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  • 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. Contents DIAGNOSIS MEDICAL TREATMENT SURGICAL TREATMENT ASSISTED REPRODUCTION Esteves, 2 ANDROFERT, Referral Center for Male Reproduction
  • 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. Semen Analysis Central Laboratory Investigation Esteves, 4 Functional Status of Reproductive Tract Seminal Fluid and Sperm ANDROFERT, Referral Center for Male Reproduction
  • 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. Esteves, 6 ANDROFERT, Referral Center for Male Reproduction
  • 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. 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. 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. 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. 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. 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. 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. Contents DIAGNOSIS MEDICAL TREATMENT SURGICAL TREATMENT ASSISTED REPRODUCTION Esteves, 14 ANDROFERT, Referral Center for Male Reproduction
  • 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. Varicocele Surgery and Spontaneous Pregnancy Marmar et al., Fertil Steril 2008 Esteves, 16 ANDROFERT, Referral Center for Male Reproduction
  • 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. 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. 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. http://androfert.com.br/videos Esteves, 20 ANDROFERT, Referral Center for Male Reproduction
  • 21. http://androfert.com.br/videos Esteves, 21 ANDROFERT, Referral Center for Male Reproduction
  • 22. Esteves SC, Int Braz J Urol 2013 http://androfert.com.br/videos
  • 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. 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. Thank You