|Classification and external resources|
|Patient UK||Male infertility|
Male infertility refers to a male's inability to cause pregnancy in a fertile female. In humans it accounts for 40-50% of infertility. Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.
Factors relating to male infertility include:
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:
- Hypogonadotropic hypogonadism due to various causes
- Drugs, alcohol
- Strenuous riding (bicycle riding, horseback riding)
- Medications, including those that affect spermatogenesis such as chemotherapy, anabolic steroids, cimetidine, spironolactone; those that decrease FSH levels such as phenytoin; those that decrease sperm motility such as sulfasalazine and nitrofurantoin
- Genetic abnormalities such as a Robertsonian translocation
Male smokers also have approximately 30% higher odds of infertility. There is increasing evidence that the harmful products of tobacco smoking kill sperm cells. 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.
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. As men age there is a consistent decline in semen quality, and this decline appears to be due to DNA damage. (Silva et al., 2012). These findings suggest that DNA damage is an important factor in male infertility.
Testicular factors refer to conditions where the testes produce semen of low quantity and/or poor quality despite adequate hormonal support and include:
See also: Paternal age effect
- Genetic defects on the Y chromosome
- Abnormal set of chromosomes
- Neoplasm, e.g. seminoma
- Idiopathic failure
- Varicocele (14% in one study)
- Testicular cancer
- Defects in USP26 in some cases
- Acrosomal defects affecting egg penetration
- Idiopathic oligospermia - unexplained sperm deficiencies account for 30% of male infertility.
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:
- Vas deferens obstruction
- Lack of Vas deferens, often related to genetic markers for Cystic Fibrosis
- Infection, e.g. prostatitis
- Retrograde ejaculation
- Ejaculatory duct obstruction
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.
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.
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.
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. Semen deficiencies are often labeled as follows:
- Oligospermia or Oligozoospermia - decreased number of spermatozoa in semen
- Aspermia - complete lack of semen
- Hypospermia - reduced seminal volume
- Azoospermia - absence of sperm cells in semen
- Teratospermia - increase in sperm with abnormal morphology
- Asthenozoospermia - reduced sperm motility
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.
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.
Some strategies suggested or proposed for avoiding male infertility include the following:
- Avoiding smoking as it damages sperm DNA
- Avoiding heavy marijuana and alcohol use.
- Avoiding excessive heat to the testes.
- Sperm counts can be depressed by daily coital activity and sperm motility may be depressed by coital activity that takes place too infrequently (abstinence 10–14 days or more).
- When participating in contact sports, wear a Protective Cup and Jockstrap to protect the testicles. Sports such as Baseball, Football, Cricket, Lacrosse, Hockey, Softball, Paintball, Rodeo, Motorcross, Wrestling, Soccer, Karate or other Martial Arts or any sport where a ball, foot, arm, knee or bat can come into contact with the groin.
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. Vitamin E helps counter oxidative stress, which is associated with sperm DNA damage and reduced sperm motility. A hormone-antioxidant combination may improve sperm count and motility. The Low dose Estrogen Testosterone Combination Therapy may improve sperm count and motility in some men. including severe oligospermia.
Future potential treatments
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. If reproduced in humans, this could potentially enable infertile men to father children with their own sperm.
Researchers from Montana State University developed precursor of sperm from skin of infertile men. Its a ray of hope in real mean for future treatment of infertility in men.
- Female infertility
- Fertility preservation
- Fertility testing
- "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.
- 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.
- Hirsh A (2003). "Male subfertility". BMJ 327 (7416): 669–72. doi:10.1136/bmj.327.7416.669. PMC 196399. PMID 14500443.
- 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.
- 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.
- 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.
- 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.
- "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.
- 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.
- 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.
- 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.
- 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
- 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
- "Infertility in men". Retrieved 2007-11-21.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Speroff L, Glass RH, Kase NG (1999). Clinical Endocrinology and Infertility (6th ed.). Lippincott Williams and Wilkins. p. 1085. ISBN 0-683-30379-1.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- "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.
- Farquhar, C.; Rishworth, J. R.; Brown, J.; Nelen, W. L. M.; Marjoribanks, J. (2013). "Assisted reproductive technology: an overview of Cochrane Reviews". In Brown, Julie. "Cochrane Database of Systematic Reviews". doi:10.1002/14651858.CD010537.pub2. PMID 23970457.
- 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.
- James G (2012-01-03). "Sperm Grown In Laboratory In Fertility Breakthrough". Huffingtonpost.co.uk. Retrieved 2012-08-26.
- "Scientists grow sperm in laboratory dish". Health News (London: The Daily Telegraph). 2012-01-02.
- "Researchers made Sperm Cells from Skin of infertile men". Retrieved 2014-05-08.