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

NCT ID: NCT05638529

Last Updated: 2023-07-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-01
• Study Completion Date: 2023-12-31

Brief Summary

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.

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.

Conditions

Ovarian Hyperstimulation Syndrome; Infertility, Female

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Pregnyl (1,500) IU

Intervention Type: DRUG

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.

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).

Group Type: PLACEBO_COMPARATOR

1.5 mL of normal saline

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Hcg; Normal Saline

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Mount Sinai Hospital, Canada

OTHER

Sponsor Role: lead

Responsible Party

Miguel Angel Russo

Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Miguel Russo, MD

Role: PRINCIPAL_INVESTIGATOR

Mount Sinai Hospital, Canada

Locations

Mount Sinai Hospital, Fertility Clinic

Toronto, Ontario, Canada

Countries

Canada

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Other Identifiers

17-0302-A

Identifier Type: -

Identifier Source: org_study_id