Male infertility

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

Male infertility refers to the inability of a male to achieve a pregnancy in a fertile female. In humans it accounts for 40-50% of infertility.^[1][2][3] Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.^[4]

Causes

Factors relating to male infertility include^[5]:

Pre-testicular causes

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
  • Obesity increases the risk of hypogonadotropic hypogonadism.^[6] Animal models indicate that obesity causes leptin insensitivity in the hypothalamus, leading to decreased Kiss1 expression, which, in turn, alters the release of gonadotropin-releasing hormone (GnRH).^[6]
• Drugs, alcohol
• Strenuous riding (bicycle riding,^[7] 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

Tobacco smoking

Male smokers also have approximately 30% higher odds of infertility.^[8] There is increasing evidence that the harmful products of tobacco smoking kill sperm cells.^[9][10] 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.^[11]

Testicular factors

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

• Age
  See also: Paternal age effect
• Genetic defects on the Y chromosome
  • Y chromosome microdeletions
• Abnormal set of chromosomes
  • Klinefelter syndrome
• Neoplasm, e.g. seminoma
• Idiopathic failure
• Cryptorchidism
• Varicocele (14% in one study)^[12][13]
• Trauma
• Hydrocele
• Mumps^[14]
• Malaria
• Testicular cancer
• Defects in USP26 in some cases^[15]
• Acrosomal defects affecting egg penetration
• Idiopathic oligospermia - unexplained sperm deficiencies account for 30 % of male infertility.^[16]

Radiation therapy to a testis decreases its function, but infertility can efficiently be avoided by avoiding radiation to both testes.^[17]

Post-testicular causes

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
• Hypospadias
• Impotence

Diagnosis

The diagnosis of infertility begins with a medical history and physical exam by a physician, preferably a specialist with experience or who specializes in male infertility. 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

The cornerstone of the male partner evaluation is the history. It should note the duration of infertility, earlier pregnancies with present or past partners, and whether there was previous difficulty with conception.

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

A complete examination of the infertile male is important to identify general health issues associated with infertility. For example, the patient should be adequately virilized; signs of decreased body hair or gynecomastia may suggest androgen deficiency.

Usually, the patient disrobes completely and puts on a gown. The physician will perform a thorough examination of the penis, scrotum, testicles, anus and rectum.

The scrotal contents should be carefully palpated with the patient standing. As it is often psychologically and physically uncomfortable for men to be examined, one helpful hint is to make the examination as efficient and as matter of fact as possible.

The peritesticular area should also be examined. Irregularities of the epididymis, located posterior-lateral to the testis, include induration, tenderness, or cysts.

Sperm sample

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.^[18] 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.

Blood sample

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.

Prevention

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

• Avoiding smoking^[19] as it damages sperm DNA
• Avoiding heavy marijuana and alcohol use.^[20]
• Avoiding excessive heat to the testes.^[20]
• Sperm counts can be depressed by daily coital activity^[20] and sperm motility may be depressed by coital activity that takes place too infrequently (abstinence 10–14 days or more).^[20]
• When participating in contact sports, wear an 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.

Treatment

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.^[21] Vitamin E helps counter oxidative stress, which is associated with sperm DNA damage and reduced sperm motility.^{[citation needed]} A hormone-antioxidant combination may improve sperm count and motility.^[22]

See also

• Fertility preservation

References

1. ^ "Men's Health - Male Factor Infertility". Archived from the original on 2007-07-04. http://web.archive.org/web/20070704064049/http://healthcare.utah.edu/healthinfo/adult/men/infertil.htm. Retrieved 2007-11-21. 
2. ^ Brugh VM, Lipshultz LI (2004). "Male factor infertility: evaluation and management". Med. Clin. North Am. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=196399. 
4. ^ Cooper TG, Noonan E, von Eckardstein S, et al. (2010). "World Health Organization reference values for human semen characteristics". Hum. Reprod. Update 16 (3): 231–45. doi:10.1093/humupd/dmp048. PMID 19934213. 
5. ^ Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA. WHO Manual for the Standardized Investigation, Diagnosis and Management of the Infertile Male. Cambridge University Press, 2000. ISBN 0-521-77474-8.
6. ^ ^{a b} Teerds, K. J.; De Rooij, D. G.; Keijer, J. (2011). "Functional relationship between obesity and male reproduction: From humans to animal models". Human Reproduction Update 17 (5): 667–683. doi:10.1093/humupd/dmr017. PMID 21546379.  edit
7. ^ Leibovitch I, Mor Y (2005). "The vicious cycling: bicycling related urogenital disorders". Eur. Urol. 47 (3): 277–86; discussion 286–7. doi:10.1016/j.eururo.2004.10.024. PMID 15716187. 
8. ^ Centers for Disease Control and Prevention. 2009. Preventing Smoking and Exposure to Secondhand Smoke Before, During, and After Pregnancy. http://www.cdc.gov/chronicdisease/resources/publications/fact_sheets/smoking.htm.
9. ^ Agarwal A, Prabakaran SA, Said TM (2005). "Prevention of oxidative stress injury to sperm". J. Androl. 26 (6): 654–60. doi:10.2164/jandrol.05016. PMID 16291955. 
10. ^ Robbins WA, Elashoff DA, Xun L, et al. (2005). "Effect of lifestyle exposures on sperm aneuploidy". Cytogenet. Genome Res. 111 (3-4): 371–7. doi:10.1159/000086914. PMID 16192719. 
11. ^ Emsley, John. Nature's Building Blocks. 2001. Oxford University Press.
12. ^ "Infertility in men". http://www.umm.edu/patiented/articles/what_causes_of_male_infertility_000067_4.htm. Retrieved 2007-11-21. 
13. ^ 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. 
14. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1633545. 
15. ^ Zhang J, Qiu SD, Li SB, et al. (2007). "Novel mutations in ubiquitin-specific protease 26 gene might cause spermatogenesis impairment and male infertility". Asian J. Androl. 9 (6): 809–14. doi:10.1111/j.1745-7262.2007.00305.x. PMID 17968467. 
16. ^ Cavallini G (2006). "Male idiopathic oligoasthenoteratozoospermia". Asian J Androl 2006;8(2):143-157 8 (2): 143–57. doi:10.1111/j.1745-7262.2006.00123.x. PMID 16491265. 
17. ^ O. Gutfeld, M. Wygoda, L. Shavit & T. Grenader : Fertility After Adjuvant External Beam Radiotherapy For Stage I Seminoma . The Internet Journal of Oncology. 2007 Volume 4 Number 2
18. ^ Fertility Testing
19. ^ 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. 
20. ^ ^{a b c d} Speroff L, Glass RH, Kase NG. Clinical Endocrinology and Infertility, 6th Edition. Lippincott Williams and Wilkins, 1999. p. 1085. ISBN 0-683-30379-1. 
21. ^ Pasqualotto FF, Fonseca GP, Pasqualotto EB. (2008). "Azoospermia after treatment with clomiphene citrate in patients with oligospermia.". Fertil Steril. 2008 Nov;90(5):2014.e11-2. Epub 2008 Jun 16. 90 (5): 2014.e11–2. doi:10.1016/j.fertnstert.2008.03.036. PMID 18555230. 
22. ^ Ghanem H, Shaeer O, El-Segini A. (2010). "Combination clomiphene citrate and antioxidant therapy for idiopathic male infertility: A randomized controlled trial.". Fertil Steril 2010 May 1;93(7):2232-5. Epub 2009 Mar 6. 93 (7): 2232–5. doi:10.1016/j.fertnstert.2009.01.117. PMID 19268928.