Browse > Article
http://dx.doi.org/10.5653/cerm.2014.41.3.108

Empirical medical therapy in idiopathic male infertility: Promise or panacea?  

Jung, Jae Hung (Department of Urology, Yonsei University Wonju College of Medicine)
Seo, Ju Tae (Department of Urology, Cheil General Hospital, Kwandong University College of Medicine)
Publication Information
Clinical and Experimental Reproductive Medicine / v.41, no.3, 2014 , pp. 108-114 More about this Journal
Abstract
Male factors account for 20%-50% of cases of infertility and in 25% of cases, the etiology of male infertility is unknown. Effective treatments are well-established for hypogonadotropic hypogonadism, male accessory gland infection, retrograde ejaculation, and positive antisperm antibody. However, the appropriate treatment for idiopathic male infertility is unclear. Empirical medical treatment (EMT) has been used in men with idiopathic infertility and can be divided into two categories based on the mode of action: hormonal treatment and antioxidant supplementation. Hormonal medications consist of gonadotropins, androgens, estrogen receptor blockers, and aromatase inhibitors. Antioxidants such as vitamins, zinc, and carnitines have also been widely used to reduce oxidative stress-induced spermatozoa damage. Although scientifically acceptable evidence of EMT is limited because of the lack of large, randomized, controlled studies, recent systematic reviews with meta-analyses have shown that the administration of gonadotropins, anti-estrogens, and oral antioxidants results in a significant increase in the live birth rate compared with control treatments. Therefore, all physicians who treat infertility should bear in mind that EMT can improve semen parameters and subsequent fertility potential through natural intercourse.
Keywords
Drug therapy; Infertility, male; Pregnancy outcome; Semen analysis;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Gnoth C, Godehardt E, Frank-Herrmann P, Friol K, Tigges J, Freundl G. Definition and prevalence of subfertility and infertility. Hum Reprod 2005;20:1144-7.   DOI   ScienceOn
2 Irvine DS. Epidemiology and aetiology of male infertility. Hum Reprod 1998;13 Suppl 1:33-44.
3 Sabanegh EJ, Agarwal A. Male infertility. In: Campbell MF, Walsh PC, Wein AJ, editor. Campbell-Walsh urology. 10th ed. Philadelphia: Saunders Elsevier; 2012. p. 616-47.
4 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;187:973-8.   DOI   ScienceOn
5 Kumar R, Gautam G, Gupta NP. Drug therapy for idiopathic male infertility: rationale versus evidence. J Urol 2006;176:1307-12.   DOI   ScienceOn
6 Rittenberg V, El-Toukhy T. Medical treatment of male infertility. Hum Fertil (Camb) 2010;13:208-16.   DOI   ScienceOn
7 Valenti D, La Vignera S, Condorelli RA, Rago R, Barone N, Vicari E, et al. Follicle-stimulating hormone treatment in normogonadotropic infertile men. Nat Rev Urol 2013;10:55-62.   DOI
8 Iacono F, Barra S, Montano L, Lotti T. Value of high-dose pure FSH in the treatment of idiopathic male infertility. J Urol (Paris) 1996;102:81-4.
9 Foresta C, Bettella A, Ferlin A, Garolla A, Rossato M. Evidence for a stimulatory role of follicle-stimulating hormone on the spermatogonial population in adult males. Fertil Steril 1998;69:636-42.   DOI   ScienceOn
10 Paradisi R, Busacchi P, Seracchioli R, Porcu E, Venturoli S. Effects of high doses of recombinant human follicle-stimulating hormone in the treatment of male factor infertility: results of a pilot study. Fertil Steril 2006;86:728-31.   DOI   ScienceOn
11 Arnaldi G, Balercia G, Barbatelli G, Mantero F. Effects of long-term treatment with human pure follicle-stimulating hormone on semen parameters and sperm-cell ultrastructure in idiopathic oligoteratoasthenozoospermia. Andrologia 2000;32:155-61.   DOI   ScienceOn
12 Piomboni P, Serafini F, Gambera L, Musacchio C, Collodel G, Morgante G, et al. Sperm aneuploidies after human recombinant follicle stimulating hormone therapy in infertile males. Reprod Biomed Online 2009;18:622-9.   DOI   ScienceOn
13 Attia AM, Abou-Setta AM, Al-Inany HG. Gonadotrophins for idiopathic male factor subfertility. Cochrane Database Syst Rev 2013;8:CD005071.
14 Knuth UA, Honigl W, Bals-Pratsch M, Schleicher G, Nieschlag E. Treatment of severe oligospermia with human chorionic gonadotropin/human menopausal gonadotropin: a placebo-controlled, double blind trial. J Clin Endocrinol Metab 1987;65:1081-7.   DOI
15 Kamischke A, Behre HM, Bergmann M, Simoni M, Schafer T, Nieschlag E. Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: a randomized, double-blind, placebo-controlled, clinical trial. Hum Reprod 1998;13:596-603.   DOI   ScienceOn
16 Vandekerckhove P, Lilford R, Vail A, Hughes E. Androgens versus placebo or no treatment for idiopathic oligo/asthenospermia. Cochrane Database Syst Rev 1996;18:CD000150.
17 Foresta C, Bettella A, Garolla A, Ambrosini G, Ferlin A. Treatment of male idiopathic infertility with recombinant human folliclestimulating hormone: a prospective, controlled, randomized clinical study. Fertil Steril 2005;84:654-61.   DOI   ScienceOn
18 Matorras R, Perez C, Corcostegui B, Pijoan JI, Ramon O, Delgado P, et al. Treatment of the male with follicle-stimulating hormone in intrauterine insemination with husband's spermatozoa: a randomized study. Hum Reprod 1997;12:24-8.   DOI   ScienceOn
19 Baccetti B, Piomboni P, Bruni E, Capitani S, Gambera L, Moretti E, et al. Effect of follicle-stimulating hormone on sperm quality and pregnancy rate. Asian J Androl 2004;6:133-7.
20 Gregoriou O, Papadias C, Gargaropoulos A, Konidaris S, Kontogeorgi Z, Kalampokas E. Treatment of idiopathic infertility with testosterone undecanoate. A double blind study. Clin Exp Obstet Gynecol 1993;20:9-12.
21 Liu PY, Handelsman DJ. The present and future state of hormonal treatment for male infertility. Hum Reprod Update 2003;9:9-23.   DOI   ScienceOn
22 Kamischke A, Nieschlag E. Analysis of medical treatment of male infertility. Hum Reprod 1999;14 Suppl 1:1-23.
23 Fronczak CM, Kim ED, Barqawi AB. The insults of illicit drug use on male fertility. J Androl 2012;33:515-28.   DOI   ScienceOn
24 de Souza GL, Hallak J. Anabolic steroids and male infertility: a comprehensive review. BJU Int 2011;108:1860-5.   DOI   ScienceOn
25 Patankar SS, Kaore SB, Sawane MV, Mishra NV, Deshkar AM. Effect of clomiphene citrate on sperm density in male partners of infertile couples. Indian J Physiol Pharmacol 2007;51:195-8.
26 Hayes FJ, Seminara SB, Decruz S, Boepple PA, Crowley WF Jr. Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. J Clin Endocrinol Metab 2000;85:3027-35.
27 Pavlovich CP, King P, Goldstein M, Schlegel PN. Evidence of a treatable endocrinopathy in infertile men. J Urol 2001;165:837-41.   DOI   ScienceOn
28 Vandekerckhove P, Lilford R, Vail A, Hughes E. Clomiphene or tamoxifen for idiopathic oligo/asthenospermia. Cochrane Database Syst Rev 1996;4:CD000151.
29 Chua ME, Escusa KG, Luna S, Tapia LC, Dofitas B, Morales M. Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis. Andrology 2013;1:749-57.   DOI   ScienceOn
30 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;10:240-7.   DOI
31 Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol 2002;167:624-9.   DOI   ScienceOn
32 Lee JS, Park YS, Lee JS, Seo JT. Appropriate Testosterone-to-Estradiol Ratios for Aromatase Inhibitor Usage in Oligoasthenospermic Men. Korean J Androl 2004;22:31-5.
33 Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44-84.   DOI   ScienceOn
34 Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Mens Health 2014;32:1-17.   DOI
35 Sanocka D, Kurpisz M. Reactive oxygen species and sperm cells. Reprod Biol Endocrinol 2004;2:12.   DOI   ScienceOn
36 Sharma RK, Agarwal A. Role of reactive oxygen species in male infertility. Urology 1996;48:835-50.   DOI   ScienceOn
37 Chen H, Zhao HX, Huang XF, Chen GW, Yang ZX, Sun WJ, et al. Does high load of oxidants in human semen contribute to male factor infertility? Antioxid Redox Signal 2012;16:754-9.   DOI   ScienceOn
38 Kessopoulou E, Powers HJ, Sharma KK, Pearson MJ, Russell JM, Cooke ID, 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;64:825-31.   DOI
39 Jensen TK, Skakkebaek NE, Jorgensen N, Jensen MB, Juul A. Antioxidants and male subfertility--a survey of a Cochrane review. Ugeskr Laeger 2011;173:3253-5.
40 Suleiman SA, Ali ME, Zaki ZM, el-Malik EM, Nasr MA. Lipid peroxidation and human sperm motility: protective role of vitamin E. J Androl 1996;17:530-7.
41 Showell MG, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database Syst Rev 2011:CD007411.
42 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.   DOI
43 Akmal M, Qadri JQ, Al-Waili NS, Thangal S, Haq A, Saloom KY. Improvement in human semen quality after oral supplementation of vitamin C. J Med Food 2006;9:440-2.   DOI   ScienceOn
44 Bray TM, Bettger WJ. The physiological role of zinc as an antioxidant. Free Radic Biol Med 1990;8:281-91.   DOI   ScienceOn
45 Zago MP, Oteiza PI. The antioxidant properties of zinc: interactions with iron and antioxidants. Free Radic Biol Med 2001;31:266-74.   DOI   ScienceOn
46 Gavella M, Lipovac V, Vucic M, Sverko V. In vitro inhibition of superoxide anion production and superoxide dismutase activity by zinc in human spermatozoa. Int J Androl 1999;22:266-74.   DOI
47 Turk S, Mandar R, Mahlapuu R, Viitak A, Punab M, Kullisaar T. Male infertility: decreased levels of selenium, zinc and antioxidants. J Trace Elem Med Biol 2014;28:179-85.   DOI   ScienceOn
48 Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebocontrolled trial. Fertil Steril 2002;77:491-8.   DOI   ScienceOn
49 Omu AE, Al-Azemi MK, Kehinde EO, Anim JT, Oriowo MA, Mathew TC. Indications of the mechanisms involved in improved sperm parameters by zinc therapy. Med Princ Pract 2008;17:108-16.   DOI   ScienceOn
50 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;79:179-84.   DOI   ScienceOn
51 Jeulin C, Lewin LM. Role of free L-carnitine and acetyl-L-carnitine in post-gonadal maturation of mammalian spermatozoa. Hum Reprod Update 1996;2:87-102.   DOI
52 Zhou X, Liu F, Zhai S. Effect of L-carnitine and/or L-acetyl-carnitine in nutrition treatment for male infertility: a systematic review. Asia Pac J Clin Nutr 2007;16 Suppl 1:383-90.
53 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;84:662-71.   DOI   ScienceOn
54 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;81:1578-84.   DOI   ScienceOn
55 Peivandi S, Abasali K, Narges M. Effects of L-carnitine on infertile men's spermogram; a randomised clinical trial. J Reprod Infertil 2010;10:331.
56 Mancini A, Conte B, De Marinis L, Hallgass ME, Pozza D, Oradei A, et al. Coenzyme Q10 levels in human seminal fluid: diagnostic and clinical implications. Mol Aspects Med 1994;15 Suppl:s249-55.   DOI   ScienceOn
57 Lafuente R, Gonzalez-Comadran M, Sola I, Lopez G, Brassesco M, Carreras R, et al. Coenzyme Q10 and male infertility: a meta-analysis. J Assist Reprod Genet 2013;30:1147-56.   DOI   ScienceOn
58 Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-ace tyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol 2009;181:741-51.
59 Zavaczki Z, Szollosi J, Kiss SA, Koloszar S, Fejes I, Kovacs L, et al. Magnesium-orotate supplementation for idiopathic infertile male patients: a randomized, placebo-controlled clinical pilot study. Magnes Res 2003;16:131-6.
60 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;40:358-65.   DOI
61 Adamopoulos DA, Pappa A, Billa E, Nicopoulou S, Koukkou E, Michopoulos J. Effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in men with idiopathic oligozoospermia. Fertil Steril 2003;80:914-20.   DOI   ScienceOn
62 Adamopoulos DA, Nicopoulou S, Kapolla N, Karamertzanis M, Andreou E. 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;67:756-62.   DOI   ScienceOn
63 Dohle GR, Colpi GM, Hargreave TB, Papp GK, Jungwirth A, Weidner W, et al. EAU guidelines on male infertility. Eur Urol 2005;48:703-11.   DOI   ScienceOn
64 Jungwirth A, Giwercman A, Tournaye H, Diemer T, Kopa Z, Dohle G, et al. European Association of Urology guidelines on Male Infertility: the 2012 update. Eur Urol 2012;62:324-32.   DOI   ScienceOn
65 Moradi M, Moradi A, Alemi M, Ahmadnia H, Abdi H, Ahmadi A, et al. Safety and efficacy of clomiphene citrate and L-carnitine in idiopathic male infertility: a comparative study. Urol J 2010;7:188-93.
66 Ghanem H, Shaeer O, El-Segini A. Combination clomiphene citrate and antioxidant therapy for idiopathic male infertility: a randomized controlled trial. Fertil Steril 2010;93:2232-5.   DOI   ScienceOn
67 Paradiso Galatioto G, 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.   DOI
68 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;14:1028-33.   DOI   ScienceOn
69 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;26:349-53.   DOI   ScienceOn
70 Scott R, MacPherson A, Yates RW, Hussain B, Dixon J. The effect of oral selenium supplementation on human sperm motility. Br J Urol 1998;82:76-80.   DOI   ScienceOn
71 Derman SG, Adashi EY. Adverse effects of fertility drugs. Drug Saf 1994;11:408-21.   DOI   ScienceOn
72 Cavallini G, Ferraretti AP, Gianaroli L, Biagiotti G, Vitali G. Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-associated oligoasthenospermia. J Androl 2004;25:761-70.   DOI
73 Kim JW, Moon DG. Diagnosis and treatment of sexual dysfunctions in late-onset hypogonadism. Korean J Urol 2011;52:725-35.   DOI   ScienceOn
74 Jan Z, Pfeifer M, Zorn B. Reversible testosterone-induced azoospermia in a 45-year-old man attending an infertility outpatient clinic. Andrologia 2012;44 Suppl 1:823-5.   DOI   ScienceOn
75 Nudell DM, Monoski MM, Lipshultz LI. Common medications and drugs: how they affect male fertility. Urol Clin North Am 2002;29:965-73.   DOI