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Sperm Disorders


Robert W. Rebar

, MD, Western Michigan University Homer Stryker M.D. School of Medicine

Last full review/revision Jan 2019| Content last modified Jan 2019
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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.


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. 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 (oligozoospermia) or none (azoospermia)

  • Defects in sperm quality, such as abnormal motility or structure


Impaired spermatogenesis

Spermatogenesis can be impaired (see table Causes of Impaired Spermatogenesis) by the following, resulting in an inadequate quantity or defective quality of sperm:

  • Heat

  • Disorders (GU, endocrine, or genetic)

  • Drugs

  • Toxins


Causes of Impaired Spermatogenesis



Endocrine disorders

Abnormalities of the hypothalamic-pituitary-gonadal axis

Hypogonadism, sometimes related to obesity

Genetic disorders

Gonadal dysgenesis

Microdeletions of sections of the Y chromosome (in 10–15% of men with severely impaired spermatogenesis)

GU disorders



Mumps orchitis

Testicular atrophy



Exposure to excessive heat within the last 3 mo


Drugs and toxins

Anabolic steroids


Antiandrogens (eg, bicalutamide, cyproterone, flutamide)

Antimalarial drugs

Aspirin when taken long term

Caffeine in excessive amounts (possibly)









Gonadotropin-releasing hormone (GnRH) agonists (to treat prostate cancer)





Monoamine oxidase inhibitors






Impaired sperm emission

Sperm emission may be impaired because of retrograde ejaculation into the bladder.

Retrograde ejaculation is often due to

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, but the vasa deferentia may also be absent in men with mutations of CTFR that do not cause symptomatic cystic fibrosis.

Other causes

Men with microdeletions affecting the Y chromosome, particularly in the AZFc (azoospermia factor c) region, can develop oligozoospermia 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.


  • 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). Volume of each testis should be determined; normal is 20 to 25 mL. Semen analysis should be done.

If oligozoospermia or azoospermia is detected, genetic testing should be done. These tests include

  • Standard karyotyping

  • PCR of tagged chromosomal sites (to detect microdeletions affecting the Y chromosome)

  • Evaluation for mutations of the CFTR gene

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.

Semen analysis

Before semen analysis, the man is typically asked to refrain from ejaculation for 2 to 3 days. However, 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 clean jar, preferably at the laboratory site. The jar should be sterile if the sperm is to be stored. 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 Semen Analysis).

Additional computer-assisted measures of sperm motility (eg, linear sperm velocity) are available; however, their correlation with fertility is unclear.


Semen Analysis



Lower Reference Limits (5th percentile)


2 to 6 mL

1.5 mL


Beginning to liquefy within 30 min; completely liquefied within 1 h

Gross and microscopic appearance

Opaque, cream-colored, 1–3 WBC/high-power field



Sperm count

> 20 million/mL

15 million/mL

Sperm motility at 1 and 3 h

> 50% motile

40% motile

Percentage of sperm with normal morphology

> 5.5% using 1999 WHO strict criteria

4% using 2010 WHO criteria


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.

Other tests

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) levels

  • Testosterone levels

If testosterone is low, serum luteinizing hormone (LH) and prolactin should also be measured. 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 on 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. They include the following:

  • The immunobead test detects sperm antibodies.

  • 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 and unproved.

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


  • Clomiphene

  • Assisted reproductive techniques if clomiphene is ineffective

Underlying GU disorders are treated.

For men with sperm counts of 10 to 20 million/mL and no endocrine disorder, clomiphene citrate (25 to 50 mg po once/day taken 25 days/mo for 3 to 4 mo) can be tried. Clomiphene, 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 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 stimulation 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. In the US, the CDC recommends postponing collection of semen for 6 mo if donors have been diagnosed with Zika virus infection or have lived in or traveled to an area with active Zika virus transmission.

Key Points

  • Impairment of spermatogenesis or impaired sperm emission can result in deficient sperm quantity or quality.

  • Diagnose sperm disorders starting with semen analysis and sometimes genetic testing.

  • Correct underlying GU disorders if present, or treat with clomiphene citrate or with in vitro fertilization and intracytoplasmic sperm injection.

Drugs Mentioned In This Article

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