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To Investigate the Cumulative Live Birth Rates Using GnRH Antagonist or Agonist Protocol for COS in ART Treatment (CLBR)

Primary Purpose

Sterility

Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
GnRH-ant protocol
GnRH-a long protocol
Sponsored by
Peking University Third Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sterility focused on measuring assisted reproductive technology, live birth, fertilization

Eligibility Criteria

18 Years - 38 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Infertile women planning to undergo IVF/ICSI cycle using conventional GnRH agonist long protocol or GnRH antagonist protocol
  • Age ≤ 38 years old
  • Basal AFC 8~20
  • Basal FSH≤10 IU/L
  • Basal E 2 <200pmol/L
  • Normal uterus and at least one side of the normal ovary
  • Informed consent form signed
  • Willing to follow the study protocol, and able to complete this study

Exclusion Criteria:

  • Previous IVF/ICSI cycles >2
  • Severe hydro-salpinx (Ultrasound shows hydro salpinx﹥2cm)
  • Severe endometriosis (Grade III - IV)
  • Polycystic ovarian syndrome (PCOS)
  • History of recurrent miscarriages (>2 times of miscarriages)
  • Plan to undergo ovarian stimulation for preimplantation genetic diagnosis or preimplantation genetic screening, oocyte donation, and social or medical freezing of oocytes
  • Any major systemic disease that as per Investigator's discretion precludes subject for participation in the study
  • With pregnancy contraindications
  • Alcoholism, drug abuse, drug addiction or patients with uncured sexually transmitted disease
  • According to the judgment of the Investigator, any medical condition or any concomitant surgery/medications that would interfere with evaluation of study medications
  • Simultaneous participation in another clinical study
  • Plan to use urinary gonadotrophin during COS treatment

Sites / Locations

  • Peking University Third HospitalRecruiting
  • The second hospital of Hebei Medical UniversityRecruiting
  • The third hospital of Zhengzhoui Medical UniversityRecruiting
  • Jiangsu Provincial HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

GnRH-ant protocol

GnRH-a long protocol

Arm Description

Recombinant FSH (Gonal-f®) will be administrated as routinely practiced by investigators. FSH doses will be adjusted according to the clinical experiences of investigators.The GnRH-ant (Cetrotide®) will be initiated in a fixed protocol on stimulation days 5 or 6 per the investigator's ART protocol.

The GnRH-a (Diphereline® or Decapetyl®) 0.1mg will be administered for about 14 to 20 days for down-regulation. Gonal-f® will be administrated as routinely practiced by investigators. GnRH-a types, GnRH-a and FSH doses will be adjusted according to the clinical experiences of investigators in each site.

Outcomes

Primary Outcome Measures

the cumulative live birth rates
To investigate the cumulative live birth rates in infertile women ≤ 38 years old with normal ovarian from one initiated COS cycle. reserve using GnRH antagonist or agonist protocol for COS in ART treatment Numerator is the No. of women got their first live birth, the Denominator is the No. of women who attempt the ovarian stimulation. There will be two ways to calculate the CLBR: The conservative estimate of the cumulative live birth rate, which is based on the assumption that none of the women who do not return for a subsequent embryo transfer would have had a live birth. The optimal estimate of the cumulative live birth rate, which is based on the assumption that women who do not return for a subsequent embryo transfer would have had the same live birth rates as those who do return.

Secondary Outcome Measures

Number of oocytes retrieved
recorded Number of oocytes retrieved on DOPU
Good-quality embryo rate (The Istanbul Consensus29)
Total the number of good quality embryos divided by Total the number of embryos
hCG positive rate
Numerator is the No.of β-hCG blood test which is positive results, he Denominator is the No. of β-hCG blood test. HCG test is Serum β-hCG test after 11 to 17
Implantation rate
the number of gestational sacs observed divided by the number of embryos transferred
Clinical pregnancy rate
the number of clinical pregnancies expressed per 100 initiated cycles, aspiration cycles, or embryo transfer cycles. Note: When clinical pregnancy rates are given, the denominator (initiated, aspirated, or embryo transfer cycles) must be specified.
Ongoing pregnancy rate
the number of . Ongoing pregnancy divided by the number of Clinical pregnancy . Ongoing pregnancy is intrauterine pregnancy continued for 12 gestational weeks (detection of presence of gestational sac with fetal heartbeat by transvaginal ultrasound examination in week 12).
Live birth rate
Numerator is the No. of women got live birth resulting from fresh cycle (multiple births considered as one live birth), the Denominator is the No. of women who attempt the ovarian stimulation.
Cumulative clinical pregnancy rate
Numerator is the No. of women got their first clinical pregnancy, the Denominator is the No. of women who attempt the ovarian stimulation.
Miscarriage rate
the number of Miscarriage which is the natural death of an embryo or fetus before it is able to survive independently divided by the number of Clinical pregnancy .
Ectopic pregnancy rate
the number of .extrauterine pregnancy divided by the number of Clinical pregnancy .
Cycle cancelled rate and reason
Cancelled cycle is an ART cycle in which ovarian stimulation or monitoring has been carried out with the intention to treat, but which did not proceed to follicular aspiration or, in the case of a thawed embryo, to embryo transfer. Cycle cancelled rate is the number of Cancelled cycle divided by the number of embryos transferred.
severity of OHSS
Assessed the severity of OHSS.
Rate of OHSS
the number of OHSS divided by the number of ovum pick up. Assessed the severity of OHSS.
Time to pregnancy
time from Gn Initiation to the first clinical pregnancy.
Time to live birth
time from Gn Initiation to the first live birth
the Safety
Data on AEs will be collected at scheduled and unscheduled visits, based on information spontaneously provided by the subject and/or through questioning of the subject.

Full Information

First Posted
February 21, 2019
Last Updated
November 6, 2019
Sponsor
Peking University Third Hospital
Collaborators
Merck Serono GmbH, Germany, Fountain Medical Development Co., Ltd., Guangzhou KingMed Center for Clinical Lab.Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT04026282
Brief Title
To Investigate the Cumulative Live Birth Rates Using GnRH Antagonist or Agonist Protocol for COS in ART Treatment
Acronym
CLBR
Official Title
A Prospective, Randomized Controlled Study to Investigate the CLBRs of GnRH Antagonist Protocol Compared With the Standard GnRH Agonist Long Protocol for Controlled Ovarian Stimulation in Supposed Normal Ovarian Responders
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 27, 2018 (Actual)
Primary Completion Date
October 30, 2021 (Anticipated)
Study Completion Date
July 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University Third Hospital
Collaborators
Merck Serono GmbH, Germany, Fountain Medical Development Co., Ltd., Guangzhou KingMed Center for Clinical Lab.Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Phase IV, prospective, randomized controlled study to investigate the cumulative live birth rates (CLBRs) of gonadotrophin-releasing hormone (GnRH) antagonist protocol (GnRH-ant group) compared with the standard GnRH agonist long protocol (GnRH-a group) for controlled ovarian stimulation in supposed normal ovarian responders.
Detailed Description
This is a Phase IV, prospective, randomized controlled study to investigate the cumulative live birth rates (CLBRs) of gonadotrophin-releasing hormone (GnRH) antagonist protocol (GnRH-ant group) compared with the standard GnRH agonist long protocol (GnRH-a group) for controlled ovarian stimulation in supposed normal ovarian responders. In this study, patients who are planning to undergo IVF/ICSI cycle aged ≤38 years old with normal ovarian reserve will be considered for enrollment. Approximately 888 patients will be enrolled at approximately 5 centers in China over a period of 10 months. About 12-20 visits will be performed in this study for each patient. The CLBR with first live birth resulting from one initiated COS cycle will be compared between GnRH-a group and GnRH-ant group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sterility
Keywords
assisted reproductive technology, live birth, fertilization

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
When patients enter this study, they will be randomly assigned to GnRH-ant group or GnRH-a group at ratio1:1 by the randomization schedule generated by a computer program.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
888 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GnRH-ant protocol
Arm Type
Experimental
Arm Description
Recombinant FSH (Gonal-f®) will be administrated as routinely practiced by investigators. FSH doses will be adjusted according to the clinical experiences of investigators.The GnRH-ant (Cetrotide®) will be initiated in a fixed protocol on stimulation days 5 or 6 per the investigator's ART protocol.
Arm Title
GnRH-a long protocol
Arm Type
Active Comparator
Arm Description
The GnRH-a (Diphereline® or Decapetyl®) 0.1mg will be administered for about 14 to 20 days for down-regulation. Gonal-f® will be administrated as routinely practiced by investigators. GnRH-a types, GnRH-a and FSH doses will be adjusted according to the clinical experiences of investigators in each site.
Intervention Type
Procedure
Intervention Name(s)
GnRH-ant protocol
Intervention Description
Recombinant FSH (Gonal-f®) will be administrated as routinely practiced by investigators. FSH doses will be adjusted according to the clinical experiences of investigators.The GnRH-ant (Cetrotide®) will be initiated in a fixed protocol on stimulation days 5 or 6 per the investigator's ART protocol.
Intervention Type
Procedure
Intervention Name(s)
GnRH-a long protocol
Intervention Description
The GnRH-a (Diphereline® or Decapetyl®) 0.1mg will be administered for about14 to 20 days for down-regulation. Gonal-f® will be administrated as routinely practiced by investigators. GnRH-a types, GnRH-a and FSH doses will be adjusted according to the clinical experiences of investigators in each site.
Primary Outcome Measure Information:
Title
the cumulative live birth rates
Description
To investigate the cumulative live birth rates in infertile women ≤ 38 years old with normal ovarian from one initiated COS cycle. reserve using GnRH antagonist or agonist protocol for COS in ART treatment Numerator is the No. of women got their first live birth, the Denominator is the No. of women who attempt the ovarian stimulation. There will be two ways to calculate the CLBR: The conservative estimate of the cumulative live birth rate, which is based on the assumption that none of the women who do not return for a subsequent embryo transfer would have had a live birth. The optimal estimate of the cumulative live birth rate, which is based on the assumption that women who do not return for a subsequent embryo transfer would have had the same live birth rates as those who do return.
Time Frame
two years
Secondary Outcome Measure Information:
Title
Number of oocytes retrieved
Description
recorded Number of oocytes retrieved on DOPU
Time Frame
24 hours after Oocytes pick up
Title
Good-quality embryo rate (The Istanbul Consensus29)
Description
Total the number of good quality embryos divided by Total the number of embryos
Time Frame
24 hours after Oocytes pick up
Title
hCG positive rate
Description
Numerator is the No.of β-hCG blood test which is positive results, he Denominator is the No. of β-hCG blood test. HCG test is Serum β-hCG test after 11 to 17
Time Frame
after 11 to 17 days of ET
Title
Implantation rate
Description
the number of gestational sacs observed divided by the number of embryos transferred
Time Frame
4 to 6 weeks after ET
Title
Clinical pregnancy rate
Description
the number of clinical pregnancies expressed per 100 initiated cycles, aspiration cycles, or embryo transfer cycles. Note: When clinical pregnancy rates are given, the denominator (initiated, aspirated, or embryo transfer cycles) must be specified.
Time Frame
after 4 to 6 weeks of ET
Title
Ongoing pregnancy rate
Description
the number of . Ongoing pregnancy divided by the number of Clinical pregnancy . Ongoing pregnancy is intrauterine pregnancy continued for 12 gestational weeks (detection of presence of gestational sac with fetal heartbeat by transvaginal ultrasound examination in week 12).
Time Frame
after 12 weeks of ET
Title
Live birth rate
Description
Numerator is the No. of women got live birth resulting from fresh cycle (multiple births considered as one live birth), the Denominator is the No. of women who attempt the ovarian stimulation.
Time Frame
two years
Title
Cumulative clinical pregnancy rate
Description
Numerator is the No. of women got their first clinical pregnancy, the Denominator is the No. of women who attempt the ovarian stimulation.
Time Frame
two years
Title
Miscarriage rate
Description
the number of Miscarriage which is the natural death of an embryo or fetus before it is able to survive independently divided by the number of Clinical pregnancy .
Time Frame
after 12 weeks of ET
Title
Ectopic pregnancy rate
Description
the number of .extrauterine pregnancy divided by the number of Clinical pregnancy .
Time Frame
after 4 to 6 weeks of ET
Title
Cycle cancelled rate and reason
Description
Cancelled cycle is an ART cycle in which ovarian stimulation or monitoring has been carried out with the intention to treat, but which did not proceed to follicular aspiration or, in the case of a thawed embryo, to embryo transfer. Cycle cancelled rate is the number of Cancelled cycle divided by the number of embryos transferred.
Time Frame
On ART cycle
Title
severity of OHSS
Description
Assessed the severity of OHSS.
Time Frame
two weeks after Oocytes pick up
Title
Rate of OHSS
Description
the number of OHSS divided by the number of ovum pick up. Assessed the severity of OHSS.
Time Frame
two weeks after Oocytes pick up
Title
Time to pregnancy
Description
time from Gn Initiation to the first clinical pregnancy.
Time Frame
4 to 6 weeks after ET
Title
Time to live birth
Description
time from Gn Initiation to the first live birth
Time Frame
nine months after pregnancy
Title
the Safety
Description
Data on AEs will be collected at scheduled and unscheduled visits, based on information spontaneously provided by the subject and/or through questioning of the subject.
Time Frame
Two years after signature of informed consent

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Infertile women planning to undergo IVF/ICSI cycle aged ≤38 years old with normal ovarian reserve
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
38 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Infertile women planning to undergo IVF/ICSI cycle using conventional GnRH agonist long protocol or GnRH antagonist protocol Age ≤ 38 years old Basal AFC 8~20 Basal FSH≤10 IU/L Basal E 2 <200pmol/L Normal uterus and at least one side of the normal ovary Informed consent form signed Willing to follow the study protocol, and able to complete this study Exclusion Criteria: Previous IVF/ICSI cycles >2 Severe hydro-salpinx (Ultrasound shows hydro salpinx﹥2cm) Severe endometriosis (Grade III - IV) Polycystic ovarian syndrome (PCOS) History of recurrent miscarriages (>2 times of miscarriages) Plan to undergo ovarian stimulation for preimplantation genetic diagnosis or preimplantation genetic screening, oocyte donation, and social or medical freezing of oocytes Any major systemic disease that as per Investigator's discretion precludes subject for participation in the study With pregnancy contraindications Alcoholism, drug abuse, drug addiction or patients with uncured sexually transmitted disease According to the judgment of the Investigator, any medical condition or any concomitant surgery/medications that would interfere with evaluation of study medications Simultaneous participation in another clinical study Plan to use urinary gonadotrophin during COS treatment
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qiao Jie
Phone
010-82265080
Email
jie.qiao@263.net
First Name & Middle Initial & Last Name or Official Title & Degree
Rui Yang
Phone
13810002416
Email
yrjeff@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qiao Jie
Organizational Affiliation
Peking University Third Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University Third Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Qiao
Phone
010-82265080
Email
jie.qiao@263.net
Facility Name
The second hospital of Hebei Medical University
City
Baoding
State/Province
Hebei
ZIP/Postal Code
300000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiamin Hao
Facility Name
The third hospital of Zhengzhoui Medical University
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xingling Wang
Facility Name
Jiangsu Provincial Hospital
City
Nanjing
State/Province
Zhejiang
ZIP/Postal Code
210000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Feiyang Diao
Email
phenix_y@163.com

12. IPD Sharing Statement

Learn more about this trial

To Investigate the Cumulative Live Birth Rates Using GnRH Antagonist or Agonist Protocol for COS in ART Treatment

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