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Infertility
Edmond Wong
Outline
• Spermatogenesis
• Hormonal effect
• Infertility (workup)
• Obstructive azzospermia
– Idiopathic (+ scrotal exploration & testicular bx)
– CBAVD
– Post vastectomy (vasectomy + reversal)
• Non obstructive azzospermia
– Klienfilter syndrome
– YCMD
• OAT: varicocele
• Sperm retrieval technique
• Assisted reproductive technique
• Fertility issue in oncological patient
What is spermatogenesis?
• Spermatogonium 
• Primary spermatocyte  first meiosis
• Secondary spermatocyte  second meiosis
• Spermatid  spermatozoa
• Spermatozoa
– Can be used for ICSI
• Process takes 70 days
What is the definition of
infertility?
• Inability of a sexually active, non-
contracepting couple to achieve pregnancy in
one year
–WHO
What is the epidemiology?
• Normal couple pregnancy rate – 20-25% per month
• 80% of couples will conceive within 1 year or
unprotected SI
• Abnormal couple pregnancy rate – 1-3% per month
• 15 % of population
• 5% remain unwillingly childless
• 30% will conceived at some time if left untreated
Contributing factors
• Female factor 40%
• Male factor 30%
• Female + Male factor 30%
Cause
• Pre-testicular cause:
– Hypothalamic disease
– Pituitary disease (hypogonadotropic hypogonadism)
• Testicular cause:
– Varicocele
– Chromosomal abnormalities
• Klinefelter’s syndrome (XXY)
• Y-chromosome microdeletion (sertoli cell only , maturation arrest , etc)
– Orchiditis
– Trauma
– Torsion
– Cryptorchidism
– Gonadotoxins : chemo , radiation
– Systemic disease
Cause
Post-Testicular cause:
• Disorder of sperm transport
– Congenital bilateral absence of vas (CBAVD)
– Acquired disorders (vasectomy , infection)
– Functional disorders (ejaculatory disorder)
• Disorder of sperm motility
– Congenital defect of sperm
– Immunologic disorder
– Infection (liver cirrhosis, renal failure)
What are the prognostic factors?
• Duration of infertility
• Primary or secondary infertility
• Results of semen analysis
• Age (most important) and fertility status of
female partner
– Compared to a woman at 25 years old, the fertility potential is
reduced to 50% at age 35
Common complaints
• Male factor infertility
o Abnormalities in S.A.
o Varicocele
What is history taking of infertility
(preferably with partner)?
• AGE
• Sexual :
– Duration of infertility
– Primary or secondary
– Frequency and timing of intercourse
– Use of contraceptive or history
– Use of vaginal lubricant (affect sperm function)
– Erectile or ejaculatory dysfunction
• Partner history - Previous pregnancy, age
• Developmental :
– Age at puberty;
– Undescended testis
– History of torsion
– Prepubertal mumps (asso with NOA)
– Y-V plasty of the bladder
History
• Medical and surgical -
– Orchitis; Epididymal-orchidits; STD
– varicocele;
– testicular torsion, trauma, or tumour;
– inguinoscrotal surgery; pelvic injury or RPLND
– radiotherapy/chemotherapy
– respiratory diseases associated with ciliary dysfunction
– DM
• Drugs and environmental –
– alcohol consumption; smoking habits;
– hot baths;
– anabolic steroids (hypogonadotropic hypogonadism)
• Family - Hypogonadism; cryptorchidism, cystic
Fibrosis
What is physical examination?
• Secondary sexual development
– Habitus ?KFS; body hair distribution; gynaecomastia (KFS)
• Genitourinary
– Inguinoscrotal scars (hernia)
– Penis: Peyronie's plaque, phimosis, hypospadias/chordee
– Scrotum
• Testes size, tumor
– Volume with a Prader orchidometer (normal >20ml; varies with
race)
• Epididymus : induration or dilatation (obstruction)
• Vas presence
– CBAVD
– Unilateral vasal agenesis has unilateral renal agenesis
• Varicocele: grade
• Digital rectal examination of prostate
What are the investigations?
• Initial tests - Semen analysis x 2
– Azzospermia
– Oligo-astheno-teratosepmai (OAT)
• Save post-ejaculatory urine (5-10sperm / HPF) if low volume
sperm
• Initial tests - Hormonal measurement
– Indications:
• Symptoms of endocrinopathy (decrease libido)
• Oligospermia (< 10million/ml)
• Abnormal scrotal exam
– 1st
line : Morning testosterone + FSH
– 2nd
line : LH/testosterone/prolactin
– FSH is a marker for spermatogenesis
Others:
• Chromosome analysis
– Pimary spermatogenic failure – azoospermia, atrophy
testes, increase FSH
• Scrotal USG
– Varicocele, testicular abnormalities
• TRUS
– Ejaculatory duct obstruction
• Testicular biopsy
What is the semen analysis?
• At least 2 samples
– If the results of semen analysis are normal according to
WHO criteria, one test should be sufficient
• Abstains for 3-5 days (>7 day reduce motility)
• Should be produced by masturbation without use
of latex condoms (spermicide)
• Wide mouthed container
• Avoided coitus interruptus
– Lost initial part of semen, bacteria, acidic vaginal
secretions contaminate the specimen
• Specimen kept in pocket (close to body
temperature)
• Examined within 1-2 hour
WHO Semen Analysis 2009
• WHO SA criteria
– Vol 2ml or above
– Conc >20 million / ml
– pH >7.2
– Motility 25% GA or 50% GA+B
– Morphology >14% normal by Kruger’s criteria
– Viability 75% or more viable
What is the grading of sperm
motility?
Grade Sperm motility
0 No motility
1 Sluggish; no progressive movement
2 Slow, meandering forward progression
3 Moving in a straight line with moderate
speed
4 Moving in a straight line at high speed
Sperm Penetration Assay
• aka “zona-free hamster ova assay”
• Dynamic test of fertilization capacity of
sperm
• Failure to penetrate at least 10% of zona-
free ova consistent with male factor
• False positives and negatives exist
SA
• What are the parameters, lower reference limits
(WHO)?
– Extreme cases of OAT < 1 million spermatozoa/mL
• SA: on at least 2 occasions
– Volume > 2.0ml
– Sperm density >20x10^6/ml
– Motility >50% forward progression
• And :
– No significant sperm agglutination
• Possible antisperm antibodies (ASA)  IgA & IgG bound to sperm
– NO pyospermia (semen round cell)  leukocytes or
immature germ cell
Kruger Morpholoic criteria
• Normal sperm:
– Smooth , oval head
– Acrosome 40-70% of head volume
– No abnormalities of the neck , midpiece or tail
What are the contributions in
seminal fluid?
• 30% prostate (acidic)
• 60% SV (Alkaline)
• 10% testis
• Thus if blockage of SV and proximal
– Small volume (< 1ml) , acidic SA  CBAVD
• Why fructose level:
– Fructose is secreted by SV , if low , obstruction
distal to SV
What are DDx of azoospermia?
• Azzospermia in 1% of general male population
• 10% of infertile male population
• 2/3 are non-obstructive in nature:
– testicular failure
– Genetic disorder : KFS , YCMD , etc
– Varicocele
– Post-chemo/ RT
– Unexplained testicular dysfunction
• 1/3 are obstructive in nature:
– Genetic: CBAVD
– Vasectomy
– Infection (epieidymo-orchitis/ STD) , previous surgery
• cryptozoospermia
o Sperms were found in 20% of pellet after
centrifugation
Azzospermia
• Low volume azoospermia
– CBAVD
– Ejaculatory duct obstruction (EDO)
• A semen volume <1.5 mL and with an acid pH and
low fructose level suggests ejaculatory duct
obstruction or CBAVD
– Hypogonadism
– Retrograde ejaculation
– Failure of emission / ejaculation
• Normal volume azoospermia
– Spermatogenic failure
– Varicocoele
• Approach to low volume azoospermia
– Save PEU (5-10sperm / HPF)
– Check FSH, testosterone
– Exam for vas
– TRUS + SVG to confirm EDO, if all normal
• Approach to normal volume azoospermia
– Rule out varicocele
• Hudson
– G3 : visible
– G2 : Palpable on standing
– G1 : Palpable on Valsalva
• Check FSH for spermatogenic failure
– Testicular failure : small testes
– Y chromosome microdeletions : normal sized testes
• If not, then either SCOS or obstruction (testicular
Bx)
Approach to man with azoospermia
• Exam : CBAVD, varicocele, testes size
• Check SA, to see whether NV or LV
• NV : check FSH
• LV : PEU, testosterone, FSH
• NOA : small sized testes, FSH raised
• OA : except CBAVD, normal volume
azoospermic, normal FSH
What are DDx of OAT?
• Varicocele
• Systemic illness
• Bil cryptochidism
• Gonadotoxins
– heavy metals
• Lead, cadmium, mercury, pesticides, herbicides, carbon
disulphide
– Alcohol
• Spermatogenesis, reduced sexual function
– Tobacco smoking
• Oxidative damage to sperm DNA
– Steroid (for body-building)
• Spermatogenesis
– Heat
What are DDx of isolated
asthenospermia?
• Antisperm antibody
– Acquired or congenital ductal obstruction
– Vasectomy
– Testicular/epididymal infections
– Testicular torsion/trauma
– Cryptorchidism
– Varicoceles
• Prolonged abstinence
• Varicocele
• GU infection
• Spermatozoal motility defect
What are DDx of no abnormality
found in semen analysis?
• Female factor
• Coital problem
• Acrosomal defect
Azzospermia
Centrifuge sample +
Post-ejaculatory urine

Azzospermia confirmed
 FSH
N 3x
Testicular bx+/-
Scrotal exploration + Testicular failure
Vasogram
Holistic Management
• Treatment Options
o Consider risks of surgery/ ART
 Remained childless
 Adoption
 Donor insemination
o Scrotal exploration +/- Reconstructive Surgery
o Varicocelectomy
o Sperm retrieval + ART
• FEMALE FACTORS
Pragmatic Management
• Obstructive Azoospermia
o Congenital absence of vas
 Genetic counseling
 Sperm retrieval + ART
o Suspected Obstructive Azoospermia
 Options of Sperm retrieval/ ART vs Scrotal
exploration/ reconstructive surgery
 If scrotal exploration/ reconstructive surgery is
contemplated, testicular biopsy is done to confirm
normal spermatogenesis
 If ART is chosen, proceed to sperm retrieval
Pragmatic Management
• Non-obstructive azoospermia
o Overall 50% success of sperm retrieval by
TESE
o Consider genetic study
 Karyotyping: Klinefelter’s syndrome
 Y-chromosome microdeletion (Azoospermic Factor
AZF)
 AZFa or AZFb: complete absence of spermatogenesis
 AZFc: 60% success of sperm retrieval by TESE
 Overall 15% NOA patients have positive genetic
studies
 Risks of transfer of abnormal genes to offspring's
o NO NEED of pre-TESE testicular biopsy
Pragmatic Management
• Oligo-astheno-teratospermia (OAT)
o Any components
o Clinically significant varicoceles
 4 criteria fulfilled
 Subinguinal microsurgical varicocelectomy
 90% technical success
 70% patients have improvement in S.A. parameters
 Spontaneous pregnancy 30-40% (consider FEMALE
FACTOR)
 1% testicular artery injury
General advice to promote fertility
• Wear loose underwear
• Avoid excessive hot baths
• Avoid regular or heavy drinking
• Quit smoking
• Healthy, fit life , taking holidays and
regular exercise
• Have intercourse every other day around
the time of ovulation
Hormonal base therpay?
Gonadotrophins
• HCG+ hMG
• Use in hypogonadotrophic hypogonadism (Low
FSG, LH and Testosterone)
• SE: expensive, mood and libido change
Clomiphene Citrate:
• Anti-estrogen  increase GnRH output 
increase serum testosterone
• SE : gynaecomastia, wt gain , acnes, mood
change
Non-hormonal base therapy
• Anti-oxidant therapy:
– Glutahione
– Vit E
• Micronutrient supplements:
– Zinc
– Folate
• L-acetylcarnitien (ProXeed)
Obstructive azoospermia
•((40% of Azoospermic Patients)
•40% of Azoospermic Patients)
Obstructive Azoospermia
• (40% of Azoospermic Patients)
o History of vasectomy/ epididymo-orchitis/ STD
o Primary or Secondary infertility
o Normal sized testes
o Distended or Indurated epididymes
o Congenital absence of vas
o Normal hormonal profiles
Obstructive Azoospermia
Low volume ejaculate and acidic pH
• Idiopathic OA (previous infection)
• Congenital absence of vas
– IRREVERSIBLE > ART
– Clinical Diagnosis
– Confusion in patients with Partial vasal agenesis
– Bilateral abdominal vas stopped abruptly at inguinal canal
– In doubt, TRUS to confirm seminal vesicle absence
• Vas obstruction + previous vasectomy
• Ejaculatory Duct Obstruction
– REVERSIBLE > surgical correction (VE)
– Pain on ejaculation
– TRUS to confirm Distended seminal vesicle
Case 1: Idiopathic OA
• Mr. Chan visit your clinic for subfertility
problem
• 2 sets of semen analysis are done
SA
Semen analysis Value
Semen volume (ml) 2ml
pH 7.2
Total sperm count 3 x 106
Sperm concentration 1.5 x 106
Sperm motility 50% (PR+NP)
Sperm morphology 15%
Viability 80%
Time to liquefy 10mins
Semen fructose 20umol
MAR test negative
Frag.1
• Q1. Please comment on the SA
• A1. Oligospermia with normal motility and
morphology
Frag.2
• Medical history – Hx of gonococcal
infection
• Physical exam – vas deferens presence,
both testes normal size, indurate
epieidymis
• Endocrine – FSH 2 IU/L and testosterone
500ng/dL (normal range > 300ng/dL)
What’s your further workup ?
• Testicular biopsy:
• Although in pt with normal FSH & testicular volume, obstructive cause is
likely , however, there is still chance of maturation arrest which have the
similar clinical picture
• Purpose is to differentiate btw obstructive and non obstructive
azzospermia when the clinical picture is not clear, when ductal
obstruction is suspected base on a normal serum FSH and normal
testiscular volume & we are planning for a reconstruction (VE)
• Clear picture of CBAVD or testicular failure do not require testicular
biopsy
• Vasogram should not be done during Testicular bx , it should be done
before reconstruction because it carries a risk of obstructing the vas
• Another role of testicular biopsy in NOA is for sperm retrieval & ART
• Tescticular bx is not indicated in patient with oligospermia
Testicular biopsy
• Types of testicular Bx
– Open testicular Bx under GA
– Percutaneous testicular Bx using trucut needle
• A small scrotal incision that does not deliver the testis
outside the skin or tunica vaginalis minimizes
postoperative scarring and facilitates subsequent scrotal
reconstructive surgery
• Both sides, upper medial and lateral surfaces
• Medium : Bouin’s solution
– (Picric acid, formaldehyde, acetic acid)
– Other solution: Zenker’s, or glutaraldehyde; formalin should not
be used
– Eppendorf tubes if sperm cryopreservation as well
• What is this? (1)
• What is it used for? (1)
• What is it composed of? (1)
Q31
• Bouin’s solution (1)
• Medium to transport testicular biopsy (1)
• Picric acid, formaldehyde, acetic acid (1 for
mentioning any of these 3 components)
• Others preservation solutions:
– Zenker’s / collidine buffered glutaraldehyde solution
What is the scoring system for
testicular biopsies ?(Johnsen score)
Score Histological criteria
10 Full spermatogenesis
9 Slightly impaired spermatogenesis, many late
spermatids, disorganized epithelium
8 Less than five spermatozoa per tubule, few late
spermatids
7 N o spermatozoa, no late spermatids, many early
spermatids
6 N o spermatozoa, no late spermatids, few early spermatids
5 N o spermatozoa or spermatids, many spermatocytes
4 N o spermatozoa or spermatids, few spermatocytes
3 Spermatogonia only
2 N o germinal cells, Sertoli cells only
1 N o seminiferous epithelium
Frag.3
• USG: testes normal, dilated epididymis
without cyst, seminal vesicle normal, no
Mullerian cyst
• Testicular biopsy: presence of
spermatozoa
Management
• Counseling:
– This is likely to be obstructive azzospermia
– Remain childless
– Adoption
– Donor insemination
• Definitive treatment :
– Sperm retrieval technique with ART
– Reconstructive surgery (VE) + vasogram
• When no female factors presence
Patient opt for ART
• Sperm retrieval and IVF/ICSI generally is the
best choice of treatment for obstructive
azoospermia when
– [1] the female partner is over age 37
– [2] there are coexisting female infertility factors that
require IVF
– [3] the likelihood for success with sperm retrieval/ICSI
is greater than with surgical treatment
• Options: PESA, MESA
MESA
• Advantage:
– Allow meticulous hemostasis during retrieval
– Allow ample amount of sperm to be retrieved
Pt opt for reconstructive surgery
• Vaso-epieidymostomy
– Microsurgical Intussuception Technique (Berger)
• Vas lumen 400um
• Epididymal tubule 150um
• Technically demanding
• Patency 70-80%
• Spontaneous pregnancy 20-40%
• Anatomical recanalisation following surgery may require 3-18
months
• Before microsurgery (and in all cases where recanalisation is
impossible), epididymal spermatozoa should be aspirated and
cryopreserved for use in ICSI in case of surgical failure
• Distal patency confirmed by vasogram
• Proximal patency : microscopic visulaization of intravasal fluid
Vasography
• Vasography may help to identify distal obstruction in the vas
deferens or ejaculatory ducts. However, due to the risk for
vasal scarring and obstruction, vasography should be
performed at the same time with reconstructive surgery
• Can be percutaneous or open vasogram
• How to perform:
– At straight portion of the scrotal vas
– Saline vasography : 0.5-1ml NS
– Dye vasography : indigo carmine
– Contrast vasography
• Normal vasogram:
– Contrast agent seen in vas deferens, SV , Ejaculatory duct +
Bladder
Three sutures end to side
intussusception VE technique (Berger)
Two sutures end to side
intussusception VE technique
(Marmar and Chan)
Case 2: CBAVD
• Gentleman with azzospermia
• P/E: bilateral absence of vas
• Dx: Congenital bilateral absence of vas
deference
What is the association between
cystic fibrosis and infertility?
• The most common is congenital bilateral absent vas
deferens which occur in 95% of men
• They typically have azoospermia
• Autosomal recessive
• SA: low volume ejaculate & acidic pH
– Because also absence of SV, ejaculate only contributed by
prostate (which is acidic)
• The defective gene (CFTR) is on chromosome 7
• Cystic fibrosis transmembrane conductance regulator
Gene
• CFTR protein is a chloride channel which when defective
causes thick mucus secretions that result in the typical
presentation with recurrent upper respiratory tract
infections
CFTR gene in CBAVD
• The CFTR gene provides instructions for making a protein called the cystic
fibrosis transmembrane conductance regulator.
• This protein functions as a channel across the membrane of cells that
produce mucus, sweat, saliva, tears, and digestive enzymes.
• The channel transports negatively charged particles called chloride ions into
and out of cells. The transport of chloride ions helps control the movement
of water in tissues, which is necessary for the production of thin, freely
flowing mucus.
• Mutations in the CFTR gene disrupt the function of the chloride channel,
preventing the usual flow of chloride ions and water into and out of cells.
• As a result, cells in the male genital tract produce mucus that is abnormally
thick and sticky.
• This mucus clogs the tubes that carry sperm from the testes (the vas
deferens) as they are forming, causing them to deteriorate before birth.
• Without the vas deferens, sperm cannot be transported from the testes to
become part of semen.
Treatment options
• The obstructions in CBAVD is IRREVERSIBLE
 no reconstructive surgery
– Sperm retrieval
• PESA (Percutaneous Epididymal Sperm Aspiration)
• MESA
• ICSI assisted reproduction
• Genetic counselling
• Non-invasive”
• Multiple epididymal tubules punctured
Case 3: vasectomy + reversal
Scenario
• M/35
• Good past health
• 1st marriage for 5 years
• 4 daughters
• Sole bread winner of the family
• Request vasectomy
• How would you counsel the patient ?
• What other alternatives ?
• What are the potential risk and
complication
History
• To attend the clinic with partner
• Age
• Marital status
• Number of previous children
• Previous contraceptive method
• Previous surgery on inguinal region
• Why he wish to have vasectomy
• Discuss with other contraceptive method
Physical examination
• Specifically look at
– Laxity of the scrotum
– Whether vas are palpable
– Rule out other scrotal pathology
Indication
• Every man of legal age and able to give
consent may decided in favor of vas
ligation or occlusion for the purpose of
sterilization
• Other consideration : no of children ,
stable relationship with written consent
from partner, chances of refertilization
discussed
Informed consent
• Procedure, written consent, with partner
• Consider as a irreversible process
• Early failure (surgical error): 1 in 200
• Late failure (recanalization): 1 in 2000
• Subsequent refertilization: 70-90%
• Acute complication:
– Bruising & swelling
– Hematoma (2%)
– Infection (3%)
• Long term complications:
– Testicular and epididymal pain (5%)
– Sperm granuloma (10%)
– Serum antisperm antibody (70%)
• Need of post-op semen analysis
• Must continue contraception until azzospermic (3m)
Vasectomy
• LA, warm room & antiseptic solution
• Isolate vas from cord vessels
• Vas trapped btw mid, index and thumb
• Use bilateral small incision
– Reduce division of same side twice
• Vas is expose, dissected free from artery , vein and
nerves
• 1cm segment is removed
• Occlusion: suture ligated, clip, division btw ligatures
• Ends are occluded by intra-luminal cautery (reduce
recanlization to 0.5%)
• End separate in different facial plane
• Skin closed with 4/0 vicryl
• Dressing
Modification
• No scalpel technique (China 1993)
• Electrocoagulation of the cut edges
• Fascial interposition
No scalpel technique
• Developed by Dr. S. Li in China
• Compared with conventional vasectomy
o Less haematoma
o Less pain
o Less infection
o Less OT time (<40%)
o Li S, Goldstein M, Zhu J, Huber D: The no-scalpel vasectomy. J Urol 1991; 145:341-344.
o Nirapathpongporn A, Huber DH, Krieger JN: No-scalpel vasectomy at the King's birthday
vasectomy festival. Lancet 1990; 335:894-895.
Effectiveness
• Safest contraceptive methods
• Most cost-efficient method (Nakhaee
2002)
• Early and late failure rates are 1/200 and
1/2000 respectively
• More effective than tubal ligation and less
morbidity
Complication
• Acute:
– Bleeding/ hematoma (2%)
– Epididymitis/ wound infection (3%)
• Long term:
– Recanalization: <1%
– Sperm granuloma 3-75%  sperm antibodies
– Chronic testicular or epididymal pain of
unknown pathology (5%)
• Prudent to send vas for histology to show complete
diameter
– (Tam: no need to send if precise excision)
Post vasectomy SA
• General recommendation : at 3 & 4m, after 24
ejaculations
• Obtaining at least one and preferably two absolutely
azoospermic specimens 4 to 6 weeks apart
• A ‘special clearance’
– Consecutive 2 SA showing non-motile sperm <
10, 000 mil/ml at more than 7 months after
vasectomy (no pregnancy on prospective FU)
– No more than risk of pregnancy after two
azoospermic semen samples, as a result of
recanalisation, ~1/2000
– Discontinue contraceptive precautions after
appropriate counselling
Psychosexual effect
• Positive:
– Problem of contraception resolved
– Fear of unwanted pregnancy gone
• Negative:
– If patient are forces to have vasectomy
– If partners not involved in decision
What to do if failed vasectomy?
• Confirmed presence of sperm by SA x2
• Explained that quoted risk is : 1 in 2000
• Offer scrotal exploration  identify vas 
further occlusion
• Advice alternative form of contraceptions
5 years later….
• M/40
• Same wife
• Very successful in business and become
a millionaire
• Would want a son
Questions
• What are the options
• How to counsel the patient?
Indication for vas reversal
• Divorce followed by remarriage or a new
partnership
• Unexpected death of one of their children
• Improved economic standing
• 5% of men with vasectomy
Workup ?
• Reproductive history, same partner ?
• PE:
– Size , consistency of testis
– Epididymis
– Vas palpable? Sperm grauloma
– Vasal gap, location
– Groin scar (second site of obstruction)
• SA
• Likely hood of success?
– Experience of surgeon
– Time since vasectomy
– Partner age and reproductive status
Consider
• Female factors e.g. age, ovarian reserve,
tubal status
• Surgical expertise/ ART success
• Side effects of different treatments
• Patient preference
Options
• Remain status-quo
• Adoptions
• Donar insemination
• Vasovasotomy or Vaso-epididymostomy
• Sperm retrieval +/- ART
– PESA, MESA
Reasons for reconstructive surgery over
direct sperm retrieval and ART
• Allows couples to have offspring in a natural
manner
• Obviates the need for sperm retrieval for every
other child they want to have
• More cost effective by Schlegel’s analysis
• Reconstructive surgery is relatively safe
procedure in relations to the possible risks
involved in the stimulated cycle ART eg. OHSS
• Despite some patients may need ART after
reconstructive surgery, a less invasive form of
ART often is required than when reconstructive
surgery not done
Why obstruction at epididymis after
vasectomy?
• High intraluminal pressures after
vasectomy
• Rupture of the delicate epididymal tubule
• Secondary obstruction in the epididymis
Types of reconstruction :What are
the factors to consider ?
• Obstructive interval
– Secondary epididymal obstruction rarely
occurs within 4 years of a vasectomy, present
in > 60% of patients after 15 years of vasal
obstruction (Fuchs and Burt 2002)
• Quality of fluid from the proximal vas
segment (sperm count)
• Partner factors such as age, fertility status,
and parity
Proximal vas fluid
• Copious clear fluid with motile sperm  94%
sperm in ejaculate after VV
• NO sperm in vasal fluid  60% (Belker,1991)
• Thick or absent vas fluid, no sperm  VE
• Proximal vas length 2.7cm + sperm in vasal fluid
 favor VV over VE (Witt 1994)
• Sperm granuloma  improved patency rate
(pop off valve pressure release)
How to perform scrotal exploration?
• GA , patient supine
• Microsurgical technique
• Bilateral 1.5cm longitudinal incision over vas
• Vas identified above the previous vasectomy, vasal gap
identified
• Dissection of vas proximally and distally until sufficient
length for cut ends to slightly overlap one another
• Held in vasectomy reversal clamp above skin level
• Both end are transected into normal area  inspected
and gently dilated with forceps
• Few drops of fluid from testicular end of vas placed on
glass slide and examine undermicroscopy or decision
base on quality of the return fluid
• VV & VE performed
When is VV indicated?
Features where VV indicated base on
testicular side vasal fluid:
• Sperm or sperm part seen in large number
• Clear and copious fluid
When is VE indicated?
1. Thick material from proximal vas and
devoid of sperm
2. Fluid is creamy and contain only debris
3. No fluid even when vas is milked
towards the cut end
4. Irrigation of proximal vas with 0.2ml NS
failed to wash out any sperm
Vaso-vasostomy(VV)
• Average patency rate: 70-90%
• Average pregnancy rate: 30-60%
Vasovasostomy Study Group, J Urol 1991
Vasovasostomy Study Gp 1991
Success is determine by:
• Microsurgical technique vs macrosurgical
– Sperm +ve: 85% (vs 40%)
– Pregnancy: 50% (vs 20%)
• Anastomotic technique:
– Similar patency rate btw 2-layer and modified one-
layer
• Time since vasectomy: < 3yr vs >15yr
– Sperm +ve: 97% vs 70%
– Pregnancy: 70% vs 30%
Other factors to determine success
1. Time since vasectomy
2. Surgical technique and skill
3. Level of obstruction (more distal the better
because of larger lumen)
4. Proximal length
5. Use of surgical clips
6. Presence of granuloma (+ve)
7. Age and reproductive capacity of the female
partner: > 40 , rate of pregnancy decrease
from 50% to 14%
Modified one-layer VV
• Full thickness 9/0
nylon suture at
posterior
• 3 anterior suture
• Anastomosis
support by 9/0
nylon seromuscular
layer
Multi-layer Vasovasostomy: standard
Vaso-vasostomy
• Vas transected
• Vasal fluid aspirated
from testicular vas
• Verified under
microscope for sperm
parts
Abdominal vas dilated
with fine forceps
• 9/0 nylon to re-
apposed the serosa
layer at 5 and 7oc
• Vas end brought in
close proximity with
5/0 PDS in perivasal
tissue
• Suture placed at
4,6,8,oc within
mucosa
• 10/O nylon to suture
vasal mucosa
• 9/0 nylon suture in
vasal serosa to
complete the outer
anastomosis
• 5 additional suture at
1,3,9,11,12 oc
position
Vaso-epididymostomy(VE)
• VE is require in vas-reversal in 20%
• In terms of delivery rate for patient with
vasectomy, it has proved more successful and
more cost-effective than ICSI
• Results:
– Average Patency rates : 50-70%
– Cumulative pregnancy rates : 40%
– Delay sperm at 6m: 20%
– ART should not be use until 2yr
Vasoepididymostomy
Microsurgical single-tubule anastomoses
• End-to-end anastomosis (Silber)
• End-to-side anastomosis
• Intussusception technique end-to-side (Berger)
– Earlier return of ejaculate
– Lower rate of restenosis
– Easier and shorter time to perform
• Vas lumen 400um m, Epididymal tubule 150um
• Better success with anastomosis to corpus (body) than
head of epididymis
• Result of microsurgical one-layer (Schmidt 1978) vs Two
layer (Belker 1980) technique are comparable (Belker
1991)
Surgical technique
Vaso-epididymosotomy:
• End-to-side:
• Three suture triangulation intussusception
• Two suture longitudinal intussusception (QMH
preference)
Post-Op care
• Scrotal support
• Avoid heavy physical activity : 4 weeks
• Avoid sexual intercourse: 2 weeks
• Most patients will have sperm in their semen
within 4 weeks after vasovasostomy
• If sperm are not present by 6 months, the
operation is considered a failure.
• SA : 2-3 monthly interval until semen
parameters stable for pregnant
• Average time to pregnancy: 1 year (Belker
1991)
Complications
• Bleeding and infection : rare
• Pain: brief duration
• NO report on change in sexual
performance
vasectomy reversal remains the gold standard for treatment
of postvasectomy obstructive azoospermia. Ultimately, it is recommended
that the physician understands the Vasectomy reversal versus IVF
limitations of the current data and offer all of the options, along with the
pros and cons of each, including outcomes and cost based on the
providing institution, in order to help the couple arrive at an informed
decision.
Case 4: Ejaculatory Duct
obstruction
• Dx:
– Low volume ejaculate
– TRUS: Dilated SV
– Pain on ejaculation
• Txn:
– Resection of ejaculatory duct
– Risk : retrograde ejaculation , incontinence &
infection
Non-obstructive azoospermiaNon-obstructive azoospermia
Azoospermia
• Non-obstructive azoospermia (60%)
o Classical
 Small testes and High FSH
o Features of Klinefelter’s syndrome
o Most patients have normal appearance
Non-obstructive azoospermia
• Common causes
o Idiopathic (unknown)
o Genetic
 Numerical chromosomal disorder 15% e.g.
Klinefelter’s syndrome
 Y-chromosome microdeletion 10-15%
o History of undescended testis
o Mumps orchitis
o Chemo/ Radiotherapy
o Varicocele (OAT)
oHypogonadotrophism:
o Kallman’s syndrome
o Pituitary tumor
Hypogonadotrophic hypogonadism
o Low testosterone, Low FSH
o Gonadotropin treatment induces
normal spermatogenesis in most
patients
o May take one year
Case 1: NOA
• A 35 year men presented to infertility clinic
• Wife is 28 year old, normal work up for
infertility by gyn before
• Pt have SA in private before, told to have
no sperm in ejaculate
• How to evaluate him?
• Hx
• PE:
– Secondary sexual charactre
– Body habitus
– Gynaecomastia
– Size and consistency of testis
– Palpable vas
• Semen analysis
– Need at least 2 abnormal SA to confirm dx
How to confirm azoospermia?
• Centrifuge at 1000g x 15 min
• Then examine the pallet
Scenario
• Pt got no child before, examination
showed small soft bilateral testis, with
FSH 3x (ie 3x of 18mIU/ml) of upper
normal limit
• What is the likely dx?
• How to manage him?
• Pt is likely suffered from NOA
• As small bil testes and high FSH reflect
testicular/ spermatogenesis failure
• If there is not obvious cause of testicular
failure identified, like torsion, prior
RT/chemo, or viral orchitis, I would
perform karyotyping and Y(q)CMD for him
• Commonly seen is Klinefelter sx in NOA,
account for 15%
• For YCMD assay, mainly is PCR based assay
for the deletion of AZFa(Sertolic cells only),
b(maturation arrest), c(severe
oligozoospermia) located in the long arm of Y
chromosome
• Overall 15% NOA patients have positive
genetic studies
What is the relationship between
klinefelters syndrome and infertility?
• 47XXY
• 1 in 600 male
• 10% of NOA men
• P/E: Gynecomastia, small firm gonads,
azoospermia, long limbs
• Investigation
– FHS are typically raised
– Testosterone is only low in 50% of cases
• Sperm retrieval rate 70%
Why important to dx Klinefelter?
• Testicular biopsy feature – small hyalinised
seminiferous tubules and pseudoadenomatous
clusters of Leydig cells
• Related to pt’s health
– Androgen deficiency – early osteoporosis, metabolic
syndrome DM, (pt may been T replaced)
– Increase risks of undescended testis, extra-gonadal
GCT, ca breast, NHL
• Related to subsequent fertilization tx
– TESE still have 70% sperm retrieval rate in Azoospermic
men (but not those eunuchoid men)
– Lower in pt with exogenous testosterone
– Live birth : 46%
Y-chromosome microdeletion
• Phenotypically normal
• 9 % of HK Chinese
• Only defect: defect in spermatogenesis
• Defect of one of the three non-overlapping
regions in long arm of Y chromosome
– AZFa  Sertoli cell only
– AZFb  Maturation arrest
– AZFc  severe oligospermia (no histological
pattern)
What is the significance of the dx?
• For complete AZF a and b deletion, no
spermatogenesis, no sperm can be found
• For AZFc deletion, able to have sperm
retrieval in TESE (~60%)
• For genetic counselling all male offspring
inherited YCMD  impact on fertility > ?
Cryopreservation the early age
or Preimplantation genetic diagnosis
(PGD) > female embryo only
Krausz et al. Andrology Unit
Department of Clinical Physiopathology
Viale Pieraccini, 6 Florence 50139 Italy
What are the options of couple?
• Childless
• Adoption
• Donor sperm insemination
• ART with pt sperm (IVF-ICSI)
Couple opt for ART, what will u do?
• Liaise with reproductive team
• For urologist perspective – sperm retrieval
• Option of testicular sperm retrieval
– Percutaneous – TESA (I thin no one do now)
– Open: TESE
• Multiple Random bx (more tissue ~500mg, more
hematoma, more affect T production)
• MicroTESE (less tissue ~10mg, less cx, more
sperm)
Percutaneous Testicular Sperm
Aspiration
• TESA • Success usually in men
with more advanced
spermatogenesis
• Most patients with NOA
will have inadequate
sperm retrieval by this
method
Operative Urology at the Cleveland Clinic p443
Harris and Sandlow. Urol Clin N Am 35
(2008): 235-242
Operative Urology at the Cleveland Clinic p473
Multiple random biopsies
(TESE)
Microdissection TESE
Identification of enlarged tubules was possible in 56%
Schlegel. Hum Reprod 1999; 14(1): 131-5Ramasamy et al. Urology 2005; 65(6): 1190-4
Operative Urology at the Cleveland Clinic p474
Microdissection TESE
• Schlegel et al 1999
o MicroTESE: 160,000
spermatozoa per
9.4mg of testicular
tissue
o Conventional TESE:
64,000 spermatozoa
per 720mg of testicular
tissue
Hum Reprod 1999; 14(1): 131-5
(P<0.05)
TESE
• Conventional TESE:
– Multiple blind testis bx
– Excision of large volume (> 500mg)
– Can result in permanent damage to testis
• Microsurgical technique:
– Spermatogenesis is often sporadic and focal in testes of patients
with NOA
– Conventional TESE is a blind procedure
– Sequential excision of microdissected seminiferous tubules (10-
15mg)
– Try to identify spermatogenically active regions of testis by
direction examination of individual seminiferous tubules
– Minimal amount of testicular tissue with Maximal sperm yield
– Reduced –ve impact of testicular fxn
– Adv over conventional: less hematoma and reduce testis size
What is the success rate of TESE?
• Depends on the stage of spermatogenesis
– Hypospermatogenesis 80%
• Clinical Predictors of Sperm Retrieval
– T, FSH, testis vol are not predictor of outcome of TESE
• Previous TESE sperm retrieval rates
– DOES NOT rule out sperm retrieval in subsequent TESE
– 0,1 or 2 negative TESE: 50%
– 3 or more negative TESE: 20%
– Repeat TESE > 6 months later yield more sperms (80%) than <
6 months after first TESE (25%)
What is the outcome of ART in
NOA?
• Sperm retrieval 50%
• Fertilization rate 55%
• Pregnancy rate 47%
• Live birth rate 40%
VaricoceleVaricocele
Case 1
• M/32
• Good past health
• Wife/33
• Fail conception for 2yr
• PE: Grade III varicocele
Semen Analysis
•
•
•
• 1
•
•
• :
• :
Volume: 2.4ml
pH: 7.5
Sperm concentration: 6x10n6 sperm/ml
Total sperm no.: 14.4x10n6 spermatozoa
Motility: 20% with progressive motility and
11% grade 4 motility
Morphology: 1% of normal forms
White blood cells: <1 million/ml
Hormonal profile: normal
OAT
• NOT obstruction
• Clinically significant varicocele
o Grade 2 or above
o The ONLY surgically reversible factor
What is his diagnosis and its
causes?
• Combined defects in sperm density, motility and
morphology are known as
oligoasthenotetraspemia OAT syndrome – can
even cause azoospermia
• It is commonly associated with clinical
varicocele.
• Other causes include cryptorchidism, temporary
insults to spermatogenesis such as heat, drugs
or environmental toxin, or idiopathic causes
What is the etiology of Varicocele?
• 90% decreased motility
• 15% in population, 40% in
primary infertility, 80% in
secondary infertility
• Dilatation of the pampiniform
plexus of spermatic veins
• Etiology of left testicular vein
dilatation
– Raised pressure in left
sided renal vein outflow
– Absent / dysfunctional
valve in testicular vein
– Nutcracker phenomenon of
left renal vein by SMA and
aorta
What is the pathophysiology
varicocele causing infertility?
1. Alteration of testicular temperature (0.6 degree)
2. Pantesticular defect with abnormal hormone
production and spermatogenesis
3. Stagnation of blood with testicular hypoxia
4. Reflux of renal and adrenal metabolites which
may alter spermatogenesis
PC Tam. Varicocele: Current controversies in
pathophysiology and treatment. Ann. Coll. Surg. H.K.
(2004) 8, 90-97
New Theory
What is the Hudson Classification?
• Standing posture
• Persistent on recumbent posture (think about
RCC with renal vein/ IVC thrombus)
• Grade 0 : Subclinical: Not palpable or visible, but
demonstrable Doppler examination
–Veins ≥ 3.5mm in diameter
–Reversal of venous flow after the Valsalva maneuver
• Grade 1: Palpable during Valsalva manoeuvre
• Grade 2: Palpable on standing , but not visible
• Grade 3: Visible and palpable at rest
Is varicocele repair the
answer ?
Methodologically flawed studies
• Marmar and Kim 1994
o Surgery group (n=186): preg 35.6%
o Conservative group (n=19): preg 15.8%
o Critics: Discrepancy in sample size
• Madgar 1995
o Immediate surgery (n=25): preg 60% at 1st
year
o Control (n=20) : pregnancy 10% at 1st
year
o Critics: SMALL sample size
o Goldstein
o Increase sperm analysis 70%
More flawed studies
• Cochrane review 2004
o 8 RCTS
o 3 studies evaluated men with subclinical
varicoceles
o 2 studies included men with normal SA
o Concluded that varicocele repair for
unexplained infertility could not be
recommended
Evers et at. Cochrane
Database Syst Rev
2004: CD000479.
More flawed studies
• Cochrane review 2006
o Repeat the Cochrane review in 2004 but
excluding 5 RCTs with subclinical varicoceles
or normal SA
o Statistically significant difference in preg rates
between treatment (40%) and control (20%)
o ONLY 3 RCTs with total 237 patients
o Defer to future studies and NOT recommend
varicocele repair
Ficarra et al. Eur Urol
2006; 49: 258-263
More meta-analyses
• Agarwal et al 2007
o Combined observational studies with RCTs
o 17 studies (10 microsurgery, 7 high ligation)
o Sperm density improved by 9.7-12 M/ml
o Sperm motility improved by 10-12%
o Sperm morphology improved by 3%
o NO data on PREGNANCY
Urology 2007; 70: 532-538
More meta-analyses
• Marmar et al 2007
o Included RCTs and observational studies
involving only infertile men with palpable
varicocele and abnormal SA
o 5 studies only
o Odds of spontaneous pregnancy after
varicocelectomy vs conservative treatment is
2.63-2.87
Fertil Steril 2007; 88: 639-648
What conclusion
• Explain to couple that varicocele repair can improve seminal
parameters but uncerntain benefit of conception rate
• KL: varicocelectomy in properly selected couple will have
improved pregnancy rate
• AUA:
– Varicocele txn suitable for pt with palpable varicocele & abnormal
semen parameter
• NICE :
– Men should not be offered surgical txn for varicocele because it does
not improve pregnancy rate
• (EAU guideline 2010: No evidence indicates benefit from
varicocele treatment in infertile men who have normal
semen analysis or in men with subclinical varicocele. In this
situation, varicocele treatment cannot be recommended)
Indications for varicocele treatment
• Well known criteria: AUA best practice
1. Palpable varicocele
2. Known infertility
3. Female partner has normal fertility or
treatable female factor
4. Abnormal semen parameters
• (Adult male with palpable varicocele,
abnormal SA and desire for future
fertility)
Need of monitoring
• Young adult males with varicoceles
and normal SA
o SA every one to two years
• Adolescent males with varicoceles
with normal testicular growth
o Annual objective measurements of testis
size +/- SA
Predictive factors of success
PC Tam. Ann. Coll. Surg. H.K. (2004) 8, 90-97
Oxidative stress markers in semen ??
Cost Effectiveness
• IVF/ ICSI was 3 times as costly as
varicocele ligation Schlegel et al. Urology 1997; 49: 83-90
What are the treatment options of
Varicocele?
• There are two approaches to varicocele repair: surgery
and percutaneous intervention
– Surgical repair of a varicocele may be accomplished by
various surgical methods, including
• Retroperitoneal
• Laparoscopy
• Inguinal
• Subinguinal microsurgical approaches
– Percutaneous intervention treatment of a varicocele is
accomplished by
• Antegrade or retrograde sclerotherapy
• Retrograde embolization
– None of these methods has been proven to be superior to
the others in its ability to improve fertility
Methods of varicocelctomy
• Retroperitoneal high ligation
– Recurrence 15%, hydrocele 10%, not artery
preserving
• Laparoscopic
– Recurrence 2%, hydrocele 5%, not artery
preserving
• Microsurgical subinguinal / inguinal approach
– Recurrence <2%, hydrocele 0%, artery
preserving (<1% injury)
– (Testicular artery, vasal artery, vasal vein,
lymphatics preserved)
• Radiological
– Recurrence 10%, hydrocele 0%, artery not
affected
Classical Method of
Varicocelectomy
• Open Retroperitoneal (Palomo’s
operation)
o High ligation of internal spermatic veins
o Above the internal inguinal ring
Familiar to most General
Surgeons
Cannot tackle
varicocele collaterals
(external spermatic
veins)
Cannot preserve
lymphatics
Laparoscopic approach
• Better don’t mention in
examination
• Ipsilateral side rotated up & in
Trendelenburg position
• Parietal peritoneum is incised
just lateral to spermatic cord
• Spermatic veins isolated then
clipped transected
• Advantages
– Minimal Access
– Bilateral pathologies
• Disadvantages
– Small but non-negligible risks of
major vessel or bowel injury
– Same problems with collaterals
and lymphatics
Varicocelectomy
Open inguinal (Modified Ivanissevich)
o 3 - 4cm oblique incision,
2 fingerbreadths above the pubic
symphysis and just above external ring
o EOA incised
o Preservation of the ilioinguinal nerve
o Spermatic cord is mobilized near the
pubic tubercle
o Double ligation / clipping of dilated
spermatic veins & external cremasteric
veins
o Preservation of testicular artery
o Unable to identify & preserve lymphatics
Subinguinal microsurgical
• 2-3cm transverse incision at the level of external ring
• EOA not incised: less pain
• Spermatic cord identified as it exit the external ring
• Double ligation of the dilated spermatic veins & external
cremasteric vein
• Preservation of testicular artery
• Can tackle external spermatic perforator and gubernacular
vein
• Microscopic advantage:
– To see testicular artery and preserve it (< 1% injury)
– To preserve lymphatics (lymphocele)
– Preserve vasal vein (the only venous return after varicocelectomy)
Subinguinal Microsurgical
Varicocelectomy
Clinical Andrology. EAU/ ESAU Course Guidelines
Subinguinal Microsurgical
Varicocelectomy
Avoid Vesectomy in post-varicocelectomy patients and vice versa as
vasal vein was the only venous return which may cause venous
congestion of the testis
Varicocele Collaterals
Clinical Andrology. EAU/ ESAU Course Guidelines
2010
I will chose microsurgical subinguinal
approach
• Al-Said et al 2008
o Largest prospective randomized trial
(n=446)
o Open, laparoscopic, microsurgical
varicocelectomy
o Single surgeon
• Microsurgical group
o Fewer hydroceles and varicocele
recurrences
o More improvement in SA parameters
J Urol 2008; 180:266
1%
Result of varicocelectomy
• Technical success rate: 90%
• Seminal improvement: 70%
• Natural pregnancy: 40% at 1 year, 70% at 2 year
[Goldstein result]
• Need FU with semen analysis, about 3 monthly for 1y or
until pregnancy occurs
• Consider ART for persistent infertility despite
anatomically successful varicocele repair
• Predictor of success:
– Lack of testicular atrophy
– Sperm density 5mil.ml
– Resonable sperma motility
– Normal FSH
Non-obstructive
azoospermia + Varicocele
Varicocele Repair or TESE ?
Induction of spermatogenesis
• Varicocelectomy in azoospermic men
o Restoration of motile sperm to ejaculate in 21-55% of
patients
• < 10% had sufficient number of motile sperm to avoid
TESE [Schlegel 2004]
• Unlikely to improve SA to an extent that IUI is feasible
• More than 50% of those who showed initial benefit
returned to azoospermic status within 1 year
PC Tam. Ann. Coll. Surg. H.K. (2004) 8, 90-97
Curr Opin Obstet Gynecol 2008, 20: 269-274
Induction of spermatogenesis
• Testicular biopsy is often done
o Germ cell aplasia may predict poor outcome
o Induction of spermatogenesis has been shown
in all testicular histologies
o Prognostic value in potential TESE procedures
PC Tam. Ann. Coll. Surg. H.K. (2004) 8, 90-97
Fertil and Steril 2006; 85: 635-639
Important notice
• IVF/ ICSI is likely even if sperms return to
ejaculate
• Waiting time of up to 12 months for
varicocelectomy to show any benefit
• Karyotyping and Y microdeletion are important
tests before varicocele surgery
• Semen cryopreservation should be done once
sperms return to ejaculate
Fertil and Steril 2006; 85: 635-639
Sperm retrieval technique
Sperm retrieval Technique
• In patient with OA  spermatogenesis is
normal but cannot pass out
– PESA (Percutaneous Epididymal Sperm Aspiration)
– MESA (Microsurgical Epididymal Sperm Aspiration)
• In patient with NOA  abnormal
spermatogenesis (no sperm in epididymis)
– TESA (Testicular Sperm Aspiration)
– TESE (Testicular Sperm Extraction)
Sperm retrieval technique
• VAS Vasal aspiration of Sperm
• SVA Seminal vesicle aspiration
Sperm retrieval in Azoospermia (Obstructive and non-
obstructive)
Obstructive
Azoospermia
Non-obstructive
Azoospermia
Retrieval from
ductal system
Retrieval from
testis
SV aspiration or
Vasal aspiration
Percutaneous
epididymal
sperm
aspiration
(PESA)
Microsurgical
epididymal sperm
aspiration
(MESA)
Testicular
sperm
aspiration
(TESA)
Testicular sperm
extraction (TESE)
Microsurgical
TESE
Testicular biopsy
Percutaneous Open
• OA: No difference in pregnancy
rates by ICSI between techniques,
and frozen or fresh sperm
• NOA: Open technique preferred as
higher sperm yield
Indication of Sperm Aspiration
• Obstructive azzospermia:
– MESA, PESA, TESA & TESE
• Non-obstructive azzospermia:
– TESE
• Severe OAT (motile sperm not reliably
found in ejaculate)
– TESE
• Patient with ejaculatory failure
– Vasal aspiration , TRUS + SVG
Epididymal aspiration of sperm
Sperm retrieval OA, epididymal sperm
Indication:
• Prior vasectomy with no wish of reversla
• CBAVD
• PESA
– For irreversible OA (e.g CBAVD)
– 23G needle, 5ml sperm nutrient medium
– LA, no microsurgical skills required
– Multiple epididymal tubules punctured
– Needle move back and forth within epiedymal
head while side of epididymis and gently
compressed to encourage sperm into needle
– Often leave no microsurgical potential
– For ICSI
• Bleeding, hematoma
– Success 90%
• MESA
– GA, under microscope
– Best tubules can be selected
– With chronic obstruction,
optimal sperm quality is
found in proximal epididymis
– Tuble and tunic closed with
suture
– Less complications
– Success ~100%
– Longer OT time
What are the methods of sperm retrieval?
NOA, testicular sperm required
• TESE
– GA, less chance of injuries to other structures because under direct
vision
– Can be cryopreserved due to larger quantity
– Can enable microTESE in severe cases of NOA
• More meticulous opening of TA, less bleeding
• Identification of enlarged tubules was possible in 60%
– Retrieval success 50% with less tissue removed
• TESA - Percutaneous testicular sperm aspiration
– Office, LA
– Chance of injury / hematoma
– Success usually in men with more advanced spermatogenesis
– Most patients with NOA will have inadequate sperm retrieval by this
method
– Shorter procedure: Cameco syringe holder
– Success 10-50%
Vasal Aspiration of Sperm
• Procedure similar to
vasectomy
• For cases with distal
obstruction or anejaculation
What is the solution to preserve
sperm after TESE
• Human Tubule solution
• NOT Bouin’s solution !!!!!!!! That is for
testicular biopsy
Assisted Reproductive
technique
What is the ART and sperm requirement?
• ART – small significant malformations (6%) as compared to normal
pregnancy (4%)
• Need chromosome analysis before ART
• IUI : 5-10 million sperm at least
• IVF : 0.1-0.5 million
– Ovarian stimulation to produce multiple oocytes
– USG guided aspiration of ova
– Mixed with sperm
– Embryos incubated for 3 days and placed in uterus
– One third pregnancy rate
• ICSI : one sperm is needed
– Should have chromosome analysis before
– ~50% of all ART
– One third pregnancy rate, dependent to female age
– More malformation rate than IVF
How is IVF performed?
• Gonadotropins used to recruit multiple oocytes in each
cycle
• USG to monitor follicular development
• Ova harvested before ovulation with USG guided needle
aspiration
• In-vitro fertilization : mixing processed sperm with
recovered oocytes (90% success if normal sperm fxn)
• When fertilization occur  developing embryos are
incubated for 2-3 days in culture
• Then placed trans-cervically into the uterus
• Successful pregnancy : 20-30%
• Malformation rate: 4%
How is ICSI performed?
• Indicated in
– severe male factor infertility
– Failed prior regular IVF cycle
– Sperm show significant defect in fertilising ability
• Single sperm injected into individual ova
• Pregnancy rate: 20-37%
• Take home baby rate: 31%
• Malformation rate: 6% (not significant different
from IVF)
What are the risks of ART ?
• Medication :
– Ovarian hyperstimulation syndrome
– Ovarian torsion
• Procedure related :
– Associate with sperm / oocyte retrieval: rare
• Procedure associated:
– Multiple births
– Preterm delivery
• Offspring:
– Inherited YCMD from father  infertility
OHSS
• Ovarian enlargement due to multiple ovarian cyst & acute
fluid shift to extracellular space
  ascites, hemoconcentration , hypovolemia, electrolyte
disturbance
• Mild (20%)
– Abd distension , nausea, vomiting , diarrhoea
– Ovarian enlargement (5-12cm)
• Moderate (5%)
– Features of mild + USG show ascites
• Severe (1%)
– Ascites +/- hydrothorax & SOB
– Hypovolemia
– Coagulation abnormalities
– Hemoconcentration (increase blood viscosity)
– Decrease renal perfusion and function
Multiple gestation
• Most ART pregnancy are multiple birth
• Associated with increase:
– Preterm delivery
– Low birth weight
– Perinatal mortality
• Single embryo transfer (SET) vs multiple
embryos
– Preg rate not lower in SET
– Number of multiple birth dramatically reduce
CryptorchidismCryptorchidism
What is cryptorchidism?
• Cryptorchidism is multifactorial in origin and can be
caused by genetic factors and endocrine disruption
early in pregnancy
• Cryptorchidism is often associated with testicular
dysgenesis and is a risk factor for infertility and germ
cell tumours
• In a randomised study, it orchidopexy improved
testicular growth in boys treated at the age of 9 months
compared to those aged 3 years
• Paternity in men with unilateral cryptorchidism in almost
equal to that in men without cryptorchidism
• Bilateral cryptorchidism significantly reduces the
likelihood of paternity
What are the recommendations of
treatment?
• Hormonal treatment of cryptorchidism should be
abolished because of the risk of germ cell apoptosis and
subsequent reduction of sperm production
• Early orchidopexy (6–12 months of age) might be
beneficial for testicular development in adulthood
• Post-pubertal orchidopexy is advisable with potential
fertility preservation
• If undescended testes are corrected in adulthood,
testicular biopsy for detection of CIS which can be
removed, thus preventing development of a malignant
tumour
• TESE for NOA with cryptorchidism
– Sperm retrieval rate: 70%
– Pregnancy rate: 40%
– Comparable to non-cryptorchid patient
What is the surgical treatment?
• Success rate of surgical treatment for
undescended testes is 70–90%
• When the spermatic cords or the
spermatic vessels are too short to allow
proper mobilisation of the testis into the
scrotum, a staged orchidopexy (Fowler–
Stephenson procedure)
• Sperm retrieval rate 70%
Ejaculatory disorderEjaculatory disorder
What are the facts of ejaculatory
disorder?
• Aetiological treatments for ejaculatory disorders should be
offered before sperm collection and ART is performed
• Premature ejaculation can be treated successfully with either
topical anaesthetic creams or SSRIs
• In men with spinal cord injury / DM neuropathy, vibro-
stimulation at glans penis and electro-ejaculation are effective
methods of sperm retrieval
• Retrograde ejaculation was caused by spinal cord injury / DM /
TURP / alpha-blocker / retroperitoneal LN dissection
– Sympathomimetics, Ephedrine / pseudoephedrine / TCA - 50%
successful rate
– If failed > alkalinised post-ejaculate urine specimen for IUI / IVF – 50%
successful rate
• What is this and what is it used for? (2)
• Name 1 life-threatening complication from its
use (1)
• Alternative treatment if this method fails? (1)
Q58
• Electoejaculator (1). For use in patients
with male infertility due to anejaculation as
a result of neuropathic cause eg. spinal
cord injury (1)
• Autonomic dysreflexia (1)
• Vasal aspiration of sperm (1)
Electroejaculation
• Indicated in patients with anejaculation due to neurological cause (eg. spinal cord
injury) but unsuitable for penile vibratory stimulation to induce ejaculation
1) Spinal cord injury (SCI) below T10 (reflex arc level for ejaculation)
2) Patients failing penile vibratory stimulation for other reasons
• Use of rectal probe to stimulate electrically the perirectal, periprostatic sympathetic
nerves
• Requires general anesthesia for patients with incomplete / no / low SCI
• Spinal cord-injured patients with lesions above T6 or a hx of autonomic dysreflexia 
BP monitor for autonomic dysreflexia & severe hypertension mandatory
• Pre-treatment: pseudoephedrine 7-10 days to facilitate ejaculation, Potassium citrate
to alkalinize the urine
• Bladder emptied, then filled with 30ml alkalinizing medium. Mineral oil for Foley
insertion as commonly used lubricants are spermicidal
• Electrical stimulation till ejaculation. Collect antegrade & retrograde ejaculation
separately
• Sperm from EEJ: poor motility & viability, decreased ability to penetrate cervical
mucus and impaired fertilizing capacity
Autonomic Dysreflexia.
• Uncontrolled sympathetic response classically seen in patients with spinal
cord injury T6 or above (above the splanchnic circulation)
• Pathophysiology : due to spinal cord lesion above the level of thoracolumbar sympathetic
outflow (hence lack of inhibitory control from higher centre) +/- synaptic re-organisation after
SCI leading to exaggerated reflex arcs below the lesion level => exaggerated and aberrant
sympathetic response to stimulus (rise in BP) but symptoms of parasympathetic response
(flushing, nasal congestion) of regions above the lesion level
• Common symptoms and signs
– Headache, Hypertension, Flushing/blotching of skin above level of injury, Sweating above
level of injury, nausea, nasal congestion, tachy/bradycardia
– (Left untreated) intracranial pressure rise (from hypertension) and seizures and
intracerebral bleed
• The main precipitants
– Urological – Bladder distension (accounts for 85% of AD), UTI, urological procedures
eg. UD / cystoscopy, genital stimulation
– Gastrointestinal – Rectal distension (electroejaculation), anorectal procedures, acute
abdomen
– Musculoskeletal –Fractures, dislocation
– Others – Skin problems (for example, ulceration, infection), pregnancy and labour.
• Management (prevention)
– Awareness of such an entity!
– Avoidance of build-up of intravesical pressure in susceptible patients eg.
CISC
– Use of general / spinal anesthesia during at-risk procedures /
intervention
– Pharmacological prophylaxis before procedure : alpha blockers,
nifedipine
• Management (treatment)
– REMOVE THE PRECIPITANT eg, STOP INFUSION
DURING URODYNAMIC STUDY
– Sit up the patient to provide orthostatic decrease in BP
– Look for other precipitants eg. remove faecal impaction
– Sublingual nifedipine, consider intravenous agent e.g hydralazine or
diazoxide
Cryopreservation
Fresh vs Frozen sperm
• Similar fertilization rate
• Similar clinical pregnancy rate
• Ongoing pregnancy or delivery
– Trend favouring fresh spermatozoa
–Loss of vitality secondary to Freeze-
Thaw process up to 50%
–Not a good option for patients with very
low retrieval numbers
HaematospermiaHaematospermia
What is the cause of
haematospermia?
• Infection – TB, HIV
• STD
• Prostatitis
• Ca prostate
• Post-TRUS Bx
• Urethritis
• Systemic disease (bleeding tendency)
What is the investigation?
• MSU
• EMU
• Urine cytology
• PSA
• TRUS (prostatic calcification / BPH /
ejaculatory duct cyst)
• FC
If all normal > reassurance
What is the relationship between
Ca testis and infertility?
• Infertile men with abnormal semen analyses have 20-fold greater incidence
of testicular cancer
• About 25% of men diagnosed with ca of testis have oligospermia at
presentation
• Chemotherapy induced azoospermia typically occurs at 3 months. The
reason is that spermatocytes are not rapidly proliferating and survive
chemotherapy. These cells will take 1-3 months to become mature sperm
and therefore there will be sperm in the ejaculate for that period of time
• The germ cells that are most susceptible to chemotherapy are the rapidly
proliferating spermatogonia
• Leydig cells are not rapidly proliferating and survive chemotherapy but their
function may be impaired
• Alkylating agents are among the high risk chemotherapeutic agents for
causing azoospermia
• Sperm cryopreservation (Onco-TESE at the same time of orchidectomy)
should preferably be done before the initiation of cytotoxic therapy but could
be carried out after
Onco-TESE
• High cure rates of testicular germ cell tumours and
lymphoma with cytotoxic chemotherapy
o Standard: cryopreservation of ejaculated
spermatozoa before chemotherapy
• Tumour-induced azoospermia in some patients
o TESE in azoospermic cancer patients after
chemotherapy may not succeed
Chan et al. Cancer 92: 1632-1637, 2001
Onco-TESE
• TESE in azoospermic cancer patients
BEFORE chemotherapy
o Contralateral TESE in patients with germ
cell tumours following inguinal
orchidectomy (sperm retrieval 43%)
o Unilateral or Bilateral TESE in patients
with lymphoma (sperm retrieval 47%)
Schrader et al. Urology 61: 421-425, 2003

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Infertility [Dr. Edmond Wong]

  • 2. Outline • Spermatogenesis • Hormonal effect • Infertility (workup) • Obstructive azzospermia – Idiopathic (+ scrotal exploration & testicular bx) – CBAVD – Post vastectomy (vasectomy + reversal) • Non obstructive azzospermia – Klienfilter syndrome – YCMD • OAT: varicocele • Sperm retrieval technique • Assisted reproductive technique • Fertility issue in oncological patient
  • 3. What is spermatogenesis? • Spermatogonium  • Primary spermatocyte  first meiosis • Secondary spermatocyte  second meiosis • Spermatid  spermatozoa • Spermatozoa – Can be used for ICSI • Process takes 70 days
  • 4.
  • 5. What is the definition of infertility? • Inability of a sexually active, non- contracepting couple to achieve pregnancy in one year –WHO
  • 6. What is the epidemiology? • Normal couple pregnancy rate – 20-25% per month • 80% of couples will conceive within 1 year or unprotected SI • Abnormal couple pregnancy rate – 1-3% per month • 15 % of population • 5% remain unwillingly childless • 30% will conceived at some time if left untreated
  • 7. Contributing factors • Female factor 40% • Male factor 30% • Female + Male factor 30%
  • 8. Cause • Pre-testicular cause: – Hypothalamic disease – Pituitary disease (hypogonadotropic hypogonadism) • Testicular cause: – Varicocele – Chromosomal abnormalities • Klinefelter’s syndrome (XXY) • Y-chromosome microdeletion (sertoli cell only , maturation arrest , etc) – Orchiditis – Trauma – Torsion – Cryptorchidism – Gonadotoxins : chemo , radiation – Systemic disease
  • 9. Cause Post-Testicular cause: • Disorder of sperm transport – Congenital bilateral absence of vas (CBAVD) – Acquired disorders (vasectomy , infection) – Functional disorders (ejaculatory disorder) • Disorder of sperm motility – Congenital defect of sperm – Immunologic disorder – Infection (liver cirrhosis, renal failure)
  • 10. What are the prognostic factors? • Duration of infertility • Primary or secondary infertility • Results of semen analysis • Age (most important) and fertility status of female partner – Compared to a woman at 25 years old, the fertility potential is reduced to 50% at age 35
  • 11. Common complaints • Male factor infertility o Abnormalities in S.A. o Varicocele
  • 12. What is history taking of infertility (preferably with partner)? • AGE • Sexual : – Duration of infertility – Primary or secondary – Frequency and timing of intercourse – Use of contraceptive or history – Use of vaginal lubricant (affect sperm function) – Erectile or ejaculatory dysfunction • Partner history - Previous pregnancy, age • Developmental : – Age at puberty; – Undescended testis – History of torsion – Prepubertal mumps (asso with NOA) – Y-V plasty of the bladder
  • 13. History • Medical and surgical - – Orchitis; Epididymal-orchidits; STD – varicocele; – testicular torsion, trauma, or tumour; – inguinoscrotal surgery; pelvic injury or RPLND – radiotherapy/chemotherapy – respiratory diseases associated with ciliary dysfunction – DM • Drugs and environmental – – alcohol consumption; smoking habits; – hot baths; – anabolic steroids (hypogonadotropic hypogonadism) • Family - Hypogonadism; cryptorchidism, cystic Fibrosis
  • 14. What is physical examination? • Secondary sexual development – Habitus ?KFS; body hair distribution; gynaecomastia (KFS) • Genitourinary – Inguinoscrotal scars (hernia) – Penis: Peyronie's plaque, phimosis, hypospadias/chordee – Scrotum • Testes size, tumor – Volume with a Prader orchidometer (normal >20ml; varies with race) • Epididymus : induration or dilatation (obstruction) • Vas presence – CBAVD – Unilateral vasal agenesis has unilateral renal agenesis • Varicocele: grade • Digital rectal examination of prostate
  • 15. What are the investigations? • Initial tests - Semen analysis x 2 – Azzospermia – Oligo-astheno-teratosepmai (OAT) • Save post-ejaculatory urine (5-10sperm / HPF) if low volume sperm • Initial tests - Hormonal measurement – Indications: • Symptoms of endocrinopathy (decrease libido) • Oligospermia (< 10million/ml) • Abnormal scrotal exam – 1st line : Morning testosterone + FSH – 2nd line : LH/testosterone/prolactin – FSH is a marker for spermatogenesis
  • 16. Others: • Chromosome analysis – Pimary spermatogenic failure – azoospermia, atrophy testes, increase FSH • Scrotal USG – Varicocele, testicular abnormalities • TRUS – Ejaculatory duct obstruction • Testicular biopsy
  • 17. What is the semen analysis? • At least 2 samples – If the results of semen analysis are normal according to WHO criteria, one test should be sufficient • Abstains for 3-5 days (>7 day reduce motility) • Should be produced by masturbation without use of latex condoms (spermicide) • Wide mouthed container • Avoided coitus interruptus – Lost initial part of semen, bacteria, acidic vaginal secretions contaminate the specimen • Specimen kept in pocket (close to body temperature) • Examined within 1-2 hour
  • 19. • WHO SA criteria – Vol 2ml or above – Conc >20 million / ml – pH >7.2 – Motility 25% GA or 50% GA+B – Morphology >14% normal by Kruger’s criteria – Viability 75% or more viable
  • 20. What is the grading of sperm motility? Grade Sperm motility 0 No motility 1 Sluggish; no progressive movement 2 Slow, meandering forward progression 3 Moving in a straight line with moderate speed 4 Moving in a straight line at high speed
  • 21. Sperm Penetration Assay • aka “zona-free hamster ova assay” • Dynamic test of fertilization capacity of sperm • Failure to penetrate at least 10% of zona- free ova consistent with male factor • False positives and negatives exist
  • 22. SA • What are the parameters, lower reference limits (WHO)? – Extreme cases of OAT < 1 million spermatozoa/mL • SA: on at least 2 occasions – Volume > 2.0ml – Sperm density >20x10^6/ml – Motility >50% forward progression • And : – No significant sperm agglutination • Possible antisperm antibodies (ASA)  IgA & IgG bound to sperm – NO pyospermia (semen round cell)  leukocytes or immature germ cell
  • 23. Kruger Morpholoic criteria • Normal sperm: – Smooth , oval head – Acrosome 40-70% of head volume – No abnormalities of the neck , midpiece or tail
  • 24. What are the contributions in seminal fluid? • 30% prostate (acidic) • 60% SV (Alkaline) • 10% testis • Thus if blockage of SV and proximal – Small volume (< 1ml) , acidic SA  CBAVD • Why fructose level: – Fructose is secreted by SV , if low , obstruction distal to SV
  • 25. What are DDx of azoospermia? • Azzospermia in 1% of general male population • 10% of infertile male population • 2/3 are non-obstructive in nature: – testicular failure – Genetic disorder : KFS , YCMD , etc – Varicocele – Post-chemo/ RT – Unexplained testicular dysfunction • 1/3 are obstructive in nature: – Genetic: CBAVD – Vasectomy – Infection (epieidymo-orchitis/ STD) , previous surgery • cryptozoospermia o Sperms were found in 20% of pellet after centrifugation
  • 26. Azzospermia • Low volume azoospermia – CBAVD – Ejaculatory duct obstruction (EDO) • A semen volume <1.5 mL and with an acid pH and low fructose level suggests ejaculatory duct obstruction or CBAVD – Hypogonadism – Retrograde ejaculation – Failure of emission / ejaculation • Normal volume azoospermia – Spermatogenic failure – Varicocoele
  • 27. • Approach to low volume azoospermia – Save PEU (5-10sperm / HPF) – Check FSH, testosterone – Exam for vas – TRUS + SVG to confirm EDO, if all normal
  • 28. • Approach to normal volume azoospermia – Rule out varicocele • Hudson – G3 : visible – G2 : Palpable on standing – G1 : Palpable on Valsalva • Check FSH for spermatogenic failure – Testicular failure : small testes – Y chromosome microdeletions : normal sized testes • If not, then either SCOS or obstruction (testicular Bx)
  • 29. Approach to man with azoospermia • Exam : CBAVD, varicocele, testes size • Check SA, to see whether NV or LV • NV : check FSH • LV : PEU, testosterone, FSH • NOA : small sized testes, FSH raised • OA : except CBAVD, normal volume azoospermic, normal FSH
  • 30. What are DDx of OAT? • Varicocele • Systemic illness • Bil cryptochidism • Gonadotoxins – heavy metals • Lead, cadmium, mercury, pesticides, herbicides, carbon disulphide – Alcohol • Spermatogenesis, reduced sexual function – Tobacco smoking • Oxidative damage to sperm DNA – Steroid (for body-building) • Spermatogenesis – Heat
  • 31. What are DDx of isolated asthenospermia? • Antisperm antibody – Acquired or congenital ductal obstruction – Vasectomy – Testicular/epididymal infections – Testicular torsion/trauma – Cryptorchidism – Varicoceles • Prolonged abstinence • Varicocele • GU infection • Spermatozoal motility defect
  • 32. What are DDx of no abnormality found in semen analysis? • Female factor • Coital problem • Acrosomal defect
  • 33. Azzospermia Centrifuge sample + Post-ejaculatory urine  Azzospermia confirmed  FSH N 3x Testicular bx+/- Scrotal exploration + Testicular failure Vasogram
  • 34. Holistic Management • Treatment Options o Consider risks of surgery/ ART  Remained childless  Adoption  Donor insemination o Scrotal exploration +/- Reconstructive Surgery o Varicocelectomy o Sperm retrieval + ART • FEMALE FACTORS
  • 35. Pragmatic Management • Obstructive Azoospermia o Congenital absence of vas  Genetic counseling  Sperm retrieval + ART o Suspected Obstructive Azoospermia  Options of Sperm retrieval/ ART vs Scrotal exploration/ reconstructive surgery  If scrotal exploration/ reconstructive surgery is contemplated, testicular biopsy is done to confirm normal spermatogenesis  If ART is chosen, proceed to sperm retrieval
  • 36. Pragmatic Management • Non-obstructive azoospermia o Overall 50% success of sperm retrieval by TESE o Consider genetic study  Karyotyping: Klinefelter’s syndrome  Y-chromosome microdeletion (Azoospermic Factor AZF)  AZFa or AZFb: complete absence of spermatogenesis  AZFc: 60% success of sperm retrieval by TESE  Overall 15% NOA patients have positive genetic studies  Risks of transfer of abnormal genes to offspring's o NO NEED of pre-TESE testicular biopsy
  • 37. Pragmatic Management • Oligo-astheno-teratospermia (OAT) o Any components o Clinically significant varicoceles  4 criteria fulfilled  Subinguinal microsurgical varicocelectomy  90% technical success  70% patients have improvement in S.A. parameters  Spontaneous pregnancy 30-40% (consider FEMALE FACTOR)  1% testicular artery injury
  • 38. General advice to promote fertility • Wear loose underwear • Avoid excessive hot baths • Avoid regular or heavy drinking • Quit smoking • Healthy, fit life , taking holidays and regular exercise • Have intercourse every other day around the time of ovulation
  • 39. Hormonal base therpay? Gonadotrophins • HCG+ hMG • Use in hypogonadotrophic hypogonadism (Low FSG, LH and Testosterone) • SE: expensive, mood and libido change Clomiphene Citrate: • Anti-estrogen  increase GnRH output  increase serum testosterone • SE : gynaecomastia, wt gain , acnes, mood change
  • 40. Non-hormonal base therapy • Anti-oxidant therapy: – Glutahione – Vit E • Micronutrient supplements: – Zinc – Folate • L-acetylcarnitien (ProXeed)
  • 41. Obstructive azoospermia •((40% of Azoospermic Patients) •40% of Azoospermic Patients)
  • 42. Obstructive Azoospermia • (40% of Azoospermic Patients) o History of vasectomy/ epididymo-orchitis/ STD o Primary or Secondary infertility o Normal sized testes o Distended or Indurated epididymes o Congenital absence of vas o Normal hormonal profiles
  • 43. Obstructive Azoospermia Low volume ejaculate and acidic pH • Idiopathic OA (previous infection) • Congenital absence of vas – IRREVERSIBLE > ART – Clinical Diagnosis – Confusion in patients with Partial vasal agenesis – Bilateral abdominal vas stopped abruptly at inguinal canal – In doubt, TRUS to confirm seminal vesicle absence • Vas obstruction + previous vasectomy • Ejaculatory Duct Obstruction – REVERSIBLE > surgical correction (VE) – Pain on ejaculation – TRUS to confirm Distended seminal vesicle
  • 44. Case 1: Idiopathic OA • Mr. Chan visit your clinic for subfertility problem • 2 sets of semen analysis are done
  • 45. SA Semen analysis Value Semen volume (ml) 2ml pH 7.2 Total sperm count 3 x 106 Sperm concentration 1.5 x 106 Sperm motility 50% (PR+NP) Sperm morphology 15% Viability 80% Time to liquefy 10mins Semen fructose 20umol MAR test negative
  • 46. Frag.1 • Q1. Please comment on the SA • A1. Oligospermia with normal motility and morphology
  • 47. Frag.2 • Medical history – Hx of gonococcal infection • Physical exam – vas deferens presence, both testes normal size, indurate epieidymis • Endocrine – FSH 2 IU/L and testosterone 500ng/dL (normal range > 300ng/dL)
  • 48. What’s your further workup ? • Testicular biopsy: • Although in pt with normal FSH & testicular volume, obstructive cause is likely , however, there is still chance of maturation arrest which have the similar clinical picture • Purpose is to differentiate btw obstructive and non obstructive azzospermia when the clinical picture is not clear, when ductal obstruction is suspected base on a normal serum FSH and normal testiscular volume & we are planning for a reconstruction (VE) • Clear picture of CBAVD or testicular failure do not require testicular biopsy • Vasogram should not be done during Testicular bx , it should be done before reconstruction because it carries a risk of obstructing the vas • Another role of testicular biopsy in NOA is for sperm retrieval & ART • Tescticular bx is not indicated in patient with oligospermia
  • 49. Testicular biopsy • Types of testicular Bx – Open testicular Bx under GA – Percutaneous testicular Bx using trucut needle • A small scrotal incision that does not deliver the testis outside the skin or tunica vaginalis minimizes postoperative scarring and facilitates subsequent scrotal reconstructive surgery • Both sides, upper medial and lateral surfaces • Medium : Bouin’s solution – (Picric acid, formaldehyde, acetic acid) – Other solution: Zenker’s, or glutaraldehyde; formalin should not be used – Eppendorf tubes if sperm cryopreservation as well
  • 50. • What is this? (1) • What is it used for? (1) • What is it composed of? (1) Q31
  • 51. • Bouin’s solution (1) • Medium to transport testicular biopsy (1) • Picric acid, formaldehyde, acetic acid (1 for mentioning any of these 3 components) • Others preservation solutions: – Zenker’s / collidine buffered glutaraldehyde solution
  • 52. What is the scoring system for testicular biopsies ?(Johnsen score) Score Histological criteria 10 Full spermatogenesis 9 Slightly impaired spermatogenesis, many late spermatids, disorganized epithelium 8 Less than five spermatozoa per tubule, few late spermatids 7 N o spermatozoa, no late spermatids, many early spermatids 6 N o spermatozoa, no late spermatids, few early spermatids 5 N o spermatozoa or spermatids, many spermatocytes 4 N o spermatozoa or spermatids, few spermatocytes 3 Spermatogonia only 2 N o germinal cells, Sertoli cells only 1 N o seminiferous epithelium
  • 53. Frag.3 • USG: testes normal, dilated epididymis without cyst, seminal vesicle normal, no Mullerian cyst • Testicular biopsy: presence of spermatozoa
  • 54. Management • Counseling: – This is likely to be obstructive azzospermia – Remain childless – Adoption – Donor insemination • Definitive treatment : – Sperm retrieval technique with ART – Reconstructive surgery (VE) + vasogram • When no female factors presence
  • 55. Patient opt for ART • Sperm retrieval and IVF/ICSI generally is the best choice of treatment for obstructive azoospermia when – [1] the female partner is over age 37 – [2] there are coexisting female infertility factors that require IVF – [3] the likelihood for success with sperm retrieval/ICSI is greater than with surgical treatment • Options: PESA, MESA
  • 56. MESA • Advantage: – Allow meticulous hemostasis during retrieval – Allow ample amount of sperm to be retrieved
  • 57. Pt opt for reconstructive surgery • Vaso-epieidymostomy – Microsurgical Intussuception Technique (Berger) • Vas lumen 400um • Epididymal tubule 150um • Technically demanding • Patency 70-80% • Spontaneous pregnancy 20-40% • Anatomical recanalisation following surgery may require 3-18 months • Before microsurgery (and in all cases where recanalisation is impossible), epididymal spermatozoa should be aspirated and cryopreserved for use in ICSI in case of surgical failure • Distal patency confirmed by vasogram • Proximal patency : microscopic visulaization of intravasal fluid
  • 58. Vasography • Vasography may help to identify distal obstruction in the vas deferens or ejaculatory ducts. However, due to the risk for vasal scarring and obstruction, vasography should be performed at the same time with reconstructive surgery • Can be percutaneous or open vasogram • How to perform: – At straight portion of the scrotal vas – Saline vasography : 0.5-1ml NS – Dye vasography : indigo carmine – Contrast vasography • Normal vasogram: – Contrast agent seen in vas deferens, SV , Ejaculatory duct + Bladder
  • 59. Three sutures end to side intussusception VE technique (Berger)
  • 60. Two sutures end to side intussusception VE technique (Marmar and Chan)
  • 61. Case 2: CBAVD • Gentleman with azzospermia • P/E: bilateral absence of vas • Dx: Congenital bilateral absence of vas deference
  • 62. What is the association between cystic fibrosis and infertility? • The most common is congenital bilateral absent vas deferens which occur in 95% of men • They typically have azoospermia • Autosomal recessive • SA: low volume ejaculate & acidic pH – Because also absence of SV, ejaculate only contributed by prostate (which is acidic) • The defective gene (CFTR) is on chromosome 7 • Cystic fibrosis transmembrane conductance regulator Gene • CFTR protein is a chloride channel which when defective causes thick mucus secretions that result in the typical presentation with recurrent upper respiratory tract infections
  • 63. CFTR gene in CBAVD • The CFTR gene provides instructions for making a protein called the cystic fibrosis transmembrane conductance regulator. • This protein functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. • The channel transports negatively charged particles called chloride ions into and out of cells. The transport of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. • Mutations in the CFTR gene disrupt the function of the chloride channel, preventing the usual flow of chloride ions and water into and out of cells. • As a result, cells in the male genital tract produce mucus that is abnormally thick and sticky. • This mucus clogs the tubes that carry sperm from the testes (the vas deferens) as they are forming, causing them to deteriorate before birth. • Without the vas deferens, sperm cannot be transported from the testes to become part of semen.
  • 64. Treatment options • The obstructions in CBAVD is IRREVERSIBLE  no reconstructive surgery – Sperm retrieval • PESA (Percutaneous Epididymal Sperm Aspiration) • MESA • ICSI assisted reproduction • Genetic counselling • Non-invasive” • Multiple epididymal tubules punctured
  • 65. Case 3: vasectomy + reversal
  • 66. Scenario • M/35 • Good past health • 1st marriage for 5 years • 4 daughters • Sole bread winner of the family • Request vasectomy
  • 67. • How would you counsel the patient ? • What other alternatives ? • What are the potential risk and complication
  • 68. History • To attend the clinic with partner • Age • Marital status • Number of previous children • Previous contraceptive method • Previous surgery on inguinal region • Why he wish to have vasectomy • Discuss with other contraceptive method
  • 69. Physical examination • Specifically look at – Laxity of the scrotum – Whether vas are palpable – Rule out other scrotal pathology
  • 70. Indication • Every man of legal age and able to give consent may decided in favor of vas ligation or occlusion for the purpose of sterilization • Other consideration : no of children , stable relationship with written consent from partner, chances of refertilization discussed
  • 71. Informed consent • Procedure, written consent, with partner • Consider as a irreversible process • Early failure (surgical error): 1 in 200 • Late failure (recanalization): 1 in 2000 • Subsequent refertilization: 70-90% • Acute complication: – Bruising & swelling – Hematoma (2%) – Infection (3%) • Long term complications: – Testicular and epididymal pain (5%) – Sperm granuloma (10%) – Serum antisperm antibody (70%) • Need of post-op semen analysis • Must continue contraception until azzospermic (3m)
  • 72.
  • 73.
  • 74. Vasectomy • LA, warm room & antiseptic solution • Isolate vas from cord vessels • Vas trapped btw mid, index and thumb • Use bilateral small incision – Reduce division of same side twice • Vas is expose, dissected free from artery , vein and nerves • 1cm segment is removed • Occlusion: suture ligated, clip, division btw ligatures • Ends are occluded by intra-luminal cautery (reduce recanlization to 0.5%) • End separate in different facial plane • Skin closed with 4/0 vicryl • Dressing
  • 75.
  • 76.
  • 77. Modification • No scalpel technique (China 1993) • Electrocoagulation of the cut edges • Fascial interposition
  • 78. No scalpel technique • Developed by Dr. S. Li in China • Compared with conventional vasectomy o Less haematoma o Less pain o Less infection o Less OT time (<40%) o Li S, Goldstein M, Zhu J, Huber D: The no-scalpel vasectomy. J Urol 1991; 145:341-344. o Nirapathpongporn A, Huber DH, Krieger JN: No-scalpel vasectomy at the King's birthday vasectomy festival. Lancet 1990; 335:894-895.
  • 79. Effectiveness • Safest contraceptive methods • Most cost-efficient method (Nakhaee 2002) • Early and late failure rates are 1/200 and 1/2000 respectively • More effective than tubal ligation and less morbidity
  • 80. Complication • Acute: – Bleeding/ hematoma (2%) – Epididymitis/ wound infection (3%) • Long term: – Recanalization: <1% – Sperm granuloma 3-75%  sperm antibodies – Chronic testicular or epididymal pain of unknown pathology (5%) • Prudent to send vas for histology to show complete diameter – (Tam: no need to send if precise excision)
  • 81. Post vasectomy SA • General recommendation : at 3 & 4m, after 24 ejaculations • Obtaining at least one and preferably two absolutely azoospermic specimens 4 to 6 weeks apart • A ‘special clearance’ – Consecutive 2 SA showing non-motile sperm < 10, 000 mil/ml at more than 7 months after vasectomy (no pregnancy on prospective FU) – No more than risk of pregnancy after two azoospermic semen samples, as a result of recanalisation, ~1/2000 – Discontinue contraceptive precautions after appropriate counselling
  • 82. Psychosexual effect • Positive: – Problem of contraception resolved – Fear of unwanted pregnancy gone • Negative: – If patient are forces to have vasectomy – If partners not involved in decision
  • 83. What to do if failed vasectomy? • Confirmed presence of sperm by SA x2 • Explained that quoted risk is : 1 in 2000 • Offer scrotal exploration  identify vas  further occlusion • Advice alternative form of contraceptions
  • 84. 5 years later…. • M/40 • Same wife • Very successful in business and become a millionaire • Would want a son
  • 85. Questions • What are the options • How to counsel the patient?
  • 86. Indication for vas reversal • Divorce followed by remarriage or a new partnership • Unexpected death of one of their children • Improved economic standing • 5% of men with vasectomy
  • 87. Workup ? • Reproductive history, same partner ? • PE: – Size , consistency of testis – Epididymis – Vas palpable? Sperm grauloma – Vasal gap, location – Groin scar (second site of obstruction) • SA • Likely hood of success? – Experience of surgeon – Time since vasectomy – Partner age and reproductive status
  • 88. Consider • Female factors e.g. age, ovarian reserve, tubal status • Surgical expertise/ ART success • Side effects of different treatments • Patient preference
  • 89. Options • Remain status-quo • Adoptions • Donar insemination • Vasovasotomy or Vaso-epididymostomy • Sperm retrieval +/- ART – PESA, MESA
  • 90. Reasons for reconstructive surgery over direct sperm retrieval and ART • Allows couples to have offspring in a natural manner • Obviates the need for sperm retrieval for every other child they want to have • More cost effective by Schlegel’s analysis • Reconstructive surgery is relatively safe procedure in relations to the possible risks involved in the stimulated cycle ART eg. OHSS • Despite some patients may need ART after reconstructive surgery, a less invasive form of ART often is required than when reconstructive surgery not done
  • 91. Why obstruction at epididymis after vasectomy? • High intraluminal pressures after vasectomy • Rupture of the delicate epididymal tubule • Secondary obstruction in the epididymis
  • 92. Types of reconstruction :What are the factors to consider ? • Obstructive interval – Secondary epididymal obstruction rarely occurs within 4 years of a vasectomy, present in > 60% of patients after 15 years of vasal obstruction (Fuchs and Burt 2002) • Quality of fluid from the proximal vas segment (sperm count) • Partner factors such as age, fertility status, and parity
  • 93. Proximal vas fluid • Copious clear fluid with motile sperm  94% sperm in ejaculate after VV • NO sperm in vasal fluid  60% (Belker,1991) • Thick or absent vas fluid, no sperm  VE • Proximal vas length 2.7cm + sperm in vasal fluid  favor VV over VE (Witt 1994) • Sperm granuloma  improved patency rate (pop off valve pressure release)
  • 94. How to perform scrotal exploration? • GA , patient supine • Microsurgical technique • Bilateral 1.5cm longitudinal incision over vas • Vas identified above the previous vasectomy, vasal gap identified • Dissection of vas proximally and distally until sufficient length for cut ends to slightly overlap one another • Held in vasectomy reversal clamp above skin level • Both end are transected into normal area  inspected and gently dilated with forceps • Few drops of fluid from testicular end of vas placed on glass slide and examine undermicroscopy or decision base on quality of the return fluid • VV & VE performed
  • 95. When is VV indicated? Features where VV indicated base on testicular side vasal fluid: • Sperm or sperm part seen in large number • Clear and copious fluid
  • 96. When is VE indicated? 1. Thick material from proximal vas and devoid of sperm 2. Fluid is creamy and contain only debris 3. No fluid even when vas is milked towards the cut end 4. Irrigation of proximal vas with 0.2ml NS failed to wash out any sperm
  • 97. Vaso-vasostomy(VV) • Average patency rate: 70-90% • Average pregnancy rate: 30-60% Vasovasostomy Study Group, J Urol 1991
  • 98. Vasovasostomy Study Gp 1991 Success is determine by: • Microsurgical technique vs macrosurgical – Sperm +ve: 85% (vs 40%) – Pregnancy: 50% (vs 20%) • Anastomotic technique: – Similar patency rate btw 2-layer and modified one- layer • Time since vasectomy: < 3yr vs >15yr – Sperm +ve: 97% vs 70% – Pregnancy: 70% vs 30%
  • 99. Other factors to determine success 1. Time since vasectomy 2. Surgical technique and skill 3. Level of obstruction (more distal the better because of larger lumen) 4. Proximal length 5. Use of surgical clips 6. Presence of granuloma (+ve) 7. Age and reproductive capacity of the female partner: > 40 , rate of pregnancy decrease from 50% to 14%
  • 100. Modified one-layer VV • Full thickness 9/0 nylon suture at posterior • 3 anterior suture • Anastomosis support by 9/0 nylon seromuscular layer
  • 102. • Vas transected • Vasal fluid aspirated from testicular vas • Verified under microscope for sperm parts Abdominal vas dilated with fine forceps
  • 103. • 9/0 nylon to re- apposed the serosa layer at 5 and 7oc • Vas end brought in close proximity with 5/0 PDS in perivasal tissue
  • 104. • Suture placed at 4,6,8,oc within mucosa • 10/O nylon to suture vasal mucosa
  • 105. • 9/0 nylon suture in vasal serosa to complete the outer anastomosis • 5 additional suture at 1,3,9,11,12 oc position
  • 106.
  • 107. Vaso-epididymostomy(VE) • VE is require in vas-reversal in 20% • In terms of delivery rate for patient with vasectomy, it has proved more successful and more cost-effective than ICSI • Results: – Average Patency rates : 50-70% – Cumulative pregnancy rates : 40% – Delay sperm at 6m: 20% – ART should not be use until 2yr
  • 108. Vasoepididymostomy Microsurgical single-tubule anastomoses • End-to-end anastomosis (Silber) • End-to-side anastomosis • Intussusception technique end-to-side (Berger) – Earlier return of ejaculate – Lower rate of restenosis – Easier and shorter time to perform • Vas lumen 400um m, Epididymal tubule 150um • Better success with anastomosis to corpus (body) than head of epididymis • Result of microsurgical one-layer (Schmidt 1978) vs Two layer (Belker 1980) technique are comparable (Belker 1991)
  • 109. Surgical technique Vaso-epididymosotomy: • End-to-side: • Three suture triangulation intussusception • Two suture longitudinal intussusception (QMH preference)
  • 110.
  • 111.
  • 112. Post-Op care • Scrotal support • Avoid heavy physical activity : 4 weeks • Avoid sexual intercourse: 2 weeks • Most patients will have sperm in their semen within 4 weeks after vasovasostomy • If sperm are not present by 6 months, the operation is considered a failure. • SA : 2-3 monthly interval until semen parameters stable for pregnant • Average time to pregnancy: 1 year (Belker 1991)
  • 113. Complications • Bleeding and infection : rare • Pain: brief duration • NO report on change in sexual performance
  • 114. vasectomy reversal remains the gold standard for treatment of postvasectomy obstructive azoospermia. Ultimately, it is recommended that the physician understands the Vasectomy reversal versus IVF limitations of the current data and offer all of the options, along with the pros and cons of each, including outcomes and cost based on the providing institution, in order to help the couple arrive at an informed decision.
  • 115. Case 4: Ejaculatory Duct obstruction • Dx: – Low volume ejaculate – TRUS: Dilated SV – Pain on ejaculation • Txn: – Resection of ejaculatory duct – Risk : retrograde ejaculation , incontinence & infection
  • 117. Azoospermia • Non-obstructive azoospermia (60%) o Classical  Small testes and High FSH o Features of Klinefelter’s syndrome o Most patients have normal appearance
  • 118. Non-obstructive azoospermia • Common causes o Idiopathic (unknown) o Genetic  Numerical chromosomal disorder 15% e.g. Klinefelter’s syndrome  Y-chromosome microdeletion 10-15% o History of undescended testis o Mumps orchitis o Chemo/ Radiotherapy o Varicocele (OAT) oHypogonadotrophism: o Kallman’s syndrome o Pituitary tumor
  • 119. Hypogonadotrophic hypogonadism o Low testosterone, Low FSH o Gonadotropin treatment induces normal spermatogenesis in most patients o May take one year
  • 120. Case 1: NOA • A 35 year men presented to infertility clinic • Wife is 28 year old, normal work up for infertility by gyn before • Pt have SA in private before, told to have no sperm in ejaculate • How to evaluate him?
  • 121. • Hx • PE: – Secondary sexual charactre – Body habitus – Gynaecomastia – Size and consistency of testis – Palpable vas • Semen analysis – Need at least 2 abnormal SA to confirm dx
  • 122. How to confirm azoospermia? • Centrifuge at 1000g x 15 min • Then examine the pallet
  • 123. Scenario • Pt got no child before, examination showed small soft bilateral testis, with FSH 3x (ie 3x of 18mIU/ml) of upper normal limit • What is the likely dx? • How to manage him?
  • 124. • Pt is likely suffered from NOA • As small bil testes and high FSH reflect testicular/ spermatogenesis failure • If there is not obvious cause of testicular failure identified, like torsion, prior RT/chemo, or viral orchitis, I would perform karyotyping and Y(q)CMD for him
  • 125. • Commonly seen is Klinefelter sx in NOA, account for 15% • For YCMD assay, mainly is PCR based assay for the deletion of AZFa(Sertolic cells only), b(maturation arrest), c(severe oligozoospermia) located in the long arm of Y chromosome • Overall 15% NOA patients have positive genetic studies
  • 126. What is the relationship between klinefelters syndrome and infertility? • 47XXY • 1 in 600 male • 10% of NOA men • P/E: Gynecomastia, small firm gonads, azoospermia, long limbs • Investigation – FHS are typically raised – Testosterone is only low in 50% of cases • Sperm retrieval rate 70%
  • 127. Why important to dx Klinefelter? • Testicular biopsy feature – small hyalinised seminiferous tubules and pseudoadenomatous clusters of Leydig cells • Related to pt’s health – Androgen deficiency – early osteoporosis, metabolic syndrome DM, (pt may been T replaced) – Increase risks of undescended testis, extra-gonadal GCT, ca breast, NHL • Related to subsequent fertilization tx – TESE still have 70% sperm retrieval rate in Azoospermic men (but not those eunuchoid men) – Lower in pt with exogenous testosterone – Live birth : 46%
  • 128. Y-chromosome microdeletion • Phenotypically normal • 9 % of HK Chinese • Only defect: defect in spermatogenesis • Defect of one of the three non-overlapping regions in long arm of Y chromosome – AZFa  Sertoli cell only – AZFb  Maturation arrest – AZFc  severe oligospermia (no histological pattern)
  • 129. What is the significance of the dx? • For complete AZF a and b deletion, no spermatogenesis, no sperm can be found • For AZFc deletion, able to have sperm retrieval in TESE (~60%) • For genetic counselling all male offspring inherited YCMD  impact on fertility > ? Cryopreservation the early age or Preimplantation genetic diagnosis (PGD) > female embryo only
  • 130. Krausz et al. Andrology Unit Department of Clinical Physiopathology Viale Pieraccini, 6 Florence 50139 Italy
  • 131. What are the options of couple? • Childless • Adoption • Donor sperm insemination • ART with pt sperm (IVF-ICSI)
  • 132. Couple opt for ART, what will u do? • Liaise with reproductive team • For urologist perspective – sperm retrieval • Option of testicular sperm retrieval – Percutaneous – TESA (I thin no one do now) – Open: TESE • Multiple Random bx (more tissue ~500mg, more hematoma, more affect T production) • MicroTESE (less tissue ~10mg, less cx, more sperm)
  • 133. Percutaneous Testicular Sperm Aspiration • TESA • Success usually in men with more advanced spermatogenesis • Most patients with NOA will have inadequate sperm retrieval by this method Operative Urology at the Cleveland Clinic p443 Harris and Sandlow. Urol Clin N Am 35 (2008): 235-242
  • 134. Operative Urology at the Cleveland Clinic p473 Multiple random biopsies (TESE)
  • 135. Microdissection TESE Identification of enlarged tubules was possible in 56% Schlegel. Hum Reprod 1999; 14(1): 131-5Ramasamy et al. Urology 2005; 65(6): 1190-4
  • 136. Operative Urology at the Cleveland Clinic p474 Microdissection TESE • Schlegel et al 1999 o MicroTESE: 160,000 spermatozoa per 9.4mg of testicular tissue o Conventional TESE: 64,000 spermatozoa per 720mg of testicular tissue Hum Reprod 1999; 14(1): 131-5 (P<0.05)
  • 137. TESE • Conventional TESE: – Multiple blind testis bx – Excision of large volume (> 500mg) – Can result in permanent damage to testis • Microsurgical technique: – Spermatogenesis is often sporadic and focal in testes of patients with NOA – Conventional TESE is a blind procedure – Sequential excision of microdissected seminiferous tubules (10- 15mg) – Try to identify spermatogenically active regions of testis by direction examination of individual seminiferous tubules – Minimal amount of testicular tissue with Maximal sperm yield – Reduced –ve impact of testicular fxn – Adv over conventional: less hematoma and reduce testis size
  • 138. What is the success rate of TESE? • Depends on the stage of spermatogenesis – Hypospermatogenesis 80% • Clinical Predictors of Sperm Retrieval – T, FSH, testis vol are not predictor of outcome of TESE • Previous TESE sperm retrieval rates – DOES NOT rule out sperm retrieval in subsequent TESE – 0,1 or 2 negative TESE: 50% – 3 or more negative TESE: 20% – Repeat TESE > 6 months later yield more sperms (80%) than < 6 months after first TESE (25%)
  • 139. What is the outcome of ART in NOA? • Sperm retrieval 50% • Fertilization rate 55% • Pregnancy rate 47% • Live birth rate 40%
  • 141. Case 1 • M/32 • Good past health • Wife/33 • Fail conception for 2yr • PE: Grade III varicocele
  • 142. Semen Analysis • • • • 1 • • • : • : Volume: 2.4ml pH: 7.5 Sperm concentration: 6x10n6 sperm/ml Total sperm no.: 14.4x10n6 spermatozoa Motility: 20% with progressive motility and 11% grade 4 motility Morphology: 1% of normal forms White blood cells: <1 million/ml Hormonal profile: normal
  • 143. OAT • NOT obstruction • Clinically significant varicocele o Grade 2 or above o The ONLY surgically reversible factor
  • 144. What is his diagnosis and its causes? • Combined defects in sperm density, motility and morphology are known as oligoasthenotetraspemia OAT syndrome – can even cause azoospermia • It is commonly associated with clinical varicocele. • Other causes include cryptorchidism, temporary insults to spermatogenesis such as heat, drugs or environmental toxin, or idiopathic causes
  • 145. What is the etiology of Varicocele? • 90% decreased motility • 15% in population, 40% in primary infertility, 80% in secondary infertility • Dilatation of the pampiniform plexus of spermatic veins • Etiology of left testicular vein dilatation – Raised pressure in left sided renal vein outflow – Absent / dysfunctional valve in testicular vein – Nutcracker phenomenon of left renal vein by SMA and aorta
  • 146. What is the pathophysiology varicocele causing infertility? 1. Alteration of testicular temperature (0.6 degree) 2. Pantesticular defect with abnormal hormone production and spermatogenesis 3. Stagnation of blood with testicular hypoxia 4. Reflux of renal and adrenal metabolites which may alter spermatogenesis PC Tam. Varicocele: Current controversies in pathophysiology and treatment. Ann. Coll. Surg. H.K. (2004) 8, 90-97
  • 148. What is the Hudson Classification? • Standing posture • Persistent on recumbent posture (think about RCC with renal vein/ IVC thrombus) • Grade 0 : Subclinical: Not palpable or visible, but demonstrable Doppler examination –Veins ≥ 3.5mm in diameter –Reversal of venous flow after the Valsalva maneuver • Grade 1: Palpable during Valsalva manoeuvre • Grade 2: Palpable on standing , but not visible • Grade 3: Visible and palpable at rest
  • 149. Is varicocele repair the answer ?
  • 150. Methodologically flawed studies • Marmar and Kim 1994 o Surgery group (n=186): preg 35.6% o Conservative group (n=19): preg 15.8% o Critics: Discrepancy in sample size • Madgar 1995 o Immediate surgery (n=25): preg 60% at 1st year o Control (n=20) : pregnancy 10% at 1st year o Critics: SMALL sample size o Goldstein o Increase sperm analysis 70%
  • 151. More flawed studies • Cochrane review 2004 o 8 RCTS o 3 studies evaluated men with subclinical varicoceles o 2 studies included men with normal SA o Concluded that varicocele repair for unexplained infertility could not be recommended Evers et at. Cochrane Database Syst Rev 2004: CD000479.
  • 152. More flawed studies • Cochrane review 2006 o Repeat the Cochrane review in 2004 but excluding 5 RCTs with subclinical varicoceles or normal SA o Statistically significant difference in preg rates between treatment (40%) and control (20%) o ONLY 3 RCTs with total 237 patients o Defer to future studies and NOT recommend varicocele repair Ficarra et al. Eur Urol 2006; 49: 258-263
  • 153. More meta-analyses • Agarwal et al 2007 o Combined observational studies with RCTs o 17 studies (10 microsurgery, 7 high ligation) o Sperm density improved by 9.7-12 M/ml o Sperm motility improved by 10-12% o Sperm morphology improved by 3% o NO data on PREGNANCY Urology 2007; 70: 532-538
  • 154. More meta-analyses • Marmar et al 2007 o Included RCTs and observational studies involving only infertile men with palpable varicocele and abnormal SA o 5 studies only o Odds of spontaneous pregnancy after varicocelectomy vs conservative treatment is 2.63-2.87 Fertil Steril 2007; 88: 639-648
  • 155. What conclusion • Explain to couple that varicocele repair can improve seminal parameters but uncerntain benefit of conception rate • KL: varicocelectomy in properly selected couple will have improved pregnancy rate • AUA: – Varicocele txn suitable for pt with palpable varicocele & abnormal semen parameter • NICE : – Men should not be offered surgical txn for varicocele because it does not improve pregnancy rate • (EAU guideline 2010: No evidence indicates benefit from varicocele treatment in infertile men who have normal semen analysis or in men with subclinical varicocele. In this situation, varicocele treatment cannot be recommended)
  • 156. Indications for varicocele treatment • Well known criteria: AUA best practice 1. Palpable varicocele 2. Known infertility 3. Female partner has normal fertility or treatable female factor 4. Abnormal semen parameters • (Adult male with palpable varicocele, abnormal SA and desire for future fertility)
  • 157. Need of monitoring • Young adult males with varicoceles and normal SA o SA every one to two years • Adolescent males with varicoceles with normal testicular growth o Annual objective measurements of testis size +/- SA
  • 158. Predictive factors of success PC Tam. Ann. Coll. Surg. H.K. (2004) 8, 90-97 Oxidative stress markers in semen ??
  • 159. Cost Effectiveness • IVF/ ICSI was 3 times as costly as varicocele ligation Schlegel et al. Urology 1997; 49: 83-90
  • 160. What are the treatment options of Varicocele? • There are two approaches to varicocele repair: surgery and percutaneous intervention – Surgical repair of a varicocele may be accomplished by various surgical methods, including • Retroperitoneal • Laparoscopy • Inguinal • Subinguinal microsurgical approaches – Percutaneous intervention treatment of a varicocele is accomplished by • Antegrade or retrograde sclerotherapy • Retrograde embolization – None of these methods has been proven to be superior to the others in its ability to improve fertility
  • 161. Methods of varicocelctomy • Retroperitoneal high ligation – Recurrence 15%, hydrocele 10%, not artery preserving • Laparoscopic – Recurrence 2%, hydrocele 5%, not artery preserving • Microsurgical subinguinal / inguinal approach – Recurrence <2%, hydrocele 0%, artery preserving (<1% injury) – (Testicular artery, vasal artery, vasal vein, lymphatics preserved) • Radiological – Recurrence 10%, hydrocele 0%, artery not affected
  • 162. Classical Method of Varicocelectomy • Open Retroperitoneal (Palomo’s operation) o High ligation of internal spermatic veins o Above the internal inguinal ring Familiar to most General Surgeons Cannot tackle varicocele collaterals (external spermatic veins) Cannot preserve lymphatics
  • 163. Laparoscopic approach • Better don’t mention in examination • Ipsilateral side rotated up & in Trendelenburg position • Parietal peritoneum is incised just lateral to spermatic cord • Spermatic veins isolated then clipped transected • Advantages – Minimal Access – Bilateral pathologies • Disadvantages – Small but non-negligible risks of major vessel or bowel injury – Same problems with collaterals and lymphatics
  • 164. Varicocelectomy Open inguinal (Modified Ivanissevich) o 3 - 4cm oblique incision, 2 fingerbreadths above the pubic symphysis and just above external ring o EOA incised o Preservation of the ilioinguinal nerve o Spermatic cord is mobilized near the pubic tubercle o Double ligation / clipping of dilated spermatic veins & external cremasteric veins o Preservation of testicular artery o Unable to identify & preserve lymphatics
  • 165. Subinguinal microsurgical • 2-3cm transverse incision at the level of external ring • EOA not incised: less pain • Spermatic cord identified as it exit the external ring • Double ligation of the dilated spermatic veins & external cremasteric vein • Preservation of testicular artery • Can tackle external spermatic perforator and gubernacular vein • Microscopic advantage: – To see testicular artery and preserve it (< 1% injury) – To preserve lymphatics (lymphocele) – Preserve vasal vein (the only venous return after varicocelectomy)
  • 167. Subinguinal Microsurgical Varicocelectomy Avoid Vesectomy in post-varicocelectomy patients and vice versa as vasal vein was the only venous return which may cause venous congestion of the testis
  • 168. Varicocele Collaterals Clinical Andrology. EAU/ ESAU Course Guidelines 2010
  • 169. I will chose microsurgical subinguinal approach • Al-Said et al 2008 o Largest prospective randomized trial (n=446) o Open, laparoscopic, microsurgical varicocelectomy o Single surgeon • Microsurgical group o Fewer hydroceles and varicocele recurrences o More improvement in SA parameters J Urol 2008; 180:266
  • 170. 1%
  • 171. Result of varicocelectomy • Technical success rate: 90% • Seminal improvement: 70% • Natural pregnancy: 40% at 1 year, 70% at 2 year [Goldstein result] • Need FU with semen analysis, about 3 monthly for 1y or until pregnancy occurs • Consider ART for persistent infertility despite anatomically successful varicocele repair • Predictor of success: – Lack of testicular atrophy – Sperm density 5mil.ml – Resonable sperma motility – Normal FSH
  • 173. Induction of spermatogenesis • Varicocelectomy in azoospermic men o Restoration of motile sperm to ejaculate in 21-55% of patients • < 10% had sufficient number of motile sperm to avoid TESE [Schlegel 2004] • Unlikely to improve SA to an extent that IUI is feasible • More than 50% of those who showed initial benefit returned to azoospermic status within 1 year PC Tam. Ann. Coll. Surg. H.K. (2004) 8, 90-97 Curr Opin Obstet Gynecol 2008, 20: 269-274
  • 174. Induction of spermatogenesis • Testicular biopsy is often done o Germ cell aplasia may predict poor outcome o Induction of spermatogenesis has been shown in all testicular histologies o Prognostic value in potential TESE procedures PC Tam. Ann. Coll. Surg. H.K. (2004) 8, 90-97 Fertil and Steril 2006; 85: 635-639
  • 175. Important notice • IVF/ ICSI is likely even if sperms return to ejaculate • Waiting time of up to 12 months for varicocelectomy to show any benefit • Karyotyping and Y microdeletion are important tests before varicocele surgery • Semen cryopreservation should be done once sperms return to ejaculate Fertil and Steril 2006; 85: 635-639
  • 177. Sperm retrieval Technique • In patient with OA  spermatogenesis is normal but cannot pass out – PESA (Percutaneous Epididymal Sperm Aspiration) – MESA (Microsurgical Epididymal Sperm Aspiration) • In patient with NOA  abnormal spermatogenesis (no sperm in epididymis) – TESA (Testicular Sperm Aspiration) – TESE (Testicular Sperm Extraction)
  • 178. Sperm retrieval technique • VAS Vasal aspiration of Sperm • SVA Seminal vesicle aspiration
  • 179. Sperm retrieval in Azoospermia (Obstructive and non- obstructive) Obstructive Azoospermia Non-obstructive Azoospermia Retrieval from ductal system Retrieval from testis SV aspiration or Vasal aspiration Percutaneous epididymal sperm aspiration (PESA) Microsurgical epididymal sperm aspiration (MESA) Testicular sperm aspiration (TESA) Testicular sperm extraction (TESE) Microsurgical TESE Testicular biopsy Percutaneous Open • OA: No difference in pregnancy rates by ICSI between techniques, and frozen or fresh sperm • NOA: Open technique preferred as higher sperm yield
  • 180. Indication of Sperm Aspiration • Obstructive azzospermia: – MESA, PESA, TESA & TESE • Non-obstructive azzospermia: – TESE • Severe OAT (motile sperm not reliably found in ejaculate) – TESE • Patient with ejaculatory failure – Vasal aspiration , TRUS + SVG
  • 181. Epididymal aspiration of sperm Sperm retrieval OA, epididymal sperm Indication: • Prior vasectomy with no wish of reversla • CBAVD • PESA – For irreversible OA (e.g CBAVD) – 23G needle, 5ml sperm nutrient medium – LA, no microsurgical skills required – Multiple epididymal tubules punctured – Needle move back and forth within epiedymal head while side of epididymis and gently compressed to encourage sperm into needle – Often leave no microsurgical potential – For ICSI • Bleeding, hematoma – Success 90%
  • 182. • MESA – GA, under microscope – Best tubules can be selected – With chronic obstruction, optimal sperm quality is found in proximal epididymis – Tuble and tunic closed with suture – Less complications – Success ~100% – Longer OT time
  • 183. What are the methods of sperm retrieval? NOA, testicular sperm required • TESE – GA, less chance of injuries to other structures because under direct vision – Can be cryopreserved due to larger quantity – Can enable microTESE in severe cases of NOA • More meticulous opening of TA, less bleeding • Identification of enlarged tubules was possible in 60% – Retrieval success 50% with less tissue removed • TESA - Percutaneous testicular sperm aspiration – Office, LA – Chance of injury / hematoma – Success usually in men with more advanced spermatogenesis – Most patients with NOA will have inadequate sperm retrieval by this method – Shorter procedure: Cameco syringe holder – Success 10-50%
  • 184.
  • 185. Vasal Aspiration of Sperm • Procedure similar to vasectomy • For cases with distal obstruction or anejaculation
  • 186. What is the solution to preserve sperm after TESE • Human Tubule solution • NOT Bouin’s solution !!!!!!!! That is for testicular biopsy
  • 188. What is the ART and sperm requirement? • ART – small significant malformations (6%) as compared to normal pregnancy (4%) • Need chromosome analysis before ART • IUI : 5-10 million sperm at least • IVF : 0.1-0.5 million – Ovarian stimulation to produce multiple oocytes – USG guided aspiration of ova – Mixed with sperm – Embryos incubated for 3 days and placed in uterus – One third pregnancy rate • ICSI : one sperm is needed – Should have chromosome analysis before – ~50% of all ART – One third pregnancy rate, dependent to female age – More malformation rate than IVF
  • 189. How is IVF performed? • Gonadotropins used to recruit multiple oocytes in each cycle • USG to monitor follicular development • Ova harvested before ovulation with USG guided needle aspiration • In-vitro fertilization : mixing processed sperm with recovered oocytes (90% success if normal sperm fxn) • When fertilization occur  developing embryos are incubated for 2-3 days in culture • Then placed trans-cervically into the uterus • Successful pregnancy : 20-30% • Malformation rate: 4%
  • 190. How is ICSI performed? • Indicated in – severe male factor infertility – Failed prior regular IVF cycle – Sperm show significant defect in fertilising ability • Single sperm injected into individual ova • Pregnancy rate: 20-37% • Take home baby rate: 31% • Malformation rate: 6% (not significant different from IVF)
  • 191. What are the risks of ART ? • Medication : – Ovarian hyperstimulation syndrome – Ovarian torsion • Procedure related : – Associate with sperm / oocyte retrieval: rare • Procedure associated: – Multiple births – Preterm delivery • Offspring: – Inherited YCMD from father  infertility
  • 192. OHSS • Ovarian enlargement due to multiple ovarian cyst & acute fluid shift to extracellular space   ascites, hemoconcentration , hypovolemia, electrolyte disturbance • Mild (20%) – Abd distension , nausea, vomiting , diarrhoea – Ovarian enlargement (5-12cm) • Moderate (5%) – Features of mild + USG show ascites • Severe (1%) – Ascites +/- hydrothorax & SOB – Hypovolemia – Coagulation abnormalities – Hemoconcentration (increase blood viscosity) – Decrease renal perfusion and function
  • 193. Multiple gestation • Most ART pregnancy are multiple birth • Associated with increase: – Preterm delivery – Low birth weight – Perinatal mortality • Single embryo transfer (SET) vs multiple embryos – Preg rate not lower in SET – Number of multiple birth dramatically reduce
  • 195. What is cryptorchidism? • Cryptorchidism is multifactorial in origin and can be caused by genetic factors and endocrine disruption early in pregnancy • Cryptorchidism is often associated with testicular dysgenesis and is a risk factor for infertility and germ cell tumours • In a randomised study, it orchidopexy improved testicular growth in boys treated at the age of 9 months compared to those aged 3 years • Paternity in men with unilateral cryptorchidism in almost equal to that in men without cryptorchidism • Bilateral cryptorchidism significantly reduces the likelihood of paternity
  • 196. What are the recommendations of treatment? • Hormonal treatment of cryptorchidism should be abolished because of the risk of germ cell apoptosis and subsequent reduction of sperm production • Early orchidopexy (6–12 months of age) might be beneficial for testicular development in adulthood • Post-pubertal orchidopexy is advisable with potential fertility preservation • If undescended testes are corrected in adulthood, testicular biopsy for detection of CIS which can be removed, thus preventing development of a malignant tumour • TESE for NOA with cryptorchidism – Sperm retrieval rate: 70% – Pregnancy rate: 40% – Comparable to non-cryptorchid patient
  • 197. What is the surgical treatment? • Success rate of surgical treatment for undescended testes is 70–90% • When the spermatic cords or the spermatic vessels are too short to allow proper mobilisation of the testis into the scrotum, a staged orchidopexy (Fowler– Stephenson procedure) • Sperm retrieval rate 70%
  • 199.
  • 200. What are the facts of ejaculatory disorder? • Aetiological treatments for ejaculatory disorders should be offered before sperm collection and ART is performed • Premature ejaculation can be treated successfully with either topical anaesthetic creams or SSRIs • In men with spinal cord injury / DM neuropathy, vibro- stimulation at glans penis and electro-ejaculation are effective methods of sperm retrieval • Retrograde ejaculation was caused by spinal cord injury / DM / TURP / alpha-blocker / retroperitoneal LN dissection – Sympathomimetics, Ephedrine / pseudoephedrine / TCA - 50% successful rate – If failed > alkalinised post-ejaculate urine specimen for IUI / IVF – 50% successful rate
  • 201. • What is this and what is it used for? (2) • Name 1 life-threatening complication from its use (1) • Alternative treatment if this method fails? (1) Q58
  • 202. • Electoejaculator (1). For use in patients with male infertility due to anejaculation as a result of neuropathic cause eg. spinal cord injury (1) • Autonomic dysreflexia (1) • Vasal aspiration of sperm (1)
  • 203. Electroejaculation • Indicated in patients with anejaculation due to neurological cause (eg. spinal cord injury) but unsuitable for penile vibratory stimulation to induce ejaculation 1) Spinal cord injury (SCI) below T10 (reflex arc level for ejaculation) 2) Patients failing penile vibratory stimulation for other reasons • Use of rectal probe to stimulate electrically the perirectal, periprostatic sympathetic nerves • Requires general anesthesia for patients with incomplete / no / low SCI • Spinal cord-injured patients with lesions above T6 or a hx of autonomic dysreflexia  BP monitor for autonomic dysreflexia & severe hypertension mandatory • Pre-treatment: pseudoephedrine 7-10 days to facilitate ejaculation, Potassium citrate to alkalinize the urine • Bladder emptied, then filled with 30ml alkalinizing medium. Mineral oil for Foley insertion as commonly used lubricants are spermicidal • Electrical stimulation till ejaculation. Collect antegrade & retrograde ejaculation separately • Sperm from EEJ: poor motility & viability, decreased ability to penetrate cervical mucus and impaired fertilizing capacity
  • 204. Autonomic Dysreflexia. • Uncontrolled sympathetic response classically seen in patients with spinal cord injury T6 or above (above the splanchnic circulation) • Pathophysiology : due to spinal cord lesion above the level of thoracolumbar sympathetic outflow (hence lack of inhibitory control from higher centre) +/- synaptic re-organisation after SCI leading to exaggerated reflex arcs below the lesion level => exaggerated and aberrant sympathetic response to stimulus (rise in BP) but symptoms of parasympathetic response (flushing, nasal congestion) of regions above the lesion level • Common symptoms and signs – Headache, Hypertension, Flushing/blotching of skin above level of injury, Sweating above level of injury, nausea, nasal congestion, tachy/bradycardia – (Left untreated) intracranial pressure rise (from hypertension) and seizures and intracerebral bleed • The main precipitants – Urological – Bladder distension (accounts for 85% of AD), UTI, urological procedures eg. UD / cystoscopy, genital stimulation – Gastrointestinal – Rectal distension (electroejaculation), anorectal procedures, acute abdomen – Musculoskeletal –Fractures, dislocation – Others – Skin problems (for example, ulceration, infection), pregnancy and labour.
  • 205. • Management (prevention) – Awareness of such an entity! – Avoidance of build-up of intravesical pressure in susceptible patients eg. CISC – Use of general / spinal anesthesia during at-risk procedures / intervention – Pharmacological prophylaxis before procedure : alpha blockers, nifedipine • Management (treatment) – REMOVE THE PRECIPITANT eg, STOP INFUSION DURING URODYNAMIC STUDY – Sit up the patient to provide orthostatic decrease in BP – Look for other precipitants eg. remove faecal impaction – Sublingual nifedipine, consider intravenous agent e.g hydralazine or diazoxide
  • 207. Fresh vs Frozen sperm • Similar fertilization rate • Similar clinical pregnancy rate • Ongoing pregnancy or delivery – Trend favouring fresh spermatozoa –Loss of vitality secondary to Freeze- Thaw process up to 50% –Not a good option for patients with very low retrieval numbers
  • 209. What is the cause of haematospermia? • Infection – TB, HIV • STD • Prostatitis • Ca prostate • Post-TRUS Bx • Urethritis • Systemic disease (bleeding tendency)
  • 210. What is the investigation? • MSU • EMU • Urine cytology • PSA • TRUS (prostatic calcification / BPH / ejaculatory duct cyst) • FC If all normal > reassurance
  • 211. What is the relationship between Ca testis and infertility? • Infertile men with abnormal semen analyses have 20-fold greater incidence of testicular cancer • About 25% of men diagnosed with ca of testis have oligospermia at presentation • Chemotherapy induced azoospermia typically occurs at 3 months. The reason is that spermatocytes are not rapidly proliferating and survive chemotherapy. These cells will take 1-3 months to become mature sperm and therefore there will be sperm in the ejaculate for that period of time • The germ cells that are most susceptible to chemotherapy are the rapidly proliferating spermatogonia • Leydig cells are not rapidly proliferating and survive chemotherapy but their function may be impaired • Alkylating agents are among the high risk chemotherapeutic agents for causing azoospermia • Sperm cryopreservation (Onco-TESE at the same time of orchidectomy) should preferably be done before the initiation of cytotoxic therapy but could be carried out after
  • 212. Onco-TESE • High cure rates of testicular germ cell tumours and lymphoma with cytotoxic chemotherapy o Standard: cryopreservation of ejaculated spermatozoa before chemotherapy • Tumour-induced azoospermia in some patients o TESE in azoospermic cancer patients after chemotherapy may not succeed Chan et al. Cancer 92: 1632-1637, 2001
  • 213. Onco-TESE • TESE in azoospermic cancer patients BEFORE chemotherapy o Contralateral TESE in patients with germ cell tumours following inguinal orchidectomy (sperm retrieval 43%) o Unilateral or Bilateral TESE in patients with lymphoma (sperm retrieval 47%) Schrader et al. Urology 61: 421-425, 2003

Editor's Notes

  1. The Chinese have been using a refined method of vasectomy that eliminates the scalpel, results in fewer hematomas, and leaves a much smaller wound than conventional techniques used in other countries. The [no-scalpel vasectomy] has been performed for 4-8 million men in Sichuan Province since its introduction in 1974. After application of local anesthesia, a specially designed vas fixing forceps encircles and firmly secures the vas without penetrating the skin. A curved hemostat with sharpened points is used to puncture the skin and vas sheath and stretch a small opening in the scrotum. The vas is lifted out and occluded as in other vasectomy techiques. This same midline puncture site is used to deliver the other vas in an almost bloodless procedure. The first [no-scalpel vasectomy] training outside China took place in November 1986 in Bangkok. Through May 1987, approximately 1,500 [no-scalpel vasectomies] were performed in Thailand, Sri Lanka, Nepal, and the US. Each surgeon reported a significant reduction in bleeding from the wound. The client response is favorable, the elimination of the scalpel and the smaller wound apparently being important to men in these countries just as in China. (Huber 1987, 176)
  2. Resection of larger sec- tions of the vas, burying the ends of the ducts in differ- ent planes of tissue, the use of fi brin glue or fulguration of the lumen are all useful methods for minimizing the rate of recanalization
  3. SV aspiration or Vasal aspiration: Limited to cases with distal obstruction or anejaculation