Male Reproductive Health

The evolution of male reproductive health

In recent years, a sense of urgency regarding male reproductive health has been escalating worldwide and for many reasons. Perhaps the most conspicuous reason is the reported global decline in sperm counts being broadcast by popular media channels to the lay community. Coffee table books have even been published on the same. While confounders to the quality of the datasets can be argued, in the scientific community, there seems to be general agreement that sperm numbers have been and continue to be dropping. However, the interpretation and response to the information in the lay community is not easy to characterize. One reason might be the inability for many men to personalize the significance of the news on an emotional level. Another reason might simply be due to the overwhelming stream of other news, e.g., economy, joblessness, global unrest.

Critical to the sperm count decline argument regards the ‘old standard’ manual semen analysis, which seems to be perpetually debated for its modern-day relevance, less than optimal discriminatory power to identify fertile from infertile men, and lack of adherence to recent iterations of WHO standards as evidenced in a plethora of research publications. It is important to remark that while high quality assessment of sperm parameters is important for contributing to accurate clinical diagnoses, the results are also critical for characterizing the proportion of infertile men in a population.

With evidence of global sperm count declines and a consequent increase in male infertility, questions are being raised regarding potential causes. To better understand a ‘cause’ requires a better ability to detect an ‘effect’. Thus, to better understand what the potential impact of changing lifestyle and environmental factors may cause to effect a change in reproductive health requires testing methods more advanced than the semen analysis. Technological advances being adopted from other areas of scientific research are proving to be consequential for advancing reproductive health research.

Modern technologies for determining the sequence (termed: next generation sequencing) of the whole genome (the entire sequence of DNA coding for the whole of who we are) and whole exome (the protein-encoding region of the DNA) are quickly contributing to advances in male infertility diagnosis. For example, whole exome sequencing is increasing our understanding of what may be genetic causes of ill health and infertility. Epigenetics is another field that is beginning to have a tremendous impact on male reproduction research. The definition of epigenetics can be grossly simplified to mean those factors that are attached to DNA to regulate the activity of genes without changing their sequence. This regulatory process influences the production of proteins, i.e., the ‘building blocks of life’. Collectively, these new technologies are beginning to reveal that lifestyle, e.g., overweight, environmental factors, occupational hazards, can impact the overall and reproductive health of the individual, e.g., infertility, cardiovascular disease, diabetes, and the health of offspring born to that individual (termed: transgenerational inheritance).

These new areas of translational reproductive health research, while simplistically described here, are likely to be transformational for understanding the origin and consequence of infertility, and how such causes might be mitigated by, for example, lifestyle changes. Lastly, for the aforementioned to be fully realized requires a heroic coordinated approach from research centers around the world to generate more quickly the massive datasets necessary to yield clear understanding of cause/effect on both good and ill-health. To support research of this magnitude requires significant policy and funding changes, and across borders.

Anticipated progress in the development of more accurate diagnostic tests contributes directly to the development of better and more effective treatment strategies. These changes can be anticipated to occur more quickly than in the past. Therefore, access to and delivery of health care will also need to evolve to accommodate new diagnostic and therapeutic technologies. This will compel rapid change and adaptation by medical educational programs so that providers are current on the new technologies. Importantly, social education programs must be updated so that the communities being served are well informed.

This brief blog post is meant to stimulate curiosity and the desire to learn more. To address the latter, inquiring minds are suggested to read an ‘Expert recommendation’ recently published in Nature Reviews Urology (https://doi.org/10.1038/s41585-023-00820-4) entitled ‘Frequency, morbidity and equity – the case for increased research on male fertility’. Novel data along with a synthesis of relevant publications by members of the Male Reproductive Health Initiative (MRHI; https://www.eshre.eu/Specialty-groups/Special-Interest-Groups/Andrology/MRHI; https://www.instagram.com/repromale) and invited experts in the field culminates in a 10-point list of recommendations that serve to fill knowledge gaps and advance the field of reproductive medicine to the level of care as for health conditions with similar societal impact.

CJ De Jonge, CLR Barratt, N Garrido, A Pacey, MH Vazquez-Levin
Male Reproductive Health Initiative (MRHI)