MALE INFERTILITY

dr. Syah Mirsya Warli, SpU

dr. Bungaran Sihombing, SpU

Urology Division, Surgery Department

Medical Faculty,
University of Sumatera Utara
1
 References:

z Guidelines on Male Infertility, European Association

of Urology,gy, March 2007
z Clinical Manual of Urology, (Philip M. Hanno et al
eds), McGraw-Hill Int ed, 3rd ed, 2001
z Smith’s
Smith s General Urology (Tanagho & McAninch
eds), Lange Medical Books, 15th ed, 2000
z Infertility in The Male, (Lipshultz & Howards eds),
Mosby, 1997

2
 Definition

z Infertility Æ the inability of a sexually active, non-

contracepting couple to achieve pregnancy in one
year (WHO)
z Male causes are 50%
z Can be the result of many factors
z No causal factors is found in 60-75%
60 75% (idiopathic)

3
 Aetiology

Sexual factors 1.7%

Urogenital infection 6 6%
6.6%
Congenital anomalies 2.1%
Acquired
q factors 2.6%
Varicocele 12.3%
Endocrine disturbances 0.6%
I
Immunological
l i l ffactors
t 3 1%
3.1%
Other abnormalities 3.0%
Idiopathic abnormal semen (OAT syndr) 75.1%

4
 Etiology of infertility
75.1 OAT
80
70 varicocele
P e rc e n tta g e

60 infection
50
40 imunological
30 others
20 12.3
6.6 3.1 3 2.6 2.1 1.7 acquired
10 06
0.6
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Etiology

5
 Aetiology

Unexplained forms may be caused by :

- chronic
h i stresst
- endocrine disruption due to environmental
pollution
- reactive oxygen species
- genetic abnormalities

6
 Prognostic factors

z Duration of infertility
z Primary or secondary infertility
z Results of semen analysis
z A and
Age d ffertility
tilit status
t t off ffemale
l partner
t

Duration > 4 yrs of unprotected Æ conception

rate / mo 1.5%

7
 History
1. Fertility history
● Present relationship history
- duration of infertility
- contraceptive methods and length of time
used
- number of pregnancies
● Previous history & relationship

Clinical Manual of Urology

8
 History
2. Sexual history
- freq of intercourse & masturbation Æ frequent
(daily) or infrequent (> 48 hours)
- libido and potency
- ejaculation Æ problem with premature
ejaculation or severe hypospadias
- dyspareunia & the use of lubrication Æ most
of accessory lubricants used are spermicidal
- understanding of the ovulatory cycle
Clinical Manual of Urology
9
 History
3. Genitourinary history
- testicular descent:
- sexual development & onset of puberty
- infections
- trauma or torsion
- exposure to chemicals
- exposure to heat
- exposure to radiation

Clinical Manual of Urology

10
 History
4. General medical history
- medical illnesses : DM
DM, hypertension

5. Surgical
g historyy
- inguinal herniorraphy
- surgery on the ureter, bladder, bladder neck, urethra
- retroperitoneal
t it l surgery

6. Current & past medications

- usually reversible upon discontinuation
Clinical of the of Urology
Manual
11 medication
 Drugs & chemicals with potential
adverse fertility effects
z Alcohol z MAO inhibitors
z Alkylating agents (e.g.
(e g z Marijuana
cyclophosphamide) z Medoxyprogesterone
z Arsenic z Nicotine
z Aspirin (large doses)
z Nitrofurantoins
z Caffeine
z Phenytoin
z Cimetidine
z Colchicine z Spironolactone
z Pesticide z Sulfasalazine
z DES z Testosterone
z Lead
12
 Physical examination
z General examination
z Examination of genitalia
- penis
- testes
- epididymis
- vasa deferentia
- spermatic cord
- inguinal region
z Rectal examination

13
 Semen analysis

Standard values for semen analysis (WHO criteria, 1999)

Volume ≥ 22.0
0 mL
pH 7.0 – 8.0
Sperm concentration ≥ 20 million/mL
Total no. of spermatozoa ≥ 40 million/ejaculate
Motility ≥ 50% with progressive motility or 25% with
rapid motility within 60 min after
ejaculation
Morphology ≥ 14% of normal shape and form
Viability > 50% of spematozoa
Leucocytes < 1 million/mL
I
Immunobead
b d ttestt (IBT) < 50% off spermatozoa
t with
ith adherent
dh t particles
ti l
MAR test < 50% of spermatozoa with adherent particles
14
 Semen analysis
z Frequency :
- If Normal (WHO criteria) Æ one test should be
sufficient
- Further investigation is only indicated if the
results are abN in at least 2 test
z Abnormal :
- Oligozoospermia (< 20 million spermatozoa/mL)
- Astenozoospermia (< 50% motile spermatozoa)
- Teratozoospermia ( < 14% normal forms)
15 Æ OAT syndrome
 Hormone assessment
Indications :
- sperm density of < 10 x 106 sperm/mL on
semen analysis
- evidence of impaired sexual function (impotence,
low libido)
- findings suggestive of a specific endocrinopathy
(e.g. thyroid)

16
 Primary spermatogenic failure

z Any spermatogenic alteration caused by conditions

other
th ththan h
hypothalamic-pituitary
th l i it it di
disease
z Present clinically as non obstructive azoospermia

17
 Aetiology
Primary spermatogenic failure
z Anorchia
z Congenital factor (testicular
dysgenesis)
z Acquired factor (trauma,
testicular torsion,
torsion tumor
tumor,
surgery)
z Maldescended testes
z Kli f lt ’ syndrome
Klinefelter’s d z
z Germ cell aplasia
z Complete & focal germ cell
aplasia (Sertoli-cell only syndr)
z Spermatogenic arrest
18
z Post inflammatory
z Exogenous factors
(medications, toxins,
irradiation, heat)
z Systemic disease (liver
cirrhosis, renal failure)
z Testicular tumor
V i
Varicocele
l
z Surgeries that can damage
vascularization of the testes
z idiopathic
 Primary spermatogenic failure
z Impaired spermatogenesis is often associated with
elevated FSH concentration
z Testicular biopsy is the best procedure to define the
histological diagnosis & the possibility of finding
sperm
z A diagnostic testicular biopsy is indicated in patient
without evident factors (FSH and testicular volume is
normal) to differentiate between obstructive and non
obstructive azoospermia (NOA)

19
 Primary spermatogenic failure
z NOA who have spermatozoa in testicular biopsy Æ
Intracytoplasmic sperm injection (ICSI) is the only
therapeutic option
z About 50-60 % of man with NOA have some
seminiferous tubules with spermatozoa
Æ sperm retrievals for TESE (testis sperm
extraction) Æ ICSI
z Fertilization & pregnancy are achieved in 30 – 50%
of couples with NOA, when spermatozoa are found
p y
in the testicular biopsy

20
 Intra-Cytoplasmic Sperm Injection

z Sperm is injected
directly into the eggs in
a laboratory.
z Used if infertilityy
originates from the
male such as:
– Low numbers of sperm
– Severe Teratospermia

21
 Genetic disorders

z Chromosomal abnormalities
1. Sperm
S chromosomal
h l abnormalities
b liti
2. Sex chromosome abnormalities (Klinefelter’s
syndrome & variants)
3. Autosomal abnormalities
4. Translocations

22
 Obstructive azoospermia
z The absence of both spermatozoa & spermatogenic
cells in semen & post-ejaculate
post ejaculate urine due to bilateral
obstruction of the seminal ducts
z Less common than NOA
z Occurs in 15 – 20% of men with azoospermia

23
 Obstructive azoospermia
on the basis of ductal obstruction

z Present with normal size testes & normal FSH

z E l
Enlargement t off the
th epididymis
idid i can b be ffoundd
z In 25% men Æ no spermatozoa in the epididymis
during scrotal exploration Æ intratesticular
obstruction

24
 Classification
obstructive azoospermia on the basis of ductal obstruction

1. Intratesticular obstruction
2. E idid
Epididymal b t ti Æ mostt common
l obstruction
3. Vas deferens obstruction
4
4. Ejaculatory duct obstruction
5. Functional obstruction of the distal seminal ducts

25
 Classification
obstructive azoospermia on the basis of ductal obstruction
due to congenital & acquired causes

Classification Conditions
Epididymal obstruction Idiopathic epididymal obstruction
- congenital forms Post-infective (epididymitis)
- acquired forms Post-surgical (epididymal cysts)

Vas deferens obstruction Congenital absence of vas deferens

- congenital forms Post-vasectomy
- acquired forms Post-surgical (hernia, scrotal surgery)

Ejaculatory duct obstruction Prostatic cysts (Mullerian cysts)

- congenital forms Post-surgical
Post surgical (bladder neck surgery)
- acquired forms Post-infective
26
27
 Varicocele

z Dilated & tortuous veins within

the pampiniform
f plexus off
scrotal veins
z The most surgically
g y correctable
cause of male subfertility
z Diagnosis : clinical examination
& may be confirmed by color
Doppler analysis

28
 Varicocele

z Common abnormality with andrological implications :

- failure
f il off ipsilateral
i il t l ttesticular
ti l growth
th &
development
- symptoms of pain & dyscomfort
- infertility

29
 Varicocele

30
 Classification

z Subclinical : not palpable or visible at rest or

during valsalva manoeuvre
z Grade 1 : palpable during valsalva manoeuvre but
not otherwise
z Grade 2 : palpable at rest, but not visible
z G d 3 : visible
Grade i ibl & palpable
l bl att restt

31
 Varicocele

z Exact association Æ not known, analysis :

- semen abnormalities
b liti
- È testicular volume
- È Leydig cell function

32
 Treatment varicocelle

z Antegrade sclerotherapy
z R t
Retrograde
d sclerotherapy
l th
z Retrograde embolization
z Open operation :
- scrotal operation
- inguinal approach
- high ligation
- microsurgical
- laparoscopy

33
 Hypogonadism
z Deficient androgen secretion
z Etiology & pathogenetic mechanism :
1. primary (hypergonadotropic) hypogonadism due
to testicular failure
2. secondary (hypogonadotropic) hypogonadism
caused by insufficient gonadotrophin releasing
h
hormone (G
(GnRH)
RH) and/or
d/ gonadotrophin
d t hi secretionti
3. Androgen insensitivity (end-organ resistance)

34
 Hypogonadism

z Primary or secondary hypogonadism should receive

testosterone substitution therapy
z Effective drug therapy is available to achieve fertility
in men with hypogonadotropic
yp g p hypogonadism
yp g

35
 Cryptorchidism

z Most frequent male congenital abnormality

z Multifactorial in origin and may be caused by genetic
factors and endocrine disruption early in pregnancy
z Often associated with testicular dysgenesis and is a
risk factor for infertility & germ cell tumors

36
 Treatment of Cryptorchidism

z Hormonal treatment
- currentt protocol
t l : hCG injection
i j ti
- considered safe, few side-effects
z Surgical treatment
- success rate 70 – 90%
- open surgery, laparoscopy or microsurgery
- vascular damage is the most severe
complication Æ testicular atrophy (1-2%)

37
 Treatment of Cryptorchidism

z The success rate of hormonal treatment has only

been shown for prescrotal & high scrotal testes
z Nan-palpable testes rarely descend by hormonal
treatment

38
 Idiopathic male infertility

z No demonstrable cause, except OAT

z 40 – 75% of infertile men
z Medical treatment of male infertility can only be
advised in cases of hypogonadotropic
hypogonadism
z Drugs are usually ineffective in the treatment of
idiopathic male infertility

39
 Empirical therapy of idiopathic
OAT syndrome
Hormonal EAU recommendation
GnRH Contradictory result
No controlled trials
Further trials are needed
hCG/hMG Lack of efficacy
Not recommended
FSH Efficacy not yet shown
Further trials are needed
Androgens Lack of efficacy
N t recommended
Not d d
Anti-oestrogens (clomiphene Potentially effective
citrate, tamoxifen-testosterone used must be counterbalanced against
undecanoate ) possible side effects
p
further studies are needed

40
 Empirical therapy of idiopathic
OAT syndrome

Non-hormonal EAU recommendation

Kinin-enhancing drugs unproven efficacy
clinical trials only
Bromocriptine Lack of efficacy
Not recommended
Antioxidants May benefit selected patients
Clinical trials only
y
Mast cell blockers Some efficacy shown
Further evaluation needed
Clinical trials only
y

41
 Empirical therapy of idiopathic
OAT syndrome

Non-hormonal EAU recommendation

Alpha blockers
Alpha-blockers Lack of efficacy
Not recommended
Systemic corticosteroids Lack of efficacy
Patients with high levels of antisperm
antibodies should enter an ART
programme
Magnesium
g supplementation
pp Unproven
p efficacy
y
Not recommended

42
 Male accessory gland infections

z Potentially curable causes of infertility

z WHO : urethritis,
th iti prostatitis,
t titi orchitis,
hiti epididymitis
idid iti
z Antibiotic treatment often only eradicates micro-
organism; it has no positive effect on inflammatory
alteration and/or cannot reverse functional deficits
and anatomical dysfunctions

43
 Male accessory gland infections

z Although antibiotic procedures for MAGI’s may

provide improvement in sperm quality
quality, therapy does
not necessarily enhance the probability of conception
z Patients who have epididymitis
p y known or suspected
p to
be caused by N.gonorrhoe or C.trachomatis should
be instructed to refer sex partners for evaluation &
treatment

44
 Germ cell malignancies

z TGCC
- È sperm quality
lit
- orchidectomy Æ risk of azoospermia
- semen cryopreservation prior to
orchidectomy should be considered

45
 Semen cryopreservation

z Storage of a biological material at low subzero

temperatures
z Purpose : to secure future pregnancies by ART
(Assisted Reproductive Techniques)
z Should be offered to all men who are candidates for
chemotherapy radiation or surgical interventions
chemotherapy,
that might interfere with spermatogenesis or cause
ejaculatory disorders

46
 What is ART?

z Group of high tech treatment methods to improve

infertility.
f
z Techniques include
– In Vitro Fertilization
– Artificial Insemination
– Gamete Intra
Intra-Fallopian
Fallopian Transfer
– And many more

47
 Disorders of ejaculation

z Uncommon, but important causes of infertility

z Classification :
- anejaculation
- anorgasmia
- delayed ejaculation
- retrograde
g ejaculation
j
- asthenic ejaculation
- premature ejaculation
- painful
i f l ejaculation
j l ti
48
 Disorders of ejaculation

z Anejaculation
j :
- complete absence of an antegrade or
retrograde ejaculation
- caused dbby ffailure
il off emission
i i off semen ffrom
the seminal vesicles, prostate & ejaculatory
ducts into the urethra
- Usually associated with a normal orgasmic
sensation

49
 Disorders of ejaculation

z Anorgasmia
- inability to reach orgasm
- may give rise to anejaculation
- the cause is usuallyy p
psychological
y g
z Delayed ejaculation
- abnormal stimulation of the erected penis is
necessary to t obtain
bt i an orgasm with
ith ejaculation
j l ti
- the cause may be psychological or organic
(incomplete spinal cord lesion, iatrogenic penile
damage, pharmacological)
50
 Disorders of ejaculation

z Retrograde ejaculation
- total or partial, absence of an antegrade
ejaculation due to semen passing backwards
- N or È orgasmic sensation (except paraplegia)
- The cause may be neurogenic, urethral,
pharmacological,
h l i l or blbladder
dd neck k iincompetence
t

51
 Disorders of ejaculation

z Asthenic ejaculation
- altered
lt d propulsive
l i phase
h with
ith a normall
emission phase
z Premature ejaculation
- inability to control ejaculation for a sufficient
length of time during vaginal penetration
- may be organic or psychogenic

52
 Disorders of ejaculation

z Painful ejaculation
- usually
ll acquired,
i d often
ft related
l t d tto LUTS
(lower urinary track symptom)
- painful sensation : in the perineum
perineum, urethra
or urethral meatus

53
 Th k You
Thank Y

54 wr’07