Can GnRH Agonist Trigger Prevent Ovarian Hyperstimulation Syndrome?

Ovarian Hyperstimulation Syndrome Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01714648
• Other study ID #: MSD-ELISHA1
• Secondary ID: 8328-086
• Status: Terminated
• Phase: Phase 4
• First received: October 20, 2012
• Last updated: August 3, 2015
• Start date: November 2012
• Est. completion date: January 2014

Study information

• Verified date: August 2015
• Source: Elisha Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Ovarian Hyperstimulation Syndrome

Intervention

Drug:
• Triptorelin 0.2 mg
A single bolus of 0.2 mg triptorelin given 34-36 hours before oocyte retrieval.

Locations

Country	Name	City	State
Israel	IVF Unit, Elisha Hospital	Haifa

Sponsors (2)

Lead Sponsor	Collaborator
Elisha Hospital	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Secondary	Ongoing pregnancies following FTET cycles of cryopreserved embryos obtained following one treatment cycle of follitropin beta.		One month from embryo transfer date	No