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

Primary Purpose

Ovarian Hyperstimulation Syndrome, Infertility, Female

Status
Active
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Pregnyl (1,500) IU
1.5 mL of normal saline
Sponsored by
Mount Sinai Hospital, Canada
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Hyperstimulation Syndrome focused on measuring oocyte Maturity, Dual Trigger, Infertility, Female

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Mount Sinai Hospital, Fertility Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment Arm- Group A

Control Arm- Group B

Arm Description

A subcutaneous injection of a GnRH agonist (Suprefact 0.5 mg) and a separate intramuscular injection of hCG (Pregnyl 1,500 IU).

A subcutaneous injection of a GnRH agonist (Suprefact 0.5 mg) and a separate intramuscular injection of normal saline (1.5 mL) (sham-placebo).

Outcomes

Primary Outcome Measures

Total number of Day 5 embryos
Total number of "good quality" Day 5 embryos available for cryopreservation.

Secondary Outcome Measures

Total number of oocytes retrieved per cycle.
Total number of mature oocytes (MII) retrieve per IVF/ICSI cycle.
Total number of fertilized zygotes.
Fertilization rate
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.
Total number of Day 3 embryos.
Pregnancy Rate
A serum b-hCG > 5 mIU/mL per transfer
Clinical pregnancy rate
Number of gestational sac(s) with a positive fetal heart per transfer.
Implantation rate
Number of gestational sac(s) divided by the number of embryo(s) transferred per FET.
Miscarriage rate
The number of spontaneous pregnancy losses before 20 weeks gestation divided by the number of clinical pregnancies
Live birth rate
The number of live born neonates over 24 weeks gestation divided by the number of clinical pregnancies
Incidence of moderate to critical OHSS
Based on the classification criteria by Mathur et al. (2007).

Full Information

First Posted
November 23, 2022
Last Updated
June 29, 2023
Sponsor
Mount Sinai Hospital, Canada
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1. Study Identification

Unique Protocol Identification Number
NCT05638529
Brief Title
Dual Trigger" in IVF Patients at High Risk of Ovarian Hyper Stimulation Syndrome
Official Title
Dual Versus Single Trigger in IVF Patients at High Risk of Ovarian Hyper Stimulation Syndrome: a Randomized, Double-blinded, Controlled Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 1, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mount Sinai Hospital, Canada

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Hyperstimulation Syndrome, Infertility, Female
Keywords
oocyte Maturity, Dual Trigger, Infertility, Female

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm- Group A
Arm Type
Experimental
Arm Description
A subcutaneous injection of a GnRH agonist (Suprefact 0.5 mg) and a separate intramuscular injection of hCG (Pregnyl 1,500 IU).
Arm Title
Control Arm- Group B
Arm Type
Placebo Comparator
Arm Description
A subcutaneous injection of a GnRH agonist (Suprefact 0.5 mg) and a separate intramuscular injection of normal saline (1.5 mL) (sham-placebo).
Intervention Type
Drug
Intervention Name(s)
Pregnyl (1,500) IU
Other Intervention Name(s)
Hcg
Intervention Description
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
Intervention Name(s)
1.5 mL of normal saline
Other Intervention Name(s)
Normal Saline
Intervention Description
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.
Primary Outcome Measure Information:
Title
Total number of Day 5 embryos
Description
Total number of "good quality" Day 5 embryos available for cryopreservation.
Time Frame
after 5 days of oocyte fertilization
Secondary Outcome Measure Information:
Title
Total number of oocytes retrieved per cycle.
Time Frame
within 1-2 days of oocyte retrieval
Title
Total number of mature oocytes (MII) retrieve per IVF/ICSI cycle.
Time Frame
2-3 days after oocyte retrieval
Title
Total number of fertilized zygotes.
Time Frame
3-5 days after the egg retrieval
Title
Fertilization rate
Description
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.
Time Frame
3-5 days after the egg retrieval
Title
Total number of Day 3 embryos.
Time Frame
3 days after the fertilization of oocyte
Title
Pregnancy Rate
Description
A serum b-hCG > 5 mIU/mL per transfer
Time Frame
Upto 13 weeks after the embryo transfer
Title
Clinical pregnancy rate
Description
Number of gestational sac(s) with a positive fetal heart per transfer.
Time Frame
Upto 13 weeks after the embryo transfer
Title
Implantation rate
Description
Number of gestational sac(s) divided by the number of embryo(s) transferred per FET.
Time Frame
3-4 weeks after implantation of embryos
Title
Miscarriage rate
Description
The number of spontaneous pregnancy losses before 20 weeks gestation divided by the number of clinical pregnancies
Time Frame
Within 20 weeks from the date of the clinical intrauterine pregnancy confirmation ultrasount
Title
Live birth rate
Description
The number of live born neonates over 24 weeks gestation divided by the number of clinical pregnancies
Time Frame
Per embryo(s) transferred during the study period and follow-up for up to 10 months after last transfer.]
Title
Incidence of moderate to critical OHSS
Description
Based on the classification criteria by Mathur et al. (2007).
Time Frame
Upto 2 weeks from the date of intervention

10. Eligibility

Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miguel Russo, MD
Organizational Affiliation
Mount Sinai Hospital, Canada
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mount Sinai Hospital, Fertility Clinic
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G1X6
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
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Dual Trigger" in IVF Patients at High Risk of Ovarian Hyper Stimulation Syndrome

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