INFERTILITY
Infertility is the inability of a sexually active, non-contracepting couple to
achieve pregnancy in one year (WHO).
Prognostic factors
The main factors influencing the prognosis in infertility are:
" Duration of infertility (< 4 yr)
" Primary or secondary infertility
" Age and fertility status of the female partner (< 35 yr)
" Results of semen analysis
standard values for semen analysis according to the 1999 WHO criteria
> 2.0 ml
Volume
pH 7.2
Sperm concentration > 20 million/ml
Total no. of spermatozoa > 40 million/ejaculate
Motility 25% type a or
50% type a+b within 60 min after ejaculation
Morphology 14% of normal shape and form*
Viability > 50% of spermatozoa
Leukocytes < 1 million/ml
* Assessment according to Kruger and Menkfeld criteria.
** MAR = Mixed antiglobulin reaction.
History:
" duration of infertility, coital frequency, sexual dysfunction
" previous fertility
" results of any pervious evaluation and treatment for infertility
" previous surgery of the testes, genital trauma
" systemic medical illnesses, current medications
" childhood illnesses and developmental history
" family history of birth defects, mental retardaton, cystis fibrosis
" exposure to environmental gonadotoxins (heat, radiation, chemoth, fever)
" occupations and use of tobacco, alcohol, drugs
Physical examination
" examination of penis to include the location of the urethral meatus
" palpation of the testes and measurement of their size (normal 12  20 ml )
" the presence and consistency of both the vasa and epidydymides
" secondary sex characteristics (body habitus, hair distribution, gynecomastia)
" DRE
" additional: ultrasound examination, testicular biopsy, vesiculovasography
Causes of male infertility
1. ABNORMALITIES OF SPERM PRODUCTION
(hypospermatogenesis, spermatogenetic arrest, Sertolii cell only syndrome, tubular damage)
Øð primary testicular failure  FSH elevation
o Sex chromosome abnormalities (Klinefelter s syndrome and variants)
o Autosomal abnormalities
o X-linked genetic disorders and male fertility
o Kallmann s syndrome - X-linked recessive mutation in the KALIG-1 gene on Xp 22.3. Rarer forms
syndrome include an autosomal-dominant form. Clinical features: hypogonadotrophic hypogonadism,
other: including anosmia, facial asymmetry, cleft palate, colour blindness, deafness, maldescended
testes and renal abnormalities
o Androgen insensitivity: Reifenstein s syndrome - defect in the androgen receptor gene located on
Xq 11-12. The phenotype varies widely, from complete testicular feminization to an apparently normal
man with infertility, although the latter is rare
o Other X-disorders - spermatogenetic arrest and submicroscopic interstitial deletion on the Xp
pseudoautosomal region
o Y microdeletions - AZF a-b-c (spermatogenetic arrest, sertoli cell only syndrome, hypospermatogenesis)
cryptorchidism
infections
gonadotoxins
o environmental exposures to pesticides, herbicides, organic solvent (tyre), heavy metals (lead,
cadmium, carbon disulfide CS2)
o heat, radiation
o malnutrition (Zn, Mg, vit A, E, C deficiency)
o smoking, heavy use of marijuana, cocaine alcohol
Reproductive toxicity
- limited human data, usually retrospective epidemi ological analysis
- experimental data in animals
Targets for toxicity
1.pre-testicular: exposure to estrogen mimicking compounds (chemical industry, food, water pollution)
mechanisms: FSH, LH inhibition, reduction in Sertoli cell proliferation, fall daily sperm production
2. testicular
" EDS dimethane sulphonate - Leydig cell damage,
" phtalates, nitroaromatic compounds, gamma diketones used as solvents - direct toxicity to
Sertoli cells  difficult to identifications (vacuolisation, loss if tubular fluid)
3. post-testicular very rare
" gossypol - epididymal fluid secretion
" ornidazole  loss of motility
Treatment of primary spermatogenic failure:
TESE (testicular sperm extraction) + ICSI
after a karyotype and Yq deletions screening
TESE techniques:
fine-needle aspiration enables more areas of the testis to be reached
open testicular biopsy allows more tissue and sperm to be retrieved.
TESE is always performed in both testes.
The fragments of testicular tissue are immediately placed in a Petri dish containing 2 ml of
culture medium and transferred to the in-vitro fertilization (IVF) laboratory.
2. OBSTRUCTION OF THE DUCTAL SYSTEM
Øð Intratesticular obstruction - 15%
" congenital forms  disjunction between rete testis and efferent ductules (rare)
" acquired forms, i.e. post-inflammatory or posttraumatic obstructions
Øð Epididymal obstruction - 30-67%
" CBAVD - 82% -Congenital bilateral absence of the vas deferens (CBAVD) is associated with CFTR
mutations (semen volume < 1.5 ml, pH < 7.0).
" Inborn forms chronic sinopulmonary infections (Young s syndrome) - mechanical blockage due
to debris within the proximal epididymal lumen.
" acquired - acute (gonococcal) and subclinical (chlamydial) epididymitis, after surgery
(epididymal cyst removal)
Øð Vas deferens obstruction - following vasectomy, herniotomy, CBAVD
Øð Ejaculatory duct obstruction - 1-3%
" Müllerian duct cyst or ejaculatory duct cysts are medially located in the prostate and ejaculatory
ducts are laterally displaced and compressed by the cyst or one or both ejaculatory ducts empty
into the cyst.
CFTR gene is located on the short arm of chromosome 7, encodes a membrane protein that functions as an ion channel
and also influences the formation of the ejaculatory duct, seminal vesicle, vas deferens and distal two-thirds of the
epididymis. CFTR mutation may resulted cystic fibrosis and/or CBAVD.
OBSTRUCTIVE AZOOSPERMIA - TREATMENT
1. Intratesticular obstruction  TESE
2. Epididymal obstruction
" CBAVD - microsurgical epididymal sperm aspiration (MESA)
" azoospermia due to acquired epididymal obstruction, end-to-end or end-to-side
microsurgical epididymovasostomy is recommended
3. Vas deferens obstruction  microsurgical vasovasostomy or vasoepididymostomy, or
TESA/MESA + ICSI.
4. Ejaculatory duct obstruction 
" transurethral resection of the ejaculatory ducts  TURED. Resection may remove part
of the verumontanum.
" incision or unroofing of the cyst in cases of obstruction due to a midline intraprostatic
cyst. Complications following TURED include retrograde ejaculation due to bladder
neck injury, reflux of urine into ducts, seminal vesicles and vasa.
" MESA, TESE, proximal vas deferens sperm aspiration, seminal vesicle aspiration and
direct ultrasonically-guided cyst aspiration
3. ABNORMALITIES OF SPERM FUNCTION
" abnormal motility
" failure of acrosome reaction
genital tract inflammation
varicocele
biochemical abnormalities (oxygen species)
MALE ACCESSORY GLAND INFECTION
Urethritis
Infectious - most commonly by Chlamydia trachomatis, Ureaplasma urealyticum and Neisseria
gonorrhoeae.
Non-infectious causes of urethritis include irritations due to allergic reactions, trauma and
manipulations.
Symptoms: urethral discharge and bladder voiding difficulties, urethral strictures and ejaculatory
disturbances
Treatment: one single dose of a fluoroquinolone, followed by a 2-week regimen of doxycycline.
Treatment is effective both for gonococcal and (co-existing) chlamydial/ureaplasmal infections.
Prostatitis
I Acute bacterial prostatitis (ABP) Acute infection of the prostate gland
II Chronic bacterial prostatitis (CBP) Recurrent infection of the prostate
III Chronic abacterial prostatitis/chronic pelvic pain syndrome (CPPS)
No demonstrable infection
IIIA Inflammatory chronic pelvic
White cells in semen, expressed prostatic pain syndrome
secretions or post-prostatic massage urine
IIIB Non-inflammatory chronic pelvic
No white cells in semen, expressed prostatic pain syndrome
secretions or post-prostatic massage urine
IV Asymptomatic inflammatory prostatitis
No subjective symptoms
Inflammation detected either by prostate biopsy or the presence of white cells in expressed
prostatic secretions or semen during evaluation for other disorders
Orchitis
Symptoms: pain and swelling
Orchitis is resulting in:
tubular sclerosis,
chronic inflammatory disrupt the normal spermatogenesis (spermatogenetic arrest),
testicle atrophy may occurs
Acute bacterial epididymo-orchitis
" N. gonorrhoeae
Tetracyclines
" C. trachomatis
Tetracyclines
" E. coli, Enterobacteriaceae
Fluoroquinolones, Amnoglicosides
Mumps orchitis Interferon alpha-2b
Granulomatous (idiopathic) orchitis Semicastration
Specific orchitis According to therapy of underlying diseases
Epididymitis
Symptoms: pain and swelling, which is almost unilateral. In many cases, the testicle is involved in
the inflammatory process known as epididymo-orchitis.
men younger than 35 years: C. trachomatis or N. gonorrhoeae. Sexually transmitted epididymitis is usually
accompanied by urethritis.
men over 35 years: non-sexually transmitted epididymitis is associated with UTI, after urinary tract instrumentation
or surgery, and those who have anatomical abnormalities.
Altered motility
1. Genetic causes
" syndrome 9+0  deletion of central tubules
" immotile cilia syndrome  general absence or reduced
ciliar movements (Kartagener syndrome, accompanied by
a situs inversus and bronchiectasies)
2. Abnormal sperm maturation within epididymis
3. Abnormal semen plasma composition
" inflammation of prostate and seminal vesicles