Tests

WHAT TESTS ARE USED TO DIAGNOSE MALE INFERTILITY?

In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. It should be done earlier if a woman is over 35 years old or if either has known risk factors for infertility. [For tests on female infertility, see the Well-Connected Report #22, Infertility in Women .]

Fertility History

The patients will provide the physician with a detailed history of any medical or sexual factors that might affect fertility. The history should include the following:

Frequency and timing of sexual intercourse.
Duration of infertility and any previous fertility events.
Childhood illnesses and any problems in development.
Any serious illness (diabetes, respiratory infections, cancer, previous surgeries).
Sexual history, including any sexually transmitted diseases.
Any exposure to toxins, such as chemicals or radiation).
History of any medications and allergies.
Any family history of reproductive problems.

Physical Exam

A fertility specialist, usually a urologist, will perform a physical examination. A physical examination of the scrotum, including the testes, is essential for any male fertility work-up. It is useful for detecting large varicoceles, undescended testes, absence of vas deferens, cysts, or other physical abnormalities.

Varicoceles large enough to be associated with infertility can be felt during examination of the scrotum. In such cases, they are described as feeling like "a bag of worms." They disappear or are very reduced when the patient lies down, so the patient should be examined for varicocele while standing.
Checking the size of the testicles is helpful. Smaller-sized and softer testicles along with tests that show low sperm count are strongly associated with problems in sperm formation. Normal testicles accompanied by a low-sperm count, however, suggest possible obstruction. The physician may also take the temperature of the scrotum with a test called scrotal thermography.
The physician will also check the prostate gland for abnormalities.
The penis is checked for warts, discharge from the urinary tract, and hypospadias (incorrect location of the urethra opening).

Post-Ejaculatory Urine Sample

A urine sample to detect sperm after ejaculation may rule out or indicate retrograde ejaculation. It also may be used to test for infections.

Semen Analysis

The basic test to evaluate a man's fertility is a semen analysis. The sperm collection test for men who can produce semen involves the following procedures:

A man should abstain from ejaculation for several days before the test because each ejaculation can reduce the number of sperm by as much as a third. (The maximum number of sperm is usually obtained by abstaining for about four days.)
A man collects a sample of his semen in a collection jar during masturbation either at home or at the physician's office. Proper collection procedure is important, since the highest concentration of sperm is contained in the initial portion of the ejaculate. Specially designed condoms may be available that will enable collection of a sample during sexual intercourse. (Regular condoms are not useful, since they often contain substances that kill sperm.)
The sample should be kept at body temperature and delivered promptly, because if the sperm are not analyzed within two hours or kept reasonably warm, a large proportion may die or lose motility.
A semen analysis should be repeated at least three times over several months.

Both the man and the woman should be present when the physician discusses the results of this analysis so that both partners will understand the implications. The analysis report should contain results of any abnormalities in sperm count, motility, and morphology as well as any problem in the semen.

Sperm Count. A low sperm count should not be viewed as a definitive diagnosis of infertility but rather as one indicator of a fertility problem. Counts of less than 20 million per milliliter are currently considered strong indicators of infertility, although pregnancy is sometimes possible even with lower counts if the woman is fertile. If there are no sperm cells at all in the semen, the physician checks for obstruction in the tubes or for Sertoli cell-only syndrome, in which there are no sperm-producing cells in the testes.

Sperm Motility. At least half of total sperm count and no less than 10 million/mL of the sperm should be motile for normal fertility. Motility (the speed and quality of movement) is graded on a 1 to 4 ranking system. For fertility, motility should be greater than 2.

Grade 1 sperm wriggle sluggishly and make little forward progress. (Sperm that, in fact, clump together may indicate that antibodies to the sperm are present.)
Grade 2 sperm move forward, but they are either very slow or do not move in a straight line.
Grade 3 sperm move in a straight line at a reasonable speed and can home on an egg accurately.
Grade 4 sperm are as accurate as Grade 3 sperm, but move at terrific speed.

Testing for sperm motility is particularly valuable for predicting the success of artificial insemination and which men might be candidates for the intracytoplasmic sperm injection ICSI fertilization technique, in which the sperm is inserted directly into the egg and motility plays almost no role.

Sperm Morphology. Morphology is the structure of the sperm. About 60% of the sperm should be normal in size and shape for adequate fertility. Determining the morphology of the sperm is particularly important for the success of the fertility treatments in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

Seminal Fluid. The seminal fluid (semen) itself is analyzed for abnormalities.

The color is checked and should be gray colored.

The amount of semen is important. Most men ejaculate 2.5 to 5 cc (1/2 to 1 teaspoon) of semen:

Amounts greater than 1 cc but lower than 2.5 cc may indicate prostate problems or frequent intercourse.
A semen sample that is less than 1 cc could indicate a blockage of the ejaculatory ducts or other tubular abnormalities.
No ejaculate at all may signal retrograde ejaculation.
High amounts of ejaculate may, in some cases, also contribute to infertility.

The semen will be tested for how liquid it is. (Normal semen is liquefied within 20 minutes after adding certain enzymes.) Abnormal results suggest the following:

Overly sticky fluid suggests problems in the prostate gland (which adds fluid to sperm).
Overly watery fluid suggests lack of sperm.

The amount of sugar (fructose) in sperm will be measured.

Since fructose is added to the semen in the epididymis, an absence of fructose indicates that an obstruction has occurred either in the vas deferens or the epididymis.
Conversely, if there is fructose in the semen but no sperm, then the channel from the epididymis is open but there is a defect in sperm production.

Other factors may also be measured in semen.

White blood cell counts are taken to detect infection.
Low levels of inhibin B, which appears to be produced only in the testes, may indicate blockage or abnormalities in the seminiferous tubules.
Low levels of another compound, alpha-glucosidase, may also indicate blockage in the epididymis.

Hormone Tests

Tests for hormonal levels are indicated if semen analysis is abnormal (especially if sperm concentration is less than 10 million per milliliter) or there are other indications of hormonal disorders.

Blood tests for testosterone and follicle-stimulating hormone (FSH) levels are usually taken first.
If testosterone levels are low, then luteinizing hormone (LH) and prolactin levels are measured.

The balance of these four hormones can help determine specific problems are present. Very high FSH levels, for example, with normal levels of other hormones indicate abnormalities in initial sperm production. Usually this occurs only if the testicles are severely defective, causing Sertoli cell-only syndrome in which sperm-manufacturing cells are absent.

Postcoital Test

The postcoital test, also known as the cervical mucus penetration test, is designed to evaluate the effect of a woman's cervical mucus on a man's sperm. Typically, a woman is asked to come into the physician's office within two to 24 hours after intercourse at mid-cycle (when ovulation should occur). A small sample of her cervical mucus is examined under a microscope. If the physician observes no surviving sperm or no sperm at all, the cervical mucus should then be cultured for the presence of infection. The test cannot evaluate sperm movement from the cervix into the fallopian tubes or the sperm's ability to fertilize an egg.

Sperm Antibodies

If a man has had a vasectomy reversed and still cannot conceive or if semen analysis shows sperm clumping together, blood tests for anti-sperm antibodies will be conducted. Anti-sperm antibodies may also develop after genital infection or injury to the testes. The primary negative effect of these antibodies is to bind the sperm to the woman's cervical mucus, preventing the sperm from swimming further up.

Testicle Biopsy

Occasionally, a testicle biopsy may be performed, particularly for the following:

If Sertoli cell-only syndrome is suspected, in which sperm-producing cells in the testes are absent. It should be noted that specific cellular patterns can determine whether this condition is congenital (in-born) or caused by some later injury. This distinction is important in predicting the potential success of later sperm retrieval procedures.
For detecting obstruction in the transport system when sperm production looks normal but the count is low.

The standard biopsy procedure requires incisions (called an open approach) under anesthesia. It can be painful afterward. More than one biopsy may be needed in the case of suspected Sertoli cell-only syndrome, since one area may not have cell-producing cells, but other regions may contain normal sperm. Biopsies of both testes are more accurate than one. (Physicians must be careful not to avoid the epididymis during a biopsy, since it is a continuous tiny tube and would be destroyed.)

The use of needle aspiration, which is less invasive than standard biopsies, is proving to be as effective in evaluating infertility as the open approach and is able to retrieve sperm. Patients may consider freezing any sperm retrieved during biopsy for later use in assisted reproductive technologies.

Ultrasound

Ultrasound imaging may be used to accurately determine the size of the testes or to detect cysts, tumors, abnormal blood flow, or varicoceles that are too small for physical detection (although such small veins may have little effect on fertility). It also can detect testicular cancer, which some experts believe make it worthwhile as a routine procedure for any male infertility work-up.

Genetic Testing

Genetic testing may be warranted in men who are severely deficient in sperm and who show no evidence of obstruction, particularly in men undergoing the ICSI procedure. [ See What Are Assistant Reproductive Technologies?, below.] If genetic abnormalities are suspected in either partner, counseling is recommended. Researchers have developed a technique that can examine all the chromosomes in a human embryo. If it proves useful, it may help identify abnormalities that increase the risk for infertility, treatment failures, or genetic defects in the offspring.

Fertilization Tests

In men who wish to undergo fertility treatments, certain tests will help determine the right strategies.

The Hamster Test. The hamster test, or micro-penetration assay test, uses the sperm sample to fertilize hamster eggs that have had their covering removed to allow penetration. If less than 5% to 20% of the eggs are fertilized, infertility is diagnosed. It may be useful for determining the best assisted reproductive treatment options for men with infertility.

The Human Zona Penetration Test. A newer procedure, the human zona penetration test, uses sperm to fertilize dead human eggs, which are usually obtained from an ovary that was removed for medical purposes. (Like the hamster test, the procedure cannot result in a living embryo.) Researchers hope it will provide the same information as the hamster test and also indicate whether the sperm can penetrate the outer coating of an egg.