Evaluation of male infertility k.priyatham

Evaluation of Male Infertility
K.Priyatham

Definition
• Failure to conceive after one year of regular unprotected sexual
intercourse.
• Primary infertility refers for couple who have had no previous
pregnancy
• Secondary infertility refers for couple who have conceived previously;
although pregnancy may not have been successful (e.g. miscarriage,
ectopic pregnancy).

• Affects 15% of reproductive couples
• 6.1 million couples
• Men aged 25 to 34 years had higher usage with an average rate of
126 per 1,00,000 compared with men aged 35 to 44 with 83 per
1,00,000 and those aged 45 and older at 20 per 1,00,000
(Meacham et al, 2007)
• Younger men represent over half of male infertility cases, and nearly
one in 11 cases occurs in men in the fifth decade and older
• Total expenditures for treating primary male infertility at 17 million
U.S. dollars (USD) in the year 2000
• Because a significant amount of male reproductive medical care
delivery involves assisted technologies for the female partner,
accounting for this care the assessed total cost is a sizable 18 billion
USD

Chances of spontaneous conception
• 20% to 25% per
month
• 75% by 6 months
• 90% by 1 year
• Fertility rates are at
their peak in men
and women at age
24.

Etiology of Male Infertility
 Varicocele (35-40%)
 Idiopathic (25%)
 Infection (~10%)
 Genetic (~10%)
 Endocrine (<5%)
 Immunologic (<5%)
 Obstruction (<5%)
 Cryptorchidism (<5%)
Greenberg et al, J Urology 1978

Causes of male infertility
1. Pre-testicular
2. Testicular
3. Post-testicular
4. idiopathic

Pretesticular causes of infertility

Testicular causes of infertility

Medications associated with infertility
• Ketoconazole, spironolactone, alcohol inhibit T synthesis
• Cimetidine: androgen antagonist
• Marijuana, heroin, methadone: lower T levels
• Pesticides, estrogen like activity
• Chemotherapy
• Calcium channel blockers; sulfasalazine; colchicine;
allopurinol; alpha-blockers; nitrofurantoin; antipsychotics;
antidepressants

Posttesticular causes of infertility

Evaluation of male infertility k.priyatham

When to start evaluation
• Infertility is not considered to exist until after 12 months
of attempted conception.
• Evaluation should be done before one year if
• male infertility risk factors such as a history of bilateral
cryptorchidism are known to be present;
• female infertility risk factors, including advanced
female age (over 35 years), are suspected; or
• the couple questions the male partner's fertility
potential

Whom to evaluate
• Only male factor – 1/3rd cases
• Only female factor – 1/3rd cases
• Both partners – 1/3rd cases
• Both male and female partners should be evaluated

Evaluation of Male for Infertility

• The goals of the optimal evaluation of the infertile male are to
identify:
1. Potentially correctable conditions;
2. Irreversible conditions that are amenable to assisted reproductive
techniques using the sperm of the male partner;
3. Irreversible conditions that are not amenable to the above, and for
which donor insemination or adoption are possible options;
4. Life- or health-threatening conditions that may underlie the
infertility and require medical attention; and
5. Genetic abnormalities that may affect the health of offspring if
assisted reproductive techniques are to be employed.

Male Infertility: Evaluation
 Basic Evaluation:
 History (Questionnaire)
 Physical examination
 Standard semen analysis
 Hormonal evaluation
 Optional Additional Evaluation:
 Genetic counseling and evaluation
 Specialized sperm function tests
 Imaging studies
 Testis biopsy

History
• The timing of sexual intercourse:
• sperm remain viable within the cervical mucus for 48 hours or longer.
• conception may occur when sexual relations take place up to 5 days before
ovulation
• owing to the short life span of oocytes, conception will not occur if sexual
relations are performed the day after ovulation.
• Most experts advise vaginal intercourse every 2 days near the time of
ovulation.

Sexual history
• Duration of sexual relations with and without birth control
• Methods of birth control
• Sexual technique: potency, use of lubricants (some are spermicidal)
• Frequency, timing of coitus, erection, ejaculation
• STD

Past history (Developmental)
• History of cryptorchidism
• Age at puberty
• Gynecomastia
• Congenital abnormalities of urinary tract or central nervous system
• Childhood illness & developmental history
• School performance - determine if he has a history of learning
disabilities suggestive of Klinefelter's syndrome

Past surgical history
• Orchidopexy
• Pelvic, scrotal, inguinal, or retroperitoneal surgery
• Herniorrhaphy
• Sympathectomy
• Vasectomy
• Scrotal trauma
• Spinal cord injury
• Testicular torsion

Past medical history
• Urinary infections
• Sexually transmitted diseases
• Viral orchitis
• Renal disease
• Diabetes
• Radiotherapy
• Recent febrile illness
• Epididymitis
• Tuberculosis or other chronic diseases
• Anosmia
• Midline defects (cleft palate)

Family history
• Hypogonadism
• Cryptorchidism
• Congenital midline defects
• Cystic fibrosis

• Occupation and Habits
• Exposure to chemicals and heat, hot baths, steam baths, radiation,
cigarettes, alcohol, illicit drugs, and anabolic steroids
• Past Reproductive History (including pregnancies and offspring with
other partners)
• Previous Infertility Evaluation and Treatment

Physical Examination
 General
 Female facial characteristics should alert the examining
physician to potential sex chromosomal and androgenization
disorders
 increased body fat and decreased muscle mass:
 androgen deficiency antedating puberty.
 current androgen deficiency.

 Skin -
 Loss of pubic, axillary, and facial hair,
 decreased oiliness of the skin, and
 fine facial wrinkling: long-standing androgen deficiency.
 Breasts -
 Gynecomastia suggests a decreased androgen to
estrogen ratio.

 CNS
 visual fields (r/o pituitary adenoma)
 sense of smell (Kallmann’s Syndrome - HypoHypo)
 Abdomen/Pelvis
 Surgical scars

Genital
• Scrotum:
• One or both sides may be hypoplastic, indicating
an absence of the scrotal contents since birth
(Niederberger, 2011).
• One side may be substantially larger than the
other, suggesting a reactive hydrocele or tumor.
• A varicocele may be so large as to be visible.

Testis:
-position (cryptorchid?)
-volume (normal ~15-25ml)*
-firmness (normal = firm)
*Note: Normally, >70% of testis
volume is from germ cells alone.
Therefore, a soft and/or small testis
is indicative of abnormal
spermatogenesis.

• The size of the testis
may be assessed by
calipers often
referred to as the
Seager orchidometer
• The long axis of the
testis is gently
grasped between the
jaws of the calipers,
and a measurement
of 4.6 cm or less is
associated with
spermatogenic
impairment

• A second method to ascertain
testis size is to compare the
examiner’s palpation findings
with a string of ellipsoids of
increasing size with marked
volumes
• A volume of 20 mL or less is
considered low

Testis:
-Seminiferous tubules
Germ cells
Sertoli cells
-Interstitium
Leydig cells
macrophages, endothelial cells
Spermatogenesis
~64 days in humans (epididymal transit ~15
days)
Clinical correlate: Need to wait 3 months
after any intervention (medical or surgical) to
see a change in semen quality

Epididymis:
-The epididymis is typically difficult to appreciate; if
it is easily palpated, it is likely engorged, which
suggests obstruction.
Segmentation of the epididymis is also worthwhile
to note:
If the portion near the upper pole is easy to discern
but the lower pole is not, wolffian ductal
development may have been incomplete

Spermatic cord:
• Palpation of the spermatic cord yields two features of reproductive
significance: whether the vas deferens is palpable, and whether a
varicocele is present.
• The vas is a firm cordlike structure differentiated from vasculature
within the spermatic cord by the compressibility of the vessels.
• Because the vein within the cord may be mistaken for the vas on
manual examination of the upper scrotum, absence of the vas can be
a difficult physical sign to identify.

Vas deferens:
-congenital absence of vas (CAVD)
Cystic fibrosis mutations – B/L absence mostly
suggestive
Woolfian duct anomalies – unilateral absence may
be associated with renal agenesis

• The modern evidence-based clinical grading system for varicocele
includes :
• grade I, which is not palpable or visible and can only be detected by
radiographic evaluation such as Doppler ultrasound;
• grade II, which is palpable but not visible; and
• grade III, a varicocele that is so large as to be visible by the
examining physician through the rugae of the scrotum

Penis:
 length (normal development) , micro-penis
 position of urethral meatus (deposition of semen), evidence
of hypospadias
 Phimosis
 Significant penile curvature

Examining the Prostate and Seminal Vesicles
 Prostate :
 size
 firmness
 tenderness
 presence of cysts (ejaculatory duct)

• IT Does not add a significant amount of information to the evaluation
of the infertile male, and if the patient is sufficiently apprehensive
about digital rectal examination, it may be prudently omitted.
• The seminal vesicles cannot typically be palpated; if they are
palpable, it is an abnormal finding suggesting engorgement and
possible ejaculatory ductal obstruction (Niederberger, 2011).

Basic laboratory evaluation
• All patients should have at least two or three semen analyses
• For comparison maintain consistency in the duration of sexual
abstinence
• Increases in sperm concentration of 25% per day of abstinence for
the first 4 days have been reported.
• Clean, wide-mouthed containers should be used for specimen
collection

• The specimen may be collected at lab or at home
• If collected at home it should be brought to lab by placing the
container in a shirt pocket next to the body to keep it warm during
transit.
• The specimen should be examined in the laboratory within 1 to 2
hours of collection
• Occasionally when parameters differ markedly in the initial two
semen specimens collected over weeks, additional specimens,
collected over a 2- to 3-month period, may be obtained.

Physical characteristics of semen
• Freshly ejaculated semen is a coagulum
• that liquefies over a 5- to 25-minute period.
• Cowper's glands account for 0.1 to 0.2 mL
• Prostatic secretions account for 0.5 mL
• Seminal vesicles account for 1.5 to 2.0 mL.
• Semen in patients with CBAVD or SV hypoplasia does not coagulate,
is acidic, and has a low volume.

Sperm parameters
• Count
• Motility
• Morphology
• Viability
• Volume
• Morphology
• Leukocytes

Rigid criteria for normal morphology
• Head; 5-6um length and 2.5-3.5 um
width.
• Acrosome is 40-70% of head.
• Midpeice; Width <= 1um and length
is 1.5 times head length.
• Tail; 45 um long, uniform, thinner
than midpiece, uncoiled, free from
kinks.
• Cytoplasmic droplets; in midpiece
only and less than one half of head
area.

Computer-assisted sperm analysis (CASA)
• provides data on
• sperm density,
• motility,
• Straightline and curvilinear velocity,
• average path velocity,
• amplitude of lateral head displacement,
• flagellar beat frequency,
• hyperactivation.
• requires expensive equipment and active participation of a
technician.

Semen Analysis: Critical Review
 Guzick et al, NEJM 2001
Evaluated 765 infertile men and 696 fertile controls to
determine semen parameter thresholds that best
discriminate between fertile and infertile men.
 Infertile couples
– part of a randomized Assisted Reproduction trial.
– female partners had a normal, complete evaluation (poorly
controlled in prior studies).
 Fertile controls
– recruited from prenatal classes.
– wives were pregnant or had delivered in the previous 2
yrs

 Guzick et al, NEJM 2001
Methods:
2 semen samples were collected from each patient.
Technicians from the 9 centers were trained at a central site.
Stained sperm smears were sent to a central site for
strict morphology assessment (by a single technician).

Guzick et al, NEJM 2001
 Results:
 Considerable overlap between sperm measurements
from fertile and infertile men noted
 The odds of infertility increased with an increasing
number of abnormal sperm measurements.
 % normal morphology has the greatest (albeit
poor) discriminatory power

SEMINAL FRUCTOSE AND
POSTEJACULATE URINALYSIS
• Seminal fructose testing is indicated in men with low ejaculate volumes
and no sperm.
• Absent –
• seminal vesicle agenesis
• Ductal obstruction
• CBAVD
• Postejaculate urinalysis
• The presence of sperm in the urine → retrograde ejaculation.
• Indicated in
• diabetic patients with low semen volume and sperm counts;
• patients with a history of pelvic, bladder, or retroperitoneal
• surgery;
• patients receiving medical therapy for prostatic enlargement.

Sperm-Mucus Interaction (Postcoital Test)
• Penetrability of the spermatozoa through the cervical mucus can be
detected
• Postcoital test (PCT).
• ? cervical environment is cause of infertility.
• Timing of the test: conducted when the cervical mucus is thin and
clear just before ovulation.
• cervical mucus is examined 2 to 8 hours after normal intercourse.
• motile sperm ˃ 10–20/HPF → normal.
• Abnormal PCT- causes
• Persistently abnormal PCT→ advised to undergo IUI

Antisperm Antibodies (ASAs)
5-10% of male infertility attributed to ASAs
causative factor in male infertility
association with motility
association with sperm-egg binding

Antisperm Antibodies: Etiology & Incidence
In women:
Incidence: 9% of infertile vs 4% of fertile women
Etiology: chronic exposure to sperm antigens?
In men:
Incidence: 10% of infertile vs 3% of fertile men
Etiology: injury to blood-testis barrier?
Obstruction (post-vasectomy reversal)
Infection (orchitis)
Trauma/Torsion
Varicocele/cryptorchidism

Antisperm Antibodies: Types
•Sperm agglutinating
•Sperm immobilising
•Spermotoxic

Antisperm Antibodies: Testing
Indications: ↓ motility, sperm agglutination
Available tests:
 Direct: (detects sperm-bound immunoglobulins)
 immunobead or MAR (mixed antiglobulin reaction)
 Indirect: (biologic activity of circulating ASA)
 ELISA, MAR
 Others (flow cytometry, radio-labeled)
Direct (on sperm) is more valid than indirect (serum, mucus, seminal
plasma) ASA test.
Therefore, must be cautious about studies reporting indirect ASA test
results.

Hypo-Osmotic Swelling Test (HOST)
• Jeyendran et al.1984,
• The Hypo-osmotic Swelling
Test is a semi-quantitative test
based on the semi-
permeability of the intact cell
membrane, which causes
spermatozoa to “swell” under
hypo-osmotic conditions,
when an influx of water results
in an expansion of cell volume
• Principle: that ‘viable’ sperm
have functionally intact plasma
membrane
• Poor viability predicts poor IVF
success
• May use to select ‘viable’
testicular (often immotile)
sperm

Hormone evaluation
• Less than 3% of infertile men have a
primary hormonal etiology.
• Most common is elevated serum
FSH.
• Indications: sperm density less than
10 million/mL, clues from
history/exam.
• Measure T, FSH
• If abnormal, repeat with T, LH,
Prolactin.

• If prolactin is raised-- MRI Brain
• Most prolactin-secreting tumors in men are macroadenomas (>1 cm)
with Prolactin levels >50 ng/mL, and low LH, FSH, T.
• Mild elevations of prolactin (<50 ng/mL) are more frequently discovered
in infertile patients, and their clinical significance is questionable.
• An elevated serum FSH is indicative of a significant problem with
spermatogenesis whereas a normal serum FSH does not guarantee intact
spermatogenesis.

• Complete testicular failure:
• elevated gonadotropin levels
• normal or low T levels.
• Pituitary dysfunction:
• low serum gonadotropin
• Low T levels
• (hypogonadotropic hypogonadism).

• Given the negative feedback on FSH, a “high” FSH
can be indicative of testicular failure.
• What is “normal”? as 1.4-18.1
• Wide range
• Nearly all male patients have “normal” FSH.

• FSH level > 4.5 miU/ml (normal range 1.4-18.1
mIU/ml ) showed statistically significant
associations with abnormal sperm motility,
concentration, and morphology (p<0.0001).
o Semen parameters were more likely to be abnormal
with decreasing testosterone/FSH ratios.
• Redefining normal FSH in infertile men would be
valuable.
(O’Brien et al, AUA Chicago 2009)

IMAGING IN THE EVALUATION OF MALE
INFERTILITY
• Radiographic or ultrasonographic imaging is infrequently needed in
the diagnosis of male reproductive dysfunction and should be
ordered cautiously.
• Likely benign conditions such as testicular microlithiasis may be
detected, resulting in patient distress and often unnecessary
additional testing.

Transrectal Ultrasonography
• Used to examine patients suspected to have ejaculatory duct
obstruction.
• Careful examination may identify midline prostatic cysts such as
müllerian or wolffian duct cysts or stones obstructing the ejaculatory
duct
• Seminal vesicle aspiration – 3 or more sperm per HPF in the seminal
vesicle aspirate → EDO
• Seminovesiculography

Scrotal Ultrasonography
•Varicoceles
•Epididymitis
•Epididymal cysts
•spermatoceles
•Testicular tumors

Color Doppler image
revealing typical venous
reflux with Valsalva
maneuver
Dilated veins in spermatic
cord

Abdominal Ultrasonography
• To rule out associated renal anomalies in patients with vasal
agenesis.
• Up to 20% of men with CFTR mutation-negative vasal agenesis will
have ipsilateral renal anomalies

Vasography
• Gold standard test for assessing the patency of the male ductal system.
• Indicated for determination of the site of obstruction in the azoospermic patient
with confirmed normal spermatogenesis on testis biopsy.
• It is currently rarely performed because image modalities such as TRUS and
magnetic resonance imaging (MRI) have superseded it;

Normal vasogram with clearly
defined VD, SV, ED and
contrast spilling into bladder.
Antegrade injection of contrast
into proximal VD

• It is invasive and may result in scar tissue formation in the vasal
lumen and obstruction; and injection of saline into the vasal lumen
during intended vassal reconstructive procedures with the manual
feedback of whether fluid flows easily or backflow occurs offers
similar information
• Fluid, contrast or otherwise, should never be injected into the vasal
lumen in the direction of the epididymis because it will rupture the
delicate epididymal tubules

Transrectal Imaging
• The diagnosis of ejaculatory
ductal obstruction is considered
when azoospermia in
conjunction with low seminal
volume is encountered
• TRUS imaging evidence of
ejaculatory duct obstruction
includes an anteroposterior
seminal vesicle diameter of
greater than 1.5 cm with or
without a midline prostatic cyst

Other assessments
• These other assessments include radiographic imaging after injection
of contrast directly into the seminal vesicles, or vesiculography;
• aspiration of the seminal vesicles to determine whether sperm is
present;
• and injection of diluted indigo carmine or methylene blue dye into
the seminal vesicles and
• observation by cystoscopy of whether the colored dye flows from the
ductal orifices at the verumontanum, a technique referred to as
chromotubation.

• In a small series, vesiculography and chromotubation were more
accurate than TRUS by a margin of 25% (Purohit et al, 2004).
• However, these techniques are more invasive and expensive, and an
incremental improvement in diagnostic accuracy compared with
TRUS if conclusively demonstrated in larger studies may not justify
the additional risk and cost

Cranial Imaging
• Cranial MRI allows assessment
of whether hyperprolactinemia
is associated with an anatomic
pituitary lesion (Niederberger,
2011).
• MRI may distinguish between
microadenomas and
macroadenomas and may assist
in judging whether medical or
surgical therapy is indicated
(Johnsen et al, 1991).
• Figure demonstrates a cranial
MRI revealing a large pituitary
macroadenoma.

Genetic Evaluation
Karyotype analysis
Abnormal karyotype in ~3-5% of infertile men
Klinefelter’s (47 XXY): most common
Y- chromosome micro-deletions
7-10% of infertile men vs. ~2% of fertile men
Cystic Fibrosis (CF) gene mutations
Carrier frequency;
~80% in CBAVD vs. ~30% of infertile vs. ~4% fertile men
Pryor et al, 1997, Oates et al, 1992, Mak & Jarvi, 1997
Genetic evaluation is recommended in all infertile men with severe
semen parameters in order to assess and prevent possible iatrogenic transmission of
genetic mutations

• •Gene regions (AZF a, b, c) on the
long arm of Y chromosome are
deleted.
• 6-8% of oligospermic men
• 13-15% of azoospermic men
• No health issues besides infertility
• Are passed to offspring with ICSI
• Other treatments unlikely to help in
presence of Y deletions
• If AZFa or b deleted, predicts no
sperm in ejaculate or testis.

Sperm DNA Integrity
Why examine sperm DNA integrity?
 A need for better markers of male fertility potential
 Advances in ART (IVF/ICSI) have led us to be more
concerned about sperm DNA integrity
- because we have removed the natural barriers
to fertilization
- Reports indicate increased birth defects with IVF/ICSI
- To understand the causes of IVF/ICSI failures
 To better understand the basic biology of sperm function

DNA, fertilization, and pregnancy
 High levels of sperm DNA damage probably do not affect
fertilization or early embryo development
 May have an effect on pregnancy rates with advanced
reproductive technologies (IVF and IVF/ICSI) and recurrent
pregnancy loss with spontaneous conception
Fertilization Pregnancy
Sperm DNA damage
(Lopes, 1998; Host, 2000; Tomlinson, 2001, Tomsu, 2002; Benchaib, 2003; Carrell, 2003)

2 cell embryo 4 cell embryo 8 cell embryo
blastocyst
2 pronuclei, fertilization
Sperm DNA
integrity
important here –
embryonic
genome expressed

Potential causes of DNA fragmentation
 Varicoceles (Saleh, 2003; Fischer, 2003; Zini, 2000)
 Chemotherapy and radiation (Chatterjee, 2000; Deane,
2004; Kobayashi, 2001)
 Cigarette smoking (Mak, 2000; Kunzle, 2003; Potts, 1999, Sun,
1993)
 Reactive oxygen species and
leukocytospermia (de Laminrande, 1993; Zini, 1995, Twigg,
1998; Iwasaki, 1992; Zini, 1993)
 Apoptosis (Baccetti, 1996; Sakkas, 2003)
 Protamine deficiency (Cho, 2003)

Human Sperm DNA Damage: Etiology
 Intra-Testicular Causes
Protamine (P1,P2) deficiency is an important cause of sperm DNA damage
(found in ~5% of infertile men) and mutations in the protamine
gene cluster have been described.
De Yebra et al, J Biol Chem 1993
Bianchi et al, Biol Reprod 1993
Kramer et al, Genet Test 1997
Topoisomerase II and transition protein abnormalities may be
a cause of sperm DNA damage (required for repair of induced DNA breaks
during super-coiling)
Balhorn, J Cell Biol 1982
Kierzenbaum, Mol Reprod Dev 2001
Bissoneault, FEBS Lett 2002
 Cellular apoptosis
Sakkas et al, Exp Cell Res 1999

Human Sperm DNA Damage: Etiology
Post-Testicular or External Causes
 Febrile Illness may be a cause of sperm DNA damage
Evenson et al, J Androl 2000
 Semen oxidants (or reactive oxygen species - ROS)
can induce sperm DNA damage
-ROS cause sperm DNA oxidation and fragmentation in
vitro
Aitken et al, Biol Reprod 1998
Irvine et al, J Androl 2000
-Residual sperm cytoplasm (a cytologic feature associated
with ROS production) correlates with sperm DNA damage
Fischer et al, Urology 2003

Sperm Aneuploidy Test
• The sperm aneuploidy test is a genetic test that determines if a male
parent has an increased chance of carrying chromosomal
abnormalities in his sperm.
• The sperm aneuploidy tests analyzes 5 chromosomes: 13, 18, 21, X
and Y.
• This test can provide an indication of the chances of abnormal
genetic development in the sperm.

Classification of infertility based on semen
analysis criterias
• Low volume ejaculate
• Azoospermia
• Oligoasthenospermia
• Normal but infertile
• Asthenospermia

Low volume ejaculate
• Drugs
• Retroperitoneal or bladder neck surgery
• Ejaculatory duct obstruction, CBAVD
• Diabetes mellitus
• Spinal cord injury
• Androgen deficiency
• Psychologic disturbances
• Idiopathic
• Incomplete collection
• Partial EDO is an investigative diagnosis at this time. Cases of true
partial EDO are extremely rare.

Azoospermia
• Hypogonadotropic hypogonadism
• Kallmann syndrome
• Pituitary tumor
• Ductal obstruction
• Spermatogenic abnormalities
• Chromosomal abnormalities (XXY)
• Y-chromosome microdeletions
• Gonadotoxins
• Varicocele
• Viral orchitis
• Torsion
• Idiopathic

OA: Etiology
• Idiopathic OA
• Iatrogenic OA (hernia repair,
orchidopexy)
• Infectious (gonorrhea,
chlamydia)
• Traumatic
• Genetic - CF with CBAVD or
variant thereof

OA: Clinical features
•Normal testicular volume (>15 cc)
•Normal serum levels of FSH, LH, testosterone
•
•Normal or reduced semen volume (obstructive)
•CBAVD - congenital bilateral absence of the vas
•Normal testicular biopsy (normal
spermatogenesis)

Azoospermia – further evaluation
•Testicular biopsy / FNAC
• Normal (at least one) vas and testicular volume with
normal (or slightly raised) FSH
• In presence of marked elevation (≥2 times of normal) of
FSH testicular biopsy is indicated only if sperm retrieval
with ICSI is being considered.
• Unilateral or bilateral -– larger testis if unilateral

•Testicular biopsy (contd)
• Medial or lateral surface of the upper pole
• Bouin’s, zenker’s or collidine buffered glutaraldehyde
• Formalin fixation results in distortion of testicular histology
and should not be used
• Classification pattern
• Normal spermatogenesis – ductal obstruction
• Hypospermatogenesis
• Maturation arrest
• Sertoli cell only syndrome (germinal aplasia)
• End stage testis

• Semen fructose
• All patients with obstructive azoospermia
• Absence of fructose indicates ejaculatory duct obstruction / seminal vesicle
agenesis
• Thus helps in assessing level of obstruction
• Normal = 120-450 mg%

• Radiologic evaluation
• TRUS - Not routinely indicated except if
• Ejaculatory duct obstruction is suspected – low ejaculate volume,
acidic pH, absent fructose and failure to coagulate
• Midline cysts, dilated ejaculatory ducts, dilated seminal
vesicles (>1.5 cm) – suggests ejaculatory duct obstruction
• Seminal aspiration and vesiculography may be done to confirm
• Unilateral vasal agenesis – can be associated with contralateral
segmental atresia of the vas deferens or seminal vesicle

•Radiologic evaluation (contd)
• Abdominal USG
• To assess for kidneys in cases with absent vas deferens
• Ipsilateral renal anamolies – 80% cases with unilateral absence
of vas deferens
• Renal agenesis – most common.
• 25% - unilateral absence of vas deferens
• 10% - CBAVD

• Radiologic evaluation (contd)
• Scrotal USG
• To assess for varicocele - only in patients with inadequate physical examination – obese,
high testicular sensitivity
• To detect testicular tumors – only in patients with suggestive history, examination or
hormonal values

•Genetic testing
• Indicated in non-obstructive azoospermia [and severe
oligospermia (<5 million/ml)]
• Genetic causes for male infertility
• Karyotypic abnormalities (structural or numerical)
• 6% of infertile men
• Prevalence increases with decreasing sperm counts
• Klinefelter’s syndrome, XX male, XYY syndrome,Translocations
• Y chromosome microdeletions
• Involve 3 non overlapping regions of long arm of Y
chromosome - AZFa (proximal), AZFb (middle), AZFc (distal)
• Normal phenotype
• Defect in spermatogenesis

•Genetic testing (contd)
• Prevalence of Y chromosome microdeletions (Foresta C et al. Endocr Rev 2001)
Semen parameters / pathologic condition Prevalence (%)
Fertile males 0.4
Unselected infertile patients 7.5
Unselected oligospermia 2.9
Idiopathic severe oligospermia (< 5 million) 14.3
Unselected azoospermia 7.3
Idiopathic azoospermia 18.0
Sertoli cell only 34.5

Oligospermia
• sperm densities of less than 20 million sperm/mL.
• In cases with less than 10 million sperm/mL, testosterone and FSH
levels should be determined.
Oligospermia as an isolated abnormality is uncommon and
most often due to either androgen deficiency or, more often, is
idiopathic.
Whereas varicoceles are the most common identifiable
etiology for oligospermia there are usually abnormalities in
other semen parameters as well.

Asthenospermia
• Spermatozoal structural defects
• Prolonged abstinence
• Idiopathic
• Genital tract infection
• Antisperm antibodies
• Varicocele
• Partial obstruction
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Oligoasthenospermia
• Varicocele
• Cryptorchidism
• Idiopathic
• Heat
• Toxins
• Systemic infection

Oligoasthenospermia – initial
evaluation
• History
• Examination – varicocele
• Hormonal evaluation – Serum testosterone and FSH – for
patients with sperm concentration of <10 million/ml

Oligoasthenospermia – further
evaluation
• Repeat semen analysis
• All patients should have at least 2 or 3 semen analysis
• Recent history of febrile illness, Heat, drugs, environmental toxins to be
eliminated if present and repeat SA after 3-6 months

Oligoasthenospermia – further
evaluation
•Antisperm antibodies
• Impaired sperm motility – particularly if isolated
• Post vasectomy reversal patients, history of previous acute
epididymitis, cryptorchidism and genital trauma
• Direct assays - Mixed antiglobulin reaction, immunobead
assay, ELISA
• Detect presence of antibodies on the patient’s sperm
• Positive if >20-50% of sperms demonstrate binding
• Advantage – detect only sperm bound Ig’s

• Indirect assays –
• Tray agglutination test,
• sperm immobilisation assay,
• ELISA
• Measure antibodies in patient’s serum
• Higher the titre of antibodies in serum – more likely there will be
antibodies in the semen

Teratospermia
• Defects in morphology
• Temporary insults to spermatogenesis and varicoceles are potential
causes

Morphologic Abnormalities
Sperm head defects
Sperm mid-piece defects
Sperm tail defects

Conclusion
• Male infertility is multifactorial
• Hormones, physiology, environment, anatomy and
DNA all play a role
• It is the delicate balance of all of these factors that must
be weighed in order to optimize male fertility
• Every evaluation is different and every treatment
strategy is geared toward the individual patient and
circumstance and must always take into account the
female partner

Evaluation of male infertility k.priyatham

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