male infertility: etiology & evaluation
Infertility is defined as the unable to conceive despite having one year of regular unprotected intercourse. It affects both genders globally. The increase in incidence is also due to delaying the start of families by many couples. Infertility is generally classified into two categories when a couple is unable to conceive after at least 1 year of unprotected sexual intercourse is termed primary, while any couple who has conceived previously but is not unable to conceive again is called secondary. The couple should consider the evaluation, if either partner has any known risk factor for infertility (e.g., advanced female age, male with a history of undescended testicles), or if the couple has concerns about their fertility potential. In most cases, it is recommended that both partners be evaluated simultaneously to prevent any delays in successful treatment. According to the WHO report on reproductive health, infertility may affect 15% of couples per year globally, of these, 20% will have a male factor that is solely responsible; male factors will contribute in an additional 30% of cases. When a man has any problem with his reproductive system it can lead to male infertility. Exposure to toxic substances, chemotherapy, radiation, and physical problems with the testes. Lifestyle, notably poor health habits and conditions (smoking, obesity, excessive alcohol consumption, use of drugs, testosterone, or anabolic steroids) may cause infertility in both sexes. Undescended testicle (cryptorchidism), Past inflammation of the prostate or past genital infections and/or high fever, Injury to or Torsion (constricted blood flow to a testicle), exposure to certain medications, pesticides, and other toxins, injury to the spinal cord, prostate surgery, hormone problems, genetic or chromosomal conditions testicular cancer, vasectomy, sexually transmitted diseases, varicocele (dilated veins in the scrotum), Ejaculatory disturbances Early or late puberty, Exposure of the genitals to high temperatures, Hernia repair can cause infertility.
1. Abad C, Amengual M, Gosálvez J, Coward K, Hannaoui N, Benet J, et al. Effects of oral antioxidant treatment upon the dynamics of human sperm DNA fragmentation and subpopulations of sperm with highly degraded DNA. Andrologia. 2013;45:211–216.
2. Agarwal A, P. N. (2019). Male oxidative stress infertility (Mosi): proposed terminology and clinical practice guidelines for management of idiopathic male infertility. World J Mens Health, 37(3), 296-312.
3. Agarwal A, Said TM. Oxidative stress, DNA damage and apoptosis in male infertility: a clinical approach. BJU Int. 2005;95:503–507.
4. Aitken R, Irvine D, Wu F. Prospective analysis of sperm-oocyte fusion and reactive oxygen species generation as criteria for the diagnosis of infertility. Am J Obstet Gynecol. 1991;164:542–551.
5. Arduini A, Bonomini M, Savica V, Amato A, Zammit V. Carnitine in metabolic disease: potential for pharmacological intervention. Pharm Ther. 2008;120:149–156.
6. Balercia G, Buldreghini E, Vignini A, Tiano L, Paggi F, Amoroso S, et al. Coenzyme Q 10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Fertil Steril. 2009;91:1785–1792.
7. Balercia G, Regoli F, Armeni T, Koverech A, Mantero F, Boscaro M. Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia. Fertil Steril. 2005;84:662–671.
8. Brigelius-Flohe R, Traber MG. Vitamin E: function and metabolism. FASEB J. 1999;13:1145–55.
9. Brugh VM, Lipshultz LI. Male factor infertility: evaluation and management. Med Clin North Am. 2004;88:367–385.
10. Colagar AH, Marzony ET. Ascorbic acid in human seminal plasma: determination and its relationship to sperm quality. J Clin Biochem Nutr. 2009;45:144–149.
11. Cooper TG, N. E. (2010). World Health Organization reference values for human semen characteristics. Hum Reprod Update, 16(3), 231-245.
12. Dawson EB, Harris WA, Rankin WE, Charpentier LA, McGanity WJ. Effect of ascorbic acid on male fertility. Ann N Y Acad Sci. 1987;498:312–23.
13. Ebisch I, Thomas C, Peters W, Braat D, Steegers-Theunissen R. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update. 2007;13:163–174.
14. Eisenberg ML, L. L. (2010). Estimating the number of vasectomies performed annually in the United States: data from the National Survey of Family Growth. J Urol, 184(5), 2068-2072.
15. Elgazar V, Razanov V, Stoltenberg M, Hershfinkel M, Huleihel M, Nitzan YB, et al. Zinc-regulating proteins, ZnT-1, and metallothionein I/II are present in different cell populations in the mouse testis. J Histochem Cytochem. 2005;53:905–912.
16. Enomoto A, Wempe MF, Tsuchida H, Shin HJ, Cha SH, Anzai N, et al. Molecular identification of a novel carnitine transporter specific to human testis insights into the mechanism of carnitine recognition. J Biol Chem. 2002;277:36262–36271.
17. Ernster L, Forsmark-Andree P. Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Invest. 1993;71:S60–S65.
18. Eskenazi B, Kidd S, Marks A, Sloter E, Block G, Wyrobek A. Antioxidant intake is associated with semen quality in healthy men. Hum Reprod. 2005;20:1006–1012.
19. Flohe L. Selenium in mammalian spermiogenesis. Biol Chem. 2007;388:987–995. 53. Mistry HD, Pipkin FB, Redman CW, Poston L. Selenium in reproductive health. Am J Obstet Gyn. 2012;206:21–30.
20. Galatioto GP, Gravina GL, Angelozzi G, Sacchetti A, Innominato PF, Pace G, et al. May antioxidant therapy improve sperm parameters of men with persistent oligospermia after retrograde embolization for varicocele? World J Urol. 2008;26:97–102.
21. Garolla A, Maiorino M, Roverato A, Roveri A, Ursini F, Foresta C. Oral carnitine supplementation increases sperm motility in asthenozoospermic men with normal sperm phospholipid hydroperoxide glutathione peroxidase levels. Fertil Steril. 2005;83:355–361.
22. Gopinath P, Kalra B, Saxena A, Malik S, Kochhar K, Kalra S, et al. Fixed Dose Combination Therapy of Antioxidants in Treatment of Idiopathic Oligoasthenozoospermia: Results of a Randomized, Double-blind, Placebo-controlled Clinical Trial. Int JInfertil Fetal Med. 2013;4:6–13.
23. Greco E, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Tesarik J. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl. 2005;26:349–353.
24. Gvozdjáková A, Kucharská J, Dubravicky J, Mojto V, Singh RB. Coenzyme Q10, α-Tocopherol, and Oxidative Stress Could Be Important Metabolic Biomarkers of Male Infertility. Dis mark. 2015;2015:ID 827941.
25. Hadwan MH, Almashhedy LA, Alsalman ARS. Oral zinc supplementation restore high molecular weight seminal zinc binding protein to normal value in Iraqi infertile men. BMC Urol. 2012;12:32.
26. Hosen MB, Islam MR, Begum F, Kabir Y, Howlader MZH. Oxidative stress induced sperm DNA damage, a possible reason for male infertility. Iran J Reprod Med. 2015;13:525–532.
27. Irvine DS. Epidemiology and aetiology of male infertility. Hum Reprod. 1998;13 (suppl.):33–44.
28. Johansen L, Bøhmer T. Carnitine-binding related supressed oxygen uptake by spermatozoa. Arch Androl. 1978;1:321–324.
29. Kefer JC, Agarwal A, Sabanegh E. Role of antioxidants in the treatment of male infertility. Int J Urol. 2009;16:449–57.
30. Keskes-Ammar L, Feki-Chakroun N, Rebai T, Sahnoun Z, Ghozzi H, Hammami S, et al. Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Arch Androl. 2003;49:83–94.
31. Khan MS, Zaman S, Sajjad M, Shoaib M, Gilani G. Assessment of the level of trace element zinc in seminal plasma of males and evaluation of its role in male infertility. Int J Appl Bas Med Res. 2011;1:93–96.
32. Ko EY, Sabanegh ES. The Role of Over‐the‐Counter Supplements for the Treatment of Male Infertility-Fact or Fiction? J Androl. 2012;33:292–308.
33. Lafuente R, González-Comadrán M, Solà I, López G, Brassesco M, Carreras R, et al. Coenzyme Q10 and male infertility: a meta-analysis. J Assis Reprod Gen. 2013;30:1147–1156.
34. Lenzi A, Sgro P, Salacone P, Paoli D, Gilio B, Lombardo F, et al. A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Fertil Steril. 2004;81:1578–1584.
35. Linster CL, Van Schaftingen E. Vitamin C. FEBS J. 2007;274:1–22.
36. Makker K, Agarwal A, Sharma R. Oxidative stress & male infertility. Ind J Med Res. 2009;129:357–367.
37. Matsuda T, M. K. (1998). Seminal tract obstruction caused by childhood inguinal herniorrhaphy: results of microsurgical reanastomosis. J Urol(159), 837-40.
38. Moslemi MK, Tavanbakhsh S. Selenium-vitamin E supplementation in infertile men: effects on semen parameters and pregnancy rate. Int J Gen Med. 2011;4:99–104.
39. Nadjarzadeh A, Sadeghi M, Amirjannati N, Vafa M, Motevalian S, Gohari M, et al. Coenzyme Q10 improves seminal oxidative defense but does not affect on semen parameters in idiopathic oligoasthenoteratozoospermia: a randomized double-blind, placebo controlled trial. J Endocrin Invest. 2011;34:e224–e228.
40. Olayemi F. review on some causes of male infertility. Afr J Biotech. 2010;
41. Radigue C, Es-Slami S, Soufir J. Relationship of carnitine transport across the epididymis to blood carnitine and androgens in rats. Arch Androl. 1996;37:27–31.
42. Raigani M, Yaghmaei B, Amirjannti N, Lakpour N, Akhondi M, Zeraati H, et al. The micronutrient supplements, zinc sulphate and folic acid, did not ameliorate sperm functional parameters in oligoasthenoteratozoospermic men. Andrologia. 2014;46:956–962.
43. Rao B, Soufir J, Martin M, David G. Lipid peroxidation in human spermatozoa as relatd to midpiece abnormalities and motility. Gamete Res. 1989;24:127–134.
44. Ross C, Morriss A, Khairy M, Khalaf Y, Braude P, Coomarasamy A, et al. A systematic review of the effect of oral antioxidants on male infertility. Reprod Biomed Online. 2010;20:711–723.
45. Safarinejad MR, Safarinejad S, Shafiei N, Safarinejad S. Effects of the reduced form of coenzyme Q 10 (ubiquinol) on semen parameters in men with idiopathic infertility: a double-blind, placebo controlled, randomized study. J Urol. 2012;188:526–531.
46. Saleh RA, HCLD AA. Oxidative stress and male infertility: from research bench to clinical practice. J Androl. 2002;23:737–752.
47. Sandström B, Sandberg A-S. Inhibitory effects of isolated inositol phosphates on zinc absorption in humans. J Trace Elements Electrol Health Dis. 1992;6:99–103.
48. Sharlip ID, Jarow JP, Belker AM, Lipshultz LI, Sigman M, Thomas AJ, et al. Best practice policies for male infertility. Fertil steril. 2002;77:873–882.
49. Sheweita SA, Tilmisany AM, Al-Sawaf H. Mechanisms of male infertility: role of antioxidants. Curr Drug Metab. 2005;6:495–501.
50. Sigman M, Glass S, Campagnone J, Pryor JL. Carnitine for the treatment of idiopathic asthenospermia: a randomized, double-blind, placebo-controlled trial. Fertil Steril. 2006;85:1409–1414.
51. Smits RM, M.-P. R. (2019). Antioxidants for male subfertility. Cochrane Database Syst Rev, 3, CD007411.
52. Sukcharoen N, Keith J, Irvine DS, Aitken RJ. Predicting the fertilizing potential of human sperm suspensions in vitro: importance of sperm morphology and leukocyte contamination. Fertil Steril. 1995;63:1293–1300.
53. Tadros, N. N., & Sabanegh Jr., E. (2017). Ch. 12: Varicocele. In Treatment of Male Infertility: a Case-based Guide for Clinicians. Springer.
54. Thakur AS, Littarru GP, Funahashi I, Painkara US, Dange NS, Chauhan P. Effect of Ubiquinol Therapy on Sperm Parameters and Serum Testosterone Levels in Oligoasthenozoospermic Infertile Men. J Clin Diagn Res. 2015;9:BC01–BC03.
55. Thonneau P, M. S. (1991). Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989). Hum Reprod, 6, 811.
56. Tremellen K. Oxidative stress and male infertility-a clinical perspective. Hum Reprod Update. 2008;14:243–258.
57. Wong WY, Thomas CM, Merkus JM, Zielhuis GA, Steegers-Theunissen RP. Male factor subfertility: possible causes and the impact of nutritional factors. Fertil Steril. 2000;73:435–442.
58. World Health Organization. (2010). WHO laboratory manual for the examination and processing of human semen (5th ed.). Geneva: World Health Organization.
59. Wu Z, Lu X, Wang Y, Sun J, Tao J, Yin F, et al. [Short-term medication of L-carnitine before intracytoplasmic sperm injection for infertile men with oligoasthenozoospermia] Zhonghua Nan Ke Xue. 2012;18:253–256.
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