Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Causes of male infertility

Ronald S Swerdloff, MD
Christina Wang, MD
Section Editor
Alvin M Matsumoto, MD
Deputy Editor
Kathryn A Martin, MD


The fertility rate in a couple is influenced by several factors. These include: the age of the female partner, age of the male partner, exposure to sexually transmitted diseases and to environmental and medical toxins, coexistent disease states, and the specific disorders described below.

While many men with male infertility have oligozoospermia (decrease in number of sperm cells in the ejaculate compared with reference ranges) or azoospermia (no sperm cells in the ejaculate), some infertile men have normal sperm counts. Over 80 percent of men with infertility have low sperm concentrations associated with a decrease in sperm motility (asthenozoospermia) and spermatozoa with normal morphology. Others may have a decrease in sperm motility and abnormal sperm morphology (teratozoospermia).

The causes of male infertility will be reviewed here. The evaluation and treatment of male infertility and issues related to unexplained infertility are discussed separately. (See "Evaluation of male infertility" and "Treatment of male infertility" and "Unexplained infertility".)


Trends in male infertility — Reports of declining sperm counts and increasing incidence of urogenital abnormalities and testicular cancer in some regions of the world have stirred public interest and concern [1-7]. Whether there is deterioration of semen quality is controversial [8-12]. Recent data in fertile men in Europe and the United States show marked differences in sperm concentration between different countries and different regions of the same country [13-15]. The role of environmental pollutants or toxins remains unclear [16,17].

A cross-sectional survey of men in the United States ages 15 to 44 years showed a prevalence of male infertility of 12 percent (95% CI 7-23) [18]. Epidemiology studies suggest that fertility rates are lower in men over age 40 years [19,20], but results from assisted reproduction technologies (ART) have not confirmed this observation [21,22]. In about 40 percent of cases of male infertility, the cause is unknown, but genetic factors may explain many of these cases in the future [18,23].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Apr 2017. | This topic last updated: Jan 05, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ 1992; 305:609.
  2. Irvine DS. Falling sperm quality. BMJ 1994; 309:476.
  3. Auger J, Kunstmann JM, Czyglik F, Jouannet P. Decline in semen quality among fertile men in Paris during the past 20 years. N Engl J Med 1995; 332:281.
  4. Ministry of Environment and Energy, Denmark. Male reproductive health and environmental chemicals with estrogenic effect. Miljoprojekt no. 290. Copenhagen: Danish Environmental Protection Agency, 1995.
  5. Irvine S, Cawood E, Richardson D, et al. Evidence of deteriorating semen quality in the United Kingdom: birth cohort study in 577 men in Scotland over 11 years. BMJ 1996; 312:467.
  6. Nordkap L, Joensen UN, Blomberg Jensen M, Jørgensen N. Regional differences and temporal trends in male reproductive health disorders: semen quality may be a sensitive marker of environmental exposures. Mol Cell Endocrinol 2012; 355:221.
  7. Juul A, Almstrup K, Andersson AM, et al. Possible fetal determinants of male infertility. Nat Rev Endocrinol 2014; 10:553.
  8. Suominen J, Vierula M. Semen quality of Finnish men. BMJ 1993; 306:1579.
  9. Ginsburg J, Okolo S, Prelevic G, Hardiman P. Residence in the London area and sperm density. Lancet 1994; 343:230.
  10. Finch, A, Goluhoff, ET, Olson, JH, et al. Semen analyses in 1283 men from the United States over a 25-year period; no decline in quality. Fertil Steril 1969; 65:1009.
  11. Paulsen CA, Berman NG, Wang C. Data from men in greater Seattle area reveals no downward trend in semen quality: further evidence that deterioration of semen quality is not geographically uniform. Fertil Steril 1996; 65:1015.
  12. Bujan L, Mansat A, Pontonnier F, Mieusset R. Time series analysis of sperm concentration in fertile men in Toulouse, France between 1977 and 1992. BMJ 1996; 312:471.
  13. Jørgensen N, Andersen AG, Eustache F, et al. Regional differences in semen quality in Europe. Hum Reprod 2001; 16:1012.
  14. Jørgensen N, Carlsen E, Nermoen I, et al. East-West gradient in semen quality in the Nordic-Baltic area: a study of men from the general population in Denmark, Norway, Estonia and Finland. Hum Reprod 2002; 17:2199.
  15. Swan SH, Brazil C, Drobnis EZ, et al. Geographic differences in semen quality of fertile U.S. males. Environ Health Perspect 2003; 111:414.
  16. Hauser R, Skakkebaek NE, Hass U, et al. Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union. J Clin Endocrinol Metab 2015; 100:1267.
  17. Bergman A, Heindel JJ, Kasten T, et al. The impact of endocrine disruption: a consensus statement on the state of the science. Environ Health Perspect 2013; 121:A104.
  18. Louis JF, Thoma ME, Sørensen DN, et al. The prevalence of couple infertility in the United States from a male perspective: evidence from a nationally representative sample. Andrology 2013; 1:741.
  19. de La Rochebrochard E, Thonneau P. Paternal age >or=40 years: an important risk factor for infertility. Am J Obstet Gynecol 2003; 189:901.
  20. De La Rochebrochard E, Thonneau P. Paternal age: are the risks of infecundity and miscarriage higher when the man is aged 40 years or over? Rev Epidemiol Sante Publique 2005; 53 Spec No 2:2S47.
  21. Aboulghar M, Mansour R, Al-Inany H, et al. Paternal age and outcome of intracytoplasmic sperm injection. Reprod Biomed Online 2007; 14:588.
  22. Bellver J, Garrido N, Remohí J, et al. Influence of paternal age on assisted reproduction outcome. Reprod Biomed Online 2008; 17:595.
  23. Krausz C, Chianese C. Genetic testing and counselling for male infertility. Curr Opin Endocrinol Diabetes Obes 2014; 21:244.
  24. World Health Organization. Towards more objectivity in diagnosis and management of male infertility. Int J Androl 1987; 7(Suppl):1.
  25. de Kretser DM. Male infertility. Lancet 1997; 349:787.
  26. Spratt DI, Carr DB, Merriam GR, et al. 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; 64:283.
  27. Grigorova M, Punab M, Ausmees K, Laan M. FSHB promoter polymorphism within evolutionary conserved element is associated with serum FSH level in men. Hum Reprod 2008; 23:2160.
  28. Grigorova M, Punab M, Poolamets O, et al. Increased Prevalance of the -211 T allele of follicle stimulating hormone (FSH) beta subunit promoter polymorphism and lower serum FSH in infertile men. J Clin Endocrinol Metab 2010; 95:100.
  29. Grigorova M, Punab M, Zilaitienė B, et al. Genetically determined dosage of follicle-stimulating hormone (FSH) affects male reproductive parameters. J Clin Endocrinol Metab 2011; 96:E1534.
  30. Tapanainen JS, Aittomäki K, Min J, et al. Men homozygous for an inactivating mutation of the follicle-stimulating hormone (FSH) receptor gene present variable suppression of spermatogenesis and fertility. Nat Genet 1997; 15:205.
  31. Simoni M, Gromoll J, Höppner W, et al. Mutational analysis of the follicle-stimulating hormone (FSH) receptor in normal and infertile men: identification and characterization of two discrete FSH receptor isoforms. J Clin Endocrinol Metab 1999; 84:751.
  32. Castro-Magaña M, Bronsther B, Angulo MA. Genetic forms of male hypogonadism. Urology 1990; 35:195.
  33. Bouchard P, Lagoguey M, Brailly S, Schaison G. Gonadotropin-releasing hormone pulsatile administration restores luteinizing hormone pulsatility and normal testosterone levels in males with hyperprolactinemia. J Clin Endocrinol Metab 1985; 60:258.
  34. Charbonnel B, Chupin M, Le Grand A, Guillon J. Pituitary function in idiopathic haemochromatosis: hormonal study in 36 male patients. Acta Endocrinol (Copenh) 1981; 98:178.
  35. Falorni A, Minarelli V, Bartoloni E, et al. Diagnosis and classification of autoimmune hypophysitis. Autoimmun Rev 2014; 13:412.
  36. Veldhuis JD, Dufau ML. Estradiol modulates the pulsatile secretion of biologically active luteinizing hormone in man. J Clin Invest 1987; 80:631.
  37. MacAdams MR, White RH, Chipps BE. Reduction of serum testosterone levels during chronic glucocorticoid therapy. Ann Intern Med 1986; 104:648.
  38. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil Steril 1996; 65:821.
  39. Matsumoto AM, Bremner WJ. Modulation of pulsatile gonadotropin secretion by testosterone in man. J Clin Endocrinol Metab 1984; 58:609.
  40. Schürmeyer T, Knuth UA, Belkien L, Nieschlag E. Reversible azoospermia induced by the anabolic steroid 19-nortestosterone. Lancet 1984; 1:417.
  41. Bonaccorsi AC, Adler I, Figueiredo JG. Male infertility due to congenital adrenal hyperplasia: testicular biopsy findings, hormonal evaluation, and therapeutic results in three patients. Fertil Steril 1987; 47:664.
  42. Freeman DA. Steroid hormone-producing tumors of the adrenal, ovary, and testes. Endocrinol Metab Clin North Am 1991; 20:751.
  43. Swerdloff RS, Steiner B, Callegari C, Bhasin S. GnRH analogues and male contraception. In: Pharmacology, biology, and clinical applications of androgens, Bhasin S, Gabelnick HL, Spieler JM, Swerdloff RS, Wang C (Eds), Wiley-Liss, Inc., New York 1996. p.355.
  44. Smith SR, Chhetri MK, Johanson J, et al. The pituitary-gonadal axis in men with protein-calorie malnutrition. J Clin Endocrinol Metab 1975; 41:60.
  45. Allen NE, Appleby PN, Davey GK, Key TJ. Lifestyle and nutritional determinants of bioavailable androgens and related hormones in British men. Cancer Causes Control 2002; 13:353.
  46. Gapstur SM, Gann PH, Kopp P, et al. Serum androgen concentrations in young men: a longitudinal analysis of associations with age, obesity, and race. The CARDIA male hormone study. Cancer Epidemiol Biomarkers Prev 2002; 11:1041.
  47. Jensen TK, Andersson AM, Jørgensen N, et al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril 2004; 82:863.
  48. Camacho EM, Huhtaniemi IT, O'Neill TW, et al. Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Eur J Endocrinol 2013; 168:445.
  49. Rastrelli G, Carter EL, Ahern T, et al. Development of and Recovery from Secondary Hypogonadism in Aging Men: Prospective Results from the EMAS. J Clin Endocrinol Metab 2015; 100:3172.
  50. Hammoud AO, Gibson M, Peterson CM, et al. Obesity and male reproductive potential. J Androl 2006; 27:619.
  51. Isidori AM, Caprio M, Strollo F, et al. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab 1999; 84:3673.
  52. Sethi JK, Vidal-Puig AJ. Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res 2007; 48:1253.
  53. Tsai EC, Matsumoto AM, Fujimoto WY, Boyko EJ. Association of bioavailable, free, and total testosterone with insulin resistance: influence of sex hormone-binding globulin and body fat. Diabetes Care 2004; 27:861.
  54. Stokes VJ, Anderson RA, George JT. How does obesity affect fertility in men - and what are the treatment options? Clin Endocrinol (Oxf) 2015; 82:633.
  55. Kort HI, Massey JB, Elsner CW, et al. Impact of body mass index values on sperm quantity and quality. J Androl 2006; 27:450.
  56. Martini AC, Tissera A, Estofán D, et al. Overweight and seminal quality: a study of 794 patients. Fertil Steril 2010; 94:1739.
  57. Eisenberg ML, Kim S, Chen Z, et al. The relationship between male BMI and waist circumference on semen quality: data from the LIFE study. Hum Reprod 2014; 29:193.
  58. Duits FH, van Wely M, van der Veen F, Gianotten J. Healthy overweight male partners of subfertile couples should not worry about their semen quality. Fertil Steril 2010; 94:1356.
  59. Relwani R, Berger D, Santoro N, et al. Semen parameters are unrelated to BMI but vary with SSRI use and prior urological surgery. Reprod Sci 2011; 18:391.
  60. Magnusdottir EV, Thorsteinsson T, Thorsteinsdottir S, et al. Persistent organochlorines, sedentary occupation, obesity and human male subfertility. Hum Reprod 2005; 20:208.
  61. Macdonald AA, Stewart AW, Farquhar CM. Body mass index in relation to semen quality and reproductive hormones in New Zealand men: a cross-sectional study in fertility clinics. Hum Reprod 2013; 28:3178.
  62. Sermondade N, Faure C, Fezeu L, et al. BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Hum Reprod Update 2013; 19:221.
  63. McLachlan RI, O'Bryan MK. Clinical Review#: State of the art for genetic testing of infertile men. J Clin Endocrinol Metab 2010; 95:1013.
  64. Griffin JE. Androgen resistance--the clinical and molecular spectrum. N Engl J Med 1992; 326:611.
  65. Aiman J, Griffin JE, Gazak JM, et al. Androgen insensitivity as a cause of infertility in otherwise normal men. N Engl J Med 1979; 300:223.
  66. Gottlieb B, Lombroso R, Beitel LK, Trifiro MA. Molecular pathology of the androgen receptor in male (in)fertility. Reprod Biomed Online 2005; 10:42.
  67. von Eckardstein S, Syska A, Gromoll J, et al. Inverse correlation between sperm concentration and number of androgen receptor CAG repeats in normal men. J Clin Endocrinol Metab 2001; 86:2585.
  68. Wallerand H, Rémy-Martin A, Chabannes E, et al. Relationship between expansion of the CAG repeat in exon 1 of the androgen receptor gene and idiopathic male infertility. Fertil Steril 2001; 76:769.
  69. Casella R, Maduro MR, Misfud A, et al. Androgen receptor gene polyglutamine length is associated with testicular histology in infertile patients. J Urol 2003; 169:224.
  70. Dowsing AT, Yong EL, Clark M, et al. Linkage between male infertility and trinucleotide repeat expansion in the androgen-receptor gene. Lancet 1999; 354:640.
  71. Rajpert-De Meyts E, Leffers H, Petersen JH, et al. CAG repeat length in androgen-receptor gene and reproductive variables in fertile and infertile men. Lancet 2002; 359:44.
  72. Davis-Dao CA, Tuazon ED, Sokol RZ, Cortessis VK. Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis. J Clin Endocrinol Metab 2007; 92:4319.
  73. Johnson L, George FW, Neaves WB, et al. Characterization of the testicular abnormality in 5 alpha-reductase deficiency. J Clin Endocrinol Metab 1986; 63:1091.
  74. Hess RA, Bunick D, Lee KH, et al. A role for oestrogens in the male reproductive system. Nature 1997; 390:509.
  75. Smith EP, Boyd J, Frank GR, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994; 331:1056.
  76. Robertson KM, O'Donnell L, Jones ME, et al. Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene. Proc Natl Acad Sci U S A 1999; 96:7986.
  77. Krege JH, Hodgin JB, Couse JF, et al. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci U S A 1998; 95:15677.
  78. Nuti F, Krausz C. Gene polymorphisms/mutations relevant to abnormal spermatogenesis. Reprod Biomed Online 2008; 16:504.
  79. Takeda R, Ueda M. Pituitary-gonadal function in male patients with myotonic dystrophy- serum luteinizing hormone, follicle stimulating hormone and testosterone levels and histological dmaage of the testis. Acta Endocrinol (Copenh) 1977; 84:382.
  80. Adamopoulos DA, Lawrence DM, Vassilopoulos P, et al. Pituitary-testicular interrelationships in mumps orchitis and other viral infections. Br Med J 1978; 1:1177.
  81. Beard CM, Benson RC Jr, Kelalis PP, et al. The incidence and outcome of mumps orchitis in Rochester, Minnesota, 1935 to 1974. Mayo Clin Proc 1977; 52:3.
  82. Morley JE, Distiller LA, Sagel J, et al. Hormonal changes associated with testicular atrophy and gynaecomastia in patients with leprosy. Clin Endocrinol (Oxf) 1977; 6:299.
  83. Krieger JN, Coombs RW, Collier AC, et al. Fertility parameters in men infected with human immunodeficiency virus. J Infect Dis 1991; 164:464.
  84. Umapathy E. STD/HIV association: effects on semen characteristics. Arch Androl 2005; 51:361.
  85. Carlson HE, Ippoliti AF, Swerdloff RS. Endocrine effects of acute and chronic cimetidine administration. Dig Dis Sci 1981; 26:428.
  86. Rowley MJ, Leach DR, Warner GA, Heller CG. Effect of graded doses of ionizing radiation on the human testis. Radiat Res 1974; 59:665.
  87. Schrag SD, Dixon RL. Occupational exposures associated with male reproductive dysfunction. Annu Rev Pharmacol Toxicol 1985; 25:567.
  88. Becker S, Berhane K. A meta-analysis of 61 sperm count studies revisited. Fertil Steril 1997; 67:1103.
  89. Aston KI, Carrell DT. Prospects for clinically relevant epigenetic tests in the andrology laboratory. Asian J Androl 2014; 16:782.
  90. Dada R, Kumar M, Jesudasan R, et al. Epigenetics and its role in male infertility. J Assist Reprod Genet 2012; 29:213.
  91. Kotaja N. MicroRNAs and spermatogenesis. Fertil Steril 2014; 101:1552.
  92. Ferfouri F, Boitrelle F, Ghout I, et al. A genome-wide DNA methylation study in azoospermia. Andrology 2013; 1:815.
  93. Chiu YH, Afeiche MC, Gaskins AJ, et al. Fruit and vegetable intake and their pesticide residues in relation to semen quality among men from a fertility clinic. Hum Reprod 2015; 30:1342.
  94. Montjean D, Ravel C, Benkhalifa M, et al. Methylation changes in mature sperm deoxyribonucleic acid from oligozoospermic men: assessment of genetic variants and assisted reproductive technology outcome. Fertil Steril 2013; 100:1241.
  95. Deepinder F, Makker K, Agarwal A. Cell phones and male infertility: dissecting the relationship. Reprod Biomed Online 2007; 15:266.
  96. Agarwal A, Deepinder F, Sharma RK, et al. Effect of cell phone usage on semen analysis in men attending infertility clinic: an observational study. Fertil Steril 2008; 89:124.
  97. Vine MF, Margolin BH, Morrison HI, Hulka BS. Cigarette smoking and sperm density: a meta-analysis. Fertil Steril 1994; 61:35.
  98. Jensen TK, Jørgensen N, Punab M, et al. Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries. Am J Epidemiol 2004; 159:49.
  99. Jensen MS, Mabeck LM, Toft G, et al. Lower sperm counts following prenatal tobacco exposure. Hum Reprod 2005; 20:2559.
  100. Marczylo EL, Amoako AA, Konje JC, et al. Smoking induces differential miRNA expression in human spermatozoa: a potential transgenerational epigenetic concern? Epigenetics 2012; 7:432.
  101. Kandeel FR, Swerdloff RS. Role of temperature in regulation of spermatogenesis and the use of heating as a method for contraception. Fertil Steril 1988; 49:1.
  102. Wang C, Cui YG, Wang XH, et al. transient scrotal hyperthermia and levonorgestrel enhance testosterone-induced spermatogenesis suppression in men through increased germ cell apoptosis. J Clin Endocrinol Metab 2007; 92:3292.
  103. Thonneau P, Ducot B, Bujan L, et al. Effect of male occupational heat exposure on time to pregnancy. Int J Androl 1997; 20:274.
  104. Wong WY, Zielhuis GA, Thomas CM, et al. New evidence of the influence of exogenous and endogenous factors on sperm count in man. Eur J Obstet Gynecol Reprod Biol 2003; 110:49.
  105. Bronson R, Cooper G, Rosenfeld D. Sperm antibodies: their role in infertility. Fertil Steril 1984; 42:171.
  106. Elder M, Maclaren N, Riley W. Gonadal autoantibodies in patients with hypogonadism and/or Addison's disease. J Clin Endocrinol Metab 1981; 52:1137.
  107. Spratt DI, Bigos ST, Beitins I, et al. Both hyper- and hypogonadotropic hypogonadism occur transiently in acute illness: bio- and immunoactive gonadotropins. J Clin Endocrinol Metab 1992; 75:1562.
  108. Handelsman DJ, Dong Q. Hypothalamo-pituitary gonadal axis in chronic renal failure. Endocrinol Metab Clin North Am 1993; 22:145.
  109. Wang, C, Chan, V, Tse, TF, Yeung, RTT. Effect of acute myocardial infarction on pituitary-testicular function. Clin Endocrinol 1974; 9:249.
  110. Zou S, Li Z, Wang Y, et al. Association study between polymorphisms of PRMT6, PEX10, SOX5, and nonobstructive azoospermia in the Han Chinese population. Biol Reprod 2014; 90:96.
  111. Yatsenko AN, Georgiadis AP, Röpke A, et al. X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med 2015; 372:2097.
  112. Chianese C, Gunning AC, Giachini C, et al. X chromosome-linked CNVs in male infertility: discovery of overall duplication load and recurrent, patient-specific gains with potential clinical relevance. PLoS One 2014; 9:e97746.
  113. Tahmasbpour E, Balasubramanian D, Agarwal A. A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART). J Assist Reprod Genet 2014; 31:1115.
  114. Ferlin A, Arredi B, Speltra E, et al. Molecular and clinical characterization of Y chromosome microdeletions in infertile men: a 10-year experience in Italy. J Clin Endocrinol Metab 2007; 92:762.
  115. Kuroda-Kawaguchi T, Skaletsky H, Brown LG, et al. The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat Genet 2001; 29:279.
  116. Krausz C, Degl'Innocenti S. Y chromosome and male infertility: update, 2006. Front Biosci 2006; 11:3049.
  117. Giachini C, Laface I, Guarducci E, et al. Partial AZFc deletions and duplications: clinical correlates in the Italian population. Hum Genet 2008; 124:399.
  118. Krausz C, Giachini C, Xue Y, et al. Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background. J Med Genet 2009; 46:21.
  119. Visser L, Westerveld GH, Korver CM, et al. Y chromosome gr/gr deletions are a risk factor for low semen quality. Hum Reprod 2009; 24:2667.
  120. Luddi A, Margollicci M, Gambera L, et al. Spermatogenesis in a man with complete deletion of USP9Y. N Engl J Med 2009; 360:881.
  121. Tyler-Smith C, Krausz C. The will-o'-the-wisp of genetics--hunting for the azoospermia factor gene. N Engl J Med 2009; 360:925.
  122. Krausz C, Quintana-Murci L, Barbaux S, et al. A high frequency of Y chromosome deletions in males with nonidiopathic infertility. J Clin Endocrinol Metab 1999; 84:3606.
  123. Foresta C, Moro E, Garolla A, et al. Y chromosome microdeletions in cryptorchidism and idiopathic infertility. J Clin Endocrinol Metab 1999; 84:3660.
  124. McLachlan RI, Aitken RJ, Cram D, et al. Need for standardization and confirmation of STS deletions on the Y chromosome. Fertil Steril 2008; 90:463.
  125. Teng, YN, Lin, YM, Lin, YH, et al. Association of a single-nucleotide polymorphism of the deleted-in-azoospermia-like gene with susceptibility to spermatogenic failure. J Clin Endocrinol 2002; Metab 2002; 87:5258.
  126. Teng YN, Lin YM, Sun HF, et al. Association of DAZL haplotypes with spermatogenic failure in infertile men. Fertil Steril 2006; 86:129.
  127. Becherini L, Guarducci E, Degl'Innocenti S, et al. DAZL polymorphisms and susceptibility to spermatogenic failure: an example of remarkable ethnic differences. Int J Androl 2004; 27:375.
  128. Tung JY, Rosen MP, Nelson LM, et al. Variants in Deleted in AZoospermia-Like (DAZL) are correlated with reproductive parameters in men and women. Hum Genet 2006; 118:730.
  129. Tung JY, Rosen MP, Nelson LM, et al. Novel missense mutations of the Deleted-in-AZoospermia-Like (DAZL) gene in infertile women and men. Reprod Biol Endocrinol 2006; 4:40.
  130. Hu Z, Xia Y, Guo X, et al. A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia. Nat Genet 2011; 44:183.
  131. Lo Giacco D, Chianese C, Ars E, et al. Recurrent X chromosome-linked deletions: discovery of new genetic factors in male infertility. J Med Genet 2014; 51:340.
  132. Carrell DT. Epigenetics of the male gamete. Fertil Steril 2012; 97:267.
  133. Boissonnas CC, Jouannet P, Jammes H. Epigenetic disorders and male subfertility. Fertil Steril 2013; 99:624.
  134. Luk AC, Chan WY, Rennert OM, Lee TL. Long noncoding RNAs in spermatogenesis: insights from recent high-throughput transcriptome studies. Reproduction 2014; 147:R131.
  135. Yao C, Liu Y, Sun M, et al. MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and spermiogenesis. Reproduction 2015; 150:R25.
  136. Aston KI, Punj V, Liu L, Carrell DT. Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis. Fertil Steril 2012; 97:285.
  137. Hammoud SS, Nix DA, Hammoud AO, et al. Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men. Hum Reprod 2011; 26:2558.
  138. Jenkins TG, Aston KI, Pflueger C, et al. Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. PLoS Genet 2014; 10:e1004458.
  139. Crujeiras AB, Casanueva FF. Obesity and the reproductive system disorders: epigenetics as a potential bridge. Hum Reprod Update 2015; 21:249.
  140. Paoloni-Giacobino A. Epigenetic effects of methoxychlor and vinclozolin on male gametes. Vitam Horm 2014; 94:211.
  141. Chianese C, Fino MG, Riera Escamilla A, et al. Comprehensive investigation in patients affected by sperm macrocephaly and globozoospermia. Andrology 2015; 3:203.
  142. Lee PA, Coughlin MT, Bellinger MF. Inhibin B: comparison with indexes of fertility among formerly cryptorchid and control men. J Clin Endocrinol Metab 2001; 86:2576.
  143. Aynsley-Green A, Zachmann M, Illig R, et al. Congenital bilateral anorchia in childhood: a clinical, endocrine and therapeutic evaluation of twenty-one cases. Clin Endocrinol (Oxf) 1976; 5:381.
  144. Tal R, Holland R, Belenky A, et al. Incidental testicular tumors in infertile men. Fertil Steril 2004; 82:469.
  145. Raman JD, Nobert CF, Goldstein M. Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol 2005; 174:1819.
  146. Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2010; 16:231.
  147. Walsh TJ, Croughan MS, Schembri M, et al. Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med 2009; 169:351.
  148. Howards, SS. Varicocele. Infert Reprod Med Clin North Am 1992; 3:429.
  149. Pryor JL, Howards SS. Varicocele. Urol Clin North Am 1987; 14:499.
  150. Stillman RJ. In utero exposure to diethylstilbestrol: adverse effects on the reproductive tract and reproductive performance and male and female offspring. Am J Obstet Gynecol 1982; 142:905.
  151. Hikim AP, Lue YH, Wang C, et al. Posttesticular antifertility action of triptolide in the male rat: evidence for severe impairment of cauda epididymal sperm ultrastructure. J Androl 2000; 21:431.
  152. Belker AM, Thomas AJ Jr, Fuchs EF, et al. Results of 1,469 microsurgical vasectomy reversals by the Vasovasostomy Study Group. J Urol 1991; 145:505.
  153. Patrizio P, Asch RH, Handelin B, Silber SJ. Aetiology of congenital absence of vas deferens: genetic study of three generations. Hum Reprod 1993; 8:215.
  154. Munro NC, Currie DC, Lindsay KS, et al. Fertility in men with primary ciliary dyskinesia presenting with respiratory infection. Thorax 1994; 49:684.
  155. Zariwala MA, Knowles MR, Omran H. Genetic defects in ciliary structure and function. Annu Rev Physiol 2007; 69:423.
  156. Storm van's Gravesande K, Omran H. Primary ciliary dyskinesia: clinical presentation, diagnosis and genetics. Ann Med 2005; 37:439.
  157. Morillas HN, Zariwala M, Knowles MR. Genetic causes of bronchiectasis: primary ciliary dyskinesia. Respiration 2007; 74:252.
  158. Wilton LJ, Teichtahl H, Temple-Smith PD, et al. Young's syndrome (obstructive azoospermia and chronic sinobronchial infection): a quantitative study of axonemal ultrastructure and function. Fertil Steril 1991; 55:144.
  159. Ichioka K, Kohei N, Okubo K, et al. Obstructive azoospermia associated with chronic sinopulmonary infection and situs inversus totalis. Urology 2006; 68:204.e5.