Find information on medical topics, symptoms, drugs, procedures, news and more, written for the health care professional.

* This is a professional Version *

Sperm Disorders

by Robert W. Rebar, MD

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 . 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 Causes of Impaired Spermatogenesis), resulting in an inadequate quantity or defective quality of sperm.

Causes of Impaired Spermatogenesis

Condition

Examples

Endocrine disorders

Abnormalities of the hypothalamic-pituitary-gonadal axis

Adrenal disorders

Hyperprolactinemia

Hypogonadism, sometimes related to obesity

Hypothyroidism

Genetic disorders

Gonadal dysgenesis

Klinefelter 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

Antiandrogens (eg, bicalutamide, cyproterone, flutamide)

Antimalarial drugs

Aspirin when taken long term

Caffeine in excessive amounts (possibly)

Chlorambucil

Cimetidine

Colchicine

Corticosteroids

Cotrimoxazole

Cyclophosphamide

Ethanol

Estrogens

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

Ketoconazole

Marijuana

Medroxyprogesterone

Methotrexate

Monoamine oxidase inhibitors

Nitrofurantoin

Opioids

Spironolactone

Sulfasalazine

Toxins

Impaired sperm emission

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

  • Diabetes

  • Neurologic dysfunction

  • Retroperitoneal dissection (eg, for Hodgkin lymphoma)

  • Transurethral resection of the prostate

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). Volume of each testis should be determined; normal 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 Semen Analysis). Additional computer-assisted measures of sperm motility (eg, linear sperm velocity) are available; however, their correlation with fertility is unclear.

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 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. 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 and unproved.

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

Treatment

  • 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 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.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • DELATESTRYL
  • FURADANTIN, MACROBID, MACRODANTIN
  • CYTOXAN (LYOPHILIZED)
  • No US brand name
  • NIZORAL
  • CASODEX
  • PROVERA
  • LEUKERAN
  • COLCRYS
  • AZULFIDINE
  • TAGAMET
  • OTREXUP
  • ALDACTONE
  • CLOMID

* This is a professional Version *