clinical management of men with nonobstructive azoospermia - steps before sperm retrieval
TRANSCRIPT
REPRODUCTIVE ANDROLOGY SURGERY WORKSHOP III 17-21 January 2016 – Reproductive Medicine Unit – Jahra Hospital
KUWAIT
CLINICAL MANAGEMENT OF MEN WITH NONOBSTRUCTIVE AZOOSPERMIA Lesson 3: Steps Before Sperm Retrieval
Dr Sandro ESTEVES Medical and Scientific Director ANDROFERT - Andrology & Human Reproduction Clinic Campinas, Brazil
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 2 2016
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Interven'ons to infer'le males men with SF prior to a sperm retrieval a5empt
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 3 2016
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Medica'on Hypogonadism (TT<300 ng/dl) in up to 50% men with SF High ITT levels essen-al for regula-ng spermatogenesis in combina-on with Sertoli cell s-mula-on by FSH
Paradoxically weak s'mula'on of Leydig and Sertoli cells by endogenous gonadotropins Due to high baseline FSH and LH levels the rela-ve amplitudes are low
Shiraishi et al Hum Reprod 2012;27:331-‐9; Sussman et al Urol Clin N Am 2008;35:147-‐55
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 4 2016
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Study Study design Study group Medication Findings
Pavlovich et al. 2001 Case series 43 men with
T/E ratio <10 Testolactone No effect
Hussein et al. 2005
Prospective cohort
42 men with favorable hystology
Clomiphene Sperm found in SA in 64.3%; All men
who remained azoospermic had success at SR
Selman et al. 2006
Prospective cohort
49 men with maturation
arrest rec-hFSH and hCG No return of sperm in ejaculate;
posttreatment SRR were 21.4%
Ramasamy et al. 2009 Case series
56 men with nonmosaic Klinefelter
Testolactone or anastrozole, alone or combined with hCG SRR increased by 1.4-fold
Reifsnyder et al. 2012
Retrospective cohort
307 men with hypogonadis
m
Aromatase inhibitors, hCG or Clomiphene, alone or
combined No effect
Shiraishi et al. 2012
Prospective cohort
28 men with idiopathic SF
hCG alone or combined with rec-hFSH
SR success in 21% of the treated men vs. none in untreated men
Hussein et al. 2013
Prospective cohort
612 unselected
men
Clomiphene alone or combined with hCG or hMG
Sperm found in SA in 10.9% of treated males; SRR higher in men who
remained azoospermic and treated (57.0 vs. 33.6%, p<0.001)
!
Aromatase inhibitors and gonadotropins have been used with variable results
Esteves Asian J Androl 2015;17:1-‐12
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 5 2016
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ITT levels increase aVer hCG; s'mulatory effect on residual spermatogenic areas
Shinjo E et al Andrology 2013;1:929-‐35; Shiraishi et al Hum Reprod 2012;27:331-‐9
273
1348
Before After
ITT (ng/dl)
ITT levels increased aVer hCG-‐based therapy
Spermatogonial DNA synthesis increased
PCNA expression
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 6 2016
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Testosterone and estradiol levels
<300 ng/dL
(10.4 nmol/L)
Hypogonadism category
Pure
Medica'on algorithm at Androfert Tx aimed at boos'ng T
Aromatase inhibitor (anastrozole 1mg orally
qid)
Rec-‐hCG (250 mcg SC qw); rec-‐FSH added (75 IU SC biw) if FSH levels <1.5 mIU/ml
T/E ra'o <10
Aromatase hyperac'vity
T/E ra'o >10 (nl)
Esteves Asian J Androl 2015;17:1-‐12
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 7 2016
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1Shiraishi et al Hum Reprod 2012;27:331-‐9; Esteves Int Braz J Urol 2013;39:440
Medical therapy may increase SR success in men with SF
Microdissec'on TESE Rescue ~15% of pa'ents with previous failed SR a5empts1
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 8 2016
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Esteves Asian J Androl 2015;17:1-‐12
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 9 2016
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Varicocele associated with impaired spermatogenesis
Proposed mechanisms
include heat-mediated stress and ischemia
Spermatogonia B, pachytene spermatocytes and early spermatids highly vulnerable to heat stress
Agarwal, Hamada & Esteves Nature Rev Urol 2012; 9: 678-90
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 10 2016
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Rationale for varicocele repair Catch-up testicular growth among
adolescents following varicocele repair
Improvement in sperm parameters after varicocele repair
Abnormally-low T restored to normal levels in some men after varicocele repair
Wang et al Fertil Steril 1991; 55: 152-5; Su et al J Urol 1995; 154: 1752-5; Çayan et al J Urol 2002; 168: 929731-4; Hamada et al Nat Rev Urol 2013; 10: 26-37
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 11 2016
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Among 233 men with SF and clinical varicocele, about 1/3 had motile sperm in
postoperative ejaculate
Weedin et al J Urol 2010; 183: 2309-15
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 12 2016
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Matura'on arrest and hypospermatogenesis favorable prognosis
Weedin et al J Urol 2010;183:2309-‐15
Among 233 men with SF and treated varicocele, 1/3 had mo'le sperm in postop.
ejaculate
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 13 2016
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Inci et al J Urol 2009; 182: 1500-5; Haydardedeoglu et al Urology 2010; 75:83-6
§ Inci 2009 OR: 2.63; 95% CI: 1.05-6.60; p=0.03)
Although 2/3 remain azoospermic after varicocele repair, sperm retrieval success
increased in treated individuals
§ Haydardedeoglu 2010
53 30
Treated (N=66)
Untreated (N=30)
SR success (%)
61 38
Treated (N=31)
Untreated (N=65)
p<0.01
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 14 2016
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Key Messages – Day 3 Steps before Sperm Retrieval
ANDROFERT
§ Medication to boost endogenous T production seems beneficial to improve spermatogenesis, particularly in men with low T levels and low T/E ratio
§ Repair of clinical varicocele should be considered in ICSI candidates before SR
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 15 2016
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