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

Mỹ Đức Hospital

Status: Begins enrollment this month

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

Treatments: Procedure: IVM-Fresh (No gonadotropin + Fresh embryo transfer); Procedure: IVF-FET (GnRH-Antagonist - Agonist Trigger - Frozen embryo transfer)

Study type: Interventional

Funder types: Other

Identifiers

NCT07171970

10/25/DD-BVMD

Details and patient eligibility

About

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.

Full 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.

Enrollment: 600 estimated patients

Sex: Female

Ages: 18 to 42 years old

Volunteers: No Healthy Volunteers

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.

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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600 participants in 2 patient groups

IVM-Fresh (No gonadotropin + Fresh embryo transfer)

Experimental group

Description:

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.

Treatment:

Procedure: IVM-Fresh (No gonadotropin + Fresh embryo transfer)

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

Active Comparator group

Description:

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.

Treatment:

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