Female Infertility Due to Diminished Ovarian Reserve

Female fertility declines with advancing age, largely because of deteriorating oocyte quality driven by mitochondrial dysfunction and oxidative stress within the ovarian microenvironment. Alpha-lipoic acid (ALA) is a potent antioxidant that crosses cell and mitochondrial membranes, regenerates other antioxidants (vitamin C, vitamin E, glutathione, coenzyme Q10), and supports mitochondrial respiratory chain activity and ATP production. This prospective study will enroll 60 infertile women aged 35-45 years undergoing in vitro fertilization (IVF) treatment. Thirty participants will receive oral ALA 600 mg/day for two months before their IVF cycle, and thirty will proceed directly to IVF without supplementation. The study will compare oocyte and embryo quality, cumulus cell mitochondrial function and metabolic gene expression, and clinical pregnancy and live birth rates between the two groups.

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.