The Role of Erzhi Tiangui Formula in Expected POR Women Undergoing IVF-ET

Phase 3

• Conditions: Infertility, Female
• Interventions: Drug: Erzhi Tiangui Granule; Drug: Erzhi Tiangui Placebo

• Registration Number: NCT05698550
• Lead Sponsor: Shandong University of Traditional Chinese Medicine

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.

Study Timeline

• Study First Submitted: 2023-01-11
• Study First Submitted QC: 2023-01-16
• Study First Posted: 2023-01-26
• Study Start: 2023-09-15
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-28
• Last Update Posted: 2023-10-31
• Primary Completion: 2024-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: Female
• Target Recruitment: 480

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EZTG group	Erzhi Tiangui Granule	-
Control group	Erzhi Tiangui Placebo	-

Primary Outcome Measures

Name	Time	Method
Cumulative live birth rate	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	One month	After oocyte retrieval by transvaginal puncture, the number of collected oocytes was observed microscopically.

Secondary Outcome Measures

Name	Time	Method
Cycle cancellation rate	One month	Cycle cancellation is defined as cycle cancelled before obtaining at least one viable embryo for any reason. And cycle cancellation rate is calculated by dividing the number of women cancelled their cycle before obtaining at least one viable embryo for any reason by the total number of women randomized to the specific group.
Number of Metaphase II (MII) oocytes	One month	MII oocytes is defined as oocytes retrieved that reach the MII phase.
The number of good quality embryo	One month	Good quality embryo is defined as embryo that is graded as 6-cell grade 2 (6CII) or better or blastocyst. And good quality embryo rate is calculated by dividing the number of good quality embryo by the total number of embryo obtained after fertilization in the specific group.
Implantation rate	Fourteen months	Number of gestation sac detected / number of embryo transferred.
Cumulative Clinical pregnancy rate	Fourteen months	Clinical pregnancy will be diagnosed with the detection of an intrauterine gestation sac. And cumulative clinic pregnancy rate is calculated by the number of women who achieves clinical pregnancy after transfers of all study-specific embryos (within 1 year after randomization) by the total number of women randomized to the specific group.

Trial Locations

Locations (1)

The Affiliated Hospital of Shandong University of Traditional Chinese Medicine; 🇨🇳 Jinan, Shandong, China