Clinical trial NCT01714648: Can GnRH Agonist Trigger Prevent Ovarian Hyperstimulation Syndrome?
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Ovarian Hyperstimulation Syndrome
Keywords: OVULATION INDUCTION
Lead sponsor: Elisha Hospital
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2012-10-26
Enrollment: 6
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

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 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

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety: The adverse event is the development of OHSS following oocyte retrieval.
timeFrame: 12 day from GnRH agonist trigger day.
Secondary outcomes:
measure: Ongoing pregnancies following FTET cycles of cryopreserved embryos obtained following one treatment cycle of follitropin beta.
timeFrame: One month from embryo transfer date
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: IVF Unit, Elisha Hospital
Study officials:
affiliation: Elisha Hospital, Haifa, Israel
name: Shahar Kol, MD
role: PRINCIPAL_INVESTIGATOR
References: