Clinical management of men with nonobstructive azoospermia - Steps Before Sperm Retrieval

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

ANDROFERT

Interven'ons to infer'le males men with SF prior to a sperm retrieval a5empt


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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


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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


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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


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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)



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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


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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


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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


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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


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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


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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


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Key Messages – Day 3 Steps before Sperm Retrieval

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§  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


ANDROFERT

Thank you

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Clinical management of men with nonobstructive azoospermia - Steps Before Sperm Retrieval

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