Sperm Und Drang
The sudden rise in male infertility is a scary national crisis, and we can’t blame it on Trump—or can we?
HAGAI LEVINE DOESN’T SCARE EASILY. THE HEBREW UNIVERSITY PUBLIC HEALTH
researcher is the former chief epidemiologist for the Israel Defense Forces, which means he’s acquainted with danger and risk in a way most of his academic counterparts aren’t. So when he raises doubts about the future of the human race, it’s worth listening. Together with Shanna Swan, a professor of environmental medicine and public health at the Icahn School of Medicine at Mount Sinai, Levine authored a major new analysis that tracked male sperm levels over the past few decades, and what he found frightened him. “Reproduction may be the most important function of any species,” says Levine. “Something is very wrong with men.”
That's something you may not be used to hearing. It takes a man and a woman—or at least a sperm and an egg—to create life, but women bear the medical and psychological burden of trying to get—and stay—pregnant. It is women whose lifestyle choices are endlessly dissected for their supposed impact on fertility, and women who hear the ominous tick of the biological clock. Women are bombarded with fertility diets, special fertility-boosting yoga practices and all the fertility apps they can fit on their phone. They are the targets of a fertility industry expected to be valued at more than $21 billion globally by 2020. Even the Centers for Disease Control and Prevention fixates on women, tracking infertility in the U.S. by tallying the number of supposedly infertile women. “It is as if the entire medical realm is shaped to cater to women’s infertility and women’s bodies,” says Liberty Barnes, a sociologist and the author of Conceiving Masculinity: Male Infertility, Medicine, and Identity. “For men, there’s just nothing there.”
That absence might be understandable if women were solely responsible for the success of a pregnancy. But they’re not. According to the American Society for Reproductive Medicine, the male partner is either the sole or contributing cause in about 40 percent of infertility cases. Past infections, medical conditions, hormonal imbalances and more can cause what is known as male factor infertility. Men even have their version of a biological clock. Beginning around the mid-30s, fertility gradually degrades, and while most men produce sperm to their dying day, those past 40 who help conceive have a greater risk of passing on genetic abnormalities to their children, including autism. “Men are a huge part of this problem,” says Barbara Collura, the president and CEO of Resolve: the National Infertility Association.
Startling new evidence suggests male infertility may be much worse than it appears. According to Levine and Swan’s work, sperm levels—the most important measurement of male fertility— are declining throughout much of the world, including the U.S. The report, published in July, reviewed thousands of studies and concluded that sperm concentration fell 59.3 percent in Western countries between 1973 and 2011. Four decades ago, the average Western man had a sperm concentration of 99 million per milliliter. By 2011, that had fallen to 47.1 million. The plummet is alarming because sperm concentrations below 40 million per milliliter are considered below normal and can impair fertility. (The researchers found no significant declines for non-western men, in part because of a lack of quality data, though other studies have found major drops in countries like China and Japan.) And the decline has grown steeper in recent years, which means that the crisis is deepening. “This is pretty scary,” says Swan, who has long studied reproductive health. “I think we should be very concerned about this trend.”
There have reports of declining sperm counts before, but they were easy to ignore. Research has been spotty, using different methodologies and drawing from varying groups, making it difficult to know if declines some scientists observed were real, and not a function of miscounting. Skeptics of the latest conclusions countered that the new report was a study of many studies—it could only be as good as the work from which it drew. And even if the conclusions of the meta-analysis are accurate, the average sperm count still leaves most men on the normal side of fertile. Just barely.
Yet fertility rates—live births per woman— have drastically declined in the same countries with falling sperm counts. That includes the U.S., where fertility rates hit a record low this year, and where women are no longer bearing enough children to replace the existing population. Women need to average roughly 2.1 children—enough to replace themselves and their partner, with a spare bit to offset kids who don’t survive to reproductive age—to keep a country’s population stable through birth alone. The U.S. is at 1.8 and dependent on immigration to keep the population growing. Sociological and economic factors play a role in the changing size of the American family. Fertility rates were above the replacement level until the 2007 recession, then plunged. And despite a years-long economic recovery, they’re still falling. Pair that with studies showing that nearly one in six couples in the U.S. trying to get pregnant can’t do so over the course of a year of unprotected sex—the medical definition of infertility—and it’s clear that something beyond economic insecurity is preventing Americans from having as many babies as they want. “When I see birth rates going down, I worry as a fertility doctor that men’s sperm counts are declining,” says Harry Fisch, a urologist at Weill Cornell Medicine in New York.
THE MALE PARTNER IS EITHER THE SOLE OR CONTRIBUTING CAUSE IN ABOUT 40% OF CASE OF INFERTILITY
This would seem to be the moment for the medical world to throw everything at understanding what is happening, yet researchers are forced to rely on less-than-perfect data because comprehensive, longitudinal studies have never been done. The irony is that the medical establishment has been accused—with reason—of ignoring the needs of women over the years, yet in reproduction it is men whose problems are poorly studied and often misunderstood. Some experts even wonder whether an unconscious desire to ignore threats to male fertility may be tied up in fears over the future of masculinity. “Here is direct evidence that that function of reproduction is failing,” says Michael Eisenberg, a urologist and an associate professor at Stanford University, referring to the latest sperm-level research. “We should try to figure out why that is.”
What we do know tells us a great deal about not only reproduction but also the health of men. Young men may think they're invincible, but the male reproductive system is a temperamental machine. Obesity, inactivity, smoking—your basic poor modern lifestyle—can dramatically reduce sperm counts, as can exposure to some environmental toxins. Low sperm counts may presage a premature death, even among men in their prime who might seem otherwise healthy. “Sperm count decline is the canary in the coal mine,” says Levine. “There is something very wrong in the environment.” Which means there may be something very wrong with men.
Why Johnny Can’t Breed
IN 167 7, THE DUTCH DRAPER AND AMATEUR scientist Antony van Leeuwenhoek collected his semen immediately after having sex with his wife, examined it under a microscope of his own creation and saw millions of wriggling, tiny “animalcules” swimming in the seminal fluid. The Dutchman was the first person to observe human sperm cells, though he insisted that the sperm alone made an embryo that was merely nourished by the female egg and ovaries. Van Leeuwenhoek was simply following the example of classical thinkers like Aristotle, who believed female partners at most provided a fertile bed of soil in which the seed provided by a man could germinate and flower into a child. It wouldn’t be until the 19th century that the true roles of
“SPERM COUNT DECLINE IS THE CANARY IN THE COAL MINE. THERE IS SOMETHING VERY WRONG IN THE ENVIRONMENT."
the sperm and the egg were finally sorted out.
All those wriggling “swimmers” van Leeuwenhoek saw are what you would see if you magnified the sample of a healthy fertile man. A sperm cell is built for one thing: motion. Its torpedo-like head is a DNA nugget containing the 23 chromosomes the male partner contributes to his future child, connected to a long tail that propels the sperm to the egg, running on the cellular rocket fuel of the fructose in the semen. Most sperm will never come close to an egg—while a fertile man ejaculates 20 million to 300 million sperm per milliliter of semen, only a few dozen might reach their destination, and only one can drill through the egg’s membrane and achieve conception. The chemical makeup of the vagina is actively hostile to sperm, which can only survive because semen contains alkaline substances that offset the acidic environment. That’s the paradox of sperm counts— although one healthy sperm is enough to make a baby, it takes tens of millions of sperm to beat the odds, which means that significant declines in sperm counts will eventually degrade overall male fertility. Notes Swan: “Even a relatively small change in the mean sperm count has a big impact on the percentage of men who will be classified as infertile or subfertile”—meaning a reduced level of fertility that makes it harder to conceive.
The fears about male infertility go beyond the stuff of dry science. “It’s the virility and fertility dilemma,” says Sharon Covington, an infertility therapist in Maryland. “How a man sees himself, and how the world sees him as a man, is often tied to his ability to impregnate a woman.” So perhaps it’s not surprising that the argument over how much sperm counts are declining—if they are declining—has been less a courteous scientific debate than a ferocious battle that has gone on for more than two decades.
This war began in Denmark, in 1990, with Danish pediatric endocrinologist Niels Skakkebaek. For years, he had been troubled by the rise in testicular cancer, as well as an increase in the number of boys with malformed testes. He thought assessing sperm quality and quantity might give him a clue to what was happening to his patients.
In 1992, Skakkebaek and colleagues reviewed all the published studies of sperm counts from around the world. (Sperm counts are done by tallying the number of sperm cells in one microliter of semen and then multiplying by 10,000 to estimate the total sperm in a milliliter—not dissimilar from the way police try to estimate the size of a large crowd from a geographic sample.) They calculated that the average sperm count in 1940 was about 113 million per milliliter of semen, and that by 1990 it had fallen to 66 million. In addition, they saw a threefold increase in the number of men with a sperm count below 20 million, the point at which infertility becomes a serious risk.
Skakkebaek’s 1992 paper raised concern about the ability of the human species to continue reproducing itself, but skeptics questioned the reliability of the sperm studies the analysis was based on. The studies drew from very different groups of men of varying age and fertility. (Sperm count tends to decline with age, and men who gave a semen sample in a visit to a fertility clinic can reasonably be expected to have a lower count than, say, healthy men selected as donors for a sperm bank.) Some scientists believe older and less precise techniques for sperm counting may have artificially inflated the sperm levels of our fathers and
grandfathers, which would make the drop to current counts appear steeper than it is.
That’s why the new meta-analysis is so important. Swan, Levine and their colleagues sorted through more than 7,500 peer-reviewed papers before focusing on 185 papers involving 43,000 men from around the world. By excluding studies before 1973, they cut out some of the less reliable measurements, and they discarded any studies of men with known fertility complications or who were smokers, since smoking lowers sperm count. It’s not perfect, but this evidence is the best we have, and the conclusions are disturbing. “The community is coming around on this,” says Eisenberg. “There have been some good counterarguments about sperm-level decline, but this paper really puts a lot of those arguments to bed.”
PROVING THAT SPERM LEVELS ARE DROPPING HAS been difficult enough, and teasing out the cause is even tougher. Obesity, which has risen dramatically in Western countries while sperm counts have supposedly dropped, is linked to poor semen quality, as is physical inactivity. A 2013 study of American college students found that men who exercised more than 15 hours a week had sperm counts 73 percent higher than men who exercised less than five hours a week. And men who watched 20 or more hours of TV a week had much lower sperm counts than those who watched little to no TV. Stress is also a risk factor, as is alcohol use, which is on an upswing in the U.S., and drug use, which is increasing thanks to the opioid epidemic. Some scientists have theorized that electromagnetic fields from devices like cellphones degrade semen, leading to weak, immobile sperm. Even heat can play a role. We know that high temperatures can kill sperm, which is why the testicles are outside the body, keeping them up to 5.4 degrees cooler. Researchers know that birth rates decline nine months after a heat wave, leading some infertility experts to believe that climate change may actually be a factor in sperm count decline.
Age also matters. In a recent study, Laura Dodge of Beth Israel Deaconess Medical Center looked at thousands of attempts at in vitro fertilization (IVF) performed in the Boston area and tried to gauge the impact of both male and female age on success. Female age remained the dominant factor, but male age factored in as well—women under the age of 30 with a male partner between 40 and 42 were significantly less likely to give birth than those whose male partner was between 30 and 35. That dovetails with research showing that as men age, their sperm suffers increasing numbers of mutations, which can make it slightly more likely their children will be born with disorders like autism and schizophrenia. Older mothers may get blamed for infertility, but a new study found that new fathers in the U.S. are on average nearly four years older than they were in 1972, while almost 9 percent of new fathers are over 40, double the percentage from 45 years ago. “We tell men that age is not an issue, but now we know that the male biological clock is real,” says Fisch.
So is it simply modern life—obesity, inactivity, stress, cellphones, older parenthood—that’s driving down sperm levels? That’s only the beginning of an answer. Tobacco use definitely hurts sperm counts, yet smoking has fallen significantly in the U.S. That’s one reason a growing band of researchers have come to suspect the influence of toxins in the environment—specifically, endocrine-disrupting chemicals found in compounds like bisphenol A (BPA) and phthalates.
The theory is straightforward: These chemi- cals mimic the effect of the feminizing hormone estrogen and can interfere with masculinizing hormones like testosterone. The chemicals, found in many plastics throughout the environment, may be rewiring the sensitive male reproductive system, eroding sperm quality and quantity and even contributing to the sort of testicular disorders that first alarmed Skakkebaek years ago. The production of sperm is tightly regulated by the body’s hormones, and so any interference with those hormones—say, through exposure to endocrine-disrupting chemicals—could make itself felt first through damage to sperm quantity or quality. “You could still have sperm, but [levels] might be significantly lower than your father’s,” says Germaine Louis, the director and senior investigator at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Most evidence for how these chemicals affect sperm comes from animal studies. One in 2011 found that mice who got daily BPA injections had lower sperm counts and testosterone levels than mice who got saline injections. A startling study
MEN WHO EXERCISED MORE THAN 15 HOURS A WEEK HAD SPERM COUNTS 73% HIGHER THAN MEN WHO EXERCISED LESS THAN 5 PER WEEK.
from 2016 of fish in U.S. wildlife refuges in the Northeast found that 60 to 100 percent of all the male smallmouth bass studied had eggs growing in their testes—a startling feminization—which researchers linked to endocrine disrupters in the waters. Other studies have shown that phthalates appear to disrupt the masculinization of young lab rats. Animal models aren’t perfect, but as University of Texas toxicologist Andrea Gore notes, “the biology of reproduction is incredibly similar in all mammals. We are all vertebrates, and we have the same reproductive organs and processes that develop similarly with the same hormones.”
Scientists can’t expose humans to endocrine disrupters in an experiment, but recent research has found associations between exposure to BPA and phthalates in the world, and declining sperm counts and male infertility in adults. A 2010 study of Chinese factory workers by De-kun Li at Kaiser Permanente found that increasing levels of BPA in urine were significantly linked with decreased sperm count and quality, even among men who were exposed to levels of BPA comparable to men in the general American population. Another study from 2014 followed about 500 couples trying to conceive and found that phthalate exposure among men was tied to reduced fertility. These findings are all associations, which means that while exposure to endocrine disrupters is more likely to be found in men suffering from reduced fertility, it doesn’t mean that the chemicals themselves are definitively the cause. But the studies are stacking up. “For some of the endocrine disrupters like phthalates, the basic evidence is strong that they affect reproductive health,” says Louis, who carried out the phthalates study.
Even more concerning, but harder to prove, is the damage endocrine disrupters may be doing in utero. As a fetus develops in a mother’s uterus, it is barraged by hormones and other chemicals that sculpt development. That includes the male reproductive system—testicles are formed in the womb, and although sperm levels can be altered in adulthood, they seem to be largely set before a boy is born. That means we could see sperm levels continue to decline for years, as boys who were exposed to endocrine disrupters before birth reach reproductive age and run into problems trying to have children of their own. “This trend hasn’t turned around, and it’s not going