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