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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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Shahar Kol , IVF Unit Rambam Health Care Campus and Macabbi Health Services, Haifa, Israel

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Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

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

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

How do we routinely trigger ovulation ?

  • We have only one option: hCG.


Is it in agreement with physiology

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

Do we have other options?

JCEM 2001


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

15,000+10,000 IU gave 20% live birth rate but with a 12% OHSS rate.


The physiology of agonist trigger

The physiology of agonist trigger.

LH surge

Humaidan et al, 2011


The physiology of agonist trigger1

The physiology of agonist trigger.

FSH surge

Gonen et al, 1990


Does it make a difference 1

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

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

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

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.


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

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


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

“agonist trigger provides a safe and OHSS-free clinical environment”


Agonist trigger main advantage ohss free clinic no need to cancel cycles ever

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.”


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

16 publications

Agonist: 2005 patients, not a single case of OHSS!

hCG: 92 cases in 1810 patients, 5.1%


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

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.


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

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

Hyper-responder: How to prevent OHSS + good clinical outcome?

  • Trigger with agonist.

  • Intensive luteal support.


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

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


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

Engmann et al, 2008


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

How high can we go?


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

The advantage for the “normal responder”

Agonist

trigger

OPU

ET

antagonist

36h

4 days

FSH/hMG

1,500 IU hCG

1,500 IU hCG


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

Kol et al 2011


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

”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


Shahar kol ivf unit rambam health care campus and macabbi health services haifa israel

Crystal ball: where are we heading?

Thank you


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