Latif, T., Kold Jensen, T., Mehlsen, J., Holmboe, S. A., Brinth, L., Pors, K., Skouby, S. O., Jørgensen, N., & Lindahl-Jacobsen, R. (2017). Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of 4,712 Men With Long-Term Follow-up. American journal of epidemiology, 186(8), 910-917. https://doi.org/10.1093/aje/kwx067
Latif T, Kold Jensen T, Mehlsen J, Holmboe SA, Brinth L, Pors K, Skouby SO, Jørgensen N, Lindahl-Jacobsen R. Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of 4,712 Men With Long-Term Follow-up. American journal of epidemiology. 2017;186(8):910-917. doi:10.1093/aje/kwx067
Latif, T., et al. "Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of 4,712 Men With Long-Term Follow-up." American journal of epidemiology, vol. 186, no. 8, 2017, pp. 910-917.
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Abstract
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.
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.
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.
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.
Male Endocrine and Genetic Factors · Male Hormonal Axis
Some evidence suggests that infertile men, who are at increased risk for hypogonadism, metabolic derangements, and osteoporosis, have higher long-term morbidity and mortality than controls, but data are scarce and not conclusive.
We tested whether semen quality and reproductive function could represent a marker of general male health.
DESIGN, SETTING, A retrospective study of 5177 individuals from a prospectively collected database of 11516 males of infertile couples who had semen analysis in a tertiary university center.
OUTCOME MEASUREMENTS Of them, 5177 had all data for reproductive hormones, testis ultrasound, and biochemical determinations for glucose and lipid metabolism. Hypogonadism was defined as testosterone <10.5nmol/l and/or luteinizing hormone >9.4 IU/l. Individuals with a total sperm count of <10 million had genetic testing (karyotype, Y chromosome microdeletions, and CFTR gene mutations) and those with hypogonadism underwent dual-energy x-ray absorptiometry for bone mineral density. Descriptive statistics and odds ratio (OR) calculation were used.
Men with a low sperm count (<39 million/ejaculate) are at a high risk of hypogonadism (OR 12.2, 95% confidence interval [CI] 10.2-14.6) and have higher body mass index, waist circumference, systolic pressure, low-density lipoprotein cholesterol, triglycerides, and homeostatic model assessment (HOMA) index; lower high-density lipoprotein cholesterol; and a higher prevalence of metabolic syndrome (OR 1.246, 95 CI 1.005-1.545). All data are worse in men with hypogonadism, but a low sperm count per se is associated with a poor metabolic parameter. Men with hypogonadism have lower bone mineral density and 51% prevalence of osteoporosis/osteopenia. Longitudinal studies are necessary to support these data.
This is the largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment, performed in men referred for fertility evaluation. A low sperm count is associated with poorer metabolic, cardiovascular, and bone health. Hypogonadism is mainly involved in this association, but a low sperm count in itself is a marker of general health.
This large study evaluated semen quality, reproductive function, and metabolic risk in men referred for fertility evaluation, and showed that a man's semen count is a marker of his general health. Men with low sperm counts are more likely than those with normal sperm counts to have greater body fat, higher blood pressure, higher "bad" (low-density lipoprotein) cholesterol and triglycerides, and lower "good" (high-density lipoprotein) cholesterol. They also have a higher frequency of metabolic syndrome and insulin resistance, a condition that can lead to diabetes. Men with low sperm counts had a 12-fold increased risk of hypogonadism or low testosterone levels, and half of them had osteoporosis or low bone mass. Fertility evaluation gives men the unique opportunity for health assessment and disease prevention.
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.
Delbarba A et al., 2025·Andrology·Free full text on PubMed Central
The potential impact of diabetes mellitus type 1 (DM1) on male fertility is currently poorly defined. Hyperglycaemia and insulin deficiency may affect spermatogenesis. Some evidence suggests that men with DM1 have a significant reduction in progressive sperm motility, sperm morphology and semen volume, without significant changes in sperm concentration and count, but definite data are lacking.
To evaluate the impact of DM1 on clinical parameters related to male fertility and semen analysis.
We compared a court of 42 male DM1 patients with 43 nondiabetic subjects overlapping in age and remaining clinical data in an observational case-control study. All subjects underwent a comprehensive andrological reproductive evaluation, including medical history, physical examination, and semen analysis. We collected biochemical data in all patients with DM1, while diabetic patients with any alteration in semen parameters underwent sperm culture and scrotal ultrasound. In addition, all men completed the IIEF-5 questionnaire (International Index of Erectile Function-5) and the AMS (Aging Male Symptom score) questionnaire.
Patients with DM1 had a higher prevalence of infertility, erectile dysfunction and worse semen parameters compared with controls. In particular, semen volume, total sperm count, and total and progressive sperm motility were significantly lower (p < 0.001, p = 0.003, p = 0.048, and p = 0.022 respectively). In addition, the rate of semen anti-sperm antibody positivity, the AMS score and FSH levels were higher.
Several mechanisms may contribute to these semen alterations in DM1 patients, such as oxidative damage to spermatogenesis, seminal infections and pelvic neurological changes. These data suggest that patients with DM1 should be counselled from an andrological-reproductive point of view.
Male Fertility › Semen Analysis › Reference Standards
PMID 28498890 28498890 DOI 10.1093/aje/kwx067 10.1093/aje/kwx067 Latif et al. 2017, Latif 2017
Cite this article
Latif, T., Kold Jensen, T., Mehlsen, J., Holmboe, S. A., Brinth, L., Pors, K., Skouby, S. O., Jørgensen, N., & Lindahl-Jacobsen, R. (2017). Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of 4,712 Men With Long-Term Follow-up. American journal of epidemiology, 186(8), 910-917. https://doi.org/10.1093/aje/kwx067
Latif T, Kold Jensen T, Mehlsen J, Holmboe SA, Brinth L, Pors K, Skouby SO, Jørgensen N, Lindahl-Jacobsen R. Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of 4,712 Men With Long-Term Follow-up. American journal of epidemiology. 2017;186(8):910-917. doi:10.1093/aje/kwx067
Latif, T., et al. "Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of 4,712 Men With Long-Term Follow-up." American journal of epidemiology, vol. 186, no. 8, 2017, pp. 910-917.