Clinical management of men with nonobstructive azoospermia - Role of IVF Laboratory

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

KUWAIT

CLINICAL MANAGEMENT OF MEN WITH NONOBSTRUCTIVE AZOOSPERMIA Lesson 5: Role of IVF Laboratory

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

• Minimal tissue excision • Mechanical mincing • Enzymatic tissue digestion •  Tubule measurement •  Laboratory environment • Sperm vitrification

Esteves & Varghese. J Hum Reprod Sci 2012; 5:233-43


ANDROFERT

Tissue removed (mg) Conventional TESE Micro-TESE P-value

65 ± 25 8.9 ± 2.5 <0.01 Conven'onal TESE Micro-‐TESE

Verza Jr & Esteves Fertil Steril 2011; Esteves & Varghese J Reprod Sci 2013

Micro-TESE more efficient than conventional TESE


ANDROFERT

Verza Jr & Esteves Fertil Steril 2011; Esteves & Varghese J Reprod Sci 2013

Seminiferous tubule diameter associated with presence of sperm

Verza Jr S, Esteves SC. Fer$l Steril 2012; 98: S242; Esteves & Varghese J Reprod Sci 2012; 5(3):233-‐43

Median 25%-75% 5%-95% Raw Data

yes No

Presence of Sperm

160

180

200

220

240

260

280

300

320

340

360

380

400

420

Ma

x. T

ub

ule

Dia

me

ter

N=54; Tubule Diameter: KW-H (1;54) = 25.2; P<0.001


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ANDROFERT

AIR-‐HANDLING VENTILATION SYSTEM (with carbon + KMnO4 filtra[on)


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ISO 5 Cleanroom IVF lab + VOC filtra[on


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0

50

100

before a7er

% TQE

0

20

40

before a7er

% miscarriage

0

50

before a7er

% LBR 2.3

3.2

Average No. Top Quality Embryos ET

Conven[onal lab Cleanroom lab

P=0.01

N=2,315


ANDROFERT

“Vitrifica[on” of few sperm in Cell Sleepers

2 μL microdroplet sperm freezing media + sperm washing media (1:1 ra'o)


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ANDROFERT

1. Sperm pick-‐up 2. Sperm load

3. Placing inner tray into outer vial

5. Storage

4. Vapor freezing

4-‐5cm above LN2 surface for 2 minutes (pre-‐calibrated minus 115-‐130oC, using a thermocouple, Cole-‐Parmer Instrument Company, USA)


ANDROFERT

3,412 cycles; Androfert

Individualized COS strategies to retrieve 10 to 15 oocytes per treatment cycle

0%

10%

20%

30%

40%

50%

60%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 20 25 Number of oocytes retrieved

Clinical pregnancy Live birth


ANDROFERT

47 43.3 64 61

2PN Fertilization (%) Top Quality Embryos (%)

Non-obstructive (N=365) Obstructive (N=146)

P<0.01


ANDROFERT

COS in cycles involving NOA •  Main goal: effec[veness •  Clinical quality indicator: number oocytes •  Protocol of choice: Antagonist + tailored recFSH dose according to pa[ent subgroup

cetrorelix (flexible); 150-‐300 IU/d pen injector >35yr and DOR: Antagonist + recFSH/recLH

cetrorelix (flexible); follitropin alfa + lutropin alfa 2:1 ra'o (1-‐2 vials/d); from s'mula'on D1


ANDROFERT

COS in poor responders involving NOA

•  Goal: minimum of 8 MII oocytes •  Strategy: Oocyte banking + fresh cycle and micro-‐TESE (day prior OPU)

-‐ Antagonist + recFSH/recLH (2:1 ra[o; 2 vials/d from Sd1) -‐ Minimal IVF s[mula[on

ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION

S ESTEVES, 17 2016

ANDROFERT

What about the health of resulting offspring

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


ANDROFERT

Region N Outcome analyzed Main findings

Palermo et al. 1999

USA 22 Congenital abnormalities

No difference with obstructive azoospermia 4.5% vs 1.3%

Vernaeve et al. 2005

Belgium 61 Perinatal data; Congenital

abnormalities

Lower gestational age (singletons); Increased frequency of premature twins;

No difference with OA (4% vs 3%)

Fedder et al 2007

Denmark 76 Congenital abnormalities

No difference with other infertility categories (0% vs 4.0%)

Belva et al.; 2011

Belgium 193 Perinatal data; Congenital

abnormalities

Similar perinatal outcomes; no difference 4.2% SF vs 5.2% OA (ns)

Esteves & Agarwal. Clinics 2013; 68 (Suppl.1): 141-50

Neonatal Outcome of Babies Born Health of offspring reassuring

but a call for continuous monitoring needed due to limited data and lack of long-term follow-up


ANDROFERT

Final Remarks 1.   Nonobstruc[ve azoospermia worst

prognos[c condi[on in male infer[lity 2.   Best management of NOA seeking

fer[lity includes proper diagnosis, interven[ons to op[mize sperm produc[on, microsurgical SR, state-‐of-‐art laboratory care & individualized COS

3.  Mul[disciplinary team work is key


ANDROFERT

Empirical treatments

Reproduc[ve Andrology Empowering clinical decisions & treatment efficiency

Conventional semen analysis

Conventional surgeries

Microsurgery

Genetic diagnosis

YCMD molecular diagnosis

ANDROFERT

Targeted therapy

Thank you

This presenta[on is available at hnp://www.slideshare.net/

sandroesteves

شكرا

Clinical management of men with nonobstructive azoospermia - Role of IVF Laboratory

Health & Medicine

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