Male Infertility – Sperm Disorders

Spermatogenesis

This process is continuous and requires about 72-74 days for maturation from germ (stem) cell, or spermatogonium, to spermatozoon. It is most efficient at 34 degrees centigrade, so exposure to excessive heat or prolonged fever within 2-3 months of evaluation can adversely affect sperm count, motility, and morphology. Within the seminiferous tubules, Sertoli’s cells sustain and regulate maturation, and Leydig’s cells produce testosterone required for maintenancde of spermatogenesis.

Azoospermia

No sperm in semen. This may be due to obstruction or congenital absence of the vas deferens or to a primary testicular disorder. The presence of fructose (which is normally secreted in the seminal vesicles) in semen indicates that the ejaculatory ducts are unobstructed.

Varicocele

Abnormal dilation of pampiniform plexus veins draining the testes. This is the most common anatomic abnormality in infertile men (25% vs. 10-15% in the general population). Varicoceles are more common on the left side, where the spermatic vein empties into the left renal vein. A varicocele results in pooling of blood and higher intrascrotal temperatures.

Retrograde Ejaculation

Occasionally some semen meant for ejaculation to the outside of the body backs up into the urinary bladder. This happens especially in men who have neurologic dysfunction or who have had a retroperitoneal dissection (eg. for Hodgkin’s disease) or prostatectomy.

Endocrine Disorders

The following are quite uncommon, although they are known to be associated with defective spermatogenesis. These are hyperprolactinemia, hypothyroidism, adrenal disorders, abnormalities of the hypothalamic-pituitary-gonadal axis, and hypogonadism.

Genetic Disorders

Genetic causes of defective spermatogenesis include Klinefelter’s syndrome and gonadal dysgenesis.

Diagnosis

A history is obtained and physical examination is performed to search for causes of infertility. Mumps, orchitis, cryptorchidism, testicular injury, exposure to industrial or environmental toxins, excessive heat exposure, acute illness or prolonged fever within the previous 3 months, recreational drug use, alcohol intake and exposure to diethylstilbesterol or anabolic steroids should be excluded. Physical examination should focus on anatomis abnormalities, eg. decreased testicular volume (normal; 20-25 ml), prostatitis, hypospadias, or a varicocele.

Semen Analysis

This is the major test for evaluating male infertility. It should be performed after 2-3 days of sexual abstinence. At least 2-3 ejaculates obtained at intervals of no less than 1 week should be examined because sperm count varies; each ejaculate is obtained by masturbation into a clean glass jar, preferably at the lab site. For men who have difficulty with this method, special condoms free of lubricants and chemicals toxic to sperm can be used.

After the ejaculate is liquefied at room temperature for 20-30 minutes, the following parameters should be evaluated: ejaculate volume (normal; 2-6ml), viscosity (normally liquefies within 1 hour), gross and microscopic appearance (normally opaque, cream coloured, 1 to 3 WBC/high-power field [hpf]), pH (normal; 7-8), sperm count (normal; >20 million/ml), sperm motility at 1 and 3 hours (normal; >50%), and sperm morphology (normal; >60%). Additional computer assisted measures of sperm motility (eg. linear sperm velocity) are available, however, correlation of velocity with fertility is unclear at this time.

Specialized Tests

These tests are used more when artificial reproductive techniques are being performed (IVF, etc). The immunobead test, the most common test for detecting antisperm antibodies, uses small beads coated with antibodies that bind to IgG and IgA on the sperm head, midpiece, or tail. The hypo-osmotic swelling test, which measures the structural integrity of sperm plasma membranes, is performed by placing sperm in a hypo-osmolar culture medium. Normally, excess extra cellular water shifts into the sperm head, causing it to swell, and the tail coils. These changes do not occur in abnormal sperm.

Two tests can determine the ability of sperm to fertilize the egg in vitro. The hemizona assay evaluates sperm binding to protein receptors on the surface of the isolated shell (zona pellucida) of human oocytes (eggs). The sperm penetration assay evaluates sperm penetration of hamster eggs after the zona pellucida has been removed.

A testicular biopsy may be required to assess function of the seminiferous tubules.

Treatment

Varicoceles are usually treated. In uncontrolled studies, ligation of the internal spermatic vein results in a 30-50% pregnancy rate, but controlled, randomized studies are needed to confirm these rates.

In men with moderate oligospermia (10 to 20 million/ml) but no endocrine defects, clomiphene citrate (25 to 50 mg/day for 25 days/month for 3-4 months) may improve sperm counts. However, sperm motility and morphology do not seem to improve significantly, and no controlled studies indicate increased fertility.

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Artificial Insemination

This technique focuses on sperm selection. Use of whole sperm ejaculates, obtained with a cervical cup, does not appear to enhance pregnancy rates. When ejaculate volumes are large, using a split ejaculate (the first portion, with the greatest sperm density and motility) may slightly enhance pregnancy rates. Intrauterine insemination with washed semen samples can be performed when intertility is associated with abnormal cervical mucus. The ejaculate is washed several times with tissue culture medium, the motile sperm swim up from the sperm pellet and are selected for insemination. This approach appears to be most successful when the man has low sperm counts and normal sperm motility and when cervical mucus is abnormal; most pregnancies are achieved by the sixth treatment cycle. For oligospermia, decreased sperm motility, and antisperm antibodies, controlled ovarian hyperstimulation with intrauterine insemination and/or in vitro fertilization and other assisted reproductive techniques can be used. In some cases, intracytoplasmic sperm injection may be used (ICSI).

For azoospermia, insemination with donor sperm is an option timing is critical and is based on monitoring ovulation. Because sexually transmitted diseases, including AIDS, are a concern, frozen sperm specimens from reputable sperm banks should be used rather than fresh donor semen specimens.