Efficacy of Traditional Chinese Medicine on Ameliorating IVF-ET Outcomes of Diminished Ovarian Reserve Patients

October 26, 2022 updated by: Peking University Third Hospital

Non-inferiority Randomized Controlled Study on Kidney Tonifying and Blood Circulation Regulating Therapy (Bu Shen Tiao Xue) of Different Intervention Courses in Improving IVF-ET Pregnancy Outcomes in DOR Patients

Patients with diminished ovarian reserve (DOR) who undergo in vitro fertilization and embryo transfer (IVF-ET) are included as the research subjects. The effects of Traditional Chinese Medicine (TCM) for kidney tonifying and blood circulation regulating of different intervention courses on ovarian hyporesponsiveness, IVF-ET outcome and clinical compliance in DOR patients are studied by a non-inferiority randomized controlled trial. The purpose is to identify the breakthrough point and treatment timing of TCM treatment, explore the best treatment course of TCM, and optimize the TCM therapeutic regimen.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

IVF-ET is one of the major techniques to treat infertility in DOR patients, but poor ovarian response and low pregnancy rate have been the bottleneck problems. China has original advantages in Traditional Chinese Medicine (TCM) treatment. The kidney tonifying and blood circulation regulating therapy is a pre-IVF-ET intervention treatment characterized by sequential treatment according to menstrual cycle formed in the previous investigations by the research group. It can ameliorate ovarian hyporesponsiveness and improve the success rate of IVF-ET, but the compliance is poor due to the long intervention course. Identifying the time point of TCM intervention to further optimize the treatment plan is the key to improving the pregnancy rate. Therefore, DOR patients who receive IVF-ET are enrolled as the research objects in this project, who are divided into the experimental group and control group with a randomized controlled non-inferiority design, and receive sequential TCM therapy for kidney tonifying and blood circulation regulating from the fifth day of menstruation at the second menstrual cycle and the third menstrual cycle prior to IVF-ET, respectively, until the day of human chorionic gonadotrophin (hCG) administration. The number of oocytes retrieved, the rate of high-quality embryos, the dosage and administration days of Gn, the levels of estradiol (E2) and progesterone (P) and the clinical pregnancy rate on hCG day are compared between the two groups. Meanwhile, the compliance of patients in the two groups with different treatment regimens is compared. This project aims to verify that the efficacy of the treatment plan implemented from the second menstrual cycle prior to IVF-ET may not be inferior to that from the third menstrual cycle prior to IVF-ET on improving the pregnancy outcomes of DOR patients, while the compliance is better. The results of the study will provide a reference basis for the precise treatment of TCM prior to IVF-ET.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
266

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 42 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Female, 20 years old ≤ age ≤ 42 years old;
  2. The menstrual cycle is generally regular; 21 days < menstrual cycle < 35 days;
  3. Those who meet the diagnostic criteria for DOR in Western medicine;
  4. Those who meet the TCM differential criteria of kidney deficiency syndrome;
  5. Those who are scheduled to undergo IVF-ET;
  6. Those who voluntarily participate in this clinical trial and sign a written informed consent.

Exclusion Criteria:

  1. Those who have a history of two or more spontaneous abortions (excluding biochemical pregnancy abortion) or three or more previous transplantations without achieving clinical pregnancy;
  2. Those who have premature ovarian failure or ovarian gonadotropin resistance syndrome;
  3. Those who have untreated uterine malformation or abnormality: double uterus, septate uterus (complete or incomplete);
  4. Those who have untreated unilateral or bilateral hydrosalpinx;
  5. Those who have uncured endometrial diseases (such as endometritis, endometrial polyps, endometriosis), adenomyosis, intrauterine adhesions, etc., and those with uterine fibroids of more than 4 cm;
  6. Those who have endocrine diseases such as polycystic ovary syndrome, hyperprolactinemia, hyperandrogenism, hypothyroidism, abnormal adrenal function, etc., which affect ovulation;
  7. Infertile patients with abnormal ovarian function caused by immunological factors, genetic factors or congenital physiological defects;
  8. Those who have received pelvic radiotherapy;
  9. Those who are known or suspected of having sex hormone-related malignant tumors;
  10. Those who are allergic or intolerable to the medications involved in the study;
  11. Those with contraindications to assisted reproductive technology or pregnancy, such as uncontrolled abnormal liver and renal function, diabetes, hypertension, thyroid disease, symptomatic heart disease, moderate to severe anemia, history of malignant tumor or history of thromboembolism or thrombosis formation tendency, serious mental illness, acute infection of urogenital system, sexually transmitted disease, extremely bad habits such as drug use, exposure to teratogenic radiation, poison, drugs (such as prednisone and other hormones, epinephrine, antibiotics, antihypertensive drugs, cardiovascular and cerebrovascular drugs, antiviral drugs) and are still under the effect of the drugs; and those whose uterus is unable to perform the function of pregnancy or who are intolerant of pregnancy due to physical diseases during pregnancy;
  12. Those who have taken other TCMs or proprietary Chinese medicines that can invigorate the kidney or affect the evaluation of drug efficacy in the past 30 days;
  13. Other patients who are deemed unsuitable to participate in this study by the researchers;
  14. Those who are participating in other clinical trials;
  15. Those who do not agree to participate in this study or do not sign the informed consent form.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: administration for 2 menstrual cycles group
This group will receive TCM treatment before 2 menstrual cycles of IVF-ET.
Drug: Medical prescription before ovulation
Medical prescription before ovulation, modified two solstices pill and Si-Wu-Tang: 15g of Nv Zhen Zi (Fructus Ligustri Lucidi), 10g of Mo Han Lian (Yerbadetajo herb), 15g of Gou Qi Zi (Fructus lycii), 20g of Tu Si Zi (Semen cuscutae), 15g of Shu Di (Radix Rehmanniae Preparata), 10g of Dang Gui (Angelica sinensis), 10g of Bai Shao (Paeonia lactiflora Pallas), 20g of Sheng Shan Yao (Rhizoma Dioscoreae), 15g of Fu Pen Zi (Raspberry), and 15g of Shan Yu Rou (Fructus corni). The medical prescription is initiated on the fifth day of menstruation and is taken continuously for 10-15 days.
Drug: Medical prescription after ovulation
Medical prescription after ovulation, modified Er Xian decoction for promoting fertilization and Si-Wu-Tang: 10g of Xian Mao (Curculigo orchioides), 15g of Xian Ling Pi (Epimedium Herb), 15g of Ba Ji Tian (Morinda officinalis), 20g of Tu Si Zi (Semen cuscutae), 15g of Nv Zhen Zi (Fructus Ligustri Lucidi), 15g of Zi Shi Ying (Fluoritum), 15g of Shu Di (Radix Rehmanniae Preparata), 10g of Dang Gui (Angelica sinensis), 10g of Bai Shao (Paeonia lactiflora Pallas), and 10g of Chuan Xiong (Szechwan Lovage Rhizome). The medical prescription is administered continuously for 10-15 days after ovulation, based on follicle development and endometrial growth monitored by ultrasound.
ACTIVE_COMPARATOR: administration for 3 menstrual cycles group
This group will receive TCM treatment before 3 menstrual cycles of IVF-ET.
Drug: Medical prescription before ovulation
Medical prescription before ovulation, modified two solstices pill and Si-Wu-Tang: 15g of Nv Zhen Zi (Fructus Ligustri Lucidi), 10g of Mo Han Lian (Yerbadetajo herb), 15g of Gou Qi Zi (Fructus lycii), 20g of Tu Si Zi (Semen cuscutae), 15g of Shu Di (Radix Rehmanniae Preparata), 10g of Dang Gui (Angelica sinensis), 10g of Bai Shao (Paeonia lactiflora Pallas), 20g of Sheng Shan Yao (Rhizoma Dioscoreae), 15g of Fu Pen Zi (Raspberry), and 15g of Shan Yu Rou (Fructus corni). The medical prescription is initiated on the fifth day of menstruation and is taken continuously for 10-15 days.
Drug: Medical prescription after ovulation
Medical prescription after ovulation, modified Er Xian decoction for promoting fertilization and Si-Wu-Tang: 10g of Xian Mao (Curculigo orchioides), 15g of Xian Ling Pi (Epimedium Herb), 15g of Ba Ji Tian (Morinda officinalis), 20g of Tu Si Zi (Semen cuscutae), 15g of Nv Zhen Zi (Fructus Ligustri Lucidi), 15g of Zi Shi Ying (Fluoritum), 15g of Shu Di (Radix Rehmanniae Preparata), 10g of Dang Gui (Angelica sinensis), 10g of Bai Shao (Paeonia lactiflora Pallas), and 10g of Chuan Xiong (Szechwan Lovage Rhizome). The medical prescription is administered continuously for 10-15 days after ovulation, based on follicle development and endometrial growth monitored by ultrasound.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of oocytes retrieved
Time Frame: up to 15 weeks from enrollment
The number of oocytes retrieved by puncture under the guidance of vaginal ultrasound
up to 15 weeks from enrollment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
High-quality embryo rate (%)
Time Frame: up to 15 weeks from enrollment
Number of high-quality embryos / the total number of normal cleavage embryos × 100%
up to 15 weeks from enrollment
Clinical pregnancy rate
Time Frame: up to 15 weeks from enrollment
Ultrasound monitoring is performed 30 days after embryo transfer
up to 15 weeks from enrollment
Compliance with the treatment plan
Time Frame: up to 15 weeks from enrollment
The situation of continuous treatment of the research subjects is recorded; the compliance of the experimental group = the number of cases who receive continuous treatment for 2 months / the total number of patients in the experimental group; the compliance of the control group = the number of cases who receive continuous treatment for 3 months / the total number of patients in the control group
up to 15 weeks from enrollment
Gonadotrophin (Gn) administration day
Time Frame: up to 15 weeks from enrollment
Record the total gonadotrophin (Gn) administration day
up to 15 weeks from enrollment
Gn dosage
Time Frame: up to 15 weeks from enrollment
Record the average dose of Gn administration
up to 15 weeks from enrollment
Levels of LH
Time Frame: up to 15 weeks from enrollment
Obtained by blood sampling
up to 15 weeks from enrollment
Levels of E2
Time Frame: up to 15 weeks from enrollment
Obtained by blood sampling
up to 15 weeks from enrollment
Levels of P
Time Frame: up to 15 weeks from enrollment
Obtained by blood sampling
up to 15 weeks from enrollment
Antral follicle count (AFC)
Time Frame: up to 15 weeks from enrollment
Changes of AFC before and after TCM intervention
up to 15 weeks from enrollment
Levels of FSH
Time Frame: up to 15 weeks from enrollment
Obtained by blood sampling
up to 15 weeks from enrollment
Levels of AMH
Time Frame: up to 15 weeks from enrollment
Obtained by blood sampling
up to 15 weeks from enrollment
Health economics indicators
Time Frame: up to 15 weeks from enrollment
Average daily cost and total cost
up to 15 weeks from enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Peking University Third Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 10, 2022

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2024

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 9, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2022

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 13, 2022

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 27, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 26, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00006761-M2022270

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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