Can GnRH Agonist Trigger Prevent Ovarian Hyperstimulation Syndrome?

This study has been terminated.
(Terminated: recruiting or enrolling participants has halted prematurely and will not resume; participants are no longer being examined or treated)
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Dr. Shahar Kol, Elisha Hospital
ClinicalTrials.gov Identifier:
NCT01714648
First received: October 20, 2012
Last updated: January 4, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Ovarian Hyperstimulation Syndrome
Drug: Triptorelin 0.2 mg
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Elisha Hospital:

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


Secondary Outcome Measures:
  • Ongoing pregnancies following FTET cycles of cryopreserved embryos obtained following one treatment cycle of follitropin beta. [ Time Frame: One month from embryo transfer date ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: November 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Decapeptyl 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.

  Eligibility

Ages Eligible for Study:   18 Years to 42 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01714648

Locations
Israel
IVF Unit, Elisha Hospital
Haifa, Israel, 31064
Sponsors and Collaborators
Elisha Hospital
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Shahar Kol, MD Elisha Hospital, Haifa, Israel
  More Information

No publications provided

Responsible Party: Dr. Shahar Kol, Principal Investigator, Elisha Hospital
ClinicalTrials.gov Identifier: NCT01714648     History of Changes
Other Study ID Numbers: MSD-ELISHA1, 8328-086
Study First Received: October 20, 2012
Last Updated: January 4, 2014
Health Authority: Israel: Ministry of Health

Keywords provided by Elisha Hospital:
OVULATION INDUCTION

Additional relevant MeSH terms:
Ovarian Hyperstimulation Syndrome
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Triptorelin
Deslorelin
Luteolytic Agents
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014