Azoospermia how to manage azoospermia

2. Definition:
Azoospermia is defined as the absence of sperm in the
ejaculate and is identified in 1% of all men and up to 10%
to 15% of infertile males
The initial diagnosis of azoospermia is made when no
spermatozoa can be detected on high-powered
microscopic Examination of centrifuged seminal fluid on at
Least two occasions.
The WHO Laboratory Manual for The Examination of
Human Semen recommends that the seminal fluid be
centrifuged for 15 minutes

4. Hypothalamic disease
• Gonadotropin deficiency
(Kallmann syndrome)
• Isolated LH deficiency (“fertile
eunuch”)
• Isolated FSH deficiency
• Congenital hypogonadotrophic
syndromes
Pituitary disease
• Pituitary insufficiency
• Hyperprolactinemia
• Exogenous hormones (estrogen–
androgen excess, glucocorticoid
excess, hyper- and hypothyroidism)
• Growth hormone deficiency
Testicular causes:
• Chromosomal :
o Klinefelter syndrome
o Y chromosome microdeletions
o Noonan syndrome
o Vanishing testis syndrome
o Sertoli-cell-only syndrome (germ cell
aplasia)
• Gonadotoxins:
o Radiation
o Drugs
o Systemic disease (renal failure, liver
failure, sickle cell anemia)
• Defective androgen activity
• Testis injury (orchitis, torsion, trauma)
• Cryptorchidism
• Varicocele
Posttesticular causes:
• Reproductive tract obstruction
o Congenital blockages
o Congenital absence of the vas
deferens (CAVD)
o Young syndrome
o Polycystic kidney disease
o Ejaculatory duct obstruction
o Vasectomy
o Groin surgery
o Infection
o Pharmacologic
• Premature ejaculation

6. Azoospermia
Congenital bilateral absence of the vas deferens
(CBAVD).
Semen volume
>1 ml <1ml
Sperms present Sperms absent
Scrotal ex. Of vas diff
Postejaculatory urinalysis
TRUS
Ejaculatory duct obstruction
Normal
Functional causes:
*RPDLN
*M.S. *D.M
Spermatogenic causes
Testicular biopsy
Retrograde ejaculation
L FSH &
TES &LH
H FSH &
TES &LH
L FSH
NL TES &LH
H Prolactin
NL FSH &
TES &LH
H FSH &LH
L TES
Vasal or epidydimal
obstruction
Vasography
• Vanishing Testis Syndrome
• Cryptorchidism
1ry testicular failure
Genetic tests
• Klinefelter Syndrome .
• Y Chromosome Microdeletions
Testicular biopsy
Hyperprolactinemia
Isolated FSH
Deficiency
Androgen Receptor
Deficiency
Hypogonadotrophic
Hypogonadism
Palpable testes
NO
Yes

11. 1. Laboratory testing:
A. Semen analysis.
B. Hormone Assessment.
C. Genetic tests.
2. Radiologic Testing:
A. Scrotal Ultrasound.
B. Transrectal Ultrasound.
C.Vasography.
D. Venography.

12. Semen Analysis
i. Physical examination
1. Visual appearance
2. Viscosity
3. Volume
4. PH
ii. Microscopic examination
1. Motility
2. Viability
3. Count
4. Morphology
iii. immunologic analysis
1. sperm MAR test – direct, indirect
2. immunobead test
iv. biochemical analysis
1. fructose – seminal vesicle marker
2. total zinc
3. total acid phosphatase prostate marker
4. total citric acid
5. alpha glucosidase epididymis
6. carnitine
v. sperm function tests
1. post coital (Sims-Huhner test)
2. Cervical mucous penetration test
3. Hamster egg penetration test
4. Hypoosmotic swelling of flagella
5. computer assisted semen analysis

13. Seminal Fructose and Postejaculate Urinalysis
• Fructose is a carbohydrate that is secreted in high
concentration from the seminal vesicles and is normally
present in the ejaculate.
• When absent, seminal vesicle agenesis or obstruction may
exist.
• Seminal fructose testing is indicated in men with low
ejaculate volumes and no sperm.

14. Antisperm Antibody Test:
*Autoimmune infertility may result when the blood– testis barrier is
broken and the body is exposed to sperm antigens.
*Trauma to the testis and vasectomy are two common ways in which this
occurs, giving rise to ASAs.
*An assay for ASA should be considered when:
(1) semen analyses show persistent sperm agglutination or clumping;
(2) low sperm motility with history of testis injury or surgery;
(3) idiopathic leukocytospermia; or
(4) Unexplained infertility.

15. Hypoosmotic Swelling Test:
*Motility is the most commonly used measure of a sperm’s
viability.
* Studies have suggested, however, that some
nonmotile sperm may still be viable.
*Cell viability can be evaluated noninvasively by using the
physiologic principle of hypoosmotic swelling.
*Viable cells with functional membranes swell when placed in a
hypoosmotic environment.
*This response is easily observed in sperm as tail coiling
accompanies head swelling.
*This sperm test is indicated in cases of complete absence of
sperm motility eg. immotile-cilia syndrome.

16. Sperm Penetration Assay:
• It is possible to measure the ability of human sperm to penetrate
a specially prepared hamster egg in the laboratory setting.
• This form of bioassay can give important information about the
ability of sperm to penetrate and fertilize the egg.
• Indications:
-Unexplained infertility.
-Help couples decide whether intrauterine insemination (IUI)
(good SPA result) or in vitro fertilization (IVF) (poor SPA result) is
the appropriatenext treatment.

17. Post coital (Sims-Huhner test):
• PRINCIPLE –
1. Examination of quality of cervical mucous post coitus can give an idea about
the quality of cervical mucous and ability of the sperms to penetrate it .
2. Normally in proliferative phase (estrogen phase) the mucous is watery (fluid)
and sperms can penetrate easily.
3. During secretory phase (progesterone phase), the mucous is viscous.
4. Hence mucous testing is scheduled just before ovulation.
• METHOD –
Cervical mucous is aspirated with a syringe 2-12 hours after intercourse.Gross
and microsocopic examination is carried out.

18. Cervical mucous penetration test:
• Semen is injected in capillary tube containing cervical
mucous
• See for distance traveled in capillary by sperms:
Fertile men: Sperms travel >30mm
Infertile men: sperms travel <20mm

19. Hormone Assessment
• In general, FSH and testosterone should be measured in infertile men with sperm
concentrations of <10 × 106 sperm/mL.
• This combination of tests will detect most (99%) endocrine abnormalities
• Serum LH and prolactin levels may be obtained if testosterone and FSH are abnormal.
• In the setting of low testosterone, free testosterone should be assessed.
• Given the role of estradiol in regulating the HPG axis, it too should be assessed if
there is evidence of poor virilization or obesity.

20. GENETIC TESTS
1.Chromosomal Studies
• It is estimated that between 2% and 15% of infertile men with
azoospermia (no sperm count) or severe oligospermia (low sperm
counts) will harbor a chromosomal abnormality on either the sex
chromosomes or autosomes.
• A blood test for cytogenetic analysis (karyotype) can determine if
such a genetic anomaly is present.
• Patients at risk for abnormal cytogenetic findings include men with
small, atrophic testes; elevated FSH values; and azoospermia.
• Klinefelter syndrome (XXY) is the most frequently detected sex
chromosomal abnormality among infertile men.

21. 2.Cystic Fibrosis Mutation Testing
A blood test is indicated for infertile men who:
1. Present with CF or the much more subtle condition, CAVD.
2. Azoospermic men with idiopathic obstruction.
3. Men with a clinical triad of chronic sinusitis, bronchiectasis, and
obstructive azoospermia (OA) (Young syndrome)

22. 3.Y Chromosome Microdeletion Analysis
• As many as 15% of men with azoospermia
have small, underlying deletions in one or
more gene regions on the long arm of the
Y chromosome (Yq).
• Recommended for men with low or no
sperm counts and small, atrophic testes.
• A polymerase chain reaction–based blood
test can examine the Y chromosome from
peripheral leukocytes for these gene
deletions

23. Radiologic Testing
A. Scrotal Ultrasound
• Scrotal ultrasound is indicated in men who have a hydrocele,
whereby the testis is nonpalpable and any abnormality of the
peritesticular region.
• Scrotal color Doppler ultrasonography has been used to
investigate varicoceles

24. B. Transrectal Ultrasound
• High-frequency (5–7 mHz) transrectal ultrasound (TRUS) can provide good anatomic
detail of the prostate, seminal vesicles, and ejaculatory ducts
• Dilation of the seminal vesicles (>1.5 cm in width) or ejaculatory ducts (>2.3 mm)
in association with a cyst, calcification, or stones along the duct is highly
suggestive of obstruction
• Among infertile men, TRUS is indicated in cases of low ejaculate volume (<1.5 mL)
not explained by retrograde ejaculation or abnormal hormones.

25. C.Vasography
• In azoospermic men with normal ejaculate volume and evidence of normal
spermatogenesis by testis biopsy, formal investigation of the reproductive tract to
identify the site of obstruction is warranted.
• Vasography can be performed with ultrasound(US) or fluoroscopic guidance and
requires cannulation of the vas deferens and injection of contrast material to
opacify the ejaculatory apparatus. It is invasive and carries a risk of post-
procedure stricture of the vas deferens

26. D. Venography
• Historically, venography has been
described as the most sensitive
way to diagnose varicoceles.
• at present, its main indications
are to guide simultaneous
percutaneous varicocele
embolization and it is virtually
never utilized as a stand-alone
diagnostic test.
• Venographically, a varicocele is
defined by a Valsalva-induced
retrograde flow, of contrast
material from the renal vein into
the scrotal pampiniform plexus.

28. Recommendation 1:
The diagnosis of azoospermia requires the absence of sperm from at least two
separate centrifuged semen samples.
Recommendation 2:
The minimum initial evaluation of an azoospermic patient should include a full
medical history, physical examination, and measurement of serum testosterone
and follicle-stimulating hormone levels.

29. Recommendation 3:
Men with congenital bilateral absence of the vasa deferentia should be
offered genetic counseling and testing for cystic fibrosis transmembrane
conductance regulator mutations. The female partner should also be offered
cystic fibrosis transmembrane conductance regulator mutations testing before
proceeding with treatments that utilize the sperm of a man with congenital
bilateral absence of the vasa deferentia.
Recommendation 4:
Imaging for renal abnormalities should be offered to men with unilateral vasal
agenesis or congenital bilateral absence of the vasa deferentia and no
evidence of cystic fibrosis transmembrane conductance regulator
abnormalities.

30. Recommendation 5:
Testing for cystic fibrosis transmembrane conductance regulator abnormalities
should include at minimum a panel of common point mutations and the 5T allele.
There currently is no consensus on the minimum number of mutations that
should be tested.
Recommendation 6:
Gene sequencing may be considered in couples where the wife is a carrier and
the husband with congenital bilateral absence of the vasa deferentia tests
negative on a routine panel of cystic fibrosis transmembrane conductance
regulator mutations.

31. Recommendation 7 :
All patients with non-obstructive azoospermia due to primary testicular failure
should be offered genetic testing. Patients with acquired hypogonadotropic
hypogonadism should be evaluated for functioning and non-functioning pituitary
tumors by measurement of serum prolactin and imaging of the pituitary gland.

32. Recommendation 8:
Transrectal ultrasonography, with or without seminal vesicle aspiration and
seminal vesiculography, should be considered as an initial minimally invasive
diagnostic choice to identify ejaculatory duct obstruction in azoospermic men
with low ejaculate volume and bilateral palpable vasa. In patients with
ejaculatory duct obstruction demonstrated by TRUS, testis biopsy may be
considered if needed to confirm normal spermatogenesis. Vasography with or
without testicular biopsy should be considered a second line choice to identify
the site of reproductive tract obstruction in these patients, and should not be
done unless reconstructive surgery is undertaken at the same surgical
procedure. Patients with unilateral absence of the vas and low volume
azoospermia, may have a varient of CBAVD and should have CFTR and 5T
testing and if positive do not need TRUS.

33. Recommendation 9:
Karyotyping and genetic counseling should be offered to all patients with
nonobstructive azoospermia and severe oligospermia (<5 million sperm/mL).
Recommendation 10:
Although the prognosis for sperm retrieval is poor for patients with large
deletions involving AZF region a or b, the results of Y chromosome deletion
analysis cannot absolutely predict the absence of sperm.

34. Congenital bilateral absence of the vas deferens (CBAVD).
• Most of them ass with cystic fibrosis.
• CF typically presents with chronic lung obstruction and pulmonary infections,
pancreatic insufficiency, and infertility.
• In addition to the vas, parts of the epididymis, seminal vesicles, and
ejaculatory ducts may be atrophic or absent, causing obstruction
• Although spermatogenesis is quantitatively normal, recent data suggest that
sperm from men with CF may lack the normal capacity to fertilize an egg.
• 15% of these men will have renal malformations, most commonly unilateral
agenesis.
• Investigations to be done:
1. Cystic Fibrosis Mutation Testing
2. Pelviabdominal U/S.
3. Sperm function tests.

35. Retrograde ejaculation:
*Definition:
Backflow ofsemen into UB during ejaculaion.
*Search for the cause:
1. Anatomical (operation).
2. Neurological(RPLND , lower abd surgery and DM).
3. Medication:
A. α blockers
B. Antipsychotic eg chlorpromazine.
C. Antidepressent eg. Imipramine hydrochloride.
D. Antihypertensive eg. Thiazide.
4. Spinal cord injury.

36. Ejaculatory duct obstruction:
*Part of disease:
1. Cystic fibrosis.
2. Adult polycystic kidney disease:
• AD , associated with numerous cysts of the kidney, liver, spleen,
pancreas, epididymis, seminal vesicle, and testis.
• Infertility with this disease is usually secondary to obstructing cysts in
the epididymis or seminal vesicle.
* Congenital:
* Utricular cyst
* Wolffian duct cyst
* Acquired:
* SV calculi
* Post surgical or inflamatory scae

37. Y Chromosome Microdeletions:
•13% of men with azoospermia have a structural alteration
in the long arm of the Y chromosome (Yq).
•A quantitative polymerase chain reaction–based assay is
used to test blood for these deletions.
•In the future, sperm DNA may also be tested as part of a
semen analysis.
•Since men with these microdeletions can have sperm in
the ejaculate, they are likely to pass them on to offspring
if ART is used.

38. Klinefelter Syndrome:
*Klinefelter syndrome is the most common chromosomal
aneuploidy and a common genetic cause of azoospermia,
accounting for up to 14% of cases in some series
*The classic triad of findings is small,firm testes;
gynecomastia; and azoospermia.
*The testes are usually <2 cm in length; biopsies show sclerosis
and hyalinization of the seminiferous tubules with normal
numbers of Leydig cells.
*Hormones usually demonstrate decreased testosterone and
frankly elevated LH and FSH levels.

39. Isolated LH Deficiency:
• there is enough LH to stimulate intratesticular testosterone
production and spermatogenesis but insufficient testosterone to
promote virilization
• Clinically there are: variable virilization, gynecomastia,
normal size testes, but sperm concentration is low.
• Plasma FSH levels are normal, but serum LH and testosterone
levels are low normal.
Isolated FSH Deficiency:
• Patient is normally virilized, testicular size is normal, and LH
and testosterone levels are normal. FSH levels are uniformly
Low
•
azoospermia to severely low numbers
(oligospermia).
Isolated Gonadotropin Deficiencies

40. Androgen Receptor Deficiency:
•Androgen receptor deficiency is an X-linked genetic
condition marked by resistance to androgens.
•The androgen receptor, a nuclear protein, is absent or
functionally altered such that testosterone or DHT
cannot bind to it and activate target cell genes.
•Since androgens have no effect on tissues, both
internal and external genitalia are affected.
•Fertility effects depend on the specific receptor
abnormality.

41. Hyperprolactinemia:
• The most common and important cause of hyperprolactinemia
is a prolactin-secreting pituitary adenoma, or prolactinoma
• MRI of the sella turcica has classically been used to distinguish
between microadenoma (<10 mm) and macroadenoma (>10
mm) forms of tumor.
• Elevated prolactin typically results in suppression of
gonadotropin production, with subsequent declines in
testosterone levels and spermatogenesis.
• Symptoms of hyperprolactinemia may include loss of libido,
erectile dysfunction, gynecomastia, and galactorrhea.

42. Hormonal assessment revealing low testosterone, low LH, low
FSH, and normal prolactin levels.
Gonadotropin Deficiency (Kallmann Syndrome):
Kallman syndrome
GnRH deficiency +
Red-green blindness
Anosmia
Cleft palate
Neurosensory
hearing loss
Synkinesis
Renal anomalies

43. Caused by a deficiency of hypothalamic GnRH
Prader–Willi syndrome
obesity, mental retardation, small extremities, and
hypogonadism
Bardet–Biedl syndrome
mental retardation, retinitis pigmentosa, polydactyly, and
hypogonadism and Obesity
Congenital Hypogonadotrophic Syndromes

44. Reproductive Tract Obstruction:
A. Congenital Blockages:
1. Young syndrome:
• Presents with a triad of chronic sinusitis, bronchiectasis, and OA.
• The obstruction is in the epididymis.
2. Idiopathic epididymal obstruction:
B. Acquired Blockages:
1. Vasectomy
2. Groin surgery
3. Bacterial infection:
(E. coli in men age >35 or Chlamydia trachomatis in young men)