Female Infertility Due to Diminished Ovarian Reserve, Low Prognosis in Assisted Reproductive Technology, POSEIDON Category 4
Conditions
Keywords
fresh embryo transfer, in-vitro fertilization, POSEIDON, low prognosis, diminished ovarian reserve
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.
Interventions
PROCEDUREDay 2 Fresh Embryo Transfer
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.
Sponsors
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Live birth rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Congenital malformation rate | From enrollment to 1 month after delivery | The proportion of participants who achieved a live birth and delivered a newborn diagnosed with a congenital malformation according to the International Classification of Diseases (ICD-10). |
| Low birth weight rate | From enrollment to the delivery | The proportion of participants who achieved a live birth and delivered a newborn with a birth weight of less than 2500g. |
| Embryo utilization rate | Day 2 or Day 3 after oocyte retrieval | The proportion of all obtained fertilized embryos (2PN zygotes) that are available for subsequent embryo transfer. |
| Moderate/severe OHSS incidence rate | From oocyte retrieval to 12 weeks of gestation | The proportion of participants enrolled in the study who developed moderate or severe ovarian hyperstimulation syndrome (OHSS), meeting the criteria of the Royal College of Obstetricians and Gynaecologists (RCOG), between oocyte retrieval and 12 weeks of gestation. |
| Miscarriage rate | From enrollment to ≤28 weeks of gestation | The proportion of participants who experienced a clinical pregnancy and subsequently had a spontaneous pregnancy loss before 28 weeks of gestation. |
| Clinical pregnancy rate | From enrollment to 28 days after embryo transfer | The proportion of participants enrolled in the study who experienced a clinical pregnancy, defined as the confirmation of an intrauterine gestational sac via ultrasound examination 28 days after embryo transfer. |
| Implantation rate | From enrollment to 28 days after embryo transfer | The proportion of all transferred embryos that developed into an intrauterine gestational sac, as confirmed by ultrasound examination 28 days after embryo transfer. |
| Rate of no available embryos | Day 2 or Day 3 after oocyte retrieval | The proportion of participants enrolled in the study who, following ovarian stimulation, oocyte retrieval, and embryo culture, have no embryos available for transfer. |
| Biochemical pregnancy rate | From enrollment to 14 days (D3) or 15 days (D2) after embryo transfer | The proportion of participants enrolled in the study who experienced a biochemical pregnancy, defined as a serum HCG level ≥25 IU/L measured 14 or 15 days after embryo transfer. |
| Preterm birth rate | From enrollment to the delivery | The proportion of participants who achieved a live birth and delivered between 28 and 36⁺⁶ weeks of gestation. |
| Ongoing pregnancy rate | From enrollment to 12 weeks of gestation | The proportion of participants enrolled in the study who experienced an ongoing pregnancy, defined as the confirmation of an intrauterine viable fetus via ultrasound examination at 12 weeks of gestation. |
Contacts
CONTACTSHUTIAN JIANG, Medical Doctor
Outcome results
None listed