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GnRH-a trigger and individualized luteal phase hCG support will avoid OHSS in PCOS patients.

GnRH-a trigger and individualized luteal phase hCG support will avoid OHSS in PCOS patients. Shahar Kol , IVF Unit Rambam Health Care Campus, and Faculty of Medicine, Technion , Israel Institute of Technology, March, 2014. content. OHSS: is it still a problem?

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GnRH-a trigger and individualized luteal phase hCG support will avoid OHSS in PCOS patients.

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  1. GnRH-a trigger and individualized luteal phase hCG support will avoid OHSS in PCOS patients. ShaharKol, IVF Unit Rambam Health Care Campus, and Faculty of Medicine, Technion, Israel Institute of Technology, March, 2014

  2. content • OHSS: is it still a problem? • No OHSS post agonist trigger! • Mechanism? • Failures? • The question of pregnancy rate. • Agonist trigger: back to physiology. • Agonist trigger is not the issue, luteal support is. • A revolution in the making.

  3. OHSS: Is it still a problem? “We did not have a single case in years.”

  4. SEVERE OHSS: IS IT STILL A PROBLEM? “In 2003-2005, 4 deaths (of the 12) were due to OHSS”. ~3 OHSS-related deaths per 100,000 ART cycles.

  5. Three OHSS-related deaths (3:100,000 ART cycles), all had their embryos frozen. Braat et al, 2010

  6. How to prevent OHSS? • Agonist trigger is the most effective approach.

  7. PRE-ANTAGONIST ERA

  8. Antagonist era • Use of a single bolus of GnRH agonist triptorelin to trigger ovulation after GnRH antagonist ganirelix treatment in women undergoing ovarian stimulation for assisted reproduction, with special reference to the prevention of ovarian hyperstimulation syndrome: preliminary report: Short communication . Itskovitz-Eldor et al. 2000

  9. 16 publications Agonist: 2,005 patients, not a single case of OHSS! hCG: 92 cases in 1,810 patients, 5.1%

  10. What really works: • GnRH agonist versus hCG for oocyte triggering in GnRH antagonist ART cycles Total events 0 (GnRH) 21 (hCG) Youssef MA, et al. Human Reprod Update 2010;16:459–466

  11. Lower levels of inhibin A and pro-alpha C during the luteal phase after triggering oocyte maturation with GnRH agonist versus hCG Mechanism of OHSS prevention? Nevo et al. 2003

  12. Luteal phase Natural cycle day 7-9= 75 pg/ml vs. 18 Natural cycle day 7-9= 750 pg/ml vs. 184 Nevo et al, 2003

  13. A safe and OHSS-free clinical environment

  14. Pregnancy rate post agonist trigger • We showed that agonist trigger causes quick and irreversible luteolysis. • Therefore, the right luteal support is crucial. • The evolution of post agonist luteal support.

  15. Luteal phase – non-supplemented • Beckers et al (2003) – very low pregnancy rate.

  16. Luteal phase – conventional support Not good enough!

  17. Luteal phase – modified support We are getting there!

  18. LUTEAL PHASE: INTENSIVE E+P OHSS high-risk patients Engmann et al, 2008

  19. All freeze advantages • No OHSS • Better endometrium in thaw cycles. • Less ectopic pregnancies in thaw cycles. • Comparable, or even better, clinical outcome in thaw cycles. • Better obstetric outcome? • Fresh transfer post agonist trigger requires daily IM injections of progesterone in oil.

  20. …AND WHEN OHSS IS NOT THE MAIN ISSUE?... “… 42% of those who received hCG reported subjective complaints (mostly abdominal discomfort), whereas this percentage was 0% in those who received GnRH agonist to trigger ovulation. Cerrillo et al, 2009

  21. hCG does not imitate physiology! LH surge goes together with FSH surge. Is FSH surge redundant? Gonen et al 1990

  22. Dual role of hCG trigger • Final oocyte maturation. • Early luteal phase stimulation. • Same dose for both functions? hCG

  23. Non OHSS-high-risk patients: side benefits • Agonist trigger: more MII oocytes compared with hCG trigger1-4 • Potential benefit of FSH surge:5-9 • Promotes LH receptor formation in luteinizing granulosa cells • Promotes nuclear maturation (i.e. resumption of meiosis) • Promotes cumulus expansion Humaidan P, et al. Reprod Biomed Online 2005;11:679–684 Humaidan P, et al. Human Reprod2009;24:2389–2394 Imoedemhe DA, et al. FertilSteril 1991;55:328–332 Oktay K, et al. Reprod Biomed Online 2010;20:783–788 Eppig JJ. Nature 1979;281:483–484 Strickland and Beers. J BiolChem1976;251:5694–5702 Yding Andersen C. Reprod Biomed Online 2002;5:232–239 Yding Andersen C, et al. Mol Hum Reprod1999;5:726–731 Zelinski-Wooten MB, et al. Human Reprod1995;10:1658–1666

  24. What do practitioners say? Among the five most downloaded papers

  25. TAKE HOME MESSAGE “The results of this survey indicate that GnRH trigger is widely used worldwide and therefore has become part of the standard of care today. Hence, doctors are entitled to prescribe it just as patients may ask that this option is considered in their case.”

  26. “Agonist triggering is viewed as one of the major advances in ovarian stimulation, with the potential to eliminate OHSS…”

  27. Revolution in the making

  28. Thank you

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