• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
GnRH antagonists
 

GnRH antagonists

on

  • 4,565 views

safer drug with similar live birth rates

safer drug with similar live birth rates

Statistics

Views

Total Views
4,565
Views on SlideShare
4,552
Embed Views
13

Actions

Likes
2
Downloads
246
Comments
0

4 Embeds 13

http://ebwhs.com 7
http://www.ebwhs.com 3
http://www.linkedin.com 2
http://www.slashdocs.com 1

Accessibility

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment
  • 06/28/11
  • 06/28/11
  • 06/28/11
  • * *
  • * *
  • 06/28/11
  • IBSA Institut Biochimique SA 28/06/11

GnRH antagonists GnRH antagonists Presentation Transcript

  • kasr al ainy school of Medicine Cairo University CHANGING ATTITUDES IN OVARIAN STIMULATION
  • CHANGING ATTITUDE IS A FACT OF LIFE
    • To improve efficacy : better results: pregnancy
    • To improve safety : less complications: OHSS
  • THE BEST MODEL
    • Breech Trial
  • WHAT ABOUT GYNECOLOGY
    • HRT: WHI study
  • IVF
    • Safety comes first
  • 16 follicles 12 mature oocytes 14 oocytes Extras frozen if good 2 to 3 transferred 9 fertilize normally 5 divide normally 30-40% of couples 4 stop dividing & sperm Typical progression
  • OHSS is the most serious complication of ovulation induction.
  • PROTOCOLS FOR IVF GnRH Antagonist Protocols GnRH Agonist Protocols 225 IU per day (150 IU Europe ) Individualized Dosing of FSH/HMG 250 mg per day antagonist Individualized Dosing of FSH/HMG GnRHa 1.0 mg per day up to 21 days 0.5 mg per day of GnRHa 225 IU per day (150 IU Europe ) Day 6 of FSH/HMG Day of hCG Day 1 of FSH/HMG Day 6 of FSH/HMG Day of hCG 7 – 8 days after estimated ovulation Down regulation Day 2 or 3 of menses Day 1 FSH/HMG
  • SHOULD BE EVIDENCE BASED
    • RCT
    • Systematic Reviews
  • AL-INANY & ABOULGHAR, 2001
  • AL-INANY ET AL., 2006
    • O.R = 0.82, 95% CI = 0.68 to 0.97
  • AL-INANY ET AL., 2010
    • 45 RCTs
    • 7532 participants
    • Many subgroup analyses:
    • - Poor responders
    • - PCOS
    • - OCP pretreatment
    • - LH stability examined
    • - Cetrotide vs. ganerilix
    • - Fixed vs. flexible protocol
    • Conclusion differed
  • IT IS JUSTIFIED TO
    • Shift from GnRH agonist to GnRH antagonist for IVF/ ICSI cycles
  • WHY: (AL-INANY ET AL, 2010)
  • HOW TO EXPLAIN
    • OHSS is an uncommon complication
    • Uncommon complications need large number of participants to show if there is a real difference between two drugs
    • In our current situation: agonist vs. antagonist
    • OHSS in agonist group: 3.74% (84/3165)
    • OHSS in antagonist group: 1.91% (149/ 2252)
  • NUMBER NEEDED TO HARM
    • NNH= 25 (95%CI = 19 to 36)
    • This clinically means : for every 25 women underoing downregulation by Agonist , you may expect one more case of severe OHSS
  • CANCELLATION FOR RISK OF OHSS
  • CONSIDERING CYCLES CANCELLED FOR RISK OF OHSS
    • Then the difference will more statistically significant if cancellation was not done
    • This difference is highly significant both from statistical significance and clinical significance
    • So we may say confidently that GnRH antagonist is safer than GnRH agonist in IVF/ ICSI cycles
  • LIVE BIRTH RATE
  • CPR
  • MISCARRIAGE RATE
  • IN FAVOR OF ANTAGONIST
    • much shorter duration of GnRH analogue treatment (OR -20.90, 95% CI -22.20 to -19.60)
    • less days of stimulation (OR -1.54, 95% CI -2.42 to -0.66).
    • reduction in the amount of gonadotrophins (OR -4.27, 95% CI -10.19 to 1.65)
  • 3. 0 ampoules less with GnRH antagonists p<0.0 7 FSH requirement
  • 1. 1 less days with antagonists p<0.001 Duration of FSH treatment
  • HOW TO EXPLAIN IMPROVED EFFICACY
    • LH-instability incidence per woman randomised: defined as any fluctuation in LH-level, either a LH-surge or rise in LH-concentration as defined by the study protocol
  • LH STABILITY: AGONIST VS. ANATGONIST
  • FIXED DOSE PROTOCOL
  • Flexible antagonist stimulation
  • Meta-analysis of clinical pregnancy rate in fixed and flexible protocols for GnRH antagonist protocols Al-Inany et al. 2005
  • FURTHER ANALYSIS
    • LH instability is more reported in studies using flexible antagonist protocol
    • Al-Inany et al, 2005 showed fixed protocol achieve better results than flexible
    • Clinicians tend to use fixed protocol more now
    • Thus better LH stability
  • SO OUR CONCLUSION:
    • There are no significant differences in the efficacy of GnRH antagonist and long agonist protocols with a significant reduction in the incidence of severe OHSS with the antagonist.
  • BUT NOT ALL DOCTORS WOULD GO FOR ANTAGONIST
  • (GNRH) ANTAGONISTS: OFF LABEL INDICATION
    • unique Idea
    • Administration during GnRH agonist cycle
    • when follicle reach ~16mm and E2 level > 4000pmol
    • Decrease but Continue hMG (step down protocol)
    • Monitor by E2
    • Not more than 3 days
  • VALUE
    • allow continued stimulation while rapidly decreasing the E2 level to a range that is clinically acceptable.
  •  
  • OUR RESULTS Parameter Coasting (n = 96) Antagonist (n = 94) P-value Age (years) 30.0 ± 4.9 29.6 ± 4.6 NS Duration of infertility (years) 6.64 ± 4.45 7.07 ± 4.3 NS No. of HMG injections 30.52 ± 8.9 29.94 ± 8.8 NS Days of stimulation 1 9.1 ± 1.5 9.4 ± 1.5 NS Peak oestradiol (pg/ml) 5087 ± 1589 5305 ± 1680 NS Oestradiol on day of HCG (pg/ml) 2605 ± 790 2721 ± 699 NS Range of oestradiol on day of HCG (pg/ml) 1110–4136 1223–4093 NS Day of intervention 2.82 ± 0.97 1.74 ± 0.91 <0.0001 No. of oocytes 14.06 ± 5.20 16.5 ± 7.60 0.02 No. of MII oocytes 11.13 ± 4.60 13.14 ± 6.60 NS No. of fertilized oocytes   7.97 ± 3.80   9.14 ± 4.70 NS No. of high quality embryos   2.21 ± 1.10   2.87 ± 1.20 0.0001 No. of embryos transferred   2.83 ± 0.50   2.79 ± 0.40 NS No. of cryopreserved embryos   4.50 ± 3.93   5.77 ± 4.87 NS Clinical pregnancy (%) 46/96 (47.9) 52/94 (55.3) NS Multiple pregnancy (%) 15/46 (32.6) 17/52 (32.7) NS
  • THE FUTURE
    • Simplifying IVF procedure
    • ELONVA
  • JUST A QUESTION
    • Would u change ur protocol from agonist to antagonist??
  • SIMPLE, SHORTER SAFER
  • WHY CHANGING ATTITUDE
    • For Tomorrow Better
    • Health
  • THANK YOU Dr. Hesham Al-Inany MD, PhD e-mail : hesham@khosoba.com