1. SL ‘00 Antagonists in patients with previous poor ovarian response Antagonists in patients with previous poor ovarian response Geoffrey H Trew Consultant in Reproductive Medicine & Surgery, Hammersmith Hospital Chief of Service, Imperial College NHS Trust London

2. Poor responders………. Difficult group for ; PatientsPatients StaffStaff ResultsResults

3. Definitions……. Main ; number of egg < 5, cancelled cyclesMain ; number of egg < 5, cancelled cycles But also a lot of American studies use ; Raised FSH Female age >40 AFC < 5 Endometriosis grade III or IV

4. Variation The greater the number of protocols there are - the poorer the evidence for any particular one.....

5. Evidence Based Medicine Archie CochraneArchie Cochrane Do we need evidence ?Do we need evidence ? Why ?Why ? What evidence do we have ?What evidence do we have ?

6. The evidence Or some of it ……

7. Best outcome………… But…. There are other important outcomes as well ; Egg collectionEgg collection Embryo transferEmbryo transfer

8. Agonist v Antagonist Cancellation RatesCancellation Rates Previous agonist cycle cancelledPrevious agonist cycle cancelled New cycle – increased doseNew cycle – increased dose Randomised to either agonist or antagonistRandomised to either agonist or antagonist

9. Cancellation Rate on following cycle with poor responders Brook…Trew, J Obstet & Gynecol, 2006 0 5 10 15 20 25 30 35 40 45 50 AntagonistBuserelin % 9.4 47.5 P=0.011

10. …… A Prospective RCT of microdose leuprolide v ganirelix …… Pilot study - 48 ptsPilot study - 48 pts previous poor response previous poor response … ganirelix appears to be as effective as the microdose protocol and may be a superior choice in terms of cost and convenience… ganirelix appears to be as effective as the microdose protocol and may be a superior choice in terms of cost and convenience Schmidt et al Fertil steril May 2005

11. Antagonists in IVF poor responders – results of randomised trial Antagonist v standard long ; 60 ptsAntagonist v standard long ; 60 pts Antagonist group ; less drugs P = 0.0001less drugs P = 0.0001 more eggs P = 0.02more eggs P = 0.02 Fewer cycles cancelledFewer cycles cancelled PR 17% per ET v 7% per ETPR 17% per ET v 7% per ET Marci et al RBM Online Aug 2005

12. Flexible GnRH Antagonist v flare up GnRH Agonist in poor responders…a RCT 5 or less oocytes with dose = or > 300iu5 or less oocytes with dose = or > 300iu Antagonist (180pts) v flare agonist (90pts)Antagonist (180pts) v flare agonist (90pts) PR ; 12.2% v 4.4%PR ; 12.2% v 4.4% ( p<0.048) Lainas…Kolibianakis, et al : Hum Reprod April 2008

13. Poor responders Just about every different protocol triedJust about every different protocol tried Different FSH dosesDifferent FSH doses Different Agonist dosesDifferent Agonist doses Antagonists fixed / flexibleAntagonists fixed / flexible Various additives inc LH growth hormone etcVarious additives inc LH growth hormone etc ‘Soft’ / Natural protocols‘Soft’ / Natural protocols Still poor results!Still poor results!

14. What is your preferred ovarian stimulation regime for “poor responders” ? Clomifene/ gonadotrophin26%Clomifene/ gonadotrophin26% Ultrashort agonist23%Ultrashort agonist23% Short agonist30%Short agonist30% Long agonist17%Long agonist17% Antagonist 58% (Serono Symposia Mtg Athens Dec 2006)

15. What is your preferred ovarian stimulation dose for “poor responders” 200 iu2%200 iu2% 225 iu4%225 iu4% 300 iu21%300 iu21% 375 iu 9%375 iu 9% 450 iu 47%450 iu 47% > 450 iu15%> 450 iu15%

16. What should the maximum FSH dose be in poor responders ? “ little or no clinical benefit in doses > 300 iu”“ little or no clinical benefit in doses > 300 iu” “…but costs and side effects were higher”“…but costs and side effects were higher” Siristatidis & Hamilton, J Obstet Gynecol May 2007

17. Other options Give up / expectant management Give up / expectant management Corrective surgery of underlying problem Corrective surgery of underlying problem Natural cycle IVF Natural cycle IVF IUI - If no significant male factor / tubal factor IUI - If no significant male factor / tubal factor IUI and donor sperm if significant male factor IUI and donor sperm if significant male factor Egg Donation Egg Donation 50% + pregnancy rates 50% + pregnancy rates

18. Conclusions Difficult group to treatDifficult group to treat Poor pregnancy rates in true poor respondersPoor pregnancy rates in true poor responders Antagonist protocolsAntagonist protocols High dose of FSHHigh dose of FSH

19. Please ! Do not use antagonists just for poor responders use them for all groups of patients !!Do not use antagonists just for poor responders use them for all groups of patients !! Results are goodResults are good Patients love them !Patients love them !

20. Thank You ! g.trew@imperial.ac.uk