Clinical trial NCT05638529: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Ovarian Hyperstimulation Syndrome
Infertility, Female
Keywords: oocyte Maturity
Dual Trigger
Infertility, Female
Lead sponsor: Mount Sinai Hospital, Canada
Sponsor class: OTHER
First posted: 2022-12-06
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Total number of Day 5 embryos
timeFrame: after 5 days of oocyte fertilization
Secondary outcomes:
measure: Total number of oocytes retrieved per cycle.
timeFrame: within 1-2 days of oocyte retrieval
measure: Total number of mature oocytes (MII) retrieve per IVF/ICSI cycle.
timeFrame: 2-3 days after oocyte retrieval
measure: Total number of fertilized zygotes.
timeFrame: 3-5 days after the egg retrieval
measure: Fertilization rate
timeFrame: 3-5 days after the egg retrieval
measure: Total number of Day 3 embryos.
timeFrame: 3 days after the fertilization of oocyte
measure: Pregnancy Rate
timeFrame: Upto 13 weeks after the embryo transfer
measure: Clinical pregnancy rate
timeFrame: Upto 13 weeks after the embryo transfer
measure: Implantation rate
timeFrame: 3-4 weeks after implantation of embryos
measure: Miscarriage rate
timeFrame: Within 20 weeks from the date of the clinical intrauterine pregnancy confirmation ultrasount
measure: Live birth rate
timeFrame: Per embryo(s) transferred during the study period and follow-up for up to 10 months after last transfer.]
measure: Incidence of moderate to critical OHSS
timeFrame: Upto 2 weeks from the date of intervention
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital, Fertility Clinic
state: Ontario
Study officials:
affiliation: Mount Sinai Hospital, Canada
name: Miguel Russo, MD
role: PRINCIPAL_INVESTIGATOR
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