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