Male infertility

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Male infertility
Classification and external resources
ICD-10 N46
ICD-9 606
DiseasesDB 7772
MedlinePlus 001191
eMedicine med/3535 med/1167
Patient UK Male infertility
MeSH D007248

Male infertility refers to a male's inability to cause pregnancy in a fertile female. In humans it accounts for 40-50% of infertility.[1][2][3] It affects approximately 7% of all men.[4] Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.[5]


Factors relating to male infertility include:[6]

Pre-testicular causes[edit]

Pre-testicular factors refer to conditions that impede adequate support of the testes and include situations of poor hormonal support and poor general health including:

Tobacco smoking[edit]

Male smokers also have approximately 30% higher odds of infertility.[9] There is increasing evidence that the harmful products of tobacco smoking kill sperm cells.[10][11] Therefore, some governments require manufacturers to put warnings on packets. Smoking tobacco increases intake of cadmium, because the tobacco plant absorbs the metal. Cadmium, being chemically similar to zinc, may replace zinc in the DNA polymerase, which plays a critical role in sperm production. Zinc replaced by cadmium in DNA polymerase can be particularly damaging to the testes.[12]

DNA damage[edit]

Common inherited variants in genes that encode enzymes employed in DNA mismatch repair are associated with increased risk of sperm DNA damage and male infertility.[13] As men age there is a consistent decline in semen quality, and this decline appears to be due to DNA damage.[14] (Silva et al., 2012). These findings suggest that DNA damage is an important factor in male infertility.

Testicular factors[edit]

Testicular factors refer to conditions where the testes produce semen of low quantity and/or poor quality despite adequate hormonal support and include:

Radiation therapy to a testis decreases its function, but infertility can efficiently be avoided by avoiding radiation to both testes.[20]

Post-testicular causes[edit]

Post-testicular factors decrease male fertility due to conditions that affect the male genital system after testicular sperm production and include defects of the genital tract as well as problems in ejaculation:


The diagnosis of infertility begins with a medical history and physical exam by a physician or nurse practitioner. Typically two separate semen analyses will be required. The provider may order blood tests to look for hormone imbalances, medical conditions, or genetic issues.

Medical history[edit]

The history should include prior testicular or penile insults (torsion, cryptorchidism, trauma), infections (mumps orchitis, epididymitis), environmental factors, excessive heat, radiation, medications, and drug use (anabolic steroids, alcohol, smoking).

Sexual habits, frequency and timing of intercourse, use of lubricants, and each partner's previous fertility experiences are important.

Loss of libido and headaches or visual disturbances may indicate a pituitary tumor.

The past medical or surgical history may reveal thyroid or liver disease (abnormalities of spermatogenesis), diabetic neuropathy (retrograde ejaculation), radical pelvic or retroperitoneal surgery (absent seminal emission secondary to sympathetic nerve injury), or hernia repair (damage to the vas deferens or testicular blood supply).

A family history may reveal genetic problems.

Physical examination[edit]

Usually, the patient disrobes completely and puts on a gown. The physician or NP will perform a thorough examination of the penis, scrotum, testicles, anus and rectum. An orchidometer can measure testicular volume, which in turn is tightly associated with both sperm and hormonal parameters.[4] A physical exam of the scrotum can reveal a varicocele, but the impact of detecting and surgically correct a varicocele on sperm parameters or overall male fertility is debated.[4]

Sperm sample[edit]

Main article: Semen analysis
Further information: Semen quality

The volume of the semen sample, approximate number of total sperm cells, sperm motility/forward progression, and % of sperm with normal morphology are measured. This is the most common type of fertility testing.[21][22] Semen deficiencies are often labeled as follows:

There are various combinations of these as well, e.g. Teratoasthenozoospermia, which is reduced sperm morphology and motility. Low sperm counts are often associated with decreased sperm motility and increased abnormal morphology, thus the terms "oligoasthenoteratozoospermia" or "oligospermia" can be used as a catch-all.

Blood sample[edit]

Common hormonal test include determination of FSH and testosterone levels. A blood sample can reveal genetic causes of infertility, e.g. Klinefelter syndrome, a Y chromosome microdeletion, or cystic fibrosis.


Ultrasonography of the scrotum is useful when there is a suspicion of some particular diseases. It may detect signs of testicular dysgenesis, which is often related to an impaired spermatogenesis and to a higher risk of testicular cancer.[4] Scrotum ultrasonography may also detect testicular lesions suggestive of malignancy. A decreased testicular vascularization is characteristic of testicular torsion, whereas hyperemia is often observed in epididymo-orchitis or in some malignant conditions such as lymphoma and leukemia.[4] Doppler ultrasonography useful in assessing venous reflux in case of a varicocele, when palpation is unreliable or in detecting recurrence or persistence after surgery, although the impact of its detection and surgical correction on sperm parameters and overall fertility is debated.[4]

Dilation of the head or tail of the epididymis is suggestive of obstruction or inflammation of the male reproductive tract.[4] Such abnormalities are associated with abnormalities in sperm parameters, as are abnormalities in the texture of the epididymis.[4] Scrotal and transrectal ultrasonography (TRUS) are useful in detecting uni- or bilateral congenital absence of the vas deferens (CBAVD), which may be associated with abnormalities or agenesis of the epididymis, seminal vesicles or kidneys, and indicate the need for testicular sperm extraction.[4] TRUS plays a key role in assessing azoospermia caused by obstruction, and detecting distal CBAVD or anomalies related to obstruction of the ejaculatory duct, such as abnormalities within the duct itself, a median cyst of the prostate (indicating a need for cyst aspiration), or an impairment of the seminal vesicles to become enlarged or emptied.[4]


Some strategies suggested or proposed for avoiding male infertility include the following:


Treatments vary according to the underlying disease and the degree of the impairment of the male fertility. Further, in an infertility situation, the fertility of the female needs to be considered.

Pre-testicular conditions can often be addressed by medical means or interventions.

Testicular-based male infertility tends to be resistant to medication. Usual approaches include using the sperm for intrauterine insemination (IUI), in vitro fertilization (IVF), or IVF with intracytoplasmatic sperm injection (ICSI). With IVF-ICSI even with a few sperm pregnancies can be achieved.

Obstructive causes of post-testicular infertility can be overcome with either surgery or IVF-ICSI. Ejaculatory factors may be treatable by medication, or by IUI therapy or IVF.

The off-label use of Clomiphene citrate, an anti-estrogen drug designed as a fertility medicine for women, is controversial.[25] Vitamin E helps counter oxidative stress,[26] which is associated with sperm DNA damage and reduced sperm motility.[27] A hormone-antioxidant combination may improve sperm count and motility.[28] The Low dose Estrogen Testosterone Combination Therapy may improve sperm count and motility in some men.[29] including severe oligospermia.[30][31]

Oral antioxidants given to males in couples undergoing in vitro fertilisation for male factor or unexplained subfertility result in significantly higher live birth rate.[32]

Future potential treatments[edit]

Researchers at Münster University developed in vitro culture conditions using a three-dimensional agar culture system which induces mouse testicular germ cells to reach the final stages of spermatogenesis, including spermatozoa generation.[33] If reproduced in humans, this could potentially enable infertile men to father children with their own sperm.[34][35]
Researchers from Montana State University developed precursor of sperm from skin of infertile men. It is a ray of hope in real mean for future treatment of infertility in men.[36]

See also[edit]


  1. ^ "Men's Health - Male Factor Infertility". University of Utah Health Sciences Center. 2003-04-01. Archived from the original on 2007-07-04. Retrieved 2007-11-21. 
  2. ^ Brugh VM, Lipshultz LI (2004). "Male factor infertility". Medical Clinics of North America 88 (2): 367–85. doi:10.1016/S0025-7125(03)00150-0. PMID 15049583. 
  3. ^ Hirsh A (2003). "Male subfertility". BMJ 327 (7416): 669–72. doi:10.1136/bmj.327.7416.669. PMC 196399. PMID 14500443. 
  4. ^ a b c d e f g h i j Lotti, F.; Maggi, M. (2014). "Ultrasound of the male genital tract in relation to male reproductive health". Human Reproduction Update 21 (1): 56–83. doi:10.1093/humupd/dmu042. ISSN 1355-4786. 
  5. ^ Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HWG, Behre HM, Haugen TB, Kruger T, Wang C (2009). "World Health Organization reference values for human semen characteristics". Human Reproduction Update 16 (3): 231–45. doi:10.1093/humupd/dmp048. PMID 19934213. 
  6. ^ Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA (2000). "Chapter 2: History taking". WHO manual for the standardized investigation, diagnosis and management of the infertile male. Cambridge [England]: Published on behalf of the World Health Organization by Cambridge University Press. pp. 5–16. ISBN 0-521-77474-8. 
  7. ^ a b Teerds KJ, de Rooij DG, Keijer J (2011). "Functional relationship between obesity and male reproduction: from humans to animal models". Hum. Reprod. Update 17 (5): 667–83. doi:10.1093/humupd/dmr017. PMID 21546379. 
  8. ^ Leibovitch I, Mor Y (2005). "The Vicious Cycling: Bicycling Related Urogenital Disorders". European Urology 47 (3): 277–86; discussion 286–7. doi:10.1016/j.eururo.2004.10.024. PMID 15716187. 
  9. ^ "Preventing Smoking and Exposure to Secondhand Smoke Before, During, and After Pregnancy" (pdf). factsheet. United States Centers for Disease Control (CDC). Retrieved 2012-08-27. 
  10. ^ Agarwal A, Prabakaran SA, Said TM (2005). "Prevention of Oxidative Stress Injury to Sperm". Journal of Andrology 26 (6): 654–60. doi:10.2164/jandrol.05016. PMID 16291955. 
  11. ^ Robbins WA, Elashoff DA, Xun L, Jia J, Li N, Wu G, Wei F (2005). "Effect of lifestyle exposures on sperm aneuploidy". Cytogenetic and Genome Research 111 (3–4): 371–7. doi:10.1159/000086914. PMID 16192719. 
  12. ^ Emsley J (2001). Nature's building blocks: an A-Z guide to the elements. Oxford [Oxfordshire]: Oxford University Press. p. 76. ISBN 0-19-850340-7. 
  13. ^ Ji G, Long Y, Zhou Y, Huang C, Gu A, Wang X (2012). Common variants in mismatch repair genes associated with increased risk of sperm DNA damage and male infertility. BMC Med 10:49. doi: 10.1186/1741-7015-10-49. PMID 22594646
  14. ^ Silva LF, Oliveira JB, Petersen CG, Mauri AL, Massaro FC, Cavagna M, Baruffi RL, Franco JG Jr (2012). The effects of male age on sperm analysis by motile sperm organelle morphology examination (MSOME). Reprod Biol Endocrinol 10:19. doi: 10.1186/1477-7827-10-19. PMID 22429861
  15. ^ "Infertility in men". Retrieved 2007-11-21. 
  16. ^ Costabile RA, Spevak M (2001). "Characterization of patients presenting with male factor infertility in an equal access, no cost medical system". Urology 58 (6): 1021–4. doi:10.1016/S0090-4295(01)01400-5. PMID 11744480. 
  17. ^ Masarani M, Wazait H, Dinneen M (2006). "Mumps orchitis". Journal of the Royal Society of Medicine 99 (11): 573–5. doi:10.1258/jrsm.99.11.573. PMC 1633545. PMID 17082302. 
  18. ^ Zhang J, Qiu S-D, Li S-B, Zhou D-X, Tian H, Huo Y-W, Ge L, Zhang Q-Y (2007). "Novel mutations in ubiquitin-specific protease 26 gene might cause spermatogenesis impairment and male infertility". Asian Journal of Andrology 9 (6): 809–14. doi:10.1111/j.1745-7262.2007.00305.x. PMID 17968467. 
  19. ^ Cavallini G (2006). "Male idiopathic oligoasthenoteratozoospermia". Asian Journal of Andrology 8 (2): 143–57. doi:10.1111/j.1745-7262.2006.00123.x. PMID 16491265. 
  20. ^ Gutfeld O, Wygoda M, Shavit L, Grenader T (2007). "Fertility After Adjuvant External Beam Radiotherapy for Stage I Seminoma". The Internet Journal of Oncology 4 (2). doi:10.5580/2188. 
  21. ^ Hargreave TB, McGowan B, Harvey J, McParland M, Elton RA (April 1986). "Is a male infertility clinic of any use?". Br. J. Urol. 58 (2): 188–93. doi:10.1111/j.1464-410x.1986.tb09024.x. PMID 3697634. 
  22. ^ Hwang K, Walters RC, Lipshultz LI (February 2011). "Contemporary concepts in the evaluation and management of male infertility". Nature Reviews Urology 8 (2): 86–94. doi:10.1038/nrurol.2010.230. PMID 21243017. 
  23. ^ Gaur DS, Talekar M, Pathak VP (2007). "Effect of cigarette smoking on semen quality of infertile men". Singapore Medical Journal 48 (2): 119–23. PMID 17304390. 
  24. ^ a b c d Speroff L, Glass RH, Kase NG (1999). Clinical Endocrinology and Infertility (6th ed.). Lippincott Williams and Wilkins. p. 1085. ISBN 0-683-30379-1. 
  25. ^ Pasqualotto FF, Fonseca GP, Pasqualotto EB (2008). "Azoospermia after treatment with clomiphene citrate in patients with oligospermia". Fertility and Sterility 90 (5): 2014.e11–2. doi:10.1016/j.fertnstert.2008.03.036. PMID 18555230. 
  26. ^ Traber MG, Stevens JF (2011). "Vitamins C and E: Beneficial effects from a mechanistic perspective". Free Radical Biology and Medicine 51 (5): 1000–13. doi:10.1016/j.freeradbiomed.2011.05.017. PMC 3156342. PMID 21664268. 
  27. ^ Lombardo F, Sansone A, Romanelli F, Paoli D, Gandini L, Lenzi A (2011). "The role of antioxidant therapy in the treatment of male infertility: An overview". Asian Journal of Andrology 13 (5): 690–7. doi:10.1038/aja.2010.183. PMID 21685925. 
  28. ^ Ghanem H, Shaeer O, El-Segini A (2010). "Combination clomiphene citrate and antioxidant therapy for idiopathic male infertility: A randomized controlled trial". Fertility and Sterility 93 (7): 2232–5. doi:10.1016/j.fertnstert.2009.01.117. PMID 19268928. 
  29. ^ Sah P (1998). "Role of low-dose estrogen–testosterone combination therapy in men with oligospermia". Fertility and Sterility 70 (4): 780–1. doi:10.1016/S0015-0282(98)00273-8. PMID 9797116. 
  30. ^ Sah P (2002). "Oligospermia due to partial maturation arrest responds to low dose estrogen-testosterone combination therapy resulting in live-birth: A case report". Asian Journal of Andrology 4 (4): 307–8. PMID 12508135. 
  31. ^ "Oligospermia in a Man with Small Testes and Elevated Serum FSH Responds to Low Dose Estrogen-Testosterone Combination Therapy, Resulting in His Wife's Pregnancy and Live Birth". The Internet Journal of Endocrinology 2. 2005. doi:10.5580/1f84. 
  32. ^ Farquhar, C.; Rishworth, J. R.; Brown, J.; Nelen, W. L. M.; Marjoribanks, J. (2013). Brown, Julie, ed. "Assisted reproductive technology: an overview of Cochrane Reviews". The Cochrane Library. doi:10.1002/14651858.CD010537.pub2. PMID 23970457.  edit
  33. ^ Abu Elhija M, Lunenfeld E, Schlatt S, Huleihel M (2011). "Differentiation of murine male germ cells to spermatozoa in a soft agar culture system". Asian Journal of Andrology 14 (2): 285–93. doi:10.1038/aja.2011.112. PMID 22057383. 
  34. ^ James G (2012-01-03). "Sperm Grown In Laboratory In Fertility Breakthrough". Retrieved 2012-08-26. 
  35. ^ "Scientists grow sperm in laboratory dish". Health News (London: The Daily Telegraph). 2012-01-02. 
  36. ^ "Researchers made Sperm Cells from Skin of infertile men". Retrieved 2014-05-08.