Cabergoline and Coasting to Prevent OHSS (OHSS)

Combining Cabergoline and Coasting in Gonadotropin Releasing Hormone(GnRH)Agonist Protocol in Intracytoplasmic Sperm Injection (ICSI) to Prevent Ovarian Hyperstimulation Syndrome (OHSS): a Randomized Clinical Trial

The effectiveness of cabergoline to prevent moderate-severe OHSS to coasting.

Study Overview

• Status: Completed
• Conditions: OHSS
• Intervention / Treatment: Procedure: ICSI

Detailed Description

To randomly compare three study groups under a high risk of developing OHSS to one of three arms of management, either coasting for 1 to 3 days or receiving cabergoline for 8 days or coasting for 1 day plus receiving cabergoline for 8 days in ICSI patients following the long luteal GnRH agonist protocol.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • IVF centre, Obstetrics and Gynaecology Department, Cairo University Hospitals (Kasr EL Aini)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age <or= 35, BMI <or= 30
2. Long protocol GnRH agonist cycles
3. Estradiol level on day of HCG >or= 3500 pg/ml
4. Retrieving more than 15 oocytes

Exclusion Criteria:

1. Male factor
2. Uterine factor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Coasting; In their ICSI cycle patients will continue their agonist treatment while stopping the human menopausal gonadotropin (hMG) injections for 1 to 3 days until drop of estradiol to a safe level to prevent OHSS. Early OHSS is assessed at day of embryo transfer and 7 days after this date. Late OHSS is assessed 14 days after embryo transfer.	Procedure: ICSI; Long luteal GnRH agonist protocol: patients will receive GnRH agonist from day 21 of the previous cycle of stimulation and then on day 3 of the stimulation cycle they will start hMG injections with 225 IU/day. Folliculometry will start on day 6 stimulation by vaginal ultrasound. Estradiol levels will be measured on day 8, 10 and 12 of stimulation if appropriate. According to ultrasound and estradiol level patients will be randomized to either one of the study arms. When ready final triggering will be done by human chorionic gonadotropin (10000 IU) and oocyte collection is done at 36 hour from triggering. Embryo transfer is then done 3 days afterwards with ultrasound guidance.
Active Comparator: Cabergoline; In their ICSI cycle patients will take 0.25 mg of cabergoline daily for 8 days from HCG triggering day to prevent OHSS. Early OHSS is assessed at day of embryo transfer and 7 days after this date. Late OHSS is assessed 14 days after embryo transfer.	Procedure: ICSI; Long luteal GnRH agonist protocol: patients will receive GnRH agonist from day 21 of the previous cycle of stimulation and then on day 3 of the stimulation cycle they will start hMG injections with 225 IU/day. Folliculometry will start on day 6 stimulation by vaginal ultrasound. Estradiol levels will be measured on day 8, 10 and 12 of stimulation if appropriate. According to ultrasound and estradiol level patients will be randomized to either one of the study arms. When ready final triggering will be done by human chorionic gonadotropin (10000 IU) and oocyte collection is done at 36 hour from triggering. Embryo transfer is then done 3 days afterwards with ultrasound guidance.
Active Comparator: Coasting and Cabergoline; In their ICSI cycle patients will continue their agonist treatment while stopping the human menopausal gonadotropin (hMG) injections for 1 day plus receiving 0.25 mg of cabergoline daily for 8 days from HCG triggering day to prevent OHSS. Early OHSS is assessed at day of embryo transfer and 7 days after this date. Late OHSS is assessed 14 days after embryo transfer.	Procedure: ICSI; Long luteal GnRH agonist protocol: patients will receive GnRH agonist from day 21 of the previous cycle of stimulation and then on day 3 of the stimulation cycle they will start hMG injections with 225 IU/day. Folliculometry will start on day 6 stimulation by vaginal ultrasound. Estradiol levels will be measured on day 8, 10 and 12 of stimulation if appropriate. According to ultrasound and estradiol level patients will be randomized to either one of the study arms. When ready final triggering will be done by human chorionic gonadotropin (10000 IU) and oocyte collection is done at 36 hour from triggering. Embryo transfer is then done 3 days afterwards with ultrasound guidance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate and degree of OHSS (composite outcome)	Symptoms of nausea, vomiting, shortness of breath, abdominal pain,abdominal distension. Ovarian size and fluid in douglas pouch by ultrasound. Haematocrit, total leucocytic count, creatinine and Estradiol level as biochemical markers. Early OHSS first 9 days after ovum pickup and late is after 9 days till 14 days (time of pregnancy test)	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of oocytes	Number of oocytes collected on the day of oocyte collection	1 day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Metaphase II (MII) oocytes	Number of MII oocytes collected on the day of oocyte collection	1 day
Fertilization rate	Number of embryos that show signs of fertilization in each patient	2 days
Number of embryos	Number of embryos assessed for embryo transfer in each patient	3 to 5 days
Implantation rate	the ratio of the number of gestational sacs to the number of embryos transferred	5 weeks
Chemical pregnancy rate	The patients who have a positive quantitative Beta human chorionic gonadotrophin (BHCG) and do not continue their pregnancy with a drop in the result and start of menstruation	14 days
Clinical pregnancy rate	patients who show an intra-uterine gestational sac with positive fetal pulsations on ultrasound 14 days after their pregnancy test	28 days
Early miscarriage rate	pregnancy loss in the first 12 weeks of gestation	12 weeks
Ongoing pregnancy rate	pregnancies going beyond 12 weeks of gestation	12 weeks
Live birth rate	live births occuring	40 weeks

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Study Chair: Mohamed Roushdy, MD, Cairo university

Publications and helpful links

General Publications

• Esinler I, Bozdag G, Karakocsokmensuer L. Preventing ovarian hyperstimulation syndrome: cabergoline versus coasting. Arch Gynecol Obstet. 2013 Nov;288(5):1159-63. doi: 10.1007/s00404-013-2875-z. Epub 2013 May 16.
• Bassiouny YA, Dakhly DMR, Bayoumi YA, Salaheldin NM, Gouda HM, Hassan AA. Randomized trial of combined cabergoline and coasting in preventing ovarian hyperstimulation syndrome during in vitro fertilization/intracytoplasmic sperm injection cycles. Int J Gynaecol Obstet. 2018 Feb;140(2):217-222. doi: 10.1002/ijgo.12360. Epub 2017 Nov 9.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: October 31, 2013
• First Submitted That Met QC Criteria: November 7, 2013
• First Posted (Estimate): November 14, 2013

Study Record Updates

• Last Update Posted (Actual): August 14, 2017
• Last Update Submitted That Met QC Criteria: August 11, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: ICSI; OHSS; Cabergoline; Coasting
• Other Study ID Numbers: 92013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No