Traditional Chinese Medicine Herbs in the Freeze-all IVF Cycle

Phase 3

• Conditions: Infertility, Female
• Interventions: Drug: Prescription of traditional Chinese Medicine named Er Zhi Wan combined with Si Wu Tang; Drug: Recombinant Human Follitropin Alfa for Injection、Fructose Injection、Tetyacycline Hydrochloride Capsules、Cetrorelix Acetate Powder for Injection

• Registration Number: NCT04935073
• Lead Sponsor: Peking University Third Hospital

Brief Summary

In the early stage, the preliminary study found that traditional Chinese medicine (TCM) intervention aimed at Nourishing kidney and regulating blood circulation in freeze-all IVF cycles can improve the clinical pregnancy rate. In order to further study the role of TCM in improving the pregnancy outcome of IVF-ET in infertility. A randomized controlled clinical trial will be used in this study. 90 infertile patients are randomly divided into two groups. The control group will be treated with conventional modern medicine, and the treatment group will be treated with traditional Chinese herbs on the basis of conventional modern medicine. The intervention starts from the 5th day of the menstrual cycle and lasts until the day before IVF-ET. After the transplantation, the TCM treatment continues for 14 days. The number of oocytes, antral follicles, AMH, serum FSH, and clinical pregnancy rate will be observed to evaluate the effect of TCM herbs on the improvement of pregnancy outcomes. In addition, all the participants will be asked to complete the self-evaluation of the anxiety/depression scale on the 7th day of the menstrual cycle, before and after transplantation, to analyze the emotional changes of the subjects during the study. The study will also observe the safety and health economic indicators of TCM treatment, so as to improve the overall efficacy of TCM Combined Application in assisted reproductive technology in the future.

Detailed Description

The trial is designed as a randomized, controlled clinical trial with two groups established by 1:1 equal allocation, a treatment group with interventions using herbs to tonify the kidneys and regulate blood and a control group treated using conventional Western medicine. Random numbers will be prepared by an independent third-party statistician who prepared a list of random group codes for this study. Enrolled subjects will be given a subject number during the screening process and, upon formal enrolment, will be randomly assigned to either the test or control group with a corresponding random number.

Interventions Treatment method Phase 1: The control group will be treated with conventional Western medicine, whereas the treatment group will receive treatment with the Chinese herbal formula. Treatment with the Chinese herbal formula will start on the 5th day of menstruation cycle. The medicines used will be Er Zhi Wan combined with Si Wu Tang (Radix et Rhizoma Ligustrum 15 g, Radix Morindae Sinensis 12 g, Fructus Lycii 15 g, Semen Cuscutae 20 g, Radix Rehmanniae 15 g, Radix Angelicae Sinensis 10 g, Radix Paeoniae Alba 10 g, Ligusticum wallichii 6 g, Poria cocos 15g,Polygonatum 15g,eclipta 10g); which will be taken for 10-15days.

Phase 2: After ET, the control group will be treated conventionally with no TCM intervention, and the treatment group will continue to take Chinese herbal medicine, changing to Shou Tai pills ( Morinda officinalis 15 g, Teasel 15g，Cuscutae 20 g, Eucommia ulmoides 15 g, Rehmannia 15 g, Cornus officinalis 15 g, loranthus parasiticus 20 g, Ligustrum lucidum 15g, Salvia miltiorrhiza 10g, Scutellaria baicalensis 10g, Atractylodes macrocephala 15g); which will be taken for 14days. The hospital will be responsible for the decoction of 200 mL per dose, 1 dose per day, divided into 2 doses in the morning and in the evening.

Serum human chorionic gonadotropin (hCG) will be measured, and an hCG\>30 IU will be considered to indicate biochemical pregnancy. Ultrasound monitoring will be performed 30 days after ET to calculate the clinical pregnancy rate.

Study Timeline

• Study First Submitted: 2021-05-13
• Status Verified: 2021-06
• Study Start: 2021-06-15
• Study First Submitted QC: 2021-06-21
• Last Update Submitted: 2021-06-21
• Study First Posted: 2021-06-22
• Last Update Posted: 2021-06-23
• Primary Completion: 2022-12-30
• Study Completion: 2022-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 90

Inclusion Criteria

1. Meet the diagnostic criteria for infertility.
2. Meet the criteria for identifying kidney deficiency in TCM.
3. Patients who Planning to undergo IVF-ET for pregnancy in our center, Age ≤40 years and ≥25 years.
4. Previous embryo transfer failure ≥ 2 times.
5. Menstrual cycle is basically normal, and normal ovulation has been monitored in the past.
6. There were more than 1 blastocyst /more than 2 high-quality embryos with more than 6 cells on day 3/more than 2 high-quality embryos with more than 4 cells on day 2.
7. Consent to participate in this clinical trial and sign an informed consent form.

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Exclusion Criteria

1. Patients with endometritis, acute pelvic inflammatory disease, mycotic vaginitis, bacterial vaginitis, adnexitis or other systemic infections.
2. It has been confirmed that there are obvious and serious other organic lesions in the reproductive organs.
3. Patients with allergic constitution
4. Infertility caused by genetic factors
5. Patients with serious primary diseases such as cardio cerebrovascular, kidney, liver and hematopoietic system and psychosis
6. A person who is unable to cooperate (such as a combination of neurological or mental illness, or a reluctance to cooperate)
7. The endometrial thickness on the day of hCG was less than 6 mm or the endometrial morphology on the day of hCG was type C
8. Those who did not agree to participate in the study

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Traditional Chinese Medicine herbs treatment group	Prescription of traditional Chinese Medicine named Er Zhi Wan combined with Si Wu Tang	the treatment group will receive treatment with the Chinese herbal formula on the 5th day of the menstrual cycle and lasts to 14 days after IVF-ET.
Western medicine group	Recombinant Human Follitropin Alfa for Injection、Fructose Injection、Tetyacycline Hydrochloride Capsules、Cetrorelix Acetate Powder for Injection	The control group will be treated with conventional Western medicine
Traditional Chinese Medicine herbs treatment group	Recombinant Human Follitropin Alfa for Injection、Fructose Injection、Tetyacycline Hydrochloride Capsules、Cetrorelix Acetate Powder for Injection	the treatment group will receive treatment with the Chinese herbal formula on the 5th day of the menstrual cycle and lasts to 14 days after IVF-ET.

Primary Outcome Measures

Name	Time	Method
Clinical pregnancy rate (%)	up to 6 weeks from enrollment	Follow up by telephone calls 14days after the IVF-ET

Secondary Outcome Measures

Name	Time	Method
Concentration of β-human Choriogonadotropin(β-HCG)	up to 6 weeks from enrollment	Obtained by blood sampling 14days after the proposed IVF-ET