2. Moderators:
Professors:
0 Prof. Dr. G. Sivasankar, M.S., M.Ch.,
0 Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
0 Dr. J. Sivabalan, M.S., M.Ch.,
0 Dr. R. Bhargavi, M.S., M.Ch.,
0 Dr. S. Raju, M.S., M.Ch.,
0 Dr. K. Muthurathinam, M.S., M.Ch.,
0 Dr. D. Tamilselvan, M.S., M.Ch.,
0 Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC,
Chennai.
2
3. Infertility
0 “A disease of the reproductive system defined by the failure to
achieve a clinical pregnancy after 12 months or more of regular
unprotected sexual intercourse.”(WHO)
3
Dept of Urology, GRH and KMC,
Chennai.
4. Incidence
o 75 % of the couples achieve conception, if desired
within 1 year of having regular intercourse with
adequate frequency.
o Another 10-15% achieve the objective by the end of
2nd year.
o As such, rest 15% remains infertile by the end of
second year.
4
Dept of Urology, GRH and KMC,
Chennai.
6. Primary infertility :
Those patients who have never conceived
Secondary infertility :
Indicates previous pregnancy but failure to
conceive subsequently
Primary testicular failure- testicular cause-
irreversible
Secondary testicular failure
6
Dept of Urology, GRH and KMC,
Chennai.
13. Posttesticularcauses
Obstruction of efferent
duct
Congenital
• Absence of Vas deference
(cystic fibrosis)
• Young’s syndrome
Acquired infections
• Tuberculosis
• Gonorrhoea
Surgical
• Herniorrhaphy
• Vasectomy
• Testicular torsion
Others
Ejaculatory failure
Retrograde ejaculation
Hypospadias
Bladder neck surgery
13
Dept of Urology, GRH and KMC,
Chennai.
14. CLINICAL HISTORY
0 FAMILY HISTORY
0 Infertility
0 Cystic fibrosis
0 Androgen receptor deficiency
14
Dept of Urology, GRH and KMC,
Chennai.
15. Female factors
0 Fifty percent of infertility can be attributed to the
female side
0 Advanced age On averagefemale, fecundity declines
precipitously after age 35
• Ovulatory dysfunction occurs in 40% of infertile
women (largest single cause)
• Abnormalities of uterine cavity or tubal anatomy
occur in 25% of infertile women
15
Dept of Urology, GRH and KMC,
Chennai.
21. Investigationsofinfertility
0 Objectives of investigations :
o To detect Aetiological factors.
o To rectify abnormality in an attempt to improve the
fertility.
o To give assurance with explanation to the couple
if no abnormality is detected.
21
Dept of Urology, GRH and KMC,
Chennai.
22. 0 When to investigate? :
0 Recommended - deferring medical assessment until 12 months
of unprotected intercourse
0 Evaluation begin after 6 moths if
0 (1) male infertility risk factors such as a history of bilateral
cryptorchidism
0 (2) female infertility risk factors - advanced female age (older than
35 years), or
0 (3) the couple questions the male partner’s fertility potential
0 Concurrent basic evaluation of the female partner is also
prudent
22
Dept of Urology, GRH and KMC,
Chennai.
23. Clinicalapproachto maleinfertility
ClinicalDetails
0 Infertility History
• Previous pregnancy (current partner / other partner)
• Age of partners, length of time the couple has been attempting to
conceive
• Contraceptive methods / duration
• Previous treatments
• Treatments / evaluations of female partner.
0 Sexual History
• Potency, libido, lubricant use
• Ejaculation, timed intercourse, frequency of masturbation
0 Childhood and Development
• Cryptorchidism, Hernia, Testicular trauma
• Testicular torsion, Infection (e.g. mumps)
• Sexual development, Puberty onset 23
Dept of Urology, GRH and KMC,
Chennai.
24. 0 Personal History
• Systemic diseases (Diabetes, Cirrhosis, Hypertension)
• Sexually transmitted diseases, tuberculosis, viral
infections
0 Previous Surgeries
• Orchidopexy, herniorrhaphy, orchidectomy
(testicular cancer, torsion)
• Retroperitoneal and pelvic surgery
• Other inguinal, scrotal and perineal surgery
• Bariatric surgery, Bladder neck surgery
• Transurethral resection of the Prostate
24
Dept of Urology, GRH and KMC,
Chennai.
25. 0 Gonadotoxin Exposure
• Alcohol, cocaine, marijuana abuse
• Medication
• Anabolic steroids, tobacco use
• High temperatures – Hot furnaces, brick workers
• Radiation (Therapeutic, Nuclear power plant workers)
0 Family History
• Cystic fibrosis
• Infertility in the family
0 Current Health Status
• Respiratory infection
• Obesity
25
Dept of Urology, GRH and KMC,
Chennai.
26. Physicalexamination
0 Appropriate sexual development :
o Presence of diminished body hair distribution.
o Gynaecomastia – Androgen deficiency suspected.
0 Height:Pubic to heal height >5cm than the upper
body
segment
0 Obesiity
0 Genital examination :
Look for presence of
• Hypospadiasis
• Pathological curvature of phallus
• An active STD
26
Dept of Urology, GRH and KMC,
Chennai.
27. Genital Examination
Examination of the scrotum & its contents
0 Examined in both supine and standing positions
0 In a warm room to assist relaxation of the cremasteric
muscle
0 The entire testicular surface should be palpated to
assess
0 consistency
0 rule out masses factor for testicular carcinoma)
27
Dept of Urology, GRH and KMC,
Chennai.
28. 0 Testicular size should be assessed with either an
orchidometer, calipers, or sonographic measurement
0 Normal adult testicular measurements to be at least 4 × 3
cm or 20 mL in volume
0 Because 85% of the testicular volume involves sperm
production, decreased testicular size portends impaired
spermatogenic potential
28
Dept of Urology, GRH and KMC,
Chennai.
29. The epididymis
0 Palpated for enlargement or induration, which can
indicate downstream obstruction or inflammatory
conditions such as epididymitis
0 Granulomatous changes of the epididymis
Tuberculosis, bacile Calmette-Guerin (BCG)
treatments, and sarcoidosis
29
Dept of Urology, GRH and KMC,
Chennai.
30. 0 Small cystic lesions of the epididymis are common
and are usually spermatoceles, which are often
nonobstructing
0 palpable at Upper pole but nonpalpaible at lower
pole :incomplete wolffian development
30
Dept of Urology, GRH and KMC,
Chennai.
31. Examination of the spermatic cord
0 By palpation for asymmetry of the spermatic cord, or an
impulse, during the Valsalva maneuver
0 Gentle traction on the testis during examination can be
helpful in more difficult examinations such as patients with
high riding testes or exaggerated cremasteric muscle
response to Valsalva
0 vas disappears from the examiner's fingers three times, the
clinician can be confident that the vas is absent: Meacham's
maxim
31
Dept of Urology, GRH and KMC,
Chennai.
32. Palpation of the vas deferens
0 Inability to palpate the vas deferens indicates
unilateral or bilateral vasal agenesis
0 Nodularity of the vas -- prior infections such as
tuberculosis
0 Vasal thickening is associated with prior scrotal
surgery or downstream obstructions such as
inguinal vasal obstruction, potentially from prior
surgery ( HERNIA MESH ) or ejaculatory duct
obstruction.
32
Dept of Urology, GRH and KMC,
Chennai.
33. 0 Varicoceles are present in 15-20% normal males
0 incidence of varicocele in infertile males to be
between 30-50%
0 Left side is common
0 Due to the right-angle insertion of the left gonadal vein
into the renal vein
0 Turbulent flow
0 90% present on the left side alone
33
Dept of Urology, GRH and KMC,
Chennai.
34. Rectal examination
• Prostatic midline cysts such as müllerian duct cysts,
which can obstruct the ejaculatory ducts
• Prostatic induration or tenderness may be seen in
acute or chronic prostatitis
• The seminal vesicles are not palpable normally but
prominent in the setting of ejaculatory duct
obstruction
34
Dept of Urology, GRH and KMC,
Chennai.
36. Investigations
1) Semen analysis
2) Sperm function tests
3) Endocrine evaluation
4) Genetic evaluation
5) Transrectal, Scrotal and Renal Ultrasonography
6) Magnetic resonance imaging
7) Vasography
8) Testicular biopsy.
36
Dept of Urology, GRH and KMC,
Chennai.
37. Semenanalysis
Cornerstone of the initial evaluation.
Status of the germ epithelium, epididymis and the
accessory sexual glands.
Collected and analyzed in specialized laboratory
under quality control standards.
Before a definitive conclusion, results from at least two
out of preferably three, separate seminal analyses must
be obtained.
The interval between the analyses is arbitrary and is
generally recommended to be 1-2 weeks.
37
Dept of Urology, GRH and KMC,
Chennai.
38. Collection
o Semen specimen is collected after about 1-2 days of
sexual abstinence.
o Longer period of abstinence reduces the motility of
sperms.
o Shorter duration (< 1days) leads to lower
sperm count
38
Dept of Urology, GRH and KMC,
Chennai.
39. Don’t….
o Condom collection is usually not recommended
[ Spermicidal agents interfere with the motility of spermatozoa]
o Coitus interruptus is not a reliable means of semen collection
First portion of the ejaculate may be lost
Cellular & bacteriological contamination of the sample
Low pH of the vaginal fluid could affect sperm motility
39
Dept of Urology, GRH and KMC,
Chennai.
40. o Clean, Dry, Sterile and Wide mouthed plastic container.
o Avoid spillage outside the container - Hypospermia.
o Entire ejaculate should be collected.
o Sample must be brought to the laboratory within1 hr of
collection.
o Transport to the laboratory
[Tempt. 20 °C - 37 °C].
o Microbiological laboratory
- Within 3 hours.
Collection
40
Dept of Urology, GRH and KMC,
Chennai.
41. (I) Initialmacroscopicexamination
0 Liquefaction :
- The complete sample usually liquefies within 30
minutes at room temperature, Although rarely it may
take up to 60 minutes or more.
- If complete liquefaction does not occur within
60 minutes, this should be recorded.
41
Dept of Urology, GRH and KMC,
Chennai.
42. (a)Semenviscosity
It can be estimated by aspirating it into a wide-bore plastic
disposable pipette (1.5 mm diameter) allowing the semen to drop by
gravity.
A normal sample leaves the pipette in small discrete drops.
If viscosity is abnormal, the drop will form a thread more than 2 cm
long.
Impression - High viscosity can interfere with
Determination of sperm motility
Sperm concentration
Detection of antibody-coated spermatozoa
Measurement of biochemical markers
42
Dept of Urology, GRH and KMC,
Chennai.
43. (b)Appearanceoftheejaculate
A normal liquefied semen sample has a
homogeneous, grey-opalescent appearance.
Brown : Spinal cord injury
Red : When red blood cells are present
(haemospermia)
Yellow/green : In case of infection,jaundice or T/t with
certain
vitamins or drugs.
43
Dept of Urology, GRH and KMC,
Chennai.
44. (c) Semenvolume
0 Contributed by seminal vesicles, prostate gland,
bulbourethral glands and epididymis.
0 Normal volume : 1.5 mL
0 Low semen volume :
- Collection problems (loss of a fraction of the ejaculate)
0 anatomic factors, CBAVD
0 Retrograde ejaculation;
0 Neurologic conditions,
0 pharmacologic factors,
0 High semen volume :
0 Active inflammation of the accessory organs., the sperm may be
reconstituted by processing into a smaller volume and IUI
performed
44
Dept of Urology, GRH and KMC,
Chennai.
45. (d)SemenpH
o The pH values of accessory gland secretions mainly alkaline seminal
vesicular secretion & acidic prostatic secretion.
o Role??
o Normal pH: 6.0 to 10.0 [Reference values - 7.2].
o pH is less than 7.0 - Ejaculatory duct obstruction, Congenital
bilateral absence of the vas deferens.
o pH is more than 7.0 -
pH increases with time as natural buffering
decreases, provides little clinically
useful information.
45
Dept of Urology, GRH and KMC,
Chennai.
46. (II)Initialmicroscopicinvestigation
A phase-contrast microscope is recommended
for all examinations of unstained preparation.
This provides Overview of the sample:
• Mucus strand formation;
• Sperm aggregation or agglutination;
• Other cells e.g. Epithelial cells, leukocytes, immature germ
cells) and isolated sperm heads or tails of fresh semen.
• Assessment of sperm motility.
46
Dept of Urology, GRH and KMC,
Chennai.
48. (b)Agglutinationof spermatozoa
o Agglutination specifically refers to motile
spermatozoa sticking to each other, head-to-head,
tail-to-tail or in a mixed way
Grade 1:
Isolated
<10 spermatozoaper agglutinate,many free spermatozoa
Grade 2:
Moderate
10–50 spermatozoaper agglutinate,free spermatozoa
Grade 3:
Large
Agglutinatesof >50 spermatozoa, some spermatozoastill free
Grade 4:
Gross
All spermatozoaagglutinatedand agglutinatesinterconnected
48
Dept of Urology, GRH and KMC,
Chennai.
50. o Remember :
The presence of agglutination is not sufficient evidence to
deduce an immunological cause of infertility, but is suggestive
of the presence of anti-sperm antibodies; further testing is
required.
Severe agglutination can affect the assessment of sperm
motility and concentration.
50
Dept of Urology, GRH and KMC,
Chennai.
51. (c) Cellularelementsotherthan
spermatozoa
• The ejaculate contains cells other than spermatozoa.
• These include epithelial cells from the genitourinary tract,
as well as leukocytes and immature germ cells, the latter
two collectively referred to as “round cells”.
• They can be identified by examining a stained smear at
x1000 magnification.
51
Dept of Urology, GRH and KMC,
Chennai.
52. (III)Spermmotility
Sperm motility within semen should be assessed as soon
as possible after liquefaction of the sample, preferably at
30 minutes to limit the deleterious effects of dehydration,
pH or changes in temperature on motility.
52
Dept of Urology, GRH and KMC,
Chennai.
53. Categoriesofspermmovement
0 Progressive motility (PR) :
Spermatozoa moving actively, either linearly or swimming
in a large circle, regardless of speed.
0 Non-progressive motility (NP) :
All other patterns of motility with an absence of progression
e.g. swimming in small circles, the flagellar force hardly
displacing the head or when only a flagellar beat can be
observed.
0 Immotility (IM) : No movement.
53
Dept of Urology, GRH and KMC,
Chennai.
54. Normalrange
The lower reference limit for total motility (PR + NP) is
40%
The lower reference limit for progressive motility (PR) is
32%
54
Dept of Urology, GRH and KMC,
Chennai.
55. (IV)Spermvitality
0 The percentage of live spermatozoa is
assessed by identifying those with an intact
cell membrane from dye exclusion or by hypotonic
swelling.
0 The presence of a large proportion of vital but immotile
cells may be indicative of structural defects in the
flagellum.
0 A high percentage of immotile and non-viable cells
(necrozoospermia) may indicate epididymal
pathology.
55
Dept of Urology, GRH and KMC,
Chennai.
56. (a)Vitalitytestusingeosin–nigrosin
o Principle :
A cell with intact cell membrane (a viable cell) will not take
up the eosin Y and will not be stained. While a non-viable
or dead cell will have damaged cell membrane will take up
the dye and will be stained pink red.
o Method :
• 1 drop of semen + 1 drop of eosin nigrosin solution,
incubate
• Prepare smear
• Air dry and observe under oil immersion objective
• Atleast 200 spermatozoa are observed. 56
Dept of Urology, GRH and KMC,
Chennai.
57. Spermatozoa with red (D1) or dark pink (D2) heads are considered dead
(membrane-damaged) whereas spermatozoa with white heads (L) or light
pink heads are considered alive (membrane intact).
57
Dept of Urology, GRH and KMC,
Chennai.
58. (b)Vitalitytestusinghypo-osmoticswelling
0 As an alternative to dye exclusion, the hypo-osmotic
swelling (HOS) test may be used to assess vitality.
0 This is useful when staining of spermatozoa must be
avoided.
0 Spermatozoa with intact membranes swell within 5
minutes in hypo-osmotic medium and all flagellar shapes
are stabilized by 30 minutes
58
Dept of Urology, GRH and KMC,
Chennai.
59. Schematic representation of typical morphological
changes in human spermatozoa subjected
to hypo-osmotic stress
59
Dept of Urology, GRH and KMC,
Chennai.
60. (V)Sperm numbers
The number of spermatozoa in the ejaculate is calculated
from the concentration of spermatozoa.
For normal ejaculates, when the male tract is unobstructed
and the abstinence time short, the total number of
spermatozoa in the ejaculate is correlated with testicular
volume and thus is a measure of the capability of the testes
to produce spermatozoa and the patency of the male tract.
0 lower limit sperm conc is > 15x 106 /mL
60
Dept of Urology, GRH and KMC,
Chennai.
61. Related Terminologies:
0 Azoospermia : Absence of sperms in seminal fluid
0 Aspermia : Absence of ejaculate
0 Asthenozoospermia : Reduced sperm motility After
liquifaction
0 Teratozoospermia : Spermatozoa with reduced proportion of
normal morphology
0 Leucocytospermia : > 1 million WBCs/ mL of semen
0 Oligoasthenospermia : All sperm variables abnormal
0 Necrozoospermia : All sperms are non-motile or
non-viable
61
Dept of Urology, GRH and KMC,
Chennai.
63. (VI)Spermmorphology
3 main components :
Head
Neck
Tail : Middle piece
End piece
0 Lower limit is 4%
0 50th percentile is 15%
63
Dept of Urology, GRH and KMC,
Chennai.
64. Schematicdrawingsof someabnormalformsof
humanspermatozoa
0 WHO morphological classification of human spermatozoa
(2010)
Normal sperm
Defects in head :
Large heads
Small heads
Tapered heads
Pyriform heads
Round heads
Amorphous heads
Vacuolated heads
Small acrosomes
64
Dept of Urology, GRH and KMC,
Chennai.
65. 0 globozoospermia : acrosome fail to form, sperm will
have small, round heads, a
0 pinhead sperm: During spermiation, if the basal plate
does not attach to the nucleus opposite the acrosome,
the heads are absorbed ,results in only tails
65
Dept of Urology, GRH and KMC,
Chennai.
66. Defects in neck :
Bent neck and tail forming an angle > 90 to the
long axis of head
Defects in middle piece :
Asymmetric insertion of midpiece into head
Thick or irregular midpiece
Abnormally thin midpiece
66
Dept of Urology, GRH and KMC,
Chennai.
67. Defects in tail :
Bent tails
Short tails
Coiled tails
Irregular tails
Multiple tails
Tails with irregular width
Pin heads
Cytoplasmic droplets
67
Dept of Urology, GRH and KMC,
Chennai.
68. Countingof cellsotherthanspermatozoa
o The presence of non-sperm cells in semen may be
indicative of
Testicular damage (immature germ cells),
Pathology of the efferent ducts (ciliary tufts)
Inflammation of the accessory glands (leukocytes).
o The number of non-sperm cells in semen (epithelial cells,
“round cells” (germ cells and leukocytes) or isolated
(sperm heads and tails) can be estimated in fixed wet
preparations by the use of a haemocytometer.
68
Dept of Urology, GRH and KMC,
Chennai.
69. (VII)Testingforantibodycoatingof
spermatozoa
o If spermatozoa demonstrate agglutination (i.e. motile
spermatozoa stick to each other head-to-head, tail-to-tail
or in a mixed way), the presence of sperm antibodies may
be the cause.
o Anti-sperm antibodies (ASAs) in semen belong almost
exclusively to two immunoglobulin classes: IgA and IgG.
o IgM antibodies because of their larger size are rarely
found in semen.
o IgA antibodies may have greater clinical importance
than IgG antibodies
69
Dept of Urology, GRH and KMC,
Chennai.
70. 0 direct tests:immunoglobulins on the surface of sperm,preffered,
target IgA &IgG
Type:mixed antiglobulin reaction (MAR) test &immunobead assay
0 indirect test:measure antibodies in fluid such as seminal plasma
or serum
0 Pyospermia :threshold for leukocytes is 1 million/mL(WHO),
Papanicolaou stain is used to differentiate leukocytes from
immature germ cells
70
Dept of Urology, GRH and KMC,
Chennai.
71. In-vivo(postcoital)test
(Sims-Huhner)test
The aims of a postcoital test are to determine the number
of active spermatozoa in the cervical mucus and to
evaluate sperm survival and sperm behaviour some hours
after coitus
Postcoital tests should be performed as close as possible
to, but before the time of ovulation, as determined by
clinical criteria
71
Dept of Urology, GRH and KMC,
Chennai.
72. Interpretation :
Normal – Sperms normal in amount and
moving in forward direction, mucus
stretches atleast 2 inches and dries in
a fern like manner
Abnormal – Absence of sperms or large no of sperms are
clumped, cervical mucus cannot stretch 2 inches or does not
dry in a fern like manner
72
Dept of Urology, GRH and KMC,
Chennai.
73. Tertiary and Investigational Sperm Assays
0 An assessment of sperm DNA integrity(lack of standardized
testing protocols and diagnostic thresholds)
Infertile men present with a normal semen analysis as
determined by conventional methods
Recurrent spontaneous abortion
To determine the most suitable assisted reproductive
technology
0 TUNEL Assay, Comet Assay, Denatured Sperm DNA Assays.
73
Dept of Urology, GRH and KMC,
Chennai.
74. Spermfunctiontests
1) Hypo-osmotic swelling test
2) Acrosome test
3) Sperm Fluorescence in situ Hybridization : detect high
levels of sperm aneuploidy Currently, it has been used as a
diagnostic tool for couples with recurrent pregnancy loss
or recurrent implantation failure
74
Dept of Urology, GRH and KMC,
Chennai.
81. Semen Hormonal control
0 FSH stimulates sertoli cells
which produce androgen
binding protein (ABP).
0 ABP binds testosterone
which induce high
concentration of
testosterone to initiate and
control spermatogenesis
0 Inhibin B and activin
regulate FSH
81
Dept of Urology, GRH and KMC,
Chennai.
83. Endocrine evaluation
Endocrine evaluation is suggested when the following
scenarios are present :
A sperm concentration, 10 million/mL;
Hypospermia (volume ,1 mL)
Erectile dysfunction
Signs and symptoms of endocrinopathies or
hypogonadism
0 Initial evaluation include: morning total testosterone,
SHBG, and albumin to calculate bioavailable testosterone;
LH and FSH to gauge pituitary function; and estradiol to
evaluate aromatization
83
Dept of Urology, GRH and KMC,
Chennai.
84. (a)Testosterone,FSHandLH
0 spermatogenesis is dependent on intratesticular testosterone
synthesis
0 Testosterone levels in men 280 ng/dL - 300 ng/dL
0 free and loosely bound to albumin,bioavailable testosterone
54.4%(164ng/dl)
0 Androgenization should be assessed in all men for infertility,
even if sperm count is greater than 20million/mL
0 bioavailable testosterone demonstrates a marked circadian
rhythm in young, healthy men, with a peak in the early
morning and trough in the late afternoon
84
Dept of Urology, GRH and KMC,
Chennai.
85. 0 In the case of hypoandrogenism, a pituitary or testicular
source is identified by assessing LH
0 Because testosterone and LH are released in a pulsatile
fashion, borderline results may be evaluated by obtaining
three morning samples at 20-minute intervals
0 Sertoli cell products inhibin B and activin regulate pituitary
folliclestimulating hormone (FSH)
85
Dept of Urology, GRH and KMC,
Chennai.
86. Gonadatrophin
o Isolated FSH elevationis usually indicativeof severe germ cell epithelium damage.
o ElevatedFSH and LH levels, when associatedwith low-normal or below normal
testosteronelevels, suggest diffuse testicularfailureand may have either a
congenital (e.g., Klinefeltersyndrome) or acquired cause.
o Concomitant lowlevels of FSH and LH may implicate hypogonadotropic
hypogonadism.
This conditionmay be congenitalor secondary to a prolactin-producingpituitary
tumour.
Gonadotropinvalues within the normal range suggest an extraductal obstruction
in azoospermic subjects.
However, azoospermicpatientswith testicular failure andtestis histology
exhibiting spermmaturation arrest and 10% of those diagnosedwith Sertoli-cell-
only syndrome may present with non-elevatedFSH levels.
86
Dept of Urology, GRH and KMC,
Chennai.
87. 0 Combined with testis size as measured by a caliper orchidometer, FSH is
an accurate predictor of whether azoospermia is a result of obstruction
or spermatogenic dysfunction
0 96%of men with obstructive azoospermia had FSH assay values of
7.6 IU/L or less and testis long axis greater than 4.6 cm, whereas
89% of men with azoospermia caused by spermatogenic
dysfunction had FSH values greater than 7.6 IU/L and testis long
axis 4.6 cm or less
0 Odds ratio of abnormal sperm concentration increased markedly at an
FSH value of 4.5 IU/L
87
Dept of Urology, GRH and KMC,
Chennai.
88. 0 AMH & inhibin b assessment is an alternative to can
be performed for spermatogenic function assessment
0 Prolactin is commonly a labile assay; if its levels are
elevated,repetition of the test is warranted
0 Men with a history of CAH may develop testicular
adrenal rest tumors and infertility later in life
In these patients, serum 17-hydroxyprogesterone, δ4-
Androstenedione, renin, and testosterone can be used
to assess response to therapy
88
Dept of Urology, GRH and KMC,
Chennai.
89. (c) Serumestradiol
0 Serum estradiol levels should be determined in patients
presenting with gynecomastia.
0 Infertile patients with a testosterone to estradiol ratio
less than 10 can harbor significant but reversible seminal
alterations.
0 It has been also suggested that hyperestrogenism
secondary to a higher conversion rate of testosterone
into estradiol in Klinefelter syndrome patients.
89
Dept of Urology, GRH and KMC,
Chennai.
91. Karyotyping
0 AUA Guidline recommend : Genetic testing including
karyotype be performed in all males with azoospermia caused
by spermatogenic dysfunction and in those with severe
oligospermia defined as less than 5 million sperm/mL
0
The long and short arms of the Y chromosome are related
to spermatogenesis and testicle development, espectively.
AZF is present on long arm
91
Dept of Urology, GRH and KMC,
Chennai.
92. Indications
Men with infertility of unknown
etiology and sperm concentrations,
5 million/mL who are candidates
for ART
Y chromosome microdeletion
and G-band karyotyping
Non-obstructive azoospermia in a male
considering testicular sperm retrieval for
ART
Yq chromosome microdeletion
and G-band karyotyping
Azoospermic or oligozoospermic men
with the absence of at least one vas
deferens at physical examination
CFTR gene mutation analysis
Azoospermic men with signs of normal
spermatogenesis (e.g., obstructive
azoospermia of unknown origin)
CFTR gene mutation analysis
History of recurrent miscarriage or
personal/familiar history of genetic
syndromes
G-band karyotyping
92
Dept of Urology, GRH and KMC,
Chennai.
93. Recent data suggest that azoospermic men with an
idiopathic obstruction and those presenting with the triad
composed by chronic sinusitis, bronchiectasis and
obstructive azoospermia (Young’s Syndrome) have an
elevated risk for the CFTR mutation.
93
Dept of Urology, GRH and KMC,
Chennai.
94. Transrectal,ScrotalandRenal
Ultrasonography
o Transrectal ultrasonography (TRUS) is recommended in
certain situations, including low semen volumes (1.5 mL),
abnormal digital rectal examination (DRE) and ejaculatory
disorders (anejaculation, hematospermia, painful
ejaculation).
o TRUS allows for the evaluation of the distal extraductal
system
o Seminal vesicles diameter >1.5cm: ductal obstruction
94
Dept of Urology, GRH and KMC,
Chennai.
95. o Scrotal ultrasonography should be performed to evaluate
palpable nodules or testicular masses,varicocele
o Urinary tract ultrasonography is suggested for the
evaluation of renal status in patients diagnosed with
Congenital Absence of Vas Deferens.
95
Dept of Urology, GRH and KMC,
Chennai.
96. Magneticresonanceimaging
0 Done to assess :
TRUS results are ambiguous
Seminal vesicle agenesis
Undescended testis
MRI has traditionally been used to exclude cranial
pathologies manifested by hormonal disturbances.
96
Dept of Urology, GRH and KMC,
Chennai.
97. Vasography
0 Saline Vasography is performed in case of obstructive
azoospermia undergoing surgery
0 Vasography and seminal vesiculography are usually
undertaken by scrotal or transrectal routes in the direction of
the abdomen
97
Dept of Urology, GRH and KMC,
Chennai.
98. Testisbiopsy
0 testis biopsy is not indicated in the initial diagnostic
evaluation
0 Testis biopsies done simultaneously with other
procedures such as testis sperm extraction may yield
pathologic information that can explain procedural
outcomes as well as provide information about other
related future diseases..
98
Dept of Urology, GRH and KMC,
Chennai.
99. 0 Percutaneous testicular biopsy may be performed using
a cutting needle of core biopsy
0 Specimens should be placed in a fixative solution such
as Bouin’s, Zenker’s or glutaraldehyde.
0 Formalin should not be used as it may disrupt the tissue
architecture.
99
Dept of Urology, GRH and KMC,
Chennai.
101. Hypospermatogenesis
o Thinner layers of germ
cells within seminiferous
tubules
o Decreased no of
elongated late spermatids/
spermatozoa
o Tunica propria thickening
o Focal interstitial fibrosis
o Focal tubular sclerosis
101
Dept of Urology, GRH and KMC,
Chennai.
103. Germinalcellaplasia
o Also known as sertoli
cell only syndrome
o Here, tubules are lined
by immature appearing
sertoli cells only
103
Dept of Urology, GRH and KMC,
Chennai.
104. Klienfilter’ssyndrome
o Diffuse and nodular
leydig cell hyperplasia
o Tubules often contain
sertoli cells only
104
Dept of Urology, GRH and KMC,
Chennai.
106. Cryptorchidism
o Some tubules
completely sclerotic
while others are lined
by sertoli cells only
o Also show moderate
tunica propria
thickening
106
Dept of Urology, GRH and KMC,
Chennai.
108. Microbiological assessment
0 Indications for microbiological assessment include
abnormal urine samples, urinary tract infections, ‘male
accessory gland infections’ (MAGI), and sexually
transmitted diseases (STDs).
0 In combination with a small ejaculate volume: this may
point to a (partial) obstruction of the ejaculatory ducts
caused by a (chronic) infection of the prostate or seminal
vesicles.
0 Genital infections may instigate the production of
spermatotoxic free oxygen radicals. Gonorrhoea and
Chlamydia trachomatis can also cause obstruction of the
genital tract.
108
Dept of Urology, GRH and KMC,
Chennai.
109. Counseling
0 Avoid alcohol, tobacco and street drugs
0 Avoid hot tubs and steam baths
Sometimes certain ‘lifestyle’ factors may be responsible for poor
semen quality:
for example, heavy smoking, alcohol abuse, use of anabolic
steroids, extreme sports (marathon training, excessive strength
sports).
An increase in scrotal temperature through thermal underwear,
sauna or hot tub
use, or occupational exposure to heat sources.
109
Dept of Urology, GRH and KMC,
Chennai.
113. In an attempt to correlate sperm nuclear ultrastructure with reproductive
outcomes, investigators examined sperm with an inverted light microscope
outfitted with high-power Nomarski differential interference contrast optics,
allowing for magnification of the field over 6000× (Bartoov et al., 2001). This
technique was termed motile sperm organelle morphology examination
(MSOME) (Bartoov et al., 2001). The theoretic advantage of MSOME is that it is
a nondestructive method of assessing sperm nuclear morphology, and a sperm
chosen by this method of high magnification visual inspection could be
subsequently used in IVF techniques (Bartoov et al., 2001). Early use of
MSOME appeared to lead to improved pregnancy rates in IVF by screening
those sperm with an overabundance of vacuoles in the sperm nucleus (Bartoov et
al., 2001, 2003; Berkovitz et al., 2006). However, later studies questioned
whether sperm so chosen actually led to improved IVF outcomes (Gatimel et al.,
2016; Perdrix and Rives, 2013). In fact, one study argued that sperm nuclear
vacuoles are a physiologic part of a normal sperm maturational process (Tanaka
et al., 2012). At this point, MSOME is best considered primarily an
investigational rather than a clinical tool.
113
Dept of Urology, GRH and KMC,
Chennai.
114. Assisted Reproduction
0 Female fecundity begins to decline after age 35, and
this decline accelerates after age 37
0 Because spermatogenesis is a lengthy process,
0 treatment directed toward improving may be
appropriate in a female age 30 years, but more
aggressive therapy for if she is 38 years of age or
older.
0 Intrauterine Insemination:in this a small catheter is
placed in cervical os to deliver sperm directly into the
uterus, bypassing the cervical barrier, IUI decreases in
effectiveness when the number of motile sperm in the
ejaculate is low
0 essential value of IUI is that it controls variables
related to the initial voyage of sperm in the
reproductive tract
114
Dept of Urology, GRH and KMC,
Chennai.
115. In vitro Fertilization
0 methods to manipulate gametes and embryos outside of a woman's body and to return the results
into the female reproductive tract.
0 ICSI was equally effective withsperm from eithertesticularor epididymal
origin,evencryopreservedsperm can be used
0 Diagnosesand Therapies
0 GeneticSyndromes
0 Klinefeltersyndrome: most commongeneticcause of male infertility;ass.
with supernumerary X chromosomeyielding 47,XXY
0 95% ass. in azoospermia,small testes, and elevatedgonadotropinlevels 75%
of childrenhave learningdisabilities,and 63% low testosteronelevels
0 Body morphology featuressuch as increasedheightare observed in only 30%
of Klinefeltermales, and condition cannot be excluded by physical
examination and physical inspection alone
0 Increased incidence mediastinal germ cell tumors
0 90% is ass with nonmosaicform xxy while remainder is mosaic form
46xy/47xxy
0 half of men have sufficientmature sperm amenableto surgicalsperm
retrieval for use with IVF and ICSI
115
Dept of Urology, GRH and KMC,
Chennai.
116. Structural Chromosomal Anomalies
0 Y chromosome microdeletion testing,three regions on the Y
chromosome, designated AZFa, AZFb, and AZFc, to be
associated with azoospermia or oligospermia
0 AZFa microdeletions have particular clinicalsignificancebecause spatially the
AZFa region appears to be localized distinctly from AZFb and AZFc, with the
latter two overlapping. Sperm conc decrease with time so cryopreservation
can be considered.
0 Other structural anomaliesof the Y chromosome:two terminalbreak and form a ring
chromosome withvariablephenotypedependingon the amount of chromosomal
material lost
0 spmatic chromosomeanamoliescan also lead perm dysfunction(eg.Mutn of HOX1,
WNT4 mutan
0 Epigenetic Anomalies: Not only must the DNA sequencebe intact for
successful function of the male gamete,but also the DNA must be tightly coiled and
packaged.protamine 2 precursorsand the protamine 1–protamine2 ratio to sperm
DNA quality and IVF outcomes
0 infertilemen have significantly decreasedlevels of histone H4 acetylationassociated
with impairedspermatogenesis. 116
Dept of Urology, GRH and KMC,
Chennai.
117. Testicular Causes
0 testisconsists of two compartments, seminiferoustubulesand interstitialspaces b
0 etweenthe tubules, inhabited by Leydig cells and transport system
0 seminiferoustubules: hpospematogenesis,sertoli cell syndrome and cause affecting
blood testis barrier: Pathologic conditionsthat disrupt bloodtestisbarriermay expose
the immunologically protected spermatidsand spermatozoato antibody formation,
which may cause sperm agglutination,impeded sperm motility, and reduced fertilizing
potentialeg. Obstructionaftervasectomy; inflammation associated withorchitis,
prostatitis,or sexually transmitteddisease;exposure to heat with varicocele,
cryptorchidism,or external sources such as hot tubs; trauma and testistorsion; and
genetic associationsincluding thymic maldevelopmentand the HLA-B28haplotype
117
Dept of Urology, GRH and KMC,
Chennai.
118. Steroidogenic Dysfunction
0 hypergonadotropic hypogonadism, primary hypogonadism,and primary
hypoandrogenism referto impairedtestosterone synthesiscaused by Leydig cell
dysfunction.Thisis typically identified byelevated LH levels and decreased
circulating testosterone
0 Increasingage is a conditionassociated with decreasingandrogen and blunted
pituitaryresponse
0 currently no acceptedtherapy for hypoandrogenismcaused by Leydig cell
insufficiency
0 Exogenous testosterone isnot indicated
0 Should azoospermia beassociatedwith low testosterone concentrationsand
significantly elevated LH levels, if the patientdesires paternity,the treatmentis
surgicalsperm extraction
118
Dept of Urology, GRH and KMC,
Chennai.
119. Microductal Obstruction
0 Either by congenitalor acquiredmeans, the epididymisor scrotal vas deferensmay
be obstructed
119
Dept of Urology, GRH and KMC,
Chennai.
120. Pituitary Dysfunction
0 Hypogonadotropic hypogonadism refersto the conditionof decreasedpituitary
hormonal secretion
0 Kallmann described anosmiaassociatedwith decreasedpituitaryfunction, most
frequently autosomal recessive,but autosomal-dominant and X-linked recessive
patternsare also observed, KAL1 gene encoding anosmin-1 responsiblefor neurotropic
growth factors during embryogenesis, the GNRHR geneencoding gonadotropin-releasing
hormone (GnRH) receptor, the pituitaryspecifictranscription factor PIT1, the PIT1-related
transcription factor PROP1,the G protein–coupled Kisspeptin receptor GPR54, the homeobox
genes HESX1,LEX3, and LEX4, and others
0 Treatment includesreplacementof LH with (hCG) and replacementof FSH
with recombinantFSH (rFSH) or hMG, which exhibits LH- and FSH-like activity
0 Typical doses for intramuscular or subcutaneous hCG are 1500
to5000 IU two to three times weekly to a maximum of 10,000
IU/wk and are titrated to serum testosterone, dose of hMG is
75 IU s/c two to three times weekly,
120
Dept of Urology, GRH and KMC,
Chennai.
121. 0 “fertile eunuchsyndrome”:Isolated LH deficiency with featuresof
hypoandrogenismbecauseof low levels of LH but who produce sperm as a result of
adequateFSH Conversely, men with isolated FSH deficiencyhave suppressed
spermatogenesisbut adequate androgenizationTreatmentof these uncommon
conditionsincludesreplacementwith the appropriategonadotropin
0 Men may also infrequently have isolatedhypothalamicGnRH deficiency.Treatment
includesGnRH administrationby a subcutaneousportable mini-infusionpump every
2 hours, and, as with treatment forKallmann syndrome, long-termcoursesof at least
6 months
0 Prader-Willisyndrome is characterized by failureto thrive in infancyassociatedwith
a poor suck reflex followed by loss of satiety in early childhood, which may lead to
markedobesity if poorly controlledIn the healthy state, the geneslocated on the
maternalchromosome15q11-q13 are silenced,and those on the paternal
chromosome areactive; in Prader-Willi syndrome, the maternal genesare silenced
and the paternalones inactive
121
Dept of Urology, GRH and KMC,
Chennai.