperm so we can then do gender selection. The point is, this is an exciting time in science when it comes to fertility, and this device gives us another tool to help those who need the help most. If you're like me and not Brad Pitt and needed help with your sperm, maybe the Zimmod chip may help you. And maybe this podcast helped you understand that there are some other tools out there to help you if you haven't had success. If you know someone who'maybe going through this, let them know about this podcast. They may not be aware of this chip. As always, I greatly appreciate everyone who listens to this podcast. If you like us and you want to support us, give us a five star review on your favorite medium. Tell your friends and family about, us, but most of all, keep coming back. I look forward to talking to you again next week on Taco Belt Fertility Tuesday.