Impact of Day 2 Versus Day 3 Fresh Embryo Transfer on Live Birth Rate in Poor-Prognosis POSEIDON Group 4 Patients: A Single-Center, Parallel-Group, Open-Label Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 470
- 主要终点
- Live birth rate
研究概览
简要总结
This study aimed to compare the efficacy (live birth rate) of fresh embryo transfer on Day 2 versus Day 3 in POSEIDON Group 4 patients, and to determine the optimal timing of embryo transfer for this population. It is a single-center, parallel-group, open-label prospective randomized controlled trial, and outcome assessors are masked. The main questions it aims to answer are:
Is there a significant difference in the live birth rate between Day 2 and Day 3 fresh embryo transfer in patients with POSEIDON Category 4 low prognosis? What are the differences in secondary outcomes (including clinical pregnancy rate, ongoing pregnancy rate, implantation rate, embryo utilization rate, miscarriage rate, incidence of moderate/severe OHSS, and adverse neonatal outcomes) between the two embryo transfer timings, and which timing is safer and more effective for this patient population?
A total of 470 patients meeting the POSEIDON Category 4 criteria will be enrolled and randomly assigned to the Day 2 Fresh Embryo Transfer Group and the Day 3 Fresh Embryo Transfer Group in a 1:1 ratio using stratified block randomization. Researchers will compare the two groups to clarify the difference in live birth rate (primary outcome) and other secondary outcomes, so as to determine the optimal embryo transfer timing.
Participants will:
- Be female patients aged ≥ 35 years with antral follicle count (AFC) < 5 or anti-Müllerian hormone (AMH) < 1.2 ng/mL, undergoing the first or second IVF/ICSI cycle, receiving controlled ovarian hyperstimulation (COH) with the GnRH antagonist protocol, and having ≥ 1 oocyte retrieved (excluding those using donor oocytes/sperm, with uterine cavity abnormalities, or complicated with severe underlying diseases).
- Be randomly assigned to either the Day 2 Fresh Embryo Transfer Group or the Day 3 Fresh Embryo Transfer Group, and receive embryo transfer according to the corresponding group's protocol
- Receive routine luteal support treatment after embryo transfer
- Attend follow-up visits at multiple time points (on the day of transfer, 12-15 days after transfer, 28 days after transfer, during pregnancy, and after delivery) to collect relevant clinical and laboratory data for outcome assessment.
- Undergo safety evaluation throughout the study; the study will adopt intention-to-treat (ITT) as the main statistical method and per-protocol (PP) as the sensitivity analysis, with subgroup analysis by age, AMH level, and number of oocytes retrieved, following ethical norms and data quality control requirements.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 35 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •1: Meet the definition of POSEIDON Category 4: age ≥ 35 years, with antral follicle count (AFC) < 5 or anti-Müllerian hormone (AMH) < 1.2 ng/mL
- •2: Undergoing first or second IVF/ICSI cycle
- •3: Undergoing controlled ovarian hyperstimulation (COH) using a gonadotropin-releasing hormone (GnRH) antagonist protocol, with at least 1 oocyte retrieved
- •4: Provide written informed consent
排除标准
- •1: Use of donor oocytes/sperm, or planned preimplantation genetic testing (PGT)
- •2: Severe immune or chromosomal abnormalities
- •3: Uterine cavity abnormalities (i.e., submucous fibroids, complete uterine septum, severe intrauterine adhesions, etc.) or untreated, ultrasound-visible hydrosalpinx
- •4: Presence of severe underlying diseases (e.g., uncontrolled hypertension/diabetes mellitus, active malignant tumors)
- •5: History of recurrent implantation failure (≥2 cycles) or recurrent miscarriage (≥2 episodes)
- •6: Progesterone level > 1.5 ng/mL on the day of human chorionic gonadotropin (hCG) trigger
研究组 & 干预措施
D2 Embryo Transfer Group
Embryos will be cultured for 44-48 hours after oocyte retrieval (Day 2), and embryos with ≥ 2 cells, grade II or above, and no multinucleation will be selected for transfer, with 1-2 embryos transferred; routine luteal support treatment will be given after transfer.
干预措施: Day 2 Fresh Embryo Transfer (Procedure)
D3 Embryo Transfer Group
Embryos will be cultured for 68-72 hours after oocyte retrieval (Day 3), and embryos with ≥ 6 cells, grade II or above, and no multinucleation will be selected for transfer, with 1-2 embryos transferred; routine luteal support treatment will be given after transfer.
结局指标
主要结局
Live birth rate
时间窗: From enrollment to delivery
Live birth rate, defined as the delivery of at least one neonate with heartbeat and breathing at ≥ 28 weeks of gestation.
次要结局
- Congenital malformation rate(From enrollment to 1 month after delivery)
- Low birth weight rate(From enrollment to the delivery)
- Embryo utilization rate(Day 2 or Day 3 after oocyte retrieval)
- Moderate/severe OHSS incidence rate(From oocyte retrieval to 12 weeks of gestation)
- Miscarriage rate(From enrollment to ≤28 weeks of gestation)
- Clinical pregnancy rate(From enrollment to 28 days after embryo transfer)
- Implantation rate(From enrollment to 28 days after embryo transfer)
- Rate of no available embryos(Day 2 or Day 3 after oocyte retrieval)
- Biochemical pregnancy rate(From enrollment to 14 days (D3) or 15 days (D2) after embryo transfer)
- Preterm birth rate(From enrollment to the delivery)
- Ongoing pregnancy rate(From enrollment to 12 weeks of gestation)