When an abnormality in the sperm is demonstrated (and confirmed with appropriate follow up semen analyses), a cost considerate and organized approach to the evaluation and treatment should be initiated. The evaluation is based on consideration of the causes for abnormal sperm production.
(1) A detailed fertility history should be taken, including:
- Prior pregnancies achieved with the current or any prior partners, regardless of outcome (such as spontaneous abortion or miscarriage, term delivery, or termination).
- Prior infertility treatments and their outcome, including infertility care for the partner (if any)
- Any noted abnormalities in completing intercourse or ejaculation.
(2) A detailed medical history, including:
- Surgery involving the region of the scrotal sac or an inguinal hernia repair
- Known exposure to increased heat, such as hot baths, tight underwear, truck driving
- Varicocele detection on exam
- Radiation or chemotherapy (the testes are very sensitive to radiation with as little as 15 rads associated with decreased spermatogenesis, 50 rads associated with transient azoospermia, 600 rads associated with permanent azoospermia)
- Cancer of the testicle(s) as well as surgical or medical treatment
- Infections involving the reproductive tract, including venereal diseases or prior prostatitis (which is not caused by a venereal disease) and their treatment
- Serious systemic viral or other disorder that is associated with a fever within the prior 3-5 months
- Trauma to the testes (even if several years prior)
- Substance abuse, including cigarettes, alcohol, cocaine, narcotics, and marijuana
- Toxin exposure, including pesticides or industrial chemicals in poorly ventilated conditions
- Medications taken in the past 3-6 months
- Prior chromosome testing results
- DES exposure in utero
- Known history of congenital absence of the vas deferens
- Known history of retrograde ejaculation or history of low ejaculatory volume
- Neurologic symptoms, including headaches, blurry vision, dizziness, vomiting without known cause
- Ongoing medical conditions requiring follow-up with a physician
- Ability to smell (tested with substances like coffee, not harsh odors)
(3) An expert physical exam should be performed (ideally by a urologist with a special interest in male infertility), including:
- Overall appearance for adequacy of virilization (hair growth and pattern, breast development which is referred to as gynecomastia if present in the male, eunuchoid dimensions with long extremities and tall stature)
- Size and consistency of the testes (with either the calipers of an orchidometer that measures testicular diameters or oval shape “ovoids” that are calibrated by volume for comparison) with a normal adult testicle being greater than 4 cc in length and 20 ml in volume. Since 85-90% of testicular volume consists of seminiferous tubules (involved in sperm production), a serious insult to spermatogenesis is often reflected by a decrease in testicular volume
- Presence of the epididymis (and any induration, irregularity or cystic changes) and vas deferens (with any nodularity noted)
- Detection, location, and size of a varicocele
(4) An initial laboratory evaluation might include:
(A) FSH (ideally with LH and total testosterone) concentration in the blood
These tests are especially important if man is azoospermic, looking to identify an endocrinologic basis.
The most common treatable finding is an insufficient amount of pituitary gonadotropins (FSH and LH). This might reflect a pituitary or CNS-hypothalamic dysfunction and a structural lesion should be ruled out as well as insufficiency of the other pituitary hormones.
An elevated LH and testosterone concentration with a low to normal FSH concentration suggests “partial androgen resistance” syndrome, which results from a deficiency in the intracellular androgen receptor number or function. There is a wide spectrum of pathology associated with this syndrome and it is now thought that a large number of previously diagnosed “idiopathic oligospermia” patients may really have “partial androgen resistance” syndrome as the underlying cause.
An elevated FSH that is 2-3 fold greater than normal reflects a poor prognosis and likely testicular spermatogenic (seminiferous tubule and Sertoli cell) compartment failure (with no Sertoli cell inhibin production to suppress the FSH).
If there is an elevated FSH and elevated LH concentration with low testosterone then there is most likely “panhypogonadism” (complete testicular failure).
If all three hormone concentrations are normal then there is most likely a nonhormonal cause for the abnormal sperm concentration (such as a varicocele) and there is no basis for hormonal treatment.
(B) Prolactin concentration
If the FSH and LH concentrations are suppressed then the prolactin concentration should be checked since treatment of hyperprolactinemia will often correct the gonadotropin abnormality. Structural lesions (including a prolactinoma) must be ruled out if hyperprolactinemia is demonstrated.
(C) Free (bioactive fraction of the total) testosterone concentration
This is important if there is a low total testosterone concentration with a normal FSH and LH concentration, especially if the man is obese, since this may only reflect a decrease in the sex hormone binding globulin (the liver protein that bindings sex hormones such as testosterone resulting in decreased bioactivity). If the free testosterone concentration is normal, no further followup for these findings is required.
(D) Anti sperm antibodies
If the abnormality is predominantly a motility or progression problem then many infertility specialists suggest highly specific antisperm antibody testing. The results of this specific testing do not change my treatment plan so I only check for antibodies with the (nonspecific) postcoital test. Treatment is based on the results of the postcoital test, endocrine evaluation, physical exam (for varicocele) and presence of elevated numbers of round cells on semen analysis.
(E) centrifugation of the semen sample
If the semen is initially considered devoid of sperm (azoospermia), one should perform a microscopic examination of the centrifuged sperm pellet. This can often identify at least a few sperm to rule out complete ductal obstruction
(F) examination of a postejaculate urine specimen
If there is both a low volume (less than 1cc) and low density of sperm (or azoospermia) the postejaculate urine should be examined to rule out retrograde ejaculation
(G) transrectal ultrasound, vasography or seminal fructose level
If azoospermia with a low ejaculatory volume and reasonable (less than 2 fold normal) FSH concentration then these tests can rule out an ejaculatory duct obstruction
(H) testicular biopsy
If azoospermia with no ejaculatory duct obstruction, low volume and reasonable (less than 2 fold normal) FSH concentration then a testicular biopsy to assess testicular sperm production is important. If the testicular biopsy is normal in this situation, vasography can confirm an obstruction (which can then be treated surgically) or an emission failure if no obstruction is present (which can be treated with medications or electroejaculation). If the testicular biopsy shows no sperm or germ cells then consideration of adoption and donor sperm is appropriate. If the testicular biopsy shows a maturational arrest in the sperm, then a large varicocele (if present) can reasonably be repaired (otherwise consideration of adoption or donor sperm is appropriate).
From this initial evaluation the physician can pull together a tremendous amount of information and usually direct management quite specifically.