male infertility

1. MALE INFERTILITY
DR. NAVNEET MISHRA

2. INFERTILITY
WHO DEFINITION
“ failure to achieve a clinical pregnancy after 12
months or more of regular unprotected sexual
intercourse.”

3. WHY???
• Normal fertile couples of reproductive age
have a conception rate of 20% to 25% per
month ,with more than 90% conceiving within
1 year.
• Male factor infertility - approx 50% of infertile
couples.
• In 30% of cases an abnormality is discovered
solely in man

4. • As many as 2% Of all men will exhibit
suboptimal sperm parematers.
• Infertility seems to have increased in past
decades.
• Androgen deficiency in aging male (ADAM)

5. INCIDENCE
• AIIMS reported that over 12-18 million couple in
India are diagnosed with infertility every year .
• They have reported that sperm count of a normal
Indian adult male used to be 60million/ml three
decades ago now stands at around 20million/ml.
• Infertility is highest in Kashmir and lowest in UP &
Himachal.
• Globally it is highest in Africa & Eastern Europe(8-
15%).

6. Physiology

9. CAUSES
IDIOPATHIC
PRIMARY GONADAL DISORDERS (30-40%)
Varicocele
Klinefelter Syndrome
Y Chromosome deletions
Single gene deletions
Cryptorchidism
Radiation
Infection(mumps orchitis)

10. SPERM TRANSPORT DISORDERS(10-20%)
Epididymal obstruction or dysfunction
vasectomy
Kartagener syndrome
Young syndrome
Ejaculatory dysfunction
Hypospadias

11. Hypothalamic & Pituitary Disorders(1-2%)
Idiopathic isolated gonadotropin deficiency
Kallmann syndrome
Hyperprolactinemia
Chronic systemic illness
Obesity
Drugs

12. Management
GOALS
• Specific cause & correct it
• Individuals who can be offered intrauterine
insemination and ART.
• Individuals with genetic abnormality that may
affect offspring conceived by ART.
• Adoption & donor sperm options for those
who are not candidate for ART
• Underlying medical condition.

13. APPROACH
HISTORY
PHYSICAL EXAMINATION
SEMEN ANALYSIS
ENDOCRINE EVALUATION
UROLOGIC EXAMINATION
POST EJACULATORY SEMEN ANALYSIS
SPECIALISED TESTS

14.  Duration of infertility & previous fertility.
 Did puberty and virilization proceed normally/
 Have there been changes in libido, potency, or
hair loss suggestive of hypogonadism?
 Are there anatomic abnormalities (e.g.,
hypospadias, microphallus)?
 Are there any voiding difficulties or recent
changes in voiding pattern?
History

15.  Is there a history of diabetes mellitus or
neuropathic injury?
 Coital frequency & sexual dysfunction.
 Childhood illness.
 Previous surgical & medical illness.
 Past episodes of STI.
 Exposure to gonadotoxins & heat.
 Occupations & addictions.

16. Physical Examination
• Sec sexual characteristics, habitus, hair &
breast development.
• Systemic examination.
• Examination of penis, location of urethral
meatus.
• Palpation of testes & size.
• Presence of consistency of vas & epididymis.
• Digital rectal examination.

17. Semen Analysis
• Sperm production.
• Patency of male ducts.
• Function of accessory glands.
• Ejaculative function.

18. When AND how?
• After abstinence of 1 day.
• In a clean container by masturbation or via
intercourse using silastic condom or
electrostimulation.
• Examined with in an hour of collection.
• At least two to three semen analyses should
be done & spaced 2 to 3 months apart.

19. CART ANALYSIS FOR SEMEN
PARAMETERS
SEMEN PARAMETERS LOWER RANGE UPPER RANGE
VOLUME 1ML -
SPERM DENSITY 13.5 MILLION/ML 48.0 MILLION/ML
SPERM MOTILITY 32% 63%
SPERM MORPHOLOGY 9% 12%
SPERM VITALITY 58% 79%

20. Lower reference limits(WHO)
Volume 1.5 ML
Sperm concentration 15 MILLION/ML
Total sperm no/ejac 39 MILLION /EJACULATE
Total motility 40%
Progressive motility 32%
Normal morphology 4%
vitality 58%

21. Endocrine evaluation
INDICATIONS TESTS
Abnormal semen parameters,
particularly sperm
concentration is<10mill/ml
Sr.FSH
Total testosterone
Sr. Free testosterone
sexual dysfunction LH
Specific endocrinopathy PRL, TSH, Sr. estradiol

22. DISORDER FSH LH FREE T3
Hypogonadotropic
hypogonadism
low low low
Abnormal
spermatogenesis
N/high N N
Testicular failure high high N/low

23. Post-ejaculatory Urine analysis
INDICATION
• A low volume or absent antegrade ejaculate.
• Centrifuging the urine specimen for 10 mins
at 300g followed by microscopic examination
of pellet at 400 magnification.

24. In men with azoospermia or aspermia the
presence of any sperm in post ejaculatory
urinalysis suggests retrograde ejaculation.
In men with low ejaculate volume and
oligospermia significant no. of sperms must
be observed to support diagnosis of
retrograde ejaculation.

25. Retrograde ejaculation

26. Urologic evaluation
• TRUS ( Transrectal USG for duct obstruction)
to visualise seminal vesicles.
INDICATION-
-oligospermic men with low ejaculative volume .
-Palpable vas and normal testicular size.
• Transscrotal USG
• Renal scan
• vasogram

27. Genetic evaluation(karyotyping)
Indication-
Azoospermia- not done for every azoospermic
patient.
Not indicated if-
Normal testis volume.
Palpable vasa on physical examination and strong
suspicion for obstruction
Normal serum FSH and normal semen volume

28. Severe oligospermia(<5million/ml)
Not indicated if
suspected congenital obsruction(normal testis
volume and FSH)
Genetic disorders
Y chromosome deletions.
chromosomal anomalies most common
klinefelter’s syndome(46XXY).
CFTR gene mutations (CABVD).

29. Specialized Test
To evaluate attachment to zona pellucida
penetration of oocyte ,release of acrosomal
enzymes.
 Sperm autoantibodies
 Sperm penetration assay
 Computer assisted sperm analysis
 Acrosome reaction
 Sperm chromatin structure & DNA

30. Anti- Sperm Antibodies
• Found in 80% of men who have undergone
vasectomy
• a/w vasoepididymostomy or vasovasostomy ,
• testicular biopsy
• infection
• varicocele
• cryptorchidism and
• testicular torsion or trauma.

31. Indication-
• Men with semen analyses that show clumping
or agglutination of sperm.
• Asthenospermia
Test
• Mixed antiglobulin reaction test
• Immunobead test

32. Sperm viability
Viability testing will differentiate viable, nonmotile
sperm from dead sperm.
Indication- If less than 50% of sperm are motile
Useful in-
• To select nonmotile, viable sperm for ICSI.
• In nonobstructive azoospermia who undergo
microdissection testicular sperm extraction.
• For cryopreserved specimens after thaw process.

33. Sperm penetration assay
hamster eggs induced to superovulate by inj.
gonadotropins
eggs enzymatically treated to remove coat
incubated with sperm overnight or short
preinduction of acrosome reaction
no of sperms penetrating /egg normal>=5%
no of eggs penetrated<15% indicates low infertilty

34. Acrosome reaction assay
• In vitro acrosome reaction dysfunction can be
detected by this assay.
• Artificial induction of acrosome reaction by
calcium ionophore A23187.
• Both fluorescent – labeled lectins and
monoclonals antibodies are used to assess
outer and inner acrosomal membranes as well
as acrosomal contents.

35. Post coital test (sims huhner test)
• Adequacy of coitus.
• Idea about quality of mucus and ability of
sperm to penetrate it.
Principle-
In proliferative phase mucus is watery and
sperms can penetrate easily.
In secretary phase mucus is viscous.
Hence mucus testing is done before ovulation.

36. Procedure-
Cervical mucus is aspirated 2-12 hrs after
intercourse and microscopic examination is
carried out.
NORMAL ABNORMAL
Mucus stretches at least
2 inches
Cannot stretch 2 inches
Dries in fern free manner Does not form fern
MICROSCOPY
>=10 motile sperm Less than10 motile sprm

37. Non routine tests
DNA FRAGMENTATION
Many studies suggest that sperm DNA
fragmentation could influence fertilization,
embryo quality and development, blastocyst
achievement and pregnancy rates and losses.

38. • TUNNEL assay
• COMET assay
• SCSA OR SPERM CHROMATIN STRUCTURE
ANALYSIS
• DBD-FISH[DNA breakage detection –
fluorescence hybridization
• Sperm chromatin dispersion tests

39. Computer assisted semen analysis
• Count and motility estimation
• High resolution camera attached to
microscope takes video of semen sample for a
prefixed time, till 200 sperms are imaged.
• Examination of video done through software
for sperms with respect to their number, their
motion characters with in frame.
• User feeds data on chamber depth, volume of
sample loaded.

40. MANAGEMENT

41. Medical management
Hypogonadotropic hypogonadism
 Hypeprolactinoma- Dopamine agonists
 Congenital hypogonadotropic
hypogonadism- hcG or exogenous
testosterone
 Adult onset hypogonadotropic hypogonadism-
hcG 2000-5000IU 3 times per week

42. • Non – responders- hcG & hmG or pure FSH
(75-100IU 3 times weekly)
• Hypogonadotropin hypogonadism unrelated
to cause- Portable programmable pulsatile
infusion pump s/c.

43. • Eugonadotropin Hypogonadism
severe oligospermia
Low serum testosterone
T/t by aromatase inhibitor
testolactone 50- 100mg BD
Anastrazole 1mg OD

44. • Hypergonadotropic Hypogonadism
Insemination with donor sperm.
IVF with ICSI with preliminary genetic
evaluation.
• Erectile dysfunction
Sildenafil 25-100mg 1hr before intercourse.

45. Artificial insemination
Indications
• Oligospermia
• Asthenospermia
• Premature or retrograde ejaculation
• Sperm autoantibodies & cervical factors
• Unexplained infertility
• Sex selection in genetic & chromosomal
anomalies
• Hypospadias

46. Types:-
1) IUI
2)INTRACERVICAL
3)PERICERVICAL & VAGINAL
4)DIPI(DIRECT INTRAPERITONEALL
INSEMINATION)

47. Intrauterine insemination
Cycle fecundity
3-10% infertile partner sperm.
9-30% donor sperm.
 Processed motile sperm count at least 1
million.
 Best results when no. Of TOTAL MOTILE
SPERMS>10 MILLION.

48. Success rates
 Highest >14% sperm have normal
morphology.
 Intermediate 4-14%
 Poor <4% (advised IVF &ICSI).

49. Donor sperm
INDICATIONS
1) Azoospermia
2)Immunological factors not correctable
3)Genetic disease in husband

50. Guideline for sperm donation
 Semen analysis- donors are selected if the post
thaw semen parameters meet a minimum
standard.
 Genetic evaluation- genetic screening for
heritable diseases.
 Testing for cystic fibrosis carrier status.
 Every 6 months screening – while remaining an
active donor, donors should undergone a
complete physical examination and every 6
monthly for STD.

51. • Quarantine- sperm specimen quarantied &
cannot be released unless remained
sequestered 180 days preceding most recent
negative test for HIV.
• Choosing donor characteristics.
• Blood type and Rh factor should be
considered, particularly for Rh negative
recipients.

52. Sperm Retrieval Technique
• Non obstructive azoospermia:
TESA- Testicular sperm aspiration
Micro-TESE- Microdissection testicular sperm
extraction.
• Obstructive Azoospermia
MESA- Microsurgical epididymal sperm aspiration.
PESA- Percutaneous epididymal sperm aspiration.

53. Open Testis Biopsy(TESE):
Microsurgical Technique
• remains the gold standard
• provides an optimal amount of tissue for
accurate diagnosis
• retrieval of sperm for IVF

54. Indications
• Failure to find sperm in the epididymis in the
presence of the spermatogenesis
• complete absence of the epididymis.
• Nonobstructive azoospermia

58. Percutaneous Testis Biopsy
• is a blind procedure
• risk of unintentional injury to either the
epididymis or the testicular artery.
• should not be used when previous surgery

59. TESA (Testicular sperm aspiration)
• Blind procedure
• Immobilization of the testicle. By grasping it
with the epididymis and cord between fingers
while pulling the scrotum skin taut.
• performed with a 23-gauge needle or
angiocath from superior pole of testes

60. • less invasive and less painful than
percutaneous biopsy
• yields few tubules with poorly preserved
architecture
• significantly lower yield of sperm than open
microsurgical TESE (micro-TESE) in men with
nonobstructive azoospermia.

62. MESA (microsurgical epididymal sperm
aspiration)
• Invasive.
• Provides retrieval of many sperm.
• Less epididymal damage.
• Can be cryopreserved and used for future
procedures.

63. MESA
can be used for either
• intraoperative sperm retrieval at the time of
vasoepididymostomy or as an
• isolated procedure in men with congenital
absence of the vas or unreconstructable
obstructions

64. MESA
• A median raphe approach through two small
transverse scrotal incisions.
• After delivery of the testis, the tunica vaginalis
is opened and the epididymis inspected under
operating microscope.
• The epididymal tunica is incised over a dilated
tubule .
• A dilated tubule is isolated and incised

65. • .The fluid is touched to a slide, and the fluid
examined.
• If no sperm are obtained, the epididymal
tubule and tunica are closed, and an incision
is made more proximally in the epididymis
until motile sperm are obtained.
• As soon as motile sperm are found, Sperm are
drawn into the micropipette by simple
capillary action.

66. PESA

67. Sprm retrieval technique

68. VASOGRAPHY
Absolute Indications
• Azoospermia, plus
• Complete spermatogenesis with many
mature spermatids on testis biopsy, plus
• At least one palpable vas

69. Relative indications
• 1. Severe oligospermia with normal testis
biopsy
• 2. High level of sperm-bound antibodies,
which indicates unilateral, bilateral, or partial
obstruction
• 3. Low semen volume and very poor sperm
motility (partial ejaculatory duct obstruction)

70. vasogram

71. vasography
• Perform vasography only at the time of planned
reconstruction.
• Always sample vasal fluid first to allow cryopreservation
of motile sperm if found.
• Use indigo carmine instead of methylene blue to confirm
patency.
• Formal vasography with x-ray contrast is needed only to
locate obstructions proximal to the internal inguinal ring.

72. • If motile sperm are found, they should be
cryopreserved.
TRANSRECTAL ULTRASOUND
DILATED SEMINAL VESICLES /
MIDLINE CYST
TRANSRECTAL FNA F/B
CONTRAST INSTILLATION

74. Scrotal incision

77. Crossed vasovasostomy
Crossover is indicated
• 1. Unilateral inguinal obstruction of the vas
deferens associated with an atrophic testis
on the contralateral side.
A crossover vasovasostomy should be
performed to connect a healthy testicle to the
contralateral unobstructed vas.

78. • 2. Obstruction or aplasia of the inguinal vas or
ejaculatory duct on one side and epididymal
obstruction on the contralateral side.
It is preferable to perform one anastomosis with
a high probability of success (vasovasostomy)
than two operations with a much lower chance of
success (e.g., unilateral
vasovasoepididymostomyand contralateral
TURED.
• Pregnancy rate -52 PERCENT

79. vasoepididymostomy
• is indicated when the testis biopsy reveals
complete spermatogenesis
• and scrotal exploration reveals the absence of
sperm in the vasal lumen with no vasal or
ejaculatory duct obstruction.

81. Anastomotic Techniques: Keys to Success.
• 1. Accurate mucosa-to-mucosa
approximation.
• 2. Leakproof anastomosis
• 3. Tension-free anastomosis
• 4. Good blood supply.

82. TURED
• Transrectal ultrasound-guided aspiration of the
cystic or dilated ejaculatory duct.
• The aspirate is examined microscopically;
• if motile sperm are found, they are cryopreserved
• 2 to 3 mL of indigo carmine diluted with water-
soluble radiographic contrast is instilled.
• If a radiograph confirms a potentially resectable
lesion, TURED is performed without the need for
prior vasography.

83. • If no sperm are found in the aspirate, vasography
is necessary.
• If no sperm are found in either vas when the
vasotomy is made and vasography reveals
ejaculatory duct obstruction
• abandon reconstruction and plan for future IVF
and ICSI.
• simultaneous vasoepididymostomy and TURED -
poor result

84. Complication of tured
Reflux
Epididymitis
Retrograde ejaculation

85. VARICOCELECTOMY
• most commonly performed operation for the
treatment of male infertility.

86. VARICOCELE
• found in approximately 15% of the general
population, 35% of men with primary
infertility, and 75% to 81% of men with
secondary infertility.
• associated with a progressive and duration-
dependent decline in testicular function

91. THANK YOU