Male infertility: A critical review of pharmacologic management

Expert Opinion on Pharmacotherapy

Volumn 13, Issue 17, 2012, Pages 2511-2531

  Hamada, Alaa J ^a   Montgomery, Brian ^a   Agarwal, Ashok ^a  

^a LERNER RESEARCH INSTITUTE   (United States)

Author keywords

Male infertility; Medical treatment; Pregnancy outcome; Semen analysis

Indexed keywords

ACETYLCYSTEINE; ALPHA TOCOPHEROL; ANASTROZOLE; ANTIOXIDANT; ASCORBIC ACID; ASTAXANTHIN; BROMOCRIPTINE; CABERGOLINE; CHORIONIC GONADOTROPIN; CLOMIFENE CITRATE; CORTICOSTEROID; DOXYCYCLINE; FOLIC ACID; FOLLITROPIN; GONADORELIN; GONADOTROPIN; HUMAN MENOPAUSAL GONADOTROPIN; IMIPRAMINE; LETROZOLE; OMEGA 3 FATTY ACID; OROTATE MAGNESIUM; PREDNISOLONE; ROFECOXIB; SELENIUM; TAMOXIFEN; TESTOLACTONE; TESTOSTERONE UNDECANOATE; UBIDECARENONE; UNINDEXED DRUG; ZINC;

ACNE; ANTIBIOTIC THERAPY; ASTHENOSPERMIA; AVASCULAR NECROSIS; CORTICOSTEROID THERAPY; DNA FRAGMENTATION; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG TARGETING; DYSPEPSIA; EVIDENCE BASED MEDICINE; HEADACHE; HORMONAL THERAPY; HUMAN; HYPERPROLACTINEMIA; HYPOTHALAMUS HYPOPHYSIS GONAD SYSTEM; INFECTION; INFERTILITY THERAPY; INTRACYTOPLASMIC SPERM INJECTION; INTRAUTERINE INSEMINATION; IRRITABILITY; LEUKOCYTOSPERMIA; MALE INFERTILITY; METABOLOMICS; NAUSEA; OLIGOSPERMIA; ORTHOSTATIC HYPOTENSION; PREGNANCY RATE; PROTEOMICS; RETROGRADE EJACULATION; REVIEW; SEMEN ABNORMALITY; SEMINAL PLASMA; SIDE EFFECT; SOMNOLENCE; SPERM; SPERMATOGENESIS; SPERMATOZOON ABNORMALITY; SPERMATOZOON DENSITY; SPERMATOZOON MOTILITY; TESTIS; UROGENITAL TRACT INFECTION; VITAMIN SUPPLEMENTATION; WEIGHT GAIN;

ADRENERGIC ALPHA-AGONISTS; ANTI-BACTERIAL AGENTS; ANTI-INFLAMMATORY AGENTS; ANTIOXIDANTS; HORMONES; HUMANS; INFERTILITY, MALE; MALE;

EID: 84869807973     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2012.740011     Document Type: Review

References (178)

1. Rowe PJ, Comhaire FH. WHO manual for the standardised investigation and diagnosis of the infertile couple. Cambridge University Press, Cambridge; 2000
2. Irvine DS. Epidemiology and aetiology of male infertility. Hum Reprod 1998;Apr13(Suppl 1):33-44
3. Nieschlag E, Behre HM, Nieschlag S. Andrology: male reproductive health and dysfunction. 3rd edition. Springer; Heidelberg; New York: 2010
4. Farhi J, Ben-Haroush A. Distribution of causes of infertility in patients attending primary fertility clinics in Israel. Isr Med Assoc J 2011;13(1):51-4
5. Dohle GR, et al. EAU guidelines on male infertility. Eur Urol 2005;Nov48(5):703-11
6. Jungwirth A, Diemer T, Dohle GR, et al. EAU guidelines on male infertility. Epub. Uroweb, 2012. Available at: http://www.uroweb.org/gls/pdf/15- Male-Infertility-LR%20II.pdf [Accessed June 1, 2012]
7. Conn PM, Crowley WF Jr. Gonadotropin-releasing hormone and its analogues. N Engl J Med 1991;Jan10324(2):93-103
8. Liu L, Banks SM, Barnes KM, Sherins RJ. Two-year comparison of testicular responses to pulsatile gonadotropin-releasing hormone and exogenous gonadotropins from the inception of therapy in men with isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1988;Dec67(6):1140-5
9. Schopohl J. Pulsatile gonadotrophin releasing hormone versus gonadotrophin treatment of hypothalamic hypogonadism in males. Hum Reprod 1993;Nov8(Suppl 2):175-9
10. Buchter D, Behre HM, Kliesch S, Nieschlag E. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol 1998;Sep139(3):298-303
11. Raivio T, Falardeau J, Dwyer A, et al. Reversal of idiopathic hypogonadotropic hypogonadism. N Engl J Med 2007;Aug30357(9):863-73
12. Schopohl J, Mehltretter G, von Zumbusch R, et al. Comparison of gonadotropin-releasing hormone and gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism. Fertil Steril 1991;Dec56(6):1143-50
13. Delemarre-Van de Waal HA. Induction of testicular growth and spermatogenesis by pulsatile, intravenous administration of gonadotrophin- releasing hormone in patients with hypogonadotrophic hypogonadism. Clin Endocrinol (Oxf) 1993;May38(5):473-80
14. Blumenfeld Z, Frisch L, Conn PM. Gonadotropin-releasing hormone (GnRH) antibodies formation in hypogonadotropic azoospermic men treated with pulsatile GnRH-diagnosis and possible alternative treatment. Fertil Steril 1988;Oct50(4):622-9
15. Badenoch DF, Waxman J, Boorman L, et al. Administration of a gonadotropin releasing hormone analogue in oligozoospermic infertile males. Acta Endocrinol (Copenh) 1988;Feb117(2):265-7
16. Pierce JG, Parsons TF. Glycoprotein hormones: structure and function. Annu Rev Biochem 1981;50:465-95
17. Liu PY, Gebski VJ, Turner L, et al. Predicting pregnancy and spermatogenesis by survival analysis during gonadotrophin treatment of gonadotrophin-deficient infertile men. Hum Reprod 2002;Mar17(3):625-33
18. Liu PY, Baker HW, Jayadev V, et al. Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab 2009;Mar94(3):801-8
19. Burgues S, Calderon MD. Subcutaneous self-administration of highly purified follicle stimulating hormone and human chorionic gonadotrophin for the treatment of male hypogonadotrophic hypogonadism. Spanish Collaborative Group on Male Hypogonadotropic Hypogonadism. Hum Reprod 1997;May12(5):980-6
20. Zitzmann M, Nieschlag E. Hormone substitution in male hypogonadism. Mol Cell Endocrinol 2000;Mar30161(1-2):73-88
21. Baccetti B, Piomboni P, Bruni E, et al. Effect of follicle-stimulating hormone on sperm quality and pregnancy rate. Asian J Androl 2004;Jun6(2):133-7
22. Foresta C, Bettella A, Garolla A, et al. Treatment of male idiopathic infertility with recombinant human follicle-stimulating hormone: a prospective, controlled, randomized clinical study. Fertil Steril 2005;Sep84(3):654-61
23. Kamischke A, Behre HM, Bergmann M, et al. Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: a randomized, double-blind, placebo-controlled, clinical trial. Hum Reprod 1998;Mar13(3):596-603
24. Knuth UA, Honigl W, Bals-Pratsch M, et al. Treatment of severe oligospermia with human chorionic gonadotropin/human menopausal gonadotropin: a placebo-controlled, double blind trial. J Clin Endocrinol Metab 1987;Dec65(6):1081-7
25. Attia AM, Al-Inany HG, Farquhar C, Proctor M. Gonadotrophins for idiopathic male factor subfertility. Cochrane Database Syst Rev 2007(4):CD005071
26. Kamischke A, Nieschlag E. Analysis of medical treatment of male infertility. Hum Reprod 1999;Sep14(Suppl 1):1-23
27. Liu PY, Handelsman DJ. The present and future state of hormonal treatment for male infertility. Hum Reprod Update 2003;Jan-Feb9(1):9-23
28. Matorras R, Perez C, Corcostegui B, et al. Treatment of the male with follicle-stimulating hormone in intrauterine insemination with husband's spermatozoa: a randomized study. Hum Reprod 1997;Jan12(1):24-8
29. Segal S, Yaffe H, Laufer N, Ben-David M. Male hyperprolactinemia: effects on fertility. Fertil Steril 1979;Nov32(5):556-61
30. Verhelst J, Abs R, Maiter D, et al. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab 1999;Jul84(7):2518-22
31. Freeman ME, Kanyicska B, Lerant A, Nagy G. Prolactin: structure, function, and regulation of secretion. Physiol Rev 2000;Oct80(4):1523-631
32. De Rosa M, Zarrilli S, Di Sarno A, et al. Hyperprolactinemia in men: clinical and biochemical features and response to treatment. Endocrine 2003;Feb-Mar20(1-2):75-82
33. Webster J, Piscitelli G, Polli A, et al. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group. N Engl J Med 1994;Oct6331(14):904-9
34. De Rosa M, Colao A, Di Sarno A, et al. Cabergoline treatment rapidly improves gonadal function in hyperprolactinemic males: a comparison with bromocriptine. Eur J Endocrinol 1998;Mar138(3):286-93
35. Walia R, Bhansali A, Dutta P, et al. Recovery pattern of hypothalamo-pituitary-testicular axis in patients with macroprolactinomas after treatment with cabergoline. Indian J Med Res 2011;Sep134:314-19
36. De Rosa M, Ciccarelli A, Zarrilli S, et al. The treatment with cabergoline for 24 month normalizes the quality of seminal fluid in hyperprolactinaemic males. Clin Endocrinol (Oxf) 2006;Mar64(3):307-13
37. Colao A, Vitale G, Cappabianca P, et al. Outcome of cabergoline treatment in men with prolactinoma: effects of a 24-month treatment on prolactin levels, tumor mass, recovery of pituitary function, and semen analysis. J Clin Endocrinol Metab 2004;Apr89(4):1704-11
38. Laufer N, Yaffe H, Margalioth EJ, et al. Effect of bromocriptine treatment on male infertility associated with hyperprolactinemia. Arch Androl 1981;Jun6(4):343-6
39. AinMelk Y, Belisle S, Kandalaft N, et al. Bromocriptine therapy in oligozoospermic infertile men. Arch Androl 1982;Mar8(2):135-41
40. Hovatta O, Koskimies AI, Ranta T, et al. Bromocriptine treatment of oligospermia: a double blind study. Clin Endocrinol (Oxf) 1979;Oct11(4):377-82
41. Lunglmayr G, Maier U, Spona J. Therapy of idiopathic oligozoospermia with bromicriptine. Results of a prospective controlled study. Andrologia 1983;15(Spec No):548-53
42. Hayes FJ, Seminara SB, Decruz S, et al. Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. J Clin Endocrinol Metab 2000;Sep85(9):3027-35
43. Richthoff J, Rylander L, Jonsson BA, et al. Serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in relation to markers of reproductive function in young males from the general Swedish population. Environ Health Perspect 2003;Apr111(4):409-13
44. Rozati R, Reddy PP, Reddanna P, Mujtaba R. Role of environmental estrogens in the deterioration of male factor fertility. Fertil Steril 2002;Dec78(6):1187-94
45. Katz DJ, Nabulsi O, Tal R, Mulhall JP. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int 2012;Aug110(4):573-8
46. Whitten SJ, Nangia AK, Kolettis PN. Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate. Fertil Steril 2006;Dec86(6):1664-8
47. World Health Organization. A double-blind trial of clomiphene citrate for the treatment of idiopathic male infertility. Int J Androl 1992;15(4):299-307
48. Hussein A, Ozgok Y, Ross L, Niederberger C. Clomiphene administration for cases of nonobstructive azoospermia: a multicenter study. J Androl 2005;Nov-Dec26(6):787-91; discussion 92-3
49. Adamopoulos DA, Nicopoulou S, Kapolla N, et al. The combination of testosterone undecanoate with tamoxifen citrate enhances the effects of each agent given independently on seminal parameters in men with idiopathic oligozoospermia. Fertil Steril 1997;Apr67(4):756-62
50. Ko EY, Siddiqi K, Brannigan RE, Sabanegh ES Jr. Empirical medical therapy for idiopathic male infertility: a survey of the American Urological Association. J Urol 2012;Mar187(3):973-8
51. Saylam B, Efesoy O, Cayan S. The effect of aromatase inhibitor letrozole on body mass index, serum hormones, and sperm parameters in infertile men. Fertil Steril 2011;Feb95(2):809-11
52. Clark RV, Sherins RJ. Treatment of men with idiopathic oligozoospermic infertility using the aromatase inhibitor, testolactone. Results of a double-blinded, randomized, placebo-controlled trial with crossover. J Androl 1989;May-Jun10(3):240-7
53. Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol 2002;Feb167(2 Pt 1):624-9
54. Gregoriou O, Bakas P, Grigoriadis C, et al. Changes in hormonal profile and seminal parameters with use of aromatase inhibitors in management of infertile men with low testosterone to estradiol ratios. Fertil Steril 2012;98:48-51
55. Ramasamy R, Ricci JA, Palermo GD, et al. Successful fertility treatment for Klinefelter's syndrome. J Urol 2009;Sep182(3):1108-13
56. Adamopoulos DA, Pappa A, Billa E, et al. Effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in men with idiopathic oligozoospermia. Fertil Steril 2003;Oct80(4):914-20
57. Koukkou E, Billa E, Kapolla N, et al. An empiric treatment for idiopathic oligozoospermia revisited: a 20-year investigative saga. Andrologia 2012;Oct44(5):337-42
58. Ghanem H, Shaeer O, El-Segini A. Combination clomiphene citrate and antioxidant therapy for idiopathic male infertility: a randomized controlled trial. Fertil Steril 2010;May193(7):2232-5
59. Marshburn PB, Kutteh WH. The role of antisperm antibodies in infertility. Fertil Steril 1994;May61(5):799-811
60. Abshagen K, Behre HM, Cooper TG, Nieschlag E. Influence of sperm surface antibodies on spontaneous pregnancy rates. Fertil Steril 1998;Aug70(2):355-6
61. Hendry WF, Hughes L, Scammell G, et al. Comparison of prednisolone and placebo in subfertile men with antibodies to spermatozoa. Lancet 1990;Jan13335(8681):85-8
62. Omu AE, al-Qattan F, Abdul Hamada B. Effect of low dose continuous corticosteroid therapy in men with antisperm antibodies on spermatozoal quality and conception rate. Eur J Obstet Gynecol Reprod Biol 1996;Nov69(2):129-34
63. Wolff H. The biologic significance of white blood cells in semen. Fertil Steril 1995;Jun63(6):1143-57
64. Fedder J, Askjaer SA, Hjort T. Nonspermatozoal cells in semen: relationship to other semen parameters and fertility status of the couple. Arch Androl 1993;Sep-Oct31(2):95-103
65. Curi SM, Ariagno JI, Chenlo PH, et al. Asthenozoospermia: analysis of a large population. Arch Androl 2003;Sep-Oct49(5):343-9
66. Lackner JE, Herwig R, Schmidbauer J, et al. Correlation of leukocytospermia with clinical infection and the positive effect of antiinflammatory treatment on semen quality. Fertil Steril 2006;Sep86(3):601-5
67. Gambera L, Serafini F, Morgante G, et al. Sperm quality and pregnancy rate after COX-2 inhibitor therapy of infertile males with abacterial leukocytospermia. Hum Reprod 2007;Apr22(4):1047-51
68. Gallegos G, Ramos B, Santiso R, et al. Sperm DNA fragmentation in infertile men with genitourinary infection by Chlamydia trachomatis and Mycoplasma. Fertil Steril 2008;Aug90(2):328-34
69. Hamada A, Agarwal A, Sharma R, et al. Empirical treatment of low-level leukocytospermia with doxycycline in male infertility patients. Urology 2011;Dec78(6):1320-5
70. Branigan EF, Spadoni LR, Muller CH. Identification and treatment of leukocytospermia in couples with unexplained infertility. J Reprod Med 1995;Sep40(9):625-9
71. Sharma RK, Agarwal A. Role of reactive oxygen species in male infertility. Urology 1996;Dec48(6):835-50
72. Chen H, Zhao HX, Huang XF, et al. Does high load of oxidants in human semen contribute to male factor infertility? Antioxid Redox Signal 2012;Apr1516(8):754-9
73. Omu AE, Al-Azemi MK, Kehinde EO, et al. Indications of the mechanisms involved in improved sperm parameters by zinc therapy. Med Princ Pract 2008;17(2):108-16
74. Aitken RJ, Clarkson JS, Fishel S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol Reprod 1989;Jul41(1):183-97
75. de Lamirande E, Gagnon C. Reactive oxygen species and human spermatozoa. I. Effects on the motility of intact spermatozoa and on sperm axonemes. J Androl 1992;Sep-Oct13(5):368-78
76. de Lamirande E, Gagnon C. Reactive oxygen species and human spermatozoa. II. Depletion of adenosine triphosphate plays an important role in the inhibition of sperm motility. J Androl 1992;Sep-Oct13(5):379-86
77. Kovalski NN, de Lamirande E, Gagnon C. Reactive oxygen species generated by human neutrophils inhibit sperm motility: protective effect of seminal plasma and scavengers. Fertil Steril 1992;Oct58(4):809-16
78. Lopes S, Jurisicova A, Sun JG, Casper RF. Reactive oxygen species: potential cause for DNA fragmentation in human spermatozoa. Hum Reprod 1998;Apr13(4):896-900
79. Kothari S, Thompson A, Agarwal A, du Plessis SS. Free radicals: their beneficial and detrimental effects on sperm function. Indian J Exp Biol 2010;May48(5):425-35
80. Showell MG, Brown J, Yazdani A, et al. Antioxidants for male subfertility. Cochrane Database Syst Rev 2011(1):CD007411
81. Ross C, Morriss A, Khairy M, et al. A systematic review of the effect of oral antioxidants on male infertility. Reprod Biomed Online 2010;Jun20(6):711-23
82. Gharagozloo P, Aitken RJ. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod 2011;Jul26(7):1628-40
83. Comhaire F, Decleer W. Quantifying the effectiveness and cost-efficiency of food supplementation with antioxidants for male infertility. Reprod Biomed Online 2011;Sep23(3):361-2
84. Dawson EB, Harris WA, Rankin WE, et al. Effect of ascorbic acid on male fertility. Ann NY Acad Sci 1987;498:312-23
85. Song GJ, Norkus EP, Lewis V. Relationship between seminal ascorbic acid and sperm DNA integrity in infertile men. Int J Androl 2006;Dec29(6):569-75
86. Colagar AH, Marzony ET. Ascorbic Acid in human seminal plasma: determination and its relationship to sperm quality. J Clin Biochem Nutr 2009;Sep45(2):144-9
87. Patel S, Panda S, Nanda R, et al. Influence of oxidants and anti-oxidants on semen parameters in infertile males. J Indian Med Assoc 2009;Feb107(2):78- 80; 2
88. Dawson EB, Harris WA, Powell LC. Relationship between ascorbic acid and male fertility. World Rev Nutr Diet 1990;62:1-26
89. Fraga CG, Motchnik PA, Shigenaga MK, et al. Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci USA 1991;88(24):11003-6
90. Akmal M, Qadri JQ, Al-Waili NS, et al. Improvement in human semen quality after oral supplementation of vitamin C. J Med Food 2006;Fall9(3):440-2
91. Brigelius-Flohe R, Traber MG. Vitamin E: function and metabolism. FASEB J 1999;13(10):1145-55
92. Burton GW, Traber MG. Vitamin E: antioxidant activity, biokinetics, and bioavailability. Annu Rev Nutr 1990;10:357-82
93. Traber MG, Ramakrishnan R, Kayden HJ. Human plasma vitamin E kinetics demonstrate rapid recycling of plasma RRR-alpha-tocopherol. Proc Natl Acad Sci USA 1994;91(21):10005-8
94. Suleiman SA, Ali ME, Zaki ZM, et al. Lipid peroxidation and human sperm motility: protective role of vitamin E. J Androl 1996;Sep-Oct17(5):530-7
95. Kessopoulou E, Powers HJ, Sharma KK, et al. A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility. Fertil Steril 1995;Oct64(4):825-31
96. Rolf C, Cooper TG, Yeung CH, Nieschlag E. Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study. Hum Reprod 1999;Apr14(4):1028-33
97. Bowry VW, Mohr D, Cleary J, Stocker R. Prevention of tocopherol-mediated peroxidation in ubiquinol-10-free human low density lipoprotein. J Biol Chem 1995;Mar17270(11):5756-63
98. Jeulin C, Lewin LM. Role of free L-carnitine and acetyl-L-carnitine in post-gonadal maturation of mammalian spermatozoa. Hum Reprod Update 1996;Mar-Apr2(2):87-102
99. Gulcin I. Antioxidant and antiradical activities of L-carnitine. Life Sci 2006;Jan1878(8):803-11
100. Moradi M, Moradi A, Alemi M, et al. Safety and efficacy of clomiphene citrate and L-carnitine in idiopathic male infertility: a comparative study. Urol J 2010;7(3):188-93
101. Lenzi A, Sgro P, Salacone P, 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;Jun81(6):1578-84
102. Cavallini G, Ferraretti AP, Gianaroli L, et al. Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele- associated oligoasthenospermia. J Androl 2004;Sep-Oct25(5):761-70; discussion 71-2
103. Vitali G, Parente R, Melotti C. Carnitine supplementation in human idiopathic asthenospermia: clinical results. Drugs Exp Clin Res 1995;21(4):157-9
104. Moncada ML, Vicari E, Cimino C, et al. Effect of acetylcarnitine treatment in oligoasthenospermic patients. Acta Eur Fertil 1992;Sep-Oct23(5): 221-4
105. Balercia G, Regoli F, Armeni T, et al. 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;Sep84(3):662-71
106. Costa M, Canale D, Filicori M, et al. L-carnitine in idiopathic asthenozoospermia: a multicenter study. Italian Study Group on Carnitine and Male Infertility. Andrologia 1994;May-Jun26(3):155-9
107. 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;May85(5):1409-14
108. Cavallini G, Ferraretti AP, Gianaroli L, et al. Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele- associated oligoasthenospermia. J Androl 2004;Sep-Oct25(5):761-70; discussion 71-2
109. Ernster L, Dallner G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1995;May241271(1):195-204
110. Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr 2001;Dec20(6):591-8
111. Kalen A, Norling B, Appelkvist EL, Dallner G. Ubiquinone biosynthesis by the microsomal fraction from rat liver. Biochim Biophys Acta 1987;Oct8926(1):70-8
112. Balercia G, Buldreghini E, Vignini A, et al. Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Fertil Steril 2009;May91(5):1785-92
113. Safarinejad MR. Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men. J Urol 2009;Jul182(1):237- 48
114. Rayman MP. The importance of selenium to human health. Lancet 2000;Jul15356(9225):233-41
115. Alvarez JG, Storey BT. Lipid peroxidation and the reactions of superoxide and hydrogen peroxide in mouse spermatozoa. Biol Reprod 1984;May30(4):833-41
116. Ursini F, Heim S, Kiess M, et al. Dual function of the selenoprotein PHGPx during sperm maturation. Science 1999;Aug27285(5432):1393-6
117. Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol 2009;Feb181(2):741-51
118. Scott R, MacPherson A, Yates RW, et al. The effect of oral selenium supplementation on human sperm motility. Br J Urol 1998;Jul82(1):76-80
119. Fawcett WJ, Haxby EJ, Male DA. Magnesium: physiology and pharmacology. Br J Anaesth 1999;Aug83(2):302-20
120. Rayssiguier Y, Durlach J, Gueux E, et al. Magnesium and ageing. I. Experimental data: importance of oxidative damage. Magnes Res 1993;6(4):369-78
121. Zavaczki Z, Szollosi J, Kiss SA, et al. Magnesium-orotate supplementation for idiopathic infertile male patients: a randomized, placebo-controlled clinical pilot study. Magnes Res 2003;16(2):131-6
122. Zago MP, Oteiza PI. The antioxidant properties of zinc: interactions with iron and antioxidants. Free Radic Biol Med 2001;Jul1531(2):266-74
123. Chimienti F, Aouffen M, Favier A, Seve M. Zinc homeostasis-regulating proteins: new drug targets for triggering cell fate. Curr Drug Targets 2003;May4(4):323-38
124. Colagar AH, Marzony ET, Chaichi MJ. Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men. Nutr Res 2009;Feb29(2):82-8
125. Hartoma TR, Nahoul K, Netter A. Zinc, plasma androgens and male sterility. Lancet 1977;Nov262(8048):1125-6
126. Tikkiwal M, Ajmera RL, Mathur NK. Effect of zinc administration on seminal zinc and fertility of oligospermic males. Indian J Physiol Pharmacol 1987;Jan-Mar31(1):30-4
127. Omu AE, Dashti H, Al-Othman S. Treatment of asthenozoospermia with zinc sulphate: andrological, immunological and obstetric outcome. Eur J Obstet Gynecol Reprod Biol 1998;Aug79(2):179-84
128. De Flora S, Cesarone CF, Balansky RM, et al. Chemopreventive properties and mechanisms of N-Acetylcysteine. The experimental background. J Cell Biochem Suppl 1995;22:33-41
129. Gressier B, Cabanis A, Lebegue S, et al. Decrease of hypochlorous acid and hydroxyl radical generated by stimulated human neutrophils: comparison in vitro of some thiol-containing drugs. Methods Find Exp Clin Pharmacol 1994;Jan-Feb16(1):9-13
130. Oeda T, Henkel R, Ohmori H, Schill WB. Scavenging effect of N-acetyl-L-cysteine against reactive oxygen species in human semen: a possible therapeutic modality for male factor infertility? Andrologia 1997;May-Jun29(3):125-31
131. Erkkila K, Hirvonen V, Wuokko E, et al. N-acetyl-L-cysteine inhibits apoptosis in human male germ cells in vitro. J Clin Endocrinol Metab 1998;Jul83(7):2523-31
132. Ciftci H, Verit A, Savas M, et al. Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status. Urology 2009;Jul74(1):73-6
133. Comhaire FH, El Garem Y, Mahmoud A, et al. Combined conventional/ antioxidant "Astaxanthin" treatment for male infertility: a double blind, randomized trial. Asian J Androl 2005;Sep7(3):257-62
134. Krinsky NI. Antioxidant functions of carotenoids. Free Radic Biol Med 1989;7(6):617-35
135. Palozza P, Krinsky NI. The inhibition of radical-initiated peroxidation of microsomal lipids by both alpha-tocopherol and beta-carotene. Free Radic Biol Med 1991;11(4):407-14
136. Krinsky NI. Effects of carotenoids on cells. Mol Aspects Med 1993;14(3):241-6
137. Liebler DC, McClure TD. Antioxidant reactions of beta-carotene: identification of carotenoid-radical adducts. Chem Res Toxicol 1996;Jan-Feb9(1):8-11
138. Gupta NP, Kumar R. Lycopene therapy in idiopathic male infertility-a preliminary report. Int Urol Nephrol 2002;34(3):369-72
139. Wong WY, Merkus HM, Thomas CM, et al. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril 2002;Mar77(3):491-8
140. James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr 2000;Jan71(1 Suppl):343S-8S 141. Hodge WG, Schachter HM, Barnes D, et al. Efficacy of omega-3 fatty acids in preventing age-related macular degeneration: a systematic review. Ophthalmology 2006;Jul113(7):1165-72; quiz 72-3, 78
141. Safarinejad MR. Effect of omega-3 polyunsaturated fatty acid supplementation on semen profile and enzymatic anti-oxidant capacity of seminal plasma in infertile men with idiopathic oligoasthenoteratospermia: a double-blind, placebo-controlled, randomised study. Andrologia 2011;Feb43(1):38-47
142. Greco E, Iacobelli M, Rienzi L, et al. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl 2005;May-Jun26(3):349-53
143. Paradiso Galatioto G, Gravina GL, Angelozzi G, et al. May antioxidant therapy improve sperm parameters of men with persistent oligospermia after retrograde embolization for varicocele? World J Urol 2008;Feb26(1):97-102
144. Vezina D, Mauffette F, Roberts KD, Bleau G. Selenium-vitamin E supplementation in infertile men. Effects on semen parameters and micronutrient levels and distribution. Biol Trace Elem Res 1996;53(1-3):65-83
145. Keskes-Ammar L, Feki-Chakroun N, Rebai T, 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;Mar-Apr49(2):83-94
146. Tremellen K, Miari G, Froiland D, Thompson J. A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF-ICSI treatment. Aust N Z J Obstet Gynaecol 2007;Jun47(3):216-21
147. Goldwasser B, Madgar I, Jonas P, et al. Imipramine for the treatment of sterility in patients following retroperitoneal lymph node dissection. Andrologia 1983;15(Spec No):588-91
148. Wabrek AJ. Sexual dysfunction associated with diabetes mellitus. J Fam Pract 1979;Apr8(4):735-40
149. Yavetz H, Yogev L, Hauser R, et al. Retrograde ejaculation. Hum Reprod 1994;Mar9(3):381-6
150. Jefferys A, Siassakos D, Wardle P. The management of retrograde ejaculation: a systematic review and update. Fertil Steril 2012;Feb97(2):306-12
151. Kamischke A, Nieschlag E. Treatment of retrograde ejaculation and anejaculation. Hum Reprod Update 1999;Sep-Oct5(5):448-74
152. Kamischke A, Nieschlag E. Update on medical treatment of ejaculatory disorders. Int J Androl 2002;Dec25(6):333-44
153. Safarinejad MR. Midodrine for the treatment of organic anejaculation but not spinal cord injury: a prospective randomized placebo-controlled doubleblind clinical study. Int J Impot Res 2009;Jul-Aug21(4):213-20
154. Hershlag A, Schiff SF, DeCherney AH. Retrograde ejaculation. Hum Reprod 1991;Feb6(2):255-8
155. Linsenmeyer TA, Perkash I. Infertility in men with spinal cord injury. Arch Phys Med Rehabil 1991;Sep72(10):747-54
156. Guttmann L, Walsh JJ. Prostigmin assessment test of fertility in spinal man. Paraplegia 1971;May9(1):39-51
157. Yamanaka K, Fujisawa M, Tanaka H, et al. Significance of human testicular mast cells and their subtypes in male infertility. Hum Reprod 2000;Jul15(7):1543-7
158. El-Karaksy A, Mostafa T, Shaeer OK, et al. Seminal mast cells in infertile asthenozoospermic males. Andrologia 2007;Dec39(6):244-7
159. Yamamoto M, Hibi H, Miyake K. New treatment of idiopathic severe oligozoospermia with mast cell blocker: results of a single-blind study. Fertil Steril 1995;Dec64(6):1221-3
160. Oliva A, Multigner L. Ketotifen improves sperm motility and sperm morphology in male patients with leukocytospermia and unexplained infertility. Fertil Steril 2006;Jan85(1):240-3
161. Azadi L, Abbasi H, Deemeh MR, et al. Zaditen (Ketotifen), as mast cell blocker, improves sperm quality, chromatin integrity and pregnancy rate after varicocelectomy. Int J Androl 2010;Oct34(5 Pt 1):446-52
162. Dimitriadis F, Giannakis D, Pardalidis N, et al. Effects of phosphodiesterase-5 inhibitors on sperm parameters and fertilizing capacity. Asian J Androl 2008;Jan10(1):115-33
163. Revelli A, Ghigo D, Moffa F, et al. Guanylate cyclase activity and sperm function. Endocr Rev 2002;Aug23(4):484-94
164. Dimitriadis F, Tsambalas S, Tsounapi P, et al. Effects of phosphodiesterase-5 inhibitors on Leydig cell secretory function in oligoasthenospermic infertile men: a randomized trial. BJU Int 2010;Oct106(8):1181-5
165. Pomara G, Morelli G, Canale D, et al. Alterations in sperm motility after acute oral administration of sildenafil or tadalafil in young, infertile men. Fertil Steril 2007;Oct88(4):860-5
166. Wayman C, Phillips S, Lunny C, et al. Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology. Int J Impot Res 2005;May-Jun17(3):216-23
167. Glenn DR, McVicar CM, McClure N, Lewis SE. Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro. Fertil Steril 2007;May87(5):1064-70
168. Essayan DM. Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol 2001;Nov108(5):671-80
169. Tesarik J, Mendoza C, Carreras A. Effects of phosphodiesterase inhibitors caffeine and pentoxifylline on spontaneous and stimulus-induced acrosome reactions in human sperm. Fertil Steril 1992;Dec58(6):1185-90
170. Tesarik J, Thebault A, Testart J. Effect of pentoxifylline on sperm movement characteristics in normozoospermic and asthenozoospermic specimens. Hum Reprod 1992;Oct7(9):1257-63
171. Garbers DL, First NL, Gorman SK, Lardy HA. The effects of cyclic nucleotide phosphodiesterase inhibitors on ejaculated porcine spermatozoan metabolism. Biol Reprod 1973;Jun8(5):599-606
172. Nassar A, Mahony M, Morshedi M, et al. Modulation of sperm tail protein tyrosine phosphorylation by pentoxifylline and its correlation with hyperactivated motility. Fertil Steril 1999;May71(5):919-23
173. Gavella M, Lipovac V. Pentoxifylline-mediated reduction of superoxide anion production by human spermatozoa. Andrologia 1992;Jan-Feb24(1):37-9
174. Okada H, Tatsumi N, Kanzaki M, et al. Formation of reactive oxygen species by spermatozoa from asthenospermic patients: response to treatment with pentoxifylline. J Urol 1997;Jun157(6):2140-6
175. Micic S, Hadzi-Djokic J, Dotlic R, Tulic C. Pentoxifyllin treatment of oligoasthenospermic men. Acta Eur Fertil 1988;May-Jun19(3):135-7
176. Marrama P, Baraghini GF, Carani C, et al. Further studies on the effects of pentoxifylline on sperm count and sperm motility in patients with idiopathic oligo-asthenozoospermia. Andrologia 1985;Nov-Dec17(6):612-16
177. Wang C, Chan CW, Wong KK, Yeung KK. Comparison of the effectiveness of placebo, clomiphene citrate, mesterolone, pentoxifylline, and testosterone rebound therapy for the treatment of idiopathic oligospermia. Fertil Steril 1983;Sep40(3):358-65
178. Safarinejad MR. Effect of pentoxifylline on semen parameters, reproductive hormones, and seminal plasma antioxidant capacity in men with idiopathic infertility: a randomized double-blind placebo-controlled study. Int Urol Nephrol 2011;Jun43(2):315-28