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Planning of GnRH antagonist cycles

Planning of GnRH antagonist cycles. Christophe Blockeel. UZ Brussel. Oocyte retrievals May 2011. Oocyte retrievals June 2011. 1. OCP PRETREATMENT. Oral Contraceptive Pill Pretreatment. Potentially relevant RCTs identified and screened for retrieval ( n=34 ). RCTs excluded ( n=27 ).

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Planning of GnRH antagonist cycles

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  1. Planning of GnRH antagonist cycles Christophe Blockeel

  2. UZ Brussel Blockeel - Planning GnRH antagonists

  3. Oocyte retrievals May 2011 Blockeel - Planning GnRH antagonists

  4. Oocyte retrievals June 2011 Blockeel - Planning GnRH antagonists

  5. 1. OCP PRETREATMENT

  6. Oral Contraceptive Pill Pretreatment Potentially relevant RCTs identified and screened for retrieval (n=34) RCTs excluded (n=27) RCTs retrieved for more detailed evaluation (n=7) RCTs excluded (n=3) RCTs with usable information, by outcome (n=4) Cedrin-Durnerin et al, 2006 Huirne et al, 2006 Kolibianakis et al, 2006 Rombauts et al, 2006 Until 3/2007 Inclusion: true RCTs Griesinger et al. Fertil Steril. 2008;90:1055. Blockeel - Planning GnRH antagonists

  7. Effect of OCP Pretreatment . Griesinger et al. Fertil Steril. 2008;90:1055. Blockeel - Planning GnRH antagonists

  8. Griesinger et al., 2010 Fertil Steril

  9. 2. Early vs Late hCG

  10. When is the correct moment to induce final oocyte maturation ? • At least 3 follicles of ≥ 17 mm present in ultrasound • Borm and Mannaerts HR 2000, The Middle East orgalutran study group HR 2001, • Fluker FS 2001, Kolibianakis FS 2002, 2003 • At least 3 follicles of ≥ 18 mm present in ultrasound • Garcia - Velasco HR 2001 • Leading follicle attained 18-20 mm and estradiol levels were indicating satisfactory follicular development • Olivennes HR 1998 • At least ≥ 1 follicle of ≥ 18 mm and 3 follicles of ≥ 15 mm • de Jong FS 2001 • At least 1 follicle of ≥ 20 mm and an estradiol level 1200 pg/ml • Albano HR 2000 • At least 1 follicle of ≥ 20 mm or an estradiol level 1200 pg/ml • Felberbaum HR 2000 Blockeel - Planning GnRH antagonists

  11. Effect of Delaying hCG by 2 Days Kolibianakis et al. Hum Reprod. 2005;20:2453. Blockeel - Planning GnRH antagonists

  12. Advancement or delay with 1 day Tremellen et al., Hum Reprod, 2010 Blockeel - Planning GnRH antagonists

  13. 3. GnRH antagonists

  14. Elevated progesterone before start Kolibianakis, Hum Reprod, 2004 Blockeel - Planning GnRH antagonists

  15. Elevated progesterone before start Kolibianakis, Hum Reprod, 2004 Blockeel - Planning GnRH antagonists

  16. Administration of a GnRH antagonist before start in case of elevated progesterone Blockeel - Planning GnRH antagonists

  17. GnRH antagonist before start Blockeel et al., CurrPharmac Biotech, 2011. Blockeel - Planning GnRH antagonists

  18. GnRH antagonist before start Blockeel et al., CurrPharmac Biotech, 2011. Blockeel - Planning GnRH antagonists

  19. Administration of a GnRH antagonist before start in case of normal progesterone Blockeel - Planning GnRH antagonists

  20. Treatment of Subjects Group A GnRH antagonist 150-225 IU recFSH Cycle day 2 5 6 9 ET OPU Group B 150-225 IU recFSH 10.000IU hCG GnRH antagonist GnRH antagonist Blockeel - Planning GnRH antagonists

  21. Results Blockeel et al.,FertilSteril, 2011 Blockeel - Planning GnRH antagonists

  22. Protocol for oocyte donors 150-225 IU recFSH GnRH antagonist GnRH antagonist Cycle day 2 5 6 9 OPU GnRH agonist trigger • Recruitment of oocytes • No OHSS Blockeel - Planning GnRH antagonists

  23. 4. ESTRADIOL

  24. Luteal estradiol pretreatment Fanchin et al. Hum Reprod. 2003;12:2698. Blockeel - Planning GnRH antagonists

  25. Luteal estradiol pretreatment • Suppression of FSH • Coordination of antral follicle growth (homogeneity - synchronisation) • More physiological than GnRH agonist or OCP Fanchin et al. Hum Reprod. 2003;12:2698. Blockeel - Planning GnRH antagonists

  26. Luteal estradiol pretreatment RCT by Guivarc’h-Levêque et al (2010) • Long GnRH agonist protocol (n=412) versus • GnRH antagonist protocol with estradiol pretreatment (n=426) • Lower proportion of OR during weekend days > programming feasible • PR equivalent with long agonist protocol (Guivarc’h-Levêque et al, GOF, 2010)

  27. Programming of egg retrievals days A Guivarc’h - Levêque et al GOF 2010 Blockeel - Planning GnRH antagonists

  28. Results A Guivarc’h - Levêque et al GOF 2010 Blockeel - Planning GnRH antagonists

  29. GnRH antagonist 150 IU recFSH No treatment 2 7 10.000IU hCG ET OPU Pretreatment Group B Estradiol valerate 4mg GnRH antagonist 150 IU recFSH 6 – 7 – 8 – 9 – 10 days 25 7 OPU ET 10.000IU hCG

  30. If day 25 is…. • Monday 6 days Progynova 4 mg • Tuesday 10 days Progynova 4 mg • Wednesday 9 days Progynova 4 mg • Thursday 8 days Progynova 4 mg • Friday 7 days Progynova 4 mg • Saturday 6 days Progynova 4 mg • Sunday 6 days Progynova 4 mg Blockeel - Planning GnRH antagonists

  31. Results Primary endpoint: proportion of patients undergoing an oocyte retrieval during weekend days P=0.029

  32. Results (2) Stimulation characteristics and embryological data * P-value for Student’s t test; P-values less than 0.5 are bold

  33. Results (3) Ongoing pregnancy rates * P-value for Fisher’s exact of Chi-squared test ° pregnancy outcome still awaited for 3 patients in the pretreatment group

  34. Conclusion Estradiol valerate pretreatment • allows scheduling of GnRH antagonist cycles, with a significantly lower proportion of patients undergoing OR during weekend days • without deleterious effects on the number of oocytes retrieved and the ongoing pregnancy rates

  35. Conclusion: planning is possible! Today’s protocol… Corifollitropin alfa: 1 injection GnRH antagonist GnRH antagonist Cycle day 2 5 6 9 ET OPU 10.000IU hCG Blockeel - Planning GnRH antagonists

  36. Conclusion: planning is possible! Or… Estradiol valerate 4mg GnRH antagonist Corifollitropin alfa: 1 injection 6 – 7 – 8 – 9 – 10 days 25 7 OPU ET 10.000IU hCG Blockeel - Planning GnRH antagonists

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