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

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

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.

Study Overview

• Status: Unknown
• Conditions: Sterility
• Intervention / Treatment: Procedure: GnRH-ant protocol; Procedure: GnRH-a long protocol

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.

• Study Type: Interventional
• Enrollment (Anticipated): 888
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qiao Jie; Phone Number: 010-82265080; Email: jie.qiao@263.net
• Study Contact Backup: Name: Rui Yang; Phone Number: 13810002416; Email: yrjeff@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Peking University Third Hospital
      • Contact: Jie Qiao; Phone Number: 010-82265080; Email: jie.qiao@263.net
  • Hebei
    • Baoding, Hebei, China, 300000
      • Recruiting
      • The Second Hospital of Hebei Medical University
      • Contact: Jiamin Hao
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • The third hospital of Zhengzhoui Medical University
      • Contact: Xingling Wang
  • Zhejiang
    • Nanjing, Zhejiang, China, 210000
      • Recruiting
      • Jiangsu Provincial Hospital
      • Contact: Feiyang Diao; Email: phenix_y@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GnRH-ant protocol; 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.	Procedure: GnRH-ant protocol; 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.
Active Comparator: GnRH-a long 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.	Procedure: GnRH-a long protocol; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of oocytes retrieved	recorded Number of oocytes retrieved on DOPU	24 hours after Oocytes pick up
Good-quality embryo rate (The Istanbul Consensus29)	Total the number of good quality embryos divided by Total the number of embryos	24 hours after Oocytes pick up
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	after 11 to 17 days of ET
Implantation rate	the number of gestational sacs observed divided by the number of embryos transferred	4 to 6 weeks after ET
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.	after 4 to 6 weeks of ET
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).	after 12 weeks of ET
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.	two years
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.	two years
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 .	after 12 weeks of ET
Ectopic pregnancy rate	the number of .extrauterine pregnancy divided by the number of Clinical pregnancy .	after 4 to 6 weeks of ET
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.	On ART cycle
severity of OHSS	Assessed the severity of OHSS.	two weeks after Oocytes pick up
Rate of OHSS	the number of OHSS divided by the number of ovum pick up. Assessed the severity of OHSS.	two weeks after Oocytes pick up
Time to pregnancy	time from Gn Initiation to the first clinical pregnancy.	4 to 6 weeks after ET
Time to live birth	time from Gn Initiation to the first live birth	nine months after pregnancy
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.	Two years after signature of informed consent

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Collaborators: Merck Serono GmbH, Germany; Fountain Medical Development Co., Ltd.; Guangzhou KingMed Center for Clinical Lab.Co., Ltd
• Investigators: Principal Investigator: Qiao Jie, Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2018
• Primary Completion (Anticipated): October 30, 2021
• Study Completion (Anticipated): July 31, 2022

Study Registration Dates

• First Submitted: February 21, 2019
• First Submitted That Met QC Criteria: July 17, 2019
• First Posted (Actual): July 19, 2019

Study Record Updates

• Last Update Posted (Actual): November 8, 2019
• Last Update Submitted That Met QC Criteria: November 6, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: live birth; assisted reproductive technology; fertilization
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: MS700623_0020

Drug and device information, study documents

• 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