Dual Ovarian Stimulation (Duostim) and Shanghai Protocols in Poor Ovarian Responders
Condition: Assisted Reproductive Techniques
Study type: Interventional
Phase: Phase 3

Summary: 
      A combination of follicular phase stimulation and luteal phase stimulation in the same cycle,
      can be a valuable choice in poor responder patients with reduced ovarian reserve, in order to
      achieve extreme the number of oocytes in a single menstrual cycle. In the present study, the
      results of two different Double stimulation cycles including shanghai protocol and Duostim
      protocol in patients with reduced ovarian reserve, compared with each other to help select a
      more appropriate treatment for this group of patients. The number of retrieved oocytes and
      the number of obtained embryos and clinical pregnancy from each protocol will be compared as
      the primary and secondary outcome.
    

Detailed description: 
      The proposal of this randomized clinical trial study is a comparison of two different type of
      double stimulation protocols in patients who meet the POSEIDON (Patient-Oriented Strategies
      Encompassing IndividualizeD Oocyte Number) stratification (group 4) criteria.

      In mild double stimualtion (Shanghai protocol), patients will be received Clomiphene citrate
      25 mg/day (Ovumid®; Iran Hormone pharmaceutical Co., Iran) co-treatment and letrozole 2.5
      mg/day (Femati®, Atipharmed Co., Iran) will be given from cycle day 3. Letrozole is given for
      4 days and clomiphene citrate is used daily before the trigger day. Patients take 150 IU of
      Human menopausal gonadotropin (HMG) (Humegnan®, Darou Pakhsh Co., Iran) every other day
      beginning on cycle day 6. When one dominant follicle will reach 18 mm, the ﬁnal triggering
      will induce 34-36 h after 0.5 cc of Buserelin acetate (CinnaFact®; CinnaGen pharmaceutical
      Co., Iran) administration. In luteal phase stimulation a total of 225 IU HMG and letrozole
      2.5 mg will administered daily from3 to 5 days after oocyte retrieval. Letrozole
      administration will be stopped when the dominant follicles reached 12 mm. When one dominant
      follicle will reach 18 mm, the ﬁnal triggering will be induced with 0.5 cc of Buserelin
      acetate (CinnaFact®; CinnaGen pharmaceutical Co., Iran).

      In the double GnRH- antagonist (Duostim protocol), both follicular and luteal phases
      stimulation will perform with 150-225 IU of recombinant FSH (Gonal-F®, Merck-sereno, Germany)
      and HMG (Humegnan, Darou Pakhsh Co., Iran) in GnRH antagonist treatment. The follicular
      stimulation will be started on day 2-3 of the menstrual. Daily administration of 0.25 mg of
      GnRH antagonist (Cetrotide®, Merck-Serono; Germany) will be started when the leading follicle
      are 13-14mm and continue until the day of the oocyte trigger. When one follicle reached 17-18
      mm ovulation will be triggered with 0.5 cc of Buserelin acetate (CinnaFact®; CinnaGen
      pharmaceutical Co., Iran) and oocyte retrieval will be performed after 34-36 hours. Five days
      after the ﬁrst oocyte retrieval, a GnRH antagonist protocol identical to the ﬁrst one will
      start. When at least two follicles reached 17-18 mm, the ovulation will be triggered with a
      subcutaneous bolus GnRH-agonist and the second oocyte retrieval will be performed.

      In all of groups all of embryos will be freeze and will be used in subsequent frozen embryo
      transfer (FET) cycles. Endometrial preparation for FET cycle will perform with hormonal
      replacement therapy (HRT) cycle protocol.
    

Intervention name(s): Doustim protocol
Intervention type(s): Other
Intervention description(s): In Duostim group, the follicular stimulation will be started with a ﬁxed dose of 150 IU of rFSH and HMG 75 IU for 4 days. Daily administration of a GnRH antagonist will be started when the leading follicle are 13-14mm in diameter and continue until the day of the trigger of the ovulation. Five days after the ﬁrst oocyte retrieval second gonadotropin stimulation will be started identical to the ﬁrst one..
Other intervention name(s): Double GnRH-antagonist stimulation
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment