Abstract
Male infertility is a relatively common condition caused by low sperm production, immobile sperm, or blockages that prevent the delivery of sperm. This condition can be caused by a variety of illnesses, injuries, chronic health problems, lifestyle choices, other factors, or idiopathic, in which abnormal semen parameters occur without an identifiable cause. Medical management traditionally focuses on correcting endocrine abnormalities related to hormone deficiencies. Clomiphene citrate is an antiestrogen thought to increase sperm parameters in males attempting to conceive. The objective of this review was to evaluate the efficacy and safety of clomiphene citrate in the treatment of male patients with infertility. A literature search of MEDLINE (1966–June 2012) and EMBASE (1980–June 2012) was conducted using the medical terms clomiphene and male infertility and 9 clinical studies were identified. Overall, only 1 study detected a statistically significant benefit on the pregnancy rate in the clomiphene group; however, the majority of the studies demonstrated a statistically significant increase in sperm concentrations. At doses used to treat male infertility, clomiphene was well tolerated with no identified serious adverse effects. Based on the reviewed studies there is insufficient evidence to indicate that clomiphene is effective for the treatment of male infertility.
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References
Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss. Fertil Steril. 2008;89(6):1603.
Quick facts about Infertility. American Society for Reproductive Medicine. 2012. http://www.reproductivefacts.org/detail.aspx?id=2322. Accessed February 21, 2012.
Turek PJ. Male infertility, Chapter 44. In: Tanagho EA, McAnich JW, eds. Smith’s General Urology. 17th ed. New York, NY: McGraw-Hill; 2008. http://www.accessmedicine.com/content.aspx?aID=3131816. Accessed February 21, 2012.
The Male Infertility Best Practice Policy Committee of the American Urological Association and the Practice Committee of the American Society for Reproductive Medicine. Report on optimal evaluation of the infertile male. Fertil Steril. 2006; 86(5 suppl 1):S202-S209.
Pryor JL, Kent-First M, Muallem A, et al. Microdeletions in the Y chromosome of infertile men. N Engl J Med. 1997;336(8): 534–539.
De Kretser DM. Male infertility. Lancet. 1997;349(9054): 787–790.
Cooper TG, Noonan E, von Eckardstein S, et al World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231–245.
Ko EY, Siddiqi K, Brannigan RE, Sabanegh ES. Empirical medical therapy for idiopathic male infertility: a survey of the American Urological Association. J Urol. 2012;187(3):973–978.
Product information. Clomid (Clomiphene Citrate). Bridgewater, NJ: Sanofi-Aventis U.S.; 2006.
Mellinger RC, Thompson RJ. The effect of clomiphene citrate in male infertility. Fertil Steril. 1966;17(1):94–103.
Mroueh A, Lytton B, Kase N. Effect of clomiphene citrate on oligospermia. Am J Obstet Gynecol. 1967;98(8):1033–1036.
Heller CG, Rowley MH, Heller GV. Clomiphene citrate: a correlation of its effect on sperm concentration and morphology, total gonadotropins, ICSH, estrogen and testosterone excretion, and testicular cytology in normal men. J Clin Endocrinol Metab. 1969;29(5):638–649.
Abel BJ, Carswell G, Elton R, et al Randomised trial of clomiphene citrate treatment and vitamin C for male infertility. Brit J Urol. 1982;54(6):780–784.
Wang C, Chan CW, Wong KK, Yeung KK. Comparison of the effectiveness of placebo, clomiphene citrate, mesterolone, pentoxifylline, and testosterone reound therapy for the treatment of idiopathic oligospermia. Fertil Steril. 1983;40(3): 358–365.
Matsumiya K, Kitamura M, Kishikawa H, et al A prospective comparative trial of a gonadotropin-releasing hormone analogue with clomiphene citrate for the treatment of oligoasthenozoospermia. Int J Urol. 1998;5(4):361–363.
Aparicio NJ, Schwarzstein L, Turner EA, Turner D, Mancini R, Schally AV. Treatment of idiopathic normogonadotropic oligoasthenozoospermia with synthetic luteinizing hormone-releasing hormone. Fertil Steril. 1976;27(5):549–555.
Moradi M, Moradi A, Alemi M, et al. Safety and efficacy of clomiphene citrate and L-carnitine in idiopathic male infertility. Urol J. 2010;7(3):188–193.
Rönnberg L. The effect of clomiphene citrate on different sperm parameters and serum hormone levels in preselected infertile men: a controlled double-blind cross-over study. Int J Androl. 1980;3(5):479–486.
Mićić S, Dotlić R. Evaluation of sperm parameters in clinical trial with clomiphene citrate of oligospermic men. J Urol. 1985; 133(2):221–222.
Sokol RZ, Steiner BS, Bustillo M, Peterson G, Swerdloff RS. A controlled comparison of the efficacy of clomiphene citrate in male infertility. Fertil Steril. 1988;49(5):865–870.
World Health Organization Task Force on the Prevention and Management of Infertility. A double-blind trial of clomiphene citrate for the treatment of idiopathic male infertility. Int J Androl. 1992;15(4):299–307.
Ghanem H, Shaeer O, El-Segini A. Combination clomiphene citrate and antioxidant for idiopathic male infertility: a randomized controlled trial. Fertil Steril. 2010;93(7): 2232–2235.
Pasqualotto FF, Fonseca GP, Pasqualotto EB. Azoospermia after treatment with clomiphene citrate in patients with oligospermia. Fertil Steril. 2008;90(5):2014.e11–2014.e12.
Kotoulas IG, Cardamakis E, Michopoulos J, Mitropoulos D, Dounis A. Tamoxifen treatment in male infertility. I. Effect on spermatozoa. Fertil Steril. 1994;61(5):911–914.
Krause W, Holland-Moritz H, Schramm P. Treatment of idiopathic oligozoospermia with tamoxifen—a randomized controlled study. Int J Androl. 1992;15(1):14–18.
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Willets, A.E., Corbo, J.M. & Brown, J.N. Clomiphene for the Treatment of Male Infertility. Reprod. Sci. 20, 739–744 (2013). https://doi.org/10.1177/1933719112466304
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DOI: https://doi.org/10.1177/1933719112466304
Keywords
- clomiphene
- male infertility
- oligozoospermia
- idiopathic