Impact of Day 2 Versus Day 3 Fresh Embryo Transfer on Live Birth Rate in Poor-Prognosis Patients

NCT07533695 | Not Yet Recruiting DMC

• 1 other identifier: SH9H-2026-T107-1
• Study Type: interventional
• Target: 470
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

POSEIDON Category 4; Low Prognosis in Assisted Reproductive Technology; Female Infertility Due to Diminished Ovarian Reserve

Keywords

fresh embryo transfer; in-vitro fertilization; POSEIDON; low prognosis; diminished ovarian reserve

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  Live birth rate, defined as the delivery of at least one neonate with heartbeat and breathing at ≥ 28 weeks of gestation.

  From enrollment to delivery

Secondary Outcomes (11)

• 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

Study Arms (2)

D2 Embryo Transfer Group

EXPERIMENTAL

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.

Procedure: Day 2 Fresh Embryo Transfer

D3 Embryo Transfer Group

NO INTERVENTION

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.

Interventions

Day 2 Fresh Embryo Transfer PROCEDURE

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.

D2 Embryo Transfer Group

Eligibility Criteria

• Age: 35 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• : 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
• : Undergoing first or second IVF/ICSI cycle
• : Undergoing controlled ovarian hyperstimulation (COH) using a gonadotropin-releasing hormone (GnRH) antagonist protocol, with at least 1 oocyte retrieved
• : Provide written informed consent

You may not qualify if:

• : Use of donor oocytes/sperm, or planned preimplantation genetic testing (PGT)
• : Severe immune or chromosomal abnormalities
• : Uterine cavity abnormalities (i.e., submucous fibroids, complete uterine septum, severe intrauterine adhesions, etc.) or untreated, ultrasound-visible hydrosalpinx
• : Presence of severe underlying diseases (e.g., uncontrolled hypertension/diabetes mellitus, active malignant tumors)
• : History of recurrent implantation failure (≥2 cycles) or recurrent miscarriage (≥2 episodes)
• : Progesterone level \> 1.5 ng/mL on the day of human chorionic gonadotropin (hCG) trigger

Sponsors & Collaborators

• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University: lead

Central Study Contacts

SHUTIAN JIANG, Medical Doctor

CONTACT

021-23271699; shutiansweet@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: April 16, 2026
• Study Start: March 30, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP