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VOLUME 4 , ISSUE 1 ( January-April, 2013 ) > List of Articles

RESEARCH ARTICLE

Fixed Dose Combination Therapy of Antioxidants in Treatment of Idiopathic Oligoasthenozoospermia: Results of a Randomized, Double-blind, Placebo-controlled Clinical Trial

Sonia Malik, Sanjay Kalra, Ajit Saxena, Bharti Kalra, Kapil Kochhar, Hemant Zaveri

Citation Information : Malik S, Kalra S, Saxena A, Kalra B, Kochhar K, Zaveri H. Fixed Dose Combination Therapy of Antioxidants in Treatment of Idiopathic Oligoasthenozoospermia: Results of a Randomized, Double-blind, Placebo-controlled Clinical Trial. Int J Infertil Fetal Med 2013; 4 (1):6-13.

DOI: 10.5005/jp-journals-10016-1053

License: CC BY-NC 4.0

Published Online: 01-08-2015

Copyright Statement:  Copyright © 2013; The Author(s).


Abstract

Introduction

To assess the effectiveness and safety of fixed dose combination (FDC) of antioxidants in treatment of idiopathic oligoasthenozoospermia.

Materials and methods

Placebo-controlled, Double-blind, randomized, Parallel three arm, Multicentric trial.

Setting

Fertility clinics of five centers across India.

Patients

One hundred and thirty-eight male subjects, aged between 21 and 50 years and subfertile for 1 year or more with the following baseline sperm selection criteria: Concentration <15 million/ml and total sperm motility <40%.

Intervention(s)

Eligible subjects were randomized to either of the three arms in a double-blind manner, i.e. arm 1 was given 2 tablets twice daily of FDC of antioxidants (coenzyme-Q10: 50 mg, L-carnitine: 500 mg, lycopene: 2.5 mg and zinc: 12.5 mg); arm 2 was given 1 tablet of FDC of antioxidants and one tablet of placebo twice daily and arm 3 was two tablets twice daily of matching placebo all for 180 days.

Main outcome measure(s)

The primary outcome measures were improvement in sperm count and sperm motility, whereas pregnancy rate was the secondary efficacy outcome.

Results

Compared to placebo, a statistically significant improvement was seen in sperm count (14.8-26.35 in arm 1 and 14.37-24.8 million/ml in arm 2, p < 0.0001), and sperm total motility (39.2-51.6% in arm 1 and 38.4-50.1% in arm 2, p < 0.0001), at 90 days, and treatment further improved these parameters at day 180. No intergroup difference was seen between arm 1 and arm 2. Mild adverse event of upper gastrointestinal discomfort by 8 subjects (three in arm 1; one in arm 2 and four subjects in arm 3) were reported. No serious adverse event was seen in the study.

Conclusion

Exogenous administration of fixed dose combination of antioxidants is a safe and effective therapy in improving the male subfertility.

How to cite this article

Gopinath PM, Kalra B, Saxena A, Malik S, Kochhar K, Kalra S, Zaveri H. Fixed Dose Combination Therapy of Antioxidants in Treatment of Idiopathic Oligoasthenozoospermia: Results of a Randomized, Doubleblind, Placebo-controlled Clinical Trial. Int J Infertility Fetal Med 2013;4(1):6-13.

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  1. Advances in development reverse fertility declines. Nature 2009;460:741-43.
  2. Fertility rates and future population trends: Will Europe's birth rate recover or continue to decline? Int J Androl 2006;29:25-33.
  3. Best practice policies for male infertility. Fertil Steril 2002;77:873-82.
  4. Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988- 1989). Hum Reprod 1991;6:811-16.
  5. Clinical use of frozen semen; report of four cases. Fertil Steril 1954;5(6):520-29.
  6. European Association of Urology. Guidelines on male infertility. Accessed on: May 29, 2012. Available from: http://www.uroweb.org/fileadmin/user_upload/Guidelines/13%20Male%20Infertility.pdf
  7. Generation of reactive oxygen species, lipid peroxidation and human sperm function. Biol Reprod 1989;40:183-97.
  8. Lipid peroxidation in human spermatozoa as related to midpiece abnormalities and motility. Gamete Res 1989;24:127-34.
  9. Heart and skeletal muscle ubiquinone or CoQ10 as protective agent against radical formation in man. Adv Myochem 1987;1:305-08.
  10. Ubiquinol: An endogenous antioxidant in aerobic organisms. Clin Invest 1993;71:60-65.
  11. Nonaprenyl- 4-hydroxibenzoate transferase, an enzyme involved in ubiquinone biosynthesis in endoplasmic reticulum–Golgi system. J Biol Chem 1990;25:1158-64.
  12. Coenzyme Q10 concentration in normal and pathological human seminal fluid. J Androl 1994;15:591-94.
  13. Role of CoQ10 in preventing peroxidation of LDL subfraction. Proc Natl Acad Sci USA 1995;92:9388-91.
  14. Relationship between sperm cell ubiquinone and seminal parameters in subjects with and without varicocele. Andrologia 1998;30:1-4.
  15. Coenzyme Q10 levels in idiopathic and varicoceleassociated asthenozoospermia. Andrologia 2002;34:107-11.
  16. Oxyradical scavenging capacity toward different reactive species in seminal plasma and sperm cells. A possible influence on kinetic parameters. Clin Chem Lab Med 2003;41:13-19.
  17. An update of coenzyme Q10 implications in male infertility: Biochemical and therapeutic aspects. Biofactors 2005;25:165-74.
  18. Safety and efficacy of clomiphene citrate and L-carnitine in idiopathic male infertility. Urol J 2010;7:188-93.
  19. Pro-inflammatory and oxidative stress pathways which compromise sperm motility and survival may be altered by L-carnitine. Oxid Med Cell Long 2009;2:73-81.
  20. Role of L-carnitine in male infertility. J Pak Med Assoc 2011;61(8):732-36.
  21. Importance of reactive oxygen species in the peritoneal fluid of women with endometriosis or idiopathic infertility. Fertil Steril 1997;68:826-30.
  22. Sies H. Lycopene as the most efficient biological cartenoid singlet oxygen quencher. Arch Biochem Biophys 1989;274:532-38.
  23. Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men. Nutr Res 2009;29(2):82-88.
  24. Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: A placebo-controlled, double-blind randomized trial. Fertil Steril 2009;91(5):1785-92.
  25. Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men. J Urol 2009;182(1):237-48.
  26. Tamoxifen combined with coenzyme Q10 for idiopathic oligoasthenospermia. Zhonghua Nan Ke Xue 2011;17(7):615-18.
  27. Coenzyme Q10 improves seminal oxidative defense but does not affect on semen parameters in idiopathic oligoasthenozoospermia: A randomized double-blind, placebo controlled trial. J Endocrinol Invest 2011;34(8):e224-28.
  28. L-carnitine in idiopathic asthenozoospermia: A multicenter study. Italian Study Group on Carnitine and Male Infertility. Andrologia 1994; 26(3):155-59.
  29. Use of carnitine therapy in selected cases of male factor infertility: A double-blind crossover trial. Fertil Steril 2003;79(2):292-300.
  30. Carnitine for the treatment of idiopathic asthenospermia: A randomized, doubleblind, placebo-controlled trial. Fertil Steril 2006;85(5):1409-14.
  31. Lycopene therapy in idiopathic male infertility—a preliminary report. Int Urol Nephrol 2002;34(3): 369-72.
  32. The effects of dietary lycopene supplementation on human seminal plasma. BJU Int 2007;99(6):1456-60.
  33. Effects of folic acid and zinc sulfate on male factor subfertility: A double-blind, randomized, placebo-controlled trial. Fertil Steril 2002;77(3):491-98.
  34. Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men? Int J Androl 2006;29(2):339-45.
  35. Laboratory manual for examination of semen and semen–cervical mucus interaction (4th ed). New York: Cambridge University Press 1999;60-63 (Appendix IA and IB).
  36. 238-41) (Appendix I). WHO Library Cataloguing 0020. http://whqlibdoc.who.int/publications/2010/9789241547789_eng.pdf
  37. Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil 1987;81:459-69.
  38. Lipid peroxidation and human sperm motility: Protective role of vitamin E. J Androl 1996;17:530-37.
  39. Oxidative stress, DNA damage and the Y chromosome. Reproduction 2001;122:497-506.
  40. Reactive oxygen species generation by human spermatozoa: A continuing enigma. Int J Androl 2002;25: 191-94.
  41. Role of nitric oxide concentration on human sperm motility. J Androl 2004;25:245-49.
  42. Estimation of plasma and saliva levels of coenzyme Q10 and influence of oral supplementation. Biofactors 2005;25:205-11.
  43. Total antioxidant capacity of seminal plasma is different in fertile and infertile men. Fertil Steril 1995;64:868-70.
  44. Quantification of the nonenzymatic fast and slow TRAP in a postaddition assay in human seminal plasma and the antioxidant contribution of various seminal compounds. J Androl 2000;21:913-20.
  45. Effect of acetylcarnitine treatment in oligoasthenospermic patients. Acta Eur Fertil 1992;23:221-24.
  46. Role of oxidative stress and antioxidant in male infertility. J Androl 1995;16:464-68.
  47. Carnitine supplementation in human idiopathic asthenozoospermia: Clinical results. Drugs Exp Clin Res 1995;21:157-59.
  48. Antioxidant treatment for male subfertility: A promise that remains unfulfilled. Hum Reprod 1998;13:1416-19.
  49. Free radicals, antioxidants and human spermatozoa: Clinical implications. Hum Reprod 1998;13:1415-24.
  50. Antioxidants may protect against infertility. Hum Reprod 1998;13:1415-16.
  51. Antioxidants for male subfertility. Cochrane Database Syst Rev 2011;19(1):CD007411.
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