3. 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
4. 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
5. 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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6. What?
Selection of protocol
Selection starting dose of Gnt
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7. 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
8. 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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10. 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
11. 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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12. 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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13. 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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14. 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
15. 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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16. 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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26. 2. AFC and age (La Marca et al., 2013)
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27. 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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35. 6. Oliveira et al (2012): Ovarian Response Prediction Index (ORPI)= AFCXAMH/Age
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36. 7. La Marca et al.(2012) Age FSH AMH
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37. 8. La Marca et al.(2013)
Age
AFC
FSH
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38. 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
39. 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
40. 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