{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:28:58Z","timestamp":1790116138310,"version":"4.0.1"},"reference-count":119,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background\/Objectives: Male infertility is a prevalent issue impacting numerous couples worldwide. This review aims to evaluate the effectiveness of empirical therapies for male infertility, focusing on both lifestyle modifications and medical treatments. This study provides a comprehensive overview of interventions aimed at improving male fertility outcomes. Methods: A thorough review of the existing literature was conducted, encompassing studies on lifestyle changes such as dietary changes, smoking cessation, alcohol moderation, and exercise. Additionally, medical treatments including selective estrogen receptor modulators, gonadotropins, aromatase inhibitors, phosphodiesterase-5 inhibitors, antioxidants, dopamine agonists, kallikrein, indomethacin, low-dose corticosteroids, alpha-blockers, and nitric oxide donors were evaluated. The study population included males diagnosed with infertility, focusing on various underlying causes. Results: Lifestyle modifications were found to have a positive impact on sperm quality. Evidence shows that a healthy diet, smoking cessation, moderate alcohol consumption, and regular exercise improve fertility outcomes. Medical treatments demonstrated significant improvements in sperm production and quality. Selective estrogen receptor modulators and gonadotropins enhanced sperm parameters. Aromatase inhibitors and phosphodiesterase-5 inhibitors specifically improved sperm motility and increased pregnancy rates. Antioxidants, such as vitamins E and C and coenzyme Q10, reduced oxidative stress and enhanced sperm counts, motility, and morphology. Dopamine agonists, particularly cabergoline, normalized prolactin levels and improved fertility outcomes. Kallikrein therapy improved sperm parameters and increased pregnancy rates. Indomethacin treatment was associated with increased sperm concentrations and motility. Low-dose corticosteroids and alpha-blockers showed variable results, and nitric oxide donors like L-arginine enhanced sperm counts and motility. Conclusions: Empirical therapies, including lifestyle modifications and medical treatments, significantly enhance sperm quality and reproductive potential. These integrated approaches are essential in improving fertility outcomes in males. However, further extensive randomized trials are necessary to definitively establish the most effective treatments.<\/jats:p>","DOI":"10.3390\/diseases12090209","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T05:45:12Z","timestamp":1726033512000},"page":"209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Empirical Treatments for Male Infertility: A Focus on Lifestyle Modifications and Medicines"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-312X","authenticated-orcid":false,"given":"Aris","family":"Kaltsas","sequence":"first","affiliation":[{"name":"Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5287-4450","authenticated-orcid":false,"given":"Athanasios","family":"Zachariou","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-9144","authenticated-orcid":false,"given":"Fotios","family":"Dimitriadis","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-005X","authenticated-orcid":false,"given":"Michael","family":"Chrisofos","sequence":"additional","affiliation":[{"name":"Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Sofikitis","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/humrep\/13.suppl_1.33","article-title":"Epidemiology and aetiology of male infertility","volume":"13","author":"Irvine","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/978-3-030-89340-8_9","article-title":"Oxidative Stress and Idiopathic Male Infertility","volume":"1358","author":"Sengupta","year":"2022","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"108","DOI":"10.5653\/cerm.2014.41.3.108","article-title":"Empirical medical therapy in idiopathic male infertility: Promise or panacea?","volume":"41","author":"Jung","year":"2014","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.eururo.2021.08.014","article-title":"European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility","volume":"80","author":"Minhas","year":"2021","journal-title":"Eur. Urol."},{"key":"ref_5","first-page":"479","article-title":"The Sertoli cell as the orchestra conductor of spermatogenesis: Spermatogenic cells dance to the tune of testosterone","volume":"14","author":"Dimitriadis","year":"2015","journal-title":"Hormones"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/andr.12502","article-title":"European Academy of Andrology guideline Management of oligo-astheno-teratozoospermia","volume":"6","author":"Colpi","year":"2018","journal-title":"Andrology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/S2213-8587(16)30040-7","article-title":"Novel concepts in the aetiology of male reproductive impairment","volume":"5","author":"Tournaye","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1742-4755-8-24","article-title":"Does weight loss improve semen quality and reproductive hormones? Results from a cohort of severely obese men","volume":"8","author":"Hakonsen","year":"2011","journal-title":"Reprod. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/17446651.2019.1657827","article-title":"Metabolically healthy and unhealthy obesity in erectile dysfunction and male infertility","volume":"14","author":"Rastrelli","year":"2019","journal-title":"Expert. Rev. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1007\/s11695-018-3557-5","article-title":"Impact of Bariatric Surgery on Male Sex Hormones and Sperm Quality: A Systematic Review and Meta-Analysis","volume":"29","author":"Lee","year":"2019","journal-title":"Obes. Surg."},{"key":"ref_11","unstructured":"World Health Organization (2018). Global Action Plan on Physical Activity 2018\u20132030: More Active People for a Healthier World, World Health Organization."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00404-019-05045-8","article-title":"An update on the implication of physical activity on semen quality: A systematic review and meta-analysis","volume":"299","author":"Matorras","year":"2019","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.eururo.2016.04.010","article-title":"Cigarette Smoking and Semen Quality: A New Meta-analysis Examining the Effect of the 2010 World Health Organization Laboratory Methods for the Examination of Human Semen","volume":"70","author":"Sharma","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Osadchuk, L., Kleshchev, M., and Osadchuk, A. (2023). Effects of cigarette smoking on semen quality, reproductive hormone levels, metabolic profile, zinc and sperm DNA fragmentation in men: Results from a population-based study. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1255304"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Henriques, M.C., Santiago, J., Patricio, A., Herdeiro, M.T., Loureiro, S., and Fardilha, M. (2023). Smoking Induces a Decline in Semen Quality and the Activation of Stress Response Pathways in Sperm. Antioxidants, 12.","DOI":"10.3390\/antiox12101828"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1439-0272.2004.00605.x","article-title":"Effects of paternal cigarette smoking on testicular function, sperm fertilizing capacity, embryonic development, and blastocyst capacity for implantation in rats","volume":"36","author":"Kapawa","year":"2004","journal-title":"Andrologia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1080\/10934529.2014.846195","article-title":"Association of cigarette smoking with reproductive hormone levels and semen quality in healthy adult men in Taiwan","volume":"49","author":"Jeng","year":"2014","journal-title":"J. Environ. Sci. Health A Tox Hazard. Subst. Environ. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.1439-0272.2010.01089.x","article-title":"Impact of spontaneous smoking cessation on sperm quality: Case report","volume":"43","author":"Chenlo","year":"2011","journal-title":"Andrologia"},{"key":"ref_19","first-page":"2757","article-title":"Changes in oxidative stress levels during two weeks of smoking cessation treatment and their association with nutritional characteristics in Japanese smokers","volume":"17","author":"Oba","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e055","DOI":"10.1097\/EE9.0000000000000055","article-title":"Semen quality and cigarette smoking in a cohort of healthy fertile men","volume":"3","author":"Tang","year":"2019","journal-title":"Environ. Epidemiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40738-017-0032-2","article-title":"Discrete survival model analysis of a couple\u2019s smoking pattern and outcomes of assisted reproduction","volume":"3","author":"Vanegas","year":"2017","journal-title":"Fertil. Res. Pract."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1071\/RD22093","article-title":"Effect of paternal smoking on pre-implantation embryonic development: A prospective cohort study","volume":"34","author":"Frappier","year":"2022","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_23","first-page":"e52788","article-title":"Effect of Male Cigarette Smoking on In Vitro Fertilization (IVF) Outcomes and Embryo Morphokinetic Parameters","volume":"16","author":"Taniguchi","year":"2024","journal-title":"Cureus"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.rbmo.2016.09.012","article-title":"Semen quality and alcohol intake: A systematic review and meta-analysis","volume":"34","author":"Ricci","year":"2017","journal-title":"Reprod. Biomed. Online"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.fertnstert.2005.04.025","article-title":"Effect of chronic alcoholism on male fertility hormones and semen quality","volume":"84","author":"Muthusami","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e15723","DOI":"10.1016\/j.heliyon.2023.e15723","article-title":"Investigating the association between alcohol intake and male reproductive function: A current meta-analysis","volume":"9","year":"2023","journal-title":"Heliyon"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Finelli, R., Mottola, F., and Agarwal, A. (2021). Impact of Alcohol Consumption on Male Fertility Potential: A Narrative Review. Int. J. Environ. Res. Public. Health, 19.","DOI":"10.3390\/ijerph19010328"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1093\/alcalc\/agt133","article-title":"Chronic excessive alcohol consumption and male fertility: A case report on reversible azoospermia and a literature review","volume":"49","author":"Guthauser","year":"2014","journal-title":"Alcohol. Alcohol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.rbmo.2009.12.003","article-title":"Progressive alcohol-induced sperm alterations leading to spermatogenic arrest, which was reversed after alcohol withdrawal","volume":"20","author":"Sermondade","year":"2010","journal-title":"Reprod. Biomed. Online"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1016\/j.ijgo.2013.09.001","article-title":"The conventional management of male infertility","volume":"123","author":"Nieschlag","year":"2013","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1080\/17512433.2018.1445969","article-title":"Pharmacological management of late-onset hypogonadism","volume":"11","author":"Rastrelli","year":"2018","journal-title":"Expert. Rev. Clin. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1111\/andr.262","article-title":"Factors affecting spermatogenesis upon gonadotropin-replacement therapy: A meta-analytic study","volume":"2","author":"Rastrelli","year":"2014","journal-title":"Andrology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/S0094-0143(02)00085-X","article-title":"A new look at the medical management of infertility","volume":"29","author":"Siddiq","year":"2002","journal-title":"Urol. Clin. N. Am."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/humrep\/12.1.24","article-title":"Treatment of the male with follicle-stimulating hormone in intrauterine insemination with husband\u2019s spermatozoa: A randomized study","volume":"12","author":"Matorras","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1093\/humrep\/13.3.596","article-title":"Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: A randomized, double-blind, placebo-controlled, clinical trial","volume":"13","author":"Kamischke","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.fertnstert.2008.07.1766","article-title":"Gonadotropin administration after gonadotropin-releasing-hormone agonist: A therapeutic option in severe testiculopathies","volume":"92","author":"Foresta","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1210\/jcem-65-6-1081","article-title":"Treatment of severe oligospermia with human chorionic gonadotropin\/human menopausal gonadotropin: A placebo-controlled, double blind trial","volume":"65","author":"Knuth","year":"1987","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/humupd\/dmg002","article-title":"The present and future state of hormonal treatment for male infertility","volume":"9","author":"Liu","year":"2003","journal-title":"Hum. Reprod. Update"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"309","DOI":"10.4103\/aja.aja_42_19","article-title":"FSH dosage effect on conventional sperm parameters: A meta-analysis of randomized controlled studies","volume":"22","author":"Cannarella","year":"2020","journal-title":"Asian J. Androl."},{"key":"ref_40","first-page":"1","article-title":"The Effect of Recombinant Human Follicle-Stimulating Hormone on Sperm Quality, Chromatin Status and Clinical Outcomes of Infertile Oligozoospermic Men Candidate for Intracytoplasmic Sperm Injection: A Randomized Clinical Trial","volume":"15","author":"Verdi","year":"2021","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.fertnstert.2020.10.005","article-title":"Efficacy of the second micro-testicular sperm extraction after failed first micro-testicular sperm extraction in men with nonobstructive azoospermia","volume":"115","author":"Ozman","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1080\/14656566.2019.1615057","article-title":"Effects of the selective estrogen receptor modulators for the treatment of male infertility: A systematic review and meta-analysis","volume":"20","author":"Cannarella","year":"2019","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_43","first-page":"66","article-title":"The Role of Estrogen Modulators in Male Hypogonadism and Infertility","volume":"18","author":"Rambhatla","year":"2016","journal-title":"Rev. Urol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/JU.0000000000001520","article-title":"Diagnosis and Treatment of Infertility in Men: AUA\/ASRM Guideline PART II","volume":"205","author":"Schlegel","year":"2021","journal-title":"J. Urol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1080\/19396368.2020.1822457","article-title":"Clomiphene citrate improved testosterone and sperm concentration in hypogonadal males","volume":"66","author":"Delu","year":"2020","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e13848","DOI":"10.1111\/and.13848","article-title":"A paradoxical decline in semen parameters in men treated with clomiphene citrate: A systematic review","volume":"53","author":"Gundewar","year":"2021","journal-title":"Andrologia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/humrep\/14.suppl_1.1","article-title":"Analysis of medical treatment of male infertility","volume":"14","author":"Kamischke","year":"1999","journal-title":"Hum. Reprod."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1111\/j.2047-2927.2013.00107.x","article-title":"Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: A meta-analysis","volume":"1","author":"Chua","year":"2013","journal-title":"Andrology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e1803","DOI":"10.1210\/clinem\/dgaa860","article-title":"Testicular Testosterone and Estradiol Concentrations and Aromatase Expression in Men with Nonobstructive Azoospermia","volume":"106","author":"Shiraishi","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"360","DOI":"10.4103\/aja.aja_101_19","article-title":"A systematic review and meta-analysis of clinical trials implementing aromatase inhibitors to treat male infertility","volume":"22","author":"Busetto","year":"2020","journal-title":"Asian J. Androl."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.21037\/tau-20-919","article-title":"Efficacy of anastrozole in the treatment of hypogonadal, subfertile men with body mass index \u226525 kg\/m2","volume":"10","author":"Shah","year":"2021","journal-title":"Transl. Androl. Urol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1177\/0748233717695160","article-title":"Endocrine-disrupting chemicals-Mechanisms of action on male reproductive system","volume":"33","author":"Sidorkiewicz","year":"2017","journal-title":"Toxicol. Ind. Health"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.fertnstert.2004.12.057","article-title":"Correlation of reactive oxygen species levels with the fertilization rate after in vitro fertilization: A qualified meta-analysis","volume":"84","author":"Agarwal","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_54","first-page":"CD007411","article-title":"Antioxidants for male subfertility","volume":"5","author":"Smits","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kaltsas, A. (2023). Oxidative Stress and Male Infertility: The Protective Role of Antioxidants. Medicina, 59.","DOI":"10.3390\/medicina59101769"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Showell, M.G., Mackenzie-Proctor, R., Brown, J., Yazdani, A., Stankiewicz, M.T., and Hart, R.J. (2014). Antioxidants for male subfertility. Cochrane Database Syst. Rev., CD007411.","DOI":"10.1002\/14651858.CD007411.pub3"},{"key":"ref_57","first-page":"CD007411","article-title":"Antioxidants for male subfertility","volume":"3","author":"Smits","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1590\/s1677-5538.ibju.2021.0604","article-title":"The combined effect of lifestyle intervention and antioxidant therapy on sperm DNA fragmentation and seminal oxidative stress in IVF patients: A pilot study","volume":"48","author":"Humaidan","year":"2022","journal-title":"Int. Braz. J. Urol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.fertnstert.2019.11.008","article-title":"The effect of antioxidants on male factor infertility: The Males, Antioxidants, and Infertility (MOXI) randomized clinical trial","volume":"113","author":"Steiner","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1007\/s10815-021-02301-2","article-title":"The relationship of plasma antioxidant levels to semen parameters: The Males, Antioxidants, and Infertility (MOXI) randomized clinical trial","volume":"38","author":"Knudtson","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.2174\/1381612826666200415173537","article-title":"Therapeutic Effects of Micronutrient Supplements on Sperm Parameters: Fact or Fiction?","volume":"27","author":"Dimitriadis","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Avila, C., Vinay, J.I., Arese, M., Saso, L., and Rodrigo, R. (2022). Antioxidant Intervention against Male Infertility: Time to Design Novel Strategies. Biomedicines, 10.","DOI":"10.3390\/biomedicines10123058"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.2174\/1381612827666210204160248","article-title":"Administration of Antioxidants in Infertile Male: When it may have a Detrimental Effect?","volume":"27","author":"Dimitriadis","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Symeonidis, E.N., Evgeni, E., Palapelas, V., Koumasi, D., Pyrgidis, N., Sokolakis, I., Hatzichristodoulou, G., Tsiampali, C., Mykoniatis, I., and Zachariou, A. (2021). Redox Balance in Male Infertility: Excellence through Moderation-\u201cMuepsilontaurhoomicronnu \u1f04rhoiotasigmatauomicronnu\u201d. Antioxidants, 10.","DOI":"10.3390\/antiox10101534"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e14385","DOI":"10.1111\/and.14385","article-title":"Predictors of pregnancy and time to pregnancy in infertile men with idiopathic oligoasthenospermia pre- and post-coenzyme Q10 therapy","volume":"54","author":"Alahmar","year":"2022","journal-title":"Andrologia"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"150","DOI":"10.5653\/cerm.2020.04084","article-title":"Coenzyme Q10, oxidative stress markers, and sperm DNA damage in men with idiopathic oligoasthenoteratospermia","volume":"48","author":"Alahmar","year":"2021","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1530\/RAF-20-0037","article-title":"l-carnitine and l-acetylcarnitine supplementation for idiopathic male infertility","volume":"1","author":"Khaw","year":"2020","journal-title":"Reprod. Fertil."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e13953","DOI":"10.1111\/and.13953","article-title":"The role of N-acetyl-cysteine (NAC) orally daily on the sperm parameters and serum hormones in idiopathic infertile men: A systematic review and meta-analysis of randomised controlled trials","volume":"53","author":"Zhou","year":"2021","journal-title":"Andrologia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"15579883211036790","DOI":"10.1177\/15579883211036790","article-title":"Comparison of 3- and 6-Month Outcomes of Combined Oral L-Carnitine Fumarate and Acetyl-L-Carnitine Therapy, Included in an Antioxidant Formulation, in Patients with Idiopathic Infertility","volume":"15","author":"Szymanski","year":"2021","journal-title":"Am. J. Men\u2019s Health"},{"key":"ref_70","first-page":"76","article-title":"Effect of antioxidant supplementation containing L-carnitine on semen parameters: A prospective interventional study","volume":"25","author":"Nazari","year":"2021","journal-title":"JBRA Assist. Reprod."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"15579883211011371","DOI":"10.1177\/15579883211011371","article-title":"A Meta-Analysis of the Efficacy of L-Carnitine\/L-Acetyl-Carnitine or N-Acetyl-Cysteine in Men with Idiopathic Asthenozoospermia","volume":"15","author":"Wei","year":"2021","journal-title":"Am. J. Men\u2019s Health"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Maghsoumi-Norouzabad, L., Zare Javid, A., Mansoori, A., Dadfar, M., and Serajian, A. (2021). The effects of Vitamin D3 supplementation on Spermatogram and endocrine factors in asthenozoospermia infertile men: A randomized, triple blind, placebo-controlled clinical trial. Reprod. Biol. Endocrinol., 19.","DOI":"10.1186\/s12958-021-00789-y"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0301-2115(95)02539-1","article-title":"Effect of low dose continuous corticosteroid therapy in men with antisperm antibodies on spermatozoal quality and conception rate","volume":"69","author":"Omu","year":"1996","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Vickram, A.S., Dhama, K., Chakraborty, S., Samad, H.A., Latheef, S.K., Sharun, K., Khurana, S.K., Tiwari, R., Bhatt, P., and Chaicumpa, W. (2019). Role of Antisperm Antibodies in Infertility, Pregnancy, and Potential forContraceptive and Antifertility Vaccine Designs: Research Progress and Pioneering Vision. Vaccines, 7.","DOI":"10.3390\/vaccines7030116"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"R55","DOI":"10.1530\/REP-21-0123","article-title":"The impact of antisperm antibodies on human male reproductive function: An update","volume":"162","author":"Silva","year":"2021","journal-title":"Reproduction"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1007\/s12020-017-1446-7","article-title":"Improvement in pregnancy outcomes in couples with immunologically male infertility undergoing prednisolone treatment and conventional in vitro fertilization preceded by sperm penetration assay: A randomized controlled trial","volume":"58","author":"Taiyeb","year":"2017","journal-title":"Endocrine"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Practice Committee of the American Society for Reproductive Medicine (2018). The role of immunotherapy in in vitro fertilization: A guideline. Fertil. Steril., 110, 387\u2013400.","DOI":"10.1016\/j.fertnstert.2018.05.009"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e13672","DOI":"10.1111\/and.13672","article-title":"The physiology of male reproduction: Impact of drugs and their abuse on male fertility","volume":"52","author":"Ajayi","year":"2020","journal-title":"Andrologia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e13207","DOI":"10.1111\/and.13207","article-title":"Therapeutic options in male genital tract inflammation","volume":"51","author":"Haidl","year":"2019","journal-title":"Andrologia"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Dimitriadis, F., Zachariou, D., Zikopoulos, A., Symeonidis, E.N., Markou, E., Tien, D.M.B., Takenaka, A., Sofikitis, N., and Zachariou, A. (2023). From Diagnosis to Treatment: Comprehensive Care by Reproductive Urologists in Assisted Reproductive Technology. Medicina, 59.","DOI":"10.3390\/medicina59101835"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.2174\/1381612826666200226121510","article-title":"The Effect of PDE5 Inhibitors on the Male Reproductive Tract","volume":"27","author":"Sofikitis","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1111\/iju.15046","article-title":"PDE5 inhibitors and male reproduction: Is there a place for PDE5 inhibitors in infertility clinics or andrology laboratories?","volume":"29","author":"Dimitriadis","year":"2022","journal-title":"Int. J. Urol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"776","DOI":"10.5534\/wjmh.200155","article-title":"Effect of Phosphodiesterase-5 Inhibitors on the Treatment of Male Infertility: A Systematic Review and Meta-Analysis","volume":"39","author":"Dong","year":"2021","journal-title":"World J. Men\u2019s Health"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1093\/oxfordjournals.humrep.a138674","article-title":"Pentoxifylline in idiopathic male-factor infertility: A review of its therapeutic efficacy after oral administration","volume":"9","author":"Tournaye","year":"1994","journal-title":"Hum. Reprod."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Lu, Y., Su, H., Zhang, J., Wang, Y., and Li, H. (2021). Treatment of Poor Sperm Quality and Erectile Dysfunction with Oral Pentoxifylline: A Systematic Review. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.789787"},{"key":"ref_86","first-page":"18","article-title":"The Role of Nitric Oxide on Male and Female Reproduction","volume":"29","author":"Dutta","year":"2022","journal-title":"Malays. J. Med. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8807","DOI":"10.3390\/cimb46080521","article-title":"Oxidative Stress and Erectile Dysfunction: Pathophysiology, Impacts, and Potential Treatments","volume":"46","author":"Kaltsas","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1095\/biolreprod.105.046896","article-title":"Mechanism of action of L-arginine on the vitality of spermatozoa is primarily through increased biosynthesis of nitric oxide","volume":"74","author":"Srivastava","year":"2006","journal-title":"Biol. Reprod."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/j.1365-2265.1992.tb01485.x","article-title":"Dose-dependent suppression of serum prolactin by cabergoline in hyperprolactinaemia: A placebo controlled, double blind, multicentre study. European Multicentre Cabergoline Dose-finding Study Group","volume":"37","author":"Webster","year":"1992","journal-title":"Clin. Endocrinol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1210\/jcem.84.7.5810","article-title":"Cabergoline in the treatment of hyperprolactinemia: A study in 455 patients","volume":"84","author":"Verhelst","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3109\/01485018208987030","article-title":"Bromocriptine therapy in oligozoospermic infertile men","volume":"8","author":"AinMelk","year":"1982","journal-title":"Arch. Androl."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3109\/01485017908987308","article-title":"Treatment of idiopathic oligozoospermia by kallikrein: Results of a double-blind study","volume":"2","author":"Schill","year":"1979","journal-title":"Arch. Androl."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1620\/tjem.164.23","article-title":"The effect of kallikrein on human sperm membrane function","volume":"164","author":"Sofikitis","year":"1991","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1439-0272.1987.tb02339.x","article-title":"Effects of kallikrein on the male reproductive system and its use in the treatment of idiopathic oligozoospermia with impaired motility","volume":"19","author":"Giovenco","year":"1987","journal-title":"Andrologia"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/S0015-0282(16)48081-7","article-title":"The prostaglandin inhibitor effect of antiinflammatory drugs in the therapy of male infertility","volume":"42","author":"Barkay","year":"1984","journal-title":"Fertil. Steril."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1620\/tjem.177.25","article-title":"Effects of alpha-blocker on daily testicular sperm production and sperm concentration, motility, intraluminal pressure and fluid movement in the rat epididymis","volume":"177","author":"Yamamoto","year":"1995","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/S0022-5347(01)67120-9","article-title":"Effects of alpha-blocker on sperm concentration, motility, intraluminal pressure and fluid movement in the rat cauda epididymis","volume":"154","author":"Hibi","year":"1995","journal-title":"J. Urol."},{"key":"ref_98","first-page":"301","article-title":"Treatment of idiopathic oligozoospermia with an alpha-blocker: A placebo-controlled double-blind trial","volume":"42","author":"Gregoriou","year":"1997","journal-title":"Int. J. Fertil. Womens Med."},{"key":"ref_99","first-page":"1","article-title":"Treating Idiopathic Male Infertility with a Combination of TamoxifenCitrate and a Natural Compost with Antioxidant and Androgen-MimeticAction","volume":"4","author":"Iacono","year":"2013","journal-title":"J. Steroids Horm. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1745-7262.2005.00047.x","article-title":"Combined conventional\/antioxidant \u201cAstaxanthin\u201d treatment for male infertility: A double blind, randomized trial","volume":"7","author":"Comhaire","year":"2005","journal-title":"Asian J. Androl."},{"key":"ref_101","first-page":"188","article-title":"Safety and efficacy of clomiphene citrate and L-carnitine in idiopathic male infertility: A comparative study","volume":"7","author":"Moradi","year":"2010","journal-title":"Urol. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1016\/j.fertnstert.2009.01.117","article-title":"Combination clomiphene citrate and antioxidant therapy for idiopathic male infertility: A randomized controlled trial","volume":"93","author":"Ghanem","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00345-007-0218-z","article-title":"May antioxidant therapy improve sperm parameters of men with persistent oligospermia after retrograde embolization for varicocele?","volume":"26","author":"Gravina","year":"2008","journal-title":"World J. Urol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/S0015-0282(03)01123-3","article-title":"Effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in men with idiopathic oligozoospermia","volume":"80","author":"Adamopoulos","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"194","DOI":"10.4103\/iju.IJU_368_16","article-title":"Empiric medical therapy with hormonal agents for idiopathic male infertility","volume":"33","author":"Tadros","year":"2017","journal-title":"Indian. J. Urol."},{"key":"ref_106","first-page":"106","article-title":"Exogenous testosterone: A preventable cause of male infertility","volume":"2","author":"Crosnoe","year":"2013","journal-title":"Transl. Androl. Urol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.2174\/1381612826666201207104340","article-title":"Suppression of Spermatogenesis by Exogenous Testosterone","volume":"27","author":"Fusco","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_108","first-page":"1287","article-title":"The impact of exogenous testosterone supplementation on spermatogenesis in a rat model of oligoasthenospermia","volume":"13","author":"An","year":"2020","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/978-3-319-69535-8_4","article-title":"Exogenous Androgens and Male Reproduction","volume":"1034","author":"Drobnis","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.juro.2011.10.137","article-title":"Empirical medical therapy for idiopathic male infertility: A survey of the American Urological Association","volume":"187","author":"Ko","year":"2012","journal-title":"J. Urol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"qdad060.174","DOI":"10.1093\/jsxmed\/qdad060.174","article-title":"(181) Combination Clomiphene Citrate and Anastrozole Therapy Iimproves Semen Parameters in a Multi-institutional Cohort of Men with Idiopathic Infertility","volume":"20","author":"Eleswarapu","year":"2023","journal-title":"J. Sex. Med."},{"key":"ref_112","first-page":"258","article-title":"Comparison of the effect of combined therapy of HCG ampule and letrozole tablet with each method separately on the spermogram parameters in the obese men with idiopathic infertility: A clinical trial","volume":"10","author":"Khanzadeh","year":"2022","journal-title":"Am. J. Clin. Exp. Urol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"296","DOI":"10.5534\/wjmh.190055","article-title":"Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility","volume":"37","author":"Agarwal","year":"2019","journal-title":"World J. Men\u2019s Health"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Monakova, A., Sagaradze, G., Basalova, N., Popov, V., Balabanyan, V., and Efimenko, A. (2022). Novel Potency Assay for MSC Secretome-Based Treatment of Idiopathic Male Infertility Employed Leydig Cells and Revealed Vascular Endothelial Growth Factor as a Promising Potency Marker. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169414"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.fertnstert.2020.01.001","article-title":"Harnessing the full potential of reproductive genetics and epigenetics for male infertility in the era of \u201cbig data\u201d","volume":"113","author":"Patel","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Zachariou, A., Markou, E., Dimitriadis, F., Sofikitis, N., and Pournaras, S. (2023). Microbial Dysbiosis and Male Infertility: Understanding the Impact and Exploring Therapeutic Interventions. J. Pers. Med., 13.","DOI":"10.3390\/jpm13101491"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.explore.2015.04.007","article-title":"Semen Quality Improvement in a Man with Idiopathic Infertility Treated with Traditional Korean Medicine: A Case Report","volume":"11","author":"Jo","year":"2015","journal-title":"Explore"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Easley, C.A., Simerly, C.R., and Schatten, G. (2014). Direct Differentiation of Human Pluripotent Stem Cells into Advanced Spermatogenic Cells: In Search of an In Vitro System to Model Male Factor Infertility. New Frontiers of Multidisciplinary Research in STEAM-H (Science, Technology, Engineering, Agriculture, Mathematics, and Health), Springer.","DOI":"10.1007\/978-3-319-07755-0_12"},{"key":"ref_119","first-page":"e31291","article-title":"A Review on the Use of Letrozole in Female and Male Infertility","volume":"14","author":"Pajai","year":"2022","journal-title":"Cureus"}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/12\/9\/209\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:53:40Z","timestamp":1760111620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/12\/9\/209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,11]]},"references-count":119,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["diseases12090209"],"URL":"https:\/\/doi.org\/10.3390\/diseases12090209","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,11]]}}}