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Dr Antima Rathore
Consultant (Infertility Specialist)
Institute Of Human
Reproduction,
Kolkata
1
Incidence
2Jarvi H et al, 2015, CUA Guidelines
Infertility
15 %
Male infertility
50 %
Azoospermia
20 %
Definition
3
What is Azoospermia?
“Azoospermia is the condition in which
sperm are not detectable in an ejaculate”
4
Normozoospermia
5
What is Azoospermia?
Oligozoospermia Azoospermia
6
What is Azoospermia?
7
What exactly is Azoospermia?
WHO 1999
No sperm seen in semen smaple
↓
centrifuged the semen sample at 3000g for 15
minutes
↓
the pellet formed must be examined for presence
of any sperm
8
Diagnosis
If any sperm is found in the pellet
↓
Cryptozoospermia
9
Diagnosis
If no sperm is found even after centrifugation
↓
repeat analysis must be done after 2-4 weeks
10
Diagnosis
• Repeat analysis
• Centrifuge
11
Why to repeat the analysis?
WHO 4th Edition
12
d/d
• Pseudo-ejaculation
– Urethral secretion alone or some urine
– If semen sample is <1 ml
or
history of difficult collection
• Major illness
– Severe oligozoospermia – temporary azoospermia
– Repeat after 3 mnths
13
Classification
14
Classification
• Testicular
Jarvi H et al, 2015, CUA Guidelines
15
Classification
• Pretesticular
• Testicular
Jarvi H et al, 2015, CUA Guidelines
16
Classification
• Pretesticular
• Testicular
• Post-testicular
Jarvi H et al, 2015, CUA Guidelines
17
Classification
• Obstructive
azoospermia
• Non-Obstructive
azoopermia
Jarvi H et al, 2015, CUA Guidelines
18
Obstructive Azoospermia
Obstruction of the passage in the male reproductive
organs
Post-testicular (7-51%)
• Sperms are produced by
the testis
• Not present in the semen
Jarvi H et al, 2015, CUA Guidelines
19
Obstructive Azoospermia
• Obstruction may be at the level of
– Epididymis
– Vas deferens
– Ampulla of the vas
– Ejaculatory duct
• Can be congenital or acquired
– CBAVD
– Vasectomy
– Infections
20
Congenital Bilateral Absence Of
Vas Deference (CBAVD)
• 2 to 6% of men with OA
• 1% of infertile men
• 65-80% have CFTR gene mutation
(cystic fibrosis transmembrane conductance regulator
gene)
– Short arm of chromosome 7
– 1,500 different mutations
21
Congenital Bilateral Absence Of
Vas Deference (CBAVD)
• Mostly normal spermatogenesis
• A large proportion exhibit impaired
spermatogenesis
• Prior to sperm harvesting, other potential
coexisting causes of impaired spermatogenesis
should be investigated
• 10% of patients with CBAVD may also exhibit
renal agenesis
22
Non Obstructive Azoospermia
“Testicular Failure”
Production of sperm
↓
either very low or
absent
23
Non Obstructive Azoospermia
 Primary Testicular Failure
or
Hypergonadotropic hypogonadism
(49-93%)
– defect in production of
sperm by testes themselves
 Secondary Testicular Failure
or
Hypogonadotropic
hypogonadism
(pre-testicular) (7-51%)
– due to defect at the level
of pituitary gland or the
hypothalamus
24
Evaluation
25
Evaluation
• History
• Examination
• Investigations
26
History
• Infertility history - including sexual history
• The general health of the man - Recent illnesses
• History of anosmia and recurrent upper respiratory tract
infection
• Any proven or suspected genitourinary Infections -
– Sexually transmitted Infections
– Epididymo-orchitis
27
History
• Exposure to medications and therapies
which might have an adverse impact on
spermatogenesis
– Hormone/steroid therapy
– Antibiotics (sulphasalazine)
– Alpha-blockers
– 5-alpha-reductase inhibitors
– Chemotherapeutic agents
– Radiation
– Finasteride
– Narcotics
28
History
29
• Any surgery of the reproductive tract
– Testis cancer
– Undescended testis
– Hydrocelectomies
– Spermatocelectomies
– Varicocelectomies
– Vasectomies
History
30
• Environmental exposures
– Pesticides
– Excessive heat on the testicles
• Any recreational drugs
– Marijuana
– Excessive alcohol
• Family History
– Genetic abnormalities
– RPL
Examination
31
Prader’s
Orchidometer
Examination
• Scrotal Examination
– Size and consistency of the testis
– Palpable vas deferens
– Presence and grade of varicoceles
– 15-25 ml
32
Examination
• Virilisation
• Abdominal examination
– Presence of scars in the inguinal area
(inguinal surgery / treatment of undescended testis)
33
Investigation
34
Investigation
 Semen Analysis
 Endocrine evaluation
a. FSH
b. Serum Testosterone
c. LH / Estrogen
d. Prolactin / TSH
 Genetic testing
a. Karyotyping
b. Y microdeletions
35
Investigation
 Transrectal ultrasonography
 Scrotal ultrasonography
 Vasography
 Patency of vas deferens
 Testicular biopsy - ?
36
Semen Analysis
37
alkaline
acidic
Semen Analysis
• Volume < 1.5 ml
if Vas palpable
Repeat after 2-3 days abstinence
Ejaculatory Duct Obstruction (EDO)
38
Semen Analysis
• Volume < 1.5 ml
if Vas palpable
Repeat after 2-3 days abstinence
Ejaculatory Duct Obstruction
(EDO)
• pH < 7.2
Acidic – prostatic secretions
EDO
39
Semen Analysis
• Volume < 1.5 ml
if Vas palpable
Repeat after 2-3 days abstinence
Ejaculatory Duct Obstruction (EDO)
• pH < 7.2
Acidic – prostatic secretions
EDO
• Fructose
Secreted from Seminal vesical
Absent In EDO
40
Semen Analysis
Volume & pH
↓
Normal
41
Hormonal profile
42
• FSH > 7.6 mIU/ml – abnormal
• Testosterone - > 298 ng/dl
• Prolactin level - erectile dysfunction
• TSH - sign and symptoms s/o hypothyroidism
Hormonal profile
43
Genetic evaluation
Non-obstructive
• Karyotype
• Y Chromosome
microdeletion
Obstructive – absence Vas
• CFTR gene mutation
44
Genetic evaluation
Karyotype
Klinefelter Syndrome (XXY)
• The most common chromosomal
• 10 % of cases
• Examination
– Tall
– Gynaecomastia
– small firm testes
45
Genetic evaluation
• Deletion in AZF region
(AZF a, AZF b, AZF c,
AZF d)
• Probability of retrieving
sperm from procedure
like TESE.
• Genetic transmission
Y Chromosome microdeletion
46
Genetic evaluation
Correlation between the location of deletion and
probability of getting a spermatozoa on TESE /
Testicular biopsy
AZFa NIL
AZFb & AZFbc Almost 0%
AZFc 50-70%
47
Genetic evaluation
CFTR Gene Sequencing
• Patients who have absent Vas
(Complete or Partial)
• Evaluation of female partner may also be needed
48
TRUS
(Transrectal Ultrasonography)
• Findings suggestive of EDO
– Midline Cyst
– Dilated ejaculatory duct
– Dilated seminal vesical
(>1.5 cm)
• Atrophy of seminal vesical
49
Others
• Scrotal Ultrasound
– testicular volume
• Testicular biopsy –
– only if the place has the facility of sperm
cryopreservation
A Trial TESA may be carried out in place of a
biopsy followed by cryopreservation of any
sperm retrieved
50
Others
• Transabdominal Ultrasound
– Rule out renal agenesis (unilateral)
10-15 % CBAVD
51
Obstructive
Azoospermia
52
53
Semen volume and pH
Normal volume Normal pHLow volume & Low pH
Retrograde
ejaculation
Post-ejaculatory urine
No Sperm seenSperm seen
Examine vas
palpable not palpable
TRUS
Dilated EDO
Ejaculatory duct
obstruction
CBAVD
Normal
spermatogenesis
on biopsy
Scrotal
exploration
Correctable
obstuction
Non-
correctable
obstructio
n
Non Obstructive
Azoospermia
54
55
•Assess testicular volume
•Hormone profile (FSH, Testosterone)
•Karyotype, Y chrom Microdeletion
Dec FSH
Dec Testosterone
Dec FSH
Normal/inc
Testosterone
Exogenous
testosterone
Rule out
central cause
Elevated FSH
Abnormal Genetic
Testing
Genetic
Abnormality
Genetic
counselling
Normal
genetic
testing
TESA/ICSI
Management
56
Management
• Pretesticular azoospermia
– GnRH therapy
– hCG followed by hMG
– Donor insemination
57
Management
• Testicular azoospermia
– TESA
– Donor insemination
58
Management
• Post testicular azoospermia
– End to end anastomosis of epididymis
– Vasoepididymostomy
– PESA
– TESA
• Surgical correction
– the success rate depends upon the expertise
of the surgeon
59
Varicocelectomy In Men With
Azoospermia?
• Controversial
• a small percentage of men with azoospermia
due to testicular failure may benefit from
treatment of a clinical varicocele
(Schlegel et al – 20%)
• Most men will still need ICSI to help conceive
(Level of Evidence 4, Grade of Recommendation D)
60
What is the role of hormone
therapy for men with azoospermia?
• Controversial
61
Thank You
62

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Azoospermia