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

Sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03703700

Collaborator

(none)

1,466

Enrollment

Locations

Arms

Anticipated Duration (Months)

146.6

Patients Per Site

6.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infertility, Female	Drug: Zishen Yutai Pill Drug: Placebo	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

1466 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jan 30, 2019

Anticipated Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Dec 31, 2020

Arms and Interventions

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.

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

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

Outcome Measures

Primary Outcome Measures

Clinical pregnancy rate [1 year]
the clinical pregnancy determined by the ultrasound, and Clinical pregnancy rate=Number of clinical pregnancy cycles / Total number of embryo transfer cycles
Live birth rate [through study completion, an average of 1 year]
Live birth rate=Number of live birth cycles / Total number of embryo transfer cycles

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 42 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chongqing Health Center For Women and Children	Chongqing	Chongqing	China
2	The First Hospital of Lanzhou University	Lanzhou	Gansu	China
3	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University	Guangzhou	Guangdong	China	510000
4	Liuzhou Maternal and Child Healthcare Hospital	Liuzhou	Guangxi	China
5	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China
6	The Third Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China
7	Reproductive and Genetic Hospital of CITIC-XIANGYA	Changsha	Hunan	China	410000
8	Northwest Women and Children's Hospital	Xi'an	Shanxi	China
9	Tangdu Hospital of Air Force Medical University	Xi'an	Shanxi	China
10	West China Second University Hospital/West China Women's and Children's Hospital	Sichuan	Sichuan	China