(See also Overview of Infertility.)
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
Spermatogenesis can be impaired (see table Causes of Impaired Spermatogenesis) by the following, resulting in an inadequate quantity or defective quality of sperm:
Causes of Impaired Spermatogenesis
Abnormalities of the hypothalamic-pituitary-gonadal axis
Hypogonadism, sometimes related to obesity
Microdeletions of sections of the Y chromosome (in 10–15% of men with severely impaired spermatogenesis)
Infections (eg, gonococcal or chlamydial urethritis)
Exposure to excessive heat within the last 3 months
Alcohol consumed in excessive amounts
Antiandrogens (eg, bicalutamide, cyproterone, flutamide)
Aspirin when taken long term
Caffeine in excessive amounts (possibly)
Gonadotropin-releasing hormone (GnRH) agonists (to treat prostate cancer)
Monoamine oxidase inhibitors
Polychlorinated biphenyl compounds [PCBs])
* Other drugs can be harmful, but those listed are more significant.
Sperm emission may be impaired because of retrograde ejaculation into the bladder.
Retrograde ejaculation is often due to
Retroperitoneal dissection (eg, for Hodgkin lymphoma)
Transurethral resection of the prostate
Sperm emission can also be impaired by
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.
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.
(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.
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 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.
After being at room temperature for 20 to 30 minutes, 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.
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.
If oligozoospermia or azoospermia is detected, genetic testing should be done. These tests include
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.
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
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.
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.
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). (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 of the woman plus artificial insemination or assisted reproductive techniques (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 infection or have lived in or traveled to an area with active Zika virus transmission.
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 and intracytoplasmic sperm injection.