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.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

De-identified individual participant data (IPD), along with the study protocol and statistical analysis plan, will be made publicly available via the National Clinical Research Data Sharing Platform (https://www.ncmc-data.org) within 12 months after study completion. The data will be accessible to qualified researchers in compliance with relevant laws, regulations, and ethical requirements.