Clinical trial NCT06199960: Dual Ovarian Stimulation (Duostim) and Shanghai Protocols in Poor Ovarian Responders
Official title: Comparison of Two Types of Dual Ovarian Stimulation: Duostim Versus Shanghai Protocols in Patients With Poor Ovarian Reserve: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Assisted Reproductive Techniques
Lead sponsor: Royan Institute
Sponsor class: OTHER_GOV
First posted: 2024-01-10
Enrollment: 116
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥35 years
2. Antimullerian hormone (AMH) \<1.2 ng/ml and/or Antral follicular count≤5 follicles
3. ≤4 oocyte retrieved from previous ART cycle 4-18.5\<BMI\<30

Exclusion Criteria:

1. Endometriosis (stage III and IV)
2. Myoma with a compression effect
3. Uterine anomalies (Unicorn, Didelphis,etc,....)
4. Male factor infertility with azoospermia, severe oligospermia and oligoasthenospermia, TESE/PESA

Primary outcomes:
measure: Number of MII oocytes
timeFrame: Immediately after oocyte puncture
Secondary outcomes:
measure: Number of cleaved embryos
timeFrame: 2-3 days after oocyte puncture
measure: Number of blastocyst embryos
timeFrame: 5 days after oocyte puncture and sperm insemination
measure: Clinical pregnancy rate
timeFrame: 4-6 weeks after embryo transfer
measure: Fertilization rate
timeFrame: 2-5 days after sperm insemination
measure: Quality of oocytes
timeFrame: Immediately after oocyte puncture
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Royan Institute
Study officials:
affiliation: Department of Endocrinology and Female Infertility
name: Mehri Mashayekhi, M.D
role: PRINCIPAL_INVESTIGATOR
References: