(See also Overview of Infertility Overview of Infertility Infertility is usually defined as the inability to conceive after 1 year of regular, unprotected sexual intercourse. Infertility is defined as a disease by the World Health Organization (WHO)... read more .)
Pathophysiology of Sperm Disorders
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
Etiology of Sperm Disorders
Impaired spermatogenesis
Spermatogenesis can be impaired (see table Causes of Impaired Spermatogenesis Causes of Impaired Spermatogenesis 
) by the following, resulting in an inadequate quantity or defective quality of sperm:
Heat
Disorders (endocrine, genetic, genitourinary)
Drugs (eg, anabolic steroids)
Toxins
Impaired sperm emission
Sperm emission may be impaired because of retrograde ejaculation into the bladder.
Retrograde ejaculation is often due to
Neurologic dysfunction
Transurethral resection of the prostate
Sperm emission can also be impaired by
Obstruction of the vas deferens or ejaculatory ducts
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 Cystic Fibrosis Cystic fibrosis is an inherited disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems. It leads to chronic lung disease, exocrine pancreatic insufficiency... read more 
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
Erectile dysfunction Erectile Dysfunction Erectile dysfunction is the inability to attain or sustain an erection satisfactory for sexual intercourse. Most erectile dysfunction is related to vascular, neurologic, psychologic, and hormonal... read more can result in infertility.
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.
Diagnosis of Sperm Disorders
Semen analysis
Sometimes genetic testing
(See also Diagnostic evaluation of the infertile male: A committee opinion, from the Practice Committee of the American Society for Reproductive Medicine.)
When couples are infertile, the man should always be evaluated for sperm disorders. History and physical examination focus on potential causes (eg, genitourinary disorders). Volume of each testis should be determined; normal is 20 to 25 mL. Semen analysis should be done.
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 ideally requires ≥ 2 specimens obtained ≥ 1 week 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. If the first semen analysis is normal, a sperm disorder is highly unlikely.
After being at room temperature for 20 to 30 minutes, the ejaculate is evaluated (see table Semen Analysis Semen Analysis ).
Additional computer-assisted measures of sperm motility (eg, linear sperm velocity) are available; however, their correlation with fertility is unclear.
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 versus semen suggests retrograde ejaculation.
Genetic testing
If oligozoospermia or azoospermia is detected, genetic testing should be done. These tests include
Standard karyotyping
Polymerase chain reaction (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.
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 illicit drugs.
Evaluation for an infection (eg, gonorrhea, chlamydial infection), including microbiologic testing, is done if the white blood cell (WBC) count in semen is ≥1,000,000/mL.
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:
Sperm antibody tests, most commonly the direct immunobead test
Sperm viability tests (eg, the hypo-osmotic swelling test, exclusion of a supravital dye from sperm)
Sperm DNA fragmentation tests, including the single-cell gel electrophoresis assay (Comet assay) and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labeling assay (TUNEL)
The usefulness of these specialized tests is controversial and unproved. Some clinicians believe that one or more of these tests may be useful in predicting success with in vitro fertilization.
If necessary, testicular biopsy can distinguish between obstructive and nonobstructive azoospermia.
Treatment of Sperm Disorders
Clomiphene
Assisted reproductive techniques if clomiphene is ineffective
Underlying genitourinary disorders are treated.
If infection is detected, appropriate antibiotics are given.
For men with sperm counts of 10 to 20 million/mL and no endocrine disorder, clomiphene citrate (25 to 50 mg orally once a day taken 25 days/month for 3 to 4 months) 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 Intracytoplasmic sperm injection (ICSI) Assisted reproductive techniques (ARTs) involve manipulation of sperm and ova or embryos in vitro with the goal of producing a pregnancy. For assisted reproductive techniques, oocytes and sperm... read more 
). (Because this procedure is widely used, sperm penetration assays are rarely done now.)
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, but this treatment is only somewhat effective.
Decreased number and viability of sperm may not preclude pregnancy. In such cases, fertility may be enhanced by controlled ovarian stimulation Treatment of the woman plus artificial insemination or assisted reproductive techniques Assisted Reproductive Techniques Assisted reproductive techniques (ARTs) involve manipulation of sperm and ova or embryos in vitro with the goal of producing a pregnancy. For assisted reproductive techniques, oocytes and sperm... read more (eg, in vitro fertilization, intracytoplasmic sperm injection). Specialists in male reproduction can often retrieve sperm for intracytoplasmic sperm injection using a simple surgical procedure, even in men with very few or no sperm in the ejaculate.
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 months, after which donors are retested for infection before insemination proceeds. In the US, the Centers for Disease Control and Prevention (CDC) recommends postponing collection of semen for 6 months if donors have been diagnosed with Zika virus Prevention The Zika virus is a mosquito-borne flavivirus that is antigenically and structurally similar to the viruses that cause dengue, yellow fever, and West Nile virus. Zika virus infection is typically... read more 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 genitourinary disorders if present, or treat with clomiphene citrate or with in vitro fertilization or intracytoplasmic sperm injection.
