sperm retreival: optimizing sperm retrieval and pregnancy in nonobstructive azoospermia

Optimizing Sperm Retrieval

Paul J. Turek M.D. Director, The Turek Clinic,

Beverly Hills and San Francisco, CA

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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

Test Answers

These can be tough cases!

Optimizing Sperm Retrieval

Patient Procedure Laboratory

Medical therapy Cryptozoospermia

TESA/TESE Microdissection FNA Mapping

Search time Sperm banking

Optimizing Sperm Retrieval

Patient Procedure Laboratory

Medical therapy Cryptozoospermia

• 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

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

Optimizing Sperm Retrieval

Patient Procedure Laboratory

Medical therapy Cryptozoospermia

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)

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

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

• 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

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?

Optimizing Sperm Retrieval

Patient Procedure Laboratory

Medical therapy Cryptozoospermia

TESA/TESE Microdissection FNA Mapping

Vasal (MVSA; PVSA)

Epididymal (MESA, PESA)

Testicular (TESA, TESE, Microdissection TESE)

Sperm Retrieval Sources

Ejaculate

Principle: Primum no nocere Least invasive, least damaging, best yield.

Turek et al. Ass Reprod Rev. 1999, 9: 60-64

Guiding Principle

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)

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

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.

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

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

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

Sperm in NOA are Like Apples on a Tree

Some branches have them, and some don’t

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

FNA Sites/Testicle

Sperm Detection

Rate

Beliveau and Turek. Asian J Androl 13; 225, 2011

Where Are We With Sperm Detection?

Microdissection FNA Mapping

NOA Strategies

Courtesy: Netter Images

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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1 2 3

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2019

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1 2 3

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2019

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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

Testis sperm aspiration (TESA)

Testis sperm extraction (TESE)

Testis microdissection (MicroTESE)

Least Invasive Most invasive

Not all sperm retrieval procedures are the same

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

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

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%

Optimizing Sperm Retrieval

Patient Procedure Laboratory

Medical therapy Cryptozoospermia

TESA/TESE Microdissection FNA Mapping

Search time Sperm banking

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

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

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.