Erkek İnfertilitesinin Cerrahi Dışı Tedavisi: Spesifik Tedavi

Evli çiftlerin yaklaşık %15’i fertilite incelemesine maruz kalmaktadır. İnfertilite vakalarının yaklaşık olarak yarısında erkek faktörü bulunmaktadır. Son yıllarda üreme tıbbında çok sayıda ilerleme kaydedilmiştir. Daha önce tedavi edilemez olduğu düşünülen infertil çiftlerin artık genetik olarak babalık şansı olmaktadır. Her ne kadar şiddetli erkek faktörü bulunan vakalarda yardımcı üreme teknikleri ile sorunu çözmek mümkün ise de, bütün infertil eşlere bu tedavi yöntemlerini uygulamak fazladan tedavi olur, maliyet yükselir ve kadın partnerde ovaryen hiperstimülasyon gibi nadir ancak ciddi riskler meydana gelebilir. Herhangi bir androlojik tedaviden önce ciddi bir tanısal çalışma yapılmalı ve seçilmiş vakalarda yeterli tedavi opsiyonları sunularak, tedavi kişiselleştirilmelidir. Öncelikle infertilitenin etiyolojik nedenine yönelik spesifik terapötik tedavi denenmelidir. İnfertilitenin spesifik medikal tedavisi, geriye dönüşlü infertilite nedenlerinin ortaya çıkarılması ve uygun ilaçlar ile tedavi edilmesi esasına dayanmaktadır. Konjenital hipogonadotropik hipogonadizm gibi hormonal bozukluklar, hiperprolaktinemi, genital sistem enfeksiyonları ve cinsel fonksiyon bozuklukları gibi infertilite nedenlerinin tanısı kolaylıkla konulabilmekte ve cerrahi gerektirmeyen medikal yöntemlerle başarılı bir şekilde tedavi edilebilmektedir. Bu derlemede, erkek infertilitesinin geriye dönüşlü nedenleri ve cerrahi dışı spesifik medikal tedavi yöntemleri mevcut literatür ışığında tartışılmıştır.

Nonsurgical Treatment of Male Infertility: Specific Therapy

Approximately 15% of married couples undergo a fertility examination. Approximately half of the infertility cases have a male factor. Numerous advances have been made in reproductive medicine in the last few years. Infertile couples who previously were considered untreatable now have a chance at genetic paternity. Although it is possible to solve the problem with assisted reproductive techniques in cases with severe male factor, applying these treatment methods to all infertile partners is extra treatment, the cost increases, and rare but serious risks such as ovarian hyperstimulation may occur in the female partner. Prior to any andrological treatment, a serious diagnostic work-up should be performed and treatment should be individualized, providing adequate treatment options in selected cases. Primarily, specific therapeutic therapy directed against the etiological cause of infertility should be attempted. Specific medical treatment of infertility is based on identifying the causes of reversible infertility and treating it with appropriate drugs. Infertility causes such as hormonal disorders, i.e. congenital hypogonadotropic hypogonadism, hyperprolactinemia, genital tract infections, and sexual dysfunctions can be easily diagnosed and successfully treated with medical methods that do not require surgery. In this review, reversible causes of male infertility and nonsurgical specific medical treatment methods are discussed in the light of the current literature.

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  • Rowe PJ, Comhaire FH, Hargreave TB, Mellows HJ. WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge: Cambridge University Press; 1993.
  • Greenhall E, Vessey M. The prevalence of subfertility: a review of the current confusion and a report of two new studies. Fertil Steril. 1990;54(6):978-83.
  • Cocuzza M, Agarwal A. Nonsurgical treatment of male infertility: specific and empiric therapy. Biologics. 2007;1(3):259-69.
  • Zitzmann M, Nieschlag E. Hormone substitution in male hypogonadism. Mol Cell Endocrinol. 2000;161(1-2):73-88.
  • Özbey İ, Ziypak T. Erkekte hipotalamus-hipofiz-testis aksı. In: Aşcı R, Çayan S, Erdemir F, Orhan İ, Yaman Ö, Usta MF, et al, editors. Erkek üreme sistemi hastalıkları ve tedavisi. 1. Baskı. İstanbul: İstanbul Medikal Yayıncılık; 2013. p.39-54. Turkish.
  • Özbey İ. Hipogonadotropik hipogonadizm tedavisi. Turkiye Klinikleri J Urology-Special Topics. 2017;10(1):19-27. Turkish.
  • Jockenhövel F. Male Hypogonadism. Bremen: UNI-MED; 2004.
  • Melmed S, Kleinberg DL. Anterior pituitary. In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, Wilson JD, Foster DW, editors. Williams textbook of endocrinology, 10th ed. Philadelphia: Saunders; 2003. p.177-279.
  • Ley SB, Leonard JM. Male hypogonadotropic hypogonadism: factors influencing response to human chorionic gonadotropin and human menopausal gonadotropin, including prior exogenous androgens. J Clin Endocrinol Metab. 1985;61(4):746-52.
  • Özbey İ. İntratestiküler testosteron: Üretimi ve klinik önemi. Androloji Bülteni. 2015;17(61):129-131. Turkish.
  • Barrio R, de Luis D, Alonso M, Lamas A, Moreno JC. Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism. Fertil Steril. 1999;71(2):244-8.
  • Özbey İ, Aksay Y, Polat Ö. Erkekte izole folikül stimüle edici hormon ve izole luteinize edici hormon eksikliği. Androloji Bülteni. 2002;4(9):11-12. Turkish.
  • Erol B, Çeltik M, Kendirci M, Özbey İ, Kadıoğlu A, Özsoy C. Isolated FSH deficiency: Rare but treatable cause of male infertility. The Journal of Urology. 2003;169(4S):11.
  • Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Dlewati A, et al. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab. 2000;85(8):2670-7.
  • Kliesch S, Behre HM, Nieschlag E. Recombinant human follicle-stimulating hormone and human chorionic gonadotropin for induction of spermatogenesis in a hypogonadotropic male. Fertil Steril. 1998;69(2):21s-3s.
  • Esteves SC, Papanikolaou V. Clinical efficacy, safety and tolerability of recombinant human chorionic gonadotropin to restore spermatogenesis and androgen production of hypogonadotropic hypogonadal men. Fertil Steril. 2011;96(3):230.
  • Young J, Couzinet B, Chanson P, Brailly S, Loumaye E, Schaison G. Effects of human recombinant luteinizing hormone and follicle-stimulating hormone in patients with acquired hypogonadotropic hypogonadism: study of Sertoli and Leydig cell secretions and interactions. J Clin Endocrinol Metab. 2000;85(9):3239-44.
  • Thau RB, Goldstein M, Yamamoto Y, Burrow GN, Phillips D, Bardin CW. Failure of gonadotropin therapy secondary to chorionic gonadotropin-induced antibodies. J Clin Endocrinol Metab. 1988;66(4):862-7.
  • Wilson JD. Hypogonadotropic hypogonadism. In: Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, et al., editors. Harrison’s principles of internal medicine. 14th ed. New York: McGraw-Hill; 1998. p.1984.
  • Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamäki J, et al. Clinical management of congenital hypogonadotropic hypogonadism. Endocr Rev. 2019;40(2):669-710.
  • Ortac M, Hidir M, Salabas E, Boyuk A, Bese C, Pazir Y, et al. Evaluation of gonadotropin-replacement therapy in male patients with hypogonadotropic hypogonadism. Asian J Androl. 2019;21(6):623-7.
  • Dwyer AA, Raivio T, Pitteloud N. Gonadotrophin replacement for induction of fertility in hypogonadal men. Best Pract Res Clin Endocrinol Metab. 2015;29(1):91-103.
  • European Metrodin HP Study Group. Efficacy and safety of highly purified urinary follicle-stimulating hormone with human chorionic gonadotropin for treating men with isolated hypogonadotropic hypogonadism. Fertil Steril. 1998;70(2):256-62.
  • Rastrelli G, Corona G, Mannucci E, Maggi M. Factors affecting spermatogenesis upon gonadotropin-replacement therapy: a meta-analytic study. Andrology. 2014;2(6):794-808.
  • Liu PY, Baker HW, Jayadev V, Zacharin M, Conway AJ, Handelsman DJ. Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab. 2009;94(3):801-8.
  • Warne DW, Decosterd G, Okada H, Yano Y, Koide N, Howles CM. A combined analysis of data to identify predictive factors for spermatogenesis in men with hypogonadotropic hypogonadism treated with recombinant human follicle-stimulating hormone and human chorionic gonadotropin. Fertil Steril. 2009;92(2):594-604.
  • 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. Fertil Steril. 2009;92(3):979-90.
  • Bouloux P, Warne DW, Loumaye E; FSH Study Group in Men's Infertility. Efficacy and safety of recombinant human follicle-stimulating hormone in men with isolated hypogonadotropic hypogonadism. Fertil Steril. 2002;77(2):270-3.
  • Pitteloud N, Hayes FJ, Dwyer A, Boepple PA, Lee H, Crowley WF Jr. Predictors of outcome of long-term GnRH therapy in men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2002;87(9):4128-36.
  • Ishikawa T, Ooba T, Kondo Y, Yamaguchi K, Fujisawa M. Assessment of gonadotropin therapy in male hypogonadotropic hypogonadism. Fertil Steril. 2007;88(6):1697-9.
  • Silveira LF, Latronico AC. Approach to the patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2013;98(5):1781-8.
  • Dwyer AA, Raivio T, Pitteloud N. Management of endocrine disease: reversible hypogonadotropic hypogonadism. Eur J Endocrinol. 2016;174(6): R267-74.
  • Spratt DI, Carr DB, Merriam GR, Scully RE, Rao PN, Crowley WF Jr. The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: clinical and laboratory correlations. J Clin Endocrinol Metab. 1987;64(2):283-91.
  • Yılmazel FK, Karabulut I, Yılmaz AH, Keskin E, Bedir F, Ozbey I. A review of hypogonadotropic hypogonadism cases followed up in our clinic in the last decade. Urologia. 2021;88(1):50-5.
  • Raivio T, Falardeau J, Dwyer A, Quinton R, Hayes FJ, Hughes VA, et al. Reversal of idiopathic hypogonadotropic hypogonadism. N Engl J Med. 2007;357(9):863-73.
  • Delemarre EM, Felius B, Delemarre-van de Waal HA. Inducing puberty. Eur J Endocrinol. 2008;159(Suppl 1):S9-15.
  • Segal TY, Mehta A, Anazodo A, Hindmarsh PC, Dattani MT. Role of gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests in differentiating patients with hypogonadotropic hypogonadism from those with constitutional delay of growth and puberty. J Clin Endocrinol Metab. 2009;94(3):780-5.
  • Farshchi HR, Shahnazi A, Azizi F. Effects of testosterone and gonadotropin therapy in men with hypogonadotropic hypogonadism. Int J Endocrinol Metab. 2009;7(4):242-7.
  • Bouloux PM, Nieschlag E, Burger HG, Skakkebaek NE, Wu FC, 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(4):604-11.
  • Özbey İ. Prolaktinoma tanı ve tedavisinde güncel yaklaşım. Androloji Bülteni. 2006;8(27):320-3. Turkish.
  • Nishimura K, Matsumiya K, Tsuboniwa N, Yamanaka M, Koga M, Miura H, et al. Bromocriptine for infertile males with mild hyperprolactinemia: hormonal and spermatogenic effects. Arch Androl. 1999;43(3):207-13.
  • Singh P, Singh M, Cugati G, Singh AK. Hyperprolactinemia: An often missed cause of male infertility. J Hum Reprod Sci. 2011 May;4(2):102-3.
  • Sohrabvand F, Jafari M, Shariat M, Haghollahi F, Lotfi M. Frequency and epidemiologic aspects of male infertility. Acta Med Iran. 2015;53(4):231-5.
  • Tsutsumi R, Webster NJ. GnRH pulsatility, the pituitary response and reproductive dysfunction. Endocr J. 2009;56(6):729-37.
  • Liu X, Tang C, Wen G, Zhong C, Yang J, Zhu J, et al. The mechanism and pathways of dopamine and dopamine agonists in prolactinomas. Front Endocrinol (Lausanne). 2019;9:768.
  • Thorner MO, McNeilly AS, Hagan C, Besser GM. Long-term treatment of galactorrhoea and hypogonadism with bromocriptine. Br Med J. 1974;2(5916):419-22.
  • De Rosa M, Colao A, Di Sarno A, Ferone D, Landi ML, Zarrilli S, et al. Cabergoline treatment rapidly improves gonadal function in hyperprolactinemic males: a comparison with bromocriptine. Eur J Endocrinol. 1998;138(3):286-93.
  • Gillam MP, Molitch ME, Lombardi G, Colao A. Advances in the treatment of prolactinomas. Endocr Rev. 2006;27(5):485-534.
  • Ribeiro RS, Abucham J. Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment. Eur J Endocrinol. 2009;161(1):163-9.
  • Sengupta P, Dutta S, Karkada IR, Chinni SV. Endocrinopathies and male infertility. Life (Basel). 2022;12(1):10.
  • Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA. WHO manual for the standardized investigation, diagnosis and management of the infertile male. Cambridge: Cambridge University Press; 2000.
  • Weidner W, Krause W, Ludwig M. Relevance of male accessory gland infection for subsequent fertility with special focus on prostatitis. Hum Reprod Update. 1999;5(5):421-32.
  • Fode M, Fusco F, Lipshultz L, Weidner W. Sexually transmitted disease and male infertility: a systematic review. Eur Urol Focus. 2016;2(4):383-393.
  • Trum JW, Mol BW, Pannekoek Y, Spanjaard L, Wertheim P, Bleker OP, et al. Value of detecting leukocytospermia in the diagnosis of genital tract infection in subfertile men. Fertil Steril. 1998;70(2):315-9.
  • Weidner W, Ludwig M, Miller J. Therapy in male accessory gland infection--what is fact, what is fiction? Andrologia. 1998;30(Suppl 1):87-90.
  • Comhaire FH, Rowe PJ, Farley TM. The effect of doxycycline in infertile couples with male accessory gland infection: a double blind prospective study. Int J Androl. 1986;9(2):91-8.
  • Ahmadi MH, Mirsalehian A, Sadighi Gilani MA, Bahador A, Afraz K. Association of asymptomatic Chlamydia trachomatis infection with male infertility and the effect of antibiotic therapy in improvement of semen quality in infected infertile men. Andrologia. 2018;50(4):e12944.
  • Solomon M, Henkel R. Semen culture and the assessment of genitourinary tract infections. Indian J Urol. 2017;33(3):188-193.
  • Yapanoglu T, Kocaturk H, Aksoy Y, Alper F, Ozbey I. Long-term efficacy and safety of interferon-alpha-2B in patients with mumps orchitis. Int Urol Nephrol. 2010;42(4):867-71.
  • Steiner AZ, Hansen KR, Barnhart KT, Cedars MI, Legro RS, Diamond MP, et al. The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial. Fertil Steril. 2020;113(3):552-60.e3.
  • Henkel R, Offor U, Fisher D. The role of infections and leukocytes in male infertility. Andrologia. 2021;53(1):e13743.
  • Liu Y, Wang Y, Pu Z, Wang Y, Zhang Y, Dong C, et al. Sexual dysfunction in infertile men: a systematic review and meta-analysis. Sex Med. 2022;10(4):100528.
  • Birch N, Shaw M. Retrograde ejaculation after anterior lumbar interbody fusion. Spine (Phila Pa 1976). 2004;29(1):106-7.
  • Ellenberg M, Weber H. Retrograde ejaculation in diabetic neuropathy. Ann Intern Med. 1966;65(6):1237-46.
  • Yavetz H, Yogev L, Hauser R, Lessing JB, Paz G, Homonnai ZT. Retrograde ejaculation. Hum Reprod. 1994;9(3):381-6.
  • Shoshany O, Abhyankar N, Elyaguov J, Niederberger C. Efficacy of treatment with pseudoephedrine in men with retrograde ejaculation. Andrology. 2017;5(4):744-748.
  • Soler JM, Previnaire JG, Plante P, Denys P, Chartier-Kastler E. Midodrine improves ejaculation in spinal cord injured men. J Urol. 2007;178(5):2082-6.
  • Ichiyanagi O, Sasagawa I, Suzuki Y, Matsuki S, Itoh K, Miura M, et al. Successful treatment of retrograde ejaculation with amezinium. Arch Androl. 2003;49(3):215-7.
  • Ebner T, Shebl O, Mayer RB, Moser M, Costamoling W, Oppelt P. Healthy live birth using theophylline in a case of retrograde ejaculation and absolute asthenozoospermia. Fertil Steril. 2014;101(2):340-3.
  • Hu J, Nagao K, Tai T, Kobayashi H, Nakajima K. Randomized crossover trial of amoxapine versus vitamin b12 for retrograde ejaculation. Int Braz J Urol. 2017;43(3):496-504.
  • Arafa M, El Tabie O. Medical treatment of retrograde ejaculation in diabetic patients: a hope for spontaneous pregnancy. J Sex Med. 2008;5(1):194-8.