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Stimulation Protocols
Prof Dr. Mohammed Hussein
Oral medications:
• Clomiphene citrate (clomide)
• Tamoxifene (Nolvadex)
• Cyclophenil
• Aromatase inhibitors
( Femara)
Intact
hypothalamic
pituitary ovarian
axis
Dose:( Clomid )
• 50- 150 mg/day
• 5-7 days
• Days 2-5 of the cycle.
Adjuvant drugs:
• Metformin
• Acetyl cysteine
• Oestrogen
• hMG
Advantages:
• cheap
• rare side effects & complications:
blurring of vision
OHSS
Multiple pregnancy
Disadvantages:
• Cervical mucous
• Endometrium
• No. of follicles
Injections:
Urinary:
hMG
uFSH
Both have LH activity
IM or subcutaneous depending on degree of
purification.
75 IU- 150 IU/ amp.
Recombinant:
• rFSH
• No LH activity
• Subcutaneous
• 75,100,150 IU/amp
Ovaries with good ovarian reserve
• FSH & E2 cycle day 3
• AFC antral follicle count cycle day 3
• AMH any day
• Ovarian volume
Regimens
No Down Regulation
• Start day 2-3 of the cycle
• Dose: 75-300 IU/day depending on:
Ovarian reserve
Age
Previous response
PCOs
Monitor by:
• TVUS
• Serum E2
Usually
• 8-10 days
• one or more follicle >17 mm
• hCG 10,000 IU
Luteal support:
• No need.
• Or micronized progesterone.
Down regulation:
• COH for ART: IUI, IVF, ICSI
• Benefits:
– Prevent premature LH surge.
– Better quality of oocytes.
– Scheduled oocyte pickup.
• Starts at least 5 days before expected date of
menses.( Long Luteal )
• 1st day of menses.( Long Follicular )
• Long acting GnRh agonist
• Short acting GnRh agonist daily dose till hCG day.
Down regulation:
• E2<50 pg/ml
• Dose: 225-300 IU/day
• Monitor with TVUS & serum E2
• Adjust the dose: ↑or ↓ after 4- 5 days.
• 3 follicles or more > 17 mm
• Stop agonist
• hCG 10,000 IU
• OPU 34-36 hours after hCG
• IUI 36-48 hours after hCG.
• Luteal Support
OOCYTE RETREIVAL
0
10
20
30
40
50
1 4 7 10 13 16 19 22 26
FSH,LH
Days
P
LH
FSH
E2
Selection
Dominance
Ovulation
Corpus Luteum
Recruitment
E2,P
Long protocol:
Stimulation day 6
tripple line endometrium 7 mm
Long protocol:
Stimulation: day hCG
tripple line endometrium 9 mm
Long protocol:
Stimulation: day hCG
early secretory endometrium
Long luteal protocol
Antagonist protocol:
• Start hMG on day 3 of menses.
• Antagonist when follicle reach 14-15 mm
– Long acting ( single injection )
– Short acting (Daily usually 3-4 injections).
• hCG 10,000 when 3 or more follicles > 17mm
• OPU 34-36 hours
• Luteal Support
Antagonist protocol
Short Protocol( Flare up )
• Agonist 2nd day
• hMG 3rd day
• Usually 9 – 10 days
• 3 0r more follicles > 17 mm
• hCG 10,000
• Luteal Support.
Short ( flare up ) protocol
Poor Responders
• 3 or less follicles
• What to do?
1- short protocol (flare up protocol)
2- Antagonist protocol.
3- No down regulation
4- COCpills + short protocol
5- Comiphene citrate
Protocol for poor responders
4- Adjuvant treatment:
• Growth hormone
• Combined oral contraceptive pills
• Clomiphene citrate.
Ovarian HyperStimulation
Syndrome:
• Pridection
History
PCOS
High AMH
During monitoring:
–E2 > 4000 pg/ml
–No of follicles.
What to do:
–Soft protocols.
–Coasting
–Metformine
–Cabergolin
–Antagonists
–Cancellation (no hCG)
–No ET
• Ultra short, highly economic and effective
protocol for ICSI patients.
• El Deeb M.W, Sami S, Sallam A, Ismail E,
Mohsen E, Darwish Y, El Sharaki A.
• INTEGRATED FERTILITY CENTER,
ALEXANDRIA, EGYPT.
• Keeping things simple without altering success rate
of ICSI is the idea behind our novel protocol. This
simple protocol aims to reduce the burden of ICSI
procedures and its related complications, thereby
giving a couple the chances to conceive using
procedures less costly in terms of physical,
emotional, social and financial costs. We had 65
cases underwent ICSI, their age ranges from (23-47)
years. Clomiphene citrate (CC ),3 tablets daily
started from the second day of the cycle for 5 days,
In the last day of CC administration HMG was
given in the form of 2 amps of Menegon 75
(Ferring) or Merional 75 (Ibsa) + 2 amps of Gonal F
75 ( Merck Serono) , till we reach one or more
follicles > 16 mm. E2 is measured. Next day early
morning one amp. Of Cetroide 0.25 mg. and the full
HMG dose was received… HCG 10,000 was
administrated when one or more follicles > 18 m.m
as usual.
• Average number of oocytes retrieved
ranges from (2-25) oocytes, number of
embryos transferred (ET) ranges from (1-
5) embryos, only one case had no ET. We
had 25 pregnant cases 38.4 % five of them
had blastocyst transfer. These
encouraging results of this highly
economic protocol should be put in
consideration as a simple and successful
ICSI protocol.
Thanks for your attention

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Stimulation Protocols

  • 2.
  • 3.
  • 4.
  • 5. Oral medications: • Clomiphene citrate (clomide) • Tamoxifene (Nolvadex) • Cyclophenil • Aromatase inhibitors ( Femara)
  • 7. Dose:( Clomid ) • 50- 150 mg/day • 5-7 days • Days 2-5 of the cycle.
  • 8. Adjuvant drugs: • Metformin • Acetyl cysteine • Oestrogen • hMG
  • 9. Advantages: • cheap • rare side effects & complications: blurring of vision OHSS Multiple pregnancy
  • 10. Disadvantages: • Cervical mucous • Endometrium • No. of follicles
  • 11. Injections: Urinary: hMG uFSH Both have LH activity IM or subcutaneous depending on degree of purification. 75 IU- 150 IU/ amp.
  • 12. Recombinant: • rFSH • No LH activity • Subcutaneous • 75,100,150 IU/amp
  • 13. Ovaries with good ovarian reserve • FSH & E2 cycle day 3 • AFC antral follicle count cycle day 3 • AMH any day • Ovarian volume
  • 15. No Down Regulation • Start day 2-3 of the cycle • Dose: 75-300 IU/day depending on: Ovarian reserve Age Previous response PCOs
  • 16. Monitor by: • TVUS • Serum E2 Usually • 8-10 days • one or more follicle >17 mm • hCG 10,000 IU Luteal support: • No need. • Or micronized progesterone.
  • 17. Down regulation: • COH for ART: IUI, IVF, ICSI • Benefits: – Prevent premature LH surge. – Better quality of oocytes. – Scheduled oocyte pickup. • Starts at least 5 days before expected date of menses.( Long Luteal ) • 1st day of menses.( Long Follicular ) • Long acting GnRh agonist • Short acting GnRh agonist daily dose till hCG day.
  • 18. Down regulation: • E2<50 pg/ml • Dose: 225-300 IU/day • Monitor with TVUS & serum E2 • Adjust the dose: ↑or ↓ after 4- 5 days. • 3 follicles or more > 17 mm • Stop agonist • hCG 10,000 IU • OPU 34-36 hours after hCG • IUI 36-48 hours after hCG. • Luteal Support
  • 19.
  • 21. 0 10 20 30 40 50 1 4 7 10 13 16 19 22 26 FSH,LH Days P LH FSH E2 Selection Dominance Ovulation Corpus Luteum Recruitment E2,P
  • 22. Long protocol: Stimulation day 6 tripple line endometrium 7 mm
  • 23. Long protocol: Stimulation: day hCG tripple line endometrium 9 mm
  • 24. Long protocol: Stimulation: day hCG early secretory endometrium
  • 26. Antagonist protocol: • Start hMG on day 3 of menses. • Antagonist when follicle reach 14-15 mm – Long acting ( single injection ) – Short acting (Daily usually 3-4 injections). • hCG 10,000 when 3 or more follicles > 17mm • OPU 34-36 hours • Luteal Support
  • 28. Short Protocol( Flare up ) • Agonist 2nd day • hMG 3rd day • Usually 9 – 10 days • 3 0r more follicles > 17 mm • hCG 10,000 • Luteal Support.
  • 29. Short ( flare up ) protocol
  • 30. Poor Responders • 3 or less follicles • What to do? 1- short protocol (flare up protocol) 2- Antagonist protocol. 3- No down regulation 4- COCpills + short protocol 5- Comiphene citrate
  • 31. Protocol for poor responders
  • 32. 4- Adjuvant treatment: • Growth hormone • Combined oral contraceptive pills • Clomiphene citrate.
  • 34. During monitoring: –E2 > 4000 pg/ml –No of follicles.
  • 35. What to do: –Soft protocols. –Coasting –Metformine –Cabergolin –Antagonists –Cancellation (no hCG) –No ET
  • 36. • Ultra short, highly economic and effective protocol for ICSI patients. • El Deeb M.W, Sami S, Sallam A, Ismail E, Mohsen E, Darwish Y, El Sharaki A. • INTEGRATED FERTILITY CENTER, ALEXANDRIA, EGYPT.
  • 37. • Keeping things simple without altering success rate of ICSI is the idea behind our novel protocol. This simple protocol aims to reduce the burden of ICSI procedures and its related complications, thereby giving a couple the chances to conceive using procedures less costly in terms of physical, emotional, social and financial costs. We had 65 cases underwent ICSI, their age ranges from (23-47) years. Clomiphene citrate (CC ),3 tablets daily started from the second day of the cycle for 5 days, In the last day of CC administration HMG was given in the form of 2 amps of Menegon 75 (Ferring) or Merional 75 (Ibsa) + 2 amps of Gonal F 75 ( Merck Serono) , till we reach one or more follicles > 16 mm. E2 is measured. Next day early morning one amp. Of Cetroide 0.25 mg. and the full HMG dose was received… HCG 10,000 was administrated when one or more follicles > 18 m.m as usual.
  • 38. • Average number of oocytes retrieved ranges from (2-25) oocytes, number of embryos transferred (ET) ranges from (1- 5) embryos, only one case had no ET. We had 25 pregnant cases 38.4 % five of them had blastocyst transfer. These encouraging results of this highly economic protocol should be put in consideration as a simple and successful ICSI protocol.
  • 39. Thanks for your attention