clinical management of men with nonobstructive azoospermia - azoospermia differential diagnosis

REPRODUCTIVE ANDROLOGY SURGERY WORKSHOP III 17-21 January 2016 – Reproductive Medicine Unit – Jahra Hospital

KUWAIT

CLINICAL MANAGEMENT OF MEN WITH NONOBSTRUCTIVE AZOOSPERMIA Lesson 1: Azoospermia Differential Diagnosis

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

Azoospermia: the complete lack of sperm in ejaculate a6er centrifuga8on

10-15% infertile males

1-3% male population

Cooper et al. Hum Reprod Update 2009; Esteves & Agarwal, Clinics 2013


ANDROFERT

Esteves et al Int Braz J Urol 2014; 40: 443-53

Goals of semen analysis are to reduce analytical error and enhance precision

Examination of pelleted semen Differentiation between ‘true’ azoospermia and cryptozoospermia

Minimum 2 analyses Transient azoospermia due to medical conditions and biological variability

Supernatant is discharged

Pellet is meticulously

examined

Centrifugation at 3,000g for 15

minutes


ANDROFERT

Prognosis and management differen8ally affected by type of azoospermia

Obstruc8ve

Non-‐obstruc8ve

Clinical picture

Normal testes & endocrine profile;

Mechanical blockage Normal

Spermatogenesis

Esteves et al, Clinics 2011


ANDROFERT

Sperm retrieval highly successful regardless of cause of obstruction and method of retrieval

Obstructive azoospermia is a favorable prognostic condition in male infertility

100% 96.6% 96.3%

CBAVD Vasectomy Post-‐infection

OBSTRUCTIVE AZOOSPERMIA

Management options include reconstructive surgery and ART

OA (N=146)

Esteves et al. J Urol. 2013;189: 232-7


ANDROFERT

ICSI outcome in obstructive azoospermia comparable with fertile donors

64 61 47

34 61 66

50 38

2PN Fertilization

(%)

High quality embryos (%)

Clinical pregnancy (%)

Live birth (%)

Obstructive azoospermia (N=146) Donor sperm (N=40) p=NS

Esteves et al. Asian J Androl 2014; 16: 602-6


ANDROFERT


Obstruc8ve

Non-‐obstruc8ve

Hypo-‐hypo

Spermatogenic failure

Clinical picture


Mechanical blockage

Disrupted

Normal

Spermatogenesis



ANDROFERT

•  Low FSH and LH levels (<1.2 mIU/L) •  Low total testosterone levels (<300 ng/dL) •  Hypotrophic testes

NOA due to hypogonadotropic hypogonadism

Congenital: Kallman syndrome Prader-Willi

Acquired: Pituitary tumor Steroid abuse Testosterone replacement therapy FraieTa et al. Clinics 68; 2013


ANDROFERT

Rec-‐hCG for male hypo-‐hypo

Esteves & Papanikolaou Fer5l Steril 2011;96:S230

Series of men with adult-‐onset HH; Recombinant hCG (Ovitrelle 250 mcg qw for 12 weeks)

Baseline Pos<reatment


ANDROFERT

Frequency of azoospermia among 2,383 patients attending an Infertility Clinic

Esteves et al. Clinics 2011; 66: 691-700.

Azoospermia 35%

61%

36%

3% Hypo-hypo

OA

SF


ANDROFERT


Obstruc8ve

Non-‐obstruc8ve

Hypo-‐hypo

Spermatogenic failure

Clinical picture

Testes: small or nl FSH/LH: ñ or nl TT: low or nL


Mechanical blockage

Small tes8s, poor viriliza8on

FSH/LH <1.2 mUI/mL, Low TT,

Disrupted

Normal

Spermatogenesis



ANDROFERT

Tes8cular torsion; trauma Post-‐inflammatory (eg. Mumps orchiBs) Exogenous factors (eg. Cytotoxic drugs, irradiaBon) Tes8cular cancer Systemic diseases (eg. Liver cirrhosis, renal failure)

Congenital Tes8cular dysgenesis/cryptorchidism Gene8c abnormali8es (Klinefelter syndrome, Yq microdeleBons, etc.)

Acquired

Idiopathic (unknown e8ology) Esteves et al. Clinics 2011; 66:691-‐700

NOA due to spermatogenic failure: an irreversible condi8on


ANDROFERT

Cryptorchidism, testicular trauma, torsion, infection, radio-/chemotherapy, congenital abnormalities, systemic diseases Small testes (<15 cc; long axis <4.6 cm) Flat epididymis, palpable vas Elevated FSH levels (>7.6 mIU/ml in 90% men) Low testosterone levels (<300 ng/dl in up to 50%)

Diagnostic parameters provide >90% prediction of whether azoospermia is due

to spermatogenic failure

Medical history

Physical examination

Endocrine profile

Esteves et al Clinics 2011


ANDROFERT

Verza Jr & Esteves, Atlas of Human Reproduction SBRH 2013

Isolated diagnostic biopsy rarely indicated provide no definitive proof of whether sperm will be

found; may jeopardize future retrieval attempts

Differential diagnosis NOA due to complete maturation arrest and obstructive azoospermia

Wet examination and cryopreservation if sperm found

Hypospermatogenesis

Maturation arrest

Sertoli cell-only


ANDROFERT

Key Messages – Day 1 Azoospermia Differential Diagnosis

§  Nonobstructive Azoospermia (Spermatogenic Failure) is the worst prognostic condition in male infertility

§  Should be differentiated from obstructive azoospermia and NOA due to hypo-hypo

§  Irreversible condition; often termed as “sterile” §  History may indicate primary testis pathology §  Usual clinical presentation: Azoospermia +

small testis + high FSH + low T ANDROFERTANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 16 2016

ANDROFERT

Thank you

This presenta8on is available at hTp://www.slideshare.net/

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clinical management of men with nonobstructive azoospermia - azoospermia differential diagnosis

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