Recruiting
Phase 4

Ovulation Medication

Sponsor:

Create Fertility Center

Code:

NCT02715336

Conditions

IVF Cycle

Ovarian Stimulation

Egg Retrieval

Pregnancy

Miscarriages

Eligibility Criteria

Sex: Female

Age: 18 - 45

Healthy Volunteers: Accepted

Interventions

Ovulation induction with hCG and Lupron (GnRH agonist)

Study Details

Brief summary:

Individuals undergoing In Vitro Fertilization must undergo controlled ovarian hyperstimulation (COH) to produce enough quality eggs for fertility treatment. Ovarian follicular responsiveness to COH with gonadotropins is extremely variable between patients and even from cycle to cycle for the same patient. Achieving an ideal follicular response is critical to the success of assisted reproduction treatment (ART). Patients have been classified as 'poor', 'normal' or 'high' responders, which dictate the amount of gonadotropins that they receive. It is still important to develop treatments with high efficacy, lower multiple birth rates, and a lower complication rate for each of these groups. In an era of evidence-based medicine and with special emphasis on reducing IVF risks (mainly OHSS and pregnancies with multiples), it is very important to find optimal and safe ovulation induction and triggering regimens for each patient population.

The use of GnRH agonist (GnRHa) triggering among high responders in order to reduce or eliminate OHSS is an example of an important breakthrough in the clinical management of IVF patients. Although GnRHa triggering was shown to be as effective as human chorionic gonadotropin (hCG) at inducing oocyte maturation more than 20 years ago, its use to trigger ovulation was not possible until the introduction of GnRH antagonists for pituitary suppression.

Another prominent trend in ART in recent years has been the introduction of dual triggering, which involves a combination of GnRHa plus hCG for triggering. This regimen creates simultaneous lutenizing hormone (LH) and follicle stimulating hormone (FSH) surges by the GnRHa, which resembles physiologic ovulation triggering, together with sustained LH-like activity from the hCG, which stimulates the corpus luteum to excrete sufficient hormonal endometrial support. Since its introduction, dual triggering has been gaining popularity due to outstanding results in retrospective studies among both normal and high responders. Moreover, in spite of the encouraging retrospective reports, prospective randomized controlled trials (RCT) on dual triggering have not been reported to date. The aim of the current proposed study is to compare the efficacy of dual triggering and conventional triggering among the three IVF populations (high, normal and poor responders).

Conditions

IVF Cycle

Ovarian Stimulation

Egg Retrieval

Pregnancy

Miscarriages

Study ID

NCT02715336

Start date

Oct, 2015

Status verified date

Jul, 2020

Completion date

Sep, 2021

Anticipated

Primary completion date

Sep, 2020

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 18 - 45

Healthy Volunteers: Accepted

A) Dual triggering vs. GnRH agonist alone in high responders IVF patients

Inclusion Criteria - At least one of the following risk factors:

  • AMH > 29 pmol/L
  • AFC > 16
  • PCOS diagnosed according to Rotterdam criteria: any two of the following three features: 1) oligo- or anovulation; 2) clinical and/or biochemical hyper-androgenemia; and 3) PCO-US with exclusion of other etiologies as mentioned in the National Institute of Child Health and Human Development (NICHD) criteria
  • Previous OHSS
  • Previous cycle cancellation due to OHSS risk
  • Previous coasting
  • Participants initially recruited to the normal responders study who exhibit excessive ovarian response markers on triggering day: high amount of middle-large follicles (> 13 follicles ≥ 11mm on triggering day). All previous inclusion criteria are assessed before initiation of the IVF cycle and ovarian stimulation, and all of them represent pre-stimulation risk factors for high ovarian response. The patient's actual response will be assessed on triggering day (after completion of ovarian stimulation). Final assignment of responder category followed by randomization will only be performed on the day of triggering
  • informed consent obtained
  • Must be 18 years or older
  • Ability to speak and read English, or understand French, Mandarin, Cantonese, Arabic, or Filipino.

Exclusion criteria:

  • Chronic disease
  • Hypogonadotrophic hypogonadism
  • Untreated uterine abnormalities
  • E2>4000 pg/ml (>14,680 pmol/L) on trigger day. These very high risk patients will undergo GnRHa only trigger and will be excluded from the trial.

B) Dual triggering vs. 5000 units hCG in normal responders

Inclusion criteria:

  • Age above 18 years and less than 40 years
  • Do not fulfill criteria for poor responder or high responder

Exclusion criteria:

  • Bologna criteria for poor responders exclusion: two of the following should need to be fulfilled:

1. Age > 40 or other risk factor for decreased ovarian reserve (ex. ovarian surgery)
2. Single abnormal test for ovarian reserve (AFC < 6 or AMH < 8 pmol/L)
3. Previous poor response in previous cycle: cancellation or < 4 retrieved oocytes in response to daily 150 FSH units
  • Criteria for high responders' exclusion

1. AMH > 29 pmol/L
2. AFC > 16
3. PCOS diagnosed according to Rotterdam criteria \[19, 28\]: any two of the following three features: 1) oligo- or anovulation; 2) clinical and/or biochemical hyper-androgenemia; and 3) PCO-US with exclusion of other etiologies as mentioned in the NICHD criteria
4. Previous OHSS
5. Previous cycle cancellation due to OHSS risk
6. Previous coasting
7. Excessive ovarian response markers on triggering day such as high amount of middle-large follicles (> 13 follicles ≥ 11mm on triggering day) and E2 concentration (optional E2 > 14500 pmol/L on triggering day). These patients will be allocated to the high responders group.
  • Untreated uterine abnormalities
  • Chronic disease

C) Dual Triggering for Poor Responders

Inclusion criteria: According to Bologna criteria two of the following should be fulfilled:

  • Age > 40 or other risk factor for decreased ovarian reserve (ex. ovarian surgery).
  • Single abnormal test for ovarian reserve (AFC < 6 or AMH < 8 pmol/L).
  • Previous poor response in previous cycle: cancellation or < 4 retrieved oocytes in response to daily 150 FSH units.

Exclusion criteria:

  • Chronic disease
  • Untreated uterine abnormalities
  • Response consistent with normal or high responder, as defined above

Study Design

Enrollment

666 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Study group: High Responders

1000 units hCG

no intervention: Control group: High Responders

1000 units hCG

experimental: Study group: Normal Responders

5000 units hCG

no intervention: Control group: Normal Responders

5000 units hCG

experimental: Study group: Low Responders

10000 units hCG

no intervention: Control group: Low Responders

10000 units hCG

Interventions

Ovulation induction with hCG and Lupron (GnRH agonist)

Patients treated for infertility are categorized as a low-, normal- or high responder according to their estimated ovarian response to hormonal stimulation. This classification dictates the hormonal stimulation regimen that they will receive. In contrast to hCG triggering, GnRHa triggering is characterized by simultaneous LH and FSH surges, similar to natural ovulation. A combination of GnRHa plus hCG for triggering creates simultaneous LH and FSH surges by the GnRHa, which resembles physiologic ovulation triggering, together with sustained LH-like activity from the hCG, stimulating the corpus luteum to excrete sufficient hormonal endometrial support.

Primary outcome measure

  • Implantation rate [ Time Frame: 14 days post IVF procedure ]
  • Human Chorionic Gonadotropin serum levels [ Time Frame: 2-4 weeks post IVF procedure ]
  • Ongoing pregnancy rate [ Time Frame: 9 months post IVF procedure ]
  • Miscarriage rate [ Time Frame: 9 months post procedure ]
  • Ovarian hyperstimulation syndrome [ Time Frame: 7 days post IVF procedure ]
  • Fetal heartbeat measured by ultrasound [ Time Frame: 2-4 weeks post IVF procedure ]

Central Contacts and Locations

Central contacts

Noga Weizman, MD

416323772drweizman@createivf.com

Kevin Quach, MSc

4163237727kev.quach@mail.utoronto.ca

Locations

Create Fertility Centre

Recruiting

Toronto, Ontario, Canada, M5G1N8

Contacts

Deborah Davies, RN

416-813-4702

Principal Investigator:

Clifford Librach, MD

More Information

Sponsor

Create Fertility Center

Last update posted

Jul 20, 2020

Last verified

Jul, 2020

Keywords

  • In vitro fertilization
  • IVF
  • Assisted Reproductive Technologies
  • ART
  • OHSS
  • Ovarian hyperstimulation
  • dual triggering
  • GnRH

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-24. This information was provided to ClinicalTrials.gov by Create Fertility Center on 2020-07-20. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.