Clinical Efficacy and Safety of Multiple Ovarian Cortex Punctures in Improving Ovarian Reserve and Ovarian Stimulation Outcomes in Patients With Diminished Ovarian Reserve (DOR): A Multicenter, Prospective, Randomized Controlled Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 214
- 试验地点
- 7
- 主要终点
- Number of oocytes retrieved during the second ovarian stimulation cycle
研究概览
简要总结
A multicenter, prospective, randomized controlled clinical trial. The target population consists of patients undergoing IVF/ICSI artificial reproduction who plan to undergo ovarian stimulation and embryo retrieval (DOR) within 4 months. A stratified block randomization method was employed to assign participants in a 1:1 ratio to the intervention group and control group. The study aims to investigate whether multiple-point ovarian cortex puncture during the initial oocyte retrieval procedure improves ovarian reserve and ovarian stimulation outcomes in DOR patients compared to conventional oocyte retrieval techniques.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age 20-45 years;
- •Infertile women meeting the diagnostic criteria for diminished ovarian reserve (DOR); The following two criteria must be met simultaneously: ① Anti-Müllerian hormone (AMH) ≤0.5 ng/ml, ② Bilateral ovarian antral follicles (AFC) ≤5 (3-9 mm).
- •Patients scheduled for IVF (in vitro fertilization)/ICSI (intracytoplasmic sperm injection) treatment;
- •Patients who plan for whole embryo cryopreservation and intend to undergo another ovulation induction cycle within 4 natural months starting from the first cycle, with the goal of embryo retrieval and embryo banking;
- •Bilateral follicles were observed during AFC examination;
- •The planned ovarian stimulation protocol is one of PPOS, antagonist, or microstimulation protocols;
- •The first ovulation induction protocol is planned to be consistent with the second ovulation induction protocol;
- •Voluntary participation in the study and signing of the informed consent form.
排除标准
- •Patients with the following reproductive and gynecological comorbidities: history of salpingectomy, ovarian cysts (e.g., chocolate cysts), ovarian tumors, or simple cysts ≥10 mm (not eligible for enrollment in the current cycle; may be enrolled after regression), history of ovarian surgery, endometriosis or adenomyosis, or acute pelvic inflammatory disease;
- •Patients with abnormal ovarian position who are expected to experience difficulties during oocyte retrieval puncture;
- •Patients with concomitant systemic severe diseases (history of severe chronic diseases such as heart failure, myocardial infarction, stroke, end-stage renal disease; advanced cancer or other terminal illnesses with an estimated survival period of less than 6 months; coagulation disorders; uncontrolled sepsis; autoimmune diseases; poor general condition rendering anesthesia and surgery intolerable);
- •Patients with contraindications to hormone replacement therapy;
- •Currently undergoing treatment with cytotoxic drugs, glucocorticoids or other immunosuppressants, radiotherapy or chemotherapy, or having previously received radiotherapy or chemotherapy;
- •One spouse has chromosomal abnormalities;
- •Patients with a history of uncontrolled epilepsy, central nervous system disorders, or psychiatric disorders, where the investigator determines that clinical severity affects compliance with the clinical study;
- •Patients who have undergone oocyte retrieval or ovarian puncture within the past year;
- •Participating in other clinical trials.
研究组 & 干预措施
intervention group (multiple ovarian cortex puncture)
The intervention group underwent combined ovarian cortex multi-point puncture in addition to conventional oocyte retrieval procedures (identical to the control group). Specifically, after completing standard oocyte retrieval under the same anesthesia/sedation conditions, multi-point ovarian cortex puncture was performed without needle replacement. The procedure was guided by real-time ultrasound to ensure operational accuracy and visualization. On ultrasound imaging, three puncture sites were selected from the ovarian cortex region (avoiding residual follicles, corpus luteum, and medullary vascular areas) for uniform distribution: the first puncture point was aligned with the oocyte retrieval puncture line, followed by the second and third puncture points located approximately 5 mm to either side of the first point after exiting the ovarian surface.
干预措施: multiple ovarian cortex punctures (Procedure)
control group (conventional oocyte retrieval procedure)
Control measures (routine oocyte retrieval procedure):The procedure was performed according to the standard oocyte retrieval protocols of each center, with ovarian follicle aspiration completed under transvaginal ultrasound guidance. All target follicles were confirmed to have undergone complete aspiration of follicular fluid.
干预措施: routine oocyte retrieval procedure (Other)
结局指标
主要结局
Number of oocytes retrieved during the second ovarian stimulation cycle
时间窗: The assessment period lasts up to 4 months, from the date of randomization to the completion of the second ovarian stimulation and oocyte retrieval.
Number of oocytes retrieved during the second ovarian stimulation cycle in DOR patients (recorded separately by investigators unaware of group assignments for left and right ovaries).
次要结局
- Key reproductive-related indicators for the second ovarian stimulation and oocyte retrieval cycle(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(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(From the date of randomization to clinical pregnancy after this embryo transfer, the assessment period can last up to 24 months.)
- Implantation rate(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(From the date of randomization to miscarriage after this embryo transfer, the assessment period can last up to 30 months.)
- Live birth rate(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(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(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(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(From the date of randomization to the date of adverse event occurrence, the assessment period lasts up to 100 months.)