ROLE OF CABERGOLIN IN MANAGEMENT OF OHSS

1. ABOUBAKR ELNASHAR
Benha University Hospital, Egypt
ROLE OF
CABERGOLIN
IN MANAGEMENT OF
OHSS
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2. CONTENTS
I. OHSS
1. DEFINITION
2. PATHOGENESIS
3. RISK FACTORS
4. TYPES
5. PREVENTION
II. CABERGOLIN
1. MECHANISM OF ACTION
2. INDICATIONS
3. DOSE
4. WHEN TO START?
5. SAFETY
6. EFFECTIVENESS
7. TREATMENT
8. LIMITATION
 CONCLUSION
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3. I. OHSS
1. DEFINE
Systemic syndrome resulting from vasoactive
products released by hyperstimulated ovaries.
An iatrogenic complication of COS.
Life threatening
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4. 2. PATHOPHYSIOLOGY
 The most widely accepted hypothesis:
increased capillary permeability: leakage of fluid
from vas compartment:
- 3rd space fluid accumulation
-IV dehydration.
Extravasation of fluid firstly into the ovaries & then
into the abdominal cavity .
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5. AboubakrElnashar

6. 3. RISK FACTORS
The most important: PCOS & history of OHSS
 Prior to an IVF cycle
Young age (22 y), lean (BMI: 19 kg/m2), PCOS
History of:
 High response during a previous COS
 Cycle cancellation related to high response
 Development of moderate or severe OHSS
(Ragni et al, 2005; Griesinger et al, 2007; Imbar et al, 2012)
Basal investigations
(NICE, 2013)
Total AFC > 16
AMH>3.5 ng/ml (25.0 pmol/l)
FSH<4 IU/l
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7. During IVF:
One of the following
Peak E2 > 3000-4000 pg/mL,
20 follicles at least 10 mm, in addition to the
leading follicles on the day of hCG
Retrieval of >15 oocytes
(Ragni et al, 2005; Griesinger et al, 2007; Imbar et al, 2012)
For GnRHan protocol:
18 follicles 11 mm on the day of hCG: 83% specificity
in predicting severe OHSS
(Papanikolaou et al.,2006)
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8. 4. TYPES
(Esteve, 2013)
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9. 5. PREVENTION: Modification + Adjuvant
I. Modified stimulation protocols
1. Antagonist protocol
2. HMG
Lower doses
Chronic low dose step up protocol
2. HCG
a. Withholding
b. Delaying (Coasting or drifting)
c. Decrease dose
d. Replacing
4. GnRHan rescue by replacing a GnRHa with a GnRHan
5. Progesterone for Luteal phase support not HCG.
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10. II. Modified techniques
1. Follicular aspiration before or after hCG
2. Cryopreservation of embryos
3. Blastocyst transfer
4. Elective single ET
Ovarian electrocautery
Selective oocyte retrieval in spontaneous conception cycles
III. Adjuvant
1. IV albumin
2. 6% Hydroxyethyl starch
3. Metformin
4. Dopamin agonist
5. Ca gluconate
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11. II. CABERGOLIN
1. MECHANISM OF ACTION
Type 2 receptors for VEGF are involved in the
pathophysiology of OHSS
Dopamine agonist (Cab) inhibit Phosphorylation
and signaling of VEGFR-2
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12. 2. INDICATIONS
1. Patients at high risk of OHSS
2. Patients with a history of previous OHSS even
without evident signs of the syndrome.
(Kasum et al, 2014)
3. Treatment of OHSS
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13. 3. DOSE
0.5 mg/d for 8 days beginning from day of hCG or
day of OR
(Alveizer et al., 2007, Seow et al, 2013)
0.5 mg/d for 3 weeks beginning on day after OR
(Carriza et al., 2008)
0.5 mg,on two successive days, repeated 1 week
later, starting from day of HCG injection
(Salah Edeen et al., 2009)
0.25 mg daily for 8 days
(Shaltout et al., 2009).
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14. 4. WHEN TO START
on day of HCG or day of OR
(Seow et al, 2013)
No significant differences in IR or CPR
on the day of hCG injection or preferably a few
hours earlier.
(Kasum et al, 2014)
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15. 5. SAFETY
Fertilization, implantation and PR, ongoing and
full-term pregnancies comparable to those of
controls
(A´ lvarez et al, 2007)
Cab in early pregnancy not harmful up to 7 mg/w:
spontaneous and induced abortions
major congenital malformations: comparable
general population.
(Ricci et al, 2002)
Cab does not affect the pregnancy outcome
(CPR, miscarriage rate), nor is there an increased
risk of adverse events. AboubakrElnashar

16. 6. EFFECTIVENESS
Effective for the prevention of OHSS.
(Esinler et al, 2013).
Reduce the incidence and severity of OHSS
(Busso et al, 2009)
Reduces the incidence of OHSS in patients at
higher risk (II-2)
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17. Reduces the incidence, but not severity of OHSS
(Yousef et al, 2010, SR and MA)
Reduce the risk of OHSS in high risk women,
especially for moderate OHSS.
(Cochrane Database Syst Rev. 2012, Tang et al)
Effective in prevention of moderate and early
onset OHSS (9.41%), compared with a placebo
(21.45%),
(Kasum et al, 2014)
Cab should definitely be considered for
prevention of both early and late OHSS
(Naredi et al, 2014)
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18. Cab VS IV albumin
(Tehraninezad et al, 2012)
More effective and less costly
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19. Cab Vs Coasting.
(Esinler 2013)
Cab group: No OHSS (0 %), whereas there were
coasting group: 2 OHSS (3.6 %)
This difference was not significant.
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20. 7. TREATMENT
Cab: 1 mg/48 h: improvement in 10 severe
OHSS pregnant women after 24–48 h
(Manno et al., 2005).
Cab can both prevent and treat OHSS
(Soares, 2012)
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21. less effective for tt of OHSS.
(S R and MA., Baumgarten et al, 2013)
Cannot be confirmed for the tt of late OHSS.
(Kasum et al, 2014)
Cab and GnRHan in OHSS:
rapidly and effectively diminish the clinical symptoms
(Rollene et al, 2009)
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22. 8. LIMITATIONS
Role in prevention of late onset OHSS is limited
(Carlos et al, 2008, RCT)
Cab should definitely be considered for
prevention of both early and late OHSS
(Naredi et al, 2014)
 less effective for tt of OHSS.
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23. CONCLUSION
Cab owing to its VEGFR-2 de phosphorylation
provide a novel, specific and non-toxic approach to
the prevention and tt of OHSS
Cab should definitely be considered for
prevention of OHSS.
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24. Thanks
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