Clinical trial NCT05698550: The Role of Erzhi Tiangui Formula in Expected POR Women Undergoing IVF-ET
Official title: The Role of Erzhi Tiangui Formula in Expected Poor Ovarian Responders Undergoing In Vitro Fertilization-Embryo Transfer: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Infertility, Female
Keywords: Erzhi Tiangui Formula
Poor ovarian response
In Vitro Fertilization and Embryo Transfer (IVF-ET)
Advanced maternal age
Lead sponsor: Shandong University of Traditional Chinese Medicine
Sponsor class: OTHER
Collaborators: name: The 960th Hospital of the PLA Joint Logistics Support Force
name: First Affiliated Hospital of Wenzhou Medical University
name: Shanxi Provincial Maternity and Children's Hospital
name: Maternity and Child Health Care of Zaozhuang
name: Yantai Shan Hospital
name: Maternal and Child Health Care Hospital of Shandong Province
name: Hospital for Reproductive Medicine Affiliated to Shandong University
name: Chongqing Medical Center for Women and Children
name: The Second Hospital of Hebei Medical University
First posted: 2023-01-26
Enrollment: 480
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Women under 42 years of age with a poor ovarian response (according to the Bologna criteria) .

Exclusion Criteria:

* Individuals with a Body Mass Index (BMI) ≥ 35 Kg/m2.
* 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.

Primary outcomes:
measure: The number of oocyte retrieved
timeFrame: One month
measure: Cumulative live birth rate
timeFrame: Eighteen months
Secondary outcomes:
measure: Cycle cancellation rate
timeFrame: One month
measure: Number of Metaphase II (MII) oocytes
timeFrame: One month
measure: The number of good quality embryo
timeFrame: One month
measure: Implantation rate
timeFrame: Fourteen months
measure: Cumulative Clinical pregnancy rate
timeFrame: Fourteen months
Other outcomes:
Locations:
city: Jinan
country: China
facility: The Affiliated Hospital of Shandong University of Traditional Chinese Medicine
state: Shandong
Study officials:
References: