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MALE INFERTILITY :
CRITICAL REVIEW OF
Assessment & treatment in India
& Way Forward
Dr. Sharda Jain
Dr. Jyoti Agarwal
ISO 14001:2004 (EMS)
…..Caring hearts, healing hands
D.G.F. ,s CME MALE INFERTILITY 2017 DELHI
DEDICATED TO
GYNAECOLOGIST OF INDIA
who don’t call themselves
Infertility / ART Expert
1 in 2 INDIAN COUPLES SUFFERING
FROM INFERTILITY have
MALE FACTOR
GYNAECOLOGIST DO NOT KNOW
ANYTHING ABOUT
MALE INFERTILITY
To become infertility or
ART expert... knowledge
& skill in male infertility is necessary
There is
NO
Elevator
to success ,
you have to take the stairs
that means step by step growth
1990..
INTRACYTOPLASMIC
SPERM INJECTION
(ICSI)
Major breakthrough in 100 years
SPERM RETRIEVAL TECHNIQUES.. are
added boon for MALE INFERTILITY
ANDROLOGY + SPERMATOLOGY
IS EXPANDING FAST
TESTES
PRODUCTION
OF SPERMS
EPIDIDYMIS
maturation
of sperms
VAS
DEFERENCE
Storage
Of sperms
GENETICS & IMMUNOLOGICAL
KNOWLEDGE HAS WIDENED
MALE INFERTILITY...IS NOW A
UNPRECEDENTED REVOLUTION IN THE TREATMENT
OF HUMAN INFERTILITY
SUPERSPECIALITY
**FERTILITY PRESERVATION**
Of Male & Female
has already become
Subspecialty of ART
due to UNPRECEDENTED REVOLUTION IN THE TREATMENT
OF young Male & female cancer cases
Next Decade will see another
NEW SUPER SUPER SPECIALITY..OF
**** REGENERATIVE MEDICINE....USING
STEM CELLS RESEARCH+ TISSUE ENGINEERING
Where man will not be
required for human
reproduction
Defining Infertility
Infertility is defined as an inability to get
pregnant after one year of trying.
Male factor is responsible
solely in about 50 %cases .
It is important that both male & female
partner is evaluated simultaneously .
The purpose of this PPT is to provide
Gynaecologist with principles & strategies
for the evaluation of couple with male
infertility problems , also manage them or
refer them timely to experts as needed.
India performs approx. 1 Lac cycles
of IVF per year
50% are
done for
MALE
infertility
Annual number of IVF cycles
 High (>10,000)
 Moderate (5,000-10,000)
 Low (<5,000)
Unfortunately, Only
50%
IVF centers
have
ICSI & FREEZING
facility
BY 2020..2.6 LAC IVF
PROCEDURES WILL BE DONE
Indication for Evaluation
• All couples who fail to achieve a successful
pregnancy after 12 months of regular
unprotected intercourse.
• Couple need earlier evaluation & treatment , if
indicated by medical history & physical findings
• After 6 months for couple in which the female
partner is 35 years old
• Men highly concerned about fertility should be
evaluated .
Why 50 millions sperms are required to
fertilize one egg-- is BIG QUESTION
1. Follicular phase – egg development
2. Ovulation – releasing egg from the ovary
3. Egg descends through the fallopian tubes
4. Egg fertilization
5. Uterus lining get ready to accept implantation
6. Implantation of embryo
Conception is a simple and yet
amazingly complex process!
• The couple is not seen together
• Husband contributes to 50% to Infertility..still
Husband’s semen analysis not performed till late.
• Investigations are performed in a piecemeal
fashion rather than as part of an overall strategy.
COMMON MISTAKES -WHICH
We Indian doctors DO !
COUPLES TOO ARE RELUCTANT FOR INVESTIGATIONS
• Experience shows …MEN LOOSE TRUST early when its
come to their treatment with Urologist.
• They want baby .. Not just increase in sperms
• Some how , the temptation to try many empirical,
possibly useless medical treatments is Considerable
• Large sums of money is often spent at the hands of
• * Quacks
* Spiritual healers
* Even self styled gynaecologists/ andrologist
Our Knee jerk reaction
is to send them to urologist
What is the Role of doctors who are
not Gynaecologist
• REFER to Trained infertility Experts
If women is not pregnant with in a
year of marriage, provided they are
staying together & not using
contraceptive.
• SEMEN Examination
• TUBE PATENCY TESTING ,
• DAY 21 , S. PROGESTERONE
WHO
SPECIAL INVESTIGATIONS…
WHICH GUIDE OUR TREATMENT
“Meet the Expert” – May 2012
CURRENT TRENDS & SCENARIO IN
MALE INFERTILITY
CRITICAL REVIEW OF SPECIAL AREAS
• Maturation cycle of sperm
• Causes of male infertility & azoospermia
• Limitations of semen analysis
• DNA fragmentation test
• Azoospermia Diagnosis
• Testicular Biopsy
• Hormonal Evaluation
• Immunological evaluation
• Geneting Testing
Treatment
• Antioxidants
• Limitation of IUI
• Azoospermia
• Vericocele
From Initiation of Sperm Production
to Ejaculation
Misell LM et al.: A stable isotope-mass spectrometric method for
measuring human spermatogenesis kinetics in vivo.
J Urol. 2006; 175: 242-6.
Old concept ~80-90 days
New concept ~60 days
Classification of Male infertility on the
Basis of initial Evaluation
Five following groups
1. Absent or low volume ejaculate ‘
2. Azoospermia
3. Oligosthenospermia (OAT)
4. Normal but infertile
5. Idiopathic infertility ..60- 70%
Male infertility
• SEXUAL DYSFUNCTIONS- non consummation
of marriage, erectile dysfunction, Anatomical
abnormalities like hypospadius, spinal cord
injury etc.
• OLIGOZOOSPERMIA- OAT- mild, moderate or
severe
• AZOOSPERMIA which can be further
subdivided between pretesticular, testicular
and post testicular or obstructive
Pretesticular:
Hypothalamic pituitary disease
(Secondary hypogonadism): 1-2%
Testicular:
Primary hypogonadism: 10-15%
Post-testicular defects
disorders of sperm transport: 10 to 20 %
Idiopathic:
Seminiferous tubule dysfunction: 60-80%
including microdeletions of the Y chromosome
CAUSES OF AZOOSPERMIA
SEMEN ANALYSIS
• Concentration
• Motility
• Morphology
Shape of Normal Sperm
WHO GIVES LOT EMPHASIS ON KRUGERS CRITERIA---BUT
NO LAB IN INDIA GIVES REPORT USING KRUGERS CRITERIA
TESTES
PRODUCTION
OF SPERMS
EPIDIDYMIS
maturation
of sperms
VAS
DEFERENCE
Storage
Of sperms
SPERM FUNTION TESTS are now available for every
movement of sperm---GOI is very keen that these
tests are offered right in beginning itself
Semen Analysis + sperm function test should be combined
New WHO Standards
Not accurate to discriminate fertile and
infertile men
A comprehensive
infertility workup,
including sperm function
testing, is crucial to
assess the male fertility
potential
INTERPRETING SEMEN ANALYSIS
Normal semen
parameters
• Despite looking
normal, sperms
may still be
damaged
• RO species
damage  DNA
fragmentation
Poor semen
parameters
• Oligospermia
• Asthenospermia
• Teratozoospermia
Azoospermia
• Obstructive
• Non obstructive
No Pregnancy
Effects of high sperm DNA
fragmentations are
• Infertility
• Recurrent pregnancy loss
• Poor outcomes in IUI and IVF
Men with poor semen parameters are
more likely to have high DNA
fragmentations
The term DNA fragmentation refers to Damaged sperm
DNA that can not be repaired
DNA Fragmentation - New
SPERM FUNCTION Test.. should Be
COMBINED with Semen Analysis
routinely
Non Fragmented SPERMATOZOA : Peripheral halo
Fragmented SPERMATOZOA : no peripheral halo
Two Tests – SCSA Test & Tunel Test
Abnormal test are 25% - 27% for SCSA test &
35% for TUNEL assay
DNA Fragmentation levels are closely correlated with
IUI, IVF and ICSI outcomes
and pregnancy rates
DFI is independent predictor
of pregnancy in couple
undergoing IUI/ IVF
ICSI Treatment is more likely to result in pregnancy than IUI
& IVF if DFI value is above 30%
Bungum et.al. Hum Reprod 2007
Sperm DNA Integrity Testing & ART
0%
5%
10%
15%
20%
Pregnancy by Sperm
DNA Integrity Results in
IUI
DFI ≤30% DFI >30%
Live birth (%)
OR 0.07 (0.01-0.48)
50,00%
40,00%
30,00%
20,00%
10,00%
0,00%
ICSI
Pregnancy by Sperm DNA
Integrity Results in IVF and
ICSI
IVF
DFI>30%
* <.05
*
Azoospermia Diagnosis
Diagnosis of Azoospermia
The diagnosis of azoospermia can be
established only when the pellet is
examined
The current WHO criteria for
evaluation sperm morphology are
similar to the “strict criteria”
described by kruger
Testicular Biopsy
• Shall we do testicular biopsy ?
• Where & who should do
testicular biopsy
• How should the information
be interpreted ?
• Which technique should be
used
Shall we do testicular biopsy ?
YES
It is both diagnostic
&
Therapeutic
(sperm retrieval techniques used before ICSI)
Testicular Sperm TESE is the technique of choice
Spermatogenesis may be focal that means in
about 50% of men with NOA sperms can be
found & use for ICSI
WHERE & WHO SHOULD DO
TESTICULAR BIOPSY
• It should be done in IVF
setting where sperm
freezing facilities are
available
• It is crime to do it
otherwise specially in
cases of non obstructive
azoospermia
How should the information be
interpreted ?
• Sertoli cell only , no germ cells
• Spermatogonia only
• Arrest at primary or secondary
spermatocyte level
• Spermatids round or elongated present
• Spermatozoa present but only in few
tubules
• Normal spermatogenesis
Hormonal evaluation
Endocrine abnormalities are
rarely present when the sperm
concentration is greater than 10
million / ml
Clinical Diagnosis based on Hormonal
Status
Clinical Status FSH LH Testosterone
Normal
men or obstruction Normal Normal Normal
Isolated spermatogenic
failure Normal Normal
Testicular failure
Normal or
Hypogonadotropic
hypogonadism
Recommendation
Recommendation Grade
Effective drug therapy is available o achieve
fertility in men with Hypogonadotrophic
Hypogonadism .
A
Testosterone replacement is
strictly contraindicated for the treatment of
male infertility (low levels of FSH & LH)
A
AGGLUTINATION of SPERMS makes
you suspect immunological problems
Antisperpm antibody
(ASA) are rare cause
of male subfertility
that do not required
routine testing & are
typically managed
with the used of ICSI)
GENETIC CAUSES
80%
10%
5%
5%
Genetic Causes of
Male Infertility
Klinefelter Syndrome (47,XXY)
Y-chromosome microdeletion
Congenital Vas Absence
GENETIC TESTS
• * Karyotyping
• * Y chromosome microdeletions
• * Cystic fibrosis conductance
regulator (CFTR) gene mutation
Recommendation For Genetic Testing &
Counselling
From a diagnostic view point , standard karyotype
analysis should be offered to all men with damaged
spermatogenesis (spermatozoa <10 million /mL) who
are seeking fertility treatment by IVF.
B
Testing for microdeletation is not necessary in men
with OA (with normal FSH) when ICSI used because
spermatogenesis should be normal
A
Men with severely damaged spermatogenesis
(spermatozoa <5 million /Ml) should be advised to
undergo Yq microdeletation testing for both diagnostic
& prognostic purpose. Yq microdeletation also has
important implication for genetic counselling
A
Recommendation For Genetic Testing &
Counselling
If complete AZFA or AZFB microdeletation are
detected , micro – TESE should not be performed
because it is extremely unlikely that any sperm will
be found
A
If a man with Yq microdeletation & his partner wish to proceed
with ICSI , they should be advised that microdeletation will be
passed to sons , but not to doughters.
A
When man has structural abnormalities of the VAS DEFERENS
(unilateral or bilateral absence), he & his partner should be
tested for CF GENE MUTATIONS
A
AZFa
deletion
No retrievable
sperm
AZFc
deletion
Sperm retrieved in
70% of cases
AZFb
deletion
No retrievable
sperm
Predictive Value of Ychromosome
Microdeletion Screening for
Sperm Retrieval in NOA
TREATMENT ASPECT OF
MALE INFERTILITY
FEW ISSUES
Antioxidants in Male Infertility
To whom?
Everyone
What Medicine
Vitamic C 500mg
Vitamin E 400 UI
LYCO Q 300 Is the dose
How long? – till she is pregnant
WHY
Antioxidants:
WHY ?
To whom and how
Seminal
Reactive Oxygen
Species (ROS)
2,5
2
1,5
1
0,5
0
Fertile Infertile
Antioxidant Treatment
Cochrane Review 2011
Outcome N
studies
N
participants
Effect size
(OR; 95% CI)
Live birth 3 214 4.85 [1.92, 12.24]
Pregnancy rate 15 964 4.18 [2.65, 6.59]
DNA fragmentation 1 64 -13.80 [-17.50, -10.10]
Miscarriage, sperm
count, sperm motility
6-16 242-700 No effect
Adverse effects 6 426 No effect
Improve the outcomes of live birth and pregnancy rate for
subfertile couples undergoing ART cycles
Showell MG, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database of
Systematic Reviews 2011, Issue 1. Art. No.: CD007411. DOI: 10.1002/14651858.CD007411.pub2.
SPERM NUTRIENTS AND ANTI-OXIDANTS
• Coenzyme Q-10
• Lycopene and Astaxanthin
• Vitamin C
• Zinc
• Vitamin B-12
• L-Arginine
• Vitamin-E
• Selenium
• L-Carnitine
Take-home Messages
Antioxidants helpful to decrease oxidative stress.
Treatment effect is noted > 60 days later.
MICRONUTRIENTS , ANTIOXIDANTS
& PROTEIN RICH DIET
to be literally
started on DAY 1
BRIEFING AT FIRST VISIT
EXERCISE,MEDITATION
TOBACCO SMOKING
In MEN smoking affects
all parameters of sperm
quality
I.U.I.
ONLY & ONLY IN LOW RESOURSE SETTING
FOR MALE INFERTILITY
Intra uterine insemination
If the sperm count is between
10 million to 20 million/ ml, IUI
offers a good pregnancy rate
provided there is no female factor
However western world does not
agree
Indications of IUI:
• Mild male factor infertility
up to 3 cycles of IUI
•(NICE, 2004; ESHRE Capri Workshop, 2009)
**************************************************************************************************************
No IUI, Advise them to try to conceive for a total of 2years
(including up to 1y before their fertility investigations)
before IVF - ICSI will be considered.
Exceptions: Social, Cultural, Religious
• (NICE, 2013)
Only
Low
recourse
setting
Treatment
is
ICSI in Male
infertility
in
infertility
centre
IN-HOUSE
IUI
Should be
done
From Sperm deposition to – sperm
Ovum interaction :
4 steps take place in cervix ,uterus & FT
1. Capacitation
2. Acrosome Reaction
3. Hyperactivation
4. Sperm- Oocyte binding I.U.I. Takes away step I & II
Male subfertility:
* OAT syndrome
*Oligospermia,Asthenozoospermia,Teratozospermia
*Severe male infertility
*Not candidate for IUI if Count<10million/ml
*Normal morphology <2.5% or
* Motility <10
Only
ICSI
ICSI is more cost effective than IUI when the
mean total motile sperm count is <10 million
(Van Voorhis et al,2001)
If no natural pregnancy - ICSI
SEMEN BANK & DONOR insemination
• Therapeutic donor insemination in
azoospermic patients
• Homologous (husband’s) sperms can also be
preserved under the following circumstances-
1. In men who have difficulty in collecting semen on demand
(for treatment or procedures)
2. Men away from treatment place
3. Prior to the starting of treatment in men undergoing
cytotoxic chemotherapy or radiotherapy
4. Prior to vasectomy or after successful vasectomy reversal
Mild Moderate, Severe
or
Azoospermia
Low Resource
Setting
3 trial IUI
H. Resources
ICSI
Out line of Male infertility
treatment
Male Fertility Declines More
Gradually
*30% decline in most men would not be
sufficient to render them infertile.
•Very important factor - If the sperm can
fertilize eggs, we usually don't see poor
embryo quality due to reduced sperm
quality.
Males retain their fertility
well into old age
very very controversial
Fertility Restoration &
Spontaneous Pregnancy
Only Indication
Treatment of Clinical
Varicoceles prior to ICSI
may be beneficial for
patient subgroups of
severe oligozoospermia
and NOA.
Other Recommendation
• Adult male with palpable
varicocele , abnormal semen
parametar , desire for future
fertility or pain related to
varicocele
• Adolescent / young adults :
reduced ipsilateral testicular size
, abnormal semen parameters
46%*
22%
66%
31% 31%
Varicocele and ICSI Outcomes
Treated Varicocele Untreated Varicocele
78%*
Fertilized Eggs
(%2PN)
Live Birth (%)
*P<0.05
Miscarriage (%)
Esteves SC, Oliveira FV, Bertolla RP. ... J Urol 2010;184:1442-1446
Odds ratio 1.87 0.43
95% CI 1.08 - 3.25 0.22 – 0.84
P-value 0.03 0.01
Azoospermia
it is not a synonymous of sterility
• Normal sperm production
• Mechanical blockage
• Vasectomy, Post-
infectious, Congenital
Obstructive
• Sperm production deficient
or absent
• Cryptorchidism, Radiation,
Chemotherapy, Trauma,
Genetic, Orchitis,
Varicocele, Gonadotoxins,
Unexplained
Non-
obstructive
AZOOSPERMIA
Determine the reason
Obstructive
Non-obstructive
• Clinical examination ( vas, epididymis, testis size)
• Volume, pH, fructose—all affected in OBST.AZOO
• FSH level—raised in NOA
Testicular failure need not mean no sperm
no sperm many spermfew sperm
Size of Testis in Azoospermia
P.T.F. Patchy spermatogenesis
Obstruction
Obstructive Azoospermia
• Microsurgical
reconstruction
• TURED
If young
patient
• Epididymis
• Testis
• Simple and
effective
Married for
long time
**Sperm
retrieval +
ICSI
Micro surgical
sperm
retrieval
techniques
MESA
Obstructive azoospermia
Recommendations
Treatment - surgery if young
Recommendation Grade
In azoospermia caused by EPIDIDYMAL
OBSTRUCTION standard procedures include
Vasovasostomy & Tubulovastomy
B
SPERM RETRIEVAL TECHNIQUES , such as MESA ,
TESA & PESA , can be used additionally . These
methods should be used only when cryostorage
of the material obtained is available.
B
Ductal Obstruction Causing
azoospermia
If old or pressure
to have a
child is more than
sperm retrieval
&
ICSI
H/O VASECTOMY...
SURGERY Results are rewarding
Esteves SC, et al. Success of percutaneous sperm retrieval and
intracytoplasmic sperm injection (ICSI) in obstructive azoospermic (OA) men
according to the cause of obstruction. Fertil Steril. 2010;94 (Suppl):S233.
Percutaneous SPERM
Retrieval –is almost 100%
Most azoospermic men with non obstructive
type are not sterile.
Sperm retrieval and reproductive potential
is dependent on the CAUSE of azoospermia.
Non-obstructive Azoospermia
TESA vs. TESE [better]
Controlled studies
for NOA men
Needle
Aspiration
Open Biopsy
Friedler et al
Human Reprod 12: 1488,
1997
4/37 (11%) 16/37 (43%)
Ezeh et al.
Human Reprod 13:3075 5/35 (14%)
22/35 (63%)
Non- Obstructive Azoospermia
Sperm
production
absent
Button
size
testis
Untreatable
condition
TESA
Can
retrieve
sperm in
50%
cases
TESA is
not
enough
BARIATRIC SURGERY
&
Infertility
Sleeve Gastrectomy &
Gastric Bypass surgery
are done routinely
Bariatric Surgery
Significant and sustained
weight loss of 40-50 kg is expected
Is Bariatric surgery safe?
It is a fact that… There are 40 Bariatric
surgeons in INDIA…it is not cup of any surgeon
In Good Hands
it is …as Safe as
Laparoscopic
Cholecystectomy
Weight loss is one of the corner stone to
achieve a healthy pregnancy and child birth
Our Experience with
Bariatric Surgery
Total cases - 23
5 had pregnancy with IUI & 6
had IVF ICSI pregnancy
11 Pregnancy
Hypertension, DM, Cholesterol has magical relief
ART has provided NOVEL PROTOCOLS for
FERTILITY PRESERVATION during
&
preceding ONCOTHERAPY in
young boys who are CANCER victims,
Fertility Preservation Male
Pre adolecents.do not produce sperm
so…testes has to saved & reimplanted
* Once semen production..then semen
samples to be saved
We work with accredited facilities that follow the
ICMR & ASRM standards andguidelines.
ADDRESS
11 Gagan Vihar, Near
Karkari Morh Flyover,
Delhi - 51
CONTACT US
9650588339
9599044257
011-22414049
WEBSITE :
www.lifecareivf.in
www.lifecarecentre.in
www.lifecareabs.in
ISO 14001:2004 (EMS)
…..Caring hearts, healing hands
ISO 9001:2008
Helpline : 9599044257
Web.www.lifecareivf.in
Helpline : 9910081484
27
Year
In
your
service

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MALE INFERTILITY TREATMENT AND ASSESSMENT GUIDE FOR INDIAN DOCTORS

  • 1. MALE INFERTILITY : CRITICAL REVIEW OF Assessment & treatment in India & Way Forward Dr. Sharda Jain Dr. Jyoti Agarwal ISO 14001:2004 (EMS) …..Caring hearts, healing hands
  • 2. D.G.F. ,s CME MALE INFERTILITY 2017 DELHI
  • 3. DEDICATED TO GYNAECOLOGIST OF INDIA who don’t call themselves Infertility / ART Expert
  • 4. 1 in 2 INDIAN COUPLES SUFFERING FROM INFERTILITY have MALE FACTOR
  • 5. GYNAECOLOGIST DO NOT KNOW ANYTHING ABOUT MALE INFERTILITY To become infertility or ART expert... knowledge & skill in male infertility is necessary
  • 6. There is NO Elevator to success , you have to take the stairs that means step by step growth
  • 8. SPERM RETRIEVAL TECHNIQUES.. are added boon for MALE INFERTILITY
  • 9. ANDROLOGY + SPERMATOLOGY IS EXPANDING FAST TESTES PRODUCTION OF SPERMS EPIDIDYMIS maturation of sperms VAS DEFERENCE Storage Of sperms
  • 11. MALE INFERTILITY...IS NOW A UNPRECEDENTED REVOLUTION IN THE TREATMENT OF HUMAN INFERTILITY SUPERSPECIALITY
  • 12. **FERTILITY PRESERVATION** Of Male & Female has already become Subspecialty of ART due to UNPRECEDENTED REVOLUTION IN THE TREATMENT OF young Male & female cancer cases
  • 13. Next Decade will see another NEW SUPER SUPER SPECIALITY..OF **** REGENERATIVE MEDICINE....USING STEM CELLS RESEARCH+ TISSUE ENGINEERING Where man will not be required for human reproduction
  • 14. Defining Infertility Infertility is defined as an inability to get pregnant after one year of trying.
  • 15. Male factor is responsible solely in about 50 %cases . It is important that both male & female partner is evaluated simultaneously . The purpose of this PPT is to provide Gynaecologist with principles & strategies for the evaluation of couple with male infertility problems , also manage them or refer them timely to experts as needed.
  • 16. India performs approx. 1 Lac cycles of IVF per year 50% are done for MALE infertility Annual number of IVF cycles  High (>10,000)  Moderate (5,000-10,000)  Low (<5,000)
  • 17. Unfortunately, Only 50% IVF centers have ICSI & FREEZING facility BY 2020..2.6 LAC IVF PROCEDURES WILL BE DONE
  • 18. Indication for Evaluation • All couples who fail to achieve a successful pregnancy after 12 months of regular unprotected intercourse. • Couple need earlier evaluation & treatment , if indicated by medical history & physical findings • After 6 months for couple in which the female partner is 35 years old • Men highly concerned about fertility should be evaluated .
  • 19. Why 50 millions sperms are required to fertilize one egg-- is BIG QUESTION
  • 20. 1. Follicular phase – egg development 2. Ovulation – releasing egg from the ovary 3. Egg descends through the fallopian tubes 4. Egg fertilization 5. Uterus lining get ready to accept implantation 6. Implantation of embryo Conception is a simple and yet amazingly complex process!
  • 21.
  • 22. • The couple is not seen together • Husband contributes to 50% to Infertility..still Husband’s semen analysis not performed till late. • Investigations are performed in a piecemeal fashion rather than as part of an overall strategy. COMMON MISTAKES -WHICH We Indian doctors DO ! COUPLES TOO ARE RELUCTANT FOR INVESTIGATIONS
  • 23. • Experience shows …MEN LOOSE TRUST early when its come to their treatment with Urologist. • They want baby .. Not just increase in sperms • Some how , the temptation to try many empirical, possibly useless medical treatments is Considerable • Large sums of money is often spent at the hands of • * Quacks * Spiritual healers * Even self styled gynaecologists/ andrologist Our Knee jerk reaction is to send them to urologist
  • 24. What is the Role of doctors who are not Gynaecologist • REFER to Trained infertility Experts If women is not pregnant with in a year of marriage, provided they are staying together & not using contraceptive.
  • 25. • SEMEN Examination • TUBE PATENCY TESTING , • DAY 21 , S. PROGESTERONE WHO
  • 27. “Meet the Expert” – May 2012 CURRENT TRENDS & SCENARIO IN MALE INFERTILITY
  • 28. CRITICAL REVIEW OF SPECIAL AREAS • Maturation cycle of sperm • Causes of male infertility & azoospermia • Limitations of semen analysis • DNA fragmentation test • Azoospermia Diagnosis • Testicular Biopsy • Hormonal Evaluation • Immunological evaluation • Geneting Testing Treatment • Antioxidants • Limitation of IUI • Azoospermia • Vericocele
  • 29. From Initiation of Sperm Production to Ejaculation Misell LM et al.: A stable isotope-mass spectrometric method for measuring human spermatogenesis kinetics in vivo. J Urol. 2006; 175: 242-6. Old concept ~80-90 days New concept ~60 days
  • 30. Classification of Male infertility on the Basis of initial Evaluation Five following groups 1. Absent or low volume ejaculate ‘ 2. Azoospermia 3. Oligosthenospermia (OAT) 4. Normal but infertile 5. Idiopathic infertility ..60- 70%
  • 31. Male infertility • SEXUAL DYSFUNCTIONS- non consummation of marriage, erectile dysfunction, Anatomical abnormalities like hypospadius, spinal cord injury etc. • OLIGOZOOSPERMIA- OAT- mild, moderate or severe • AZOOSPERMIA which can be further subdivided between pretesticular, testicular and post testicular or obstructive
  • 32. Pretesticular: Hypothalamic pituitary disease (Secondary hypogonadism): 1-2% Testicular: Primary hypogonadism: 10-15% Post-testicular defects disorders of sperm transport: 10 to 20 % Idiopathic: Seminiferous tubule dysfunction: 60-80% including microdeletions of the Y chromosome CAUSES OF AZOOSPERMIA
  • 33. SEMEN ANALYSIS • Concentration • Motility • Morphology
  • 34.
  • 35. Shape of Normal Sperm WHO GIVES LOT EMPHASIS ON KRUGERS CRITERIA---BUT NO LAB IN INDIA GIVES REPORT USING KRUGERS CRITERIA
  • 36. TESTES PRODUCTION OF SPERMS EPIDIDYMIS maturation of sperms VAS DEFERENCE Storage Of sperms SPERM FUNTION TESTS are now available for every movement of sperm---GOI is very keen that these tests are offered right in beginning itself Semen Analysis + sperm function test should be combined
  • 37. New WHO Standards Not accurate to discriminate fertile and infertile men A comprehensive infertility workup, including sperm function testing, is crucial to assess the male fertility potential
  • 38. INTERPRETING SEMEN ANALYSIS Normal semen parameters • Despite looking normal, sperms may still be damaged • RO species damage  DNA fragmentation Poor semen parameters • Oligospermia • Asthenospermia • Teratozoospermia Azoospermia • Obstructive • Non obstructive No Pregnancy
  • 39. Effects of high sperm DNA fragmentations are • Infertility • Recurrent pregnancy loss • Poor outcomes in IUI and IVF Men with poor semen parameters are more likely to have high DNA fragmentations
  • 40. The term DNA fragmentation refers to Damaged sperm DNA that can not be repaired DNA Fragmentation - New SPERM FUNCTION Test.. should Be COMBINED with Semen Analysis routinely
  • 41. Non Fragmented SPERMATOZOA : Peripheral halo Fragmented SPERMATOZOA : no peripheral halo Two Tests – SCSA Test & Tunel Test Abnormal test are 25% - 27% for SCSA test & 35% for TUNEL assay
  • 42. DNA Fragmentation levels are closely correlated with IUI, IVF and ICSI outcomes and pregnancy rates DFI is independent predictor of pregnancy in couple undergoing IUI/ IVF
  • 43. ICSI Treatment is more likely to result in pregnancy than IUI & IVF if DFI value is above 30% Bungum et.al. Hum Reprod 2007
  • 44. Sperm DNA Integrity Testing & ART 0% 5% 10% 15% 20% Pregnancy by Sperm DNA Integrity Results in IUI DFI ≤30% DFI >30% Live birth (%) OR 0.07 (0.01-0.48) 50,00% 40,00% 30,00% 20,00% 10,00% 0,00% ICSI Pregnancy by Sperm DNA Integrity Results in IVF and ICSI IVF DFI>30% * <.05 *
  • 46. Diagnosis of Azoospermia The diagnosis of azoospermia can be established only when the pellet is examined The current WHO criteria for evaluation sperm morphology are similar to the “strict criteria” described by kruger
  • 47. Testicular Biopsy • Shall we do testicular biopsy ? • Where & who should do testicular biopsy • How should the information be interpreted ? • Which technique should be used
  • 48. Shall we do testicular biopsy ? YES It is both diagnostic & Therapeutic (sperm retrieval techniques used before ICSI) Testicular Sperm TESE is the technique of choice Spermatogenesis may be focal that means in about 50% of men with NOA sperms can be found & use for ICSI
  • 49. WHERE & WHO SHOULD DO TESTICULAR BIOPSY • It should be done in IVF setting where sperm freezing facilities are available • It is crime to do it otherwise specially in cases of non obstructive azoospermia
  • 50. How should the information be interpreted ? • Sertoli cell only , no germ cells • Spermatogonia only • Arrest at primary or secondary spermatocyte level • Spermatids round or elongated present • Spermatozoa present but only in few tubules • Normal spermatogenesis
  • 51. Hormonal evaluation Endocrine abnormalities are rarely present when the sperm concentration is greater than 10 million / ml
  • 52. Clinical Diagnosis based on Hormonal Status Clinical Status FSH LH Testosterone Normal men or obstruction Normal Normal Normal Isolated spermatogenic failure Normal Normal Testicular failure Normal or Hypogonadotropic hypogonadism
  • 53. Recommendation Recommendation Grade Effective drug therapy is available o achieve fertility in men with Hypogonadotrophic Hypogonadism . A Testosterone replacement is strictly contraindicated for the treatment of male infertility (low levels of FSH & LH) A
  • 54. AGGLUTINATION of SPERMS makes you suspect immunological problems Antisperpm antibody (ASA) are rare cause of male subfertility that do not required routine testing & are typically managed with the used of ICSI)
  • 55. GENETIC CAUSES 80% 10% 5% 5% Genetic Causes of Male Infertility Klinefelter Syndrome (47,XXY) Y-chromosome microdeletion Congenital Vas Absence
  • 56. GENETIC TESTS • * Karyotyping • * Y chromosome microdeletions • * Cystic fibrosis conductance regulator (CFTR) gene mutation
  • 57. Recommendation For Genetic Testing & Counselling From a diagnostic view point , standard karyotype analysis should be offered to all men with damaged spermatogenesis (spermatozoa <10 million /mL) who are seeking fertility treatment by IVF. B Testing for microdeletation is not necessary in men with OA (with normal FSH) when ICSI used because spermatogenesis should be normal A Men with severely damaged spermatogenesis (spermatozoa <5 million /Ml) should be advised to undergo Yq microdeletation testing for both diagnostic & prognostic purpose. Yq microdeletation also has important implication for genetic counselling A
  • 58. Recommendation For Genetic Testing & Counselling If complete AZFA or AZFB microdeletation are detected , micro – TESE should not be performed because it is extremely unlikely that any sperm will be found A If a man with Yq microdeletation & his partner wish to proceed with ICSI , they should be advised that microdeletation will be passed to sons , but not to doughters. A When man has structural abnormalities of the VAS DEFERENS (unilateral or bilateral absence), he & his partner should be tested for CF GENE MUTATIONS A
  • 59. AZFa deletion No retrievable sperm AZFc deletion Sperm retrieved in 70% of cases AZFb deletion No retrievable sperm Predictive Value of Ychromosome Microdeletion Screening for Sperm Retrieval in NOA
  • 60. TREATMENT ASPECT OF MALE INFERTILITY FEW ISSUES
  • 61. Antioxidants in Male Infertility To whom? Everyone What Medicine Vitamic C 500mg Vitamin E 400 UI LYCO Q 300 Is the dose How long? – till she is pregnant
  • 62. WHY Antioxidants: WHY ? To whom and how Seminal Reactive Oxygen Species (ROS) 2,5 2 1,5 1 0,5 0 Fertile Infertile
  • 63. Antioxidant Treatment Cochrane Review 2011 Outcome N studies N participants Effect size (OR; 95% CI) Live birth 3 214 4.85 [1.92, 12.24] Pregnancy rate 15 964 4.18 [2.65, 6.59] DNA fragmentation 1 64 -13.80 [-17.50, -10.10] Miscarriage, sperm count, sperm motility 6-16 242-700 No effect Adverse effects 6 426 No effect Improve the outcomes of live birth and pregnancy rate for subfertile couples undergoing ART cycles Showell MG, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD007411. DOI: 10.1002/14651858.CD007411.pub2.
  • 64. SPERM NUTRIENTS AND ANTI-OXIDANTS • Coenzyme Q-10 • Lycopene and Astaxanthin • Vitamin C • Zinc • Vitamin B-12 • L-Arginine • Vitamin-E • Selenium • L-Carnitine
  • 65. Take-home Messages Antioxidants helpful to decrease oxidative stress. Treatment effect is noted > 60 days later.
  • 66. MICRONUTRIENTS , ANTIOXIDANTS & PROTEIN RICH DIET to be literally started on DAY 1 BRIEFING AT FIRST VISIT
  • 68. TOBACCO SMOKING In MEN smoking affects all parameters of sperm quality
  • 69. I.U.I. ONLY & ONLY IN LOW RESOURSE SETTING FOR MALE INFERTILITY
  • 70. Intra uterine insemination If the sperm count is between 10 million to 20 million/ ml, IUI offers a good pregnancy rate provided there is no female factor However western world does not agree
  • 71. Indications of IUI: • Mild male factor infertility up to 3 cycles of IUI •(NICE, 2004; ESHRE Capri Workshop, 2009) ************************************************************************************************************** No IUI, Advise them to try to conceive for a total of 2years (including up to 1y before their fertility investigations) before IVF - ICSI will be considered. Exceptions: Social, Cultural, Religious • (NICE, 2013) Only Low recourse setting Treatment is ICSI in Male infertility
  • 73. From Sperm deposition to – sperm Ovum interaction : 4 steps take place in cervix ,uterus & FT 1. Capacitation 2. Acrosome Reaction 3. Hyperactivation 4. Sperm- Oocyte binding I.U.I. Takes away step I & II
  • 74. Male subfertility: * OAT syndrome *Oligospermia,Asthenozoospermia,Teratozospermia *Severe male infertility *Not candidate for IUI if Count<10million/ml *Normal morphology <2.5% or * Motility <10 Only ICSI ICSI is more cost effective than IUI when the mean total motile sperm count is <10 million (Van Voorhis et al,2001) If no natural pregnancy - ICSI
  • 75. SEMEN BANK & DONOR insemination • Therapeutic donor insemination in azoospermic patients • Homologous (husband’s) sperms can also be preserved under the following circumstances- 1. In men who have difficulty in collecting semen on demand (for treatment or procedures) 2. Men away from treatment place 3. Prior to the starting of treatment in men undergoing cytotoxic chemotherapy or radiotherapy 4. Prior to vasectomy or after successful vasectomy reversal
  • 76. Mild Moderate, Severe or Azoospermia Low Resource Setting 3 trial IUI H. Resources ICSI Out line of Male infertility treatment
  • 77. Male Fertility Declines More Gradually *30% decline in most men would not be sufficient to render them infertile. •Very important factor - If the sperm can fertilize eggs, we usually don't see poor embryo quality due to reduced sperm quality. Males retain their fertility well into old age
  • 78. very very controversial Fertility Restoration & Spontaneous Pregnancy Only Indication Treatment of Clinical Varicoceles prior to ICSI may be beneficial for patient subgroups of severe oligozoospermia and NOA.
  • 79. Other Recommendation • Adult male with palpable varicocele , abnormal semen parametar , desire for future fertility or pain related to varicocele • Adolescent / young adults : reduced ipsilateral testicular size , abnormal semen parameters
  • 80. 46%* 22% 66% 31% 31% Varicocele and ICSI Outcomes Treated Varicocele Untreated Varicocele 78%* Fertilized Eggs (%2PN) Live Birth (%) *P<0.05 Miscarriage (%) Esteves SC, Oliveira FV, Bertolla RP. ... J Urol 2010;184:1442-1446 Odds ratio 1.87 0.43 95% CI 1.08 - 3.25 0.22 – 0.84 P-value 0.03 0.01
  • 81. Azoospermia it is not a synonymous of sterility
  • 82. • Normal sperm production • Mechanical blockage • Vasectomy, Post- infectious, Congenital Obstructive • Sperm production deficient or absent • Cryptorchidism, Radiation, Chemotherapy, Trauma, Genetic, Orchitis, Varicocele, Gonadotoxins, Unexplained Non- obstructive
  • 83. AZOOSPERMIA Determine the reason Obstructive Non-obstructive • Clinical examination ( vas, epididymis, testis size) • Volume, pH, fructose—all affected in OBST.AZOO • FSH level—raised in NOA
  • 84. Testicular failure need not mean no sperm no sperm many spermfew sperm Size of Testis in Azoospermia P.T.F. Patchy spermatogenesis Obstruction
  • 85.
  • 86. Obstructive Azoospermia • Microsurgical reconstruction • TURED If young patient • Epididymis • Testis • Simple and effective Married for long time **Sperm retrieval + ICSI Micro surgical sperm retrieval techniques MESA
  • 87. Obstructive azoospermia Recommendations Treatment - surgery if young Recommendation Grade In azoospermia caused by EPIDIDYMAL OBSTRUCTION standard procedures include Vasovasostomy & Tubulovastomy B SPERM RETRIEVAL TECHNIQUES , such as MESA , TESA & PESA , can be used additionally . These methods should be used only when cryostorage of the material obtained is available. B
  • 88. Ductal Obstruction Causing azoospermia If old or pressure to have a child is more than sperm retrieval & ICSI
  • 90. Esteves SC, et al. Success of percutaneous sperm retrieval and intracytoplasmic sperm injection (ICSI) in obstructive azoospermic (OA) men according to the cause of obstruction. Fertil Steril. 2010;94 (Suppl):S233. Percutaneous SPERM Retrieval –is almost 100%
  • 91. Most azoospermic men with non obstructive type are not sterile. Sperm retrieval and reproductive potential is dependent on the CAUSE of azoospermia.
  • 92.
  • 93. Non-obstructive Azoospermia TESA vs. TESE [better] Controlled studies for NOA men Needle Aspiration Open Biopsy Friedler et al Human Reprod 12: 1488, 1997 4/37 (11%) 16/37 (43%) Ezeh et al. Human Reprod 13:3075 5/35 (14%) 22/35 (63%)
  • 96. Sleeve Gastrectomy & Gastric Bypass surgery are done routinely Bariatric Surgery Significant and sustained weight loss of 40-50 kg is expected
  • 97. Is Bariatric surgery safe? It is a fact that… There are 40 Bariatric surgeons in INDIA…it is not cup of any surgeon In Good Hands it is …as Safe as Laparoscopic Cholecystectomy
  • 98. Weight loss is one of the corner stone to achieve a healthy pregnancy and child birth
  • 99. Our Experience with Bariatric Surgery Total cases - 23 5 had pregnancy with IUI & 6 had IVF ICSI pregnancy 11 Pregnancy Hypertension, DM, Cholesterol has magical relief
  • 100. ART has provided NOVEL PROTOCOLS for FERTILITY PRESERVATION during & preceding ONCOTHERAPY in young boys who are CANCER victims,
  • 101. Fertility Preservation Male Pre adolecents.do not produce sperm so…testes has to saved & reimplanted * Once semen production..then semen samples to be saved
  • 102. We work with accredited facilities that follow the ICMR & ASRM standards andguidelines.
  • 103. ADDRESS 11 Gagan Vihar, Near Karkari Morh Flyover, Delhi - 51 CONTACT US 9650588339 9599044257 011-22414049 WEBSITE : www.lifecareivf.in www.lifecarecentre.in www.lifecareabs.in ISO 14001:2004 (EMS) …..Caring hearts, healing hands ISO 9001:2008 Helpline : 9599044257 Web.www.lifecareivf.in Helpline : 9910081484 27 Year In your service