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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

  • Urology – Original Paper
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Abstract

Objective

To determine the safety and efficacy of oral pentoxifylline (PTX) administration in improving semen parameters in infertile men with idiopathic OAT.

Patients and methods

The study included 254 infertile men who underwent double-blind therapy with 400 mg PTX (Apotex Inc., Toronto, Canada) twice daily (group 1, n = 127), or similar regimen of placebo (group 2, n = 127). The study consisted of a 4-week screening phase, a 24-week treatment phase, and a 12-week treatment-free period. The effects of treatment on semen parameters, serum hormones including testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and inhibin B, seminal plasma catalase-like and superoxide dismutase (SOD)-like activity, and acrosome reaction test were evaluated.

Results

A significant increase in sperm concentration (mean value, 26.4 ± 4.6 × 106/ml vs. 16.2 ± 3.4 × 106/ml), sperm motility (mean value, 35.8 ± 4.2% vs. 26.4 ± 2.4%), and sperm with normal morphology (mean value, 25.4 ± 4.3% vs. 17.4 ± 4.2%) was observed after PTX administration when compared with baseline (all P = 0.001); in contrast, a subtle decreased values were observed after placebo (median values, 16.4 ± 4.1 × 106/ml vs. 16.7 ± 3.6 × 106/ml, P = 0.1; 25.7 ± 3.6% vs. 26.8 ± 2.5%, P = 0.08; and 16.9 ± 4.1% vs. 17.6 ± 4.4%, P = 0.08, respectively). Mean SOD-like and catalase-like activity in the semen of PTX group was significantly greater than in the semen of placebo group (46.4 ± 2.4 vs. 36.3 ± 1.3 U/ml and 371 ± 44 vs. 301 ± 14 U/ml, respectively, both P = 0.003). The acrosome reaction was observed to be increased in PTX group (P = 0.01). Levels of reproductive hormones were also affected.

Conclusions

PTX administration significantly improves semen parameters in infertile men with idiopathic OAT.

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References

  1. de Kretser DM (1997) Male infertility. Lancet 349:787–790

    Article  PubMed  Google Scholar 

  2. Safarinejad MR (2008) Infertility among couples in a population-based study in Iran: prevalence and associated risk factors. Int J Androl 31:303–314

    Article  PubMed  Google Scholar 

  3. Brugh VM III, Lipshultz LI (2004) Male factor infertility: evaluation and management. Med Clin North Am 88:367–385

    Article  PubMed  Google Scholar 

  4. Eugster A, Vingerhoets AJJM (1999) Psychological aspects of in vitro fertilization: a review. Soc Sci Med 48:557–559

    Article  Google Scholar 

  5. Collins J (2002) An international survey of the health economics of IVF and ICSI. Hum Reprod Update 8:265–277

    Article  PubMed  Google Scholar 

  6. Serour GI (2008) Medical and socio-cultural aspects of infertility in the Middle East. Hum Reprod 1:34–41

    Google Scholar 

  7. Serour GI (2002) Attitudes and cultural perspectives on infertility and its alleviation in the Middle East area. In: Vayena E, Rowe PJ, Griffin PD (eds) Current practices and controversies in assisted reproduction. World Health Organization, Geneva, pp 41–49

    Google Scholar 

  8. Kumar R, Gautam G, Gupta NP (2006) Drug therapy for idiopathic male infertility: rationale versus evidence. J Urol 176:1307–1312

    Article  PubMed  CAS  Google Scholar 

  9. Heller CG, Nelson WO, Hill IB et al (1950) Improvement in spermatogenesis following depression of the human testis with testosterone. Fertil Steril 1:415–422

    PubMed  CAS  Google Scholar 

  10. Clark RV, Sherins RJ (1989) 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 10:240–247

    PubMed  CAS  Google Scholar 

  11. Gross KM, Matsumoto AM, Berger RE et al (1986) Increased frequency of pulsatile luteinizing hormone releasing hormone administration selectively decreases follicle-stimulating hormone levels in men with idiopathic azoospermia. Fertil Steril 45:392–396

    PubMed  CAS  Google Scholar 

  12. Vandekerckhove P, Lilford R, Vail A et al (2000) Clomiphene or tamoxifen for idiopathic oligo/asthenospermia. Cochrane Database Syst Rev 2:CD000151

    PubMed  Google Scholar 

  13. Palan P, Naz R (1996) Changes in various antioxidant levels in human seminal plasma related to immunoinfertility. Arch Androl 36:139–143

    Article  PubMed  CAS  Google Scholar 

  14. Keskes-Ammar L, Feki-Chakroun N, Rebai T et al (2003) Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Arch Androl 49:83–94

    Article  PubMed  CAS  Google Scholar 

  15. Lenzi A, Lombardo F, Sgrò P et al (2003) Use of carnitine therapy in selected cases of male factor infertility: a double blind cross-over trial. Fertil Steril 79:292–300

    Article  PubMed  Google Scholar 

  16. Safarinejad MR, Safarinejad S (2009) Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol 181:741–751

    Article  PubMed  CAS  Google Scholar 

  17. Safarinejad MR (2009) Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men. J Urol 182:237–248

    Article  PubMed  CAS  Google Scholar 

  18. Safarinejad MR (2010) 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 41:1–10

    Google Scholar 

  19. Tesarik J, Mendoza C, Carreras A (1992) Effect of phosphodiesterase inhibitors, caffeine and pentoxifylline, on spontaneous and stimulus-induced acrosome reactions in human sperm. Fertil Steril 58:185–190

    Google Scholar 

  20. Garbers DL, Lust WD, First NL et al (1971) Effect of phosphodiesterase inhibitors and cyclic nucleotides on sperm respiration and motility. Biochemistry 10:1825–1831

    Article  Google Scholar 

  21. Nassar A, Mahony M, Morshedi M et al (1999) Modulation of sperm tail protein tyrosine phosphorylation by pentoxifylline and its correlation with hyperactivated motility. Fertil Steril 71:919–923

    Article  PubMed  CAS  Google Scholar 

  22. Oliva A, Dotta A, Multigner L (2009) Pentoxifylline and antioxidants improve sperm quality in male patients with varicocele. Fertil Steril 91(4 Suppl):1536–1539

    Article  PubMed  CAS  Google Scholar 

  23. Laokirkkiat P, Kunathikom S, Choavaratana R et al (2007) Comparison between sperm treated with pentoxifylline and 2-deoxyadenosine using hypo-osmotic swelling test. J Med Assoc Thai 90:211–215

    PubMed  Google Scholar 

  24. Maxwell DT, Jacobson JD, King A et al (2002) Effect of pentoxifylline on tumor suppressor and proto-oncogene apoptosis in sperm. J Assist Reprod Genet 19:279–283

    Article  PubMed  Google Scholar 

  25. Terriou P, Hans E, Giorgetti C et al (2000) Pentoxifylline initiates motility in spontaneously immotile epididymal and testicular spermatozoa and allows normal fertilization, pregnancy, and birth after intracytoplasmic sperm injection. J Assist Reprod Genet 17:194–199

    Article  PubMed  CAS  Google Scholar 

  26. Faka B, Api M, Fiçicioğlu C et al (1994) Pentoxifylline in male-factor infertility: its therapeutic efficacy after oral administration. Acta Eur Fertil 25:351–353

    PubMed  CAS  Google Scholar 

  27. World Health Organization (1999) WHO laboratory manual for the examination of human semen, sperm-cervical mucus interaction, 4th edn. Cambridge University Press, Cambridge

    Google Scholar 

  28. Zini A, Fischer MA, Mak V et al (2002) Catalase-like and superoxide dismutase-like activities in human seminal plasma. Urol Res 30:321–323

    Article  PubMed  CAS  Google Scholar 

  29. Yeung CH, De Geyter C, De Geyter M et al (1996) Production of reactive oxygen species by and hydrogen peroxide scavenging activity of spermatozoa in an IVF program. J Assist Reprod Genet 13:495–500

    Article  PubMed  CAS  Google Scholar 

  30. Garde JJ, Ortiz N, Garcia A et al (1997) Use of triple-stain technique to detect viability and acrosome reaction in deer spermatozoa. Arch Androl 39:1–9

    Article  PubMed  CAS  Google Scholar 

  31. Aitken RJ, Clarkson JS (1987) Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil 81:459–469

    Article  PubMed  CAS  Google Scholar 

  32. Kovacic B, Vlaisavljevic V, Reljic M (2006) Clinical use of pentoxifylline for activation of immotile testicular sperm before ICSI in patients with azoospermia. J Androl 27:45–52

    Article  PubMed  CAS  Google Scholar 

  33. Merino G, Martínez Chéquer JC, Barahona E et al (1997) Effects of pentoxifylline on sperm motility in normogonadotropic asthenozoospermic men. Arch Androl 39:65–69

    Article  PubMed  CAS  Google Scholar 

  34. Marrama P, Baraghini GF, Carani C et al (1985) Further studies on the effects of pentoxifylline on sperm count and sperm motility in patients with idiopathic oligo-asthenozoospermia. Andrologia 17:612–616

    Article  PubMed  CAS  Google Scholar 

  35. Malachi T, Bichachu S, Halbrecht I (1982) Prostaglandins and cyclic-AMP in human semen. Prostaglandins Leukot Med 8:55–62

    Article  PubMed  CAS  Google Scholar 

  36. Ahmad MK, Mahdi AA, Shukla KK et al (2008) Effect of Mucuna pruriens on semen profile and biochemical parameters in seminal plasma of infertile men. Fertil Steril 90:627–635

    Article  PubMed  CAS  Google Scholar 

  37. Lefievre L, Jha KN, de Lamirande E et al (2002) Activation of protein kinase A during human sperm capacitation and acrosome reaction. J Androl 23:709–716

    PubMed  CAS  Google Scholar 

  38. Osheroff JE, Visconti PE, Valenzuela JP et al (1999) Regulation of human sperm capacitation by a cholesterol efflux-stimulated signal transduction pathway leading to protein kinase A-mediated up-regulation of protein tyrosine phosphorylation. Mol Hum Reprod 5:1017–1026

    Article  PubMed  CAS  Google Scholar 

  39. Saleh R, Agarwal A (2002) Oxidative stress and male infertility: from research bench to clinical practice. J Androl 23:737–752

    PubMed  CAS  Google Scholar 

  40. Aitkin RJ, West K, Buckingham DW (1994) Leukocytic infiltration into the human ejaculate and its association with sperm quality, oxidative stress and sperm function. J Androl 15:343–352

    Google Scholar 

  41. Comhaire FH, Mahmoud AM, Depuydt CE et al (1999) Mechanism and effects of male genital tract infection on sperm quality and fertilizing potential: the Andrologist’s view point. Hum Reprod Update 5:393–398

    Article  PubMed  CAS  Google Scholar 

  42. Zabel P, Wolter DT, Schonharting MM et al (1989) Oxpentifylline in endotoxemia. Lancet 2:1474–1477

    Article  PubMed  CAS  Google Scholar 

  43. Thanhäuser A, Reiling N, Böhle A et al (1993) Pentoxifylline: a potent inhibitor of IL-2 and IFN-gamma biosynthesis and BCG-induced cytotoxicity. Immunology 80:151–156

    PubMed  Google Scholar 

  44. Sullivan GW, Carper HT, Novick WJ Jr et al (1988) Inhibition of the inflammatory action of interleukin-1 and tumor necrosis factor-alpha on neutrophil function by pentoxifylline. Infect Immunol 56:1722–1729

    CAS  Google Scholar 

  45. Crouch SP, Fletcher J (1992) Effect of ingested pentoxifylline on neutrophil superoxide anion production. Infect Immun 60:4504–4509

    PubMed  CAS  Google Scholar 

  46. D’Hellencourt CL, Diaw L, Cornillet P et al (1996) Differential regulation of TNF alpha, IL-1 beta, IL-6, IL-8, TNF beta, and IL-10 by pentoxifylline. Int J Immunopharmacol 18:739–748

    Article  PubMed  Google Scholar 

  47. Hammerman C, Goldschmidt D, Caplan MS et al (1999) Amelioration of ischemia-reperfusion injury in rat intestine by pentoxifylline-mediated inhibition of xantine oxidase. J Pediatr Gastroenterol Nutr 29:69–74

    Article  PubMed  CAS  Google Scholar 

  48. Cross AR, Jones OT (1991) Enzymic mechanisms of superoxide production. Biochim Biophys Acta 1057:281–298

    Article  PubMed  CAS  Google Scholar 

  49. Bilsborough W, O’Driscoll G, Stanton K et al (2002) Effect of lowering tumor necrosis factor-alpha on vascular endothelial function in type 2 diabetes. Clin Sci (Lond) 103:163–169

    Article  CAS  Google Scholar 

  50. Jackson MJ, Papa S, Bolaños J et al (2002) Antioxidants, reactive oxygen and nitrogen species, gene induction and mitochondrial function. Mol Aspects Med 23:209–285

    Article  PubMed  CAS  Google Scholar 

  51. Keskes-Ammar L, Feki-Chakroun N, Rebai T et al (2003) Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Arch Androl 49:83–94

    Article  PubMed  CAS  Google Scholar 

  52. Lenzi A, Culasso F, Gandini L et al (1993) Placebo-controlled, double blind, cross-over trial of glutathione therapy in male infertility. Hum Reprod 8:1657–1662

    PubMed  CAS  Google Scholar 

  53. Costa M, Canale D, Filicori M et al (1994) L-Carnitine in idiopathic asthenozoospermia: a multicenter study. Andrologia 26:155–159

    Article  PubMed  CAS  Google Scholar 

  54. Oates RD, Silber S, Brown LG et al (2002) Clinical characterization of 42 oligospermic or azoospermic men with microdeletion of the AZFc region of the Y chromosome, and of 18 children conceived via ICSI. Hum Reprod 17:2813–2824

    Article  PubMed  CAS  Google Scholar 

  55. Hansen M, Kurinczuk JJ, Bower C et al (2002) The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 346:725–730

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank all the participants for their enthusiastic cooperation, which made this study clinically and scientifically relevant. The authors wish to thank Shiva Safarinejad and Nayyer Shafiei for their excellent technical assistance and Saba Safarinejad for her advice regarding collection and statistical evaluation of data.

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  1. Private Practice of Urology and Andrology, P.O. Box 19395-1849, Tehran, Iran

    Mohammad Reza Safarinejad

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Correspondence to Mohammad Reza Safarinejad.

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Safarinejad, M.R. 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 43, 315–328 (2011). https://doi.org/10.1007/s11255-010-9826-4

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