Condition category
Pregnancy and Childbirth
Date applied
21/05/2011
Date assigned
19/07/2011
Last edited
30/06/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Ovarian hyperstimulation syndrome (OHSS) is a complication that can affect women taking injectable hormone medications to stimulate the development of eggs in the ovaries (controlled ovarian hyperstimulation). This can occur in women undergoing in vitro fertilization (IVF), which is a process by which egg cells are fertilized by sperm outside the body. Most cases of OHSS are mild, but a small proportion is severe. The symptoms include swollen and painful ovaries, rapid weight gain, abdominal pain, vomiting and shortness of breath. The aim of this study is to find out whether the drug cabergoline can prevent severe OHSS in women undergoing IVF who are at a high risk of developing OHSS.

Who can participate?
Women undergoing IVF who are at a high risk of developing OHSS

What does the study involve?
Participants undergo controlled ovarian hyperstimulation and are randomly allocated to be treated with cabergoline or not. The eggs are retrieved 34 - 36 hours later. The eggs are fertilized and the resulting embryos are transferred into the womb 72 hours later. The incidence, onset and severity of OHSS are compared between the two groups.

What are the possible benefits and risks of participating?
Patients who take part in this study visit the hospital more frequently and therefore are monitored more closely. Side effects from cabergoline are extremely rare. It has been reported that cabergoline is linked with the development of cardiac valvuopathy (abnormal thickening and stiffness of the heart valves).

Where is the study run from?
Dr Samir Abbas Medical Center (Saudi Arabia)

When is the study starting and how long is it expected to run for?
July 2007 to June 2009

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
Prof. Amany Shaltout
amanyshaltout@hotmail.com

Trial website

Contact information

Type

Scientific

Primary contact

Prof Amany Shaltout

ORCID ID

Contact details

Dr Samir Abbas Medical Center
PO Box 12190
Jeddah
21473
Saudi Arabia
+966 (0)50 767 5438
amanyshaltout@hotmail.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

SAC 05-12011

Study information

Scientific title

Cabergoline and OHSS - a randomized controlled study

Acronym

COHSS

Study hypothesis

Capillary permeability is the end step of the cascade of the pathophysiology of OHSS which is associated with third space fluid accumulation and fluid shift. Vascular endothelial growth factor (VEGF) is one of the vasoactive mediators which increases capillary permeability and expressed at a higher level in the granulose cells. The administration of a dopamine agonist in immature rats at low doses simultaneously with human chorionic gonadotropin (HCG) prevented an increase in vascular permeability and did not affect angiogenesis; the effect was due to the availability of dopamine type 2 receptors. Dopamine agonists prevent the phosphorylation of VEGF receptor 2 and reduce the in vitro and in vivo release of vasoactive angiogenic agents. As a result, vascular permeability is also reduce. Consequently, dopamine agonist has been supposed to be a potential new strategy to prevent OHSS and reduce the severity.

Ethics approval

Samir Abbas Ethics Board, December 2006

Study design

Single-center non-blinded randomized controlled study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Ovarian hyperstimulation syndrome (OHSS)

Intervention

1. Long mid luteal GnRH agonist protocol, 0.1 mg triptorelin SC. (Decapeptyl; Ferring; Germany) has been used for pituitary down regulation in both groups
2. Once pituitary down regulation has been confirmed, controlled ovarian hyperstimulation (COH) was started using fixed dose of HMG, 150- 225 IU (Menogon 75 IU,IM injections, Ferring, Germany), for 5 days, then the dose was adjusted according to response
3. When 3 leading follicles reached 18 mm, final oocyte maturation was triggered with a single dose of 5000 IU of hCG
4. On day of hCG administration, couples were randomized using computer generated list with closed opaque envelops into two groups, cabergoline group (Group I; n=100), received 0.25 mg daily for 8 days and non-cabergolone group (Group II; n=100), did not receive cabergoline
5. Transvaginal guided oocyte retrieval was performed 34 - 36 hours later
6. Both groups have been administrated 500 ml of hydroxyethyl starch (HES) over 30 minutes as a routine strategy in our center on the day of ovum pickup
7. Ultrasound guided transfer (ET) of 2-3 embryos was performed 72 hours later
8. Luteal phase was supported with 400 mg progesterone vaginal pessaries, twice daily up to the day of pregnancy test (Cyclogest; Cox Pharmaceuticals, Whiddon Valley, UK)
9. Haemoconcentration, presence of ascitis, measuring the perpendicular diameter of free fluid in Douglas Pouch, and the ovarian volume have been reported in both groups on day of ET

Intervention type

Drug

Phase

Not Applicable

Drug names

Cabergoline

Primary outcome measures

Incidence, onset and severity of OHSS

Secondary outcome measures

1. Oocyte recovery rate
2. Number of mature oocytes
3. Fertilization rate
4. Clinical pregnancy rate (defined as presence of fetal heart pulsation 2 weeks after a positive β-HCG test)

Overall trial start date

01/07/2007

Overall trial end date

01/06/2009

Reason abandoned

Eligibility

Participant inclusion criteria

1. 200 infertile couples undergoing ICSI and at risk of developing OHSS have been included between January 2007 and July 2009
2. The risk to develop OHSS has been defined as follows:
2.1. Dopamine E2 level on day of hCG > 3500 pg/ml
2.2. With ≥ 20 follicles > 12 mm

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

200

Participant exclusion criteria

Patients with dopamine E2 ≥5000 pg/ml

Recruitment start date

01/07/2007

Recruitment end date

01/06/2009

Locations

Countries of recruitment

Saudi Arabia

Trial participating centre

Dr Samir Abbas Medical Center
Jeddah
21473
Saudi Arabia

Sponsor information

Organisation

Samir Abbas Center (Saudi Arabia)

Sponsor details

PO Box 12190
Jeddah
21473
Saudi Arabia
+966 (0)50 767 5438
amanyshaltout@hotmail.com

Sponsor type

Hospital/treatment centre

Website

http://www.samirabbas.net/

Funders

Funder type

Other

Funder name

Investigator initiated and funded

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20354100

Publication citations

  1. Results

    Youssef MA, van Wely M, Hassan MA, Al-Inany HG, Mochtar M, Khattab S, van der Veen F, Can dopamine agonists reduce the incidence and severity of OHSS in IVF/ICSI treatment cycles? A systematic review and meta-analysis., Hum. Reprod. Update, 16, 5, 459-466, doi: 10.1093/humupd/dmq006.

Additional files

Editorial Notes

30/06/2017: Plain English summary added.