Skip to main content
SpringerLink
Log in

Male Infertility

  • Chapter
  • First Online:
Book cover Clinical Reproductive Medicine and Surgery

Abstract

Abnormalities of the male account for a substantial portion of instances of infertility. Causes encompass genetic, chromosomal, endocrine, anatomic, and vascular disorders, and compromise of spermatogenesis may be due to environmental or nutritional factors as well. Thorough, formal evaluation may identify causes amenable to specific treatment. For instances in which specific treatment is not available or no identifiable cause is found, intrauterine insemination or specific manipulations in assisted reproductive technology offer options for fertility for many men.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

Male infertility:

Defined as absence of pregnancy after 1 year of unprotected intercourse and presence of semen abnormalities on a semen analysis, abnormal sperm function, or a disruption in the semen delivery mechanisms

Semen analysis:

Defined as the study of the ejaculate. It typically reports the ejaculate volume, sperm concentration, sperm motility, sperm viability, and sperm morphology

Oligozoospermia:

Low sperm concentration defined as sperm count less than 15 million/mL

Teratozoospermia:

Abnormal sperm morphology defined as normal sperm morphology less than 4%

Asthenozoospermia:

Low sperm motility defined as sperm motility less than 40%

Azooseprmia:

Defined as absence of sperm after appropriate centrifugation

CBAVD:

Congenital bilateral absence of vas deferens linked to a mutation in the CFTR (cystic fibrosis) gene. It is one of the causes of azoospermia

Hypogonadism:

Defined as low serum testosterone level

Genetic causes of male infertility:

Typically associated with severe oligzoospermia or azoospermia, the most common are chromosomal abnormalities, such as Klinefelter syndrome, and Y chromosome micro deletions

Varicocele:

Clinically significant varicocele is an enlargement of pampiniform venous plexus surrounding the testicles, mainly of the left

ART:

Artificial reproductive technologies including in vitro fertilization and ICSI (intra cytoplasmic sperm injections)

References

  1. Check JH, Chase JS. Improved semen quality after a short-interval second ejaculation. Fertil Steril. 1985;44(3):416–8.

    Article  CAS  PubMed  Google Scholar 

  2. Hornstein MD, Cohen JN, Thomas PP, Gleason RE, Friedman AJ, Mutter GL. The effect of consecutive day inseminations on semen characteristics in an intrauterine insemination program. Fertil Steril. 1992;58(2):433–5.

    Article  CAS  PubMed  Google Scholar 

  3. Levitas E, Lunenfeld E, Weiss N, Friger M, Har-Vardi I, Koifman A, et al. Relationship between the duration of sexual abstinence and semen quality: analysis of 9,489 semen samples. Fertil Steril. 2005;83(6):1680–6.

    Article  PubMed  Google Scholar 

  4. Marshburn PB, Alanis M, Matthews ML, Usadi R, Papadakis MH, Kullstam S, et al. A short period of ejaculatory abstinence before intrauterine insemination is associated with higher pregnancy rates. Fertil Steril. 2010;93(1):286–8.

    Article  PubMed  Google Scholar 

  5. Tur-Kaspa I, Maor Y, Dor J, Mashiach S. Frequency of intercourse for couples trying to conceive. Lancet. 1994;344(8925):766.

    Article  CAS  PubMed  Google Scholar 

  6. Peterson BD, Newton CR, Feingold T. Anxiety and sexual stress in men and women undergoing infertility treatment. Fertil Steril. 2007;88(4):911–4.

    Article  PubMed  Google Scholar 

  7. Saleh RA, Ranga GM, Raina R, Nelson DR, Agarwal A. Sexual dysfunction in men undergoing infertility evaluation: a cohort observational study. Fertil Steril. 2003;79(4):909–12.

    Article  PubMed  Google Scholar 

  8. Morales A, Buvat J, Gooren LJ, Guay AT, Kaufman JM, Tan HM, et al. Endocrine aspects of sexual dysfunction in men. J Sex Med. 2004;1(1):69–81.

    Article  CAS  PubMed  Google Scholar 

  9. Wischmann TH. Sexual disorders in infertile couples. J Sex Med. 2010;7(5):1868–76.

    Article  PubMed  Google Scholar 

  10. Griffith ER, Tomko MA, Timms RJ. Sexual function in spinal cord-injured patients: a review. Arch Phys Med Rehabil. 1973;54(12):539–43.

    CAS  PubMed  Google Scholar 

  11. Hendry WF. Disorders of ejaculation: congenital, acquired and functional. Br J Urol. 1998;82(3):331–41.

    Article  CAS  PubMed  Google Scholar 

  12. Hsiao W, Deveci S, Mulhall JP. Outcomes of the management of post-chemotherapy retroperitoneal lymph node dissection-associated anejaculation. BJU Int. 2012;110(8):1196–200.

    Article  PubMed  Google Scholar 

  13. Safarinejad MR. Midodrine for the treatment of organic anejaculation but not spinal cord injury: a prospective randomized placebo-controlled double-blind clinical study. Int J Impot Res. 2009;21(4):213–20.

    Article  CAS  PubMed  Google Scholar 

  14. McGuire C, Manecksha RP, Sheils P, McDermott TE, Grainger R, Flynn R. Electroejaculatory stimulation for male infertility secondary to spinal cord injury: the Irish experience in National Rehabilitation Hospital. Urology. 2011;77(1):83–7.

    Article  PubMed  Google Scholar 

  15. Schuster TG, Ohl DA. Diagnosis and treatment of ejaculatory dysfunction. Urol Clin North Am. 2002;29(4):939–48.

    Article  PubMed  Google Scholar 

  16. Sonksen J, Fode M, Lochner-Ernst D, Ohl DA. Vibratory ejaculation in 140 spinal cord injured men and home insemination of their partners. Spinal Cord. 2012;50(1):63–6.

    Article  CAS  PubMed  Google Scholar 

  17. Steinberger RE, Ohl DA, Bennett CJ, McCabe M, Wang SC. Nifedipine pretreatment for autonomic dysreflexia during electroejaculation. Urology. 1990;36(3):228–31.

    Article  CAS  PubMed  Google Scholar 

  18. Iremashvili V, Brackett NL, Ibrahim E, Aballa TC, Lynne CM. The choice of assisted ejaculation method is relevant for the diagnosis of azoospermia in men with spinal cord injuries. Spinal Cord. 2011;49(1):55–9.

    Article  CAS  PubMed  Google Scholar 

  19. Iremashvili VV, Brackett NL, Ibrahim E, Aballa TC, Lynne CM. A minority of men with spinal cord injury have normal semen quality—can we learn from them? A case-control study. Urology. 2010;76(2):347–51.

    Article  PubMed  Google Scholar 

  20. Momen MN, Fahmy I, Amer M, Arafa M, Zohdy W, Naser TA. Semen parameters in men with spinal cord injury: changes and aetiology. Asian J Androl. 2007;9(5):684–9.

    Article  PubMed  Google Scholar 

  21. Jorgensen N, Meyts ER, Main KM, Skakkebaek NE. Testicular dysgenesis syndrome comprises some but not all cases of hypospadias and impaired spermatogenesis. Int J Androl. 2010;33(2):298–303.

    Article  CAS  PubMed  Google Scholar 

  22. Toppari J, Virtanen HE, Main KM, Skakkebaek NE. Cryptorchidism and hypospadias as a sign of testicular dysgenesis syndrome (TDS): environmental connection. Birth Defects Res A Clin Mol Teratol. 2010;88(10):910–9.

    Article  CAS  PubMed  Google Scholar 

  23. Akre O, Richiardi L. Does a testicular dysgenesis syndrome exist? Hum Reprod. 2009;24(9):2053–60.

    Article  PubMed  Google Scholar 

  24. Thorup J, McLachlan R, Cortes D, Nation TR, Balic A, Southwell BR, et al. What is new in cryptorchidism and hypospadias—a critical review on the testicular dysgenesis hypothesis. J Pediatr Surg. 2010;45(10):2074–86.

    Article  PubMed  Google Scholar 

  25. Everaert K, Mahmoud A, Depuydt C, Maeyaert M, Comhaire F. Chronic prostatitis and male accessory gland infection—is there an impact on male infertility (diagnosis and therapy)? Andrologia. 2003;35(5):325–30.

    Article  CAS  PubMed  Google Scholar 

  26. Menkveld R, Huwe P, Ludwig M, Weidner W. Morphological sperm alternations in different types of prostatitis. Andrologia. 2003;35(5):288–93.

    Article  CAS  PubMed  Google Scholar 

  27. Menkveld R, Kruger TF. Sperm morphology and male urogenital infections. Andrologia. 1998;30(Suppl 1):49–53.

    PubMed  Google Scholar 

  28. Jahnukainen K, Heikkinen R, Henriksson M, Cooper TG, Puukko-Viertomies LR, Makitie O. Semen quality and fertility in adult long-term survivors of childhood acute lymphoblastic leukemia. Fertil Steril. 2011;96(4):837–42.

    Article  PubMed  Google Scholar 

  29. Nurmio M, Keros V, Lahteenmaki P, Salmi T, Kallajoki M, Jahnukainen K. Effect of childhood acute lymphoblastic leukemia therapy on spermatogonia populations and future fertility. J Clin Endocrinol Metab. 2009;94(6):2119–22.

    Article  CAS  PubMed  Google Scholar 

  30. Pacey AA. Fertility issues in survivors from adolescent cancers. Cancer Treat Rev. 2007;33(7):646–55.

    Article  CAS  PubMed  Google Scholar 

  31. Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2010;28(2):332–9.

    Article  PubMed  Google Scholar 

  32. Holoch P, Wald M. Current options for preservation of fertility in the male. Fertil Steril. 2011;96(2):286–90.

    Article  PubMed  Google Scholar 

  33. Leader A, Lishner M, Michaeli J, Revel A. Fertility considerations and preservation in haemato-oncology patients undergoing treatment. Br J Haematol. 2011;153(3):291–308.

    Article  PubMed  Google Scholar 

  34. Muthusami KR, Chinnaswamy P. Effect of chronic alcoholism on male fertility hormones and semen quality. Fertil Steril. 2005;84(4):919–24.

    Article  CAS  PubMed  Google Scholar 

  35. Said TM, Ranga G, Agarwal A. Relationship between semen quality and tobacco chewing in men undergoing infertility evaluation. Fertil Steril. 2005;84(3):649–53.

    Article  PubMed  Google Scholar 

  36. Soares SR, Melo MA. Cigarette smoking and reproductive function. Curr Opin Obstet Gynecol. 2008;20(3):281–91.

    Article  PubMed  Google Scholar 

  37. Jensen TK, Hjollund NH, Henriksen TB, Scheike T, Kolstad H, Giwercman A, et al. Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy. BMJ. 1998;317(7157):505–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Martini AC, Molina RI, Estofan D, Senestrari D, Fiol de Cuneo M, Ruiz RD. Effects of alcohol and cigarette consumption on human seminal quality. Fertil Steril. 2004;82(2):374–7.

    Article  PubMed  Google Scholar 

  39. Povey AC, Clyma JA, McNamee R, Moore HD, Baillie H, Pacey AA, et al. Modifiable and non-modifiable risk factors for poor semen quality: a case-referent study. Hum Reprod. 2012;27(9):2799–806.

    Article  CAS  PubMed  Google Scholar 

  40. Fuentes A, Munoz A, Barnhart K, Arguello B, Diaz M, Pommer R. Recent cigarette smoking and assisted reproductive technologies outcome. Fertil Steril. 2010;93(1):89–95.

    Article  CAS  PubMed  Google Scholar 

  41. Hammoud AO, Gibson M, Peterson CM, Meikle AW, Carrell DT. Impact of male obesity on infertility: a critical review of the current literature. Fertil Steril. 2008;90(4):897–904.

    Article  PubMed  Google Scholar 

  42. Roth MY, Amory JK, Page ST. Treatment of male infertility secondary to morbid obesity. Nat Clin Pract Endocrinol Metab. 2008;4(7):415–9.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Hammoud AO, Carrell DT, Gibson M, Peterson CM, Meikle AW. Updates on the relation of weight excess and reproductive function in men: sleep apnea as a new area of interest. Asian J Androl. 2012;14(1):77–81.

    Article  PubMed  Google Scholar 

  44. Relwani R, Berger D, Santoro N, Hickmon C, Nihsen M, Zapantis A, et al. Semen parameters are unrelated to BMI but vary with SSRI use and prior urological surgery. Reprod Sci. 2011;18(4):391–7.

    Article  PubMed  Google Scholar 

  45. Rybar R, Kopecka V, Prinosilova P, Markova P, Rubes J. Male obesity and age in relationship to semen parameters and sperm chromatin integrity. Andrologia. 2011;43(4):286–91.

    Article  CAS  PubMed  Google Scholar 

  46. Hammoud AO, Griffin J, Meikle AW, Gibson M, Peterson CM, Carrell DT. Association of aromatase (TTTAn) repeat polymorphism length and the relationship between obesity and decreased sperm concentration. Hum Reprod. 2010;25(12):3146–51.

    Article  CAS  PubMed  Google Scholar 

  47. Hofny ER, Ali ME, Abdel-Hafez HZ, Kamal Eel D, Mohamed EE, Abd El-Azeem HG, et al. Semen parameters and hormonal profile in obese fertile and infertile males. Fertil Steril. 2010;94(2):581–4.

    Article  CAS  PubMed  Google Scholar 

  48. Soubry A, Guo L, Huang Z, Hoyo C, Romanus S, Price T, Murphy SK. Obesity-related DNA methylation at imprinted genes in human sperm: results from the TIEGER study. Clin Epigenetics. 2016;8:51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Sermondade N, Massin N, Boitrelle F, Pfeffer J, Eustache F, Sifer C, et al. Sperm parameters and male fertility after bariatric surgery: three case series. Reprod BioMed Online. 2012;24(2):206–10.

    Article  PubMed  Google Scholar 

  50. Arce JC, De Souza MJ. Exercise and male factor infertility. Sports Med. 1993;15(3):146–69.

    Article  CAS  PubMed  Google Scholar 

  51. Gebreegziabher Y, Marcos E, McKinon W, Rogers G. Sperm characteristics of endurance trained cyclists. Int J Sports Med. 2004;25(4):247–51.

    Article  CAS  PubMed  Google Scholar 

  52. Vaamonde D, Da Silva ME, Poblador MS, Lancho JL. Reproductive profile of physically active men after exhaustive endurance exercise. Int J Sports Med. 2006;27(9):680–9.

    Article  CAS  PubMed  Google Scholar 

  53. Wu FC, Aitken RJ, Ferguson A. Inflammatory bowel disease and male infertility: effects of sulfasalazine and 5-aminosalicylic acid on sperm-fertilizing capacity and reactive oxygen species generation. Fertil Steril. 1989;52(5):842–5.

    Article  CAS  PubMed  Google Scholar 

  54. de Souza GL, Hallak J. Anabolic steroids and male infertility: a comprehensive review. BJU Int. 2011;108(11):1860–5.

    Article  PubMed  CAS  Google Scholar 

  55. Lombardo F, Sgro P, Salacone P, Gilio B, Gandini L, Dondero F, et al. Androgens and fertility. J Endocrinol Investig. 2005;28(3 Suppl):51–5.

    CAS  Google Scholar 

  56. Boxmeer JC, Smit M, Utomo E, Romijn JC, Eijkemans MJ, Lindemans J, et al. Low folate in seminal plasma is associated with increased sperm DNA damage. Fertil Steril. 2009;92(2):548–56.

    Article  CAS  PubMed  Google Scholar 

  57. Colagar AH, Marzony ET, Chaichi MJ. Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men. Nutr Res. 2009;29(2):82–8.

    Article  CAS  PubMed  Google Scholar 

  58. Ebisch IM, Thomas CM, Peters WH, Braat DD, Steegers-Theunissen RP. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update. 2007;13(2):163–74.

    Article  CAS  PubMed  Google Scholar 

  59. Mendiola J, Torres-Cantero AM, Vioque J, Moreno-Grau JM, Ten J, Roca M, et al. A low intake of antioxidant nutrients is associated with poor semen quality in patients attending fertility clinics. Fertil Steril. 2010;93(4):1128–33.

    Article  CAS  PubMed  Google Scholar 

  60. Mistry HD, Broughton Pipkin F, Redman CW, Poston L. Selenium in reproductive health. Am J Obstet Gynecol. 2012;206(1):21–30.

    Article  CAS  PubMed  Google Scholar 

  61. Murphy LE, Mills JL, Molloy AM, Qian C, Carter TC, Strevens H, et al. Folate and vitamin B12 in idiopathic male infertility. Asian J Androl. 2011;13(6):856–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Safarinejad MR, Shafiei N, Safarinejad S. Relationship between genetic polymorphisms of methylenetetrahydrofolate reductase (C677T, A1298C, and G1793A) as risk factors for idiopathic male infertility. Reprod Sci. 2011;18(3):304–15.

    Article  CAS  PubMed  Google Scholar 

  63. Hawkes WC, Alkan Z, Wong K. Selenium supplementation does not affect testicular selenium status or semen quality in North American men. J Androl. 2009;30(5):525–33.

    Article  CAS  PubMed  Google Scholar 

  64. Hammoud A, Carrell DT, Gibson M, Sanderson M, Parker-Jones K, Peterson CM. Decreased sperm motility is associated with air pollution in Salt Lake City. Fertil Steril. 2010;93(6):1875–9.

    Article  PubMed  Google Scholar 

  65. Benoff S, Jacob A, Hurley IR. Male infertility and environmental exposure to lead and cadmium. Hum Reprod Update. 2000;6(2):107–21.

    Article  CAS  PubMed  Google Scholar 

  66. Schuurs AH. Reproductive toxicity of occupational mercury. A review of the literature. J Dent. 1999;27(4):249–56.

    Article  CAS  PubMed  Google Scholar 

  67. Duty SM, Silva MJ, Barr DB, Brock JW, Ryan L, Chen Z, et al. Phthalate exposure and human semen parameters. Epidemiology. 2003;14(3):269–77.

    PubMed  Google Scholar 

  68. Hauser R, Meeker JD, Duty S, Silva MJ, Calafat AM. Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites. Epidemiology. 2006;17(6):682–91.

    Article  PubMed  Google Scholar 

  69. Dalvie MA, Myers JE, Thompson ML, Robins TG, Dyer S, Riebow J, et al. The long-term effects of DDT exposure on semen, fertility, and sexual function of malaria vector-control workers in Limpopo Province. South Africa Environ Res. 2004;96(1):1–8.

    CAS  PubMed  Google Scholar 

  70. Hauser R, Chen Z, Pothier L, Ryan L, Altshul L. The relationship between human semen parameters and environmental exposure to polychlorinated biphenyls and p,p′-DDE. Environ Health Perspect. 2003;111(12):1505–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Rozati R, Reddy PP, Reddanna P, Mujtaba R. Xenoesterogens and male infertility: myth or reality? Asian J Androl. 2000;2(4):263–9.

    CAS  PubMed  Google Scholar 

  72. Hanke W, Jurewicz J. The risk of adverse reproductive and developmental disorders due to occupational pesticide exposure: an overview of current epidemiological evidence. Int J Occup Med Environ Health. 2004;17(2):223–43.

    PubMed  Google Scholar 

  73. Phillips KP, Tanphaichitr N. Human exposure to endocrine disrupters and semen quality. J Toxicol Environ Health B Crit Rev. 2008;11(3–4):188–220.

    Article  CAS  PubMed  Google Scholar 

  74. Sadeu JC, Hughes CL, Agarwal S, Foster WG. Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: reproductive health consequences and clinical implications. Crit Rev Toxicol. 2010;40(7):633–52.

    Article  CAS  PubMed  Google Scholar 

  75. Toft G, Rignell-Hydbom A, Tyrkiel E, Shvets M, Giwercman A, Lindh CH, et al. Semen quality and exposure to persistent organochlorine pollutants. Epidemiology. 2006;17(4):450–8.

    Article  PubMed  Google Scholar 

  76. Kolettis PN, Sandlow JI. Clinical and genetic features of patients with congenital unilateral absence of the vas deferens. Urology. 2002;60(6):1073–6.

    Article  PubMed  Google Scholar 

  77. Stahl P, Schlegel PN. Standardization and documentation of varicocele evaluation. Curr Opin Urol. 2011;21(6):500–5.

    Article  PubMed  Google Scholar 

  78. Cocuzza M, Athayde KS, Alvarenga C, Srougi M, Hallak J. Grade 3 varicocele in fertile men: a different entity. J Urol. 2012;187(4):1363–8.

    Article  PubMed  Google Scholar 

  79. Li F, Yue H, Yamaguchi K, Okada K, Matsushita K, Ando M, et al. Effect of surgical repair on testosterone production in infertile men with varicocele: a meta-analysis. Int J Urol. 2012;19(2):149–54.

    Article  CAS  PubMed  Google Scholar 

  80. Mostafa T, Anis T, El Nashar A, Imam H, Osman I. Seminal plasma reactive oxygen species-antioxidants relationship with varicocele grade. Andrologia. 2012;44(1):66–9.

    Article  CAS  PubMed  Google Scholar 

  81. Chen SS, Chen LK. Risk factors for progressive deterioration of semen quality in patients with varicocele. Urology. 2012;79(1):128–32.

    Article  PubMed  Google Scholar 

  82. Ammar T, et al. Male infertility: the role of imaging in the diagnosis and management. Br J Radiol. 2012;85:S59–68.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Lotti F, et al. Ultrasound of the male genital tract in relation to male reproductive health. Hum Reprod Update. 2015;21(1):56–83.

    Article  PubMed  Google Scholar 

  84. Abdulwahed SR, Mohamed EE, Taha EA, Saleh MA, Abdelsalam YM, ElGanainy EO. Sensitivity and specificity of ultrasonography in predicting etiology of azoospermia. Urology. 2013;81(5):967–71.

    Article  PubMed  Google Scholar 

  85. Cozzolino DJ, Lipshultz LI. Varicocele as a progressive lesion: positive effect of varicocele repair. Hum Reprod Update. 2001;7(1):55–8.

    Article  CAS  PubMed  Google Scholar 

  86. Mac LJ, Gold RZ. The male factor in fertility and infertility. IV. Sperm morphology in fertile and infertile marriage. Fertil Steril. 1951;2(5):394–414.

    Article  Google Scholar 

  87. Macleod J. Semen quality in 1000 men of known fertility and in 800 cases of infertile marriage. Fertil Steril. 1951;2(2):115–39.

    Article  CAS  PubMed  Google Scholar 

  88. Macleod J, Gold RZ. The male factor in fertility and infertility. II. Spermatozoon counts in 1000 men of known fertility and in 1000 cases of infertile marriage. J Urol. 1951;66(3):436–49.

    CAS  PubMed  Google Scholar 

  89. WHO. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: WHO Press; 2010.

    Google Scholar 

  90. Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231–45.

    Article  PubMed  Google Scholar 

  91. Guzick DS, Overstreet JW, Factor-Litvak P, Brazil CK, Nakajima ST, Coutifaris C, et al. Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med. 2001;345(19):1388–93.

    Article  CAS  PubMed  Google Scholar 

  92. Mallidis C, Howard EJ, Baker HW. Variation of semen quality in normal men. Int J Androl. 1991;14(2):99–107.

    Article  CAS  PubMed  Google Scholar 

  93. Hammoud AO, Gibson M, Peterson MC, Carrell DT. Effect of sperm preparation techniques by density gradient on intra-individual variation of sperm motility. Arch Androl. 2007;53(6):349–51.

    Article  PubMed  Google Scholar 

  94. Bonde JP, Ernst E, Jensen TK, Hjollund NH, Kolstad H, Henriksen TB, et al. Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet. 1998;352(9135):1172–7.

    Article  CAS  PubMed  Google Scholar 

  95. Ho LM, Lim AS, Lim TH, Hum SC, Yu SL, Kruger TF. Correlation between semen parameters and the Hamster Egg Penetration Test (HEPT) among fertile and subfertile men in Singapore. J Androl. 2007;28(1):158–63.

    Article  PubMed  Google Scholar 

  96. Menkveld R. Clinical significance of the low normal sperm morphology value as proposed in the fifth edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen. Asian J Androl. 2010;12(1):47–58.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Slama R, Eustache F, Ducot B, Jensen TK, Jorgensen N, Horte A, et al. Time to pregnancy and semen parameters: a cross-sectional study among fertile couples from four European cities. Hum Reprod. 2002;17(2):503–15.

    Article  CAS  PubMed  Google Scholar 

  98. Bjorndahl L. What is normal semen quality? On the use and abuse of reference limits for the interpretation of semen analysis results. Hum Fertil (Camb). 2011;14(3):179–86.

    Article  Google Scholar 

  99. De Jonge C. Semen analysis: looking for an upgrade in class. Fertil Steril. 2012;97(2):260–6.

    Article  PubMed  Google Scholar 

  100. Eliasson R. Semen analysis with regard to sperm number, sperm morphology and functional aspects. Asian J Androl. 2010;12(1):26–32.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Esteves SC, Zini A, Aziz N, Alvarez JG, Sabanegh ES, Agarwal A. Critical appraisal of World Health Organization’s new reference values for human semen characteristics and effect on diagnosis and treatment of subfertile men. Urology. 2012;79:16–22.

    Article  PubMed  Google Scholar 

  102. Franken DR, Oehninger S. Semen analysis and sperm function testing. Asian J Androl. 2012;14(1):6–13.

    Article  PubMed  Google Scholar 

  103. Menkveld R, Stander FS, Kotze TJ, Kruger TF, van Zyl JA. The evaluation of morphological characteristics of human spermatozoa according to stricter criteria. Hum Reprod. 1990;5(5):586–92.

    Article  CAS  PubMed  Google Scholar 

  104. Guven S, Gunalp GS, Tekin Y. Factors influencing pregnancy rates in intrauterine insemination cycles. J Reprod Med. 2008;53(4):257–65.

    PubMed  Google Scholar 

  105. Kruger TF, Coetzee K. The role of sperm morphology in assisted reproduction. Hum Reprod Update. 1999;5(2):172–8.

    Article  CAS  PubMed  Google Scholar 

  106. Kruger TF, Swanson RJ, Hamilton M, Simmons KF, Acosta AA, Matta JF, et al. Abnormal sperm morphology and other semen parameters related to the outcome of the hamster oocyte human sperm penetration assay. Int J Androl. 1988;11(2):107–13.

    Article  CAS  PubMed  Google Scholar 

  107. Morelli SS, Seungdamrong A, McCulloh DH, McGovern PG. Abnormal sperm count and motility on semen analysis are not sufficiently predictive of abnormal Kruger morphology. Fertil Steril. 2010;94(7):2882–4.

    Article  PubMed  Google Scholar 

  108. Van Waart J, Kruger TF, Lombard CJ, Ombelet W. Predictive value of normal sperm morphology in intrauterine insemination (IUI): a structured literature review. Hum Reprod Update. 2001;7(5):495–500.

    Article  CAS  PubMed  Google Scholar 

  109. Esterhuizen AD, Franken DR, Lourens JG, van Rooyen LH. Clinical importance of zona pellucida-induced acrosome reaction and its predictive value for IVF. Hum Reprod. 2001;16(1):138–44.

    Article  CAS  PubMed  Google Scholar 

  110. Menkveld R, Rhemrev JP, Franken DR, Vermeiden JP, Kruger TF. Acrosomal morphology as a novel criterion for male fertility diagnosis: relation with acrosin activity, morphology (strict criteria), and fertilization in vitro. Fertil Steril. 1996;65(3):637–44.

    Article  CAS  PubMed  Google Scholar 

  111. Oehninger S, Acosta AA, Veeck LL, Brzyski R, Kruger TF, Muasher SJ, et al. Recurrent failure of in vitro fertilization: role of the hemizona assay in the sequential diagnosis of specific sperm-oocyte defects. Am J Obstet Gynecol. 1991;164(5 Pt 1):1210–5.

    Article  CAS  PubMed  Google Scholar 

  112. Bastiaan HS, Windt ML, Menkveld R, Kruger TF, Oehninger S, Franken DR. Relationship between zona pellucida-induced acrosome reaction, sperm morphology, sperm-zona pellucida binding, and in vitro fertilization. Fertil Steril. 2003;79(1):49–55.

    Article  PubMed  Google Scholar 

  113. Zahalsky MP, Zoltan E, Medley N, Nagler HM. Morphology and the sperm penetration assay. Fertil Steril. 2003;79(1):39–41.

    Article  PubMed  Google Scholar 

  114. Natali A, Turek PJ. An assessment of new sperm tests for male infertility. Urology. 2011;77(5):1027–34.

    Article  PubMed  Google Scholar 

  115. Evenson DP, Jost LK, Marshall D, Zinaman MJ, Clegg E, Purvis K, et al. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod. 1999;14(4):1039–49.

    Article  CAS  PubMed  Google Scholar 

  116. Muratori M, Tamburrino L, Marchiani S, Guido C, Forti G, Baldi E. Critical aspects of detection of sperm DNA fragmentation by TUNEL/flow cytometry. Syst Biol Reprod Med. 2010;56(4):277–85.

    Article  CAS  PubMed  Google Scholar 

  117. Tamburrino L, Marchiani S, Montoya M, Elia Marino F, Natali I, Cambi M, et al. Mechanisms and clinical correlates of sperm DNA damage. Asian J Androl. 2012;14(1):24–31.

    Article  CAS  PubMed  Google Scholar 

  118. Bungum M, Humaidan P, Spano M, Jepson K, Bungum L, Giwercman A. The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination. IVF and ICSI Hum Reprod. 2004;19(6):1401–8.

    Article  CAS  PubMed  Google Scholar 

  119. Irvine DS, Twigg JP, Gordon EL, Fulton N, Milne PA, Aitken RJ. DNA integrity in human spermatozoa: relationships with semen quality. J Androl. 2000;21(1):33–44.

    CAS  PubMed  Google Scholar 

  120. Virro MR, Larson-Cook KL, Evenson DP. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil Steril. 2004;81(5):1289–95.

    Article  PubMed  Google Scholar 

  121. Werthman P, Wixon R, Kasperson K, Evenson DP. Significant decrease in sperm deoxyribonucleic acid fragmentation after varicocelectomy. Fertil Steril. 2008;90(5):1800–4.

    Article  PubMed  Google Scholar 

  122. Alvarez JG, Sharma RK, Ollero M, Saleh RA, Lopez MC, Thomas Jr AJ, et al. Increased DNA damage in sperm from leukocytospermic semen samples as determined by the sperm chromatin structure assay. Fertil Steril. 2002;78(2):319–29.

    Article  PubMed  Google Scholar 

  123. Evenson DP, Wixon R. Environmental toxicants cause sperm DNA fragmentation as detected by the Sperm Chromatin Structure Assay (SCSA). Toxicol Appl Pharmacol. 2005;207(2 Suppl):532–7.

    Article  PubMed  CAS  Google Scholar 

  124. Silver EW, Eskenazi B, Evenson DP, Block G, Young S, Wyrobek AJ. Effect of antioxidant intake on sperm chromatin stability in healthy nonsmoking men. J Androl. 2005;26(4):550–6.

    Article  CAS  PubMed  Google Scholar 

  125. Tanrikut C, Feldman AS, Altemus M, Paduch DA, Schlegel PN. Adverse effect of paroxetine on sperm. Fertil Steril. 2010;94(3):1021–6.

    Article  CAS  PubMed  Google Scholar 

  126. Barratt CL, De Jonge CJ. Clinical relevance of sperm DNA assessment: an update. Fertil Steril. 2010;94(6):1958–9.

    Article  PubMed  Google Scholar 

  127. Carrell DT, Aston KI, Oliva R, Emery BR, De Jonge CJ. The “omics” of human male infertility: integrating big data in a systems biology approach. Cell Tissue Res. 2016;363(1):295–312.

    Article  CAS  PubMed  Google Scholar 

  128. Henkel R, Hoogendijk CF, Bouic PJ, Kruger TF. TUNEL assay and SCSA determine different aspects of sperm DNA damage. Andrologia. 2010;42(5):305–13.

    Article  PubMed  Google Scholar 

  129. Carrell DT. Epigenetics of the male gamete. Fertil Steril. 2012;97(2):267–74.

    Article  CAS  PubMed  Google Scholar 

  130. Hammoud SS, Nix DA, Hammoud AO, Gibson M, Cairns BR, Carrell DT. 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(9):2558–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Jenkins T, Carrell DT. The sperm epigenome and potential implications for the developing embryo. Reproduction. 2011;143(6):727–34.

    Article  CAS  Google Scholar 

  132. Navarro-Costa P, Nogueira P, Carvalho M, Leal F, Cordeiro I, Calhaz-Jorge C, et al. Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm. Hum Reprod. 2010;25(10):2647–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Cookson MS, Witt MA, Kimball KT, Grantmyre JE, Lipshultz LI. Can semen analysis predict the presence of antisperm antibodies in patients with primary infertility? World J Urol. 1995;13(5):318–22.

    Article  CAS  PubMed  Google Scholar 

  134. Menkveld R, Kruger TF, Kotze TJ, Windt ML, Pretorius E. Detection of sperm antibodies on unwashed spermatozoa with the immunobead test: a comparison of results with the routine method and seminal plasma TAT titers and SCMC test. Am J Reprod Immunol. 1991;25(2):88–91.

    Article  CAS  PubMed  Google Scholar 

  135. Pretorius E, Windt ML, Menkveld R, Kruger T. Evaluation of immunobead test (IBT), tray-agglutination test (TAT), and sperm immobilization test (SIT). Arch Androl. 1988;20(2):159–62.

    Article  CAS  PubMed  Google Scholar 

  136. Bohring C, Krause W. Differences in the antigen pattern recognized by antisperm antibodies in patients with infertility and vasectomy. J Urol. 2001;166(3):1178–80.

    Article  CAS  PubMed  Google Scholar 

  137. Shibahara H, Tsunoda T, Taneichi A, Hirano Y, Ohno A, Takamizawa S, et al. Diversity of antisperm antibodies bound to sperm surface in male immunological infertility. Am J Reprod Immunol. 2002;47(3):146–50.

    Article  PubMed  Google Scholar 

  138. Ombelet W, Vandeput H, Janssen M, Cox A, Vossen C, Pollet H, et al. Treatment of male infertility due to sperm surface antibodies: IUI or IVF? Hum Reprod. 1997;12(6):1165–70.

    Article  CAS  PubMed  Google Scholar 

  139. Windt ML, Menkveld R, Kruger TF, van der Merwe JP, Lombard CJ. Effect of rapid dilution of semen on sperm-bound autoantibodies. Arch Androl. 1989;22(3):227–31.

    Article  CAS  PubMed  Google Scholar 

  140. Franken D, Windt ML, Oosthuizen T, Kruger T, Menkveld R, Coddington C, et al. Assisted reproductive technologies may obviate apparent immunologic infertility. Andrologia. 1991;23(4):291–5.

    Article  CAS  PubMed  Google Scholar 

  141. Tasdemir I, Tasdemir M, Fukuda J, Kodama H, Matsui T, Tanaka T. Sperm immobilization antibodies in infertile male sera decrease the acrosome reaction: a possible mechanism for immunologic infertility. J Assist Reprod Genet. 1996;13(5):413–6.

    Article  CAS  PubMed  Google Scholar 

  142. Eliasson R, Mossberg B, Camner P, Afzelius BA. The immotile-cilia syndrome. A congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility. N Engl J Med. 1977;297(1):1–6.

    Article  CAS  PubMed  Google Scholar 

  143. Lungarella G, Fonzi L, Burrini AG. Ultrastructural abnormalities in respiratory cilia and sperm tails in a patient with Kartagener’s syndrome. Ultrastruct Pathol. 1982;3(4):319–23.

    Article  CAS  PubMed  Google Scholar 

  144. Sturgess JM, Chao J, Wong J, Aspin N, Turner JA. Cilia with defective radial spokes: a cause of human respiratory disease. N Engl J Med. 1979;300(2):53–6.

    Article  CAS  PubMed  Google Scholar 

  145. Matsumoto Y, Goto S, Hashimoto H, Kokeguchi S, Shiotani M, Okada H. A healthy birth after intracytoplasmic sperm injection using ejaculated spermatozoa from a patient with Kartagener’s syndrome. Fertil Steril. 2010;93(6):2074.e17–9.

    Article  Google Scholar 

  146. von Zumbusch A, Fiedler K, Mayerhofer A, Jessberger B, Ring J, Vogt HJ. Birth of healthy children after intracytoplasmic sperm injection in two couples with male Kartagener’s syndrome. Fertil Steril. 1998;70(4):643–6.

    Article  Google Scholar 

  147. Ochsenkuhn R, Kamischke A, Nieschlag E. Imipramine for successful treatment of retrograde ejaculation caused by retroperitoneal surgery. Int J Androl. 1999;22(3):173–7.

    Article  CAS  PubMed  Google Scholar 

  148. Tomasi PA, Fanciulli G, Delitala G. Successful treatment of retrograde ejaculation with the alpha1-adrenergic agonist methoxamine: case study. Int J Impot Res. 2005;17(3):297–9.

    Article  CAS  PubMed  Google Scholar 

  149. Gerris J, Van Royen E, Mangel-Schots K, Joostens M, de Vits A. Pregnancy after intracytoplasmic sperm injection of metaphase II oocytes with spermatozoa from a man with complete retrograde ejaculation. Hum Reprod. 1994;9(7):1293–6.

    Article  CAS  PubMed  Google Scholar 

  150. Nikolettos N, Al-Hasani S, Baukloh V, Schopper B, Demirel LC, Baban N, et al. The outcome of intracytoplasmic sperm injection in patients with retrograde ejaculation. Hum Reprod. 1999;14(9):2293–6.

    Article  CAS  PubMed  Google Scholar 

  151. Yavetz H, Yogev L, Hauser R, Lessing JB, Paz G, Homonnai ZT. Retrograde ejaculation. Hum Reprod. 1994;9(3):381–6.

    Article  CAS  PubMed  Google Scholar 

  152. Cavallini G. Male idiopathic oligoasthenoteratozoospermia. Asian J Androl. 2006;8(2):143–57.

    Article  CAS  PubMed  Google Scholar 

  153. Calogero AE, De Palma A, Grazioso C, Barone N, Burrello N, Palermo I, et al. High sperm aneuploidy rate in unselected infertile patients and its relationship with intracytoplasmic sperm injection outcome. Hum Reprod. 2001;16(7):1433–9.

    Article  CAS  PubMed  Google Scholar 

  154. Cavallini G, Crippa A, Magli MC, Cavallini N, Ferraretti AP, Gianaroli L. A study to sustain the hypothesis of the multiple genesis of oligoasthenoteratospermia in human idiopathic infertile males. Biol Reprod. 2008;79(4):667–73.

    Article  CAS  PubMed  Google Scholar 

  155. Bernardini L, Gianaroli L, Fortini D, Conte N, Magli C, Cavani S, et al. Frequency of hyper-, hypohaploidy and diploidy in ejaculate, epididymal and testicular germ cells of infertile patients. Hum Reprod. 2000;15(10):2165–72.

    Article  CAS  PubMed  Google Scholar 

  156. Gianaroli L, Magli MC, Cavallini G, Crippa A, Nadalini M, Bernardini L, et al. Frequency of aneuploidy in sperm from patients with extremely severe male factor infertility. Hum Reprod. 2005;20(8):2140–52.

    Article  PubMed  Google Scholar 

  157. Ushijima C, Kumasako Y, Kihaile PE, Hirotsuru K, Utsunomiya T. Analysis of chromosomal abnormalities in human spermatozoa using multi-colour fluorescence in-situ hybridization. Hum Reprod. 2000;15(5):1107–11.

    Article  Google Scholar 

  158. Kimura M, Nagao K, Tai T, Kobayashi H, Nakajima K. Age is a significant predictor of early and late improvement in semen parameters after microsurgical varicocele repair. Andrologia. 2016; doi:10.1111/and.12620.. [Epub ahead of print]

    PubMed  Google Scholar 

  159. Burrello N, Arcidiacono G, Vicari E, Asero P, Di Benedetto D, De Palma A, et al. Morphologically normal spermatozoa of patients with secretory oligo-astheno-teratozoospermia have an increased aneuploidy rate. Hum Reprod. 2004;19(10):2298–302.

    Article  PubMed  Google Scholar 

  160. Magli MC, Gianaroli L, Ferraretti AP, Gordts S, Fredericks V, Crippa A. Paternal contribution to aneuploidy in preimplantation embryos. Reprod BioMed Online. 2009;18(4):536–42.

    Article  CAS  PubMed  Google Scholar 

  161. Boissonnas CC, Abdalaoui HE, Haelewyn V, Fauque P, Dupont JM, Gut I, et al. Specific epigenetic alterations of IGF2-H19 locus in spermatozoa from infertile men. Eur J Hum Genet. 2010;18(1):73–80.

    Article  PubMed  CAS  Google Scholar 

  162. Liu CH, Tsao HM, Cheng TC, Wu HM, Huang CC, Chen CI, et al. DNA fragmentation, mitochondrial dysfunction and chromosomal aneuploidy in the spermatozoa of oligoasthenoteratozoospermic males. J Assist Reprod Genet. 2004;21(4):119–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Ramos L, van der Heijden GW, Derijck A, Berden JH, Kremer JA, van der Vlag J, et al. Incomplete nuclear transformation of human spermatozoa in oligo-astheno-teratospermia: characterization by indirect immunofluorescence of chromatin and thiol status. Hum Reprod. 2008;23(2):259–70.

    Article  CAS  PubMed  Google Scholar 

  164. Schlegel PN, Goldstein M. Alternate indications for varicocele repair: non-obstructive azoospermia, pain, androgen deficiency and progressive testicular dysfunction. Fertil Steril. 2011;96(6):1288–93.

    Article  PubMed  Google Scholar 

  165. Abdel-Meguid TA. Predictors of sperm recovery and azoospermia relapse in men with nonobstructive azoospermia after varicocele repair. J Urol. 2012;187(1):222–6.

    Article  PubMed  Google Scholar 

  166. Baazeem A, Belzile E, Ciampi A, Dohle G, Jarvi K, Salonia A, et al. Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair. Eur Urol. 2011;60(4):796–808.

    Article  PubMed  Google Scholar 

  167. Williams DH, Karpman E, Lipshultz LI. Varicocele: surgical techniques in 2005. Can J Urol. 2006;13(Suppl 1):13–7.

    PubMed  Google Scholar 

  168. Evers JH, Collins J, Clarke J. Surgery or embolisation for varicoceles in subfertile men. Cochrane Database Syst Rev. 2008;3:CD000479.

    Google Scholar 

  169. Ficarra V, Cerruto MA, Liguori G, Mazzoni G, Minucci S, Tracia A, et al. Treatment of varicocele in subfertile men: the Cochrane Review—a contrary opinion. Eur Urol. 2006;49(2):258–63.

    Article  PubMed  Google Scholar 

  170. Miyaoka R, Esteves SC. A critical appraisal on the role of varicocele in male infertility. Adv Urol. 2012;2012:597495.

    Article  PubMed  Google Scholar 

  171. Schlegel PN. Is assisted reproduction the optimal treatment for varicocele-associated male infertility? A cost-effectiveness analysis. Urology. 1997;49(1):83–90.

    Article  CAS  PubMed  Google Scholar 

  172. Oates R. Evaluation of the azoospermic male. Asian J Androl. 2012;14(1):82–7.

    Article  PubMed  Google Scholar 

  173. Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001;16(5):972–8.

    Article  CAS  PubMed  Google Scholar 

  174. Chen SC, Hsieh JT, Yu HJ, Chang HC. Appropriate cut-off value for follicle-stimulating hormone in azoospermia to predict spermatogenesis. Reprod Biol Endocrinol. 2010;8:108.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Bonomi M, Libri DV, Guizzardi F, Guarducci E, Maiolo E, Pignatti E, et al. New understandings of the genetic basis of isolated idiopathic central hypogonadism. Asian J Androl. 2012;14(1):49–56.

    Article  CAS  PubMed  Google Scholar 

  176. Colao A, Vitale G, Cappabianca P, Briganti F, Ciccarelli A, De Rosa M, et al. Outcome of cabergoline treatment in men with prolactinoma: effects of a 24-month treatment on prolactin levels, tumor mass, recovery of pituitary function, and semen analysis. J Clin Endocrinol Metab. 2004;89(4):1704–11.

    Article  CAS  PubMed  Google Scholar 

  177. Shimon I, Benbassat C, Hadani M. Effectiveness of long-term cabergoline treatment for giant prolactinoma: study of 12 men. Eur J Endocrinol. 2007;156(2):225–31.

    Article  CAS  PubMed  Google Scholar 

  178. Cruger DG, Agerholm I, Byriel L, Fedder J, Bruun-Petersen G. Genetic analysis of males from intracytoplasmic sperm injection couples. Clin Genet. 2003;64(3):198–203.

    Article  CAS  PubMed  Google Scholar 

  179. Foresta C, Garolla A, Bartoloni L, Bettella A, Ferlin A. Genetic abnormalities among severely oligospermic men who are candidates for intracytoplasmic sperm injection. J Clin Endocrinol Metab. 2005;90(1):152–6.

    Article  CAS  PubMed  Google Scholar 

  180. Harton GL, Tempest HG. Chromosomal disorders and male infertility. Asian J Androl. 2012;14(1):32–9.

    Article  PubMed  Google Scholar 

  181. Yoshida A, Miura K, Shirai M. Cytogenetic survey of 1,007 infertile males. Urol Int. 1997;58(3):166–76.

    Article  CAS  PubMed  Google Scholar 

  182. Van Assche E, Bonduelle M, Tournaye H, Joris H, Verheyen G, Devroey P, et al. Cytogenetics of infertile men. Hum Reprod. 1996;11(Suppl 4):1–24.. discussion 25–6

    Article  PubMed  Google Scholar 

  183. Morris JK, Alberman E, Scott C, Jacobs P. Is the prevalence of Klinefelter syndrome increasing? Eur J Hum Genet. 2008;16(2):163–70.

    Article  CAS  PubMed  Google Scholar 

  184. Ishikawa T. Surgical recovery of sperm in non-obstructive azoospermia. Asian J Androl. 2012;14(1):109–15.

    Article  PubMed  Google Scholar 

  185. Ramasamy R, Ricci JA, Leung RA, Schlegel PN. Successful repeat microdissection testicular sperm extraction in men with nonobstructive azoospermia. J Urol. 2011;185(3):1027–31.

    Article  PubMed  Google Scholar 

  186. Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum Reprod. 1999;14(1):131–5.

    Article  CAS  PubMed  Google Scholar 

  187. Lee JY, Dada R, Sabanegh E, Carpi A, Agarwal A. Role of genetics in azoospermia. Urology. 2011;77(3):598–601.

    Article  PubMed  Google Scholar 

  188. Martin RH. Cytogenetic determinants of male fertility. Hum Reprod Update. 2008;14(4):379–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Perrin A, Douet-Guilbert N, Le Bris MJ, Keromnes G, Langlois ML, Barriere P, et al. Segregation of chromosomes in sperm of a t(X;18)(q11;p11.1) carrier inherited from his mother: case report. Hum Reprod. 2008;23(1):227–30.

    Article  CAS  PubMed  Google Scholar 

  190. Harper JC, Coonen E, De Rycke M, Harton G, Moutou C, Pehlivan T, et al. ESHRE PGD Consortium data collection X: cycles from January to December 2007 with pregnancy follow-up to October 2008. Hum Reprod. 2010;25(11):2685–707.

    Article  CAS  PubMed  Google Scholar 

  191. Fischer J, Colls P, Escudero T, Munne S. Preimplantation genetic diagnosis (PGD) improves pregnancy outcome for translocation carriers with a history of recurrent losses. Fertil Steril. 2010;94(1):283–9.

    Article  PubMed  Google Scholar 

  192. Massart A, Lissens W, Tournaye H, Stouffs K. Genetic causes of spermatogenic failure. Asian J Androl. 2012;14(1):40–8.

    Article  CAS  PubMed  Google Scholar 

  193. Stouffs K, Vandermaelen D, Massart A, Menten B, Vergult S, Tournaye H, et al. Array comparative genomic hybridization in male infertility. Hum Reprod. 2012;27(3):921–9.

    Article  CAS  PubMed  Google Scholar 

  194. McLachlan RI, O’Bryan MK. Clinical Review#: state of the art for genetic testing of infertile men. J Clin Endocrinol Metab. 2010;95(3):1013–24.

    Article  CAS  PubMed  Google Scholar 

  195. Ferlin A, Vinanzi C, Garolla A, Selice R, Zuccarello D, Cazzadore C, et al. Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations. Clin Endocrinol. 2006;65(5):606–10.

    Article  CAS  Google Scholar 

  196. Gottlieb B, Lombroso R, Beitel LK, Trifiro MA. Molecular pathology of the androgen receptor in male (in)fertility. Reprod BioMed Online. 2005;10(1):42–8.

    Article  CAS  PubMed  Google Scholar 

  197. Zuccarello D, Ferlin A, Vinanzi C, Prana E, Garolla A, Callewaert L, et al. Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility. Clin Endocrinol. 2008;68(4):580–8.

    Article  CAS  Google Scholar 

  198. Griffin DK, Hyland P, Tempest HG, Homa ST. Safety issues in assisted reproduction technology: should men undergoing ICSI be screened for chromosome abnormalities in their sperm? Hum Reprod. 2003;18(2):229–35.

    Article  CAS  PubMed  Google Scholar 

  199. Sheynkin YR, Hendin BN, Schlegel PN, Goldstein M. Microsurgical repair of iatrogenic injury to the vas deferens. J Urol. 1998;159(1):139–41.

    Article  CAS  PubMed  Google Scholar 

  200. Tanrikut C, Goldstein M. Obstructive azoospermia: a microsurgical success story. Semin Reprod Med. 2009;27(2):159–64.

    Article  PubMed  Google Scholar 

  201. Vernaeve V, Festre V, Baetens P, Devroey P, Van Steirteghem A, Tournaye H. Reproductive decisions by couples undergoing artificial insemination with donor sperm for severe male infertility: implications for medical counselling. Int J Androl. 2005;28(1):22–6.

    Article  CAS  PubMed  Google Scholar 

  202. Gat Y, Bachar GN, Everaert K, Levinger U, Gornish M. Induction of spermatogenesis in azoospermic men after internal spermatic vein embolization for the treatment of varicocele. Hum Reprod. 2005;20(4):1013–7.

    Article  PubMed  Google Scholar 

  203. Pasqualotto FF, Lucon AM, Hallak J, Goes PM, Saldanha LB, Arap S. Induction of spermatogenesis in azoospermic men after varicocele repair. Hum Reprod. 2003;18(1):108–12.

    Article  PubMed  Google Scholar 

  204. Santoro N, Filicori M, Crowley Jr WF. Hypogonadotropic disorders in men and women: diagnosis and therapy with pulsatile gonadotropin-releasing hormone. Endocr Rev. 1986;7(1):11–23.

    Article  CAS  PubMed  Google Scholar 

  205. 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.

    Article  CAS  PubMed  Google Scholar 

  206. 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.

    Article  CAS  PubMed  Google Scholar 

  207. Sinisi AA, Esposito D, Bellastella G, Maione L, Palumbo V, Gandini L, et al. Efficacy of recombinant human follicle stimulating hormone at low doses in inducing spermatogenesis and fertility in hypogonadotropic hypogonadism. J Endocrinol Investig. 2010;33(9):618–23.

    Article  CAS  Google Scholar 

  208. Qu X, Wang M, Wang G, Han T, Mou C, Han L, et al. Surgical outcomes and prognostic factors of transsphenoidal surgery for prolactinoma in men: a single-center experience with 87 consecutive cases. Eur J Endocrinol. 2011;164(4):499–504.

    Article  CAS  PubMed  Google Scholar 

  209. Berezin M, Shimon I, Hadani M. Prolactinoma in 53 men: clinical characteristics and modes of treatment (male prolactinoma). J Endocrinol Investig. 1995;18(6):436–41.

    Article  CAS  Google Scholar 

  210. Ko EY, Siddiqi K, Brannigan RE, Sabanegh Jr ES. Empirical medical therapy for idiopathic male infertility: a survey of the American Urological Association. J Urol. 2012;187(3):973–8.

    Article  PubMed  Google Scholar 

  211. Adamopoulos DA. Medical treatment of idiopathic oligozoospermia and male factor subfertility. Asian J Androl. 2000;2(1):25–32.

    CAS  PubMed  Google Scholar 

  212. Attia AM, Al-Inany HG, Farquhar C, Proctor M. Gonadotrophins for idiopathic male factor subfertility. Cochrane Database Syst Rev. 2007;4:CD005071.

    Google Scholar 

  213. Comhaire F. Clinical andrology: from evidence-base to ethics. The ‘E’ quintet in clinical andrology. Hum Reprod. 2000;15(10):2067–71.

    Article  CAS  PubMed  Google Scholar 

  214. Ghanem H, Shaeer O, El-Segini A. Combination clomiphene citrate and antioxidant therapy for idiopathic male infertility: a randomized controlled trial. Fertil Steril. 2010;93(7):2232–5.

    Article  CAS  PubMed  Google Scholar 

  215. Krause W, Holland-Moritz H, Schramm P. Treatment of idiopathic oligozoospermia with tamoxifen—a randomized controlled study. Int J Androl. 1992;15(1):14–8.

    Article  CAS  PubMed  Google Scholar 

  216. Moradi M, Moradi A, Alemi M, Ahmadnia H, Abdi H, Ahmadi A, et al. Safety and efficacy of clomiphene citrate and l-carnitine in idiopathic male infertility: a comparative study. Urol J. 2010;7(3):188–93.

    PubMed  Google Scholar 

  217. Pavlovich CP, King P, Goldstein M, Schlegel PN. Evidence of a treatable endocrinopathy in infertile men. J Urol. 2001;165(3):837–41.

    Article  CAS  PubMed  Google Scholar 

  218. Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol. 2002;167(2 Pt 1):624–9.

    Article  CAS  PubMed  Google Scholar 

  219. Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2002;77(3):491–8.

    Article  PubMed  Google Scholar 

  220. Comhaire FH, El Garem Y, Mahmoud A, Eertmans F, Schoonjans F. Combined conventional/antioxidant “Astaxanthin” treatment for male infertility: a double blind, randomized trial. Asian J Androl. 2005;7(3):257–62.

    Article  CAS  PubMed  Google Scholar 

  221. Cavallini G, Ferraretti AP, Gianaroli L, Biagiotti G, Vitali G. Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-associated oligoasthenospermia. J Androl. 2004;25(5):761–70.. discussion 71–2

    Article  CAS  PubMed  Google Scholar 

  222. Lenzi A, Sgro P, Salacone P, Paoli D, Gilio B, Lombardo F, et al. A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Fertil Steril. 2004;81(6):1578–84.

    Article  CAS  PubMed  Google Scholar 

  223. Kumar R, Gautam G, Gupta NP. Drug therapy for idiopathic male infertility: rationale versus evidence. J Urol. 2006;176(4 Pt 1):1307–12.

    Article  CAS  PubMed  Google Scholar 

  224. Cantineau AE, Janssen MJ, Cohlen BJ. Synchronised approach for intrauterine insemination in subfertile couples. Cochrane Database Syst Rev. 2010;4:CD006942.

    Google Scholar 

  225. Boomsma CM, Heineman MJ, Cohlen BJ, Farquhar C. Semen preparation techniques for intrauterine insemination. Cochrane Database Syst Rev. 2007;4:CD004507.

    Google Scholar 

  226. Guzick DS, Carson SA, Coutifaris C, Overstreet JW, Factor-Litvak P, Steinkampf MP, et al. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network. N Engl J Med. 1999;340(3):177–83.

    Article  CAS  PubMed  Google Scholar 

  227. EW Group. Intrauterine insemination. Hum Reprod Update. 2009;15(3):265–77.

    Article  Google Scholar 

  228. Cohlen BJ. Should we continue performing intrauterine inseminations in the year 2004? Gynecol Obstet Investig. 2005;59(1):3–13.

    Article  CAS  Google Scholar 

  229. Dickey RP, Taylor SN, Lu PY, Sartor BM, Rye PH, Pyrzak R. Relationship of follicle numbers and estradiol levels to multiple implantation in 3,608 intrauterine insemination cycles. Fertil Steril. 2001;75(1):69–78.

    Article  CAS  PubMed  Google Scholar 

  230. Khalil MR, Rasmussen PE, Erb K, Laursen SB, Rex S, Westergaard LG. Homologous intrauterine insemination. An evaluation of prognostic factors based on a review of 2473 cycles. Acta Obstet Gynecol Scand. 2001;80(1):74–81.

    Article  CAS  PubMed  Google Scholar 

Suggested Reading

  • Bagis T, Haydardedeoglu B, Kilicdag EB, Cok T, Simsek E, Parlakgumus AH. Single versus double intrauterine insemination in multi-follicular ovarian hyperstimulation cycles: a randomized trial. Hum Reprod. 2010;25(7):1684–90.

    Article  PubMed  Google Scholar 

  • Cantineau AE, Heineman MJ, Cohlen BJ. Single versus double intrauterine insemination in stimulated cycles for subfertile couples: a systematic review based on a Cochrane review. Hum Reprod. 2003;18(5):941–6.

    Article  CAS  PubMed  Google Scholar 

  • Ghanem ME, Bakre NI, Emam MA, Al Boghdady LA, Helal AS, Elmetwally AG, et al. The effects of timing of intrauterine insemination in relation to ovulation and the number of inseminations on cycle pregnancy rate in common infertility etiologies. Hum Reprod. 2011;26(3):576–83.

    Article  PubMed  Google Scholar 

  • Tonguc E, Var T, Onalan G, Altinbas S, Tokmak A, Karakas N, et al. Comparison of the effectiveness of single versus double intrauterine insemination with three different timing regimens. Fertil Steril. 2010;94(4):1267–70.

    Article  PubMed  Google Scholar 

  • Wiser A, Shalom-Paz E, Reinblatt SL, Son WY, Das M, Tulandi T, et al. Ovarian stimulation and intrauterine insemination in women aged 40 years or more. Reprod BioMed Online. 2012;24(2):170–3.

    Article  PubMed  Google Scholar 

  • Dickey RP, Pyrzak R, Lu PY, Taylor SN, Rye PH. Comparison of the sperm quality necessary for successful intrauterine insemination with World Health Organization threshold values for normal sperm. Fertil Steril. 1999;71(4):684–9.

    Article  CAS  PubMed  Google Scholar 

  • Merviel P, Heraud MH, Grenier N, Lourdel E, Sanguinet P, Copin H. Predictive factors for pregnancy after intrauterine insemination (IUI): an analysis of 1038 cycles and a review of the literature. Fertil Steril. 2010;93(1):79–88.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology—Reproductive Endocrinology, University of Utah Healthcare Hospital, 50 North Medical Drive, Salt Lake City, UT, 84132, USA

    Mark Gibson MD & Ahmad Hammoud MD, MPH

  2. Utah Center for Reproductive Medicine, 675 Arapeen Drive, Suite 205, Salt Lake City, UT, 84108, USA

    Mark Gibson MD

  3. IVF Michigan Fertility Centers, 37000 Woodward, Bloomfield Hills, MI, 48304, USA

    Ahmad Hammoud MD, MPH

Authors
  1. Mark Gibson MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmad Hammoud MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Gibson MD .

Editor information

Editors and Affiliations

  1. Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, Ohio, USA

    Tommaso Falcone

  2. Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA

    William W. Hurd

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Gibson, M., Hammoud, A. (2017). Male Infertility. In: Falcone, T., Hurd, W. (eds) Clinical Reproductive Medicine and Surgery. Springer, Cham. https://doi.org/10.1007/978-3-319-52210-4_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-52210-4_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-52209-8

  • Online ISBN: 978-3-319-52210-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation