ppt on azoospermia which is a cause of infertility and its surgical management

1. Azoospermia and surgical
retrieval of sperms
Dr Ravishankar
Moderator: Dr Vandana

2. INTRODUCTION
• The complete absence of sperms in the
ejaculate.
• INCIDENCE- 1% of all men and 10% of all
infertile men.
• Absolute barrier against spontaneous
pregnancy

3. DIAGNOSIS
• Diagnosed by examination of the semen pellet after
centrifuging it for 15 mins at 3000g or more.
As per WHO guidelines, complete absence of spermatozoa
to be confirmed on two occasions at least two weeks apart.
• Ron-El et al have shown that sperms can be detected in
up to 35% of azoospermic males with meticulous analysis
of the sample.

4. Semen – Sources of total volume
Cowper’s gland
secretion 0.1 – 0.2 ml 0-2%
Prostate
Secretion 0.5 ml 20%
Seminal
Vesicles 1.5 – 2.0 ml 70%
Testes and
Vas deferens
0.5 ml 8-10%

5. Seminal Fructose
• Produced from Seminal vesicles
• But no need for fructose assay routinely
• Can do if a mismatch between pH and volume
is present

6. EVALUATION
Initial evaluation:
– Thorough history and physical examination.
– Semen examination on at least 2 occasions 2-4
weeks apart.
Ancillary tests:
– Hormonal assays.
– Imaging.
– Genetic testing.

7. HISTORY
• Medical history:
– Exposure to toxins/radiation.
– Drugs/allergies.
– Genital trauma/surgery.
– Chemotherapy.
– Orchitis/Cryptorchidism.
– STDs

8. • Surgical history:
– Orchidopexy- maldescent or torsion.
– Inguinal hernia repair
– Prostatectomy.
– Urethral/pelvic/scrotal surgery.
• Drug history:
– Cimetidine, spironolactone: antiandrogens
– Chemotherapy: testicular damage.
– Anabolic steroids, GnRHa: decreases GnRH
secretion.

9. EXAMINATION
– in standing and supine position.
– Testis size and consitency- average size is 4.5 x 2.5 cms, has a volume of 18-
20 cc- 85% of testis volume is involved in spermatogenesis
– Presence of varicocele
– Consistency of epididymis/presence of vas deferens- to be
confirmed.
– Secondary sexual characteristics- Body hair distribution, gynecomastia,
eunuchoid proportions should be looked for.
– Rectal examination-assess prostate and seminal vesicles (in case of
EDO)

10. HORMONAL EVALUATION
• Indications are-
– Severe oligoasthenospermia- less than 5 mill/ml
– Azoospermia
– Sexual dysfunction/loss of libido.
• Estimation of testosterone and FSH as a first line.
• If abnormal then repeat FSH and testosterone
along with PRL,LH,TSH.

12. Interpretation
FSH LH TESTO DIAGNOSIS
Spermatogenic failure –
Microdeletion
Testicular failure –
Klinifleter’s syndrome
HH- Kallmann’s
syndrome
Exogenous testosterone
Body builder

13. Imaging
• TRUS:
– Low volume, fructose negative semen samples
– Evaluation of the seminal vesicles, prostrate and
ejaculatory duct is possible
• Scrotal USG:
o Evaluation of testes and varicocele.
o Varicocele is diagnosed when
– There is 3 or more scrotal veins with at least one having a
resting diameter of 3 mm.
– Increase in diameter or features of reversal on Valsalva
manoevre.

16. PRE TESTICULAR CAUSES
Secondary testicular failure
due to endocrinopathy.
• Causes upto 3% of male
infertility.
HGH may be caused by -
 Kallman’s syndrome
 pituitary trauma/
tumours
 anabolic steroid use
FEATURES
1. LOW SERUM FSH
2. LOW SERUM TESTOSTERONE
3. LOW SERUM LH
4. EXTERNAL FEATURES OF
HYPOGONADOTROPHIC
HYPOGONADISM

17. • Hyperprolactinemia:
PRL secreting adenomas.
Medications such as tricyclic antidepressants, some
antihypertensive, imipramine, methyl dopa etc.
• Androgen insensitivity:
occurs in 1 of 60000 births
severity depends on mutations of the androgen
receptor gene in X chromosome.

18. TESTICULAR CAUSES
• primary testicular failure ; intrinsic disorders
of spermatogenesis.
• These include-
1. Varicocele
2. Testicular torsion
3. Cryptorchidism
4. Genetic causes
5. Mumps orchitis
6. surgery/ trauma/ radiation

19. VARICOCELE
• Occurs in 5-10% of the
infertile males.
• 75% of men with
varicocele have normal
semen parameters.
• Repair leads to
improved ART
outcomes.

20. • Sperms have been obtained from ejaculate in
22-55% after repair but spontaneous
pregnancies are rare.
• Biopsy at the time of repair –
– if sertoli cell only pattern then requires micro TESE
and ICSI
– if maturation arrest then patients may provide
motile sperms in the ejaculate post operatively.

21. CRYPTORCHIDISM
• the most common congenital anomaly in
boys.
• Occurs in 2.7% of newborns and 0.8% of 1
year olds.
• Should be differentiated from retractile testis.
• Suggested mechanisms for causing infertility
are:
– Testicular dysgenesis
– Impaired endocrine axis
– Immunological damage
– Obstruction

22. • Majority of men with unilateral undescended
testis are capable of paternity.
• Age and volume of testis at time of repair are
independent predictors of fertility potential
and chances of sperm retrieval.
• Incidence of azoospermia after treatment is
13% in unilateral and 34% in bilateral
undescended testis and without treatment it
is 30% and 80%.

23. TESTICULAR TORSION
• occurs in 1:4000 men before 25 years of age.
• Requires immediate surgical exploration.
• Testicular preservation is possible if
exploration is done within 6 hrs of symptoms
onset.
• Most significant complication is the loss of the
testis leading to impaired fertility.
• Endocrine function of testis is intact after
torsion.

24. • The spermatogenesis is usually impaired, and
these patients seem to have bilateral
abnormalities leading to oligo/azoospermia.
• Probably due to immunological reasons due to
the rupture of the blood-testis barrier or a
reperfusion injury.
• Contra lateral testis biopsies are abnormal in
88% of cases!

25. MUMPS ORCHITIS
• Prepubertal mumps have little impact on
fertility.
• Pubertal mumps orchitis occurs unilaterally in
67% and bilaterally in 33%.
• Testicular atrophy occurs in 36% of those
affected bilaterally.
• Infertility occurs in just 13%.
• Incidence reduced after introduction of
vaccine

26. • Drugs and gonadotoxins: may affect
spermatogenesis by-
– Direct gonadotoxic effects.
– Altering the HPG axis.
– Ejaculatory dysfunction.
– Loss of libido.

27. GENETIC CAUSES
• responsible for 15% of azoospermia and 5% of
oligospermia in men.
• These include-
1. Klinfefeter syndrome
2. 47 XYY syndrome
3. XX male syndrome
4. Mixed gonadal dysgenesis
5. Y chromosome microdeletion

28. KLINEFELTER SYNDROME
• is 45 times more
common in infertile
males.
• Most common variant is
47 XXY.
• Advanced maternal and
paternal age is
associated with
increased risk.

29. • Only 10 % of KS is diagnosed prior to puberty.
• Micro TESE may reveal sperms in 69% of cases
and live birth of children with normal
karyotype has been reported.
• Mosaic variants are less severe and may
present with normal body habitus, complete
spermatogenesis and have sperm in the
ejaculate.

32. 47 XYY SYNDROME
• due to paternal
nondisjunction leading
to YY sperms.
• Occurs in 1:1000 men.
• Biopsy varies from sertoli
cell only to maturation
arrest.
• Testosterone levels are
normal.
Exhibit tall stature, decreased
intelligence, anti social behaviour,
azoospermia/severe oligospermia.

33. XX MALE SYNDROME
• occurs 1:20000 cases.
• These patients have normal male internal and external
genitalia and hormone profile.
• Due to absence of AZF region there is no
spermatogenesis.

34. MIXED GONADAL DYSGENESIS
• have a mosaic 45 XO/46 XY genotype and
anatomically have a testis on one side and a
streak gonad on the other.
• Relatively rare disorder, the testis is usually
undescended and devoid of germ cells.
• There are varying degrees of ambiguity of
genitalia.

35. Y CHROMOSOME MICRODELETION
• Found in 10-15% of men with azoospermia
• Azoospermia factor (AZF) is located on the
short arm of Y chromosome and has three
distinct regions- AZFa, AZFb, AZFc.
• Deletions in these regions are related to
failure of spermatogenesis

41. Post testicular causes
• These are either due to obstruction or
ejaculatory dysfunction.
• Treatment is suggested accordingly and
involves surgical correction/surgical sperm
retrieval in case of obstructive azoospermia.

43. CBAVD
• seen in 1% of infertile men and 6% of azoospermic men.
• Two possible mechanisms:
– Mutations in the CFTR gene
– Abnormal differentiation of the mesonephric duct.
Clinical features-
– Normal testis size and volume.
– Caput of epididymis is always present but the cauda and corpus is
usually absent.
– Seminal vesicles may be atrophic or cystic.
– Semen volume is <1ml and acidic.
• Sperm retrieval is easily done by PESA.

44. • 80% of men with CBAVD and 43% of men with
unilateral absence of vas have mutations in
the CFTR gene.
• Secondary findings include ipsilateral renal
agenesis in 11% of CBAVD and 26% of men
with unilateral absence of vas.
• CFTR gene mutation should be checked for in
the female partner before proceeding with
ART using the husband’s sperms.

45. VASAL OBSTRUCTION
• Most commonly seen as an
inadvertent injury during
hernia repair. This injury
commonly occurs when the
procedure in done in infancy.
• Foreign body reaction to the
polypropylene mesh.
• Vasectomy is another cause.

46. EPIDIDYMAL DUCT OBSTRUCTION
• Young’s syndrome- triad of bronchiectasis, sinusitis
and azoospermia.
• Cause of azoospermia is mostly epididymal
obstruction due to inspissated secretions.
EJACULATORY DUCT OBSTRUCTION:
• 1-5% of male infertility.
• Congenital- compression by Wolffian or Mullerian
duct cysts or Acquired.- surgical trauma, prostatic
calcifications, infections, seminal vesicle calcifications
etc.

47. Clinical features:
• Testis- Normal in size and volume.
• Normal secondary sexual characteristics and
hormonal profiles.
• Seminal vesicles-dilated.
• Low volume azoospermia as 80% of the
semen volume is produced by the seminal
vesicles.
• TRUS may be performed to confirm the
diagnosis.

48. RETROGRADE EJACULATION
• due to altered neurological control- internal
urethral sphincter is open during ejaculation.
• Demonstrating sperms in the post ejaculatory
urine confirms the diagnosis.
• Treatment involves drug therapy to convert
retrograde into antegrade ejaculation/
harvesting sperms from urine for ART.

50. • Ephedrine, pseudoephedrine, imipramine etc
can be used for 3-4 weeks.
• Always ejaculate on a full bladder.
• Oral erectogenic drugs can be given to take
away the stress of performance.

51. Surgical retrieval of sperms
• This is used to retrieve sperms from the
epididymis or testes in the following conditions.
– Azoospermia (OA or NOA).
– Ejaculatory/erectile dysfunction.
– Total astheno-necrozoospermia.
• Contraindications:
– Bleeding diathesis
– UTI/GTI
– Scrotal surgery in the last 3 months.
– Previous negative micro TESE.

52. • In OA-
– If reconstruction is not possible then sperms can
be obtained from testes or epididymis.
• In NOA-
– It has to be obtained from testes.
– Multiple biopsies may be required.
– TESE may be required

53. • Epididymis:
– 1)PESA- the superior pole of the testis is
presented to the surgeon by the assistant.
– The epididymis is stabilised between the thumb
and index finger of the surgeon.
– A 18 G needle is inserted into it and the fluid is
aspirated along with gentle massaging of the
epididymis into a 1 ml syringe containing culture
media.
– Comparatively easier but a blind procedure and
may cause post op fibrosis and obstruction.

54. • 2)MESA: it is a microsurgical procedure.
• Special instruments required, has a longer
learning curve.
• Open procedure and scrotal exploration is
possible.
• More sperms retrieved and minimal post op
fibrosis.

56. • Testis:
1)TESA- it is a blind procedure.
– Using a 18 G needle attached to a 10 ml syringe
with 2 ml of media.
– After piercing the testis negative pressure is
applied and the needle is rotated in all directions.
– As it is removed, bits of seminiferous tubules are
obtained.
– These tubules are teased and presence of sperms
are checked. If no sperms are obtained the tissue
can be sent for HPE.

57. • 2) TESE: Equivalent to a testicular biopsy.
– Open procedure.
– Multiple biopsies can be taken.
• 3)Micro TESE: TESE is done with the help of an
operating microscope to delineate the areas
of possible spermatogenesis.

60. •Thank you!