Dual Trigger" in IVF Patients at High Risk of Ovarian Hyper Stimulation Syndrome

June 29, 2023 updated by: Miguel Angel Russo, Mount Sinai Hospital, Canada

Dual Versus Single Trigger in IVF Patients at High Risk of Ovarian Hyper Stimulation Syndrome: a Randomized, Double-blinded, Controlled Trial.

The present study aims to evaluate whether the use of a "dual trigger" can improve IVF outcomes, compared to GnRH agonist (GnRH-a) alone, in patients at high risk of OHSS undergoing a freeze-all cycle. By examining freeze-all cycles with frozen embryo transfer(s) (FET) only, we eliminate the potential confounding issue of inadequate luteal support to the endometrium and focus primarily on the effect of a "dual trigger" on oocyte quality and embryo potential.

To our best knowledge, there have been no randomized, controlled trials conducted to address this hypothesis.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

While the use of GnRH-a trigger has nearly eliminated the risk of OHSS, several studies have shown that this strategy may be associated with poorer IVF outcomes after a fresh embryo transfer (Engmann et al., 2008; Galindo et al., 2009; Melo et al., 2017; Sismanoglu et al., 2009; Youssef et al., 2014). These findings may be partly explained by an inadequate LH surge, following a GnRH-a trigger, and raises two separate concerns. The first concern is whether an inadequate LH surge can have an detrimental effect on luteal support following a fresh embryo transfer. The corpus luteum requires constant LH stimulation, during implantation and early gestation, in order to optimize endometrial receptivity via the production of progesterone. The second concern is whether a suboptimal LH surge can reduce the number or quality of mature oocytes retrieved during a treatment cycle. Immature oocytes will not fertilize invitro and, therefore, can decrease a woman's overall success rate with IVF. Based on this second premise, another strategy was developed whereby a "dual trigger", using a combination of a GnRH-a and a lower dose of hCG (1,500 IU), is used to help maximize the number of "mature eggs" retrieved during an IVF cycle without increasing the risk of OHSS. Two recent retrospective studies have evaluated the administration of a "dual trigger" with GnRH agonist in combination with low-dose hCG (1,000 IU), compared to GnRH agonist alone (O'Neill et al., 2016; Griffin et al., 2012). Both studies revealed a significant improvement in the number of mature oocytes retrieved between treatment and controls (Griffin et al., 2012). While these findings are promising, it is important to note that oocyte maturity does not equate to embryo potential. Therefore, whether the use of a "dual trigger" improves embryo development and competency, thus increasing a patient's success rate, remains to be determined.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G1X6
        • Mount Sinai Hospital, Fertility Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • They are between the ages of 18 and 40.
  • They are undergoing IVF treatment with a GnRH antagonist protocol.

  • During their current treatment cycle, they have at least one of the following risk factors for OHSS:

    • Greater or equal to 13 follicles measuring at least 11 mm on the day of trigger.
    • Serum estradiol levels greater or equal to 15,000 pmol/L on the day of trigger.

Exclusion Criteria:

  • They are using a GnRH agonist protocol (which is a contraindication to using a GnRH agonist trigger).
  • They are planning on using a "dual trigger" (based on poor outcomes in a previous IVF cycle using a GnRH agonist trigger).
  • They have a low ovarian reserve (AFC < 7 follicles or AMH < 10 pmol/L).
  • They have had a previous failed GnRH agonist trigger.
  • They have a known diagnosis of hypogonadotropic hypogonadism.
  • They have had a previous adverse or allergic reaction to GnRH agonist in the past.
  • They are using surgically retrieved sperm.
  • They are undergoing treatment for fertility preservation (oncofertility patients).
  • They have a history of recurrent implantation failure (defined as no clinical pregnancy after transfer of > 4 good-quality embryos).
  • They have any congenital or acquire uterine anomalies distorting the uterine cavity.
  • If serum estradiol levels are equal or exceed 28,000 pmol/L on the day of trigger

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Arm- Group A
A subcutaneous injection of a GnRH agonist (Suprefact 0.5 mg) and a separate intramuscular injection of hCG (Pregnyl 1,500 IU).
Drug: Pregnyl (1,500) IU
Patients will self-administer a subcutaneous injection of a GnRH agonist (Suprefact 0.5 mg) and a separate intramuscular injection of hCG (Pregnyl 1,500 IU) on their assigned trigger day.
Other Names:
  • Hcg
Placebo Comparator: Control Arm- Group B
A subcutaneous injection of a GnRH agonist (Suprefact 0.5 mg) and a separate intramuscular injection of normal saline (1.5 mL) (sham-placebo).
Drug: 1.5 mL of normal saline
Patients will self-administer a subcutaneous injection of a GnRH agonist (Suprefact 0.5 mg) and a separate intramuscular injection of normal saline (1.5 mL - sham placebo) on their assigned trigger day.
Other Names:
  • Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total number of Day 5 embryos
Time Frame: after 5 days of oocyte fertilization
Total number of "good quality" Day 5 embryos available for cryopreservation.
after 5 days of oocyte fertilization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total number of oocytes retrieved per cycle.
Time Frame: within 1-2 days of oocyte retrieval
within 1-2 days of oocyte retrieval
Total number of mature oocytes (MII) retrieve per IVF/ICSI cycle.
Time Frame: 2-3 days after oocyte retrieval
2-3 days after oocyte retrieval
Total number of fertilized zygotes.
Time Frame: 3-5 days after the egg retrieval
3-5 days after the egg retrieval
Fertilization rate
Time Frame: 3-5 days after the egg retrieval
Number of 2PN zygote(s) divided by the number of mature oocyte(s) fertilized per IVF/ICSI cycle OR Number of 2PN zygote(s) divided by the number of oocytes incubated with at least 10,000 sperm per IVF cycle.
3-5 days after the egg retrieval
Total number of Day 3 embryos.
Time Frame: 3 days after the fertilization of oocyte
3 days after the fertilization of oocyte
Pregnancy Rate
Time Frame: Upto 13 weeks after the embryo transfer
A serum b-hCG > 5 mIU/mL per transfer
Upto 13 weeks after the embryo transfer
Clinical pregnancy rate
Time Frame: Upto 13 weeks after the embryo transfer
Number of gestational sac(s) with a positive fetal heart per transfer.
Upto 13 weeks after the embryo transfer
Implantation rate
Time Frame: 3-4 weeks after implantation of embryos
Number of gestational sac(s) divided by the number of embryo(s) transferred per FET.
3-4 weeks after implantation of embryos
Miscarriage rate
Time Frame: Within 20 weeks from the date of the clinical intrauterine pregnancy confirmation ultrasount
The number of spontaneous pregnancy losses before 20 weeks gestation divided by the number of clinical pregnancies
Within 20 weeks from the date of the clinical intrauterine pregnancy confirmation ultrasount
Live birth rate
Time Frame: Per embryo(s) transferred during the study period and follow-up for up to 10 months after last transfer.]
The number of live born neonates over 24 weeks gestation divided by the number of clinical pregnancies
Per embryo(s) transferred during the study period and follow-up for up to 10 months after last transfer.]
Incidence of moderate to critical OHSS
Time Frame: Upto 2 weeks from the date of intervention
Based on the classification criteria by Mathur et al. (2007).
Upto 2 weeks from the date of intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mount Sinai Hospital, Canada

Investigators

  • Principal Investigator: Miguel Russo, MD, Mount Sinai Hospital, Canada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2019

Primary Completion (Estimated)

December 31, 2023

Study Completion (Estimated)

December 31, 2023

Study Registration Dates

First Submitted

November 23, 2022

First Submitted That Met QC Criteria

December 2, 2022

First Posted (Actual)

December 6, 2022

Study Record Updates

Last Update Posted (Actual)

July 3, 2023

Last Update Submitted That Met QC Criteria

June 29, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-0302-A

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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