The Effectiveness and Safety of In Vitro Maturation With Fresh Embryo Transfer (The SAIGON Protocol) Versus In Vitro Fertilization With Frozen Embryo Transfer in Women With Polycystic Ovary Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 600
- 试验地点
- 1
- 主要终点
- Live birth rates after the one embryo transfer
研究概览
简要总结
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.
详细描述
- 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.
- 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.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 42 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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).
结局指标
主要结局
Live birth rates after the one embryo transfer
时间窗: At 24 weeks of gestation
Live birth was defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. A birth weight of 500 grams or more can be used if gestational age is unknown. Live births refer to the individual newborn; for example, a twin delivery represents two live births.
次要结局
- Cumulative ongoing pregnancy(After 12 months of follow-up after randomisation)
- Time to ongoing pregnancy(Up to 10 weeks after embryo placement)
- Positive pregnancy test rate(10-14 days after embryo transfer)
- Clinical pregnancy rate(6 weeks after embryo transfer)
- Ongoing pregnancy rate(12 weeks after embryo transfer)
- Implantation rate(3 weeks after embryo transfer)
- Ectopic pregnancy rate(2 - 4 weeks after embryo transfer)
- Miscarriage rate(2-22 weeks after embryo transfer)
- Multiple gestations rate(5 weeks after embryo transfer)
- Multiple birth rate(At 22 weeks' gestation)
- Mode of delivery(At delivery)
- Birth weight(At delivery)
- Gestational age at birth(At delivery)
- Ovarian hyperstimulation syndrome(Up to 1 week after the oocyte retrieval in the IVF arm)
- IVM oocyte retrieval cancellation(After 21 day of endometrial preparation)
- Embryo transfer cancellation(After 21 days of endometrial preparation)
- Preterm birth(At delivery)
- Gestational diabetes mellitus(At 24-28 weeks of gestation)
- Hypertensive disorders of pregnancy(After 20 weeks of gestation)
- Stillbirth(At delivery after 28 weeks of gestation)
- Very low birth weight(At delivery)
- Low birth weight(At delivery)
- High birth weight(At delivery)
- Very high birth weight(At delivery)
- Major congenital abnormalities(During pregnancy and 12 months after delivery)
- Postpartum hemorrhage(Up to one month after the delivery)
- NICU admission(Up to one month after the delivery)
- Neonatal mortality(Up to one month after the delivery)