Sandro C. Esteves, MD., PhD. Director, ANDROFERT

Campinas, Brazil

       Role of Andrologist in ART

Al  Azhar  Conference,  Cairo  2014  

 

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  

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

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  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

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  Serie

s  Sperm Retrieval in Non-Obstructive

Azoospermia

Esteves, 6 ANDROFERT, Referral Center for Male Reproduction

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 retrieval

l  Select who could benefit from interventions prior to ART

Esteves, 8 ANDROFERT, Referral Center for Male Reproduction

 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%  

Hypogonadism  (TT<300ng/dL)  

Clinical  varicocele  

Candidates  for  intervenIons  prior  to  ART  

Esteves,  10   ANDROFERT,  Referral  Center  for  Male  ReproducIon  

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  

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

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  

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  

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.)

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

Esteves, 17 ANDROFERT, Referral Center for Male Reproduction

Varicocele  Treatment  

Miyaoka  &  Esteves.  Adv  Urol  2012  

Technique   Recurrence  

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%  

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  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  

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

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

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

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  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

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  

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  

Andrologist  adds  great  value  to  ART  program