Comparison of the Live Birth Rate Between the PPOS and the GnRH Antagonist Protocol in Patients Undergoing IVF

A Randomized Comparison of the Live Birth Rate Between the Progestin-primed Ovarian Stimulation Protocol and the Gonadotrophin Releasing Hormone Antagonist Protocol in Patients Undergoing in Vitro Fertilization

A randomized comparison of the live birth rate between the progestin-primed ovarian stimulation protocol and the gonadotrophin releasing hormone antagonist protocol in patients undergoing in vitro fertilization

Research question Does the live birth rate of the progestin-primed ovarian stimulation protocol comparable with the GnRH antagonist protocol for patients undergoing IVF?

Design This is a randomized controlled trial.

Research plan

Population: Infertile women who have medical indication for IVF will be recruited for study if they fulfil the selection criteria.

Intervention: Women will receive oral dydrogesterone 20mg daily from Day 3 till the day of ovulation trigger.

Comparator: Women will receive antagonist (Cetrorelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.

Outcomes: The primary outcome is the live birth rate the first FET.

Ovarian stimulation, egg retrieval, embryos frozen and frozen embryo transfer will be performed according to the standard operating procedures of the centres.

Study Overview

• Status: Recruiting
• Conditions: Infertility; ART
• Intervention / Treatment: Drug: Duphaston; Drug: Cetrorelix

• Study Type: Interventional
• Enrollment (Anticipated): 784
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: HE LI, MD; Phone Number: +86 13817223099; Email: lihe198900@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • ShangHai JIAI Genetics&IVF Institute
    • Contact: LI HE, MD; Phone Number: +8613817223099

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 41 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age of women <43 years at the time of ovarian stimulation for IVF
• Antral follicle count (AFC) on day 2-5 of the period≥5

Exclusion Criteria:

• Presence of a functional ovarian cyst with E2>100 pg/mL
• Recipient of oocyte donation
• Undergoing preimplantation genetic testing
• Presence of hydrosalpinx which is not surgically treated or endometrial polyp on scanning during ovarian stimulation

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: PPOS group; Ovarian stimulation will use the progestin-primed ovarian stimulation (PPOS) protocol.Women will receive progesterone (oral duphaston 20mg) daily from Day 3 till the day of ovulation trigger.	Drug: Duphaston; Women will receive oral duphaston 20mg daily from Day 3 till the day of ovulation trigger.
Active Comparator: Antagonist group; Ovarian stimulation will use the antagonist protocol. Women will receive antagonist (Cetrorelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.	Drug: Cetrorelix; Women will receive antagonist (Cetrorelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
live birth rate of the first FET live birth rate of the first FET live birth rate	live birth rate of the first FET	a live birth after 22 weeks gestation, through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum estradiol level	Serum estradiol level on the day of hCG trigger	on the day of hCG trigger, an average of 2 weeks after randomization
Serum progesterone level	Serum progesterone level on the day of hCG trigger	on the day of hCG trigger, an average of 2 weeks after randomization
Serum LH level	Serum LH level on the day of hCG trigger	on the day of hCG trigger, an average of 2 weeks after randomization
Serum FSH level	Serum FSH level on Day 2 of the period	on the day of hCG trigger, an average of 2 days after randomization
oocyte retrieved number		the number of oocyte retrieved, an average of 2 weeks after randomization
embryo number		the number of embryo, an average of 3 weeks after randomization
positive hCG level	defined with the result of serum β-hCG ≥10 mIU/mL	a blood hCG test is performed 14 days after the FET, up to 14 days
clinical pregnancy rate	presence of intrauterine gestational sac on ultrasound at 6 weeks of pregnancy	presence of intrauterine gestational sac on ultrasound at 6 weeks of pregnancy, up to 6 weeks
ongoing pregnancy rate	presence of a fetal pole with pulsation at 12 weeks of gestation	viable pregnancy beyond gestation 12 weeks, up to 12 weeks
implantation rate	number of gestational sacs per embryo transferred	number of gestational sacs per embryo transferred at 6 weeks of pregnancy, up to 6 weeks
multiple pregnancy rate	more than one intrauterine sacs on scanning	multiple pregnancy beyond gestation 12 weeks up to 12 weeks
miscarriage rate	defined as a clinically recognized pregnancy loss before the 22 weeks of pregnancy. The denominator is the clinical pregnancy.	a clinically recognized pregnancy loss before the 22 weeks of pregnancy, up to 22 weeks
ectopic pregnancy rate	pregnancy outside the uterine cavity	ectopic pregnancy during first trimester, up to 12 weeks
birth weight	birth weight of the baby delivered	a live birth after 22 weeks gestation, through study completion, an average of 1 year
rate of participants with adverse events	adverse events during COH	adverse events during COH in an average of 1 month
rate of obstetric complications	obstetric complications during pregnancy or delivery. The information will be acquired by contacting all the participants through phone	obstetric complications during pregnancy or delivery in an average of 1 year
rate of fetal or congenital defects	fetal or congenital defects found during pregnancy or delivery. The information will be acquired by contacting all the participants through phone	fetal or congenital defects found during pregnancy or delivery in an average of 1 year

Collaborators and Investigators

• Sponsor: ShangHai Ji Ai Genetics & IVF Institute
• Investigators: Principal Investigator: XIAOXI SUN, PHD, Shanghai JiAi Genetics & IVF Institute

Publications and helpful links

General Publications

• Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015 Jul;104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. Epub 2015 May 5.
• Dong J, Wang Y, Chai WR, Hong QQ, Wang NL, Sun LH, Long H, Wang L, Tian H, Lyu QF, Lu XF, Chen QJ, Kuang YP. The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial. BJOG. 2017 Jun;124(7):1048-1055. doi: 10.1111/1471-0528.14622.
• Yu S, Long H, Chang HY, Liu Y, Gao H, Zhu J, Quan X, Lyu Q, Kuang Y, Ai A. New application of dydrogesterone as a part of a progestin-primed ovarian stimulation protocol for IVF: a randomized controlled trial including 516 first IVF/ICSI cycles. Hum Reprod. 2018 Feb 1;33(2):229-237. doi: 10.1093/humrep/dex367.
• Massin N. New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF. Hum Reprod Update. 2017 Mar 1;23(2):211-220. doi: 10.1093/humupd/dmw047.
• Al-Inany HG, Youssef MA, Aboulghar M, Broekmans F, Sterrenburg M, Smit J, Abou-Setta AM. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2011 May 11;(5):CD001750. doi: 10.1002/14651858.CD001750.pub3.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2020
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: September 17, 2018
• First Submitted That Met QC Criteria: September 19, 2018
• First Posted (Actual): September 21, 2018

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 21, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Progestins; Cetrorelix; Dydrogesterone
• Other Study ID Numbers: JIAI 2018-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results after deidentification (text, tables, figures, and appendices) and study protocol will be shared. Data will be available when beginning 3 months and ending 5 years following article publication. To achieve aims in the approved proposal, researchers who provide a methodologically sound proposal will be shared with.Data will be made available by the following way. Proposals should be directed to lihe198900@163.com. And data are available for 5 years at a third party website (link to be included after the article publication).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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