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OHSS Should this be treated or be prevented ? When to cancel a cycle? All cycles should be triggered with GnRH agonist and not by hCG!. Shahar Kol , IVF Unit Rambam Health Care Campus and Macabbi Health Services, Haifa, Israel. November, 2011. Content.
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OHSSShould this be treated or be prevented?When to cancel a cycle? All cycles should be triggered with GnRH agonist and not by hCG! ShaharKol, IVF Unit Rambam Health Care Campus and Macabbi Health Services, Haifa, Israel November, 2011
Content • How do we routinely trigger ovulation? • Is it in agreement with physiology? • Do we have other options? • The physiology of agonist trigger. • Agonist trigger main advantage: OHSS-free clinic. No need to cancel cycles, ever. • The advantage of agonist trigger for the “normal responder”.
How do we routinely trigger ovulation ? • We have only one option: hCG.
Is it in agreement with physiology? • Adequate final oocyte maturation. • Early luteal phase over-stimulation – main reason for luteal phase defect in IVF.* • No FSH surge. hCG *Fauser and Devroey, 2003
Do we have other options? JCEM 2001
15,000+10,000 IU gave 20% live birth rate but with a 12% OHSS rate.
The physiology of agonist trigger. LH surge Humaidan et al, 2011
The physiology of agonist trigger. FSH surge Gonen et al, 1990
Does it make a difference? (1) • Agonist trigger: more MII oocytes compared with hCG trigger. Humaidan et al, 2005, 2009 Imoedemhe et al, 1991 Octay et al, 2009
Does it make a difference? (2) The pregnancy rate in completed cycles and the ongoing pregnancy rate per ET were significantly higher in the study group (dual trigger) than in the control group (hCG only). F&S 2008 Is it possible that in some patients FSH surge is needed?
Does it make a difference? (3) The effect of adding 450 IU of FSH to the hCG trigger. Lamb et al, 2011
What happens after agonist trigger? Complete luteolysis! Induction of LH surge and oocyte maturation by GnRH analogue (Buserelin) in women undergoing ovarian stimulation for IVF “No signs of OHSS were observed in 2 patients who on previous stimulation developed severe OHSS… GnRHa offers a new means by which OHSS can be prevented.” Itskovitz et al, Gynecological Endocrinology 1988, 2:Suppl1, 165.
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
“agonist trigger provides a safe and OHSS-free clinical environment”
Agonist trigger main advantage: OHSS-free clinic. No need to cancel cycles, ever. “The utilization of GnRH agonist for triggering ovulation in antagonist cycles has been a breakthrough in the elimination of OHSS.”
16 publications Agonist: 2005 patients, not a single case of OHSS! hCG: 92 cases in 1810 patients, 5.1%
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.
Three OHSS-related deaths (3:100,000 ART cycles), all had their embryos frozen. Braat et al, 2010
Hyper-responder: How to prevent OHSS + good clinical outcome? • Trigger with agonist. • Intensive luteal support.
OHSS high risk patients Randomization N=32 N=34 Dual suppression OCP’s & luprolide HCG trigger OCP’s + Ganirelix luprolide trigger LUTEAL SUPPORT: E2 patches 0.1 mg X 3, qod P4 in oil, 50 mg/day; MONITOR E2+P4 LEVELS! Engmann, et al, 2008
The advantage for the “normal responder” Agonist trigger OPU ET antagonist 36h 4 days FSH/hMG 1,500 IU hCG 1,500 IU hCG
”The granulosa/luteal cells obtained on the day of oocyte retrieval after agonist trigger have the capacity to respond to hCG by increasing the secretion of steroids.” Engmann et al, 2011
Crystal ball: where are we heading? Thank you