Clinical trial NCT02208986: GnRHa Trigger in Asian Oocyte Donors- a Dose Finding Study
Official title: GnRHa Trigger in Asian Oocyte Donors Co-treated With a GnRH Antagonist - a Dose Finding Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Normal Oocyte Donors
Keywords: GnRH antagonist
GnRH agonist trigger
Oocyte donor
Lead sponsor: Vietnam National University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: The Fertility Clinic, Skive Regional Hospital, Denmark
name: Aarhus University Hospital
name: University of Southern Denmark
First posted: 2014-08-05
Enrollment: 165
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this randomized single center study is to explore the most optimal dose of GnRHa used for triggering of final oocyte maturation in IVF. The study group will consist of oocyte donors who have GnRHa trigger as a standard trigger concept.

Hypothesis: In an Asian oocyte donor population, the use of 0.2 mg, 0.3mg or 0.4 mg of GnRHa will lead to the retrieval of comparable numbers of mature oocytes (MII) and good quality embryos. Moreover, the reproductive outcome in the recipients will be similar regardless of the dose of GnRHa used for trigger.

Detailed description: Methods

A randomized controlled single center study. All oocyte donors, fulfilling the inclusion criteria, will be eligible for inclusion after randomization.

Stimulation, monitoring, oocyte pick-up in donors and embryo transfer in recipients On day two of the cycle, - i.e. prior to commencing stimulation with long acting FSH (Elonva) - donors will be randomized to one of three groups, using different doses of GnRHa (Triptorelin) for trigger. Stimulation will be performed according to the standard stimulation protocol of the clinic, using Elonva followed by co-treatment with a GnRH antagonist from day 5 of stimulation . The dose of Elonva used for stimulation will be either 100 or 150 µg according to the weight of the patient. The first transvaginal ultrasound scan (TVUS) will be performed after seven or eight days after the Elonva depot injection. As soon as two follicles have reached a size of ≥ 17mm, triggering of final oocyte maturation will be performed with one single bolus of Triptorelin, 0.2 mg, 0.3mg or 0.4 mg. The timing of the trigger will be 6 AM for all groups and the oocyte pick-up (OPU) will be performed after 34 hours, according to the usual practice of the clinic. Importantly, each patient will be asked to check the presence of an LH surge via a urine LH detection kit at 4 hours after the trigger bolus has been administered. Embryo transfer will be performed on day two in all recipients.

Study group I Stimulation according to the abovementioned and ovulation trigger with 0.2mg Triptorelin. All other procedures will be performed according to the practice of the clinic.

Study group II Stimulation according to the abovementioned and ovulation trigger with 0.3mg Triptorelin. All other procedures will be performed according to the practice of the clinic.

Study group III Stimulation according to the abovementioned and ovulation trigger with 0.4mg Triptorelin. All other procedures will be performed according to the practice of the clinic.

Randomization Randomization will be performed using sealed envelopes developed via a computer generated list with blocks of twelve. The randomization will be performed on day two of the cycle. Doctors will be blinded to the randomization, but not patients and nurses.

Follicular fluid (FF) collection FF from the first punctured follicle on each side will be collected and cryo-preserved at -20 degrees for subsequent analysis of steroids.

Granulosa cell gene-expression analysis Cumulus and mural granulosa cells will be preserved and snap-frozen from a sub-group of 10 patients in each group. The primary subsequent analysis will focus on possible differences in LHR gene expression according to GnRHa trigger dose.

Eligibility criteria: Inclusion Criteria:

Oocyte donors who meet the following criteria:

* Age 18 - 35
* BMI \< 28kg/m2
* Normal ovarian reserve, defined by AMH \> 1.25 ng/ml or AFC ≥ 6 measured within two months prior to stimulation start
* Receiving GnRH-antagonist protocol for ovarian stimulation,
* Agreement to participate in the study, and to disclose any medical events to the investigator. The subject must be willing and able to comply with the protocol requirements for the duration of the study.
* Have given written informed consent with the understanding that the subject may withdraw consent at any time without prejudice to future medical care.

Exclusion Criteria:

* Previous poor response (≤ 3 oocytes) after high dose FSH stimulation
* Chronical medical conditions like Diabetes, Crohns disease, Thyroid disease, Hepatitis B and Sexually Transmitted Diseases Simultaneous participation in an interventional clinical trial.
* Concommitant use of either LH or hMG/uFSH preparations in study cycle

Primary outcomes:
measure: Number of mature oocytes
timeFrame: 30 minutes after oocyte retrieval completed
Secondary outcomes:
measure: Day of bleeding after oocyte pick-up
timeFrame: in 2 weeks after oocyte pick-up
measure: Clinical pregnancy
timeFrame: 5 weeks after oocyte pick-up
Other outcomes:
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: My Duc Hospital, IVFMD
state: Ho Chi Minh
Study officials:
affiliation: CGRH, School of Medicine, Vietnam National University HCMC, Vietnam
name: Tuong M Ho, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Obstetrics and Gynecology, University of Medicine and Pharmacy HCMC, Ho Chi Minh City, Vietnam
name: Lan TN Vuong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aarhus University Hospital
name: Peter Humaidan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vuong TN, Ho MT, Ha TD, Phung HT, Huynh GB, Humaidan P. Gonadotropin-releasing hormone agonist trigger in oocyte donors co-treated with a gonadotropin-releasing hormone antagonist: a dose-finding study. Fertil Steril. 2016 Feb;105(2):356-63. doi: 10.1016/j.fertnstert.2015.10.014. Epub 2015 Oct 31.