ABOUBAKR ELNASHAR

Benha University Hospital, Egypt

ROLE OF

CABERGOLIN IN MANAGEMENT OF

OHSS

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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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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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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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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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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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4. TYPES

(Esteve, 2013) Aboubakr Elnashar

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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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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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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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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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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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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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.

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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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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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Cab VS IV albumin

(Tehraninezad et al, 2012)

More effective and less costly

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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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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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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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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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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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Thanks

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