MALE INFERTILITY

The ongoing challenges for male reproductive health

Published 02 May 2022

A Campus meeting in October organised by ESHRE’s SIG Andrology and the Male Reproductive Health Initiative will address the diagnostic and treatment gaps in male infertility and present a blueprint for improvement. Chris Barratt, a founding member of the MRHI, talks to Focus on Reproduction about the meeting and about the present status of male reproductive health.

Focus on Reproduction: This is a wide-reaching Campus meeting. Do you have specific aims?
Chris Barratt: I should say first that it’s a very different kind of Campus. We will have world experts attending – some in person, some virtually – but they’re all international authorities in male reproductive health and have an unrivalled view of its present status and where it can go. However, what the meeting is really about is how we can change the way we do things in male reproductive health. So our aims are broad, and we hope to develop strategies for politicians, policymakers and health authorities. Right now, there is only one country in the world which has a health policy specifically directed at male reproduction – and that’s Australia. We must learn from this example and attract the public and the politicians as well as doctors to raise the status of male reproductive health.

FoR: The meeting is organised by the SIG Andrology and the Male Reproductive Health Initiative (MRHI). The MRHI is supported by ESHRE, so can you tell us a little more about it?
CB: MRHI was established to bring together a lot of people working in andrology and provide a common direction. In 2017 several us were involved in assembling evidence for a WHO guideline on male reproductive health and one striking feature of that exercise was the low quality of the evidence available for clinical decisions.(1) It was a wake-up call for many of us. We needed to ask questions about what we could do, and how we could give male reproductive health a consistent blueprint for the future. Christopher de Jonge and I approached several organisations and many were enthusiastic but it was only ESHRE who provided some start-up funding. Since then we’ve published several papers and have put this Campus meeting together.(2.3)

FoR: There seem good grounds for seeing male reproductive health as the Cinderella of reproductive medicine – and certainly with fewer studies than found in female reproductive health. How would you describe its present status?
CB: I can answer part of that question by referring to a SWOT analysis which the MRHI did and which will be presented at the Campus in October. We’ve taken a global view and found that its strengths lie in a relatively high level of basic research and public and professional awareness. There have been major advances in translational research and in an understanding of the biology. Equally, the treatment of male infertility is now a fundamental part of ART, and several types of male infertility are now amenable to treatment. These are substantial strengths. But the weaknesses are as significant as they have ever been – accurate diagnosis, treatment without ART, poor public information, and still little progress in male contraception. These weaknesses are what we’ll be discussing in Budapest. So there are strengths in basic biology and translational research but we have to address bridging the gaps. For example, we need to find a way to develop more global multicentre trials and better quality funding.

FoR: What about the basics? In terms of prevalence, do you have a precise idea of how many men are affected by subfertility?
CB: No, we don’t. There are real difficulties in determining prevalence. We often hear that one in seven couples are subfertile, and that around 50% of that is attributed to the male. But if you dig down into the data in different parts of the world you find that much of the information is very sparse. So we need comprehensive mechanisms to obtain these data.

FoR: What about semen analysis? Is that still the basis of diagnosis?
CB: Yes, semen analysis is still the bedrock of diagnosis, along with a history and physical examination. But today many men don’t even have them. One objective of the Campus meeting is to find a way of discovering basic information and identifying action points.

FoR: So what are the problems with semen analysis – is it that it’s not done well or consistently, or as you’ve just suggested that it’s not done at all?
CB: Well, we do have a standardised method of semen analysis set out by the WHO, but unfortunately there seems to be great variability in how it’s done - and any quality control data you look at shows this. This needs to be urgently addressed. What is required is relatively simple – and that’s education and training. A high quality semen analysis will provide much more than a simple diagnosis of infertility, but it needs to be done right.

FoR: And I suppose on that point we must ask about other methods of diagnosis. DNA fragmentation tests, for example?
CB: Well, they’re not recommended as routine at the moment. They’re expensive, there are several tests available, and the reference limits for some assays are not completely clear. The other problem is what do you do with the results. Antioxidant treatment? That doesn’t work. We desperately need better methods to indicate the pathology of the man.

FoR: I suppose the big question about diagnosis is, why does it matter. You’ve spoken in the past about an ‘ICSI mentality’ and we can’t deny the fact that ICSI is an incredibly successful treatment.
CB: Yes, it’s a fantastic treatment but the reality is that throughout the world many people simply don’t have access to ICSI. So many more men with subfertility would benefit from an accurate diagnosis and a non-invasive method of treatment. It would be wonderful if a man could take a pill and not need ICSI. It’s the same argument about male contraception - a pill is not a complicated thing to think about. What we’ve seen in the Covid pandemic is the power of research getting together across the world with pooled resources and backing a strategy with substantial finance. This provides a classic example of where we need to go with male reproductive health.

FoR: Are there implications in your concerns for male reproductive health for general health? What’s been termed ‘the canary in the coal mine’ with reference to a decline in sperm counts over time.
CB: The study you’re referring to did suggest a strong association.(4) There are much data to support this concept and it raises the question about the somatic health of the man who has, for example, a low sperm count. The concept is that subfertile men live sicker and die younger.

FoR: And what are those implications? Cardiovascular disease? Cancers?
CB: Yes. We know, for example, that subfertile men have a higher incidence of premature death than controls, more hospitalisations. However as yet we don’t know why. Moreover, we’re still debating the questions raised by an apparent decline in sperm counts. This is another very clear gap in our knowledge. We’ve been talking about it for ages. But only a coordinated global approach would address these challenges with any robustness.

FoR: So you’re asking the questions, raising the concerns, but where can you actually go? What’s the future for male reproductive health if – as you suggest – it’s restrained by these chronic problems?
CB: It’s a very important question, and one which inspired myself and Chris De Jonge to form the MHRI. But as we stand now, all the evidence we have suggests that funding for male reproductive research – and this includes male contraception – is less than 1% of national health research budgets.(5) This is a fundamental problem. Even if overall research funding for reproduction in general is low, it’s really low for the male. This seems to me to be a huge problem, and one we must try and deal with. The extent of the funding gap actually came as a big surprise to me. Presently, it is a challenging situation, and one which must be addressed for the future. Otherwise, we’re left with an insoluble paradox, that, while male infertility poses a global health risk for many millions of men, research funding to develop better diagnostic tools and treatments is not at a level to deal with it.

FoR: So how will you move forward? MHRI is asking the question, you’ve started your publications, arranged this meeting but how can you hope to bring it all together? Is it just a question of making people aware of the gaps?
CB: No, it won’t work that way. We need research plans and training programmes, and that will require funding. And that’s where our policy papers come in, to start to influence governments. All our recommendations, which we’ll hear at the Campus meeting, must effectively be converted into cash. And that will be a big challenge.


* More information on the October Campus meeting can be found at https://www.eshre.eu/Education/Calendar-Campus-events/Male-Reproductive-Health.
* Andrologist Christopher De Jonge from the University of Minnesota and a founding member of the Male Reproductive Health Initiative will present an update on progress at this year’s annual meeting in Milan in a session on male fertility (Monday 14.00, main auditorium).
* The mission and strategic goals of the MRHI can be found at https://www.eshre.eu/Specialty-groups/Special-Interest-Groups/Andrology/MRHI




1. Barratt CLR, Björndahl L, De Jonge CJ, et al. The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities Hum Reprod Update 2017l 23: 660-680.
doi.org/10.1093/humupd/dmx021
2. Barratt CLR, De Jonge CJ, Sharpe RM. 'Man Up': the importance and strategy for placing male reproductive health centre stage in the political and research agenda Hum Reprod 2018; 33: 541-545.
doi.org/10.1093/humrep/dey020
3. De Jonge C, Barratt CLR. The present crisis in male reproductive health: an urgent need for a political, social, and research roadmap. Andrology 2017; 7: 762-68.
doi.org/10.1111/andr.12673
4. Levine H, Jørgensen N, Martino-Andrade A, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update 2017; 123: 646-659.
doi:10.1093/humupd/dmx022.
5. Gumerova E, De Jonge CJ, Barratt CLR. Research funding for male reproductive health and infertility in the UK and USA [2016 – 2019], Hum Fertil 2022; doi10.1080/14647273.2022.2045521

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