Sandro C. Esteves, MD., PhD.
Director, ANDROFERT
Campinas, Brazil
	
  	
  
	
  
	
  
Role of Andrologist in ART
Al	
  Azha...
 
Available	
  at:	
  
	
  
h8p://www.androfert.com.br/review	
  
Role	
  of	
  Andrologist	
  in	
  ART	
  	
  
Al	
  Azh...
Lecture	
  Outline	
  
Esteves,	
  3	
   ANDROFERT,	
  Referral	
  Center	
  for	
  Male	
  ReproducIon	
  
l Understand ...
Role of Andrologist in ART Program
l Sperm retrieval
in cases of
azoospermia

TESE
Esteves,	
  5	
   ANDROFERT,	
  Referral	
  Center	
  for	
  Male	
  ReproducIon	
  
30-­‐50%	
  cases:	
  minimal	
  
pro...
Schlegel	
  1999 	
   	
  
	
  	
  
Amer	
  et	
  al.	
  	
  	
  2000 	
  	
  
Okada	
  et	
  al.	
  	
  2002 	
  
	
  	
 ...
http://androfert.com.br/videos
Esteves SC, Int Braz J Urol 2013
Role of Andrologist goes far beyond
being a sperm retrieval “Technician”
l Identify who are the best
candidates for sperm...
 
SelecIng	
  candidates	
  for	
  SR	
  
YCMD	
  screening	
  by	
  PCR	
  
Hamada	
  et	
  al.	
  2012;	
  Esteves	
  &	...
Hypogonadism	
  
(TT<300ng/dL)	
  
Clinical	
  
varicocele	
  
Candidates	
  for	
  intervenIons	
  prior	
  to	
  
ART	
 ...
Medical	
  therapy	
  in	
  Azoospermia	
  
Hypogonadism	
  
Esteves,	
  11	
   ANDROFERT,	
  Referral	
  Center	
  for	
 ...
Medical	
  therapy	
  for	
  hypogonadism	
  
ART	
  Candidates	
  
Severe	
  oligozoospermia	
  
Non-­‐obstrucIve	
  azoo...
hCG	
  for	
  men	
  with	
  NOA	
  and	
  
hypogonadism	
  
Fraie8a	
  &	
  Esteves	
  Clinics	
  2013;	
  Esteves	
  &	
...
35%	
  subferIle	
  men	
  
	
  Lower	
  Sperm	
  Count	
  and	
  Quality	
  
	
  Lower	
  Sperm	
  FuncIon	
  
	
  Elevat...
Inci	
  et	
  al,	
  J	
  Urol.	
  2009	
  
Miyaoka	
  &	
  Esteves.	
  Adv	
  Urol	
  2012	
  
Esteves,	
  15	
   ANDROFE...
Varicocele Treated
prior to ICSI (N=80)
ICSI with Untreated
Varicocele (N=162)
SC	
  Esteves,	
  FV	
  Oliveira,	
  RP	
  ...
Esteves, 17 ANDROFERT, Referral Center for Male Reproduction
Varicocele	
  Treatment	
  
Miyaoka	
  &	
  Esteves.	
  Adv	
...
Microsurgical Varicocele Repair
Esteves, 18 ANDROFERT, Referral Center for Male Reproduction
What	
  else	
  an	
  Andrologist	
  can	
  offer?	
  
Esteves, 19 ANDROFERT, Referral Center for Male Reproduction
Sperm	
  DNA	
  FragmentaIon	
  
Role	
  of	
  Andrologist	
  
l Iden2fy	
  who	
  have	
  elevated	
  
levels	
  of	
  S...
Sperm	
  DNA	
  fragmentaIon	
  
single-strand
break
mis-match
damaged
base double-
strand break inter-strand
crosslink
in...
Elevated	
  SDF	
  negaIvely	
  impact	
  
reproducIve	
  outcome	
  
l InferIlity	
  
l Poor	
  outcome	
  IUI,	
  IVF	...
26%
42%
IVF ICSI
Pregnancy by Method in
Cases of Elevated Sperm DNA
Fragmentation
IVF Outcome and SDF
Robinson et al. Hum ...
Management
TESA-ICSI: ANDROFERT
Esteves, 25 ANDROFERT, Referral Center for Male Reproduction
TESA-­‐ICSI	
  and	
  SDF	
  	
  
Sperm	
   %	
  TUNEL	
  +	
   %	
  CPR	
  
Ejaculated	
  (N=18)	
   23.6	
   6	
  
TesIc...
Role	
  of	
  Andrologist	
  in	
  ART	
  	
  
Key	
  Messages	
  
Role	
  of	
  Andrologist	
  goes	
  far	
  beyond	
  
...
Role	
  of	
  Andrologist	
  in	
  ART	
  	
  
Key	
  Messages	
  
As	
  part	
  of	
  mulI-­‐specialty	
  ART	
  team,	
 ...
Andrologist	
  adds	
  great	
  value	
  to	
  ART	
  
program	
  
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Role of Andrologist in ART

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Role of Andrologist in ART

  1. 1. Sandro C. Esteves, MD., PhD. Director, ANDROFERT Campinas, Brazil         Role of Andrologist in ART Al  Azhar  Conference,  Cairo  2014  
  2. 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. 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. 4. Role of Andrologist in ART Program l Sperm retrieval in cases of azoospermia TESE
  5. 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. 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. 7. http://androfert.com.br/videos Esteves SC, Int Braz J Urol 2013
  8. 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. 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. 10. Hypogonadism   (TT<300ng/dL)   Clinical   varicocele   Candidates  for  intervenIons  prior  to   ART   Esteves,  10   ANDROFERT,  Referral  Center  for  Male  ReproducIon  
  11. 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. 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. 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. 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. 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. 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. 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. 18. Microsurgical Varicocele Repair Esteves, 18 ANDROFERT, Referral Center for Male Reproduction
  19. 19. What  else  an  Andrologist  can  offer?   Esteves, 19 ANDROFERT, Referral Center for Male Reproduction
  20. 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. 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. 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. 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. 24. Management
  25. 25. TESA-ICSI: ANDROFERT Esteves, 25 ANDROFERT, Referral Center for Male Reproduction
  26. 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. 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. 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. 29. Andrologist  adds  great  value  to  ART   program  

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