male infertility for a generalist
TRANSCRIPT
Sandro C. Esteves, MD, PhD Director, ANDROFERT
Campinas, Brazil
Male Infertility for a Generalist
What Can We Offer?
Advances in OBGYN Conference, Oman 2013
Contents
DIAGNOSIS MEDICAL TREATMENT SURGICAL TREATMENT ASSISTED REPRODUCTION
Esteves, 2 ANDROFERT, Referral Center for Male Reproduction
Available at:
http://www.androfert.com.br/review
Male Infertility for a Generalist What can we offer?
Esteves, 3 ANDROFERT, Referral Center for Male Reproduction
Semen Analysis
Functional Status of
Reproductive Tract
Seminal Fluid and Sperm
Central Laboratory
Investigation
Esteves, 4 ANDROFERT, Referral Center for Male Reproduction
Volume (mL) 1.5 Sperm count (x106/mL) 15.0 Total count (x106) 39.0 % Motile (total) 40 % Motile (progressive) 32 % Normal (strict criteria) 4 % Alive 58
Cooper et al. Hum Reprod Update 2010
WHO 2010: Recent fathers TTP≤12 mo. Percentiles
5% 50%* 95% 3.7 6.8
73.0 213.0 255.0 802.0
61 78 55 72 15 44 79 91
Esteves, 5 ANDROFERT, Referral Center for Male Reproduction
Esteves, 6 ANDROFERT, Referral Center for Male Reproduction
Quick and Easy Test Sperm Chromatin Integrity Test (SCD)
Esteves, 7 ANDROFERT, Referral Center for Male Reproduction
Feijo & Esteves Fertil Steril 2013
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
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
IUI Outcome in Men with High Sperm DNA Damage
Esteves, 8 ANDROFERT, Referral Center for Male Reproduction
26%
42%
IVF ICSI
Pregnancy by Method in Cases of Elevated Sperm DNA
Fragmentation
IVF Outcome in Men with High Sperm DNA Damage
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, 9 ANDROFERT, Referral Center for Male Reproduction
Sperm DNA Damage is Associated to Elevated Oxidative Stress
Esteves & Agarwal Int Braz J Urol 2011
Evaluation of DNA damage
DNA damage
Evaluation of DNA Damage
DNA Damage
Esteves, 10 ANDROFERT, Referral Center for Male Reproduction
Empirical Medical Treatment for Idiopathic Male Infertility
Guidelines on Male Infertility. European Association of Urology 2012
In general, NOT
EFFECTIVE
Esteves, 11 ANDROFERT, Referral Center for Male Reproduction
Androgens hCG/HMG FSH Anti-estrogens Bromocriptine Alpha-blockers Systemic corticosteroids
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
Oral Antioxidants for the Male
Showell MG et al. Cochrane Database Syst Rev 2011
Esteves, 12 ANDROFERT, Referral Center for Male Reproduction
Esteves & Papanikolaou Fertil Steril 2011 Fraietta et al, Clinics 2013
SC self-injection w/pre-filled syringe, qw
Male Hypogonadotropic Hypogonadism Specific Medical Therapy
Series of men with adult-onset HH Recombinant hCG; 250 mcg per week; 12 weeks
Esteves, 13 ANDROFERT, Referral Center for Male Reproduction
Contents
DIAGNOSIS MEDICAL TREATMENT SURGICAL TREATMENT ASSISTED REPRODUCTION
Esteves, 14 ANDROFERT, Referral Center for Male Reproduction
Miyaoka & Esteves. Adv Urol 2012 Agarwal, Esteves, Hamada. Nature Urol Rev 2013
Varicocele
35% subfertile men Lower Sperm Count and Quality Lower Sperm Function Elevated Oxidative Stress Levels Elevated Sperm DNA Damage
Esteves, 15 ANDROFERT, Referral Center for Male Reproduction
Marmar et al., Fertil Steril 2008
Esteves, 16 ANDROFERT, Referral Center for Male Reproduction
Varicocele Surgery and Spontaneous Pregnancy
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%
Embolization 2-24% NR
Inguinal (Ivanissevich)
0-37%
7%
Microsurgical Subinguinal 0-1% 0-1.6%
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
Clinical Outcome of Intracytoplasmic Sperm Injection in Infertile Men With Treated and Untreated Clinical Varicocele
Esteves, 18 ANDROFERT, Referral Center for Male Reproduction
Sperm Retrieval for ART
Normal sperm production
Mechanical blockage
Vasectomy, Post-infectious, Congenital
Sperm production deficient or absent
Cryptorchidism, Radiation, Chemotherapy, Trauma, Genetic, Orchitis, Varicocele, Gonadotoxins, Unexplained
Esteves, 19 ANDROFERT, Referral Center for Male Reproduction
Esteves, 20 ANDROFERT, Referral Center for Male Reproduction
http://androfert.com.br/videos
Esteves, 21 ANDROFERT, Referral Center for Male Reproduction
http://androfert.com.br/videos
http://androfert.com.br/videos
Esteves SC, Int Braz J Urol 2013
Esteves et al. Asian J Androl. 2013
Esteves, 23 ANDROFERT, Referral Center for Male Reproduction
Sperm Retrieval and ICSI in Azoospermia
41.4 47 43.3 20
100
64 61 34.2
Sperm retrieval (%) 2PN Fertilization (%) Top Quality Embryos (%)
Live Birth (%)
Non-obstructive Obstructive
OR=0.033 95% CI: 0.007-0.164; p<0.001
OR=0.38 95% CI: 0.23-0.61; p<0.001
P<0.01
Take-home Messages
Esteves, 24 ANDROFERT, Referral Center for Male Reproduction
Antioxidants helpful to decrease oxidative stress and DNA damage. Specific medical therapy only valid for hypogonadism.
Routine semen analysis not a good male fertility discriminator. Sperm DNA damage provides information of great prognostic value.
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..
Thank You