male infertility for a generalist

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