IVM - Fresh ET (THE SAIGON PROTOCOL) Versus IVF - FET in PCOS Women

NCT ID: NCT07171970

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-22
• Study Completion Date: 2028-01-15

Brief Summary

Assisted Reproductive Technologies (ART) aim to increase success rates while minimizing patient risks. For women with high AFC or PCOS, conventional IVF carries a high risk of OHSS (Ho et al., 2019). A modern IVF strategy to prevent this uses a GnRH agonist trigger, requiring a "freeze-all" and subsequent FET (Wong et al., 2017). This reduces OHSS risk but can increase time to pregnancy (Vuong et al., 2021) and treatment burden.

IVM is a patient-friendly alternative that eliminates OHSS risk by avoiding high-dose gonadotropins. A 2020 trial by Vuong et al. compared CAPA-IVM-FET to conventional IVF-FET in women with high AFC. IVM yielded a comparable live birth rate (35.2%) versus IVF (43.2%), with a 0% OHSS rate in IVM compared to 0.7% in IVF (Vuong et al., 2020).

The optimal transfer method (fresh or frozen) in IVM cycles is debated. A 2021 pilot RCT by Vuong et al. found a freeze-only strategy after CAPA-IVM led to a significantly higher live birth rate (60%) than a fresh transfer (20%) (Vuong et al., 2021), but increased time to pregnancy (194 vs. 150 days) (Vuong et al., 2021). A refined CAPA-IVM protocol, which uses no gonadotropins, allowed for fresh embryo transfer in the same cycle, resulting in a numerically higher ongoing pregnancy rate (43.3% vs. 33.3%) than FET (Vuong et al., 2025).

This raises an important question: how does a simplified IVM strategy with fresh transfer compare to the established "safety-net" IVF strategy with FET? These two approaches represent opposing clinical philosophies. No large-scale study has yet compared them in women with PCOS. Therefore, this study is designed to compare the SAIGON protocol (gonadotropin-free CAPA-IVM with fresh ET) against a standard GnRH-antagonist IVF protocol with agonist trigger and subsequent FET.

Detailed Description

1. Screening for eligibility and randomization: Women who are potentially eligible are provided with information about the trial. Screening is done on the day of the first visit, and patients are given informed consent form to sign before enrollment. Participants are then randomly assigned (1:1) to either the CAPA-IVM or IVF-FET group.

2. After randomisation 2.1. IVM-FRESH (The SAIGON Protocol):

• Treatment begins on day 2-4 of the menstrual cycle.
• Endometrial preparation uses oral estradiol valerate (Progynova®; Delpharm Lille SAS, France) 8mg/day for at least 10 days.
• Immature oocyte retrieval is performed when the endometrial thickness is ≥ 8 mm.
• Mature oocytes are fertilized via ICSI.
• Luteal phase support is provided with vaginal progesterone (800 mg/day) + dydrogesterone (20mg/day) starting on the day of ICSI.
• A fresh embryo transfer is performed three or five days after progesterone administration, depending on the embryo stage.

2.2. IVF-FET (Frozen Transfer Protocol):

• This protocol uses a random start approach, beginning on the day of the patient's first visit.
• Ovarian stimulation is done using a GnRH antagonist protocol with a starting dose of 150 IU/day of rFSH.
• A GnRH agonist trigger is administered when at least two leading follicles reach ≥ 17 mm in diameter.
• Insemination is performed using ICSI for matured oocytes.
• The endometrium is prepared for frozen embryo transfer using oral oestradiol valerate (8mg/day) and vaginal progesterone (800 mg/day) + dydrogesterone (20mg/day) when endometrial thickness is ≥ 8 mm.
• Surviving embryos are thawed and transferred two hours after thawing under ultrasound guidance.

3. Pregnancy and outcomes:

• A pregnancy test is performed 10-14 days after embryo transfer. A positive result is a serum hCG level of ≥ 25 mIU/mL.
• Both groups continue hormone supplementation if the pregnancy test is positive.
• The primary outcome of the study is the live birth rate after one embryo transfer. Secondary outcomes include cumulative ongoing pregnancy, time to ongoing pregnancy, clinical pregnancy rate, miscarriage, and other treatment and pregnancy complications.
• Obstetric and neonatal outcomes: All data relating to the delivery process and neonatal care will be recorded by the data management system of IVFMD.

Conditions

Polycystic Ovary Syndrome (PCOS); In Vitro Maturation of Oocytes; Fresh Embryo Transfer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IVM-Fresh (No gonadotropin + Fresh embryo transfer)

Endometrial preparation will be conducted using an artificial cycle protocol initiated on day 2-4 of the menstrual cycle (either spontaneous or induced). CAPA-IVM treatment will subsequently be performed, followed by oocyte fertilization and fresh embryo transfer.

Group Type: EXPERIMENTAL

IVM-Fresh (No gonadotropin + Fresh embryo transfer)

Intervention Type: PROCEDURE

Patients randomized to this arm will receive estradiol valerate 8 mg/day. IVM will be performed after ≥10 days of estrogen and ET ≥8 mm. From the day of ICSI, they will continue estradiol and start vaginal progesterone 800 mg/day + dydrogesterone (20mg/day). A fresh embryo transfer will subsequently be performed.

IVF-FET (GnRH-Antagonist - Agonist Trigger - Frozen embryo transfer)

Ovarian stimulation will be performed using a GnRH-antagonist protocol starting on any day of the menstrual cycle. Embryos obtained from ICSI will be cryopreserved for later transfer.

Group Type: ACTIVE_COMPARATOR

IVF-FET (GnRH-Antagonist - Agonist Trigger - Frozen embryo transfer)

Intervention Type: PROCEDURE

Patients randomized into this group will receive FSH at a dose of 150 IU/day. Oocyte retrieval will be performed once the criteria for triggering are fulfilled, followed by embryo cryopreservation and frozen embryo transfer in the subsequent cycle. Endometrial preparation for frozen embryo transfer will be conducted using an exogenous steroids regimen. Patients will receive estradiol 8 mg/day starting from cycle days 2-3 for 10 days. When the endometrial thickness reaches ≥8 mm, luteal phase support will be initiated with vaginal progesterone 800 mg/day plus dydrogesterone 20 mg/day.

Interventions

IVM-Fresh (No gonadotropin + Fresh embryo transfer)

Patients randomized to this arm will receive estradiol valerate 8 mg/day. IVM will be performed after ≥10 days of estrogen and ET ≥8 mm. From the day of ICSI, they will continue estradiol and start vaginal progesterone 800 mg/day + dydrogesterone (20mg/day). A fresh embryo transfer will subsequently be performed.

Intervention Type: PROCEDURE

IVF-FET (GnRH-Antagonist - Agonist Trigger - Frozen embryo transfer)

Patients randomized into this group will receive FSH at a dose of 150 IU/day. Oocyte retrieval will be performed once the criteria for triggering are fulfilled, followed by embryo cryopreservation and frozen embryo transfer in the subsequent cycle. Endometrial preparation for frozen embryo transfer will be conducted using an exogenous steroids regimen. Patients will receive estradiol 8 mg/day starting from cycle days 2-3 for 10 days. When the endometrial thickness reaches ≥8 mm, luteal phase support will be initiated with vaginal progesterone 800 mg/day plus dydrogesterone 20 mg/day.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Women aged 18 - 42 years old.
• Diagnosed with PCOS, followed Rotterdam 2003 criteria (Group TREP consensus workshop, 2004)
• Had fewer than three previous failed frozen embryo transfer (FET) cycles
• Transferred no more than two cleavage embryos or one good-quality blastocyst or no more than two poor-quality blastocysts.
• Agreeing to participate in the study

Exclusion Criteria

• Having allergy and contraindications for exogenous hormone administration (e.g., breast cancer, thromboembolic disease)
• Cycles with preimplantation genetic testing indication
• Oocyte donation cycles
• Having untreated uterine or adnexal abnormalities (e.g., intrauterine adhesions, unicornuate/ bicornuate/ arcuate uterus, large leiomyoma ≥5 cm in diameter; adenomyosis, endometrial polyp, hydrosalpinx).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 42 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Mỹ Đức Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lan N Vuong, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Medicine and Pharmacy at Ho Chi Minh City

Locations

IVFMD - My Duc Hospital

Ho Chi Minh City, , Vietnam

Site Status: RECRUITING

Countries

Vietnam

Central Contacts

Vu NA Ho, MD, PhD

Role: CONTACT

bsvu.hna@myduchospital.vn

+84935843336

Facility Contacts

Tuong M Ho, MD

Role: primary

tuongho.ivfmd@gmail.com

+84 90 3633377

Other Identifiers

10/25/DD-BVMD

Identifier Type: -

Identifier Source: org_study_id