This document discusses individualization of controlled ovarian stimulation (iCOS) protocols. It conducted a literature review on iCOS and found 26 relevant articles. iCOS aims to tailor treatment for each woman's characteristics to maximize success and minimize risks like ovarian hyperstimulation syndrome. Protocol selection and gonadotropin starting dose selection are the two main aspects of iCOS. For protocol selection, markers like age and BMI can predict response and guide use of antagonist or agonist protocols. For dose selection, simple models use markers like antral follicle count and AMH, while complex models combine multiple factors. iCOS may reduce inappropriate responses, cancellations and risks, while improving outcomes and cost-effectiveness through personalized protocols.

1. Individualization of COS
Literature review
Aboubakr Elnashar
Benha university Hospital
Aboubakr Elnashar

2. Objective
Why?
What?
How?
Aboubakr Elnashar

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
Aboubakr Elnashar

6. What?
Selection of protocol
Selection starting dose of Gnt
Aboubakr Elnashar

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.
Aboubakr Elnashar

9. Extremely important.
Low Gnt dose: mono follicular
development, not desired in IVF
cycles.
 Excessive Gnt dose:
excessive ovarian response:
OHSS.
Aboubakr Elnashar

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.
Aboubakr Elnashar

12. Ovarian reserve testing before the first IVF cycle
categorize patients
(NICE, 2013).
High responseLow response
16 or more4 or lessTotal AFC
3.5 or more
25
0.8 or less
5.4
AMH
ng/ml
pmol/l
Conversion ratio:7
4 or less8.9 or moreFSH IU/L
Aboubakr Elnashar

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).
Aboubakr Elnashar

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).
Aboubakr Elnashar

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).
Aboubakr Elnashar

17. La marca et al, 2013 Aboubakr Elnashar

18. II. Individualization of Gnt
Starting Dose:
A. Simple models
One or 2 parameters
1. AMH
2. AFC and age
3. AFC
Aboubakr Elnashar

19. 1. AMH:
3 studies have been published reporting simple
models for gonadotrophin dose selection
Aboubakr Elnashar

20. A. Nelson et al.(2009)
Aboubakr Elnashar

21. B. Yates et al.(2011)
Aboubakr Elnashar

22. Aboubakr Elnashar

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

24. Aboubakr Elnashar

25. Aboubakr Elnashar

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

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
Aboubakr Elnashar

28. B. Complex models
> 2 parameters
Aboubakr Elnashar

29. 1. Popovic-Todorovic et al.(2003)
Aboubakr Elnashar

30. 2. Howles et al.(2006)
Age
BMI
AFC
D3 FSH
Aboubakr Elnashar

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
Aboubakr Elnashar

32. 4. Biasoni et al (2011)
Age
BMI
AFC
D3FSH
Aboubakr Elnashar

33. 5. Yovich et al, 2012
Age
BMI
Smoking
AFC
D2 FSH
AMH
Aboubakr Elnashar

34. Aboubakr Elnashar

35. 6. Oliveira et al (2012):
Ovarian Response Prediction Index (ORPI)=
AFCXAMH/Age
Aboubakr Elnashar

36. 7. La Marca et al.(2012)
Age
FSH
AMH
Aboubakr Elnashar

37. 8. La Marca et al.(2013)
Age
AFC
FSH
Aboubakr Elnashar

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

41. Thank you
Aboubakr elnashar
elnashar53@hotmail.comAboubakr Elnashar