The document discusses optimizing sperm retrieval techniques for men with nonobstructive azoospermia, focusing on medical therapy, sperm search strategies, and laboratory methods. It highlights various research findings on sperm retrieval success rates, the effectiveness of different techniques like microdissection and FNA mapping, and the importance of adapting approaches to individual patient needs. The overarching goal is to maximize the chances of successful sperm retrieval for IVF purposes while minimizing invasiveness and preserving testosterone levels.

1. Optimizing Sperm Retrieval
Paul J. Turek M.D.
Director, The Turek Clinic,
Beverly Hills and San Francisco, CA
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2. Optimizing Sperm Retrieval
Learning Objectives
• Describe the role of medical therapy before sperm retrieval
• Delineate two strategies currently used to find and retrieve
testicular sperm in nonobstructive azoospermia
• Explain how sperm search can be optimized in the andrology
laboratory

3. Test Answers
These can be tough cases!

4. Optimizing Sperm Retrieval
Patient Procedure Laboratory
Medical therapy
Cryptozoospermia
TESA/TESE
Microdissection
FNA Mapping
Search time
Sperm banking

5. Optimizing Sperm Retrieval
Patient Procedure Laboratory
Medical therapy
Cryptozoospermia

6. • N=42
azoospermic
men
treated
with
clomid:
64%
ejaculated
sperm!
Hussein
et
al
J.
Androl.
26:
787,
2005
Medical Therapy May Help
Shiraishi
et
al,
Hum
Reprod.
2012,
27:331-­‐9
N=48 failed mTESE
No Rx
+ Rx

8. Raman and Schlegel. J Urol. 2002 167:124
Medical Therapy May Help
Motile ejaculated sperm
after varicocelectomy
N=233
Overall success=39%
Weedin et al. J Urol. 2010, 183; 2309

9. Optimizing Sperm Retrieval
Patient Procedure Laboratory
Medical therapy
Cryptozoospermia

10. Strategies-Cryptozoospermia
The Centrifuged Pellet
Jaffe et al. J Urol. 1998; 159: 1548-50
TYPE # Pts % Sperm Variability
Obstructive 70 18.6% 41%
Non obstructive 70 22.8% 12%
(NS, n=17/group)
(600-1000 x g for 15 minutes)

11. Cryptozoospermia
Reliable ejaculated sperm?
No
IVF-ICSI
Bank Ejaculated Sperm
Yes
FNA Map
(1-3 mos)
MicroTESE
(<1 mos)
Treat/
Improve(3-6
mos)
Testis Testis/Ejaculate Ejaculate
Ejaculate
The Turek Clinic
Approach

12. 2010-2012
N=40 men with
cryptozoospermia
Mean age=38 years
No sperm
Nonmotile
Motile
Motile and
nonmotile
10%
25%
60%
5%
Hagerty et al, 2012
• 85% of men able to
bank sperm
• 40% sample-to-
sample
variability
“Epidemiology” of
Cryptozoospermia

13. • 2010-2012
• N=40 men with
cryptozoospermia
• To date, 13/40 couples to IVF-ICSI
• Sperm source:
Fresh
Ejaculate
77%
Thawed
Ejaculate
8%
mTESE
15%
• Mean partner age 32 (27, 41)yr
• 60% 2PN rate
• 46% (6/13) ongoing preg. rate
Hagerty et al, 2012
“Epidemiology” of
Cryptozoospermia

14. Sperm Source and ICSI Fertilization
NOA-Testis sperm
NOA-Cryptozoospermia
X
X
What kind of performance differences do we expect
between cryptozoospermic and testicular sperm?

15. Optimizing Sperm Retrieval
Patient Procedure Laboratory
Medical therapy
Cryptozoospermia
TESA/TESE
Microdissection
FNA Mapping

16. Vasal (MVSA; PVSA)
Epididymal (MESA, PESA)
Testicular (TESA, TESE,
Microdissection TESE)
Sperm Retrieval Sources
Ejaculate

17. Principle: Primum no nocere
Least invasive, least damaging, best yield.
Turek et al. Ass Reprod Rev. 1999, 9: 60-64
Guiding Principle

18. Epididymal Sperm: Evidence-Based Guidelines
Nicopoullos et al. Fert Steril. 2004, 82: 691-701
Donoso, Tournaye, Devroey. Hum Reprod Upd. 2007, 13: 539-549
Van Peperstraten et al. Cochrane Database Syst Rev. 2006, 3:CD 002807
• For epididymal vs. testicular sperm in obstructive
azoospermia:
Insufficient evidence to detect a difference in
outcome.
• For fresh vs. frozen thawed epididymal sperm:
There is no difference in clinical outcome (FR,
OPR)

19. Testicular Sperm: Evidence-Based Guidelines
Donoso, Tournaye, Devroey. Hum Reprod Upd. 2007, 13: 539-549
Obstructive vs. Nonobstructive Azoospermia
Meta-analysis of 1103 cycles, non-randomized studies
Obstructive vs Nonobstructive
RR (CI)
2PN fertilization 1.18 (1.13-1.23)
Clinical pregnancy rate 1.36 (1.1-1.69)
Ongoing preg. rate 1.19 (0.87-1.61)
Implantation rate 1.01 (.87-1.61)
Miscarriage rate 0.84 (.48-1.48)
Fixed model
Nicopoullos et al. Fert Steril. 2004, 82: 691-701

20. Testis Sperm: Evidence-Based Guidelines
Donoso, Tournaye, Devroey. Hum Reprod Upd. 2007, 13: 539-549
Van Peperstraten et al. Cochrane Database Syst Rev. 2006, 3:CD 002807
Nicopoullos et al. Fert Steril. 2004, 82: 691-701
• For obstructive vs. nonobstructive azoospermia:
Insufficient evidence to recommend one
sperm retrieval technique over another.
• Sperm retrieval in cases of nonobstructive azoospermia
Can be very difficult due to “patchy” or “focal”
nature of production.
• In cases of nonobstructive azoospermia:
There is no relationship between the sperm
technique chosen and ICSI outcomes.

21. What About “Delayed Fresh” Sperm Retrieval?
Morris et al. J Urol. 2007, 178:2087-91
0%
5%
10%
15%
20%
25%
Initial 24 hours 48 hours
OA (n=51)
NOA (n=44)
Time After Sperm Retrieval
% Motility
Testis sperm motility

22. Study of Motility and Viability of Aspirated Sperm
Bachtell et al. Hum Reprod. 1999, 14:101
Motility *Viability
Fresh Thawed Fresh Thawed
Testis, NOA 5% 0.2% 86% 46%
Epididymis, OA 22% 7% 57% 24%
Vas deferens, fertile 71% 38% 91% 51%
*Vital Stains: carboxyfluorescein, 0.08mg/mL;
propidium iodide, 20mg/mL

23. Testicular Sperm: Evidence-Based Guidelines
Donoso, Tournaye, Devroey. Hum Reprod Upd. 2007, 13: 539-549
Van Peperstraten et al. Cochrane Database Syst Rev. 2006, 3:CD 002807
Nicopoullos et al. Fert Steril. 2004, 82: 691-701
• For fresh vs. frozen testicular sperm:
RR (CI)
Fertilization rate ND
Implantation rate 1.75 (1.1-2.8)
Clinical pregnancy rate ND
Ongoing pregnancy rate ND

24. Sperm in NOA are Like Apples on a Tree
Some branches have them, and some don’t

25. Cryptorchidism 52-74%
Varicocele 63%
Epididymitis 67%
Mumps 67%
Torsion >50%
Post-chemotherapy 55-75%
Genetic AZF a, b 0-low%
Genetic AZF c 70%
Idiopathic 50-60%
Chance of Finding Sperm by NOA Diagnosis
Shefi and Turek, RBM Online, 2009
Raman and Schlegel. J Urol.170:1287, 2003
Hopps et al. Hum Reprod. 180:1660, 2003
Damani et al. JCO. 15: 930, 2002

26. FNA Sites/Testicle
Sperm
Detection
Rate
Beliveau and Turek. Asian J Androl 13; 225, 2011
Where Are We With Sperm Detection?

27. MicrodissectionFNA Mapping
NOA Strategies
Courtesy: Netter Images

28. How is FNA Mapping Different from Microdissection?
Office FNA Map
Sperm Found?
Yes No
IVF/ICSI
"Directed" TESE
Donor Sperm
Adoption
FNA Mapping
Microdissection
TESE in OR
Sperm Found?
IVF/ICSI
Yes No
Donor Sperm
Adoption
+/- Pregn
Microdissection

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Turek et al.
ASRM 2004
FNA Map
Sperm Present (n=83)
TESE
(n=29)
MicroTESE
(n=16)
IVF-ICSI
(n=83 procedures)
<2 sites
sperm/map
Success
81%
Success
90%
TESA
(n=38)
Most FNA
sites/map
Success
98%
Map
“Directed”
TESE
>2 sites
sperm/map

30. Testis sperm
aspiration
(TESA)
Testis sperm
extraction
(TESE)
Testis
microdissection
(MicroTESE)
Least Invasive Most invasive
Not all sperm retrieval procedures are the same

31. IVF-ICSI
Bank Ejaculated Sperm
FNA Map
(1-3 mos)
MicroTESE
(<1 mos)
Treat/
Improve(3-6
mos)
Sperm Retrieval
Ejaculate
The Turek Clinic Approach
Nonobstructive Azoospermia

32. 0
20
40
60
80
100
120
100%
53%
92%
% Successful
Retrieval
mTESE
MAP +
mTESE
MAP +
TESA/E
How FNA Mapping Helps Sperm Retrieval
(N=96 cases; 12 months, 2013-2014)
49%
TESA/E
51%
mTESE

33. 19%
14%
% Bilateral
Procedures
FNA Mapping & Sperm Retrieval: Bilateral Cases
(N=96 cases; 12 months)
0
10
20
30
40
50
60
70
80
90
mTESE
MAP +
mTESE
MAP +
TESA/E
84%

34. Optimizing Sperm Retrieval
Patient Procedure Laboratory
Medical therapy
Cryptozoospermia
TESA/TESE
Microdissection
FNA Mapping
Search time
Sperm banking

35. Laboratory Effort in Sperm Retrieval Cases
Turek PJ. Sperm Retrieval Techniques. In: The Practice of Reproductive
Endocrinology and Infertility: The Practical Clinic and Laboratory. Ed. D.
Carrell. 2010.
Procedure MESA TESA TESE MicroTESE
Man-hrs 1hr 1-2hrs 2-4 hrs 4-6 hrs
needed

36. Single sperm cryopreservation on cryoloops: an
alternative to hamster zona for cryopreservation of
individual spermatozoa
Nina Desai, Heather Blackmon, James Goldfarb.
Fertil Steril, Vol 80, Suppl. 3, 2003, pp, 55-56

37. Optimizing Sperm Retrieval
Summary
• Patients really only want one sperm retrieval.
• They like their testosterone levels where they are.
• You have one good shot at them.
• So, optimize medical therapy, surgical technique
and laboratory variables for each case.