Can GnRH Agonist Trigger Prevent Ovarian Hyperstimulation Syndrome?

An Uncontrolled, Open-label Feasibility Study to Demonstrate That a GnRH Agonist (Decapeptyl) Can be Safely Administered to Trigger Final Oocyte Maturation in High Responder Patients to Mitigate the Risk of OHSS

Ovarian hyperstimulation syndrome (OHSS) is a major complication of ovarian stimulation for IVF if hCG is used to trigger final oocyte maturation. The investigators propose that using GnRH agonist as a trigger will eliminate OHSS, even in high-risk patients.

Study Overview

• Status: Terminated
• Conditions: Ovarian Hyperstimulation Syndrome
• Intervention / Treatment: Drug: Triptorelin 0.2 mg

Detailed Description

Administration of hCG (10.000 or 5.000 IU) is essential in IVF protocols to trigger final oocyte maturation after ovarian stimulation. In high responder patients with potential risk of developing OHSS, hCG is usually withheld and the treatment cycle is cancelled without obtaining (cryopreserved) embryos for replacement.

An alternative approach to trigger final oocyte maturation is to administer a GnRH agonist instead of hCG. This method is not possible following a long GnRH agonist protocol which causes down-regulation of the GnRH receptor. However, following GnRH antagonist treatment the GnRH receptor remains receptive to competitive binding by a GnRH agonist.

It has been well-described in earlier IVF trials that a bolus of GnRH agonist will displace the GnRH antagonist from the GnRH receptors in the pituitary inducing an endogenous LH (and FSH) surge resulting in the maturation of oocytes and good quality embryos. In addition, the risk of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) becomes minimal due to the rapid demise of the corpora lutea. Following luteolysis, fresh embryo transfer would require alternative luteal phase support to secure good clinical outcome. Alternatively, good quality embryos obtained after GnRH agonist triggering can be cryopreserved and replaced in following frozen-thawn embryo transfer (FTET) cycles. Thus, also eliminating late onset OHSS due to pregnancy.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 31064
    • IVF Unit, Elisha Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• A female patient who needs IVF to become pregnant.
• Regular menstrual cycle.
• Antral follicular count (AFC) > 18
• Following treatment with follitropin beta more than 18 follicles ≥ 11 mm will develop.

Exclusion Criteria:

• Hypersensitivity to the active substance or to any of the medications used.
• Tumors of the ovary, breast, uterus, pituitary or hypothalamus.
• Pregnancy.
• Abnormal (not menstrual) vaginal bleeding without a known/diagnosed cause.
• Primary ovarian failure.
• Ovarian cysts or enlarged ovaries.
• A history of Ovarian Hyperstimulation Syndrome (OHSS).
• A previous COS cycle that resulted in more than 30 follicles > 11 mm measured by ultrasound examination.
• Fibroid tumours of the uterus incompatible with pregnancy.
• Malformations of the reproductive organs incompatible with pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OHSS high risk patients; Triptorelin 0.2 mg	Drug: Triptorelin 0.2 mg; A single bolus of 0.2 mg triptorelin given 34-36 hours before oocyte retrieval.; Other Names: Decapeptyl 0.2 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety: The adverse event is the development of OHSS following oocyte retrieval.	OHSS usually occurs a few days following oocyte retrieval, and is not a threat once menses start.	12 day from GnRH agonist trigger day.

Secondary Outcome Measures

Outcome Measure	Time Frame
Ongoing pregnancies following FTET cycles of cryopreserved embryos obtained following one treatment cycle of follitropin beta.	One month from embryo transfer date

Collaborators and Investigators

• Sponsor: Elisha Hospital
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Shahar Kol, MD, Elisha Hospital, Haifa, Israel

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: October 20, 2012
• First Submitted That Met QC Criteria: October 23, 2012
• First Posted (Estimate): October 26, 2012

Study Record Updates

• Last Update Posted (Estimate): August 4, 2015
• Last Update Submitted That Met QC Criteria: August 3, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: OVULATION INDUCTION
• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Syndrome; Ovarian Hyperstimulation Syndrome; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Luteolytic Agents; Triptorelin Pamoate
• Other Study ID Numbers: MSD-ELISHA1; 8328-086 (Other Grant/Funding Number: MSD Database number 50036)