Infertility management- medical

LOWER URINARY TRACT CALCULI
Dr.Vishnuraja R
MANAGEMENT OF
INFERTILITY
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai
1

MODERATORS:
Professors:
Prof. Dr. G. Sivasankar, M.S., M.Ch.,
Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
Dr. J. Sivabalan, M.S., M.Ch.,
Dr. R. Bhargavi, M.S., M.Ch.,
Dr. S. Raju, M.S., M.Ch.,
Dr. K. Muthurathinam, M.S., M.Ch.,
Dr. D. Tamilselvan, M.S., M.Ch.,
Dr. K. Senthilkumar, M.S., M.Ch.
DEPT OF UROLOGY,GRH ANDKMC,CHENNAI. 2

MANAGEMENT OF INFERTILITY
1. Non surgical Management of Infertility
2. Urological Interventions in Infertility
3. Assisted reproduction techniques
3
DEPT OF UROLOGY,GRH ANDKMC,CHENNAI.

NON SURGICAL MANAGEMENT
4

CONSERVATIVE
MANAGEMENT
FOR
SUBNORMAL
SEMEN
QUALITY
5

FERTILITY AND DRUGS
6

OBESITY AND
REPRODUCTION
7

NUTRITIONAL
THERAPY
8

RADIATION
Ionizing Non Ionizing
9

10

MEDICAL MANAGEMENT
1. Empirical management
2. Specific management
11

EMPIRICAL MANAGEMENT
Major part of male infertility is idiopathic.
Causal treatment is not possible hence empirical treatment is applied.
12

EAU GUIDELINES-IDIOPATHIC INFERTILITY
13

EMPIRICAL TREATMENT
1. Antiestrogens
2. Aromatase inhibitors
3. Purified/Recombinant FSH
4. Antioxidants
5. Carnitines
6. Mast cell blockers
7. Phosphodiesterase inhibitors
8. Kallidinogenase
9. Alpha adrenoceptor antagonists
10. Corticosteroids
11. Antiphlogistic treatment
12. Zinc salts
14

ANTI ESTROGENS
Tamoxifen
Tamoxifen
15

ANTIESTROGENS
Appropriate in patients with idiopathic oligospermia.
Tamoxifen and Clomiphene citrate are used.
If FSH is not elevated, Tamoxifen 20 mg per day can be used.
Clomiphene citrate is less preferred because of its intrinsic estrogenic action.
Clomiphene citrate has lower effectiveness compared to Tamoxifen.
16

AROMATASE INHIBITORS
17

AROMATASE INHIBITORS
In patients with subnormal testosterone and high estradiol, leading to low
testosterone/estradiol ratio, significant increase in sperm count and motility is
observed with aromatase inhibitors.
Testolactone (50-100 mg bd) and Anastrazole (1 mg od) are used.
18

PURIFIED/RECOMBINANT FSH
Used in severely impaired fertility.
75-150 IU daily for 2 months.
Improvement in sperm substructures and function noted.
In patients who failed in IVF programs previously, improvement noted in IVF rates.
High implantation rates in ICSI.
19

OXIDATIVE
STRESS
20

ANTIOXIDANTS
Tocopherol (Vitamin E) (300-600 mg daily)
Ascorbic acid (Vitamin C)
N acetyl cysteine (600 mg od, also useful in seminal hyperviscosity)
Glutathione
Pentoxiphylline
21

L CARNITINE –MITOCHONDRIAL TRANSPORT
22

L-CARNITINE
Essential for beta oxidation of fatty acids in mitochondria.
Also acts as free radical scavenger.
Highest levels of L-carnitine in the body observed in epididymal fluid (2000 times).
Reduced in patients with oligoasthenospermia.
Stimulate sperm motility
Dose: L carnitine – 2 gms/day, L-acetyl carnitine – 1 gm/day for 6 months.
23

MAST CELL
24

MAST CELL STABILISERS
Increased numbers of MCs have been described in the testes of men with fertility
disturbances.
May be associated with dysfunctional blood-testis barrier.
The release of tryptase by MCs in the testis has been associated with fibrotic
remodeling leading to fibrotic thickening of the lamina propria of the seminiferous
tubules.
Mast cell stabilisers can be used in patients with elevated seminal fluid tryptase.
Ketotifen 1 mg bd for 3 months.
Tranilast 300 mg/day for 3 months.
25

PENTOXIFYLLINE
Increases cAMP in the sperm.
Helps in capacitation and acrosome
reaction.
Also has free radical scavenging action.
Dose: 400-600 mg tds for 3-6 months.
26

27

KALLIDINOGENASE/KALLIKREIN
Paracrine regulator of sertoli cells.
Previously used for oligoasthenoteratazoospermia (OAT).
EAU recommends only for clinical research studies at present.
28

ALPHA 1 ADRENOCEPTOR ANTAGONIST
Bunazosin 2mg/day for 6 months
In patients with idiopathic moderate oligozoospermia (5-20 million/cumm)
Small study
Increase in seminal output and semen volume.
Mechanism: Relaxation of myoid cells leading to dilatation of stenotic areas of
seminiferous tubules and subsequent good tubular fluid flow.
29

CORTICOSTEROIDS
Previously used for anti sperm antibodies in various doses.
Nowadays not recommended as a standalone treatment. (IVF < ICSI are the
preferred choices.)
Can be considered in patients with antisperm antibodies who have previously failed
IVF procedure.
30

ANTIPHLOGISTIC/ANTI INFLAMMATORY
TREATMENT
Chronic inflammation of the testis or epididymis can lead to poor semen parameters.
Mostly due to ROS damage.
Diclofenac and Indomethacin have been tried.
Dose: Diclofenac 50 mg bd for 3-6 weeks.
31

SPECIFIC TREATMENT
1. Hormonal replacement
2. Treatment of infections
3. Treatment of disturbances of emission and ejaculation
32

HORMONE REPLACEMENT
33

BETA HCG
Useful in hypogonadotropic hypogonadism
Behaves like LH.
Stimulates Leydig cells to produce testosterone.
Increases testosterone level and testicular volume.
Dose: hCG 1000-2500 IU 2-3 times a week.
Recommended for patients with sustained Leydig cell dysfunction after
varicocelectomy
Can be combined with human menopausal gonadotropin (hMG).
34

HUMAN MENOPAUSAL GONADOTROPIN
Derived from urine of pregnant females.
Has both FSH and LH activity.
Approved for male sterility and induction of spermatogenesis in cases of
hypogonadotropic hypogonadism.
Stimulates sertoli cells to sperm production.
The usual dosage is 75–150 IU hMG for 1-3 months.
May be preceded by testosterone substitution and beta hCG.
35

PURE OR RECOMBINANT FSH
Mechanism of action is identical to that of hMG.
Approved for the treatment of hypogonadism.
Dose: 150 IU pure FSH IM 3 times a week for at least 3 months.
Useful in patients to improve IVF results.
Particularly in men with lower FSH after GnRH therapy.
36

GONADOTROPIC RELEASING HORMONE (GNRH)
Gonadorelin – synthetic analog of GnRH.
Stimulates the release of FSH and LH from pituitary.
Of highest andrological-therapeutic significantly is the pulsatile subcutaneous
administration by means of a portable infusion pump.
Indication: Tertiary hypogonadotropic hypogonadism (e.g. Kallman syndrome or
idiopathic hypogonadotropic hypogonadism) and retarded puberty
Dose: 5–20 μg gonadorelin per pulse every 120 minutes over several months.
90% start producing spermatozoa in 9 months.
37

TESTOSTERONE UNDECANOATE
Approved for substitution therapy of hypogonadism, impaired spermatogenesis due to
androgen deficiency.
For substitution therapy, 80–160 mg testosterone undecanoate are administered daily.
Not approved for eugonadal men.
38

39

OTHER MEDICAL TREATMENTS
40

TREATMENT OF EMISSION AND EJACULATION
PROBLEMS
Retrograde ejaculation or aspermia due to emission failure (Diabetes,
Retroperitoneal lymphadenectomy).
Imipramine 25-75 mg od, duration is individualized.
Possibility of natural conceiving of offspring.
41

ANTI INFECTIOUS TREATMENT
MAGI – Male Accessory Gland Infection
Male genital traction should be treated with antibiotics.
Culture sensitivity based treatment for 2-3 weeks.
Aim:
Reduction or eradication of microorganisms in the prostatic and seminal fluid
secretions
Normalisation of inflammatory parameters.
Improvement in seminal parameters.
42

UROLOGICAL INTERVENTIONS IN
INFERTILITY
43

UROLOGICAL INTERVENTIONS
1. Varicocele
2. Azoospermia
3. Cryptorchidism
4. Male contraception
44

VARICOCELE
Most common correctable cause for male infertility.
Noted in15 % of general population, 30% of men with primary infertility and 80 %
of men with secondary infertility.
Theory:
Impaired venous drainage disrupts heat regulation in scrotum and cords resulting in
diminished spermatogenesis.
45

VARICOCELE AND SPERMATOGENESIS
(1) Testicular hypoxia and oxidative stress with increased seminal plama ROS and
reduced antioxidant activity,
(2) Increased rate of sperm DNA fragmentation (SDF),
(3) Diminished testicular DNA polymerase activity,
(4) Exaggerated apoptosis of testicular cells,
(5) Sertoli cell dysfunction,
(6) Leydig cell dysfunction with declined testosterone biosynthesis,
(7) Accumulation of gonadotoxins due to impaired testicular venous drainage,
(8) Reflux of renal and adrenal metabolites to spermatic venous blood, and
(9) Production of antisperm antibodies
46

VARICOCELE REPAIR
Halt any further damage to testicular function
Improved spermatogenesis
Enhanced Leydig cell function
47

48

VARICOCELE
REPAIR AND
ART
49

VARICOCELECTOMY IN NON OBSTRUCTIVE
AZOOSPERMIA
Primary pathology is testicular dysfunction.
But palpable varicoceles noted in 4.3 to 13 % of patients.
Treatment of varicocele improves mTESE sperm retrieval rate, ICSI clinical pregnancy,
lowers low birth rates and miscarriages.
Conclusion : Varicocelectomy Indicated in NOA
50

VARICOCELECTOMY IN SUBCLINICAL VARICOCELE
Non palpable varicoceles even in Valsalva maneuver.
Incidental finding in USG.
Will semen parameters improve ? Studies say YES.
Does it impact fertility? NO
Conclusion: Not recommended
51

ASRM GUIDELINES FOR VARICOCELE
52

MALE PARTNER OF A COUPLE ATTEMPTING TO
CONCEIVE HAS A VARICOCELE
Treat Varicocele if all or most of the criteria are met:
[1] the varicocele is palpable on physical examination of the scrotum;
[2] the couple has known infertility;
[3] the female partner has normal fertility or a potentially treatable cause
of infertility, and time to conception is not a concern; and
[4] the male partner has abnormal semen parameters.
53

MALE PARTNER OF A COUPLE ATTEMPTING TO
CONCEIVE HAS A VARICOCELE
Not indicated in patients with:
•Either normal semen quality,
•Isolated teratozoospermia, or
•A subclinical varicocele
54

VARICOCELE- EAU GUIDELINES
55

AZOOSPERMIA
56

AZOOSPERMIA
Urological procedures performed are:
1. Testicular biopsy
2. Vasography
3. Reconstruction for obstructive azoospermia
4. TURED
5. Sperm retrieval techniques
57

TESTICULAR BIOPSY - INDICATION
Azoospermic men with:
Testis of normal size and consistency,
Palpable vasa deferentia, and
Normal serum follicle-stimulating hormone (FSH) levels, and a
Negative serum antisperm antibody assay.
Used to differentiate obstructive from non obstructive azoospermia.
Nowadays, testicular biopsy is both diagnostic and therapeutic.
58

TESTICULAR BIOPSY – CBAVD?
If FSH is normal, Biopsy always reveals spermatogenesis and biopsy is not
necessary before definitive sperm aspiration and IVF with ICSI.
59

TESTICULAR BIOPSY-RECOMMENDATIONS
1. Examination of fresh, unfixed tissue for the presence of sperm with tails and
possible motility, and examination of multiple samples if sperm are not found initially.
2. Furthermore, optimal care requires the availability, at the time of biopsy, of an
andrology laboratory capable of processing and cryopreserving any sperm found at
the time of biopsy.
60

OPEN TESTICULAR BIOPSY – GOLD STANDARD
61

OPEN TESTICULAR BIOPSY- GOLD STANDARD
62

POINTS TO KEEP IN MIND
1. Biopsy by no touch technique
2. ‘Touch Prep’ using glass slide and add a drop of saline or RL or human tubal fluid
with IVF medium before examination under microscope.
3. If no sperm is found, second ‘squash prep’ .
4. If no sperm is found, repeat at another site.
5. Operating microscope is very useful for identifying large seminiferous tubules.
6. If sperm is found, send the glass slide and the biopsy to andrology lab.
7. Mark the site of biopsy for future TESE.
63

TESTICULAR BIOPSY - PRESERVATIVES
1. Bouin solution
2. Zenker solution
3. Collidine buffered glutaraldehyde
Formaldehyde?
Should not be used as it causes distortion of testicular histology.
64

PERCUTANEOUS TESTIS BIOPSY/PERCUTANEOUS
TESTICULAR ASPIRATION
Blind procedures
Not generally recommended
COMPLICATIONS
Hematomas
Anti sperm antibodies
Inadverdent epididymal biopsy
65

66

VASAL OR
EPIDIDYMAL
OBSTRUCTION
67

VASOGRAPHY
The absolute indications for vasography are as follows:
1. Azoospermia, plus
2. Complete spermatogenesis with many mature spermatids on testis biopsy, plus
3. At least one palpable vas.
Performed only at the time of definitive repair of obstruction in OT settings.
68

VASOGRAPHY
Relative indications for vasography are as follows:
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)
69

EXPECTED ANSWERS
1. Are there sperm in the vasal fluid?
2. Is the vas obstructed?
If the testis biopsy reveals many sperm, then:
1. Absence of sperm in vasal fluid indicates obstruction on the testicular side of the
vasotomy site, most likely an epididymal obstruction.
2. Copious vasal fluid containing many sperm indicates vasal or ejaculatory duct
obstruction.
3. Copious thick white fluid without sperm in a dilated vas indicates secondary
epididymal obstruction in addition to a potential vasal or ejaculatory duct
obstruction.
70

COMPLICATIONS
1. Hematoma
2. Injury to vasal blood suppy
3. Stricture
4. Sperm granuloma
71

VASOVASOSTOMY/ VASOEPIDIDYMOSTOMY?
72

VASOVASOSTOMY/ VASOEPIDIDYMOSTOMY?
73

VASOVASOSTOMY TECHNIQUES
74

TURED
Transurethral resection of ejaculatory ducts (TURED) done for ejaculatory duct
obstruction.
TRUS can be used for diagnosis.
TRUS guided aspiration of fluid from dilated ejaculatory ducts or seminal vesicles
have to be done before the procedure.
If sperm found in the fluid, cryopreservation to be done. Inject 2-3 ml Indigocarmine
dye.
If no sperm is found, vasography should be done.
If no sperm during vasography, abandon the procedure and perform microsurgical
epididymal aspiration and cryopreservation for IVF.
75

TURED - TECHNIQUE
24 Fr cutting loop used.
Finger in the rectum provides anterior
displacement of posterior lobe of prostate.
Verumontanum resected to view dilated
ejaculatory duct orifice.
Indigo carmine dye efflux confirms adequate
resection.
Preserve bladder neck and external sphincter.
76

TURED-COMPLICATIONS
1. Reflux of urine into ejaculatory ducts, vas and seminal vesicles.
2. Epididymitis
3. Retrograde ejaculation (Give Pseudoephedrine 120 mg orally 90 min before
ejaculation)
77

SPERM RETRIEVAL TECHNIQUES
1. Vasal sperm
2. Epididymal sperm
3. Testicular sperm
78

VASAL SPERM
Vasal sperm have presumably reached full maturation and reproductive potential.
Indications:
1. At the time of vasectomy reversal
2. Vasal occlusion after vasectomy, inguinal hernia with mesh, radical prostatectomy
3. Vasal abnormalities in cystic fibrosis.
79

TECHNIQUE
80

EPIDIDYMAL SPERM EXTRACTION
Indications:
1. Congenital bilateral absence of the vas deferens
2. Vasal occlusion after vasectomy in patients who either are not candidates
for or do not desire microsurgical reconstruction.
3. All indications for vasal sperm retrieval.
81

EPIDIDYMAL SPERM RETRIEVAL TECHNIQUES
1. MESA (Microsurgical Epididymal Sperm Aspiration)
2. PESA (Percutaneous Epididymal Sperm Aspiration)
82

MESA - TECHNIQUE
83

MESA- MOTILE
SPERMS IN
PROXIMAL
EPIDIDYMIS
84

PESA
Not recommended.
Disadvantages:
1. Blind procedure,
2. Procurement of fewer sperm for
IVF/ICSI,
3. Potential for increased bleeding,
4. Inability to examine for sites of bleeding
or to administer electrocautery.
85

TESTICULAR SPERM RETRIEVAL
Indications:
1. Failure to find sperm in the epididymis in the presence of the spermatogenesis or
complete absence of the epididymis.
2. Nonobstructive azoospermia
Techniques:
1. mTESE (microsurgical TEsticular Sperm Extraction)
2. TESA (TEsticular Sperm Aspiration)
86

MICROSURGICAL TESE
Preferred for nonobstructive azoospermia
Done under operating microscope.
Tubules with active spermatogenesis are observed and dissected.
Sperm retrieved from the tubules.
87

TESE – SERTOLI CELL ONLY VS NORMAL
88

TESE - OUTCOMES
89

RETA – Rete testis aspiration
SPAS - Spermatocele aspiration
MESA - Microsurgical epididymal
sperm aspiration
90

SPERM RETRIEVAL-EAU GUIDELINES
91

ASSISTED REPRODUCTION
TECHNIQUES
92

ART INDICATIONS
1. Oligoasthenoteratazoospermia (OATS)
2. Sperm abnormalities (Immotile cilia syndrome, Globoazoospermia,
Teratazoospermia)
93

COMMON ART TECHNIQUES
1. IUI (Intrauterine Insemination)
2. IVF (Invitro fertilization)
3. ICSI (Intracytoplasmic sperm injection)
94

WHICH ART?
95

IUI INTRA UTERINE INSEMINATION
1. Using Husband’s semen
2. Using Donor’s semen
96

HUSBAND’S SEMEN - INDICATIONS
97

DONOR’S SEMEN - INDICATIONS
98

IUI - STEPS
(1) Ovarian stimulation;
(2) Monitoring of follicular growth and endometrial
development;
(3) Timing of insemination;
(4) Semen preparation;
(5) IUI with prepared sperm.
99

IVF WITHOUT ICSI
Oocytes are prepared in tissue culture
medium after retrieval.
For routine IVF without ICSI, oocytes are
routinely inseminated with a
concentration of 100 000 normal motile
sperm per ml.
100

ICSI – INDICATIONS – EJACULATED SPERM
101

ICSI – INDICATIONS – EPIDIDYMAL SPERM
102

ICSI – INDICATIONS – TESTICULAR SPERM
103

ICSI - TECHNIQUE
A single motile spermatozoon is selected
and immobilized by pressing its tail
between the microneedle and the bottom
of the dish. The sperm cell is then
aspirated tail-first into the injection
pipette
104

ICSI - TECHNIQUE
A mature oocyte is fixed by the holding
pipette with the polar body at the 6
o’clock position. The sperm cell is brought
to the tip of the injection pipette.
105

ICSI - TECHNIQUE
The injection pipette is introduced at the
3 o’clock position.
The sperm cell is delivered into the
oocyte with a minimal volume of medium
and the pipette can be withdrawn
carefully
106

ICSI - TECHNIQUE
A single sperm cell can be seen in the
center of the ooplasm
107

PROS AND CONS
108

THANK YOU
109

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