Double Stimulation in Women With Low Prognosis in ART

Impact of Double Stimulation (DuoStim) in Women Affected by Low Prognosis to Assisted Reproductive Technologies

The main objective of this study is to compare the cumulative ongoing pregnancy rates of two different IVF protocols in women candidate for ART characterized by low prognosis.

Study Overview

• Status: Recruiting
• Conditions: Assisted Reproductive Techniques
• Intervention / Treatment: Procedure: double stimulation; Procedure: conventional ovarian stimulation

Detailed Description

The patients will be allocated into two groups: control and study group _ In study group, patients will be treated by DuoStim protocol: The first phase of ovarian stimulation is started on the second day or third day of period. GnRH agonist will be used to trigger when at least two follicles ≥ 17 mm. Approximately 36 hours later, oocytes will be retrieved vaginally under ultrasound monitoring and ICSI will be performed. Five days later after oocyte retrieval, the second stimulation will be started. All embryos will be cryopreserved.

_ In control group, patients will be treated with antagonist protocol: The cycle of ovarian stimulation is started on the second day or third day of period. hCG will be used to trigger when at least two follicles ≥ 17 mm. Approximately 36 hours later, oocytes will be retrieved vaginally under ultrasound monitoring and ICSI will be performed. If serum progesterone on the day of trigger ≥ 1.5 ng/ml, all embryos will be cryostored; otherwise, fresh embryos will be transferred.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chau TM Le, PhD; Phone Number: +84908429006; Email: dr.lethiminhchau@gmail.com
• Study Contact Backup: Name: Anh Q Nguyen, Master; Phone Number: +84976137562; Email: dr.anhquocnguyen@gmail.com

Study Locations

• Vietnam
  • Ho Chi Minh City, Vietnam, 70000
    • Recruiting
    • Department of Infertility of Tu Du hospital
    • Contact: Chau TM Le, PhD; Phone Number: 0084908429006; Email: dr.lethiminhchau@gmail.com
    • Contact: Anh Q Nguyen, MMSc; Phone Number: 0084976137562; Email: dr.anhquocnguyen@gmail.com
    • Sub-Investigator: Tu K Duong, MMSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age ≤ 40.
• AMH ≥ 0.3 ng/ml and ≤ 1.2 ng/ml.
• OR 3 ≤ AFC ≤7.
• Normal shape of uterus (based on ultrasound).
• Body mass index within 28 - 37 kg/m2

Exclusion Criteria:

• Asherman's syndrome.
• Endometriosis.
• Leiomyomas distorting the endometrium
• Sperm extracted from surgical procedures (i.e. PESA, TESE).
• Patients refuse to continue participating in the study.
• Patients injected with wrong dose of gonadotropins during the treatment.
• Serious complications or accidents arise forcing the patients to discontinue the treatments.
• Ovarian surgery
• Previous chemotherapy or pelvic irradiation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study; the patients in this group will be treated with double stimulation	Procedure: double stimulation; the patients will be treated with two consecutive ovarian stimulations in one cycle; Other Names: DuoStim
Active Comparator: Control; the patients in this group will be treated with conventional ovarian stimulation	Procedure: conventional ovarian stimulation; the patients will be treated with one conventional ovarian stimulation in one cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Ongoing pregnancy rate	calculated by the number of ongoing pregnancy patients divided by the total number of patients in appropriate group	week 11 - 14 of pregnancy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ongoing pregnancy rate	defined as the pregnancy completed 11 - 14 weeks of gestation and having vital fetus	week 11 - 14 of pregnancy
Pregnancy rate	beta-hCG test is positive	2 weeks after embryo transfer
Number of oocytes retrieved	Number of oocytes retrieved identified by the embryologists	4 hours after occyte pick-up
Number of mature oocytes	Number of mature oocytes identified by the embryologists	4 hours after oocyte pick-up
Number of competent embryos	Number of embryos that can be transferred	3 days to 5 days after oocyte pick-up
Fertilization rate	number of fertilized oocyted divided by number of mature oocytes	1 to 3 days after oocyte pick-up

Collaborators and Investigators

• Sponsor: Tu Du Hospital
• Collaborators: Federico II University; University of Medicine and Pharmacy at Ho Chi Minh City
• Investigators: Study Director: Chau TM Le, PhD, Tu Du Hospital

Publications and helpful links

General Publications

• Poseidon Group (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number); Alviggi C, Andersen CY, Buehler K, Conforti A, De Placido G, Esteves SC, Fischer R, Galliano D, Polyzos NP, Sunkara SK, Ubaldi FM, Humaidan P. A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept. Fertil Steril. 2016 Jun;105(6):1452-3. doi: 10.1016/j.fertnstert.2016.02.005. Epub 2016 Feb 26. No abstract available.
• Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, Shoham Z. Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod Biomed Online. 2014 Dec;29(6):684-91. doi: 10.1016/j.rbmo.2014.08.009. Epub 2014 Sep 6.
• Cardoso MCA, Evangelista A, Sartorio C, Vaz G, Werneck CLV, Guimaraes FM, Sa PG, Erthal MC. Can ovarian double-stimulation in the same menstrual cycle improve IVF outcomes? JBRA Assist Reprod. 2017 Sep 1;21(3):217-221. doi: 10.5935/1518-0557.20170042.
• Ubaldi FM, Capalbo A, Vaiarelli A, Cimadomo D, Colamaria S, Alviggi C, Trabucco E, Venturella R, Vajta G, Rienzi L. Follicular versus luteal phase ovarian stimulation during the same menstrual cycle (DuoStim) in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate: new insight in ovarian reserve exploitation. Fertil Steril. 2016 Jun;105(6):1488-1495.e1. doi: 10.1016/j.fertnstert.2016.03.002. Epub 2016 Mar 25.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2020
• Primary Completion (Estimated): February 28, 2024
• Study Completion (Estimated): March 30, 2024

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: double ovarian stimulation; low prognosis women; ongoing pregnancy
• Other Study ID Numbers: CS/TD/20/05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No