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2. Ovulation Induction in The New Millennium hMG vs recombinant FSH
3. Introduction Multifollicular development with gonadotropin administration is still an integral component for ovarian stimulation in IVF / ICSI cycles
4. hMG Recombinant FSH hMG extracted from the urine of menopausal women has been used successfully for many years for ovarian stimulation
6. Recombinant Insulin & Factor VIII Significant medical benefits in clinical practice have never been convincingly demonstrated for biotech substitutes
Zwart-van Rijkom et al,2002
7.
In 1995 5.0 million
volume increased by <100%
In 2000 26.8million
Zwart-van Rijkom et al,2002
8. Why recFSH was welcomed The concept that LH is redundant and the wish for a more purified product drove the conversion from hMG to recFSH.
9. Good drug OR Super drug Claimed higher efficacy and bioactivity for recombinant FSH Out et al, 1995 Coelingh Bennink et al, 1997
10. LH supplementation: is it needed!! Lisi et al., 2001
Filicori et al, 2001
Westergaard et al., 2001
Tesarik and Mendoza, 2002
Commenges-Ducos et al, 2002
11. Role of Meta-analysis The most widely cited meta-analysis to compare recFSH vs urinary gonadotrophins has focused only on uFSH-P, uFSH-HP Daya& Gunby,1999
12. Objective To compare recombinant FSH to hMG regarding their clinical efficacy.
13. Efficacy Should be based upon most up to date evidence
RCTs are considered the gold standard
Power calculation is essential
14. Methodology Meta-analysis of:
Truly randomized controlled trials
IVF/ICSI cycles
15. Search Strategy MEDLINE
EMBASE
Cochrane MDSG Specialized Register
Hand searching
16. Primary outcome
Live Birth Rate
Per Woman (Cochrane handbook, version 8)
17. Analysis The results were combined for meta-analysis with RevMan software (using the Mantel-Haenszel method).
Results were pooled using a fixed-effects model only after confirming that heterogeneity was not present
18. Results Eight truly RCTs were included in this meta-analysis
Janssen 1998
Gordon 2001
Ng 2001
Strehler 2001
Westergaard 2001
Diedrich 2002
Kilani 2003
Balasch 2003
19. Excluded Trials Balasch et al, 1996 (rFSH vs combined rFSH & hMG)
Kornilov et al, 1999 (unclear data)
Serhal et al, 2000 (Quasirandomized trial)
Mahmoud et al, 2001 (rFSH vs combined rFSH & hMG)
Meo et al, 2002 ( retrospective study)
Commenges-Ducos et al, 2002 (rFSH vs combined rFSH & hMG)
Eskandar et al, 2004 ( not RCT)
20. Power The sample size of 2105 women is needed to test whether hMG is equivalent or even superior to recombinant FSH in an IVF/ET program.
The included trials enrolled 2031 participants
21. How to interpret the figures! A benefit from recombinant FSH would be displayed graphically to the left of the centre-line.
A benefit from hMG would be displayed graphically to the right of the centre-line
22. Live Birth / Ongoing Pregnancy rate
23. Clinical pregnancy rate / woman
24. Significant result with Long Protocol
25. NNT 23
26. How To Explain GnRH agonist down-regulation may result in profound suppression of LH concentration, impairing adequate oestradiol synthesis
Fleming et al, 2000
27. LH was shown to improve the implantation rate Gordon et al, 2001 Ganirelix dose-finding study ,1998 Schoolcraft et al, 1999
Identifying which women will require additional LH is costly and unreliable Diedrich et al, 2002
28. LH is needed The low endogenous LH concentrations achieved with GnRH agonists may amplify the differences in treatment outcomes seen with the use of hMG and recombinant FSH
29. Miscarriage Rate
30. Multiple pregnancy rate
31. OHSS
32. Economic View
33. Good drug OR Super drug!!! Claimed higher efficacy and bioactivity of the recombinant FSH
Out et al, 1995
Then reduction in amount of recombinant FSH is expected
34. Significant reduction in Amount of Gonadotrophin (IU)
35. Further Support Filicori et al, 2003 IUI cases
Lloyd et al, 2003 highly purified hMG
36. How to explain LH activity supplementation enhances FSH activity and optimizes FSH ovulation induction in women undergoing COH for ART procedures
37. Safety hMG enjoy a safety proven by 30 years of post marketing use, which is the real gold standard for the safety of a pharmaceutical product.
38. Take Home message
The use of hMG is the most cost effective option for ovulation induction in ART programs
39. Decision makers should establish their choice of one drug over the other based on the most up-to-date available evidence
40. Thank You