This literature review examines individualizing controlled ovarian stimulation (COS) protocols in IVF treatment. The goals of individualization are to maximize success rates, minimize ovarian hyperstimulation syndrome and cycle cancellations, and reduce costs. Individualization involves selecting the optimal stimulation protocol and gonadotropin starting dose based on a patient's ovarian reserve markers and previous response. Studies show individualized protocols using antagnoists for expected low and high responders can improve outcomes and reduce risks like OHSS. Models have been proposed to individualize gonadotropin doses based on one or several markers like AMH, AFC, age and FSH levels. Individualization may improve pregnancy rates and cost-effectiveness by reducing inappropriate responses

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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