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OHSS FREE CLINIC

OHSS FREE CLINIC. Prof Dr P Devroey. The Era of a OHSS Free Clinic. By understanding biology By using drugs differently By innovative strategic thinking. Definition. Definition of OHSS. Iatrogenic complication (!) of “controlled” (?) ovarian stimulation

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OHSS FREE CLINIC

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  1. OHSS FREE CLINIC Prof Dr P Devroey

  2. The Era of a OHSS Free Clinic • By understanding biology • By using drugs differently • By innovative strategic thinking Definition

  3. Definition of OHSS • Iatrogenic complication (!) of “controlled” (?) ovarian stimulation • Potentially fatal (!) • Risk factor (PCOS) • Triggering mechanism of hCG ( ! ) Intriguing

  4. Intriguing • Iatrogenic Who is responsible? • Ovarian stimulation How to stimulate? • HCG is the trigger HCG to be replaced? OHSS

  5. Ovarian hyperstimulation syndrome • 01 09 2011 • PubMed n : 2 275 citations Severe OHSS

  6. Severe OHSS • IV fluid • Respiratory distress (intensive care admission) • Electrolyte imbalance • Dopamine to improve diuresis • Heparin to prevent thrombosis • Vaginal aspiration of ascitis fluid Aboulghar SRM 2010 Form

  7. Form of OHSS • Early onset (early OHSS) up to 9 days after oocyte retrieval related to excessive ovarian response • Late onset (late OHSS) 10 days after oocyte retrieval induced by endogenously produced hCG after implantation Papanikolaou HR 2005 Incidence

  8. Incidence of OHSS (hospitalized) • 2 524 IVF/ICSI cycles • 53 patients 2.1 % (95 % CI : 1.6 - 2.8) • Early OHSS (n : 31) 1.2 % (95 % CI : 0.9 - 1.8) • Late OHSS (n : 22) 0.9 % (95 % CI : 0.5 - 1.31) Papanikolaou FS 2006 Fatal

  9. Fatal OHSS • 25 years old Japanese lady • Bilateral chest pain - dyspnoea • Pleural effusion • Fatal after respiratory insufficiency • Autopsy massive pulmonary edema Semba Patol Int 2000 Fatal

  10. Fatality due to OHSS • 31 years old woman • Ovarian stimulation (Gonal F) • Fatal adult respiratory distress syndrome Fineschi Int J Legal Med 2006 Maternal death

  11. Maternal deathIn IVF in the Netherlands (1984 – 2008) • Death to OHSS : 3 / 100 000 IVF cycles • Respiratory distress (n : 2) • Cerebrovascular thrombosis (n : 1) Braat HR 2010 Does it mean 30 / 1 000 000 ?

  12. At random citations • OHSS is difficult to predict, but multiple preventive strategies and protocols are being developed that may limit it Patchava Minerva Ginecol 2009 • Ovarian stimulation carries a marked risk for … ovarian hyperstimulation syndrome Kallen Best Pract Res Clin Obstet Gynaecol 2008

  13. At random citations (continued) • Low dose hCG at the end of the follicular phase Nargund RBO 2007 • Preventive administration of IV fluid Youssef Cochrane Database Syst Rev 2011 • Continuous vaginal and thoracic fluid drainage for management of severe ovarian hyperstimulation syndrome Ceyhan Gynecol Endocrinol 2008

  14. At random citations (continued) • Severe ovarian hyperstimulation syndrome : an intensive care disease Humeeus Rev Med Chil 1998 • Coasting no benefit D’Angelo Cochrane Database Syst Rev 2011 • Dopamine antagonist significant reduction Sherwal J Human Reprod Sci 2010 Obstetrical outcome

  15. Obstetrical outcome of IVF pregnancies in OHSS syndrome Courbiere FS 2011 Iatrogenic ?

  16. The question : Is iatrogenic OHSS avoidable and erasable ? Understanding different biological mechanisms using different drugs using different treatment strategies Devroey et al HR 2011

  17. Is GnRH agonist triggering an option ? • PubMed 01.03.2011 n : 83 publications • Gonadotrophin-releasing hormone agonist triggering : the way to eliminate ovarian hyperstimulation syndrome - a 20 years experience Kol Sem Reprod Med 2010

  18. GnRH agonist triggering Segal FS 1992 Reflexion

  19. Reflection It is possible that down regulation of pituitary receptors and reduced LH support for the corpus luteum may occur even after a single administration of GnRH agonist Segal FS 1992

  20. Cycle outcome Kolibianakis HR 2005 Odds ratio (95 % CI) 0.11 (0.02 – 0.52) P level = 0.005

  21. GnRH agonist triggering in a GnRH antagonist cycle Kolibianakis HR 2005

  22. GnRH agonist triggering in GnRH antagonist cycles in OHSS risk • AIM : avoiding OHSS • Patients (n : 12) • > 25 follicles • GnRH agonist triggering and 1 500 hCG 35 hours later • COC (n : 20) • Ongoing pregnancies 50 % (6/12) • No OHSS Humaidan RBMO 2009

  23. GnRH agonist triggering in GnRH antagonist cycles (RCT) Humaidan FS 2010

  24. Oocyte donors (GnRHa donors) Melo RBMO 2009

  25. Elective vitrification of all zygotes after GnRH agonist triggering Griesinger HR 2007

  26. Oocyte donation using egg cryobanking • 153 eggs • 117 fertilized • 47 blastocysts transferred • 2.3 per ET • 26 implanted (55 %) Nagy FS 2009

  27. Oocyte banking (vitrification) Cobo HR 2010

  28. Oocyte vitrification : closed carrier Personal communication

  29. Oocyte vitrification after GnRH agonist triggering versus coasting • Observational study • Oocyte vitrification after GnRH agonist triggering (n : 152) • Classical coasting (n : 96) • Egg vitrification (pregnancy rate 50 %) • Clinical coasting (pregnancy rate 30 %) Herrero FS 2010

  30. Endometrial biopsy on the day of ovulation, natural cycle No secretory features

  31. Endometrial biopsy on the day of oocyte retrieval, GnRH agonist and gonadotrophin stimulation cycle Clear secretory features

  32. Endometrium histology at OPU and the probability of pregnancy Kolibianakis FS 2002

  33. Advanced endometrial maturation - no pregnancies • Upregulated genes • SERPINB6 • FOXO3A • SOX17 • CDC42 Van Vaerenbergh I HR 2009

  34. Past Down regulation with GnRH agonist HCG for final egg maturation OHSS ≈ 2 % Today For first cycle always GnRH antagonist GnRH agonist triggering if at risk for OHSS Freeze all ET of fresh embryo adding low dose hCG in luteal phase OHSS 0 % CONCLUSION

  35. Optimization of stimulation Optimization of embryology Optimization of endometrial implantation potential GnRH antagonist and GnRH agonist to trigger Freeze all oocytes/embryos Replacement in receptive endometrium (spontaneous or artificial) CODA OHSS FREE CLINIC AFR segmentation strategy

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