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

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

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.

Study Overview

• Status: Unknown
• Conditions: Infertility, Female
• Intervention / Treatment: Drug: Zishen Yutai Pill; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1466
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dongzi Yang, professor; Phone Number: +86-020-81332233; Email: yangdz@mail.sysu.edu.cn
• Study Contact Backup: Name: Yu Li, professor; Phone Number: +86-020-81332233; Email: liyuliyu0922@163.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China
      • Chongqing Health Center For Women and Children
  • Gansu
    • Lanzhou, Gansu, China
      • The First Hospital of Lanzhou University
      • Contact: Xuehong Zhang
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
      • Contact: Dongzi Yang, professor; Phone Number: +86-020-81332233; Email: yangdz@mail.sysu.edu.cn
      • Contact: Yu Li, professor; Phone Number: +86-020-81332233; Email: liyuliyu0922@163.com
  • Guangxi
    • Liuzhou, Guangxi, China
      • Liuzhou Maternal and Child Healthcare Hospital
      • Contact: Xinlin Li
  • Henan
    • Zhengzhou, Henan, China
      • The First Affiliated hospital of Zhengzhou University
    • Zhengzhou, Henan, China
      • The Third Affiliated Hospital of Zhengzhou University
  • Hunan
    • Changsha, Hunan, China, 410000
      • Reproductive and Genetic hospital of CITIC-xiangya
      • Contact: Fei Gong
  • Shanxi
    • Xi'an, Shanxi, China
      • Northwest Women and Children's Hospital
      • Contact: Juanzi Shi
    • Xi'an, Shanxi, China
      • Tangdu Hospital of Air Force Medical University
      • Contact: Xiaohong Wang
  • Sichuan
    • Sichuan, Sichuan, China
      • West China Second University Hospital/West China Women's and Children's Hospital
      • Contact: Shan Luo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zishen Yutai pill group; 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; 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.
Placebo Comparator: Placebo group; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Dongzi Yang, professor, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 30, 2019
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: August 5, 2018
• First Submitted That Met QC Criteria: October 11, 2018
• First Posted (Actual): October 12, 2018

Study Record Updates

• Last Update Posted (Actual): February 1, 2019
• Last Update Submitted That Met QC Criteria: January 30, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: infertility; women; aged; IVF-ET
• Additional Relevant MeSH Terms: Infertility; Infertility, Female
• Other Study ID Numbers: 2018112704

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No