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

NCT ID: NCT05698550

Last Updated: 2023-10-31

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE3
• Total Enrollment: 480 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-15
• Study Completion Date: 2025-12-31

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.

Conditions

Infertility, Female

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

EZTG group

Group Type: EXPERIMENTAL

Erzhi Tiangui Granule

Intervention Type: DRUG

The Drug Manufacturing Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine produced the EZTG granule.The EZTG was packaged as 3 g/bag, batch number 01-FZ032-03. The daily dose is equivalent to 15g of Ligustrum lucidum (Nv Zhen Zi),15g of Lotus japonicus (Han Lian Cao),15g of the fruit of Chinese wolfberry(Gou Qi Zi),15g of Cuscuta chinensis(Tu Si Zi), 15g of Radix Rehmanniae Preparata(Shu Di Huang),12g of Angelica sinensis(Dang Gui),12g of Paeonia lactiflora(Bai Shao),12g of Ligusticum wallichii(Chuan Xiong),12g of Rhizoma cyperi(Xiang Fu),and 9g of Radix Glycyrrhizae (Zhi Gan Cao).The placebo granule,which was Preparata mainly composed of dextrin, was made in a similar color and shape to EZTG.Placebo granules were packaged as 3g/bag, with the same package of the EZTG, batch number 01-FZ032-03-1. The EZTG or placebo was orally administered after being dissolved in water, 3g each time, 2 times a day.

Control group

Group Type: PLACEBO_COMPARATOR

Erzhi Tiangui Placebo

Intervention Type: DRUG

The placebo consisted mainly of yellow bean powder, starch, carbogen, molasses and could mimic the appearance, color and smell of Erzhi Tiangui granules, but without any active ingredients. Daily doses of placebo were delivered in the same packaging as Erzhi Tiangui granules.

Interventions

Erzhi Tiangui Granule

The Drug Manufacturing Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine produced the EZTG granule.The EZTG was packaged as 3 g/bag, batch number 01-FZ032-03. The daily dose is equivalent to 15g of Ligustrum lucidum (Nv Zhen Zi),15g of Lotus japonicus (Han Lian Cao),15g of the fruit of Chinese wolfberry(Gou Qi Zi),15g of Cuscuta chinensis(Tu Si Zi), 15g of Radix Rehmanniae Preparata(Shu Di Huang),12g of Angelica sinensis(Dang Gui),12g of Paeonia lactiflora(Bai Shao),12g of Ligusticum wallichii(Chuan Xiong),12g of Rhizoma cyperi(Xiang Fu),and 9g of Radix Glycyrrhizae (Zhi Gan Cao).The placebo granule,which was Preparata mainly composed of dextrin, was made in a similar color and shape to EZTG.Placebo granules were packaged as 3g/bag, with the same package of the EZTG, batch number 01-FZ032-03-1. The EZTG or placebo was orally administered after being dissolved in water, 3g each time, 2 times a day.

Intervention Type: DRUG

Erzhi Tiangui Placebo

The placebo consisted mainly of yellow bean powder, starch, carbogen, molasses and could mimic the appearance, color and smell of Erzhi Tiangui granules, but without any active ingredients. Daily doses of placebo were delivered in the same packaging as Erzhi Tiangui granules.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 42 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

The 960th Hospital of the PLA Joint Logistics Support Force

UNKNOWN

Sponsor Role: collaborator

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: collaborator

Shanxi Provincial Maternity and Children's Hospital

OTHER

Sponsor Role: collaborator

Maternity and Child Health Care of Zaozhuang

UNKNOWN

Sponsor Role: collaborator

Yantai Shan Hospital

UNKNOWN

Sponsor Role: collaborator

Maternal and Child Health Care Hospital of Shandong Province

UNKNOWN

Sponsor Role: collaborator

Hospital for Reproductive Medicine Affiliated to Shandong University

UNKNOWN

Sponsor Role: collaborator

Chongqing Medical Center for Women and Children

OTHER

Sponsor Role: collaborator

The Second Hospital of Hebei Medical University

OTHER

Sponsor Role: collaborator

Shandong University of Traditional Chinese Medicine

OTHER

Sponsor Role: lead

Responsible Party

Jing-Yan Song

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Affiliated Hospital of Shandong University of Traditional Chinese Medicine

Jinan, Shandong, China

Countries

China

Other Identifiers

SDUTCMEZTG1104

Identifier Type: -

Identifier Source: org_study_id