Dual Ovarian Stimulation (Duostim) and Shanghai Protocols in Poor Ovarian Responders

Assisted Reproductive Techniques Clinical Trial

Official title:

Comparison of Two Types of Dual Ovarian Stimulation: Duostim Versus Shanghai Protocols in Patients With Poor Ovarian Reserve: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06199960
• Other study ID #: 97000185
• Status: Completed
• Phase: Phase 3
• Start date: August 2, 2019
• Est. completion date: November 20, 2023

Study information

• Verified date: January 2024
• Source: Royan Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: November 20, 2023
• Est. primary completion date: May 10, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 35 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Assisted Reproductive Techniques

Intervention

Other:
• Doustim protocol
In Duostim group, the follicular stimulation will be started with a ?xed 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 ?rst oocyte retrieval second gonadotropin stimulation will be started identical to the ?rst one..

Locations

Country	Name	City	State
Iran, Islamic Republic of	Royan Institute	Tehran

Sponsors (1)

Lead Sponsor	Collaborator
Royan Institute

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of MII oocytes	Oocytes that were mature at the time of oocyte collection (Metaphase II)	Immediately after oocyte puncture
Secondary	Number of cleaved embryos	2-3 days embryo from fertilization	2-3 days after oocyte puncture
Secondary	Number of blastocyst embryos	The stage the embryo reaches after 5 days in culture from the oocyte retrieval	5 days after oocyte puncture and sperm insemination
Secondary	Clinical pregnancy rate	The observation of gestational sac on ultrasound examination two-three weeks after positive serum ßhCG	4-6 weeks after embryo transfer
Secondary	Fertilization rate	Percentage of transformation of micro injected oocytes into two pronuclei	2-5 days after sperm insemination
Secondary	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.	Immediately after oocyte puncture