Efficacy of Erzhi Tiangui Granules on Live Birth Rate in Advanced-age Women With Poor Ovarian Response Undergoing in Vitro Fertilization: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 480
- 试验地点
- 1
- 主要终点
- Cumulative live birth rate
研究概览
简要总结
This randomized controlled trial aims to determine whether Erzhi Tiangui Formula can optimize the reproductive outcomes of elderly patients with expected poor ovarian response, and to provide a new approach to traditional Chinese medicine assisted in vitro fertilization and embryo transfer (IVF-ET).
详细描述
In recent years, traditional Chinese medicine (TCM) has been involved with all aspects of assisted reproductive technology (ART), but it remains a long way from being applied to in vitro fertilization and embryo transfer (IVF-ET). Moreover, there is a lack of high-quality clinical research conducted on a large scale. The Erzhi Tiangui formula, which originated from Gui-Cheng Xia, a national TCM master, was composed and established by Professor Fang Lian, who was a national famous TCM practitioner and "Qi Huang scholar," based on her professional experience of more than 40 years. After more than 20 years of basic and clinical investigation, it has demonstrated its effectiveness in optimizing female reproductive function. We therefore adopt Erzhi Tiangui Fang as a pretreatment for IVF-ET in patients with expected poor ovarian response in order to improve their reproductive outcomes. Outpatient clinics at 10 public tertiary hospitals in the country are involved in the study. It is planned to enroll 480 elderly patients with poor ovarian response between January 2023 and December 2025. The Erzhi Tiangui formula group and placebo group will be randomly assigned in a 1:1 ratio through stratified block randomization. Both groups will use a fixed gonadotrophin releasing hormone (GnRH) antagonist protocol for controlled ovarian hyperstimulation. In IVF cycles, Erzhi tiangui formula and placebo will be administered from day 2 or 3 of the previous menstrual cycle to the trigger day. Approximately 5 to 6 weeks will be required for the intervention to be completed. The primary outcome is the number of retrieved oocytes, i.e., the number of oocytes observed under a microscope after oocyte retrieval monitored by transvaginal ultrasound. Secondary outcomes are the ovarian stimulation outcomes, embryonic laboratory outcomes, pregnancy outcomes, obstetric and neonatal outcomes.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 35 Years 至 43 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women aged 35 to 43 years with POR who were scheduled for IVF or intracytoplasmic sperm injection (ICSI) treatment were eligible for enrollment. The diagnosis of POR was based on the Bologna criteria.
- •Women were excluded if they: (i) had a body mass index (BMI) ≥ 35 kg/m2; (ii) failed to obtain clinical pregnancy after three or more IVF/ICSI cycles; (iii) had a history of two or more recurrent pregnancy losses; (iv) were diagnosed with uterine abnormalities using hysteroscopy or diagnosed with hydrosalpinx using hysterosalpingography; (v) had a history of chemotherapy with cytotoxic agents, pelvic radiotherapy, or severe systemic diseases; (vi) had taken Chinese herbal medicines or other therapies affecting ovarian function within three months before study enrollment; or (vii) were allergic to the ingredients of EZTG granules or placebo.
排除标准
- •Individuals with a Body Mass Index (BMI) ≥ 35 Kg/m
- •Those with a history of unilateral oophorectomy or recurrent pregnancy loss, defined as two or more spontaneous abortions.
- •Acceptors of donated oocytes or performed either In vitro Maturation (IVM) or blastocyst biopsy for Preimplantation Genetic Diagnosis (PGD) or Preimplantation Genetic Testing for Aneuploidies (PGT-A).
- •Those previously diagnosed with congenital (e.g., mediastinal uterus and double uterus) or acquired (e.g., submucosal myoma and adenomyosis) uterine abnormalities.
- •Presence of a non-surgically treated hydrosalpinx or endometrial polyp and an ovarian endometriosis cyst requiring surgery, during ovarian stimulation.
- •Allergy to or intolerance of the drugs used in the study.
- •Combined contraindications to assisted reproductive technology or pregnancy, such as uncontrolled abnormalities of liver and kidney function, diabetes mellitus (glycosylated haemoglobin ≤7%, fasting blood glucose <10 mmol/L ), hypertension, thyroid disease, symptomatic heart disease, moderate to severe anaemia, history of malignancy or thromboembolism or propensity to thrombosis, severe psychiatric disorder, acute infections of the genitourinary system, sexually transmitted diseases, serious adverse habits such as drug abuse, exposure to teratogenic amounts of radiation, toxins, or drugs (such as prednisone or other hormones, adrenaline, antibiotics, or hypertension, cardiovascular, or antiviral medications) during the active procedure period , and uterine factor infertility or physical illness which prevents the ability to bear a pregnancy.
研究组 & 干预措施
EZTG group
干预措施: Erzhi Tiangui Granule (Drug)
Control group
干预措施: Erzhi Tiangui Placebo (Drug)
结局指标
主要结局
Cumulative live birth rate
时间窗: Eighteen months
Cumulative live birth rates (CLBR), defined as the proportion of deliveries with at least one live birth per started cycle or per oocyte aspiration, including all fresh and/or frozen embryo transfers until one delivery with a live birth or until all embryos were used.
The number of oocyte retrieved
时间窗: One month
After oocyte retrieval by transvaginal puncture, the number of collected oocytes was observed microscopically.
次要结局
- Cycle cancellation rate(One month)
- Number of Metaphase II (MII) oocytes(One month)
- The number of good quality embryo(One month)
- Implantation rate(Fourteen months)
- Cumulative Clinical pregnancy rate(Fourteen months)
研究者
Jing-Yan Song
Clinical Professor
Shandong University of Traditional Chinese Medicine