The Effect of Dual Trigger for Final Oocyte Maturation on IVF/ICSI Outcomes in Patients With Suboptimal Ovarian Response
Condition: Ovarian Stimulation; Reproductive Techniques, Assisted
Study type: Interventional

Summary: 
      Recently, in patients with a suboptimal ovarian response, a study of the role of adding a
      single dose of GnRH agonist to a standard dose of hCG to initiate final oocyte maturation has
      also been studied. Griffin et al. (2014) reported that in patients who had more than 25%
      immature oocytes in their previous IVF cycle, the use of dual stimulation could increase the
      number of mature oocytes. Since studies in this field are limited, the researchers decided to
      design a clinical trial to investigate the effect of adding a GnRH agonist to a standard dose
      of hCG to initiate final oocyte maturation in patients with a sub-optimal ovarian response.
    

Detailed description: 
      Ovulation stimulation will be performed in all patients with the Standard GnRH antagonist
      Protocol with E2 priming, with the antagonist protocol administered in all patients from the
      20th cycle until the start of the next menstrual cycle with 4 mg of estradiol daily. Blood
      sampling (FSH, LH, and estradiol levels) will be performed on the second day of the menstrual
      cycle, just before gonadotropin stimulation. Ovarian stimulation will start from the second
      or third day of menstruation with a maximum dose of 225 units of rFSH (Gonal -F: Serono
      Laboratories Ltd, Geneva, Switzerland), and then if the follicle is observed, start with 13
      injections of GnRH antagonist (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc)). From
      the seventh day of the cycle, the dose of rFSH will be determined according to the rate of
      ovarian response by vaginal ultrasonography two days in advance. If you see at least 2
      follicles 18 mm in size or more, the antagonist will be injected. GnRH and gonadotropins
      (Gonal-F) will stop and (oocyte triggering) will be the final stimulation of oocyte
      maturation, at this time, the block randomization method will be designed to randomize
      allocation of patients into groups with blocks of size 4. Recently, in patients with a
      suboptimal ovarian response, a study of the role of adding a single dose of GnRH agonist to a
      standard dose of hCG to initiate final oocyte maturation has also been studied. Griffin et
      al. (2014) reported that in patients who had more than 25% immature oocytes in their previous
      IVF cycle, the use of dual stimulation could increase the number of mature oocytes. Since
      studies in this field are limited, the researchers decided to design a clinical trial to
      investigate the effect of adding a GnRH agonist to a standard dose of hCG to initiate final
      oocyte maturation in patients with a suboptimal ovarian response.

      Controlled Ovulation stimulation (COS) will be performed in all patients with the Standard
      GnRH antagonist Protocol with E2 priming, with the antagonist protocol administered in all
      patients from the 20th cycle until the start of the next menstrual cycle with 4 mg of
      estradiol daily. Blood sampling (FSH, LH, and estradiol levels) will be performed on the
      second day of the menstrual cycle, just before gonadotropin stimulation. Ovarian stimulation
      will start from the second or third day of menstruation with a maximum dose of 225 units of
      rFSH (Gonal -F: Serono Laboratories Ltd, Geneva, Switzerland), and then if the follicle is
      observed, start with 13 injections of GnRH antagonist (Cetrotide®, 0.25 mg cetrorelix
      acetate, Serono, Inc)). From the seventh day of the cycle, the dose of rFSH will be
      determined according to the rate of ovarian response by vaginal ultrasonography two days in
      advance. If you see at least 2 follicles 18 mm in size or more, the antagonist will be
      injected. GnRH and gonadotropins (Gonal-F) will stop and (oocyte triggering) will be the
      final stimulation of oocyte maturation, at this time, the block randomization method will be
      designed to randomize allocation of patients into groups with blocks of size 4. The required
      number of blocks will be randomly selected according to sample size.

      The final ovarian stimulation (oocyte triggering) will be performed in groups A and B as
      follows:

      Group A (Experimental): 0.2 mg Triptorelin (Decapeptyl; Ferring GmbH) associated with two
      ampoules of Ovitrelle (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) will be administered
      subcutaneously simultaneously.

      Group B (Control): Two ampoules of Ovitrelle® (Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc)
      will be injected subcutaneously.

      The COS cycles with less than two follicles will be cancelled s. Ovum pick up is performed
      32-34 hours after oocyte triggering, and subsequently intracytoplasmic sperm injection (ICSI)
      /in-vitro fertilization (IVF) will be done for all the patients.

      The main outcome measures are the number of dominant follicles (≥13 mm) on the day of hCG
      trigger and the number of mature (MII) oocytes collected after conventional versus
      delayed-start ovarian stimulation protocol. Secondary outcome measures are including total
      number of oocytes retrieved, oocyte maturity rate (number of MII oocytes/total number of
      oocytes), oocyte yield (total number of oocytes retrieved/ antral follicle count [AFC]),
      mature oocyte yield (number of mature oocytes retrieved/AFC), total dosage of gonadotropin
      (recombinant FSH and/or highly purified hMG) needed, number of days needed for ovarian
      stimulation, quality of obtained embryos, fertilization rate (the proportion of total number
      of two-pronuclear [2PN] stage zygotes /per total injected MII oocytes), implantation rate
      (total number of observed gestational sac/ number of transferred embryos) and clinical
      pregnancy rate (presence of fetal heart beat by transvaginal ultrasound per embryo transfer).
    

Intervention name(s): Dual triggering
Intervention type(s): Other
Intervention description(s): Adding GnRH agonist (0.2 mg Triptorelin (Decapeptyl; Ferring GmbH) to routine oocyte triggering (two ampoules of Ovitrelle®, 250 μg/0.5 ml, Merck, Serono, Inc) is defined as dual triggering.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Poor ovarian response; Dual trigger; GnRH antagonist protocol