Agarwal, A. et al. Male infertility. Lancet 397, 319–333 (2021).
Google Scholar
Sharlip, I. D. et al. Best practice policies for male infertility. Fertil. Steril. 77, 873–882 (2002).
Google Scholar
Fisher, J. R. & Hammarberg, K. Psychological and social aspects of infertility in men: an overview of the evidence and implications for psychologically informed clinical care and future research. Asian J. Androl. 14, 121–129 (2012).
Google Scholar
Hammarberg, K., Collins, V., Holden, C., Young, K. & McLachlan, R. Men’s knowledge, attitudes and behaviours relating to fertility. Hum. Reprod. Update 23, 458–480 (2017).
Google Scholar
Evens E. M. A global perspective on infertility an under recognized public health issue. Carolina Papers International Health No. 18 https://www.scribd.com/document/125595459/A-Global-Perspective-on-Infertility-an-Under-Recognized-Public-Health-Issue-original (2004).
Kimmins, S. et al. Frequency, morbidity and equity – the case for increased research on male fertility. Nat. Rev. Urol. 21, 102–124 (2024).
Google Scholar
Levine, H. et al. Temporal trends in sperm count: a systematic review and meta-regression analysis of samples collected globally in the 20th and 21st centuries. Hum. Reprod. Update 29, 157–176 (2023).
Google Scholar
Levine, H. et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum. Reprod. Update 23, 646–659 (2017).
Google Scholar
Cedars, M. I. et al. The sixth vital sign: what reproduction tells us about overall health. Proceedings from a NICHD/CDC workshop. Hum. Reprod. Open. 2017, hox008 (2017).
Google Scholar
Choy, J. T. & Eisenberg, M. L. Male infertility as a window to health. Fertil. Steril. 110, 810–814 (2018).
Google Scholar
Inhorn, M. C. & Patrizio, P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum. Reprod. Update 21, 411–426 (2015).
Google Scholar
Lee, T. Y. & Chu, T. Y. The Chinese experience of male infertility. West. J. Nurs. Res. 23, 714–725 (2001).
Google Scholar
Obst, K. L., Oxlad, M., Turnbull, D. & McPherson, N. O. “No one asked me if I’m alright”: a mixed-methods study exploring information/support needs and challenges engaging men diagnosed with male-factor infertility. Am. J. Mens Health 17, 15579883231209210 (2023).
Google Scholar
Sejbaek, C. S. et al. Depression among men in ART treatment: a register-based national cohort study. Hum. Reprod. Open. 2020, hoaa019 (2020).
Google Scholar
Fisher, J. R., Baker, G. H. & Hammarberg, K. Long-term health, well-being, life satisfaction, and attitudes toward parenthood in men diagnosed as infertile: challenges to gender stereotypes and implications for practice. Fertil. Steril. 94, 574–580 (2010).
Google Scholar
Greil, A. L., Slauson-Blevins, K. & McQuillan, J. The experience of infertility: a review of recent literature. Sociol. Health Illn. 32, 140–162 (2010).
Google Scholar
Institute for Health Metrics and Evaluation. Global burden of disease (GBD): institute for health metrics and evaluation. Institute for Health Metrics and Evaluation https://www.healthdata.org/research-analysis/gbd-data?trk=public_post-text (2021).
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. Am. J. Epidemiol. 186, 910–917 (2017).
Google Scholar
Inhorn, M. C. Global infertility and the globalization of new reproductive technologies: illustrations from Egypt. Soc. Sci. Med. 56, 1837–1851 (2003).
Google Scholar
Dyer, S. J., Abrahams, N., Mokoena, N. E. & van der Spuy, Z. M. ‘You are a man because you have children’: experiences, reproductive health knowledge and treatment-seeking behaviour among men suffering from couple infertility in South Africa. Hum. Reprod. 19, 960–967 (2004).
Google Scholar
Björndahl, L. & Kirkman Brown, J. The sixth edition of the WHO laboratory manual for the examination and processing of human semen: ensuring quality and standardization in basic examination of human ejaculates. Fertil. Steril. 117, 246–251 (2022).
Google Scholar
Wang, C. & Swerdloff, R. S. Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests. Fertil. Steril. 102, 1502–1507 (2014).
Google Scholar
Pasqualotto, F. F. et al. High percentage of abnormal semen parameters in a prevasectomy population. Fertil. Steril. 85, 954–960 (2006).
Google Scholar
Bonde, J. P. et al. Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet 352, 1172–1177 (1998).
Google Scholar
Guzick, D. S. et al. Sperm morphology, motility, and concentration in fertile and infertile men. N. Engl. J. Med. 345, 1388–1393 (2001).
Google Scholar
Esteves, S. C. Evolution of the World Health Organization semen analysis manual: where are we? Nat. Rev. Urol. 19, 439–446 (2022).
Google Scholar
Zavos, P. M. & Goodpasture, J. C. Clinical improvements of specific seminal deficiencies via intercourse with a seminal collection device versus masturbation. Fertil. Steril. 51, 190–193 (1989).
Google Scholar
Pound, N., Javed, M. H., Ruberto, C., Shaikh, M. A. & Del Valle, A. P. Duration of sexual arousal predicts semen parameters for masturbatory ejaculates. Physiol. Behav. 76, 685–689 (2002).
Google Scholar
World Health Organization. WHO laboratory manual for the examination and processing of human semen 5th edn (World Health Organization, 2010).
Slama, R. et al. Time to pregnancy and semen parameters: a cross-sectional study among fertile couples from four European cities. Hum. Reprod. 17, 503–515 (2002).
Google Scholar
Ayala, C., Steinberger, E. & Smith, D. P. The influence of semen analysis parameters on the fertility potential of infertile couples. J. Androl. 17, 718–725 (1996).
Google Scholar
Zinaman, M. J., Brown, C. C., Selevan, S. G. & Clegg, E. D. Semen quality and human fertility: a prospective study with healthy couples. J. Androl. 21, 145–153 (2000).
Google Scholar
Keihani, S. et al. Semen parameter thresholds and time-to-conception in subfertile couples: how high is high enough? Hum. Reprod. 36, 2121–2133 (2021).
Google Scholar
Robinson, L. et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum. Reprod. 27, 2908–2917 (2012).
Google Scholar
Cissen, M. et al. Measuring sperm DNA fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta-analysis. PLoS ONE 11, e0165125 (2016).
Google Scholar
Simon, L., Zini, A., Dyachenko, A., Ciampi, A. & Carrell, D. T. A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome. Asian J. Androl. 19, 80–90 (2017).
Google Scholar
Tan, J., Taskin, O., Albert, A. & Bedaiwy, M. A. Association between sperm DNA fragmentation and idiopathic recurrent pregnancy loss: a systematic review and meta-analysis. Reprod. Biomed. Online 38, 951–960 (2019).
Google Scholar
Agarwal, A. et al. Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios. Transl. Androl. Urol. 5, 935–950 (2016).
Google Scholar
Andrabi, S. W. et al. Fragmentation: causes, evaluation and management in male infertility. JBRA Assist. Reprod. 28, 306–319 (2024).
Google Scholar
Newman, H., Catt, S., Vining, B., Vollenhoven, B. & Horta, F. DNA repair and response to sperm DNA damage in oocytes and embryos, and the potential consequences in ART: a systematic review. Mol. Hum. Reprod. 28, gaab071 (2022).
Google Scholar
Peel, A., Saini, A., Deluao, J. C. & McPherson, N. O. Sperm DNA damage: the possible link between obesity and male infertility, an update of the current literature. Andrology 11, 1635–1652 (2023).
Google Scholar
Aitken, R. J. Impact of oxidative stress on male and female germ cells: implications for fertility. Reproduction 159, R189–R201 (2020).
Google Scholar
Jones, R., Mann, T. & Sherins, R. Peroxidative breakdown of phospholipids in human spermatozoa, spermicidal properties of fatty acid peroxides, and protective action of seminal plasma. Fertil. Steril. 31, 531–537 (1979).
Google Scholar
Alvarez, J. G., Touchstone, J. C., Blasco, L. & Storey, B. T. Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa. Superoxide dismutase as major enzyme protectant against oxygen toxicity. J. Androl. 8, 338–348 (1987).
Google Scholar
Aitken, R. J. & Clarkson, J. S. Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J. Reprod. Fertil. 81, 459–469 (1987).
Google Scholar
Bisht, S. & Dada, R. Oxidative stress: major executioner in disease pathology, role in sperm DNA damage and preventive strategies. Front. Biosci. 9, 420–447 (2017).
Google Scholar
O’Flaherty, C. & Matsushita-Fournier, D. Reactive oxygen species and protein modifications in spermatozoa. Biol. Reprod. 97, 577–585 (2017).
Google Scholar
Castleton, P. et al. MiOXSYS® and OxiSperm® II assays appear to provide no clinical utility for determining oxidative stress in human sperm-results from repeated semen collections. Andrology 11, 1566–1578 (2023).
Google Scholar
Heller, C. G. & Clermont, Y. Spermatogenesis in man: an estimate of its duration. Science 140, 184–186 (1963).
Google Scholar
Lyons, H. E. et al. The influence of lifestyle and biological factors on semen variability. J. Assist. Reprod. Genet. 41, 1097–1109 (2024).
Google Scholar
Li, Y. X. et al. Association between body mass index and semen quality: a systematic review and meta-analysis. Int. J. Obes. 48, 1383–1401 (2024).
Service, C. A., Puri, D., Al Azzawi, S., Hsieh, T. C. & Patel, D. P. The impact of obesity and metabolic health on male fertility: a systematic review. Fertil. Steril. 120, 1098–1111 (2023).
Google Scholar
Palmer, N. O., Bakos, H. W., Fullston, T. & Lane, M. Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis 2, 253–263 (2012).
Google Scholar
Leisegang, K., Sengupta, P., Agarwal, A. & Henkel, R. Obesity and male infertility: mechanisms and management. Andrologia 53, e13617 (2021).
Google Scholar
Neto, F. T., Bach, P. V., Najari, B. B., Li, P. S. & Goldstein, M. Spermatogenesis in humans and its affecting factors. Semin. Cell Dev. Biol. 59, 10–26 (2016).
Google Scholar
Schneider, G., Kirschner, M. A., Berkowitz, R. & Ertel, N. H. Increased estrogen production in obese men. J. Clin. Endocrinol. Metab. 48, 633–638 (1979).
Google Scholar
de Boer, H., Verschoor, L., Ruinemans-Koerts, J. & Jansen, M. Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism. Diabetes Obes. Metab. 7, 211–215 (2005).
Google Scholar
Escobar-Morreale, H. F., Santacruz, E., Luque-Ramírez, M. & Botella Carretero, J. I. Prevalence of ‘obesity-associated gonadal dysfunction’ in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis. Hum. Reprod. Update 23, 390–408 (2017).
Google Scholar
De Silva, N. L. et al. Male hypogonadism: pathogenesis, diagnosis, and management. Lancet Diabetes Endocrinol. 12, 761–774 (2024).
Google Scholar
Yeh, S. et al. Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues. Proc. Natl Acad. Sci. USA 99, 13498–13503 (2002).
Google Scholar
Smith, L. B. & Walker, W. H. The regulation of spermatogenesis by androgens. Semin. Cell Dev. Biol. 30, 2–13 (2014).
Google Scholar
Gutorova, N. V., Kleshchyov, M. A., Tipisova, E. V. & Osadchuk, L. V. Effects of overweight and obesity on the spermogram values and levels of reproductive hormones in the male population of the European north of Russia. Bull. Exp. Biol. Med. 157, 95–98 (2014).
Google Scholar
Jensen, T. K. et al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil. Steril. 82, 863–870 (2004).
Google Scholar
Liu, Y. & Ding, Z. Obesity, a serious etiologic factor for male subfertility in modern society. Reproduction 154, R123–R131 (2017).
Google Scholar
Diamanti-Kandarakis, E. et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr. Rev. 30, 293–342 (2009).
Google Scholar
Kumar, N. & Singh, A. K. Impact of environmental factors on human semen quality and male fertility: a narrative review. Environ. Sci. Eur. 34, 1–13 (2022).
Google Scholar
Ge, R. S., Chen, G. R., Tanrikut, C. & Hardy, M. P. Phthalate ester toxicity in Leydig cells: developmental timing and dosage considerations. Reprod. Toxicol. 23, 366–373 (2007).
Google Scholar
Garza, S. et al. Mitochondrial dynamics, Leydig cell function, and age-related testosterone deficiency. FASEB J. 36, e22637 (2022).
Google Scholar
Ješeta, M. et al. Overview of the mechanisms of action of selected bisphenols and perfluoroalkyl chemicals on the male reproductive axes. Front. Genet. 12, 692897 (2021).
Google Scholar
Knez, J., Kranvogl, R., Breznik, B. P., Vončina, E. & Vlaisavljević, V. Are urinary bisphenol A levels in men related to semen quality and embryo development after medically assisted reproduction? Fertil. Steril. 101, 215–221.e5 (2014).
Google Scholar
Radwan, M. et al. Urinary bisphenol A levels and male fertility. Am. J. Mens Health 12, 2144–2151 (2018).
Google Scholar
Adoamnei, E. et al. Urinary bisphenol A concentrations are associated with reproductive parameters in young men. Env. Res. 161, 122–128 (2018).
Google Scholar
Lü, L. et al. Exposure interferes with reproductive hormones and decreases sperm counts: a systematic review and meta-analysis of epidemiological studies. Toxics 12, 294 (2024).
Google Scholar
Goldstone, A. E., Chen, Z., Perry, M. J., Kannan, K. & Louis, G. M. Urinary bisphenol A and semen quality, the LIFE study. Reprod. Toxicol. 51, 7–13 (2015).
Google Scholar
Jeseta, M. et al. Cross sectional study on exposure to BPA and its analogues and semen parameters in Czech men. Env. Pollut. 345, 123445 (2024).
Google Scholar
Mruk, D. D. & Cheng, C. Y. The mammalian blood-testis barrier: its biology and regulation. Endocr. Rev. 36, 564–591 (2015).
Google Scholar
Siu, E. R. et al. An occludin-focal adhesion kinase protein complex at the blood-testis barrier: a study using the cadmium model. Endocrinology 150, 3336–3344 (2009).
Google Scholar
Chung, N. P. & Cheng, C. Y. Is cadmium chloride-induced inter-Sertoli tight junction permeability barrier disruption a suitable in vitro model to study the events of junction disassembly during spermatogenesis in the rat testis? Endocrinology 142, 1878–1888 (2001).
Google Scholar
el-Sabeawy, F. et al. Treatment of rats during pubertal development with 2,3,7,8-tetrachlorodibenzo-p-dioxin alters both signaling kinase activities and epidermal growth factor receptor binding in the testis and the motility and acrosomal reaction of sperm. Toxicol. Appl. Pharmacol. 150, 427–442 (1998).
Google Scholar
World Health Organization. Dioxins. WHO https://www.who.int/news-room/fact-sheets/detail/dioxins-and-their-effects-on-human-health (2023).
Xiao, X. et al. Differential effects of c-Src and c-Yes on the endocytic vesicle-mediated trafficking events at the Sertoli cell blood-testis barrier: an in vitro study. Am. J. Physiol. Endocrinol. Metab. 307, E553–E562 (2014).
Google Scholar
Xiao, X., Mruk, D. D., Cheng, F. L. & Cheng, C. Y. C-Src and c-Yes are two unlikely partners of spermatogenesis and their roles in blood-testis barrier dynamics. Adv. Exp. Med. Biol. 763, 295–317 (2012).
Google Scholar
Mocarelli, P. et al. Dioxin exposure, from infancy through puberty, produces endocrine disruption and affects human semen quality. Environ. Health Perspect. 116, 70–77 (2008).
Google Scholar
Quintanilla-Vega, B. et al. Lead interaction with human protamine (HP2) as a mechanism of male reproductive toxicity. Chem. Res. Toxicol. 13, 594–600 (2000).
Google Scholar
Ratcliffe, J. M. et al. Semen quality in papaya workers with long term exposure to ethylene dibromide. Br. J. Ind. Med. 44, 317–326 (1987).
Google Scholar
Schrader, S. M., Turner, T. W. & Ratcliffe, J. M. The effects of ethylene dibromide on semen quality: a comparison of short-term and chronic exposure. Reprod. Toxicol. 2, 191–198 (1988).
Google Scholar
Amir, D. The spermicidal effect of ethylene dibromide in bulls and rams. Mol. Reprod. Dev. 28, 99–109 (1991).
Google Scholar
Meistrich, M. L. Effects of chemotherapy and radiotherapy on spermatogenesis in humans. Fertil. Steril. 100, 1180–1186 (2013).
Google Scholar
Duffin, K. et al. Impacts of cancer therapy on male fertility: past and present. Mol. Aspects Med. 100, 101308 (2024).
Google Scholar
Vakalopoulos, I., Dimou, P., Anagnostou, I. & Zeginiadou, T. Impact of cancer and cancer treatment on male fertility. Hormones 14, 579–589 (2015).
Google Scholar
Aitken, R. J., Smith, T. B., Jobling, M. S., Baker, M. A. & De Iuliis, G. N. Oxidative stress and male reproductive health. Asian J. Androl. 16, 31–38 (2014).
Google Scholar
Wright, C., Milne, S. & Leeson, H. Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility. Reprod. Biomed. Online 28, 684–703 (2014).
Google Scholar
Aitken, R. J., Jones, K. T. & Robertson, S. A. Reactive oxygen species and sperm function-in sickness and in health. J. Androl. 33, 1096–1106 (2012).
Google Scholar
Aitken, R. J., Drevet, J. R., Moazamian, A. & Gharagozloo, P. Male infertility and oxidative stress: a focus on the underlying mechanisms. Antioxidants 11, 306 (2022).
Google Scholar
Aitken, R. J., Wingate, J. K., De Iuliis, G. N., Koppers, A. J. & McLaughlin, E. A. Cis-unsaturated fatty acids stimulate reactive oxygen species generation and lipid peroxidation in human spermatozoa. J. Clin. Endocrinol. Metab. 91, 4154–4163 (2006).
Google Scholar
Aitken, R. J. et al. Electrophilic aldehydes generated by sperm metabolism activate mitochondrial reactive oxygen species generation and apoptosis by targeting succinate dehydrogenase. J. Biol. Chem. 287, 33048–33060 (2012).
Google Scholar
Calamera, J., Buffone, M., Ollero, M., Alvarez, J. & Doncel, G. F. Superoxide dismutase content and fatty acid composition in subsets of human spermatozoa from normozoospermic, asthenozoospermic, and polyzoospermic semen samples. Mol. Reprod. Dev. 66, 422–430 (2003).
Google Scholar
Aitken, R. J., Clarkson, J. S. & Fishel, S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol. Reprod. 41, 183–197 (1989).
Google Scholar
Sanocka, D. & Kurpisz, M. Reactive oxygen species and sperm cells. Reprod. Biol. Endocrinol. 2, 12 (2004).
Google Scholar
Aitken, R. J., Gibb, Z., Baker, M. A., Drevet, J. & Gharagozloo, P. Causes and consequences of oxidative stress in spermatozoa. Reprod. Fertil. Dev. 28, 1–10 (2016).
Google Scholar
Aboulmaouahib, S. et al. Impact of alcohol and cigarette smoking consumption in male fertility potential: looks at lipid peroxidation, enzymatic antioxidant activities and sperm DNA damage. Andrologia 50, e12926 (2018).
Google Scholar
He, Y. et al. Ketamine inhibits human sperm function by Ca2+-related mechanism. Biochem. Biophys. Res. Commun. 478, 501–506 (2016).
Google Scholar
Safarinejad, M. R. et al. The effects of opiate consumption on serum reproductive hormone levels, sperm parameters, seminal plasma antioxidant capacity and sperm DNA integrity. Reprod. Toxicol. 36, 18–23 (2013).
Google Scholar
Amor, H., Hammadeh, M. E., Mohd, I. & Jankowski, P. M. Impact of heavy alcohol consumption and cigarette smoking on sperm DNA integrity. Andrologia 54, e14434 (2022).
Google Scholar
Nazmara, Z. et al. Correlation between protamine-2 and miRNA-122 in sperm from heroin-addicted men: a case-control study. Urol. J. 17, 638–644 (2020).
Google Scholar
Imhof ML, J. Lipovac, M. Chedraui, P. Riedl, C. Improvement of sperm quality after micronutrient supplementation. ESPEN J. 7, e50–e53 (2012).
Nguyen, N. D., Le, M. T., Tran, N. Q. T., Nguyen, Q. H. V. & Cao, T. N. Micronutrient supplements as antioxidants in improving sperm quality and reducing DNA fragmentation. Basic. Clin. Androl. 33, 23 (2023).
Google Scholar
Lipovac, M., Nairz, V., Aschauer, J. & Riedl, C. The effect of micronutrient supplementation on spermatozoa DNA integrity in subfertile men and subsequent pregnancy rate. Gynecol. Endocrinol. 37, 711–715 (2021).
Google Scholar
Komiya, A. et al. Results of lifestyle modification promotion and reproductive/general health check for male partners of couples seeking conception. Heliyon 9, e15203 (2023).
Google Scholar
Eisenberg, M. L. et al. Semen quality, infertility and mortality in the USA. Hum. Reprod. 29, 1567–1574 (2014).
Google Scholar
Del Giudice, F. et al. The association between mortality and male infertility: systematic review and meta-analysis. Urology 154, 148–157 (2021).
Google Scholar
Glazer, C. H. et al. Male factor infertility and risk of death: a nationwide record-linkage study. Hum. Reprod. 34, 2266–2273 (2019).
Google Scholar
Shiraishi, K. & Matsuyama, H. Effects of medical comorbidity on male infertility and comorbidity treatment on spermatogenesis. Fertil. Steril. 110, 1006–11.e2 (2018).
Google Scholar
Ventimiglia, E. et al. Infertility as a proxy of general male health: results of a cross-sectional survey. Fertil. Steril. 104, 48–55 (2015).
Google Scholar
Hales C. M., Carroll M. D., Fryar C. D., Ogden C. L. Prevalence of obesity and severe obesity among adults: United States, 2017–2018. NCHS Data Brief. 1–8 (2020).
Hales, C. N. Metabolic consequences of intrauterine growth retardation. Acta Paediatr. 86, 184–187 (1997).
Google Scholar
Yeh, T. L. et al. The relationship between metabolically healthy obesity and the risk of cardiovascular disease: a systematic review and meta-analysis. J. Clin. Med. 8, 1228 (2019).
Google Scholar
Salas-Huetos, A. et al. Male adiposity, sperm parameters and reproductive hormones: an updated systematic review and collaborative meta-analysis. Obes. Rev. 22, e13082 (2021).
Google Scholar
Sepidarkish, M. et al. The effect of body mass index on sperm DNA fragmentation: a systematic review and meta-analysis. Int. J. Obes. 44, 549–558 (2020).
Google Scholar
Lotti, F., Marchiani, S., Corona, G. & Maggi, M. Metabolic syndrome and reproduction. Int. J. Mol. Sci. 22, 1988 (2021).
Google Scholar
Ehala-Aleksejev, K. & Punab, M. The effect of metabolic syndrome on male reproductive health: a cross-sectional study in a group of fertile men and male partners of infertile couples. PLoS ONE 13, e0194395 (2018).
Google Scholar
Dupont, C. et al. Metabolic syndrome and smoking are independent risk factors of male idiopathic infertility. Basic. Clin. Androl. 29, 9 (2019).
Google Scholar
Zhao, L. & Pang, A. Effects of metabolic syndrome on semen quality and circulating sex hormones: a systematic review and meta-analysis. Front. Endocrinol. 11, 428 (2020).
Google Scholar
Pergialiotis, V. et al. Diabetes mellitus and functional sperm characteristics: a meta-analysis of observational studies. J. Diabetes Complications 30, 1167–1176 (2016).
Google Scholar
Torres, M. et al. Male fertility is reduced by chronic intermittent hypoxia mimicking sleep apnea in mice. Sleep 37, 1757–1765 (2014).
Google Scholar
McLachlan, R. I. Approach to the patient with oligozoospermia. J. Clin. Endocrinol. Metab. 98, 873–880 (2013).
Google Scholar
Lundy, S. D. & Vij, S. C. Male infertility in renal failure and transplantation. Transl. Androl. Urol. 8, 173–181 (2019).
Google Scholar
Zhang, Q. F. et al. Does COVID-19 affect sperm quality in males? the answer may be yes, but only temporarily. Virol. J. 21, 24 (2024).
Google Scholar
Basaria, S. Male hypogonadism. Lancet 383, 1250–1263 (2014).
Google Scholar
Bojesen, A., Juul, S. & Gravholt, C. H. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J. Clin. Endocrinol. Metab. 88, 622–626 (2003).
Google Scholar
Herlihy, A. S., Halliday, J. L., Cock, M. L. & McLachlan, R. I. The prevalence and diagnosis rates of Klinefelter syndrome: an Australian comparison. Med. J. Aust. 194, 24–28 (2011).
Google Scholar
Deebel, N. A., Bradshaw, A. W. & Sadri-Ardekani, H. Infertility considerations in Klinefelter syndrome: from origin to management. Best. Pract. Res. Clin. Endocrinol. Metab. 34, 101480 (2020).
Google Scholar
Kanakis, G. A. & Nieschlag, E. Klinefelter syndrome: more than hypogonadism. Metabolism 86, 135–144 (2018).
Google Scholar
Clemente-Suárez, V. J., Beltrán-Velasco, A. I., Redondo-Flórez, L., Martín-Rodríguez, A. & Tornero-Aguilera, J. F. Global impacts of western diet and its effects on metabolism and health: a narrative review. Nutrients 15, 2749 (2023).
Google Scholar
Naidu, R. et al. Chemical pollution: a growing peril and potential catastrophic risk to humanity. Env. Int. 156, 106616 (2021).
Google Scholar
World Health Organization. Overweight prevalence among children under 5 years of age (%weight-for-height >+2 SD). WHO https://www.who.int/data/gho/data/indicators/indicator-details/GHO/gho-jme-country-children-aged-5-years-overweight-(-weight-for-height-2-sd) (2025).
World Health Organisation. Global status report on noncommunicable diseases 2010. (World Health Organisation, 2011).
Heindel, J. J., Lustig, R. H., Howard, S. & Corkey, B. E. Obesogens: a unifying theory for the global rise in obesity. Int. J. Obes. 48, 449–460 (2024).
Google Scholar
Cancer Australia. Cancer incidence. Cancer Australia https://ncci.canceraustralia.gov.au/diagnosis/cancer-incidence/cancer-incidence (2024).
van Oostrom, S. H. et al. Time trends in prevalence of chronic diseases and multimorbidity not only due to aging: data from general practices and health surveys. PLoS ONE 11, e0160264 (2016).
Google Scholar
Ward, B. W. & Schiller, J. S. Prevalence of multiple chronic conditions among US adults: estimates from the National Health Interview Survey, 2010. Prev. Chronic Dis. 10, E65 (2013).
Google Scholar
Cristodoro, M., Zambella, E., Fietta, I., Inversetti, A. & Di Simone, N. Dietary patterns and fertility. Biology 13, 131 (2024).
Google Scholar
Salas-Huetos, A., Babio, N., Carrell, D. T., Bulló, M. & Salas-Salvadó, J. Adherence to the Mediterranean diet is positively associated with sperm motility: a cross-sectional analysis. Sci. Rep. 9, 3389 (2019).
Google Scholar
Ricci, E. et al. Semen quality and alcohol intake: a systematic review and meta-analysis. Reprod. Biomed. Online 34, 38–47 (2017).
Google Scholar
Gaskins, A. J., Colaci, D. S., Mendiola, J., Swan, S. H. & Chavarro, J. E. Dietary patterns and semen quality in young men. Hum. Reprod. 27, 2899–2907 (2012).
Google Scholar
Caruso, P. et al. Effects of Mediterranean diet on semen parameters in healthy young adults: a randomized controlled trial. Minerva Endocrinol. 45, 280–287 (2020).
Google Scholar
Montano, L. et al. Effects of a lifestyle change intervention on semen quality in healthy young men living in highly polluted areas in Italy: the FASt randomized controlled trial. Eur. Urol. Focus. 8, 351–359 (2022).
Google Scholar
Walsh, T. J., Croughan, M. S., Schembri, M., Chan, J. M. & Turek, P. J. Increased risk of testicular germ cell cancer among infertile men. Arch. Intern. Med. 169, 351–356 (2009).
Google Scholar
Walsh, T. J. et al. Increased risk of high-grade prostate cancer among infertile men. Cancer 116, 2140–2147 (2010).
Google Scholar
Eisenberg, M. L., Li, S., Brooks, J. D., Cullen, M. R. & Baker, L. C. Increased risk of cancer in infertile men: analysis of U.S. claims data. J. Urol. 193, 1596–1601 (2015).
Google Scholar
Hanson, H. A. et al. Subfertility increases risk of testicular cancer: evidence from population-based semen samples. Fertil. Steril. 105, 322–8.e1 (2016).
Google Scholar
Schultz, N., Hamra, F. K. & Garbers, D. L. A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets. Proc. Natl Acad. Sci. USA 100, 12201–12206 (2003).
Google Scholar
Mukherjee, S., Ridgeway, A. D. & Lamb, D. J. DNA mismatch repair and infertility. Curr. Opin. Urol. 20, 525–532 (2010).
Google Scholar
Belladelli, F., Basran, S. & Eisenberg, M. L. Male fertility and physical exercise. World J. Mens Health 41, 482–488 (2023).
Google Scholar
Gaskins, A. J. et al. Paternal physical and sedentary activities in relation to semen quality and reproductive outcomes among couples from a fertility center. Hum. Reprod. 29, 2575–2582 (2014).
Google Scholar
American Heart Association. Lifestyle changes to prevent a heart attack. American Heart Association https://www.heart.org/en/health-topics/heart-attack/life-after-a-heart-attack/lifestyle-changes-for-heart-attack-prevention (2025).
Mayo Clinic. Strategies to prevent heart disease. Mayo Clinic https://www.mayoclinic.org/diseases-conditions/heart-disease/in-depth/heart-disease-prevention/art-20046502 (2023).
Kim, H. L. et al. Lifestyle modification in the management of metabolic syndrome: statement from Korean society of cardiometabolic syndrome (KSCMS). Korean Circ. J. 52, 93–109 (2022).
Google Scholar
Oh, S., Kim, E. & Shoda, J. Editorial: lifestyle modification strategies as first line of chronic disease management. Front. Physiol. 14, 1204581 (2023).
Google Scholar
Greaves, C. J. et al. Systematic review of reviews of intervention components associated with increased effectiveness in dietary and physical activity interventions. BMC Public. Health 11, 119 (2011).
Google Scholar
Rhodes, R. E., Janssen, I., Bredin, S. S. D., Warburton, D. E. R. & Bauman, A. Physical activity: health impact, prevalence, correlates and interventions. Psychol. Health 32, 942–975 (2017).
Google Scholar
Cleland, V. et al. Effectiveness of interventions to promote physical activity and/or decrease sedentary behaviour among rural adults: a systematic review and meta-analysis. Obes. Rev. 18, 727–741 (2017).
Google Scholar
Rippe, J. M. Lifestyle strategies for risk factor reduction, prevention, and treatment of cardiovascular disease. Am. J. Lifestyle Med. 13, 204–212 (2019).
Google Scholar
Darkins, A., Kendall, S., Edmonson, E., Young, M. & Stressel, P. Reduced cost and mortality using home telehealth to promote self-management of complex chronic conditions: a retrospective matched cohort study of 4,999 veteran patients. Telemed. J. E Health 21, 70–76 (2015).
Google Scholar
Darkins, A. et al. Care coordination/home telehealth: the systematic implementation of health informatics, home telehealth, and disease management to support the care of veteran patients with chronic conditions. Telemed. J. E Health 14, 1118–1126 (2008).
Google Scholar
McCarthy D. Kaiser Permanente: bridging the quality divide with integrated practice, group accountability, and health information technology. The Commonwealth Fund https://www.commonwealthfund.org/publications/case-study/2009/jun/kaiser-permanente-bridging-quality-divide-integrated-practice (2009).
Rivera, A. & Scholar, J. Traditional masculinity: a review of toxicity rooted in social norms and gender socialization. ANS Adv. Nurs. Sci. 43, E1–E10 (2020).
Google Scholar
Burton M. Negotiating masculinity: how infertility impacts hegemonic masculinity. LUJA 1, 49–57 (2014).
Pakpahan, C. et al. “Masculine?” A metasynthesis of qualitative studies on traditional masculinity on infertility. F1000Res 12, 252 (2023).
Google Scholar
Trussell, J. C. et al. Association between testosterone, semen parameters, and live birth in men with unexplained infertility in an intrauterine insemination population. Fertil. Steril. 111, 1129–1134 (2019).
Google Scholar
Cervi LK, D. Organising male infertility: masculinities and fertility treatment. Gend. Work. Organ. 29, 1113–1131 (2022).
Google Scholar
Clarke, M. J., Marks, A. D. & Lykins, A. D. Effect of normative masculinity on males’ dysfunctional sexual beliefs, sexual attitudes, and perceptions of sexual functioning. J. Sex. Res. 52, 327–337 (2015).
Google Scholar
Malik, S. H. & Coulson, N. The male experience of infertility: a thematic analysis of an online infertility support group bulletin board. J. Reprod. Infant Psychol. 26, 18–30 (2008).
Google Scholar
Peronace, L. A., Boivin, J. & Schmidt, L. Patterns of suffering and social interactions in infertile men: 12 months after unsuccessful treatment. J. Psychosom. Obstet. Gynaecol. 28, 105–114 (2007).
Google Scholar
Culley, L., Hudson, N. & Lohan, M. Where are all the men? The marginalization of men in social scientific research on infertility. Reprod. Biomed. Online 27, 225–235 (2013).
Google Scholar
Wischmann, T. & Thorn, P. (Male) infertility: what does it mean to men? New evidence from quantitative and qualitative studies. Reprod. Biomed. Online 27, 236–243 (2013).
Google Scholar
Mikkelsen, A. T., Madsen, S. A. & Humaidan, P. Psychological aspects of male fertility treatment. J. Adv. Nurs. 69, 1977–1986 (2013).
Google Scholar
Arya, S. T. & Dibb, B. The experience of infertility treatment: the male perspective. Hum. Fertil. 19, 242–248 (2016).
Google Scholar
Tabong, P. T. & Adongo, P. B. Understanding the social meaning of infertility and childbearing: a qualitative study of the perception of childbearing and childlessness in Northern Ghana. PLoS ONE 8, e54429 (2013).
Google Scholar
Inhorn, M. C. Middle Eastern masculinities in the age of new reproductive technologies: male infertility and stigma in Egypt and Lebanon. Med. Anthropol. Q. 18, 162–182 (2004).
Google Scholar
Serour, G. I. & Serour, A. G. The impact of religion and culture on medically assisted reproduction in the Middle East and Europe. Reprod. Biomed. Online 43, 421–433 (2021).
Google Scholar
Nimbi, F. M., Tripodi, F., Rossi, R., Navarro-Cremades, F. & Simonelli, C. Male sexual desire: an overview of biological, psychological, sexual, relational, and cultural factors influencing desire. Sex. Med. Rev. 8, 59–91 (2020).
Google Scholar
Coward, R. M. et al. Fertility related quality of life, gonadal function and erectile dysfunction in male partners of couples with unexplained infertility. J. Urol. 202, 379–384 (2019).
Google Scholar
Ozkan, B., Orhan, E., Aktas, N. & Coskuner, E. R. Depression and sexual dysfunction in Turkish men diagnosed with infertility. Urology 85, 1389–1393 (2015).
Google Scholar
Mahalik, J. R., Di Bianca, M. & Sepulveda, J. Examining father status and purpose to understand new days’ healthier lives. Psychol. Men. Masc. 21, 570–577 (2020).
Google Scholar
Lewington, L., Sebar, B. & Lee, J. “Becoming the man you always wanted to be”: exploring the representation of health and masculinity in Men’s Health magazine. Health Promot. J. Austr. 29, 243–250 (2018).
Google Scholar
De Jonge, C. J. et al. Current global status of male reproductive health. Hum. Reprod. Open. 2024, hoae017 (2024).
Google Scholar
De Jonge, C. & Barratt, C. L. R. The present crisis in male reproductive health: an urgent need for a political, social, and research roadmap. Andrology 7, 762–768 (2019).
Google Scholar
Torkel, S. et al. Barriers and enablers to a healthy lifestyle in people with infertility: a mixed-methods systematic review. Hum. Reprod. Update 30, 569–583 (2024).
Google Scholar
Healthy male. A case for change. Healthy Male https://healthymale.org.au/plus-paternal/a-case-for-change (2024).
Vargas, C., Whelan, J., Brimblecombe, J. & Allender, S. Co-creation, co-design, co-production for public health — a perspective on definition and distinctions. Public Health Res Pract. 32, 3222211 (2022).
Google Scholar
Slattery, P., Saeri, A. K. & Bragge, P. Research co-design in health: a rapid overview of reviews. Health Res. Policy Syst. 18, 17 (2020).
Google Scholar
Sanz, M. F., Acha, B. V. & García, M. F. Co-design for people-centred care digital solutions: a literature review. Int. J. Integr. Care 21, 16 (2021).
Google Scholar
Ng, S. K., Martin, S. A., Adams, R. J., O’Loughlin, P. & Wittert, G. A. The effect of multimorbidity patterns and the impact of comorbid anxiety and depression on primary health service use: the men androgen inflammation lifestyle environment and stress (MAILES) study. Am. J. Mens. Health 14, 1557988320959993 (2020).
Google Scholar
Mursa, R., Patterson, C. & Halcomb, E. Men’s help-seeking and engagement with general practice: an integrative review. J. Adv. Nurs. 78, 1938–1953 (2022).
Google Scholar
McGraw, J., White, K. M. & Russell-Bennett, R. Masculinity and men’s health service use across four social generations: findings from Australia’s Ten to Men study. SSM Popul. Health 15, 100838 (2021).
Google Scholar
Håkonsen, L. B. et al. Does weight loss improve semen quality and reproductive hormones? results from a cohort of severely obese men. Reprod. Health 8, 24 (2011).
Google Scholar
Faure, C. et al. In subfertile couple, abdominal fat loss in men is associated with improvement of sperm quality and pregnancy: a case-series. PLoS ONE 9, e86300 (2014).
Google Scholar
Rafiee, B., Morowvat, M. H. & Rahimi-Ghalati, N. Comparing the effectiveness of dietary vitamin C and exercise interventions on fertility parameters in normal obese men. Urol. J. 13, 2635–2639 (2016).
Google Scholar
Rosety, M. et al. Exercise improved semen quality and reproductive hormone levels in sedentary obese adults. Nutr. Hosp. 34, 603–607 (2017).
Google Scholar
Mir J., Franken D., Andrabi S. W., Ashraf M., Rao K. Impact of weight loss on sperm DNA integrity in obese men. Andrologia 50, e12957 (2018).
Google Scholar
Jaffar, M. & Ashraf, M. Does weight loss improve fertility with respect to semen parameters — results from a large cohort study. Int. J. Infertil. Fetal Med. 8, 12–17 (2017).
Bisht, S. et al. Sperm methylome alterations following yoga-based lifestyle intervention in patients of primary male infertility: a pilot study. Andrologia 52, e13551 (2020).
Google Scholar
Mombeyni, A., Shakerian, S., Habibi, A. & Ghanbarzadeh, M. The effect of 12 weeks of concurrent training on hypothalamic-pituitary-gonadal axis hormones and semen fertility indices of sedentary obese men. Med. Sport 74, 269–283 (2021).
Google Scholar
Andersen, E. et al. Sperm count is increased by diet-induced weight loss and maintained by exercise or GLP-1 analogue treatment: a randomized controlled trial. Hum. Reprod. 37, 1414–1422 (2022).
Google Scholar
Humaidan, P. et al. The combined effect of lifestyle intervention and antioxidant therapy on sperm DNA fragmentation and seminal oxidative stress in IVF patients: a pilot study. Int. Braz. J. Urol. 48, 131–156 (2022).
Google Scholar
Ismail, A., Abdelghany, A. & Atef, H. Response of testosterone and semen parameters to a 14-week aerobic training in sedentary obese men with hyperglycaemia. Physiother. Q. 31, 28–33 (2023).
Google Scholar
Sharma, A. et al. Improvements in sperm motility following low- or high-intensity dietary interventions in men with obesity. J. Clin. Endocrinol. Metab. 109, 449–460 (2024).
Google Scholar
