Multi-Site Cortical Puncture for DOR

This is a multicenter, prospective, randomized controlled clinical trial designed to evaluate the efficacy of ovarian cortex multi-point puncture in improving ovarian reserve and ovarian stimulation outcomes in patients with delayed ovarian reserve (DOR). The target population consists of DOR patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with plans for subsequent ovarian stimulation and embryo retrieval within 4 months. The primary objective is to assess whether ovarian cortex multi-point puncture during the initial oocyte retrieval procedure improves ovarian reserve and ovarian stimulation outcomes compared to conventional oocyte retrieval. The study plans to continuously recruit 214 participants across seven participating centers.

The study period for the research subjects comprises three phases: screening and baseline phase, intervention phase, and follow-up phase.

During the screening and baseline phase, patients scheduled for IVF/ICSI artificial reproduction with plans to undergo ovarian stimulation, oocyte retrieval, embryo transfer, and DOR within 4 months were invited to participate in this study. Written informed consent forms were provided to potential participants, with detailed explanations of the study protocol. Prior to implementing any specific study procedures, written informed consent from participants (or their legal representatives) was obtained. After signing the informed consent form, participants were randomly assigned to the intervention group or control group using a stratified block randomization method (with research centers as stratification factors) at a 1:1 ratio, followed by baseline data collection.

During the intervention period, on the day of oocyte retrieval after the first ovarian stimulation cycle, the control group underwent conventional anesthesia (intravenous anesthesia or sedation) followed by standard oocyte retrieval procedures according to institutional protocols. A standard 17G double-lumen oocyte retrieval needle was used with transvaginal ultrasound guidance and puncture guide frame. The intervention group completed conventional oocyte retrieval under the same anesthesia/sedation conditions and immediately underwent ovarian cortical multi-point puncture under ultrasound guidance (without needle replacement). The procedure involved selecting the ovary with relatively fewer follicles larger than 14mm and establishing two evenly distributed puncture sites in the cortical region. For patients requiring continued ovarian stimulation therapy prior to the second oocyte retrieval, the ovarian stimulation protocol remained consistent with the previous cycle. Detailed records were maintained for the stimulation regimen, medication dosages, oocyte retrieval puncture documentation, and adverse event occurrences.

During the follow-up period, study subjects undergoing IVF/ICSI treatment were monitored for pregnancy outcomes (biochemical pregnancy rate, implantation rate, clinical pregnancy rate, miscarriage rate (early ≤12 weeks and mid-to-late \<28 weeks), live birth rate, cumulative pregnancy rate, cumulative live birth rate), neonatal outcomes (preterm birth, stillbirth, low birth weight infants, birth defects), and adverse event-related data.

• Key reproductive-related indicators for the second ovarian stimulation and oocyte retrieval cycle [Time frame: From the date of randomization to the third month after the second ovulation induction and oocyte retrieval surgery, the assessment period can last up to 7 months.]
• Rate of biochemical pregnancy [Time frame: From the date of randomization to the occurrence of biochemical pregnancy after this embryo transfer, the assessment period can last up to 24 months.]
• Clinical pregnancy rate [Time frame: From the date of randomization to clinical pregnancy after this embryo transfer, the assessment period can last up to 24 months.]
• Implantation rate [Time frame: From the date of randomization to implantation at the 5th week after embryo transfer, the assessment period can last up to 24 months.]
• Abortion rate [Time frame: From the date of randomization to miscarriage after this embryo transfer, the assessment period can last up to 30 months.]
• Live birth rate [Time frame: From the date of randomization to the birth of a full-term live fetus following this embryo transfer, the assessment period lasts up to 36 months.]
• Cumulative pregnancy rate [Time frame: From the date of randomization to clinical pregnancy after exhaustion of transplantable embryos, the assessment period lasts up to 100 months.]
• Cumulative live birth rate [Time frame: From the date of randomization to the birth of a full-term live fetus after exhaustion of transplantable embryos, the assessment period lasts up to 100 months.]
• Adverse neonatal outcomes [Time frame: From the date of randomization to one year after the birth of the newborn, the assessment period can last up to 100 months.]
• Incidence of adverse events [Time frame: From the date of randomization to the date of adverse event occurrence, the assessment period lasts up to 100 months.]