A Phase 3 interventional study of Doustim protocol in Assisted Reproductive Techniques, sponsored by Royan Institute. Completed at 1 site in Iran, Islamic Republic of. Open to female participants aged 35 Years to 45 Years. Per ClinicalTrials.gov, last updated 2024-01-10.
Sponsored by Royan Institute · Phase 3, Interventional, and Treatment
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.
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.
Royan Institute is the lead sponsor of 94 studies on the registry; 3 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
In Duostim group, 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.
Other: Doustim protocol
In double mild stimulation protocol, Clomiphene citrate 25 mg/day (Ovumid®; Iran Hormone pharmaceutical Co., Iran) and co-treatment with 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.
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..
Also known as: Double GnRH-antagonist stimulation
Number of MII oocytes
Oocytes that were mature at the time of oocyte collection (Metaphase II)
Time frame: Immediately after oocyte puncture
Number of cleaved embryos
2-3 days embryo from fertilization
Time frame: 2-3 days after oocyte puncture
Number of blastocyst embryos
The stage the embryo reaches after 5 days in culture from the oocyte retrieval
Time frame: 5 days after oocyte puncture and sperm insemination
Clinical pregnancy rate
The observation of gestational sac on ultrasound examination two-three weeks after positive serum βhCG
Time frame: 4-6 weeks after embryo transfer
Fertilization rate
Percentage of transformation of micro injected oocytes into two pronuclei
Time frame: 2-5 days after sperm insemination
Quality of oocytes
Oocyte quality were assessed by embryologist based on The Istanbul consensus workshop (Hum Reprod.2011). Quality of MII oocytes (based on intracytoplasmic and extracytoplasmic abnormalities) was divided into 3 groups; morph, slightly dysmorph, and dysmorph.
Time frame: Immediately after oocyte puncture
Ran from Aug 2019 to primary completion in May 2022, 33 months.
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