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

Phase 3
Not yet recruiting
Conditions
Infertility, Female
Diminished Ovarian Reserve
Interventions
Drug: Medical prescription before ovulation
Drug: Medical prescription after ovulation
Registration Number
NCT05577455
Lead Sponsor
Peking University Third Hospital
Brief Summary

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.

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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Female
Target Recruitment
266
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.
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
administration for 2 menstrual cycles groupMedical prescription before ovulationThis group will receive TCM treatment before 2 menstrual cycles of IVF-ET.
administration for 2 menstrual cycles groupMedical prescription after ovulationThis group will receive TCM treatment before 2 menstrual cycles of IVF-ET.
administration for 3 menstrual cycles groupMedical prescription before ovulationThis group will receive TCM treatment before 3 menstrual cycles of IVF-ET.
administration for 3 menstrual cycles groupMedical prescription after ovulationThis group will receive TCM treatment before 3 menstrual cycles of IVF-ET.
Primary Outcome Measures
NameTimeMethod
Number of oocytes retrievedup to 15 weeks from enrollment

The number of oocytes retrieved by puncture under the guidance of vaginal ultrasound

Secondary Outcome Measures
NameTimeMethod
Levels of Pup to 15 weeks from enrollment

Obtained by blood sampling

High-quality embryo rate (%)up to 15 weeks from enrollment

Number of high-quality embryos / the total number of normal cleavage embryos × 100%

Clinical pregnancy rateup to 15 weeks from enrollment

Ultrasound monitoring is performed 30 days after embryo transfer

Compliance with the treatment planup 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

Gonadotrophin (Gn) administration dayup to 15 weeks from enrollment

Record the total gonadotrophin (Gn) administration day

Gn dosageup to 15 weeks from enrollment

Record the average dose of Gn administration

Levels of LHup to 15 weeks from enrollment

Obtained by blood sampling

Levels of E2up to 15 weeks from enrollment

Obtained by blood sampling

Antral follicle count (AFC)up to 15 weeks from enrollment

Changes of AFC before and after TCM intervention

Levels of FSHup to 15 weeks from enrollment

Obtained by blood sampling

Levels of AMHup to 15 weeks from enrollment

Obtained by blood sampling

Health economics indicatorsup to 15 weeks from enrollment

Average daily cost and total cost

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