Male Infertility Evaluation Including Semen Analysis (“Sperm Test”)

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Male Infertility Evaluation Including Semen Analysis (“Sperm Test”)

Traditionally, the health care response to a couple with infertility has been for the female partner to visit the gynecologist for an evaluation.

The male partner may or may not be asked to give a semen analysis (often called a “sperm test”). If the semen analysis is abnormal, couples are often shuttled straight to assisted reproduction for IUI or IVF and the infertility issue bypassed. In the modern era of managed care and cost-containment, this sequence of events is now inappropriate.

The Patient History

The history reviews medical problems including recent fevers, illnesses, cancer and infections. Prior surgery, including orchidopexy, herniorraphy, trauma, open retroperitoneal, pelvic or bladder procedures and prostate surgeries should be elucidated. A family history of cryptorchidism, midline defects or hypogonadism is important. A developmental history of hypospadias, congenital anomalies and DES exposure may also be found. The use of medications including finasteride (Propecia), nitrofurantoin, sulfasalazine (and possibly other sulfa drugs), cimetidine, alpha-blockers, calcium channel blockers, allopurinol and many other medications may also impact on fertility.

PATHWAY FOR MALE INFERTILITY EVALUATION
FIGURE 1. MALE INFERTILITY EVALUATION.

The Patient Social History

A social history may elucidate the habitual use of alcohol, tobacco use, recreational drugs and anabolic steroids, all of which can hurt sperm production. The use of spermicidal lubricants, and incorrect patterns and timing of intercourse may be noted from a sexual history. Dr. Hashmi recently published the first real research study that convincingly shows that hot tubs and baths can have a major impact on semen quality. Lastly, an occupational history is important to determine exposure to ionizing radiation, chronic heat, dyes, pesticides, herbicides and heavy minerals (lead, cadmium, mercury). The vast majority of exposures discovered on the patient history are reversible and so are valuable to find and discontinue.

Key Points for Patients:

  1. Bring any information you may have from prior evaluations. Collect prior reports and bring them with you to the initial visit. Semen analyses or hormone testing can help 1) avoid duplicating tests, and 2) give further evidence (or not) of a male infertility problem.
  2. Bring your female partner. Dr. Hashmi is very interested in her history of prior pregnancies, how regular her cycles and menstrual flow are, and whether intercourse was “timed” or simply unprotected to this point. The most important piece of information about her is her age, as fertility in women declines after age 35 and is almost certainly decreased at 40.

The Physical Examination

This will assess blood pressure, height, weight and body mass as well a body habitus including obesity, gynecomastia and secondary sex characteristics. The penis may show hypospadias, chordee, plaques or venereal lesions. The testes are evaluated for size, consistency and irregularities. The epididymides should not be swollen or tender, indicative of infection or obstruction. Careful palpation of each vas deferens can show that they are missing, abnormal or inflamed. The spermatic cords above the testes should be felt for asymmetry suggestive of a lipoma or varicocele. Lastly, a rectal examination is important in evaluating the prostate (if age appropriate) and identifying large cysts, infections or dilated seminal vesicles all of which may be associated with infertility.

The Semen Analysis (“Sperm Test”)

Although not a true measure of fertility, the semen analysis, if abnormal, may suggest that the probability of achieving fertility is statistically low. Among the numbers on the test, the sperm concentration and motility appear to correlate best with fertility. Two well-performed semen analyses can often suggest a diagnosis or direction. Normal values for the semen analysis are found in Table 1.

Table 1 – SEMEN ANALYSIS-W.H.O. 2010 REFERENCE RANGES
Ejaculate Volume 1.5-5.5mL
Sperm Concentration >14 x 106 sperm/mL
Motility >43%
Forward Progression 2 (scale 1-4)
Morphology >4% Kruger
Also: No agglutination (clumping), white cells, or increased viscosity

Sperm Morphology

The evaluation of the various shapes of sperm is termed morphology. Several descriptive systems exist to evaluate morphology, and within each classification system, sperm are designated normal or abnormal based on a list of criteria. It is believed that sperm morphology may correlate with a man’s fertility potential, but in actuality, it has only been shown in studies to correlate with the ability of sperm to penetrate and fertilize eggs in the setting of in vitro fertilization (IVF) (Figure 2).

Sperm Morphology
FIGURE 2. RELATIONSHIP BETWEEN KRUGER (STRICT) MORPHOLOGY AND EGG FERTILIZATION RATES WITH IVF.

It is not been convincingly demonstrated that sperm morphology correlates with the ability of couples to conceive with either sexual intercourse or intrauterine insemination (IUI). Sperm morphology may also be a sensitive indicator of testicular health because sperm morphology is largely determined during sperm production in the testis. The main role of morphology in the male evaluation is to complement the semen analysis data and better estimate the chances of fertility.

Key Points for Patients

  1. Recognize that not all semen analysis labs are equivalent. Some labs, especially those associated with fertility centers, may be more used to doing a semen analysis and have better quality assessment and reports.
  2. Semen quality varies with collection technique, so follow the instructions as best as you can.
  3. Abstain from ejaculation for 2-4 days prior to collection. Longer or shorter abstinence than this may result in artificially high or low concentration or motility.
  4. Clean or sterile containers should be used for collection. The entire specimen must be collected. Regular condoms and lubricants should be avoided as they may kill sperm.
  5. If collecting the sample at home, keep it at body temperature during transport (shirt pocket); it should be delivered within 1 hour of collection.

Hormone Tests

Testing pituitary-gonadal hormones can provide valuable information on the state of sperm production. In turn, there are abnormalities of these hormones that can cause infertility. The standard hormone evaluation includes an FSH, testosterone, LH, and prolactin. These hormones should be considered in infertile men with sperm concentration less than 10 x 106 sperm/mL and soft testicles. The more common patterns of hormonal disorders seen with infertility are in Table 2.

TABLE 2. CHARACTERISTIC HORMONE PROFILES IN INFERTILE MEN.
Condition T FSH LH PRL
Normal NL NL NL NL
Primary Testis Failure Low High High/NL NL
Hypogonadotropic Hypogonadism Low Low Low NL
Hyperprolactinemia Low Low/NL Low High
Androgen Resistance High High High NL

Key Points for Patients

Hormone levels should be measured if:

  1. Sperm concentration is less than 10 x 106 sperm/mL
  2. There is impaired sexual function (erectile dysfunction, low libido)
  3. There are exam findings of a specific hormone disorder (i.e. thyroid).

Further Testing

Many other tests are available to help evaluate male factor infertility if the 4-point evaluation fails to find a diagnosis. One guiding principle that Dr. Hashmi uses when it comes to such tests is to only order these tests if it will change the way the patient is managed. They include:

  1. Seminal Fructose and Post Ejaculate Urinalysis Fructose is normally present in the ejaculate. If absent, or the pH in the ejaculate is low, then the seminal vesicles may be missing or obstructed. A post ejaculate urinalysis (PEU) is a microscopic inspection of the first voided urine after ejaculation for sperm. Retrograde ejaculation is diagnosed in this manner.
  2. Semen Leukocyte Analysis On a routine semen analysis, “round” cells are often found in addition to sperm with tails. These “round” cells are either immature sperm forms (spermatocytes) or white blood cells (leukocytes). It is important to distinguish between these two cell types because the treatments differ. Dr. Turek offers specific stains of the ejaculate to look for leukocytes (CD45 monoclonal antibody).
  3. Sperm DNA Fragmentation Assay Evidence suggests that the quality of sperm DNA packaging is important for fertility. High levels of reactive oxygen species and oxidative stress are known to cause sperm DNA to fragment. The structure of sperm chromatin (the DNA-associated proteins) can be measured by several methods, including the COMET and TUNEL assays as well as by flow cytometry after acid exposure and staining. These tests measure the degree of DNA fragmentation after chemically stressing the sperm DNA-chromatin complex, and can indirectly reflect the quality of sperm DNA integrity.

 

  1. FIGURE 3. EXAMPLE OF SPERM WITH NORMAL (YELLOW-GREEN) AND FRAGMENTED (RED) DNA BY FLOW CYTOMETRY.

    Abnormally fragmented sperm DNA rarely occurs in fertile men, but can be found in 5% of infertile men with normal semen analyses and 25% of infertile men with abnormal semen analyses. This testing can detect infertility that is missed on a conventional semen analysis. Often reversible, causes of DNA fragmentation include tobacco use, medical disease, hyperthermia, air pollution, infections (leukocytospermia), chemotherapy, irradiation, sperm processing and varicocele.

  2. Scrotal Doppler Ultrasound High frequency (10mHz) non-invasive ultrasound of the scrotum has become a mainstay in the evaluation testicular and scrotal lesions. Most commonly, Dr Turek will order this to look for clinically suspicious varicoceles.
  3. Transrectal Ultrasound (TRUS) High frequency (5-7mHz) transrectal ultrasound offers superb imaging of the prostate, seminal vesicles and ejaculatory ducts. This is a first-line method of diagnosing ejaculatory duct obstruction.
  4. CT Scan/MRI Pelvis Since the advent of TRUS, these studies are only rarely indicated. One reason to order this study is to further evaluate a patient with an isolated right varicocele.
  5. Karyotyping Also infrequently indicated, chromosomal analysis is performed in men with low (less than 5 million) or no sperm in the ejaculate.
  6. Y Chromosome Analysis It has become apparent that up to 8% of men with low sperm counts and 15% of men with no sperm counts may be missing small portions of the Y chromosome, termed Ymicrodeletions.

Key Points for Patients:

Additional tests should only be ordered if it would do either of the following:

  1. Delineate treatable problems
  2. Define life-threatening problems
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