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Individualization of COS
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Individualization of COS Literature review
Aboubakr Elnashar Benha university Hospital
Aboubakr Elnashar
Objective
Why?
What?
How?
Aboubakr Elnashar
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
Aboubakr Elnashar
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
Aboubakr Elnashar
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
Aboubakr Elnashar
What?
Selection of protocol
Selection starting dose of Gnt
Aboubakr Elnashar
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).
Aboubakr Elnashar
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.
Aboubakr Elnashar
Extremely important.
Low Gnt dose: mono follicular
development, not desired in IVF
cycles.
Excessive Gnt dose:
excessive ovarian response:
OHSS.
Aboubakr Elnashar
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.
Aboubakr Elnashar
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.
Aboubakr Elnashar
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).
Aboubakr Elnashar
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).
Aboubakr Elnashar
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).
Aboubakr Elnashar
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
Aboubakr Elnashar
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.
Aboubakr Elnashar
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.
Aboubakr Elnashar
