The Application of Zishen Yutai Pill in Aged Women Undergoing IVF-ET

Study Overview
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Brief Summary
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To explore the application of Zishen Yutai Pill in controlled ovarian stimulation and effect on pregnancy outcome in aged women undergoing in vitro fertilization-embryo transfer.

Detailed Description
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This will be a multi-center double-blind randomized controlled trial, which aims to explore the application of Zishen Yutai Pill in controlled ovarian stimulation and effect on pregnancy outcome in aged women undergoing in vitro fertilization-embryo transfer.The target population will be infertile women aged between 35 and 42 years, BMI<28kg/m2 and bilateral ovaries who undergo IVF-ET (long or antagonist protocol). Qualified 1,466 patients are randomized into either of two groups.They will be randomized to receive either Zishen Yutai Pill or the placebo. The pregnancy test results and pregnancy complications will be followed up by checking medical records and telephone calls.

Official Title
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The Application of Zishen Yutai Pill in Aged Women Undergoing in Vitro Fertilization-embryo Transfer: a Multi-center Double-blind Randomized Controlled Trial

Conditions
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Infertility, Female

Intervention / Treatment
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* Drug: Zishen Yutai Pill
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: infertile women aged ≥35 and ≤42 years; intend to undergo IVF-ET (long or antagonist protocol); BMI<28kg/m2; bilateral ovaries exist; patients who voluntarily signed the informed consent and agreed to be followed up as required by the study protocol. Exclusion Criteria: repeated implantation failure (previous three times or more IVF/ICSI-ET failure); adenomyosis, uterine line constricted by uterine fibroid; untreated bilateral hydrosalpinx; endometrial diseases that have not been cured ; known diseases that are not suitable for undergoing assisted reproductive technology or at the present not suitable for pregnancy; patients who have taken traditional Chinese medicine or Chinese patent medicine for infertility treatment in the last month(30 days). Exit Criteria: subjects who have adverse events cannot be tolerated; severe breach of the protocol; for subjects who exit due to personal or unpredictable reasons, please describe specific details; subjects considered inappropriate to continue to participate in the study for other medical reasons.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zishen Yutai pill group<br>Patients who undergo the long-term protocol will start taking Zishen Yutai Pill on the day of pituitary suppression, 5g three times a day (Stopping on the first 1-4 days of menstruation), and patients who undergo the antagonist protocol will start taking Zishen Yutai Pill on the 19th to 23rd day of the previous menstruation cycle, 5g three times a day (Stopping on the first 1-4 days of menstruation). The drug will be taken till 2 weeks after transplantation. If the test result is confirmed as biochemical pregnancy (HCG>50 IU/L), patients continue to take pills till 3 weeks after the clinical pregnancy determined by the ultrasound. If it is determined that the pregnancy test is negative, stop the drug. | Drug: Zishen Yutai Pill<br>* Patients who undergo the long-term protocol will start taking Zishen Yutai Pill on the day of pituitary suppression, 5g three times a day (Stopping on the first 1-4 days of menstruation), and patients who undergo the antagonist protocol will start taking Zishen Yutai Pill on the 19th to 23rd day of the previous menstruation cycle, 5g three times a day (Stopping on the first 1-4 days of menstruation). The drug will be taken till 2 weeks after transplantation. If the test result is confirmed as biochemical pregnancy (HCG>50 IU/L), patients continue to take pills till 3 weeks after the clinical pregnancy determined by the ultrasound. If it is determined that the pregnancy test is negative, stop the drug.<br>|
| Placebo Comparator: Placebo group<br>Patients who undergo the long-term protocol will start taking Placebo on the day of pituitary suppression, 5g three times a day (Stopping on the first 1-4 days of menstruation), and patients who undergo the antagonist protocol will start taking Placebo on the 19th to 23rd day of the previous menstruation cycle, 5g three times a day (Stopping on the first 1-4 days of menstruation). The drug will be taken till 2 weeks after transplantation. If the test result is confirmed as biochemical pregnancy (HCG>50 IU/L), patients continue to take pills till 3 weeks after the clinical pregnancy determined by the ultrasound. If it is determined that the pregnancy test is negative, stop the drug. | Drug: Placebo<br>* Patients who undergo the long-term protocol will start taking Placebo on the day of pituitary suppression, 5g three times a day (Stopping on the first 1-4 days of menstruation), and patients who undergo the antagonist protocol will start taking Placebo on the 19th to 23rd day of the previous menstruation cycle, 5g three times a day (Stopping on the first 1-4 days of menstruation). The drug will be taken till 2 weeks after transplantation. If the test result is confirmed as biochemical pregnancy (HCG>50 IU/L), patients continue to take pills till 3 weeks after the clinical pregnancy determined by the ultrasound. If it is determined that the pregnancy test is negative, stop the drug.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | the clinical pregnancy determined by the ultrasound, and Clinical pregnancy rate=Number of clinical pregnancy cycles / Total number of embryo transfer cycles | 1 year | 
| Live birth rate | Live birth rate=Number of live birth cycles / Total number of embryo transfer cycles | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum E2 (Estradiol) concentrations on hCG (human chorionic gonadotrophin) injection day | On the day of hCG injection | 1 year | 
| Number of retrieved oocytes and zygotes | By medical records | 1 year | 
| Rate of retrieved oocytes | Rate of retrieved oocytes =Number of retrieved oocytes/Number of follicles whose diameter ≥10mm on HCG injection day | 1 year | 
| Number of cleavage | Zygotes split into more than 2 cells | 1 year | 
| Cleavage rate | Cleavage rate=Number of cleavage/Number of zygotes | 1 year | 
| Number of available embryos | Total number of embryos transferred and frozen | 1 year | 
| Rate of available embryos | Rate of available embryos=Number of available embryos/Total number of embryos | 1 year | 
| Number of high-quality embryos | According to the Istanbul consensus workshop on embryo assessment | 1 year | 
| Rate of high-quality embryos | Rate of high-quality embryos=Number of high-quality embryos/Number of available embryos | 1 year | 
| Implantation rate | Implantation rate=Number of gestational sacs/Number of embryos transferred | 1 year | 
| Miscarriage rate | Miscarriage rate=Number of miscarriage cycles/Number of clinical pregnancy cycles | 1 year | 
| The birth weight of the newborn | By checking medical records and telephone calls | 1 year | 
| The birth height of the newborn | By checking medical records and telephone calls | 1 year | 
| The congenital malformation rate of the newborn | By checking medical records and telephone calls | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVF-ET, infertility, aged, women