Live Birth Rate Between PPOS and GnRH Antagonist Protocol in Patients With Anticipated High Ovarian Response

A Randomized Control Trial to Compare the Live Birth Rate Between the Progestin-primed Ovarian Stimulation Protocol and the GnRH Antagonist Protocol in Patients With Anticipated High Ovarian Response Undergoing IVF

Progestin can inhibit the pituitary LH surge during ovarian stimulation and various studies show progestin-primed ovarian stimulation (PPOS) is effective in blocking the LH surge in IVF. More and more centers in China are using PPOS because this regimen appears simpler and cheaper.A randomized trial to compare the effectiveness of PPOS and GnRH antagonist protocol in IVF in terms of the live birth rate is urgently needed.

Trial objectives: To compare the live birth rate between the PPOS protocol and the antagonist protocol used for ovarian stimulation during IVF

Eligible women will be randomised into one of the two groups:

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

PPOS group: Women will receive oral medroxyprogesterone 10 mg daily or duphaston 10mg bd daily from Day 3 till the day of ovulation trigger.

There will be no fresh transfer. Only one blastocyst will be allowed to replaced in the first FET and a maximum of two blastocysts will be replaced in the subsequent FET cycles.

The primary outcome is the live birth rate of the first frozen-thawed transfer cycle.

Study Overview

• Status: Completed
• Conditions: GnRH Antagonist; IVF; PPOS
• Intervention / Treatment: Drug: GnRH Antagonist; Drug: Progesterone

• Study Type: Interventional
• Enrollment (Actual): 784
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • ShangHai JIAI Genetics&IVF Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 43 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age of women <43 years at the time of ovarian stimulation for IVF
• The first IVF cycle
• Antral follicle count (AFC) >15 on day 2-5 of the period

Exclusion Criteria:

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

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
Active Comparator: Antagonist group; Women will receive antagonist (Cetrorelix or Ganirelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.	Drug: GnRH Antagonist; GnRH antagonist (Cetrorelix or Ganirelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger; Other Names: Cetrorelix; Ganirelix
Experimental: PPOS group; Women will receive oral medroxyprogesterone 10 mg daily or duphaston 10mg bd daily from Day 3 till the day of ovulation trigger.	Drug: Progesterone; oral medroxyprogesterone 10 mg daily or duphaston 10mg bd daily from Day 3 till the day of ovulation trigger; Other Names: duphaston; medroxyprogesterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
live birth rate	live birth rate of the first frozen embryo transfer cycle	deliveries ≥22 weeks gestation with heartbeat and breath

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
positive serum hCG	serum β-hCG ≥10 mIU/mL of the first FET	2 weeks after FET
clinical pregnancy	presence of intrauterine gestational sac by trans-vaginal ultrasound at 6 gestational weeks of the first FET	6 weeks' gestation
biochemical pregnancy	positive serum hCG not followed by clinical pregnancy of the first FET	6 weeks' gestation
implantation rate	the number of gestational sacs per blastocyst transferred of the first FET	6 weeks' gestation
ongoing pregnancy	a viable pregnancy beyond 12 weeks' gestation of the first FET	12 weeks' gestation
cumulative live birth	cumulative live birth within 6 months of randomization	2 years' after FET
number of oocytes retrieved	number of oocytes retrieved	1 day after oocyte retrieval
number and grading of blastocysts	number and grading of blastocysts suitable for biopsy and freezing	1 week after oocyte retrieval
multiple pregnancy	more than one intrauterine sacs on scanning	multiple pregnancy beyond gestation 12 weeks
ectopic pregnancy	pregnancy outside the uterine cavity	ectopic pregnancy during 12 weeks gestation
birthweight of newborns	the birth weight of newborns	1 year after FET
serum baseline FSH	baseline FSH of period day 2-3	day 2-3 of period
estradiol level on the trigger day		2 days before oocyte retrieval
progesterone level on the trigger day		2 days before oocyte retrieval
estradiol and progesterone levels in the follicular fluid	estradiol and progesterone levels in the follicular fluid	1 year after FET
miscarriage	clinically recognised pregnancy loss before 22 weeks of pregnancy.	22 weeks of pregnancy

Collaborators and Investigators

• Sponsor: ShangHai Ji Ai Genetics & IVF Institute
• Investigators: Study Director: 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.
• Begueria R, Garcia D, Vassena R, Rodriguez A. Medroxyprogesterone acetate versus ganirelix in oocyte donation: a randomized controlled trial. Hum Reprod. 2019 May 1;34(5):872-880. doi: 10.1093/humrep/dez034.
• 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.
• Alexandru P, Cekic SG, Yildiz S, Turkgeldi E, Ata B. Progestins versus GnRH analogues for pituitary suppression during ovarian stimulation for assisted reproductive technology: a systematic review and meta-analysis. Reprod Biomed Online. 2020 Jun;40(6):894-903. doi: 10.1016/j.rbmo.2020.01.027. Epub 2020 Feb 5.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2020
• Primary Completion (Actual): October 10, 2022
• Study Completion (Actual): October 10, 2022

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: June 2, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Fertility Agents, Female; Fertility Agents; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Progestins; Contraceptive Agents, Male; Cetrorelix; Progesterone; Dydrogesterone; Ganirelix; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: JIAI 2020-06

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.
• IPD Sharing Time Frame: Data will be available when beginning 3 months and ending 5 years following article publication.
• IPD Sharing Access Criteria: To achieve aims in the approved proposal, researchers who provide a methodologically sound proposal will be shared with. Proposals should be sent to lihe198900@163.com.
• 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