Male infertility evaluation

If a couple is unable to conceive a child after one year of unprotected intercourse, they are considered infertile.

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In man, sperm are produced in the testicles. They then travel from the testicle to the epididymis; a small half moon shaped organ attached to each testicle. The epididymis is somewhat like a reservoir that allows sperm to mature while they move through it to the vas deferens. The vas deferens is a tube that carries the sperm to the prostate. Sperm is mixed with fluid from the seminal vesicles and the prostate to produce semen. This semen travels out of body by way of the urethra and penis.




Arbitrarily, we can classify male fertility causes as:


  • Pre-testicular (hypothalamus/pituitary) 1-2%
  • Testicular 30-40%
  • Post-testicular (obstruction) 10-20%
  • Nonclassifiable 40-50%







  • Kinefelter’s syndrome (XXY) and its variants (XXY/XY ; XXXY)
  • Cryptochidism
  • Myotonic dystrophy
  • Varicocele
  • Y chromosome deletions

Hypothalamic-pituitary disorders (GnRH;LH and FSH deficiency)



  • Congenital GnRH deficiency (Kalimann syndrome)
  • Hemochromatosis



  • Viral orchitis (mumps, echovirus, arbovirus)
  • Epididymo-orchitis (gnorrhea, Chlamydia)
  • Drugs (eg, alkylating agents, alcohol, marijuana, antiandrogens, ketoconazole, spironolactone, histamine receptor antagonists)
  • Environmental toxins (eg, dibromochioropropane, carbon disulfide, cadmium, lead, mercury, environmental estrogens and phytoestrogens)
  • Hyperthermia
  • Immunologic disorders, including polyglandular autoimmune disease
  • Trauma



  • Trauma, post-surgery, post-irradiation
  • Pituitary and hypothalamic (macro-adenoma, craniopharyngioma)
  • Hormonal (hyperprolactinemia, androgen excess, estrogen excess, cortisol excess)
  • Drugs (opioids and psychotropic drugs, GnRH agonist or antagonists)



  • Epididymal dysfunction (drugs, infection)
  • Abnormalities of the vas deferens
    (congenital absence, Young’s syndrome,
    infection, vasectomy)
  • Ejaculatory dysfunction
    (spinal cord disease, autonomic
    dysfunction,premature ejaculation)



The basic evaluation includes a complete and surgical history (questionnaire), a physical examination, at least two properly performed semen analyses and a hormonal evaluation if the clinical evaluation or semen analysis warrants. A scrotal ultrasound is used to provide accurate assessment of testicular volume and intra-testicular pathology. The clinical evaluation is designed to uncover the possible etiology (cause) of the male infertility, including pathologies such as varicocele (dilated testicular veins), reproductive tract obstruction, hormonal abnormality, infection, immunologic problem, genetic abnormality or idiopathic (unknown) cause. Additional tests may be necessary and include genetic testing, trans-rectal ultrasound and specialized sperm function tests (e.g. sperm DNA damage).


In the history taking we ask questions about the duration of infertility, wheter is a female factor that may contribute
to the infertility and whether previous treatments were used. As well, a sexual history including timing and mechanics of intercourse and use of lubricants is important. Questions regarding childhood and development are important to uncover a possible history of undescended testicle (cryptorchidism) and delayed pubertal development; both associated with male infertility. Knowing the past medical history (systemic illness or genital infections such as urethritis or prostatitis) and a surgical history (particularly abdominal, pelvic or scrotal surgery) is important.


The influence of environmental toxins on sperm production has been recognised. A history of exposure to cigarette smoking, radiation or chemicals and significant alcohol consumption is important. In particular smoking has been associated with reduced sperm density and decreased sperm function. As well, certain medications can have direct or indirect effects on hormonal balance and sperm production and therefore cause infertility.


Physical examination
The physical examination includes assessment of general body habitus (shape) and hair distribution.


An abdominal and genital exam is also performed. Examination of the scrotal contents reveals the size of the testicles, presence or absence of the normal ducts and presence or absence of varicocele (dilated testicular veins). Varicoceles are the most common identifiable causes of male subfertility. They are dilated internal spermatic veins. This condition is found in 40-50% of infertile men and 15% of the general population. Varicocele can lie corrected by surgical ligature of the dilated spermatic veins or by radiographic embolisation of these veins. Between 50-75% of treated patients can expect an improvement semen quality after surgery. Thus the spontaneous pregnancy rate is improved and possibility some patients can use insemination intra uterine(counts > 5×10ª/l ) instead of IVF/ICSI procedure.


Semen analysis (w.h.o. 2000)
The man provides a semen specimen by ejaculation. This could be provided by either masturbation (semen into a jar) or intercourse with a special condom (a semen collection device). The semen is examined rapidly (30-60min) for the volume of the semen, the number of sperm seen (concentration – sometimes referred to as “count”), the percentage of sperm moving (% motility) and the number of normal-appearing sperm (% normal morphology).


With computer technology, we can also look at the speed the sperm are travelling and the pattern of sperm motion. (Fast:A / Slow:B / Stationary:C / No-motility:D) It must be remembered that there is a great variability day by day in man’s sperm quality, so we usually ask for at least 2 semen specimens (at least 1 month apart and after abstaining from intercourse for 2 to 3 days prior to each sample). Standardisation of the techniques and report of the semen analysis is an important aspect of good practice. The parameters suggested in the box are the most recent W.H.O. guidelines. Also a systematic dosage of IgG IgA antisperm antibodies is done


Also an abnormal sperm analysis can not be always equated with infertility but rather a diminished fertility potential. Finally a semen analysis does not assess sperm function. Specialized tests are under investigation to evaluate this factor (see DNA fragmentation).


Imaging studies; ultrasound

Further assessment of reproductive tract anatomy is possible with the aid of ultrasonography. A scrotal/testicular ultrasound is used for assessment of testicular volume and parenchyma, epididymal anatomy and presence or absence of varicoceles (dilated testicular veins – see figure 1). A scrotal ultrasound should be performed if the scrotal examination reveals a physical abnormality (e.g. testicular or epididymal mass, testicular atrophy). A trans-rectal ultrasound (TRUS) is primarily used to assess prostate anatomy. In infertile men, a TRUS is used to evaluate the seminal vesicles and ejaculatory ducts in order to determine whether there is a genital tract obstruction at this level.


A trans-rectal ultrasound should be performed if there is azoospermia (absence of sperm in semen) and a low semen volume.





t has been found that many cases of male infertility may be associated with a genetic defect (particularly, when the man
has very low sperm count or absence of sperm in the semen – azoospermia). One concern we have is that the genetic defect responsible for the man’s infertility may be transmitted to his child through assisted reproductive technologies
(e.g. in vitro fertilization – IVF). In many cases this only causes the same problem in the next generation (infertility in a male child), but some genetic defects may cause other diseases, miscarriage, or even early (neonatal) death. Please know that at present there are no specific treatments (for example gene therapy) for the genetic defects themselves.


Genetic disorders may be characterized as karyotype abnormalities deletion of specific area of the Y chromosome, specific mutations within genes or DNA strand breaks. Karyotype abnormalities are more common in infertile male (5.8%) than in a normal population (.5%). Sex chromosome abnormalities are more common (4.2%) than autosomal anomalies (1.5). Klinefelter syndrome (XXY) is the most common sex chromosome disorder associated with the male infertility (95% of anomalies) It is present in .002% newborn males, 11% azoospermic and .79% of men with oligospermia. Located on the long arm of the Y chromosome the azoospermic factor region (AZF) is required for normal spermatogenesis. Microdeletions on this region is the second most frequent genetic cause of infertility after Klinefelter’s syndrome.


These deletions are found in 4% of oligospermic males and 18% of non obstructive azoospermia


Current recommendations regarding genetic testing for infertile men are as follows: (1) A karyotype (chromosome) analysis and a Y-chromosome microdeletion analysis are recommended for men with severe oligospermia (<5 million sperm/mL of semen) or non-obstructive azoospermia (absence of sperm caused by testicular failure). (2) Cystic fibrosis mutation analysis is recommended for men with congenital absence of the vas deferens or those with idiopathic (unknown cause) obstructive azoospermia (absence of sperm caused by genital duct obstruction). Insertion figure 3




Sperm DNA integrity is increasingly recognized as being a valuable marker of male fertility potential. Sperm DNA damage
may predict the chances of a pregnancy both naturally (after intercourse) and with assisted reproduction (e.g. IVF or ICSI – intra-cytoplasmic sperm injection) (see Table 1). However, there is no consensus on the exact cut-off value of sperm DNA damage beyond which no pregnancy is possible and the optimal assay (test) of sperm DNA damage. (Tableau 1)


The assessment of sperm DNA damage may be useful in the following circumstances: :


  1. prior to ARTs to help predict pregnancy outcome,
  2. for couples with unexplained infertility,
  3. for couples with repeated ART failures and
  4. to assess response to male-directed therapy.


The assessment of sperm DNA damage may be useful in the following circumstances:

  1. varicocelectomy (varicocele repair),
  2. oral antioxidant therapy and
  3. oral anti-inflammatory therapy.