Advances in OBGYN Conference, Oman 2013

Male Infertility for a Generalist
What Can We Offer?
Sandro C. Esteves, MD, PhD
D...
Contents
DIAGNOSIS
MEDICAL TREATMENT
SURGICAL TREATMENT
ASSISTED REPRODUCTION
Esteves, 2

ANDROFERT, Referral Center for M...
Male Infertility for a Generalist
What can we offer?

Available at:

http://www.androfert.com.br/review

Esteves, 3

ANDRO...
Semen Analysis

Central
Laboratory
Investigation

Esteves, 4

Functional
Status of
Reproductive
Tract

Seminal Fluid
and S...
WHO 2010: Recent fathers TTP≤12 mo.

Volume (mL)
Sperm count (x106/mL)
Total count (x106)
% Motile (total)
% Motile (progr...
Esteves, 6

ANDROFERT, Referral Center for Male Reproduction
Quick and Easy Test
Sperm Chromatin Integrity Test (SCD)
Intact DNA: Sperm with “Halo”
Represents dispersed chromatin
with...
IUI Outcome in Men with
High Sperm DNA Damage
Live Birth Rates with
Intrauterine Insemination
19%

OR = 0.07
[95% CI: 0.01...
IVF Outcome in Men with
High Sperm DNA Damage
Pregnancy by Method in
Cases of Elevated Sperm DNA
Fragmentation
42%

Increa...
Sperm DNA Damage is Associated to
Elevated Oxidative Stress

DNA damage
DNA Damage

Evaluation of
Evaluation of
DNA damage...
Empirical Medical Treatment for
Idiopathic Male Infertility
Androgens
hCG/HMG
FSH
Anti-estrogens
Bromocriptine
Alpha-block...
Oral Antioxidants for the Male
Outcome

No. studies

Effect size
(OR; 95% CI)

Live birth

3

4.85 [1.92, 12.24]

Pregnanc...
Male Hypogonadotropic Hypogonadism
Specific Medical Therapy
Series of men with adult-onset HH
Recombinant hCG; 250 mcg per...
Contents
DIAGNOSIS
MEDICAL TREATMENT
SURGICAL TREATMENT
ASSISTED REPRODUCTION
Esteves, 14

ANDROFERT, Referral Center for ...
Varicocele
35% subfertile men
Lower Sperm Count and Quality
Lower Sperm Function
Elevated Oxidative Stress Levels
Elevated...
Varicocele Surgery and Spontaneous
Pregnancy

Marmar et al., Fertil Steril 2008

Esteves, 16

ANDROFERT, Referral Center f...
Varicocele Treatment
Technique	
  

Recurrence	
  

Postop
Hydrocele 	
  

Retroperitoneal
(Palomo)	
  

7-35%	
  

6-10%	...
Clinical Outcome of Intracytoplasmic Sperm Injection in Infertile Men
With Treated and Untreated Clinical Varicocele
SC Es...
Sperm Retrieval for ART

Normal sperm production
Mechanical blockage
Vasectomy, Post-infectious,
Congenital

Esteves, 19

...
http://androfert.com.br/videos
Esteves, 20

ANDROFERT, Referral Center for Male Reproduction
http://androfert.com.br/videos
Esteves, 21

ANDROFERT, Referral Center for Male Reproduction
Esteves SC, Int Braz J Urol 2013

http://androfert.com.br/videos
Sperm Retrieval and ICSI in Azoospermia
Non-obstructive

Obstructive

100
41.4

P<0.01
47

64
43.3

61
20

Sperm retrieval...
Take-home Messages
Routine semen analysis not a good male fertility discriminator.
Sperm DNA damage provides information o...
Thank You
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Male Infertility for a Generalist

  1. 1. Advances in OBGYN Conference, Oman 2013 Male Infertility for a Generalist What Can We Offer? Sandro C. Esteves, MD, PhD Director, ANDROFERT Campinas, Brazil
  2. 2. Contents DIAGNOSIS MEDICAL TREATMENT SURGICAL TREATMENT ASSISTED REPRODUCTION Esteves, 2 ANDROFERT, Referral Center for Male Reproduction
  3. 3. Male Infertility for a Generalist What can we offer? Available at: http://www.androfert.com.br/review Esteves, 3 ANDROFERT, Referral Center for Male Reproduction
  4. 4. Semen Analysis Central Laboratory Investigation Esteves, 4 Functional Status of Reproductive Tract Seminal Fluid and Sperm ANDROFERT, Referral Center for Male Reproduction
  5. 5. WHO 2010: Recent fathers TTP≤12 mo. Volume (mL) Sperm count (x106/mL) Total count (x106) % Motile (total) % Motile (progressive) % Normal (strict criteria) % Alive 5% 1.5 15.0 39.0 40 32 4 58 Percentiles 50%* 95% 3.7 6.8 73.0 213.0 255.0 802.0 61 78 55 72 15 44 79 91 Cooper et al. Hum Reprod Update 2010 Esteves, 5 ANDROFERT, Referral Center for Male Reproduction
  6. 6. Esteves, 6 ANDROFERT, Referral Center for Male Reproduction
  7. 7. Quick and Easy Test Sperm Chromatin Integrity Test (SCD) Intact DNA: Sperm with “Halo” Represents dispersed chromatin without breaks Absent/small “Halo”: Damaged DNA Represents DNA strand breaks Semen/Spermatozoa Quantitative Test: Normal: <20% sperm with fragmented DNA Feijo & Esteves Fertil Steril 2013 Esteves, 7 ANDROFERT, Referral Center for Male Reproduction
  8. 8. IUI Outcome in Men with High Sperm DNA Damage Live Birth Rates with Intrauterine Insemination 19% OR = 0.07 [95% CI: 0.01-0.48] 1.5% Normal Esteves, 8 Bungum et al. Hum Reprod 2007 Elevated ANDROFERT, Referral Center for Male Reproduction
  9. 9. IVF Outcome in Men with High Sperm DNA Damage Pregnancy by Method in Cases of Elevated Sperm DNA Fragmentation 42% Increased miscarriage in couples undergoing IVF/ICSI with high sperm DNA damage 26% IVF Meta-analysis of 16 studies and 2,969 couples ICSI Risk ratio (RR) = 2.16 95% CI: 1.54-3.03; p<0.00001 Robinson et al. Hum Reprod 2012 Bungum et al. Hum Reprod 2007 Esteves, 9 ANDROFERT, Referral Center for Male Reproduction
  10. 10. Sperm DNA Damage is Associated to Elevated Oxidative Stress DNA damage DNA Damage Evaluation of Evaluation of DNA damage DNA Damage Esteves & Agarwal Int Braz J Urol 2011 Esteves, 10 ANDROFERT, Referral Center for Male Reproduction
  11. 11. Empirical Medical Treatment for Idiopathic Male Infertility Androgens hCG/HMG FSH Anti-estrogens Bromocriptine Alpha-blockers Systemic corticosteroids In general, NOT EFFECTIVE Guidelines on Male Infertility. European Association of Urology 2012 Esteves, 11 ANDROFERT, Referral Center for Male Reproduction
  12. 12. Oral Antioxidants for the Male Outcome No. studies Effect size (OR; 95% CI) Live birth 3 4.85 [1.92, 12.24] Pregnancy rate 15 4.18 [2.65, 6.59] DNA fragmentation 1 -13.80 [-17.50, -10.10] Miscarriage, sperm count, sperm motility 6-16 No effect Showell MG et al. Cochrane Database Syst Rev 2011 Esteves, 12 ANDROFERT, Referral Center for Male Reproduction
  13. 13. Male Hypogonadotropic Hypogonadism Specific Medical Therapy Series of men with adult-onset HH Recombinant hCG; 250 mcg per week; 12 weeks SC self-injection w/pre-filled syringe, qw Esteves & Papanikolaou Fertil Steril 2011 Fraietta et al, Clinics 2013 Esteves, 13 ANDROFERT, Referral Center for Male Reproduction
  14. 14. Contents DIAGNOSIS MEDICAL TREATMENT SURGICAL TREATMENT ASSISTED REPRODUCTION Esteves, 14 ANDROFERT, Referral Center for Male Reproduction
  15. 15. Varicocele 35% subfertile men Lower Sperm Count and Quality Lower Sperm Function Elevated Oxidative Stress Levels Elevated Sperm DNA Damage Miyaoka & Esteves. Adv Urol 2012 Agarwal, Esteves, Hamada. Nature Urol Rev 2013 Esteves, 15 ANDROFERT, Referral Center for Male Reproduction
  16. 16. Varicocele Surgery and Spontaneous Pregnancy Marmar et al., Fertil Steril 2008 Esteves, 16 ANDROFERT, Referral Center for Male Reproduction
  17. 17. Varicocele Treatment Technique   Recurrence   Postop Hydrocele   Retroperitoneal (Palomo)   7-35%   6-10%   Laparoscopy   2-7%   0-9%   Embolization   2-24%   NR   Inguinal (Ivanissevich)   0-37%   7%   Microsurgical Subinguinal   0-1%   0-1.6%   Miyaoka & Esteves. Adv Urol 2012 Esteves, 17 ANDROFERT, Referral Center for Male Reproduction
  18. 18. Clinical Outcome of Intracytoplasmic Sperm Injection in Infertile Men With Treated and Untreated Clinical Varicocele 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 Varicocele Treated prior to ICSI (N=80) ICSI with Untreated Varicocele (N=162) Esteves, 18 ANDROFERT, Referral Center for Male Reproduction
  19. 19. Sperm Retrieval for ART Normal sperm production Mechanical blockage Vasectomy, Post-infectious, Congenital Esteves, 19 Sperm production deficient or absent Cryptorchidism, Radiation, Chemotherapy, Trauma, Genetic, Orchitis, Varicocele, Gonadotoxins, Unexplained ANDROFERT, Referral Center for Male Reproduction
  20. 20. http://androfert.com.br/videos Esteves, 20 ANDROFERT, Referral Center for Male Reproduction
  21. 21. http://androfert.com.br/videos Esteves, 21 ANDROFERT, Referral Center for Male Reproduction
  22. 22. Esteves SC, Int Braz J Urol 2013 http://androfert.com.br/videos
  23. 23. Sperm Retrieval and ICSI in Azoospermia Non-obstructive Obstructive 100 41.4 P<0.01 47 64 43.3 61 20 Sperm retrieval (%) 2PN Fertilization (%) Top Quality Embryos (%) OR=0.033 95% CI: 0.007-0.164; p<0.001 34.2 Live Birth (%) OR=0.38 95% CI: 0.23-0.61; p<0.001 Esteves et al. Asian J Androl. 2013 Esteves, 23 ANDROFERT, Referral Center for Male Reproduction
  24. 24. Take-home Messages Routine semen analysis not a good male fertility discriminator. Sperm DNA damage provides information of great prognostic value. Antioxidants helpful to decrease oxidative stress and DNA damage. Specific medical therapy only valid for hypogonadism. Microsurgical varicocele repair increases chances of spontaneous and assisted conception. Sperm retrieval is routinely used in ART. Reproductive potential of surgically-retrieved sperm depends on type of azoospermia.. Esteves, 24 ANDROFERT, Referral Center for Male Reproduction
  25. 25. Thank You

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