July 25, 2017

expert reaction to meta-analysis of sperm count among men in Western countries

In a meta-analysis, scientists publishing in Human Reproduction Update, report that sperm concentration has declined by more than 50% in less than 40 years among men from North America, Europe and Oceania.

Prof. Ying Cheong, Professor of Reproductive Medicine, University of Southampton, said: 

“In assessing fertility, the traditional medical emphasis is place on what can go wrong in women; but the fact is, it ‘takes two to tango’, and naturally, the part man play is also very important.  This report, albeit with its various drawbacks due to its retrospective design, is interesting but concerning as it demonstrates that male fertility, as shown by the results of sperm count, is on the decline in many parts of the world. Various factors, ranging from the environmental impact to diet, could be responsible for this, and will most definitely need further research.”

Prof. Daniel Brison, Honorary Professor of Clinical Embryology and Stem Cell Biology; Scientific Director of the Department of Reproductive Medicine, University of Manchester, said:

“The extent of the decline in sperm counts in the Western world revealed in this study is shocking.   The message is not new, we have suspected this decline for many years, however this study is the most comprehensive to date and includes analysis of nearly 200 published studies.  Previous smaller studies have suffered from confounding factors, including the fact that methods of counting sperm in the laboratory might have changed over the years, or that the populations of men being studied might have changed.  This new analysis overcomes those problems by including a large number of studies of varying design and location around the world, to confirm that the decline in sperm counts is likely to be “real”.   As the authors point out this has major implications not just for fertility but for male health and wider public health.  An unanswered question is whether the impact of whatever is causing declining sperm counts will be seen in future generations of children via epigenetic or other mechanisms operating in sperm.

“This study should act as a wake-up call to prompt active research in this area.”

Prof. Allan Pacey, Professor of Andrology, University of Sheffield, said:

“I’ve never been particularly convinced by the many studies published so far claiming that human sperm counts have declined in the recent past. This is because they have mostly all suffered from one or more fatal flaw, such as only studying a relatively small number of men, being retrospective in nature, or only including men who attend fertility clinics (and are therefore not representative of men in the general population). There is also an inherent publication bias in that studies which claim to show a decline in sperm counts are far more likely to get published than those that don’t. Finally, and most importantly in my view, is that attempts to compare different studies over time have rarely taken into account the significant changes to laboratory technique we have made across the years (the effect of which will lead to lower sperm counts in more modern times as older less reliable tests generally overestimate the true sperm count). For these reasons, and more, I have never truly been convinced that the purported decline in sperm counts is anything more than a laboratory artefact and I have written as much in my 2013 article “Are sperm counts declining? Or did we just change our spectacles?” (See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739163/)

“However, the study today by Levine and colleagues has piqued my interest because it deals head on with many of these issues. For example, it excluded studies which recruited men by virtue of their fertility status. It also included only those studies where the sperm concentration was measured using a haemocytometer (which the World Health Organisation considers the gold standard method). This latter point is particularly critical and although it does not entirely remove the scope for error, it does reduce it considerably in my view.

“Interestingly, the paper concludes that the sperm counts may have seen the greatest decline in the post industrial countries of North America, Europe and Oceania compared to others in Asia, South America and Africa. However, while it would be easy to conclude that this represents a real global difference, perhaps driven by greater exposure of pregnant women or adult men to more man-made chemicals, I think it is too premature to make this conclusion.

“In this context, I highlight a paper in the same journal (Human Reproduction Update) in December last year by Bonde and colleagues (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155570/) showing (again by meta-analysis) that there is currently very little epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders (including reduced sperm counts). Moreover my own work (see https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/des183) has also shown that there are very few identifiable risk factors for poor semen quality that can be identified in adult males.

“Whilst an apparent 52.4% decline in sperm counts may sound a lot, but from the data provided in this paper it represents an average change from ‘normal’ (99 million sperm per ml) to ‘normal’ (47 million sperm per ml). As such, I would urge journalists and editors to treat this study with caution as the debate has not yet been resolved and there is clearly much work still to be done. However, the paper does represent a step forward in the clarity of the data which might ultimately allow us to define better studies to examine this issue. Ideally, we would have funded large prospective epidemiological studies of healthy males 25 years ago and this would by now have given us a clear answer one way or the other. Unfortunately, it seems as though we might have to wait another 25 years before we might get to know the real answer.”

Prof. Richard Sharpe, Honorary Professor, MRC Centre for Reproductive Health, University of Edinburgh, said:

“This is a well-designed and statistically rigorous study that has taken on board criticisms/limitations of earlier analyses (going back beyond 1992) which reported similar decreases in sperm counts in men to that found here. Arguably, the most important modification was to restrict studies to those published since 1973, when the methodology used has been better standardised.

“The results show that average sperm counts in men, unselected for their fertility status, has declined in Western countries by 59% since 1973 and a similar rate of decline has continued beyond 1995 (i.e. It is ongoing not just historical). Considering the allowance made in analyses for potentially important confounding factors, it appears that this decrease is real beyond any reasonable doubt. As the authors point out, the continuous nature of the decline is of as much concern as the decline itself, given that we still do not know what lifestyle, dietary or chemical exposures might have caused this decrease. Research efforts to identify these causes need to be redoubled and to be non-presumptive as to cause.

“The biggest consequence of the progressive decrease in sperm counts over time is that, across Northern Europe today, >15% of young men have a sperm count low enough to impair their fertility and, as the present study indicates, this is likely to get worse rather than better as we move forwards in time. What is not so widely appreciated is that the coincidence of this change in men with delay in couples trying for a baby until the female partner is in her 30’s (when her fertility is declining progressively), creates a double whammy for couple fertility in modern Western societies. Whilst assisted reproduction techniques (ART) can potentially remedy this for some, ART is costly, highly invasive for the female partner and also becomes progressively less effective with female age. Therefore, looking ahead, I can only conclude that couple infertility is set to increase. Hopefully, this new study will serve as a wake-up call for health and research authorities as well as for the public, and for young people in particular.”

Dr Martin Blomberg-Jensen, Senior Researcher at Righospitalet (Denmark), and member of the Society for Endocrinology, said:

“For more than 20 years there has been an ongoing discussion about a decline in sperm counts and this novel meta-analysis basically supports previous meta-analysis by showing that the decline persists in the western world after including more primary studies in the analysis. This is an important finding and supported by good quality primary studies. Moreover, the authors have tried to control putative confounders such as selection bias, duration of abstinence and most importantly age.

“The meta-analysis highlights that male reproductive function may be lower today, which is supported by an increased frequency of testicular cancer and an increasing demand for assisted reproductive techniques in most of the western world.

“The main limitations of the study are the comparison of different cohorts in different countries/laboratories; the involvement of many of the authors in the previous meta-analysis;  the trend being completely opposite for fertile men outside the western world; the lack of information on putative causes identified; and the fact that the suggested gradual decline could not be identified in a 15 year long prospective cohort study of unselected men conducted from 1996 to 2010 in the same laboratory in Denmark (http://bmjopen.bmj.com/content/2/4/e000990.short)

“The implication of this work is that stronger evidence exist for the reported decrease in sperm production in the western world. I agree with the authors that we have to determine whether this decrease is functionally relevant, partly reversible if induced by lifestyle factors during adulthood, or calls for action by policymakers if caused by foetal exposure to stress, EDC or other factors such as painkillers or other medication/dietary supplements known to influence male reproductive function.”

* ‘Temporal trends in sperm count: a systematic review and meta-regression analysis’ by Levine et al. published in Human Reproduction Update on Tuesday 25 July. 

Declared interests

Prof. Ying Cheong: No declarations of interest

Prof. Daniel Brison:  “I supervise PhD students and receive academic grant funding from NIHR and MRC in the general area of fertility research including male fertility.   I have no commercial interests.”

Prof. Allan Pacey: “Chairman of the advisory committee of the UK National External Quality Assurance Schemes in Andrology, Editor in Chief of Human Fertility and Trustee of the Progress Educational Trust (all unpaid). Also, recent work for the World Health Organisation, British Broadcasting Corporation, Purple Orchid Pharma (paid consultancy with all monies going to University of Sheffield). Co-applicant on a research grant from the Medical Research Council (ref: MR/M010473/1).”

Prof. Richard Sharpe: “I have no conflicts of interest other than (a) I am a deputy editor for a sister journal (Human Reproduction) and (b) I am actively involved in research in this area.”

Dr Martin Blomberg-Jensen: No conflicts of interest declared.