2. UroToday Home
  3. Recent Abstracts
  4. Men's Health
  5. Male Infertility

Infertility Diagnosis & Classifications

Clinical Evaluation of the Subfertile Male

  • Fertility History
    • Present relationship history
      • Duration of infertility
      • Contraceptive methods and length of time used
      • Length of time trying to conceive
      • Number of pregnancies including miscarriages and therapeutic abortions, which gives an indication of the potential to conceive
    • Previous history and relationships
    • Sexual history
      • Frequency of intercourse and masturbation
      • Libido, potency, and sexual technique
      • Ejaculation
      • Dyspareunia and the use of lubrication
      • Understanding of the ovulatory cycle
    • Genitourinary history
      • Testicular descent
      • Sexual development and onset of puberty
      • Infections
      • Trauma or torsion
      • Exposure to chemicals
      • Exposure to heat
      • Exposure to radiation
    • Previous infertility evaluation
      • Patient
      • Woman


  • General Medical History
    • Medical illnesses
    • Abnormal metabolism of sex steroids
    • Surgical history
      • Inguinal hemiorrhaphy
      • Surgery on the ureter, bladder, bladder neck, or urethra can
      • Retroperitoneal surgery and other major pelvic procedures
    • Current and past medications
    • Occupation and habits
      • Occupation and stress
      • The active ingredients in cigarettes, marijuana, coffee, tea, alcohol, and some naturopathic herbs
    • Family history
      • Sibling fertility status; identify familial conditions like cystic fibrosis and congenital adrenal hyperplasia. In utero exposure to diethylstilbestrol (DES) can result in testicular, epididymal, and penile anatomic abnormalities


  • Physical Examination
    • General examination
    • Examination of the genitalia
      • Penis: size of the penis and location of the meatus
      • Testes: location, size, and consistency of the testes and should be in a dependent part of the scrotum
      • Epididymides: examined for size and consistency.
      • Vasa deferentia
      • Spermatic cords: size and consistency
      • Inguinal region: inguinal canals are palpated looking for evidence of inguinal hernias
    • Rectal examination: lower gastrointestinal pathology, prostate and seminal vesicles


  • Semen Analyses
    • Collection: At least two semen analyses are needed to establish a baseline
    • Minimal standards of adequacy:
      • No absolute measure of fertility on semen analysis
      • Minimal standards of semen adequacy have been defined by the World Health Organization (Table 1)
    • Additional physical parameters. Other properties examined at the time of a routine semen analysis include:
      • Color
      • Coagulation
      • Liquefaction
      • Viscosity
      • pH: 7.2 to 8.0.
      • Fructose


  • Other Laboratory Tests
    • Urinalysis
    • Endocrine evaluation
    • Other tests regularly recommended in the past now appear to be unnecessary on a routine basis: test of thyroid and adrenal function (less than 0.5 percent of cases)
    • Genetic testing
      • Karyotype analysis is critical for all men with azoospermia and severe oligospermia who are planning IVF/ICSI
    • Test of sperm function
      • Mucus penetration test
      • Hamster egg penetration test
    • Antisperm antibodies. Enzyme-linked immunosorbent assay (ELISA) and immunobead binding assay detect the presence of antibodies on sperm
    • White blood cells.
  • Radiologic procedures
    • Transrectal ultrasound (TRUS)
      • Indicated in infertile men with low-volume ejaculates (less than 1.5 mL)
      • Ejaculatory duct obstruction (EDO) may be identified by seminal vesicle dilatation (larger than 1.5 cm in diameter)
      • Seminal vesicle hypoplasia or absence
      • Cause EDO, stones, scar, cysts, or a persistent utricle
      • Seminal vesicle fluid can be sampled to confirm the presence of sperm in patients with suspected obstruction or seminal vesiculography can be done to demonstrate obstruction radiographically.
    • Vasography: Detects abdominal vas deferens and seminal vesicle and ejaculatory duct patency prior to definitive surgery for obstruction.
    • Scrotal ultrasound
      • Indicated when the testes are not easily palpable due to coexistent hydrocele
      • Confirm the origin and character (solid versus cystic) of intrascrotal masses
      • Confirm the presence of a clinically suspicious varicocele.

Classification of Abnormalities

  • General Information
    • Initial classification categories:
      • All parameters normal
      • Azoospermia
      • A single abnormal parameter
      • Multiple abnormal parameters.
    • Distribution of semen abnormalities among infertile men:
      Azoospermia 8%
      Single abnormal parameter 37%
      Multiple abnormal parameters 55%
      Among the single abnormal parameters, isolated abnormalities in motility account for the majority of cases.
  • All Parameters Normal
    • Further evaluation of the female partner is recommended
    • Tests of sperm function noted previously may be useful. Most couples with unexplained infertility will go on to be treated with intrauterine insemination (IUI) or in vitro fertilization (IVF).
  • Azoospermia
    • When no sperm are found on semen analysis, the specimen should be centrifuged to confirm the absence of any sperm in the specimen
    • Collection error and/or retrograde ejaculation must be ruled out as causes of azoospermia
    • If retrograde ejaculation is identified by the finding of sperm in the urine (more than 10 to 15 sperm per high-power field), treatment can be initiated with oral alkalization and sympathomimetic agents to promote antegrade ejaculation
    • Alternatively, sperm can be retrieved from the bladder, processed, and used for IUI
    • The results of the fructose test and gonadotropin levels determine what additional evaluation and treatment is necessary
      • LH, FSH, and testosterone levels can differentiate primary testicular failure from secondary testicular failure caused by either pituitary or hypothalamic dysfunction
      • A serum FSH greater than three times normal along with atrophic testicles on physical examination is essentially equivalent to a "medical biopsy" of the testis and indicates severe testicular failure. This finding obviates the need for a surgical biopsy to rule out obstructive conditions; however, sperm can be found in many of these men for use with l VF/ICSI by testicular sperm extraction techniques (TESE).
    • After ruling out a major endocrine abnormality, the major differential diagnosis is ductal obstruction or testicular failure.
      • Negative fructose test
        • Congenital bilateral absence of the seminal vesicles and vas deferens
        • Bilateral ejaculatory duct obstruction
        • A type of retrograde ejaculation with scant antegrade ejaculation that contains no sperm or fructose (rarely)
        • Treatment of CAVD is direct sperm aspiration from the remnant of the head of the epididymis. The sperm are then processed and used in combination with in vitro fertilization (IVF) techniques. Ejaculatory duct obstruction is managed by transurethrally resecting the ejaculatory ducts or unroofing midline cysts.
      • Positive fructose test
        • Rules out complete obstruction of the ejaculatory ducts and severe dysfunction of the seminal vesicles
        • Does not give an indication of the patency of the ductal system from the level of the testis to the ejaculatory ducts
        • Therefore, does not differentiate between proximal ductal obstruction and testicular failure
      • Testicular biopsy
        • Necessary in the azoospermic patient with normal hormones and normal sized testes who has fructose in the ejaculate
        • Microscopic examination of the biopsy will indicate whether spermatogenesis is progressing normally
        • Sperm found on testicular biopsy can be cryopreserved for future use.
        • If the testicular biopsy indicates active and complete spermatogenesis, scrotal exploration and vasography are indicated
        • Vasogram
          • If patency is demonstrated, then exploration of the epididymis is required to determine the site of obstruction
          • Fluid within the vas deferens lumen should also be examined microscopically to determine if sperm are present or absent
          • A microscopic vasoepididymostomy is necessary to correct intraepididymal obstruction
          • If no spermatozoa are detected in the tubules of the epididymis during this exploration, then intratesticular ductal obstruction may be the cause of azoospermia. Since these cases are difficult to correct, IVF and ICSI with testicular sperm is recommended
  • Multiple Abnormal Parameters on the Semen Analysis
    • Determination of the LH, FSH, and testosterone levels are essential to rule out an endocrine abnormality.
    • When specific factors cannot be identified by the history or physical examination, it may be beneficial to follow these patients for an additional 6 to 12 months to determine if there is any self-correction of the abnormality
    • If spontaneous correction does not occurred, nonspecific therapy can be instituted as discussed below or, more commonly, couples can be offered assisted reproductive technology (IUI, IVF)
    • Varicoceles
      • Treatment
        • Surgical: retroperitoneal, inguinal, or subinguinal ligation of the internal spermatic and collateral veins. Laparoscopy has also been used and may have a role in bilateral varicocele repair
        • Transvenous angiographic identification and embolization of the involved internal spermatic veins
  • Isolated Abnormal Parameter on Semen Analysis
    • Abnormal semen volume
      • Large ejaculate volume
        • < 5.5 mL may result in dilution of the spermatozoa and poor cervical placement of seminal fluid during intercourse
        • Mechanical concentration of the spermatozoa and artificial insemination may be employed
      • Absent or low ejaculate volume
        • Retrograde ejaculation, infection of the accessory sex glands, or endocrine dysfunction (low testosterone)

        Treatment
        • Sympathomimetic drugs with a-adrenergic activity
        • May be necessary to obtain, wash, and inseminate sperm collected from the postejaculate urine sample
        • Endocrine abnormalities and infections treated with hormones and antibiotics
    • Hyperviscosity
      • A check of the split ejaculate
      • Mechanical disruption of the sample to decrease viscosity, followed by artificial insemination
    • Decreased motility and forward progression (asthenospermia)
      • Therapy is available for endocrine dysfunction, infection of accessory glands, a varicocele dysfunction
      • Epididymal dysfunction at the present time is poorly understood and treated
      • Determine the presence and levels of antisperm antibodies in the semen
      • Several therapeutic modalities have been tried including sperm washing and short-term treatment with systemic steroids
    • Oligospermia
      • With sperm densities below 10 X 106/mL, a karyotype analysis and specific deletions in the Y chromosome should be evaluated
        Treatment
      • Stimulate the testes with a variety of drugs to increase the output of spermatozoa
      • Spermatozoa can be concentrated for use with artificial insemination with IUI
      • IVF and ICSI are very powerful methods to produce pregnancies when simpler approaches fail and may be necessary in cases where the above methods fail
    • Abnormal morphology
      • May be a transient abnormality that is self-correcting. There is no known method of treatment

References

  • Bonduelle M, Wilikens A, Buysse A, et al: Prospective follow-up study of 877 children born after intracytoplasmic sperm injection (ICSI), with ejaculated epididymal and testicular spermatozoa and after replacement of cryopreserved embryos obtained after ICSI. Hum Reprod (suppl) 4:131-155; discussion 156-159, 1996.
  • Mulhall 7P, Reijo R, Alagappan R, et al: Azoospermic men with deletion of the DAZ gene cluster are capable of completing spermatogenesis: Fertilization, normal embryonic development and pregnancy occur when retrieved testicular spermatozoa are used for intracytoplasmic sperm injection. Hum Reprod, 12:503-508, 1997.
  • Parinaud J, Le Lannou D, Vieitez G, Griveau JF, Milhet P, Richoilley G: Enhancement of motility by treating spermatozoa with an antioxidant solution (Sperm-Fit) following ejaculation. Hum Reprod 12:2434-2436, 1997.
  • Reijo R, Alagappan RK, Patrizio P, Page DC: Severe oligospermia resulting from deletions of azoospermia factor gene on Y chromosome. Lancet 347:1290-1293,1996.
  • Rolf C, Cooper TG, Yeung CH, Nieschlag E: Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with highdose vitamin C and vitamin E: A randomized, placebo-controlled, doubleblind study. Hum Reprod 14:1028-1033, 1999.
  • Schlegel PN, Chang TSK: Physiology of male reproduction. In: Walsh PC, Retik A, Vaughan ED Jr., Wein A, eds. Campbell's Urology, 7th ed. Philadelphia, Saunders, 1998, pp 1254-1286.
  • Sigman M, Howards SS: Male infertility. In: Walsh PC, Retik A, Vaughan ED Jr., Wein A, eds. Campbell's Urology, 7th ed. Philadelphia, Saunders, 1998, pp 1287-1330.
  • Sigman M, Jarow JP: Endocrine evaluation of infertile men. Urology 50:659-664, 1997.