No Sperm Left Behind: Modern Medicine’s Race to Solve Male Infertility

Under the microscope, the sperm would have looked perfectly normal by any modern standard. They had a nicely shaped head and long tail; they swam normally. And yet, as the Japanese reproductive biologist Masahito Ikawa had discovered at his lab in Osaka in 2003, this particular sperm could not fertilize an egg. It looked healthy. Any fertility clinic would have pronounced it good to go. But this sperm was broken.For Ikawa, this discovery sparked a career-long obsession. Suddenly, he was dreaming of testing every sperm gene imaginable. He saw his research as having the potential to completely recast how sperm is viewed.There is a pervasive idea out there about sperm: That the best of them are fast and powerful, the epitome of masculinity boiled down to a single cell. The strongest swimmer gets the girl. Scientifically speaking, though, that isn’t quite how it works. And this misconception has cost men a basic understanding of their own health. While female fertility has been a subject of intensive research for decades, male fertility is often treated as an afterthought.Consider, for example, that most men seeking fertility treatment are first seen by doctors trained to treat women. There is no US body that routinely collects information about male reproductive health. There are just 406 urologists focused on male infertility in the entire US, according to a recent survey by the American Urological Association. “We don’t think of men as reproductive beings,” says Lisa Campo-Engelstein, the chair of the department of bioethics and health humanities at the University of Texas Medical Branch. “We conflate reproduction with women.”But that misconception is finally starting to change. A worldwide decline in birth rates, reports of falling sperm counts, advances in technology, and a commercial boom in men’s health have all converged to drive a new interest in understanding how sperm actually works. Scientists around the world are now studying in detail everything from how sperm move to how they burn fuel. Some are even trying to grow them from stem cells. The work is urgent: Not only could it help the roughly one in six people worldwide who struggle to conceive, but it could also unlock an overlooked and poorly understood signal for overall men’s health.In an orderly research lab on the lush suburban scientific campus of the University of Osaka, Ikawa has been deciphering the many mysteries of sperm for over 35 years, long before Silicon Valley start-ups were hosting sperm races or Elon Musk was giving away his own spunk in a one-man effort to stop population decline. Ikawa’s approach is simple and systematic: One by one, he is working to create model mice that lack each of the 1,200 or so genes thought to be key for sperm production, and then observing what happens when that gene is deleted. Twenty years ago, for example, he and colleagues discovered the critical role of IZUMO1, a gene that encodes a protein on sperm’s surface that’s essential in order to fuse with an egg. (It’s named for a Japanese shrine dedicated to marriage.) The mice missing this gene had normal-looking and behaving sperm, but were infertile.Ikawa’s mice helped to challenge the basic assumption that a normal-looking sperm is a working one. And that assumption is nearly as old as the discovery of sperm itself. After Antonie van Leeuwenhoek first saw sperm under a microscope in the 1670s, many scientists became convinced each one contained a fully formed miniature human, the female egg merely a vessel. Even after that theory was debunked, for a long time many scientists assumed that sperm work the way we learned in high school sex ed: Legions of sperm race to the finish line, the strongest and fastest winning the prize. By the 1980s, researchers began undermining this idea. Sperm, for example, actually have a relatively modest forward propulsion, and they stick to an egg thanks to the adhesive properties of both sperm and egg. The feminist anthropologist Emily Martin refers to the myth of the virile sperm as a “scientific fairytale,” likening our ideas of sperm and egg to the same sort of gender dynamics you might expect in a classic rom-com.And yet, despite emerging research, the fairytale has largely persisted and, as a result, undercut the urgency for the scientific community to learn more about sperm. Then a new IVF technique called intracytoplasmic sperm injection (ICSI) was introduced in the ’90s. The widely used technique assists with fertilization by injecting a single chosen sperm directly into an egg, allowing clinics to address many sperm issues without actually knowing what’s wrong. There was suddenly even less reason to understand how sperm works. Funding for research into male reproductive health pales even in comparison to female fertility research: One study found that between 2016 and 2019, the National Institutes of Health spent about $59 million on male reproductive research, compared to $83 million for women. That accounted for less than one percent of the budget of the NIH branch responsible for the most reproductive research funding. “One of the more challenging aspects of male infertility and reproductive ill-health broadly is its lack of visibility,” a 2024 paper on the status of male reproductive health concluded. Campo-Engelstein frames the challenge a touch more bluntly: “If a man could have an erection, then therefore he was fertile. We don’t even look beyond that.”For much of his career, Ikawa was fighting against this current. “After the emergence of ICSI, clinicians lost their interest,” he says. Technology also presented a hurdle. That part shifted in 2012, after the gene-editing technology CRISPR was introduced and led to an intense acceleration in his work. His lab has now tested the role of 500 or so genes involved in the function and production of mouse sperm by creating model mice with the gene in question deleted. What’s more—since the goal isn’t just to solve mouse infertility—many of these genes are also relevant to human fertility, with some already shown to cause infertility in humans. IZUMO1 was an early sign of something the field is now finally recognizing: Standard clinical tools are often insufficient to spot misbehaving sperm. Problems with another gene he has studied, PLCζ1, can prevent a sperm from properly activating an egg after it enters, meaning even ICSI may fail to produce an embryo. There are so many basic biology questions about sperm that remain unanswered. “Still, we have no idea how sperm can fuse with egg,” he says. Science had underestimated their complexity.Read MoreYes, Men Are ‘Spermmaxxing’ NowFrom supplements to testicle ice baths, anxieties about infertility are pushing men to great lengths to preserve their sperm. But any of it actually work?Take the idea of the race to the egg. Cameron Schmidt, a reproductive biologist at East Carolina University, has recast it as something more akin to a search party. “Sperm, to me, are basically the dumbest tissues,” says Schmidt.His work demonstrates how millions of sperm move through the female reproductive tract with different strategies. Some might follow a straight path, while others zigzag. He describes it as similar to how Roombas are optimized for efficient cleaning. Sperm can survive for up to five days in the female reproductive tract, while an egg is only fertilizable for about a day. A diverse population of sperm may increase the odds that at least one is in the right place at the right time. This “dumb” sperm strategy, as Schmidt puts it, may actually be advantageous—casting a wide net instead of relying on luck. “It’s almost more like a CrossFit competition than a race,” says Christopher Geyer, who also studies sperm at East Carolina University. Sperm may even coordinate to work in teams, further complicating the notion of sperm as lone competitors, according to new research on the group of animals that includes insects, spiders, and crabs by evolutionary biologists at Syracuse University.Recent research has also shown that sperm are not simply delivering a packet of information with Dad’s DNA but also influencing the early stages of an embryo’s development; sperm, for example, have been linked to recurrent miscarriages. And we now understand that sperm metabolism shapes not only whether sperm have the fuel necessary to make it to an egg, but how they behave. In animal laboratory studies, scientists briefly starved sperm of the energy sources they rely on, then added them back, improving fertilization rates—like intermittent fasting for gametes. Something similar may happen in the female reproductive tract and replicating it could improve IVF fertilization, according to Maria Gracia Gervasi, a reproductive biologist at the University of Connecticut. Slowly, research is dismantling the idea of sperm as fast swimmers that head the same direction in a pack, and instead affirming they’re complex cells with intricate chemistry and genetics that have the power to shape the earliest stages of life.The conventional methods by which we judge sperm only capture a small slice of all this. Most fertility testing simply looks at how plentiful sperm are, whether they have a normally shaped head and tail, and how they swim. Such tests are “not that much better than a flip of a coin,” says Bobby Najari, director of male infertility at New York University Grossman School of Medicine. In other words, a lot of issues are still falling through the cracks. (And that’s if men’s sperm are even evaluated, which studies show they often aren’t.)Newer evidence also suggests that semen quality isn’t just linked to fertility, but can be a bellwether for a man’s overall health. One 2018 Danish study found that men with lower sperm counts were hospitalized at higher rates, even when accounting for factors like smoking, weight, and socioeconomic status. Another, from 2025, looked at semen quality and lifespan and found that men with more healthy moving sperm lived 2.7 years longer than men with lower counts. The American Urological Association counsels that male infertility patients are also at risk of developing other health issues, such as cancer. The connection goes both ways: Healthy lifestyle changes can also have a positive impact on quality. “It’s a measure of current health, but it kind of portends the future too,” says Michael Eisenberg, a professor of urology at Stanford University School of Medicine.Read MoreMy IVF YearsMy son and I were calling to each other across a great distance, a distance that I was aware might never close.If standard semen analysis is barely better than a coin flip, the question then becomes what should replace it. A handful of new companies think they have answers. Path Fertility, for example, offers a test that screens semen for abnormal patterns in the epigenome—chemical markers that help turn genes on and off. Another company, Paterna, is working on a method to mature sperm-producing stem cells in the lab, which they hope can help overcome infertility cases in which sperm fail to develop properly. Still further afield, researchers are also working on a technique called in vitro gametogenesis, which could one day allow sperm to be made from skin cells. (So far, it’s been done in mice.) Ikawa’s work in mice has also shown potential for future therapies; in one experiment, Ikawa and his team delivered an mRNA treatment into the testes of mice missing a gene that helps sperm fully mature and were able to temporarily restart the process of spermatogenesis.Translating this new understanding of sperm could have a real impact on men and women. Justin and Olivia, a couple that shared their story with me, had tried for over a year to conceive with no luck, first the old-fashioned way and then using artificial insemination. Extensive testing had revealed no problems for the two 32-year-olds from Kansas, so eventually Olivia’s doctor recommended they do a deeper dive on Justin’s sperm using Path’s test. It revealed his sperm suffered from genetic dysregulation, giving the couple a slim chance of conceiving naturally. Just like the sperm of Ikawa’s mice, Justin’s semen had looked fine by conventional measures. Only this time, there was a test that could see the truth. With the results in hand, they decided to pivot to IVF. Not long after, their son was born.