Clinical trial NCT02703584: Co Administration of GnRH Agonist and hCG for Final Oocyte Maturation
Official title: Co Administration of GnRH Agonist and hCG for Final Oocyte Maturation- A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility
Keywords: Double trigger
Lead sponsor: Mount Sinai Hospital, Canada
Sponsor class: OTHER
First posted: 2016-03-09
Enrollment: 276
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 41
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: All the studies, demonstrating improved oocyte maturity and high pregnancy rate with the dual trigger are all retrospective. The investigators therefore aim to perform a prospective randomized controlled study in normal responders, comparing cycles triggered with hCG to those triggered with hCG+GnRH agonist.

Detailed description: A prospective, randomized, double blinded clinical trial. Patients will undergo standard clinical and hormonal investigation as usual for IVF. Patients that will be given the standard GnRH antagonist IVF protocol will be prospectively randomized into two groups: 1. hCG group- will be triggered for final follicular maturation with hCG (Pregnyl 10,000IU) as is usual and placebo (normal saline) - 36 hours prior to oocyte aspiration. 2. The Double trigger group- will receive GnRH agonist (Suprefact 0.5 mg) and hCG (Pregnyl 10,000IU) 36 hours prior to the oocyte aspiration. All patients will be supplemented with the usual progesterone preparation (vaginal progesterone suppositories) for luteal support.

In order to increase the rate of MII from to 65% to 80% with an alpha error of 5% and beta error of 80% the sample size needed is 276 total patients in both groups or 138 patients in each group.

Eligibility criteria: Inclusion Criteria:

* Women during one of their first 3 IVF cycle attempts
* Women between the ages of 18-42.
* BMI (body mass index) of 18-35.
* AMH (Anti mullerian hormone) \> 1 ng/ml
* FSH˂ 20 IU/L.
* Informed consent.

Exclusion Criteria:

* Women with low ovarian response
* Previous enrollment in this study.
* AFC\>20
* E2 above 15,000 pmol/l at the trigger day.
* hypersensitive to Suprefact/Pregny/gonal F/Purigon/Menopur/progesterone, and/or their ingredients/components of the formulation
* primary ovarian failure
* pregnancy and breast-feeding
* active blood clots
* undiagnosed uterine or genital bleeding
* endometriosis
* uncontrolled hypertension;
* uncontrolled diabetes
* abnormal liver and kidney functions
* abnormal ECG, e.g. QT prolongation and torsades de pointes
* cancers/tumors, e.g. pituitary adenomas, ovarian cysts, etc.
* HIV, HBV and HCV infections
* low bone mineral density (BMD) and an increased risk of bone fracture, such as chronic alcohol and/or tobacco use, presumed or strong family history of osteoporosis or chronic use of drugs that can reduce bone mass such as anticonvulsants or corticosteroids
* suicidal tendency, history or disposition to seizures, state of confusion, clinically relevant psychiatric disorders, and brain lesions
* Use of an investigational drug or participation in an investigational study within 30 days prior to this study.

Primary outcomes:
measure: Number of mature oocytes
timeFrame: 2 days after randomization
Secondary outcomes:
measure: Blastocyst rate
timeFrame: 8 days after the randomization
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: TRIO Fertility
state: Ontario
Study officials:
affiliation: Scientific Director TRIO IVF
name: Robert F Casper, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haas J, Bassil R, Samara N, Zilberberg E, Mehta C, Orvieto R, Casper RF. GnRH agonist and hCG (dual trigger) versus hCG trigger for final follicular maturation: a double-blinded, randomized controlled study. Hum Reprod. 2020 Jul 1;35(7):1648-1654. doi: 10.1093/humrep/deaa107.