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: Completed
• 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 (Actual): 1467
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China
      • Chongqing Health Center for Women and Children
  • Gansu
    • Lanzhou, Gansu, China
      • The First Hospital of Lanzhou University
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
  • Guangxi
    • Liuzhou, Guangxi, China
      • Liuzhou Maternal and Child Healthcare Hospital
  • 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
  • Jiangsu
    • Suzhou, Jiangsu, China
      • The Affiliated Suzhou Hospital of Nanjing Medical University
  • Shandong
    • Jinan, Shandong, China
      • Reproductive Hospital Affiliated to Shandong University
  • Shanxi
    • Xi'an, Shanxi, China
      • Northwest Women and Children's Hospital
    • Xi'an, Shanxi, China
      • Tangdu Hospital of Air Force Medical University
  • Sichuan
    • Sichuan, Sichuan, China
      • West China Second University Hospital/West China Women's and Children's Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• infertile women aged ≥35 and ≤42 years;
• intend to undergo IVF/ICSI-ET (GnRH-a long protocol or GnRH-ant 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
Live Birth Rate	Live birth rate=Number of live birth / Paticipants randomized	1 year after embryo transfer day, up to a maximum duration of 58 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Retrieved Oocytes	The total number of oocytes retrieved through ultrasound-guided transvaginal aspiration.	On embryo transfer day, approximately 6 weeks
Rate of Retrieved Oocytes	Rate of retrieved oocytes =Number of retrieved oocytes/Number of follicles with a diameter ≥10mm on the HCG injection day.	On embryo transfer day, approximately 6 weeks
Number of Matured Oocytes Retrieved	The number of oocytes with pronuclei or polar bodies observed on Day 1 after oocyte retrieval in IVF patients, or as the number of MII oocytes on the day of oocyte retrieval in ICSI patients.	On embryo transfer day, approximately 6 weeks
Rate of Matured Oocytes	Rate of mature oocytes = Number of mature oocytes/Number of retrieved oocytes	On embryo transfer day, approximately 6 weeks
Number of Cleavage	Number of fertilized oocytes that undergo cleavage on Day 2 after oocyte retrieval.	On embryo transfer day, approximately 6 weeks
Cleavage Rate	Cleavage rate=Number of all cleaved embryos/Number of fertilized oocytes (2PN+1PN+ multiple PN)	On embryo transfer day, approximately 6 weeks
Number of Available Embryos	The sum of the number of embryos transferred and the number of embryos frozen.	On embryo transfer day, approximately 6 weeks
Rate of Available Embryos	Rate of available embryos=Number of available embryos/Number of cleaved oocytes.	On embryo transfer day, approximately 6 weeks
Number of High-quality Embryos	High-quality embryo will be defined according to the day of embryo transfer, following the Istanbul consensus and Gardner criteria, Day 2: 4 cells, cell fragments <10% and no multi-nucleus; Day 3: 8 cells, cell fragments <10%, no multi-nucleus; Day 5: stage 4 blastocyst, grade A inner cell mass, grade A trophectoderm (12,13).	On embryo transfer day, approximately 6 weeks
Rate of High-quality Embryos	Rate of high-quality embryos=Number of high-quality embryos/Number of available embryos	On embryo transfer day, approximately 6 weeks
Biochemical Pregnancy Rate	Biochemical pregnancy rate=Number of positive pregnancy tests/Paticipants randomized	14 days after ET day, approximately 8 weeks
Implantation Rate	Implantation rate=Number of gestational sacs/Number of embryos transferred	five weeks after ET day, approximately 11 weeks
Clinical Pregnancy Rate	The clinical pregnancy determined by the ultrasound, and Clinical pregnancy rate=Number of clinical pregnancies / Paticipants randomized	five weeks after ET day, approximately 11 weeks
Miscarriage Rate (Among Positive Pregnancy Test Population)	Miscarriage Rate (among positive pregnancy test population) =Number of miscarriages / Number of biochemical pregnancy	1 year after embryo transfer, up to 58 weeks
Miscarriage Rate (Among Clinical Pregnancy Population)	Miscarriage rate (among clinical pregnancy population)=Number of miscarriages / Number of clinical pregnancies	1 year after embryo transfer, up to 58 weeks
The Birth Weight of the Newborn	By checking medical records	1 year after embryo transfer, up to 58 weeks
The Birth Height of the Newborn	By checking medical records	1 year after embryo transfer, up to 58 weeks
Preterm Delivery Among Live Birth	Delivery of a fetus at less than 37 and more than 28 weeks gestational age.	1 year after embryo transfer, up to 58 weeks
Low Birth Weight Among Neonates	Neonatal birth weight ≤ 2500 g.	1 year after embryo transfer, up to 58 weeks
Congenital Anomalies Among Neonates	Congenital anomalies are defined as structural or functional anomalies that occur during intrauterine life, including minor and major anomalies.	1 year after embryo transfer, up to 58 weeks
Neonates Entering NICU	NICU, neonate intensive care unit.	1 year after embryo transfer, up to 58 weeks

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 (Actual): March 4, 2019
• Primary Completion (Actual): September 14, 2024
• Study Completion (Actual): September 14, 2024

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): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: infertility; women; aged; IVF-ET
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; 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