Individualization of COS

1. Individualization of COS Literature review Aboubakr Elnashar Benha university Hospital
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2. Objective
Why?
What?
How?
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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
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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
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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).
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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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9. Extremely important.
Low Gnt dose: mono follicular development, not desired in IVF cycles.
 Excessive Gnt dose: excessive ovarian response: OHSS.
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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.
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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).
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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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17. La marca et al, 2013
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18. 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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19. 1. AMH:
3 studies have been published reporting simple models for gonadotrophin dose selection
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20. A. Nelson et al.(2009)
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21. B. Yates et al.(2011)
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22. Aboubakr Elnashar

23. C. Leao et al (2013)
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24. Aboubakr Elnashar

25. Aboubakr Elnashar

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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28. B. Complex models > 2 parameters
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29. 1. Popovic-Todorovic et al.(2003)
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30. 2. Howles et al.(2006) Age BMI AFC D3 FSH
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31. 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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32. 4. Biasoni et al (2011) Age BMI AFC D3FSH
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33. 5. Yovich et al, 2012 Age BMI Smoking AFC D2 FSH AMH
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34. Aboubakr Elnashar

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
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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.
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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.
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41. Thank you Aboubakr elnashar elnashar53@hotmail.com
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