Sperm counts have been decreasing for decades. Nobody seems to know why it’s happening, and not much is being done to find out, but we could be facing a public health disasterby Philip Ball / July 31, 2018 / Leave a comment
Published in August 2018 issue of Prospect Magazine
Where have all the sperm gone? And why do declining sperm counts matter? Photo: Prospect The last time I checked—about 16 years ago—my sperm count was rather feeble. That didn’t feel like the devastating blow to my manhood that it might once have been. It’s a common enough problem: an estimated one in 20 young men (I was hardly that even then) have sperm counts low enough to impair fertility. But neither does it feel that the matter is taken very seriously. Doctors tend to shrug: “Oh, so that’s the problem.” “Anything I can do?” I asked my GP. “Not really,” he replied indifferently, not bothering to check if I was a heavy drinker or what my diet was like—both factors that have been shown to cause trouble for sperm. For centuries, science has ignored the potential role of the male in infertility. The default assumption that it was the woman’s fault wasn’t fair, but the consequence is that we know a lot today about the causes of female infertility, and have many -potential -treatments. Male infertility, in contrast, remains rather mysterious and little researched. One group of experts on male health wrote recently of our “andrological ignorance,” an indifference reflected also by the continued lack of a “male pill” for birth control. This ignorance about fertility in men is alarming, because sperm counts seem to have been decreasing steadily and significantly for decades. The issues involved, however, are so hopelessly tangled up with received ideas about gender roles and identity that they are being neglected. Something disturbing is going on, and the consequences for health and society could be profound. A complex legacy The lack of interest in this aspect of men’s health certainly does not reflect discrimination against them. Rather, the relative indifference to male infertility comes from a complex legacy, much of which is actually misogynistic. Aristotle’s notion that the man was primarily responsible for procreation, the woman merely providing the passive “soil” for the seed, was dominant until at least the 17th century, when William Harvey postulated that ex ova omne vivum (all living things come from eggs). But the mammalian ovum wasn’t actually discovered until 1827, and even today our cellular story of conception insists on the active, plucky role of the little sperm for which the egg sits passively in waiting. Yet while fertility might have been men’s business, infertility was always a female issue. In the book of Exodus, Rachel suffered God’s arbitrary justice when He “opened the womb” of her sister Leah to conceive a son for their joint husband Jacob but did not do so for her. “Why have I been cursed with women who destroy the children in their own wombs?” Hilary Mantel quite plausibly has Henry VIII rage in Wolf Hall—although so many miscarriages in different wives has raised retrospective suspicions about Henry’s own generative capacity. This historic silence on male infertility still too often goes unbroken. “Any admission of physical weakness or illness, including infertility, is a no-no for men… Masculinity and fertility [are viewed] as being intertwined,” says Richard Sharpe, a specialist on reproductive health at the University of Edinburgh. “The best way to avoid having to admit any fertility problem is not to measure it in any defined way in the male partner but just to blame it on the female.” Yet of the one in six couples affected by fertility problems, more than half are thought to involve some problem with the man. Now, however, this problem is becoming too severe to ignore. According to an analysis of many previous studies of sperm quality in men in westernised countries, published last year, sperm counts in men fell by a staggering 50-60 per cent between 1973 and 2011. That decline has been happening steadily over the years and there is no sign of the drop abating. When the media reports such numbers, it likes to cite dystopian fictions such as PD James’s novel The Children of Men and Margaret Atwood’s The Handmaid’s Tale, in which human reproduction has become almost vanishingly rare. There’s no reason to anticipate such drastic scenarios yet, but the issue may not be just about sperm and fertility. Low sperm counts are often an indication of other health problems, actual or incipient, including testicular cancer. So we would do well to get to the bottom of it even if we weren’t worried about the effect on fertility: the decline in sperm count may be the canary in the coal mine signalling a wider malaise. Why sperm matters But, of course, fertility also matters in its own right. As the biblical stories attest, a lack of it has been a source of heartache and stigma for millennia. For men, that’s mostly about sperm. The presence of these tadpole-like cells in semen was discovered in 1677 by the Dutch pioneer of microscopy Antonie van Leeuwenhoek, who, being a stickler for the religious prohibition of masturbation, rushed from the marital bed to put his own semen under the lens. Examination of sperm became routine enough in the 20th century that meaningful records of sperm counts exist from at least the 1930s. Using such data, in 1992—the same year that James imagined the consequences of global male sterility in The Children of Men—a team of researchers in Copenhagen reported evidence of falling sperm counts over the previous 50 years. They speculated that exposure to environmental chemicals might be the cause. The claim sparked alarm and argument, with some experts saying that the statistical analysis was faulty or the data unreliable. It’s certainly not easy to get good figures. For one thing, there’s no routine testing of a representative sample of the population. Sperm counts often become an issue only when, as in my case, infertility raises its head—but such cases obviously give a skewed picture. A good statistical analysis would require large sample sizes and ideally more than one measurement per person (sperm count can vary widely between ejaculations, depending partly on the time since the last one). There are regional and national differences too, compounding the difficulties. But an analysis last year—led by Hagai Levine of the Hebrew University-Hadassah School of Public Health, in Jerusalem—reached a rather definitive verdict. The decline among men in the US, Europe, Australia and New Zealand is real and dramatic. Whether the same is true in South America, Asia and Africa isn’t clear—the current data just isn’t good enough. While there can be upwards of 250m sperm in each millilitre of semen, numbers lower than 40m are sometimes classed as “subfertile.” Around 40 per cent of men fall into that range today, compared with around 15 per cent in the 1930s. And 1 per cent of men have no sperm in their ejaculate at all. Dramatic as the changes in quantity have been, just as important for fertility are questions of quality. It is a little-known fact that most human sperm are abnormal in their shape or ability to move, and typically only 5-15 per cent are classed as normal. In that regard the human male is off and of “naturally” low fertility compared with other animals. Yet this situation has been getting worse—in particular, there’s a decline in “motility,” or swimming ability. (Note that here as elsewhere I am using “fertility” in its proper meaning of the potential to procreate, not in the demographers’ confusing definition in terms of how many actual offspring a person has.) Something is going wrong However, the relationship between sperm count or quality and infertility is far from clear. A low sperm count doesn’t imply an inability to conceive a child—as I have discovered to my surprise—but may mean it just takes longer. So a declining sperm count doesn’t automatically imply a decline in birth rates; where they do fall, that generally reflects other factors, including choice. But if the rapid decline continues, then it seems reasonable to suppose that at some point it will have a bearing on men’s ability to conceive naturally. “We have seen an increasing frequency of men with poor semen quality over the years,” says Niels Jørgensen of the University of Copenhagen. “It has to be telling us that something is basically going wrong, and we need to figure out what.” But “we should not expect just one answer,” he adds. “It is most likely multiple causes, that individually only play a minor role and that’s also why it is so difficult to handle.” One of the most widely publicised potential culprits is environmental contamination. It’s claimed that, especially in the industrialised west, we are increasingly exposed to synthetic chemicals that can mimic natural hormones produced in the body’s endocrine system, causing havoc with reproductive functions. But hard evidence for the influence of environmental chemicals is scanty. The belief is that such chemicals exert their effects not directly in adult men but via the mother during the development of male babies in utero, and so are only seen many years later. Such an indirect link is tricky to pin down. But there is some evidence to support it: for example, the incidence of reproductive disorders in Danish men is larger than in Finnish men, and there is evidence from analysis of breast milk that exposure to the suspect chemicals has been greater in Danish women. But, as we know, correlation is not the same thing as causation. Sperm quality can be more reliably linked to lifestyle factors, such as diet and exercise. Smoking is thought to reduce sperm counts, and so does a high fat intake. Heavy smoking during pregnancy with a male child has been shown to reduce testis size and sperm count by 20-40 per cent when the child reaches adulthood. Clearly something circumstantial is behind the trend; a genetic shift couldn’t make itself felt in just a few generations. Sharpe suspects that diet, lifestyle, medications and environmental chemicals all play roles, possibly in that order. Whatever the cause, the trend is consistent with what’s seen in other aspects of male reproductive health. Tumours arising in the germ cells—the progenitors of sperm—in the testicles have become more prevalent, and testicular cancer has risen by more than a quarter in the UK since the early 1990s. Average levels of testosterone, a hormone crucial for sperm production, have also declined and Sharpe says that, while cause and effect are far from clear, reduced testosterone is associated with “virtually all of what we call modern western diseases, such as obesity, type 2 diabetes, and cardiovascular disease or hypertension.” Poor sperm counts are known to be associated with other health problems too, and lowered with average longevity. “The lower your sperm count the greater your risk of dying,” says Sharpe. “Irrespective of fertility issues, healthy testis function and a high sperm count are measures of population health for men. The fact that both sperm counts and testosterone levels have been declining in men in recent decades suggests that male health might have also declined.” What’s to be done? Currently, says Sharpe, “we have almost zero treatment options to offer infertile men, and I don’t see any real prospect of this changing any time soon.” Sure, you can try giving up smoking, drinking and chips—but there’s a good chance it’ll make no difference even if you’re prone to such indulgences in the first place. It’s a rather shocking situation for a widespread medical problem that causes so much anguish. But “you get out in proportion to what you put in,” says Sharpe, “and we have not invested enough in researching the causes of male infertility.” “It is utterly incredible that we can build space rockets and fly into space, yet we have no real idea how a sperm swims, or finds the egg, or fertilises it,” says Sarah Martins da Silva, a specialist in reproductive medicine at the University of Dundee. “Without understanding how sperm work, it is difficult to understand why they don’t, or to fix them.” Martins da Silva is part of a team at Dundee that recently reported the discovery of potential drugs for increasing sperm motility. The trick seems to be increasing the ability of calcium ions to move across membranes in sperm cells, something essential for the movements of the tail that cause swimming action. The Dundee group screened over 3,000 possible candidate molecules that might help to boost calcium ion flow, and found two that worked well both for sperm from healthy donors and for men undertaking fertility treatment. Still, the work is a long way from securing any kind of cure for infertility where motility (not sheer numbers) is the problem. The risk of complacency Ancient prejudices are part of the reason why science has not got further. But another reason for the lack of progress is, paradoxically, modern technology itself—because it supplies the illusion of a cure. IVF can help poor sperm quantity and quality because the sperm can be concentrated and introduced directly to the egg. In some cases even immotile sperm can be inserted directly into an egg using a very fine pipette. The first child to be conceived through this insertion method was born in 1992, and the technique is now widely used, even sometimes when there is no problem with the sperm; success rates are comparable to ordinary IVF. But all of these procedures are invasive, costly (£3-5,000 per cycle) and uncertain: success rates per cycle are typically about 30 per cent for women under 35 and decline sharply with age after that. In other words, a single cycle of IVF fails typically two times out of three, or more. For all its flaws, the existence of this solution can make doctors complacent. Most doctors think these new procedures have solved the infertility issue. But, says Jørgensen, “this is not really so.” Sharpe agrees. For one thing, all the burden—the gruelling rounds of ovarian stimulation, egg collection and embryo implantation—is borne by the woman. What’s more, assisted reproduction technologies are an experiment with unknown long-term consequences. While initial fears that IVF might lead to widespread birth defects were unfounded—eight million successful births so far—the cohort of people born this way is still relatively young: the first, Louise Brown, is 40 this year. Because doctors have little more to go on than intuition when selecting IVF embryos to implant, or sperm to inject, there’s no way of knowing if natural “quality control” measures are being bypassed. The available research is patchy. Attempts to survey cognitive development of children born through IVF have been conflicting: some studies report impaired behavioural and cognitive performance, others show no consequences or even slight benefits. There’s some sign that physical health risks, such as cardiovascular or metabolic problems, are greater, but it’s not clear if these are innate or due to complications arising from the fact that IVF often yields twins or even triplets. In short, we just don’t know what the effects are. So far, says Sharpe, we’ve been “riding our luck” with IVF and related technologies, pressing on with new techniques while knowing very little about how they will pan out. If these methods are for various reasons—including declining male fertility—going to become a bigger part of human procreation in the future, we can’t afford to just keep crossing our fingers. Besides, having an apparent technofix for infertility could mean that we never come to understand the cause of the problem in the first place. “As a public health professional, I strongly support a focus on prevention rather than non-sustainable technological solutions that may have unexpected, long-term, negative implications,” says Levine. “We must treat the root causes.” At the moment, though, technofixes seem the order of the day. Already IVF counts for 8 per cent of all births in Denmark, for example. And there may come a day when even a complete inability to produce viable sperm in the testes might not be an obstacle to a man having a biologically-related child. In 2016 biologists at Kyoto University reported that they had created “artificial sperm” from the skin cells of adult mice by reprogramming them—one dramatic manifestation of a more general, recently discovered, ability to interconvert different types of mature cell, which I recently wrote about in another context for Prospect (“Why I’m Growing a Second Brain,” April). They used some of this “induced sperm” to fertilise mouse eggs, which developed into embryos and then into apparently healthy mice pups. Meanwhile, efforts are under way to turn human stem cells—the versatile cells in embryos that can grow into any tissue type—into eggs and sperm in the laboratory. So far the resulting cells aren’t actual sperm but the primordial germ cells that make both sperm and eggs: we are perhaps halfway along the path to artificial sperm. In time, however, there is no obvious reason why the process of fertilisation and birth seen already in mice shouldn’t work in humans, although the idea raises big safety and ethical questions. The possibilities would be mind-boggling. Not only could we make babies without natural sperm or eggs, but either type of gamete could be made from the adult cells (skin, say) of either a man or a woman—even, in principle, from a single person. Here, then, could be the answer to a dwindling sperm count: “If the human race as a whole were seriously endangered, and if our reproductive abilities were seriously compromised, we might have to manufacture human beings,” bioethicist Ronald Green told New Scientist in April. “We will [soon] likely be able to generate human sperm or eggs in vitro, which in theory could make men, at least, redundant in the reproductive process,” says Sharpe. Does that mean we can safely forget about those falling sperm counts? Not unless, he suggests, we’re ready to surrender the fate of our species to artificial reproduction technologies which are themselves “a huge human experiment, the long-term consequences of which remain to be discovered.” Sex in a petri dish It may sound crazy to imagine that an answer to the decline in sperm counts lies in transferring sex to the petri dish, perhaps with artificially made sperm and eggs. But infertility could push things in that direction. Unless we address our andrological ignorance, say Sharpe and his colleagues in a recent paper, our “gulf in knowledge and effective therapy for infertility between male and female will grow, and it will become easier to use in vitro generated male germ cells than naturally produced sperm to achieve couple fertility.” Such developments would, like IVF itself, be driven not so much by the biomedical needs of clients as by the desire for profit. There’s an incendiary and possibly toxic mixture here: market forces acting on technologies that are hostage to all kinds of taboos and bedeviled by traditional judgments about morality, gender, conception, procreation and the obstacles to it. How we think about these challenging issues will, as always, depend on how we choose to frame them—whether that is via religious and cultural prejudices, or the Faust, Frankenstein and Brave New World narratives that have always accompanied new ideas about how to procreate or otherwise generate humans. In alluding to the idea that men could become redundant through artificial reproduction, for example, Sharpe taps into another recurring trope: much the same was said in the interwar period about putative technologies such as ectogenesis (artificial gestation) that stimulated Aldous Huxley to write his (forgive me) seminal novel. That isn’t to imply that fiction, myth and legend have no place in this discussion. It will be impossible to exclude them anyway: mythical thinking and the cultural assumptions that feed it—such as fertility being always and everywhere the woman’s problem, or assisted reproduction bearing a taint of “unnaturalness”—have long shaped and often distorted the conversation that needs to be had. Only by facing up to such fears, biases and preoccupations—like those that have inhibited us from talking about or studying the male side of the equation—can we reckon with the extraordinary and alarming evidence that confronts us. Only when we acknowledge and interrogate those factors will we be able to start—as, with urgency, we must—having a decent conversation about sperm.