With headline-making studies suggesting men’s sperm counts are in freefall, male infertility is a vital but neglected men’s health issue. What might be causing this apparent rise in infertility? How can the problem be addressed? What treatments are available for men who are struggling to have children? And what technological breakthroughs are on the horizon?
Unfiltered spoke separately to Dr Channa Jayasena, a specialist in reproductive endocrinology at Imperial College London, Professor Allan Pacey, deputy vice president and deputy dean of the faculty of Biology, Medicine and Health at the University of Manchester, and Professor Richard Sharpe, of the MRC Centre For Reproductive Health at The University of Edinburgh, to hear their own expert opinions and analysis.
Studies clearly link the apparent growth of male infertility to the rise in obesity and unhealthy lifestyles. But research suggests environmental chemicals – from phthalates in plastics, to pesticides in food, and pollution – may also be a cause. Is this true?
Dr Jayasena: It’s difficult to prove, because clearly it’s unethical to expose people to pollution and toxins… But the first convincing studies are starting to come out suggesting that if you look at very polluted parts of cities, versus less polluted parts, the male offspring of women, who would have been pregnant in those conditions, appear to have very subtly different anatomical features. If you take [the distance from] the penis to the anus, that is a measure [the anogenital distance, or AGD] of how ‘male’ you have developed. The smaller that [distance] is, the more ‘female’ you are. And there are discrepancies which suggest – and again, it’s not cast-iron proof – that environmental pollutants may be disrupting this male development. And that’s because most environmental pollutants mimic oestrogen, rather than testosterone. There are also wider issues about pesticides. And we have probably some leaching off plastics, which are inside toothpastes and drinks cans. So we can’t get away from it.
And that issue – combined with the well-known metabolic issues [obesity, diabetes etc] today – are strongly suspicious, in my mind, for being related to declines in fertility… I think it fits with the narrative that if you look worldwide, we are overall less healthy than we were, for a variety of reasons… And there’s an exquisite relationship between body mass index and obesity and male infertility.
If we could stop [environmental pollution] would everybody have a high sperm count? I don’t think it’s that straightforward
Professor Richard Sharpe, University of Edinburgh
Professor Pacey: There is some plausible experimental evidence from animal studies, but also from human case histories, that show that the most sensitive part of a man’s life is before he was born. So when the testicle is formed in the womb, before he’s even born, in some way that we don’t fully understand, [this period] sets his adult sperm production capacity… So it’s not what a man is doing now that is the cause of the problem. It’s what he was exposed to before he was born. And that makes it really difficult to study. Because we can’t look back in time at what pregnant women of the 1950s, 60s and 70s were being exposed to…
But the kinds of things that are talked about are oestrogen-mimicking compounds – things like paracetamol that are taken during pregnancy. There was even a study looking at whether or not the sperm counts of men who were born to women who were either eating beef or vegetarian during pregnancy are different. And there was a suggestion that they were. But it wasn’t the beef; it was the compounds in the beef that we use during the meat production process which were making it through to the foetus. So all of these are plausible. And they demonstrate an effect. But nobody has ever been able to pinpoint it.
Professor Sharpe: That [environmental cause] is towards the top of the list of what we think is likely. I certainly wouldn’t say that it’s by any means proven. And we don’t know how important that is. In other words, if we could stop it all, would everybody have a high sperm count and everything be hunky dory? I don’t think it’s that straightforward. If I went back to the 1990s, I would have been a fervent supporter of that thinking. But the evidence that’s come since, and the work we’ve done ourselves, has made me think it just doesn’t add up. So I am unconvinced.
But I think the best evidence that we have suggests that it’s probably related to events during early foetal development, back in the first trimester of pregnancy. And I don’t want to get side-tracked into talking all about that, because there’s nothing you can do about it! So to me the issue is, therefore, making the best of what you have… If you’ve got a high sperm count, that’s fine. But if you haven’t, if you’re one of the increasing number of men who appear to have a low sperm count, then you’ve got to make the best of it.
Where there is little doubt and controversy is in the impact of obesity and unhealthy lifestyles on male fertility. Research suggests overweight men are three times more likely to have poor semen quality. How can this lifestyle-driven infertility issue be addressed?
Dr Jayasena: It’s highly ineffective and annoying to just preach: lose weight and do this! I think what we need to do as doctors in the health system is to help people to do that. And to find [effective] approaches. So I think things like Couch to 5K, finding tangible ways and opportunities for people, particularly at the workplace, to go to gyms… all of those things are positive. But I think we need more research to tease out the big things that people can do. Is it exercise only? Is it weight loss? How much weight loss? Is it both? We need the nuts and bolts so that men – before they have [infertility] problems – can focus on staying well and fit… But in general, most exercise which is done proportionately can only be a good thing, in combination with a healthy diet.
There is no magic pill that we can give guys to boost their sperm production… but there’s lots that a man can do that make it worse
Professor Allan Pacey, University of Manchester
Professor Sharpe: I think the things that men can do are to really push aside what has become the norms in our life today. So, for example, not to eat a modern Western diet – a lot of fast food and highly processed food… They should be thinking about trying to eat a very healthy, balanced diet, with a lot of fresh fruit and veg, and low levels of processed food. But also trying to have an active life and not sitting down all the time. Just these small things can have a positive effect. I’m not saying that they’re going to cure infertility. But they can only have benefits, whether they be reproductive or in general health.
Professor Pacey: There’s two phases in a man’s life where we need to worry. One is before he’s born. And arguably a 35-year-old man can’t worry about that! But when a man is trying to conceive, then there’s a very genuine question about whether his lifestyle or his medical history is appropriate for what he’s trying to do… And it is just all of the obvious stuff…. There is no magic pill that we can give guys to boost their sperm production. But there’s lots that a man can do that make it worse. So it’s a case of taking away the risk factors as much as we can, without making you miserable. And trying to optimise [your sperm health].
What modern treatments are available to men with seriously impaired fertility?
Dr Jayasena: If you have a low sperm count, there is no medication out there that has been proven to improve your semen quality. However, research that we’ve done has shown that men with infertility – and whose partners have recurrent pregnancy loss and miscarriage – have a high risk of oxidative stress in their semen and DNA fragmentation. So one approach is to take antioxidants. But one slight caution is if you are ‘normally’ fertile, and you take antioxidants, you might actually go the other way and create reductive damage. There is oxidation and reduction in chemistry. And you could cause reductive stress. So we need to maybe take a more measured approach and actually start testing for oxidative stress in semen, which is relatively straightforward. And for DNA fragmentation, which again is relatively straightforward. Those aren’t currently available on the NHS. And I think it’d be a good next step to develop these.
Ultimately, if that doesn’t work, then assisted reproductive technologies like IVF [in vitro fertilisation] are needed. If you’re one of the 1% of men who has azoospermia (no sperm in your ejaculate), then testicular sperm retrieval [which involves making a small incision into the testicle to take a sample – or biopsy – from which sperm can be recovered] has revolutionised the treatments of these men. Fifteen percent will become fathers, so it’s not a fantastically high amount. But nevertheless, it offers hope. And we’re there to support these men. ICSI [Intracytoplasmic sperm injection] is the most common treatment in the UK. It has the highest pregnancy rates. This is when you inject sperm into the egg.
Some patients have infertility due to a deficiency of hormones in the brain, which stimulate the testes. At Imperial, we specialise in treating these people, and we can actually restore their fertility. It is amazing. After painstaking treatment with these injections, twice a week, which takes up to two years… This [condition] is uncommon. But these men are out there. And it would be a tragedy to say: there’s nothing we can do… So there’s some really exciting hormonal treatments that are available for some patients.
What technology, research and changes might improve the treatments available to men?
Dr Jayasena: Testicular sperm retrieval mapping [a minimally-invasive procedure to map out the potential location of sperm in the testes] is one such type. This is only useful if you have azoospermia – no sperm… What you try to do is essentially construct a ‘map’ and use needles to sample different bits of the testes, and see which bits of the testes have sperm, and then go in later and try and cut out some. But [in the future] there may be ways of searching for the needle in the haystack through different ways – maybe molecular approaches or imaging approaches – which might help us. I think that’s a really exciting area of development that will play out in the next five to ten years.
Professor Sharpe: Firstly, men need to be more aware, and the environment needs to change so that men feel easier exploring and talking about their fertility status and their reproductive status. Reproduction is something that is central in all our lives, whether we like it or not. And as I often have had to lecture, that’s why we’re here: to reproduce. So everything is geared around that. The way our bodies work is all to do with reproduction. That is the main focus. It isn’t to become a better runner or a better soccer player. It’s to become a parent.
But also what we have under-invested in, and chronically, is trying to get to grips with understanding the processes that underlie male reproductive development and function. We know that in men sperm production is dependent on producing enough testosterone within the testes to drive that process. But if you ask the question: how does it do that? How does that work? We still don’t know. We certainly haven’t invested enough in trying to understand.
Professor Pacey: AI (artificial intelligence) might have a role at the very sharp end, in terms of sperm selection for IVF. And there’s a lot of data coming out about that now.
But I think if we’re going to answer big questions, we need to do big studies. And what we generally lack in male reproductive health are the big coordinated multicentre studies that answer a big question. That’s where I come down to funding, and the profile that male reproductive health has. I’ve been involved in a number of consortia over the years, trying to get funding for what we thought would be big questions or big studies. But they always fail to other cancer-related or diabetes-related things that are seen as more worthy. And I’m not sure that that’s very helpful to the field. So we’ve got to change the narrative really, and get male reproductive health a bit more hype.
