Volume 10, Issue 5 (10-2012)                   IJRM 2012, 10(5): 441-452 | Back to browse issues page

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Amirzargar M A, Yavangi M, Basiri A, Hosseini Moghaddam S M, Babbolhavaeji H, Amirzargar N, et al . Comparison of recombinant human follicle stimulating hormone (rhFSH), human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) on semen parameters after varicocelectomy: a randomized clinical trial. IJRM 2012; 10 (5) :441-452
URL: http://ijrm.ir/article-1-309-en.html
Comparison of recombinant human follicle stimulating hormone (rhFSH), human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) on semen parameters after varicocelectomy: a randomized clinical trial
Mohammad Ali Amirzargar * 1, Mahnaz Yavangi2 , Abbass Basiri3 , Sayyed Mahdi Hosseini Moghaddam3 , Hooshang Babbolhavaeji4 , Nasibeh Amirzargar3 , Hossein Amirzargar3 , Leila Moadabshoar3
1- Department of Urology, Hamadan University of Medical Sciences, Hamadan, Iran , dr_amirzargar@yahoo.com
2- Department of Obstetrics and Gynecology, Fatemieh Infertility Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
3- Urology and Nephrology Research Center, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4- Department of Urology, Hamadan University of Medical Sciences, Hamadan, Iran
Abstract:   (5400 Views)
Background: The most frequent physical finding in infertile men is varicocele, in which one of the mechanisms that can affect seminal parameters is oxidative stress.
Objective: Our study aimed, for the first time, to compare the efficacy of recombinant human follicle-stimulating hormone (rhFSH), human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) on sperm parameters and fertility after varicocelectomy.
Materials and Methods: 113 infertile men with varicocele were divided into four groups. Group A received HCG 5000 IU weekly, group B received HMG 75 IU three times a week, group C received rhFSH 75 IU three times a week and group D received no medical treatment after varicocelectomy.
Results: After three months, in group A sperm morphology improved (p=0.007), causing a 32% pregnancy rate. In group B, sperm motility (p=0.023) and morphology (p=0.014) improved, causing a 57% pregnancy rate. In group C, all of the investigated semen parameters increased (p<0.05), causing a 62.5% pregnancy rate. Only rhFSH improved sperm concentrations to >20×106 mL (p=0.027). In group D, sperm morphology increased (p=0.038), but other parameters remained unchanged and no pregnancies occurred.
Conclusion: It can be concluded that drugs can reduce induction time for spermatogenesis and fertility in comparison with varicocelectomy alone. For these purposes, rhFSH is more effective than other drugs.
Keywords: Male Infertility, Semen Analyses, Varicocele, Varicocelectomy, HCG, HMG, rhFSH
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Type of Study: Original Article |
References
1. World Health Organization. Laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th Ed. Cambridge University Press, New York; 1999.
2. Lund L, Larsen SB. A follow-up study of semen quality and fertility in men with varicocele testis and in control subjects. Br J Urol 1998; 82: 682-686. [DOI:10.1046/j.1464-410X.1998.00850.x]
3. Cocuzza M, Cocuzza MA, Bragais F, Agarwal A. The role of varicocele repair in the new era of assisted reproductive technology. Clinics (Sao Paolo) 2008; 63: 395-404. [DOI:10.1590/S1807-59322008000300018]
4. Gorelick JI, Goldstein M. Loss of fertility in men with varicocele. Fertil Steril 1993; 59: 613-616. [DOI:10.1016/S0015-0282(16)55809-9]
5. Witt MA, Lipshultz LI. Varicocele: a progressive or static lesion? Urology 1993; 42: 541-543. [DOI:10.1016/0090-4295(93)90268-F]
6. Bong GW, Koo HP. The adolescent varicocele: to treat or not to treat. Urol Clin North Am 2004; 31: 509-515. [DOI:10.1016/j.ucl.2004.04.012]
7. Papadimas J, Mantalenakis S. Hormonal profile in infertile men. Arch Androl 1983; 11: 73-80. [DOI:10.3109/01485018308987463]
8. Saleh RA, Agarwal A, Sharma RK, Said TM, Sikka SC, Thomas AJ Jr. Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele. Fertil Steril 2003; 80: 1431-1436. [DOI:10.1016/S0015-0282(03)02211-8]
9. Naugton DK, Nangia AK, Agarwal A. Varicocele and male infertility: Part II. Pathophysiology of varicoceles in male infertility. Hum Reprod Update 2001; 7: 473-481. [DOI:10.1093/humupd/7.5.473]
10. Fuzisawa M, Yoshida S, Kojima K, Kamidono S. Biochemical changes in testicular varicocele. Arch Androl 1989; 22: 149-159. [DOI:10.3109/01485018908986765]
11. Hendin BN, Kolettis PN, Sharma RK, Thomas AJ Jr, Agarwal A. Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity. J Urol 1999; 161: 1831-1834. [DOI:10.1016/S0022-5347(05)68818-0]
12. Sweeney TE, Rozum JS, Gore RW. Alteration of testicular microvascular pressures during venous pressure elevation. Am J Physiol 1995; 269: 37-45. [DOI:10.1152/ajpheart.1995.269.1.H37]
13. Wright EJ, Young GP, Goldstein M. Reduction in testicular temperature after varicocelectomy in infertile men. Urology 1997; 50: 257-259. [DOI:10.1016/S0090-4295(97)00191-X]
14. Marmar JL. The pathophysiology of varicoceles in the light of current molecular and genetic information. Hum Reprod Update 2001; 7: 461-472. [DOI:10.1093/humupd/7.5.461]
15. Mostafa T, Anis TH, El-Nashar A, Imam H, Othman IA. Varicocelectomy reduces reactive oxygen species levels and increases antioxidant activity of seminal plasma from infertile men with varicocele. Int J Androl 2001; 24: 261-265. [DOI:10.1046/j.1365-2605.2001.00296.x]
16. Cervellione RM, Cervato G, Zampieri N, Corroppolo M, Camoglio F, Cestaro B, et al. Effect of varicocelectomy on the plasma oxidative stress parameters. J Pediatr Surg 2006; 41: 403-406. [DOI:10.1016/j.jpedsurg.2005.11.018]
17. Shiraishi K, Naito K. Generation of 4-hydroxy-2-nonenal modified proteins in testes predicts improvement in spermatogenesis after varicocelectomy. Fertil Steril 2006; 86: 233-235. [DOI:10.1016/j.fertnstert.2005.12.022]
18. Gemzell C, Kjessler B. Treatment of infertility after partial hypophysectomy with human gonadotrophins. Lancet 1964; 1: 644. [DOI:10.1016/S0140-6736(64)91459-X]
19. MacLeod J, Pazianos A, Ray BS. Restoration of human spermatogenesis by menopausal gonadotrophins. Lancet 1964; 1: 1196-1197. [DOI:10.1016/S0140-6736(64)91212-7]
20. De Sanctis V, Vullo C, Katz M, Wonke B, Nannetti C, Bagni B. Induction of spermatogenesis in thalassaemia. Fertil Steril 1988; 50: 969-975. [DOI:10.1016/S0015-0282(16)60382-5]
21. Vicari E, Mongioì A, Calogero AE, Moncada ML, Sidoti G, Polosa P, et al. Therapy with human chorionic gonadotrophin alone induces spermatogenesis in men with isolated hypogonadotrophic hypogonadism- long-term follow-up. Int J Androl 1992; 15: 320-329. [DOI:10.1111/j.1365-2605.1992.tb01131.x]
22. Johnsen SG. Maintenance of spermatogenesis induced by HMG treatment by means of continuous HCG treatment in hypogonadotrophic men. Acta Endocrinol (Copenh) 1978; 59: 763-769. [DOI:10.1530/acta.0.0890763]
23. Burger HG, Baker HWG. Therapeutic considerations and results of gonadotropin treatment in male hypogonadotropic hypogonadism. Ann NY Acad Sci 1984; 438: 447-453. [DOI:10.1111/j.1749-6632.1984.tb38305.x]
24. Matsumoto AM, Karpas AE, Bremner WJ. Chronic human chorionic gonadotropin administration in normal men: evidence that follicle stimulating hormone is necessary for the maintenance of quantitatively normal spermatogenesis in man. J Clin Endocrinol Metab 1986; 62: 1184-1192. [DOI:10.1210/jcem-62-6-1184]
25. Dubin L, Amelar RD. Varicocelectomy as therapy in male infertility: a study of 504 cases. J Urol 1975; 113: 640-641. [DOI:10.1016/S0022-5347(17)59542-7]
26. Mehan DJ, Chehval MJ. Human chorionic gonadotropin in the treatment of the infertile man. J Urol 1982; 128: 60-63. [DOI:10.1016/S0022-5347(17)52756-1]
27. Yamamoto M, Hibi H, Katsuno S, Miyake K. Human chorionic gonadotropin adjuvant therapy for patients with Leydig cell dysfunction after varicocelectomy. Arch Androl 1955; 35: 49-55. [DOI:10.3109/01485019508987853]
28. De Rose AF, Gallo F, Giglio M, Parisini B, Carmignani G. Early use of menotropin in the treatment of varicocele]. Arch Ital Urol Androl 2003; 75: 53-57.
29. Radicioni A, Schwarzenberg TL. The use of FSH in adolescents and young adults with left idiopathic varicocele, not submitted to surgery. Preliminary study. Minerva Pediatr 1999; 51: 361-366.
30. Zarrilli S, Paesano L, Colao A, Mirone V, Lombardi G, De Rosa M. FSH treatment improves sperm function in patients after varicocelectomy. J Endocrinol Invest 2000; 23: 68-73. [DOI:10.1007/BF03343681]
31. Baker HW. Male infertility. Endocrinol Metab Clin North Am 1994; 23: 783-793. [DOI:10.1016/S0889-8529(18)30067-7]
32. Nieschlag E. Classification of andrological disorders. In: Andrology (eds. E. Nieschlag, H.M. Behre). Spriger-Verlag, Berlin; 1997. [DOI:10.1007/978-3-662-03455-2_5]
33. Saypol DC. Varicocele. J Androl 1981; 2: 61-71. [DOI:10.1002/j.1939-4640.1981.tb00597.x]
34. Schlegel PN. Is assisted reproductive the optimal treatment for varicocele-associated male infertility? A cost-effectiveness analysis. Urology 1997; 49: 83-90. [DOI:10.1016/S0090-4295(96)00379-2]
35. Redmon JB, Carey P, Pryor JL. Varicocele-the most common cause of male factor infertility? Hum Reprod Update 2002; 8: 53-58. [DOI:10.1093/humupd/8.1.53]
36. Pryor JL, Howards SS. Varicocele. Urol Clin North Am 1987; 14: 499.
37. World Health Organization. The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. Fertil Steril 1992; 57: 1289-1293. [DOI:10.1016/S0015-0282(16)55089-4]
38. Sharma RK, Agarwal A. Role of reactive oxygen species in male infertility. Urology 1996; 48: 835-850. [DOI:10.1016/S0090-4295(96)00313-5]
39. Said TM, Agarwal A, Sharma RK, Thomas AJ, Jr Sikka SC. Impact of sperm morphology on DNA damage caused by oxidative stress induced by beta-nicotinamide adenine dinucleotide phosphate. Fertil Steril 2005; 83: 95-103. [DOI:10.1016/j.fertnstert.2004.06.056]
40. Agarwal A, Ikemoto I, Loughlin KR. Relationship of sperm parameters with levels of reactive oxygen species in semen specimens. J Urol 1994; 152: 107-110. [DOI:10.1016/S0022-5347(17)32829-X]
41. 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; 13: 379-386.
42. Armstrong JS, Rajasekaran M, Chamulitrat W, Gatti P, Hellstrom WJ, Sikka SC. Characterization of reactive oxygen species induced effects on human spermatozoa movement and energy metabolism. Free Radic Biol Med 1999; 26: 869-880. [DOI:10.1016/S0891-5849(98)00275-5]
43. Aitken RJ, Krausz C. Oxidative stress, DNA damage and the Y chromosome. Reproduction 2001; 122: 497-506. [DOI:10.1530/rep.0.1220497]
44. Zini A, Kamal K, Phang D, Willis J, Jarvi K. Biologic variability of sperm DNA denaturation in infertile men. Urology 2001; 58: 258-261. [DOI:10.1016/S0090-4295(01)01180-3]
45. Daitch JA, Bedaiwy MA, Pasqualotto EB, Hendin BN, Hallak J, Falcone T, et al. Varicocelectomy improves intrauterine insemination success rates in men with varicocele. J Urol 2001; 165: 1510-1513. [DOI:10.1016/S0022-5347(05)66338-0]
46. Penson DF, Paltiel AD, Krumholz HM, Palter S. The cost-effectiveness of treatment for varicocele related infertility. J Urol 2002; 168: 2490-2494. [DOI:10.1016/S0022-5347(05)64175-4]
47. Wagner L, Tostain J. Varicocele and male infertility: AFU 2006 guidelines. Prog Urol 2007; 17: 12-17. [DOI:10.1016/S1166-7087(07)92219-8]
48. Practice Committee of the American Society for Reproductive Medicine. Report on varicocele and infertility. Fertil Steril 2006; 86: 93-95. [DOI:10.1016/j.fertnstert.2006.07.1486]
49. Evers JL, Collins JA. Assessment of efficacy of varicocele repair for male subfertility: a systematic review. Lancet 2003; 361: 1849-1852. [DOI:10.1016/S0140-6736(03)13503-9]
50. Nilson S, Edvinsson A, Nilson B. Improvement of semen and pregnancy rate after ligation and division of the internal spermatic vein: fact or fiction? Br J Urol 1979; 51: 591-596. [DOI:10.1111/j.1464-410X.1979.tb03609.x]
51. Breznik R, Vlausavlievic V, Borko E. Treatment of varicocele and male fertility. Arch Androl 1993; 30; 157-160. [DOI:10.3109/01485019308987750]
52. Yamamoto M, Hibi H, Hirata Y, Miyake K, Ishigaki T. Effect of varicocelectomy on sperm parameters and pregnancy rate in patients with subclinical varicocele: a randomized prospective controlled study. J Urol 1996; 155: 1636-1638. [DOI:10.1016/S0022-5347(01)66149-4]
53. Grasso M, Lania C, Castelli M, Galli L, Franzoso F, Rigatti P. Low grade left varicocele in patients over 30 years old: the effect of spermatic vein ligation. BJU Int 2000; 85: 305-307. [DOI:10.1046/j.1464-410x.2000.00437.x]
54. Unal D, Yeni E, Verit A, Karatas OF. Clomiphene citrate versus varicocelectomy in treatment of subclinical varicocele: a prospective randomized study. Int J Urol 2001; 8: 227-230. [DOI:10.1046/j.1442-2042.2001.00289.x]
55. Madgar I, Weissenberg R, Lunenfeld B, Karasik A, Goldwasser B. Controlled trial of high spermatic vein ligation for varicocele in infertile men. Fertil Steril 1995; 63: 120-124. [DOI:10.1016/S0015-0282(16)57306-3]
56. Nieschlag E, Hertle L, Fischedick A, Abshagen K, Behre HM. Update on treatment of varicocele: counseling as effective as occlusion of the vena spermatica. Hum Reprod 1998; 13: 2147-2150. [DOI:10.1093/humrep/13.8.2147]
57. Nieschlag E, Hertle L, Fischedick A, Behre HM. Treatment of varicocele: councelling as effective as occlusion of the vena spermatica. Hum Reprod 1995; 10: 347-353. [DOI:10.1093/oxfordjournals.humrep.a135941]
58. Krause W, Mueller HH, Schaefer H, Weidner W. Does treatment of varicocele improve male fertility? Results of the "Deutsche Varikozelenstudie", a multicentre study of 14 collaborating centres. Andrologia 2002; 34: 164-171. [DOI:10.1046/j.1439-0272.2002.00494.x]
59. Agarwal A, Deepinder F, Cocuzza M, Agarwal R, Short RA, Sabanegh E, et al. Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach. Urology 2007; 70: 532-538. [DOI:10.1016/j.urology.2007.04.011]
60. Marmar JL, Agarwal A, Prabakaran S, Agarwal R, Short RA, Benoff S, et al. Reassessing the value of varicocelectomy as a treatment for male subfertility with a new meta-analysis. Fertil Steril 2007; 88: 639-648. [DOI:10.1016/j.fertnstert.2006.12.008]
61. Steckel J, Dicker AP, Goldstein M. Relationship between varicocele size and response to varicocelectomy. J Urol 1993; 149: 769-771. [DOI:10.1016/S0022-5347(17)36203-1]
62. Schlesinger MH, Wilets IF, Nagler HM. Treatment outcome after varicocelectomy. A critical analysis. Urol Clin North Am 1994; 21: 517-529.
63. Matkov TG, Zenni M, Sandlow J, Levine LA. Preoperative semen analysis as a predictor of seminal improvement following varicocelectomy. Fertil Steril 2001; 75: 63-68. [DOI:10.1016/S0015-0282(00)01644-7]
64. Marks JL, McMahon R, Lipshultz LI. parameters of successful varicocele repair. J Urol 1986; 136: 609-612. [DOI:10.1016/S0022-5347(17)44990-1]
65. Yoshida K, Kitahara S, Chiba K, Horiuchi S, Horimi H, Sumi S, et al. Predictive indicators of successful varicocele repair in men with infertility. Int J Fertil Women's Med 2000; 45: 279-284.
66. Colpi GM, Carmignani L, Nerva F, Piediferro G, Castiglioni F, Grugnetti C, et al. Surgical treatment of varicocele by a subinguinal approach combined with antegrade intraoperative sclerotherapy of venous vessels. BJU Int 2006; 97: 142-145. [DOI:10.1111/j.1464-410X.2006.05915.x]
67. Dubin L, Amelar RD. Varicocele size and results of varicocelectomy in selected subfertile men with varicocele. Fertil Steril 1970; 21: 606-609. [DOI:10.1016/S0015-0282(16)37684-1]
68. Van Alphen MMA, Van de Kant HJG, De Rooij DG. Follicle stimulating hormone stimulates spermatogenesis in the adult monkey. Endocrinology 1988; 123: 1449-1455. [DOI:10.1210/endo-123-3-1449]
69. Weinbauer GF, Behre HM, Nieschlag E. FSH transiently stimulates size and spermatogenesis in the adult intact non-human primate. Acta Endocrinol 1992; 126: 97.
70. Weinbauer GF, Gromoll J, Simoni M, Nieschlag E. Physiology of testicular function. In: Andrology: Male Reproductive Health and Dysfunction. Eds. E. Nieschlag and H.M. Behre, Springer, Heidelberg. 1997. [DOI:10.1007/978-3-662-03455-2_3]
71. Behre HM, Nieschlag E, Meschede D, Partsch CJ. Diseases of the hypothalamus and the pituitary gland. In: Andrology: Male Reproductive Health and Dysfunction. 2nd Ed. 2000.
72. Bouloux PG, Nieschlag E, Burger HG, Skakkebeak NE, Wu FCW, Handelsman DJ, et al. Induction of spermatogenesis by recombinant follicle-stimulating hormone (Puregon) in hypogonadotropic azoospermic men who failed to respond to human chorionic gonadotropin alone. J Androl 2003; 24: 604-611. [DOI:10.1002/j.1939-4640.2003.tb02712.x]
73. Chappel S, Kelton C, Nugent N. Expression of human gonadotropins by recombinant DNA methods. In: Proceedings of the 3rd World Congress on Gynecological Endocrinology. eds. A.R. Genazzani and F. Petraglia. Parthenon, Carnforth, Lancs, UK. 1992.
74. Olijve W, De Boer W, Mulders JWM, Van Wezenbeek PMGF. Molecular biology and biochemistry of human recombinant follicle stimulating hormone (Puregon). Mol Hum Reprod 1996; 2: 371-382. [DOI:10.1093/molehr/2.5.371]
75. Howles CM, Loumaye E, Giroud D, Luyet G. Multiple follicular development and ovarian steroidogenesis following subcutaneous administration of a highly purified urinary FSH preparation in pituitary desensitized women undergoing IVF: a multicentre European phase III study. Hum Reprod 1994; 9: 424-430. [DOI:10.1093/oxfordjournals.humrep.a138522]
76. Loumaye E, Campbell R, Salat-Baroux J. Human follicle-stimulating hormone produced by recombinant DNA technology: a review for clinicians. Hum Reprod 1995; 1: 188-199. [DOI:10.1093/humupd/1.2.188]
77. le Cotonnec JY, Porchet HC, Beltrami V, Khan A, Toon S, Rowland M. Clinical pharmacology of recombinant human follicle-stimulating hormone (FSH). I. Comparative pharmacokinetics with urinary human FSH. Fertil Steril 1994; 61: 669-678.
78. Porchet HC, Le Cotonnec JY, Loumaye E. Clinical pharmacology of recombinant human follicle-stimulating hormone. III. Pharmacokinetic–pharmacodynamic modeling after repeated subcutaneous administration. Fertil Steril 1994; 61: 687-695. [DOI:10.1016/S0015-0282(16)56646-1]
79. Handelsman DJ, Turner L, Boylan LM, Conway AJ. Pharmacokinetics of human follicle-stimulating hormone in gonadotropin-deficient men. J Clin Endocrinol Metab 1995; 80: 1657-1663.
80. Horsman G, Talbot JA, McLoughlin JD, Lambert A, Robertson WR. A biological, immunological and physico-chemical comparison of the current clinical batches of the recombinant FSH preparations rhFSH and Puregon. Hum Reprod 2000; 15: 1898-1902. [DOI:10.1093/humrep/15.9.1898]
81. Bartoov B, Eltes F, Lunenfeld E, Har-Even D, Lederman H, Lunenfeld B. Sperm quality of subfertile males before and after treatment with follicle-stimulating hormone. Fertil Steril 1994; 61: 727-734. [DOI:10.1016/S0015-0282(16)56653-9]
82. Ben Rafael Z, Ashkenazi J, Farhi J, et al. Pure FSH (pFSH) treatment to male partners in IVF cycles due to idiopathic oligo-terato asthenozoospermia (OTA) syndrome. J Assist Reprod Genet 1995; 12; 52.
83. 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:10.1093/humrep/13.3.596]
84. Liu PY, Turner L, Rushford D, McDonald J, Baker HW, Conway AJ, et al. Efficacy and safety of recombinant human follicle stimulating hormone (Gonal-F) with urinary human chorionic gonadotrophin for induction of spermatogenesis and fertility in gonadotrophin-deficient men. Hum Reprod 1999; 14: 1540-1545. [DOI:10.1093/humrep/14.6.1540]
85. 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: 133-137.
86. Matsumoto AM, Snyder PJ, Bhasin S, Martin K, Weber T, Winters S, et al. Stimulation of spermatogenesis with recombinant human follicle-stimulating hormone (follitropin alfa, GONAL-f): long-term treatment in azoospermic men with hypogonadotropic hypogonadism
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