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OVULARIAN STIMULATION  PROTOCOLS
Ovulation Induction ,[object Object],[object Object],[object Object],[object Object]
Ovulation Induction ,[object Object],[object Object],[object Object],[object Object]
Clomiphene Citrate ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Unexplained Infertility ,[object Object],[object Object]
Anovulatory cycles ,[object Object],[object Object]
hCG vs. LH monitoring   ,[object Object],[object Object],[object Object]
CC Resistant ,[object Object]
No ovulation: ,[object Object],[object Object],[object Object]
Tamoxifen ,[object Object],[object Object]
Combination therapies ,[object Object],[object Object]
So what do we use in Practice? Clomiphene Citrate Antagonists TI AIH hMG or FSH   ______________________________________________ hMG or FSH
Ovulation Induction ,[object Object],[object Object],[object Object],[object Object]
Your Aim should be  .. .. ,[object Object],[object Object],[object Object],[object Object],[object Object],BEST Most SUITABLE AVOID
IVF / ICSI cycles ,[object Object],[object Object],[object Object],[object Object]
IVF  ICSI Gonadotrophins   hMG, FSH, rec-FSH + GnRHa   - long -short -u-short Antagonists +GnRH  antagonist Always  LP++
Protocols for IVF  GnRH Antagonist Protocols GnRH  Agonist Protocols   225 IU per day (150 IU Europe) Individualized Dosing of FSH/HMG 250   g 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 OCP
Starting dose ,[object Object],[object Object]
GnRH-a protocols: ,[object Object],[object Object]
Short (flare up protocol): ,[object Object],[object Object]
Advantages of short protocol ,[object Object],[object Object],[object Object]
The protocol was criticized for being unphysiological, and increases the LH levels in the early stages of the follicular phase, which might be harmful to the growing follicles.
The long protocol ,[object Object],[object Object],[object Object]
Disadvantages of long protocol  ,[object Object],[object Object],[object Object],[object Object]
A meta analysis of 22 randomized trials comparing long and short protocols demonstrated the superiority of the long protocol of GnRH agonist regarding clinical pregnancy rate. (Daya 1999)
Ultra-short protocol ,[object Object],[object Object],[object Object]
Ultra-long protocol ,[object Object],[object Object],[object Object]
Protocols for poor responders ,[object Object],[object Object]
Type of  Gonadotropin / / / 3% glycoproteins 97% other proteins FSH 75 I.U LH 75 I.U. + detectable amounts of hCG
Recombinant FSH ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],Concerns  Price
Impact of high cost ,[object Object]
LH supplementation: is it needed!!  ,[object Object],[object Object],[object Object],[object Object],[object Object],Schats et al,2000 Balasch et al, 2001 Daya 2002 Balasch et al, 2003
Efficacy ,[object Object],[object Object]
Most important outcome   ,[object Object],[object Object],[object Object]
Effectiveness ,[object Object],[object Object],[object Object],[object Object]
Live Birth / Ongoing Pregnancy rate O.R.: 1.21 (95% CI 0.95-1.54)
Significant result with Long Protocol O.R.: 1.26 (95% CI 1.00-1.60)
NNT ,[object Object]
How to Explain!! ,[object Object]
How To Explain ,[object Object],[object Object]
Agonist vs antagonist
ongoing pregnancy/ live-birth rate   ,[object Object]
Pregnancy per woman O.R = 0.80, 95% CI = 0.69 to 0.92
[object Object],[object Object],[object Object],[object Object]
This means That ,[object Object]
Incidence of OHSS R.R. = 0.61, 95% CI = 0.42 to 0.89
No difference ,[object Object],[object Object]
In Favor of Antagonist ,[object Object],[object Object],[object Object]
The Future   ,[object Object]
(GnRH) antagonists  ,[object Object],[object Object],[object Object],[object Object],[object Object]
Luteal Phase Support ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Ovulation Induction ,[object Object],[object Object],[object Object],[object Object]
Complications of Ovulation Stimulation Drugs. OHSS Multiple Gestation
OHSS. ,[object Object],[object Object],[object Object],[object Object],[object Object]
Complications of Ovulation Stimulation Drugs. OHSS Prevention  of TI/IUI withhold  hCG use “coasting” use   Antagonist IVF
Complications of Ovulation Stimulation Drugs. ,[object Object],Multiple Gestation
Ovulation Induction ,[object Object],[object Object],[object Object],[object Object]
Reversed hMG/CC ,[object Object],[object Object]
Novel protocol 75 IU/HMG CD3 CD7 150 mg CC hCG IUI DF ≥ 18 mm 34-36h
Control group 75 IU/HMG CD3 hCG IUI DF ≥ 18 mm CD7 34-36h
Results (cont.) Variable HMG/CC (n=110) HMG (n=107) P value LH on day of  hCG (miu/ml) for cases with no premature LH surge 7.3 ± 1.8 7.8 ± 2.2 NS Number of Follicles ≥ 16 mm 2.4  ±  0.97 1.3 ± 1.1  P < 0.05 * Number of patients with premature LH surge  6 (5.45%) 17 (15.89%) P<0.001 * End. Thickness (mm) 5.9  ±  0.7 4.9  ±  1.9 NS Clinical Pregnancy 11 (10%) 9 (8.41%) NS
For whom ,[object Object],[object Object]
[object Object],[object Object]
Take Home Message ,[object Object],[object Object],[object Object],[object Object]
THANK YOU

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Ovarian Stimulation Protocols

  • 2.
  • 3.
  • 4.
  • 5.
  • 6.
  • 7.
  • 8.
  • 9.
  • 10.
  • 11.
  • 12. So what do we use in Practice? Clomiphene Citrate Antagonists TI AIH hMG or FSH ______________________________________________ hMG or FSH
  • 13.
  • 14.
  • 15.
  • 16. IVF ICSI Gonadotrophins hMG, FSH, rec-FSH + GnRHa - long -short -u-short Antagonists +GnRH antagonist Always LP++
  • 17. Protocols for IVF GnRH Antagonist Protocols GnRH Agonist Protocols 225 IU per day (150 IU Europe) Individualized Dosing of FSH/HMG 250  g 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 OCP
  • 18.
  • 19.
  • 20.
  • 21.
  • 22. The protocol was criticized for being unphysiological, and increases the LH levels in the early stages of the follicular phase, which might be harmful to the growing follicles.
  • 23.
  • 24.
  • 25. A meta analysis of 22 randomized trials comparing long and short protocols demonstrated the superiority of the long protocol of GnRH agonist regarding clinical pregnancy rate. (Daya 1999)
  • 26.
  • 27.
  • 28.
  • 29. Type of Gonadotropin / / / 3% glycoproteins 97% other proteins FSH 75 I.U LH 75 I.U. + detectable amounts of hCG
  • 30.
  • 31.
  • 32.
  • 33.
  • 34.
  • 35.
  • 36.
  • 37. Live Birth / Ongoing Pregnancy rate O.R.: 1.21 (95% CI 0.95-1.54)
  • 38. Significant result with Long Protocol O.R.: 1.26 (95% CI 1.00-1.60)
  • 39.
  • 40.
  • 41.
  • 43.
  • 44. Pregnancy per woman O.R = 0.80, 95% CI = 0.69 to 0.92
  • 45.
  • 46.
  • 47. Incidence of OHSS R.R. = 0.61, 95% CI = 0.42 to 0.89
  • 48.
  • 49.
  • 50.
  • 51.
  • 52.
  • 53.
  • 54. Complications of Ovulation Stimulation Drugs. OHSS Multiple Gestation
  • 55.
  • 56. Complications of Ovulation Stimulation Drugs. OHSS Prevention of TI/IUI withhold hCG use “coasting” use Antagonist IVF
  • 57.
  • 58.
  • 59.
  • 60. Novel protocol 75 IU/HMG CD3 CD7 150 mg CC hCG IUI DF ≥ 18 mm 34-36h
  • 61. Control group 75 IU/HMG CD3 hCG IUI DF ≥ 18 mm CD7 34-36h
  • 62. Results (cont.) Variable HMG/CC (n=110) HMG (n=107) P value LH on day of hCG (miu/ml) for cases with no premature LH surge 7.3 ± 1.8 7.8 ± 2.2 NS Number of Follicles ≥ 16 mm 2.4 ± 0.97 1.3 ± 1.1 P < 0.05 * Number of patients with premature LH surge 6 (5.45%) 17 (15.89%) P<0.001 * End. Thickness (mm) 5.9 ± 0.7 4.9 ± 1.9 NS Clinical Pregnancy 11 (10%) 9 (8.41%) NS
  • 63.
  • 64.
  • 65.

Editor's Notes

  1. HYPOTHALAMUS is a thumb-sized area in the base of the brain that controls many body functions and regulates the pituitary gland. PITUITARY GLAND is a finger-tip sized gland beneath the hypothalamus.
  2. 06/08/10
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