Dual Versus Single Trigger in IVF Patients at High Risk of Ovarian Hyper Stimulation Syndrome: a Randomized, Double-blinded, Controlled Trial.
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Total number of Day 5 embryos
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •They are between the ages of 18 and
- •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.
排除标准
- •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
研究组 & 干预措施
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).
干预措施: Pregnyl (1,500) IU (Drug)
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).
干预措施: 1.5 mL of normal saline (Drug)
结局指标
主要结局
Total number of Day 5 embryos
时间窗: after 5 days of oocyte fertilization
Total number of "good quality" Day 5 embryos available for cryopreservation.
次要结局
- Total number of mature oocytes (MII) retrieve per IVF/ICSI cycle.(2-3 days after oocyte retrieval)
- Total number of fertilized zygotes.(3-5 days after the egg retrieval)
- Pregnancy Rate(Upto 13 weeks after the embryo transfer)
- Implantation rate(3-4 weeks after implantation of embryos)
- Incidence of moderate to critical OHSS(Upto 2 weeks from the date of intervention)
- Clinical pregnancy rate(Upto 13 weeks after the embryo transfer)
- Miscarriage rate(Within 20 weeks from the date of the clinical intrauterine pregnancy confirmation ultrasount)
- Total number of oocytes retrieved per cycle.(within 1-2 days of oocyte retrieval)
- Fertilization rate(3-5 days after the egg retrieval)
- Total number of Day 3 embryos.(3 days after the fertilization of oocyte)
- Live birth rate(Per embryo(s) transferred during the study period and follow-up for up to 10 months after last transfer.])
研究者
Miguel Angel Russo
Physician
Mount Sinai Hospital, Canada