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

NCT06199960 | Completed Phase 3

• 1 other identifier: 97000185
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

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.

Conditions

Assisted Reproductive Techniques

Outcome Measures

Primary Outcomes (1)

• Number of MII oocytes

  Oocytes that were mature at the time of oocyte collection (Metaphase II)

  Immediately after oocyte puncture

Secondary Outcomes (5)

• Number of cleaved embryos

  2-3 days after oocyte puncture

• Number of blastocyst embryos

  5 days after oocyte puncture and sperm insemination

• Clinical pregnancy rate

  4-6 weeks after embryo transfer

• Fertilization rate

  2-5 days after sperm insemination

• Quality of oocytes

  Immediately after oocyte puncture

Study Arms (2)

Double GnRH-antagonist protocol (Duostim protocol)

EXPERIMENTAL

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

Double mild stimulation protocol

NO INTERVENTION

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.

Interventions

Doustim protocol OTHER

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

Double GnRH-antagonist protocol (Duostim protocol)

Eligibility Criteria

• Age: 35 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Royan Institute: lead

Study Sites (1)

Royan Institute

Tehran, Iran

Location

Study Officials

• Mehri Mashayekhi, M.D

  Department of Endocrinology and Female Infertility

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2021
• First Posted: January 10, 2024
• Study Start: August 2, 2019
• Primary Completion: May 10, 2022
• Study Completion: November 20, 2023
• Last Updated: January 10, 2024

Record last verified: 2024-01

Locations

IR (1)