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Sperm disorders include defects in quality or quantity of sperm produced and defects in sperm emission. Diagnosis is by semen and genetic testing. The most effective treatment is usually in vitro fertilization via intracytoplasmic sperm injection.

Pathophysiology

Spermatogenesis occurs continuously. Each germ cell requires about 72 to 74 days to mature fully. Spermatogenesis is most efficient at 34° C. Within the seminiferous tubules, Sertoli cells regulate maturation, and Leydig cells produce the necessary testosterone Some Trade Names
DELATESTRYL
Click for Drug Monograph
. Fructose is normally produced in the seminal vesicles and secreted through the ejaculatory ducts. Sperm disorders may result in an inadequate quantity of sperm—too few (oligospermia) or none (azoospermia)—or defects in sperm quality, such as abnormal motility or structure.

Etiology

Impaired spermatogenesis: Spermatogenesis can be impaired by heat, disorders (GU, endocrine, or genetic), drugs, or toxins (see Table 1: Infertility: Causes of Impaired Spermatogenesis), resulting in an inadequate quantity or defective quality of sperm.

Table 1
Causes of Impaired Spermatogenesis Condition Examples Endocrine disorders Abnormalities of the hypothalamic-pituitary-gonadal axis Adrenal disorders Hyperprolactinemia Hypogonadism Hypothyroidism Genetic disorders Gonadal dysgenesis Klinefelter's syndrome Microdeletions of sections of the Y chromosome (in 10–15% of men with severely impaired spermatogenesis) GU disorders Cryptorchidism Infections Injury Mumps orchitis Testicular atrophy Varicocele Heat Exposure to excessive heat within the last 3 mo Fever Drugs and toxins Anabolic steroids Androgens Antimalarial drugs Aspirin Some Trade Names BUFFERIN ECOTRIN GENACOTE Click for Drug Monograph when taken chronically Chlorambucil Some Trade Names LEUKERAN Click for Drug Monograph Cimetidine Some Trade Names TAGAMET Click for Drug Monograph Colchicine Some Trade Names No US trade name Click for Drug Monograph Corticosteroids Cotrimoxazole Cyclophosphamide Some Trade Names CYTOXAN Click for Drug Monograph Ethanol Estrogens Some Trade Names PREMARIN Click for Drug Monograph Gonadotropin-releasing hormone (GnRH) analogs (to treat prostate cancer) Marijuana Medroxyprogesterone Some Trade Names PROVERA Click for Drug Monograph , Methotrexate Some Trade Names RHEUMATREX Click for Drug Monograph Monoamine oxidase inhibitors Nicotine Some Trade Names COMMIT NICORETTE NICOTROL Click for Drug Monograph Nitrofurantoin Some Trade Names FURADANTIN MACROBID MACRODANTIN Click for Drug Monograph Opioids Spironolactone Some Trade Names ALDACTONE Click for Drug Monograph Sulfasalazine Some Trade Names AZULFIDINE Click for Drug Monograph Toxins

Impaired sperm emission: Sperm emission may be impaired because of retrograde ejaculation into the bladder, which is often due to the following:

• Diabetes
• Neurologic dysfunction
• Retroperitoneal dissection (eg, for Hodgkin lymphoma)
• Prostatectomy

Sperm emission can also be impaired by

• Obstruction of the vas deferens
• Congenital absence of both vasa deferentia or epididymides, often in men with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene
• Absence of both seminal vesicles

Almost all men with symptomatic cystic fibrosis have congenital bilateral absence of the vas deferens.

Other causes: Men with microdeletions affecting the Y chromosome can develop oligospermia via various mechanisms, depending on the specific deletion. Another rare mechanism of infertility is destruction or inactivation of sperm by sperm antibodies, which are usually produced by the man.

Diagnosis

• Semen analysis
• Sometimes genetic testing

When couples are infertile, the man should always be evaluated for sperm disorders. History and physical examination focus on potential causes (eg, GU disorders). Normal volume of each testis is 20 to 25 mL. Semen analysis should be done. If oligospermia or azoospermia is detected, genetic testing, including standard karyotyping, PCR of tagged chromosomal sites (to detect microdeletions affecting the Y chromosome), and evaluation for mutations of the CFTR gene, should be done. Before a man with a CFTR gene mutation and his partner attempt to conceive, the partner should also be tested to exclude cystic fibrosis carrier status.

Before semen analysis, the man is typically asked to refrain from ejaculation for 2 to 3 days. However, recent data indicate that daily ejaculation does not reduce the sperm count in men unless there is a problem. Because sperm count varies, testing requires ≥ 2 specimens obtained ≥ 1 wk apart; each specimen is obtained by masturbation into a glass jar, preferably at the laboratory site. If this method is difficult, the man can use a condom at home; the condom must be free of lubricants and chemicals. After being at room temperature for 20 to 30 min, the ejaculate is evaluated (see Table 2: Infertility: Semen Analysis). Additional computer-assisted measures of sperm motility (eg, linear sperm velocity) are available; however, their correlation with fertility is unclear.

Table 2
Semen Analysis Factor Normal Volume 2 to 6 mL Viscosity Beginning to liquefy within 30 min; completely liquefied within 1 h Gross and microscopic appearance Opaque, cream-colored, ≤1–3 WBC/high-power field pH 7-8 Sperm count > 20 million/mL Sperm motility at 1 and 3 h > 50% motile Percentage of sperm with normal morphology > 14% using 1999 WHO strict criteria Fructose Present (indicating at least one ejaculatory duct is patent)

If a man without hypogonadism or congenital bilateral absence of the vas deferens has an ejaculate volume < 1 mL, urine is analyzed for sperm after ejaculation. A disproportionately large number of sperm in urine vs semen suggests retrograde ejaculation.

Endocrine evaluation is warranted if the semen analysis is abnormal and especially if the sperm concentration is < 10 million/mL. Minimum initial testing should include serum follicle-stimulating hormone (FSH) and testosterone Some Trade Names
DELATESTRYL
Click for Drug Monograph
levels. If testosterone Some Trade Names
DELATESTRYL
Click for Drug Monograph
is low, serum luteinizing hormone (LH) and prolactin should be measured as well. Men with abnormal spermatogenesis often have normal FSH levels, but any increase in FSH is a clear indication of abnormal spermatogenesis. Elevations in prolactin require evaluation for a tumor involving or impinging upon the anterior pituitary or may indicate ingestion of various prescription or recreational drugs.

Specialized sperm tests, available at some infertility centers, may be considered if routine tests of both partners do not explain infertility and in vitro fertilization or gamete intrafallopian tube transfer is being contemplated. The immunobead test detects sperm antibodies, and the hypo-osmotic swelling test measures the structural integrity of sperm plasma membranes. The hemizona assay and sperm penetration assay determine the ability of sperm to fertilize the egg in vitro. The usefulness of these specialized tests is controversial.

If necessary, testicular biopsy can distinguish between obstructive and nonobstructive azoospermia.

Treatment

• Clomiphene Some Trade Names
  CLOMID
  Click for Drug Monograph
  
• Assisted reproductive techniques if clomiphene Some Trade Names
  CLOMID
  Click for Drug Monograph
  is ineffective

Underlying GU disorders are treated. For men with sperm counts of 10 to 20 million/mL and no endocrine disorder, clomiphene Some Trade Names
CLOMID
Click for Drug Monograph
citrate (25 to 50 mg po once/day taken 25 days/mo for 3 to 4 mo) can be tried. Clomiphene Some Trade Names
CLOMID
Click for Drug Monograph
, an antiestrogen, may stimulate sperm production and increase sperm counts. However, whether it improves sperm motility or morphology is unclear, and it has not been proved to increase fertility.

If sperm count is < 10 million/mL or clomiphene Some Trade Names
CLOMID
Click for Drug Monograph
is unsuccessful in men with normal sperm motility, the most effective treatment is usually in vitro fertilization with injection of a single sperm into a single egg (intracytoplasmic sperm injection). Alternatively, intrauterine insemination using washed semen samples and timed to coincide with ovulation is sometimes tried. If pregnancy is going to occur, it usually occurs by the 6th treatment cycle.

Decreased number and viability of sperm may not preclude pregnancy. In such cases, fertility may be enhanced by controlled ovarian hyperstimulation of the woman plus artificial insemination or assisted reproductive techniques (eg, in vitro fertilization, intracytoplasmic sperm injection).

If the male partner cannot produce enough fertile sperm, a couple may consider insemination using donor sperm. Risk of AIDS and other sexually transmitted diseases is minimized by freezing donor sperm for ≥ 6 mo, after which donors are retested for infection before insemination proceeds.

Last full review/revision November 2008 by Robert W. Rebar, MD

Content last modified November 2008