Individualization of COS

Individualization of COS Literature review

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Objective

Why?

What?

How?

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A literature search was conducted in Pubmed

Key words: individualized, COS, COH, IVF

Total number of citations (dated 1985−2013)

n=63

Citation excluded after

screening titles and/or

abstract n=29

Full manuscript retrieved for detailed evaluation

n=34

Article excluded n=8

(reasons

case series, reports, letter)

Articles included for review of

evidence n=26

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Why?

Objectives of individualization Offer every single woman the best

treatment tailored to her unique

characteristics:

maximizing success

eliminating OHSS

minimizing cycle cancellation:

Reduced costs

Reduce dropping out from treatment

Improve patient compliance

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Individualization is difficult: 1. Vast number of drugs and choices for

COS e.g.

GnRH analogues

Gnt preparations

adjuvant therapies

2. lack of a clear EB approach for

different subgroups of patients

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What?

Selection of protocol

Selection starting dose of Gnt

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I. Selection of protocol: cCOS Repeated cycle

Outcome of previous cycles: If good: same protocol.

1st cycle:

a. Empirical:

based on either the clinician’s or a centre’s preference.

b. Clinical criteria:

Age, BMI, PCOS (Homburg and Insler, 2002; Arslan et al., 2005).

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II. Selection of Gnt starting

dose. {variability in ovarian reserve is

very wide} (Gougeon and Lefe`vre, 1983; Gougeon, 1998; Almog et al., 2011; La Marca et al., 2011a; Monget et al., 2012):

standard fixed dose of Gnt is not

suitable for all women.

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Extremely important.

Low Gnt dose: mono follicular

development, not desired in IVF

cycles.

Excessive Gnt dose:

excessive ovarian response:

OHSS.

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The prediction of a poor or hyper

response:

allows clinicians to give women

more information on possible

protracted treatment

cycle cancellation

OHSS

treatment burden

reduced success.

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How?

I. Individualization of

stimulation protocol

Correct prediction of ovarian

response (especially the

extremes: poor and hyper

response).

By most sensitive markers of

ovarian reserve.

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Ovarian reserve testing before the first IVF cycle

categorize patients (NICE, 2013).

High response Low response

16 or more 4 or less Total AFC

3.5 or more

25

0.8 or less

5.4

AMH

ng/ml

pmol/l

Conversion ratio:7

4 or less 8.9 or more FSH IU/L

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A. Expectant low responder: Antagonist protocol

1. No evidence of superiority of one approach

over another (Pu et al., 2011; Sunkara et al., 2013).

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2. Antagonist is associated with

Reduced discomfort and treatment burden (Nelson et al. ,2009)

Fewer days of Gnt stimulation (10 Vs 14 days)

(Pandian et al., 2010): improve patient compliance.

Lower Gnt consumption: lower cost

Drop in cycle cancellation

Prognosis remained poor, with CPR 16% with

GnRHan Vs 11% with the GnRHa (Nelson et al., 2009).

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B. Expectant high responders: Antagonists

Reduction of:

high response

OHSS

cycle cancellation {risk of OHSS} (Al-Inany et al., 2007, 2011; Hosseini et al., 2010; Lainas et al., 2010; Tehraninejad et al., 2010).

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GnRHan was superior to the

GnRHa regimen for the treatment of

high responders.

fewer days of stimulation (9 Vs 13

days)

elimination of the need for

cryopreservation of embryos due to

excess response

reduced hospitalization for OHSS

(13.9% Vs 0.0%)

significantly higher CPR (61.7 Vs

31.8%) (Nelson et al., 2009).

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La marca et al, 2013 Aboubakr Elnashar

II. Individualization of Gnt

Starting Dose: A. Simple models

One or 2 parameters 1. AMH

2. AFC and age

3. AFC

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1. AMH:

3 studies have been published reporting simple

models for gonadotrophin dose selection

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A. Nelson et al.(2009)

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B. Yates et al.(2011)

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C. Leao et al (2013)

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2. AFC and age (La Marca et al., 2013)

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3. AFC:

The OPTIMIST study:

optimisation of cost

effectiveness through

individualised FSH stimulation

dosages for IVF treatment.

RCT

van Tilborg et al., 2012 Aim: assess whether an iFSH

dose regime based on ORT is

more cost-effective than a

standard dose regime.

Ongoing

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B. Complex models

> 2 parameters

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1. Popovic-Todorovic et al.(2003)

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2. Howles et al.(2006)

Age

BMI

AFC

D3 FSH

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3. Olivennes et al.(2009). The CONSORT dosing algorithm individualizes FSH

doses , assigning 37.5 IU increments acc to:

Age

BMI

AFC.

D3 FSH

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4. Biasoni et al (2011)

Age

BMI

AFC

D3FSH

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5. Yovich et al, 2012

Age

BMI

Smoking AFC

D2 FSH

AMH

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6. Oliveira et al (2012): Ovarian Response Prediction Index (ORPI)=

AFCXAMH/Age

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7. La Marca et al.(2012)

Age

FSH

AMH

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8. La Marca et al.(2013)

Age

AFC

FSH

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Conclusions

It is now very clear that the ‘one size

fits all’ approach is not recommended.

Individualizing of Gnt starting dose is

extremely important

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Individualization, will lead to a

Reduction in:

inappropriate ovarian response

cycle cancellations

withdrawals from treatment

OHSS

Cycles with poor prospects for

success

Improvement in:

overall pregnancy rates

overall cost-effectiveness.

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iCOS is based on correct prediction of

ovarian response (especially the

extremes (poor and hyper response) by

most sensitive markers of ovarian

reserve (AFC and AMH) .

A clear definition for modality of a

correct application of iCOS is required to

optimize efficacy and daily clinical

management.

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Thank you

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elnashar53@hotmail.com Aboubakr Elnashar