1. Sandro C. Esteves, MD., PhD.
Director, ANDROFERT
Campinas, Brazil
Role of Andrologist in ART
Al
Azhar
Conference,
Cairo
2014

2.
Available
at:
h8p://www.androfert.com.br/review
Role
of
Andrologist
in
ART
Al
Azhar
Conference,
Cairo
2014
Esteves,
2
ANDROFERT,
Referral
Center
for
Male
ReproducIon

3. Lecture
Outline
Esteves,
3
ANDROFERT,
Referral
Center
for
Male
ReproducIon
l Understand the role of
Andrologists in an ART
Program
l Learn how medical and
surgical andrological
interventions could
benefit patients
undergoing ART

4. Role of Andrologist in ART Program
l Sperm retrieval
in cases of
azoospermia
TESE

5. Esteves,
5
ANDROFERT,
Referral
Center
for
Male
ReproducIon
30-­‐50%
cases:
minimal
producIon
within
the
tesIs,
but
not
enough
for
sperm
to
appear
in
ejaculate
Goal
is
to
iden2fy
site
of
produc2on
and
retrieve
sperm
for
ICSI
Geographic
loca2on
unpredictable
Esteves SC & Agarwal A. Sperm Retrieval Techniques; In: Gardner D et al (Eds.), Human Assisted
Reproductive Technology. Cambridge University Press, pp. 41-53, 2011
Non-­‐Obstruc2ve
Azoospermia

6. Schlegel
1999
Amer
et
al.
2000
Okada
et
al.
2002
Okubu
et
al.
2002
Tsujimura
et
al.
2002
Ramon
et
al.
2003
Esteves
et
al.
2011
43%-­‐53%
25%-­‐41%
Controlled
Series
Sperm Retrieval in Non-Obstructive
Azoospermia
Esteves, 6 ANDROFERT, Referral Center for Male Reproduction

7. http://androfert.com.br/videos
Esteves SC, Int Braz J Urol 2013

8. Role of Andrologist goes far beyond
being a sperm retrieval “Technician”
l Identify who are the best
candidates for sperm retrieval
l Select who could benefit from
interventions prior to ART
Esteves, 8 ANDROFERT, Referral Center for Male Reproduction

9.
SelecIng
candidates
for
SR
YCMD
screening
by
PCR
Hamada
et
al.
2012;
Esteves
&
Agarwal
Int
Braz
J
Urol
2011;
Foresta
et
al
Endocr
Rev
2001.
Esteves, 9 ANDROFERT, Referral Center for Male Reproduction
AZFb
deleted
SRR
~
0%
AZFa
deleted
SRR
=
0%
AZFc
deleted
SRR
~70%

10. Hypogonadism
(TT<300ng/dL)
Clinical
varicocele
Candidates
for
intervenIons
prior
to
ART
Esteves,
10
ANDROFERT,
Referral
Center
for
Male
ReproducIon

11. Medical
therapy
in
Azoospermia
Hypogonadism
Esteves,
11
ANDROFERT,
Referral
Center
for
Male
ReproducIon
72
55
Sperm Retrieval Rate (%)
Positive Tx response (increase in TT)
No response
Klinefelter
Syndrome
with
NOA
and
hypogonadism;
N=91
Ramasamy
et
al.,
J
Urol.
2009
P
=
0.03
Anti-estrogen (CC 50mg)
every other day; no
controls
64% men had sperm in the
ejaculates post-Tx (mean:
3.8 M/mL);
Spermatozoa obtained by
SR in all who remained
azoospermic.
NOA
and
favorable
tesIcular
histopathology;
N=43
Hussein
et
al,
J
Androl
2005

12. Medical
therapy
for
hypogonadism
ART
Candidates
Severe
oligozoospermia
Non-­‐obstrucIve
azoospermia
Esteves,
12
ANDROFERT,
Referral
Center
for
Male
ReproducIon
OpIons
AnI-­‐estrogens
u-­‐hCG/rec-­‐hCG*
*Ovitrelle (choriogonadotropin alfa) is indicated for the treatment
of anovulation

13. hCG
for
men
with
NOA
and
hypogonadism
Fraie8a
&
Esteves
Clinics
2013;
Esteves
&
Papanikolaou
FerIl
Steril
2011
Esteves,
13
ANDROFERT,
Referral
Center
for
Male
ReproducIon
Classic treatment
Urinary hCG 1,000-2,000 UI IM
injections; twice or t.i.w;
minimum 12 weeks
SC
self-­‐injec2on
w/pre-­‐
filled
syringe
containing
rec-­‐hCG,
qw

14. 35%
subferIle
men
Lower
Sperm
Count
and
Quality
Lower
Sperm
FuncIon
Elevated
OxidaIve
Stress
Levels
Elevated
Sperm
DNA
Damage
FerIlity
Improvement
Sperm
Retrieval
in
Azoospermia
FerIlity
Improvement
ICSI
Outcomes
Esteves, 14 ANDROFERT, Referral Center for Male Reproduction
Varicocele
and
ART

15. Inci
et
al,
J
Urol.
2009
Miyaoka
&
Esteves.
Adv
Urol
2012
Esteves,
15
ANDROFERT,
Referral
Center
for
Male
ReproducIon
Varicocele
treatment
in
azoospermia
Weedin
JW
et
al,
J
Urol.
2010
Meta-analysis of 11 case series (N=233)
39% men had motile sperm in postop.
ejaculates (mean: 1.6 M/mL)
Retrospective study with SR in 96 pts.
with treated and untreated varicocele
Success: 53% vs 30% (increased by 2.6-
fold in treated pts.)

16. Varicocele Treated
prior to ICSI (N=80)
ICSI with Untreated
Varicocele (N=162)
SC
Esteves,
FV
Oliveira,
RP
Bertolla
ANDROFERT
and
Division
of
Urology,
São
Paulo
Federal
University,
BRAZIL
The
Journal
of
Urology;
Vol.
184:
1442-­‐6,
2010
ICSI Outcome in Men With Treated and Untreated
Clinical Varicocele
Esteves, 16 ANDROFERT, Referral Center for Male Reproduction

17. Esteves, 17 ANDROFERT, Referral Center for Male Reproduction
Varicocele
Treatment
Miyaoka
&
Esteves.
Adv
Urol
2012
Technique
Recurrenc
e
Postop
Hydrocele
Retroperitoneal
(Palomo)
7-­‐35%
6-­‐10%
Laparoscopy
2-­‐7%
0-­‐9%
EmbolizaIon
2-­‐24%
NR
Inguinal
(Ivanissevich)
0-­‐37%
7%
Microsurgical
Subinguinal
0-­‐1%
0-­‐1.6%

18. Microsurgical Varicocele Repair
Esteves, 18 ANDROFERT, Referral Center for Male Reproduction

19. What
else
an
Andrologist
can
offer?
Esteves, 19 ANDROFERT, Referral Center for Male Reproduction

20. Sperm
DNA
FragmentaIon
Role
of
Andrologist
l Iden2fy
who
have
elevated
levels
of
SDF
l Iden2fy
poten2ally
treatable
underlying
condi2on
l Counseling
about
treatment
op2ons
l Tes2cular
sperm
retrieval
for
ICSI
Esteves
&
Agarwal
Int
Braz
J
Urol
2011
Evalua2on
of
DNA
damage
DNA
damage
Assessment
of
DNA
Damage
DNA
Damage

21. Sperm
DNA
fragmentaIon
single-strand
break
mis-match
damaged
base double-
strand break inter-strand
crosslink
intra-strand
crosslink
Esteves, 21 ANDROFERT, Referral Center for Male Reproduction

22. Elevated
SDF
negaIvely
impact
reproducIve
outcome
l InferIlity
l Poor
outcome
IUI,
IVF
l Increased
risk
miscarriage
ICSI
19%
1.5%
Normal Elevated
Live Birth Rates with
Intrauterine
Insemination
OR = 0.07
[95% CI: 0.01-0.48]
Bungum et al. Hum
Reprod 2007
Esteves, 22 ANDROFERT, Referral Center for Male Reproduction

23. 26%
42%
IVF ICSI
Pregnancy by Method in
Cases of Elevated Sperm DNA
Fragmentation
IVF Outcome and SDF
Robinson et al. Hum Reprod 2012
Meta-analysis of 16 studies and
2,969 couples
Increased miscarriage in couples
undergoing IVF/ICSI with high
sperm DNA damage
Risk ratio (RR) = 2.16
95% CI: 1.54-3.03; p<0.00001
Bungum et al. Hum Reprod 2007
Esteves, 23 ANDROFERT, Referral Center for Male Reproduction

24. Management

25. TESA-ICSI: ANDROFERT
Esteves, 25 ANDROFERT, Referral Center for Male Reproduction

26. TESA-­‐ICSI
and
SDF
Sperm
%
TUNEL
+
%
CPR
Ejaculated
(N=18)
23.6
6
TesIcular
(N=18)
4.8
44
P
value
<0.001
<0.05
Greco
et
al.
Hum
Reprod
2005
DNA damage in Testicular Spermatozoa (13.3%) is three-fold
lower compared with Ejaculated Spermatozoa (39.7%)*
*Absolute
differences
between
two
specimens
ranging
from
-­‐3.3%
to
-­‐56.3%.
Moskovtsev
et
al.
Fer6l
Steril
2010
Esteves, 26 ANDROFERT, Referral Center for Male Reproduction

27. Role
of
Andrologist
in
ART
Key
Messages
Role
of
Andrologist
goes
far
beyond
performing
surgical
sperm
retrieval
Andrologist
not
only
determine
who
are
the
best
candidates
for
sperm
retrieval,
but
also
aid
in
opImizing
ART
outcome
by
medical
and
surgical
intervenIons
Esteves,
27
ANDROFERT,
Referral
Center
for
Male
ReproducIon

28. Role
of
Andrologist
in
ART
Key
Messages
As
part
of
mulI-­‐specialty
ART
team,
offer
counseling
about
treatment
opIons
and
outcome
of
cases
involving
male
inferIlity
Esteves,
28
ANDROFERT,
Referral
Center
for
Male
ReproducIon
Andrologist
can
idenIfy
men
with
elevated
levels
of
SDF,
and
tackle
potenIally
treatable
underlying
condiIons

29. Andrologist
adds
great
value
to
ART
program