Semen quality and lifespan: a study of 78,284 men followed for up to 50 years

Improving standard practices in studies using results from basic human semen examination

Björndahl L et al., 2023 · Andrology · Free to read

The purpose of this article is to provide an explanation of the background behind a checklist that declares the laboratory methods used in a scientific study. It focuses primarily on implementing laboratory procedures to yield reliable results in basic semen examinations. While the World Health Organization (WHO) and international standards provide recommendations for basic semen examination, manuscripts submitted to Andrology frequently lack transparency regarding the specific techniques used. In addition, the terminology used for semen examination results often fails to provide a clear definition of the groups under study. Furthermore, the WHO's reference limits are often misinterpreted as strict boundaries between fertility and infertility. It is important to note that valid clinical andrological diagnoses and treatments cannot rely solely on semen examination results; they require proper laboratory procedures as a foundation for diagnosing and treating male patients. Therefore, scientific journals should promote the adoption of robust laboratory practices and an accurate definition of patient groups. A checklist can facilitate the design of high-quality studies and the creation of informative publications. Further, it can help journals assess submitted manuscripts and improve the overall quality of their publications.

Standards in semen examination: publishing reproducible and reliable data based on high-quality methodology

Björndahl L et al., 2022 · Human Reproduction

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism

Kristensen DM et al., 2018 · Proc Natl Acad Sci U S A · Free full text on PubMed Central

Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.

Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of 4,712 Men With Long-Term Follow-up

Latif T et al., 2017 · American journal of epidemiology

Semen quality has been suggested to be a biological marker of long-term morbidity and mortality; however, few studies have been conducted on this subject. We identified 5,370 men seen for infertility at Frederiksberg Hospital, Denmark, during 1977-2010, and 4,712 of these men were followed in the Danish National Patient Registry until first hospitalization, death, or the end of the study. We classified patients according to hospitalizations and the presence of cardiovascular disease, diabetes, testicular cancer, or prostate cancer. We found a clear association between sperm concentration below 15 million/mL and all-cause hospitalizations (hazard ratio = 1.5, 95% confidence interval: 1.4, 1.6) and cardiovascular disease (hazard ratio = 1.4, 95% confidence interval: 1.2, 1.6), compared with men with a concentration above 40 million/mL. The probabilities for hospitalizations were also higher with a low total sperm count and low motility. Men with a sperm concentration of 195-200 million/mL were, on average, hospitalized for the first time 7 years later than were men with a sperm concentration of 0-5 million/mL. Semen quality was associated with long-term morbidity, and a significantly higher risk of hospitalization was found, in particular for cardiovascular diseases and diabetes mellitus. Our study supports the suggestion that semen quality is a strong biomarker of general health.

Spermatozoa as harbingers of mortality: the curious link between semen quality and life expectancy

Aitken RJ, 2025 · Human reproduction (Oxford, England)

Lab-based semen parameters as predictors of long-term health in men-a systematic review

Nedelcu S et al., 2024 · Hum Reprod Open · Free full text on PubMed Central

Can semen parameters predict long-term health outcomes in men? There is a lack of evidence to suggest a higher risk of comorbidities in men with poor semen concentration. Male infertility has been long associated with a higher mortality risk and possibly higher chance of developing comorbidities but there has been less focus on semen analysis as a potential predictive factor. We searched PubMed/MEDLINE, EMBASE, and EBM databases from inception to December 2023. MESH term strategy: heading 1 ('OR', semen analysis, sperm count, sperm parameter*, male infertility, azoospermia, aspermia, oligospermia, teratozoospermia, asthenozoospermia) 'AND' heading 2 ('OR', morbidity, mortality, diabetes, cancer, cardiovascular, death, hypertension, stroke, long-term health). We included all studies that analyzed the risk of mortality and/or future development of comorbidities in men with at least one semen analysis. Case series and reviews were excluded. A narrative synthesis was done for all studies and meta-analysis where possible. Odds ratio (ORs) (95% CI, P-value) were calculated for all men with one suboptimal semen parameter and associated with the risk of a particular outcome. The risk of bias was assessed with QUADAS-2. MAIN Twenty-one studies were finally included. There was either a high or unclear risk of bias in all studies. The results only allowed for meta-analysis on categories of sperm concentration. We found a 2-fold increase in mortality risk in azoospermic men compared to oligospermic (OR 1.96, 95% CI: 1.29-2.96) and normozoospermic (OR 2.00, 95% CI: 1.23-3.25) groups, but not in oligospermic compared to normozoospermic (OR 1.04, 95% CI: 0.52-2.09). There was no difference in risk of cardiovascular disease in any of the sperm concentration groups (azoospermic-oligospermic OR 0.94, 95% CI: 0.74-1.20, azoospermic-normozoospermic OR 1.11, 95% CI: 0.71-1.75, and oligospermic-normozoospermic OR 1.12, 95% CI: 0.80-1.55). OR for diabetes in azoospermic men was higher only compared to oligospermic (OR 2.16, 95% CI: 1.55-3.01). The risk of all-site cancer was higher in azoospermic men compared to oligospermic (OR 2.16, 95% CI: 1.55-3.01) and normozoospermic (OR 2.18, 95% CI: 1.20-3.96). Only azoospermic men might be at higher risk of testicular cancer when compared to men with normal sperm concentration (OR 1.80, 95% CI: 1.12-2.89). LIMITATIONS Although our pooled analysis shows an increased risk of mortality and all-site cancer risk in azoospermic men, the results show a lack of evidence to suggest a higher risk of comorbidities in men with poor semen concentration. Given the limited available data, the nature of the studies, and the high risk of bias, the results should be interpreted with caution. There is not enough data to confirm the usability of semen analysis as a predictor of poor long-term health in men, especially within the general population. No funding was obtained for this study. A.M. has received funding from Merck Serono, Ferring, Gedeon Richter, Pharmasure, and Cook Medical to attend medical conferences; has been a participant in an advisory board for Ferring; and has given an invited lecture for a Merck Serono advisory board. S.N. has received funding for medical conference attendance from Ferring and Cook Medical. PROSPERO No. CRD42024507563.

Study on Influencing Factors of Semen Quality in Fertile Men

Wang N et al., 2022 · Front Physiol · Free full text on PubMed Central

To establish a system for evaluation of semen quality in fertile men by factor analysis (FA). The FA method was used to analyze five sperm test indicators for fertile men (sperm pH, sperm motility, sperm progressive motility, semen density, and total sperm number) to determine the evaluation standard of semen quality. Pearson analysis was adopted for correlation testing. The comprehensive score formula for semen quality of normal fertile men was as follows: comprehensive score of semen quality = (0.38272 F(1) + 0.36359 F(2) + 0.20018 F (3))/94.699. Across the whole fertile population, semen quality was found to be correlated with abstinence period, age of first spermatorrhea, and frequency of intercourse. Smoking, drinking, and place of residence were correlated with semen quality in the high semen quality population. In the population with medium semen quality, only the abstinence period was associated with semen quality. It is feasible to evaluate the semen quality of fertile men using the FA method. The comprehensive indicators of semen volume, sperm motility, and semen pH can be used as evaluative measures. Across the whole fertile population, the abstinence period and age of first spermatorrhea were correlated with semen quality. In the high semen quality population, smoking and drinking were negatively correlated with semen quality, and participants living in rural areas had better semen quality.

Investigating male factors and their relationships with reproductive health outcomes: a case-control study protocol for Towards Optimal Fertility, Fathering, and Fatherhood studY (TOFFFY) in Singapore

Ku CW et al., 2025 · BMJ open · Free full text on PubMed Central

Despite the global prevalence of low fertility rates, male contributions to fertility and reproductive health outcomes have been understudied. This study aims to investigate the male contribution to fertility and explore the underlying biological mechanisms. Specifically, we aim to (1) identify male factors associated with successful pregnancy, (2) develop a fertility index incorporating modifiable factors for both males and females to predict pregnancy rate and (3) explore the relationship of male modifiable factors with semen parameters and molecular characteristics. We will conduct an unmatched case-control study involving 240 couples with impaired male fertility (cases) and 240 couples with normal male fertility (controls). Between July 2024 and June 2026, we will recruit 480 eligible couples from KK Women's and Children's Hospital, Singapore. Male and female participants will complete questionnaires on sociodemographics, general health and lifestyle factors, and their anthropometry and body fat composition will be measured. Blood and semen samples from the male participants will be collected for biochemical, molecular and semen analyses. Predictive male factors will be identified using the least absolute shrinkage and selection operator method, accounting for female factors. We will construct a logistic regression model incorporating both male and female factors to derive a fertility index, which will be evaluated using cross-validation on subsets of the study population. Multivariable linear regression will be used to explore relationships between male modifiable exposures and semen parameters. The study protocol has received approval from the Centralised Institutional Review Board of SingHealth (2024/2120), Singapore. Participants will provide written informed consent. Study results will be disseminated through conferences and peer-reviewed scientific journals. NCT06293235.