Comparison of the Euploid Rate of Blastocyst Between PPOS and GnRH Antagonist Protocol in Women With PCOS Undergoing PGT-A

A Randomized Control Trial to Compare the Euploid Rate of Blastocyst Between the PPOS (Progestin-primed Ovarian Stimulation) Protocol and the Gonadotropin-releasing Hormone (GnRH) Antagonist Protocol in Women With PCOS (Polycystic Ovary Syndrome) Undergoing PGT-A (Preimplantation Genetic Testing for Aneuploidy)

This randomized trial aims to compare the euploid rate of blastocysts between PPOS (progestin-primed ovarian stimulation) and GnRH (gonadotrophin releasing hormone) antagonist protocols in patients with PCOS (polycystic ovary syndrome) undergoing PGT-A (preimplantation genetic testing for aneuploidy). Infertile women with PCOS will be recruited for study after explanation and counseling if they fulfill the inclusion criteria and do not have the exclusion criteria. Eligible women will be randomised into one of the two groups:

Antagonist group: Women will receive antagonist once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.

PPOS group: Women will receive oral MPA (medroxyprogesterone acetate)10mg qd from Day 3 till the day of ovulation trigger.

The primary outcome is the euploidy rate of blastocysts.

Study Overview

• Status: Not yet recruiting
• Conditions: GnRH Antagonist; Polycystic Ovarian Syndrome; Preimplantation Genetic Testing; Progestin-primed Ovarian Stimulation
• Intervention / Treatment: Drug: GnRH antagonist; Drug: MPA

• Study Type: Interventional
• Enrollment (Estimated): 204
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: He Li, MD; Phone Number: +8613817223099; Email: lihe198900@163.com
• Study Contact Backup: Name: XIAOXI SUN, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 37 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women age between 20 and 37 years.
• Women diagnosed with PCOS according to the modified Rotterdam criteria: oligomenorrhea or amenorrhea, together with the presence of ≥12 antral follicles (≤9 mm) and/or ovarian volume >10 mL on transvaginal ultrasonographic scanning, and/or clinical/ biochemical hyperandrogenism. Other causes of hyperandrogenism and ovulation dysfunction-including tumours, congenital adrenal hyperplasia, hyperprolactinaemia and thyroid dysfunction-were excluded

Exclusion Criteria:

• Presence of a functional ovarian cyst with E2>100 pg/mL
• Endometriosis grade 3 or higher
• Repeated implantation failure (>=4 embryos replaced or >=2 blastocysts replaced without success)
• Women with a uterine cavity abnormality, such as a uterine congenital malformation (uterus uni-cornate, bicornate, or duplex); untreated uterine septum, adenomyosis, submucous myoma, or endo-metrial polyp(s)
• Women who are indicated and planned to undergo PGT-SR (Preimplantation genetic testing for structural rearrangement) or PGT-M (Preimplantation genetic testing for monogenic disorder), for example, parental abnormal karyo-type or diagnosed with monogenic disease;
• Recipient of oocyte donation
• Presence of hydrosalpinx 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 (Cetrotide 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.	Drug: GnRH antagonist; GnRH antagonist (Cetrorelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger; Other Names: Cetrorelix
Experimental: PPOS group; Women will receive oral MPA 10mg qd from Day 3 till the day of ovulation trigger.	Drug: MPA; oral MPA 10mg qd from Day 3 of ovarian stimulation till the day of ovulation trigger.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
euploidy rate	euploidy rate of blastocysts	1 month after oocyte retrieval

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
live birth rate	deliveries ≥22 weeks gestation with heartbeat and breath of the first frozen embryo transfer	1 year after embryo transfer
cumulative live birth rate	cumulative live birth within 6 months of randomization	1 year after embryo transfer
ongoing pregnancy	a viable pregnancy beyond 12 weeks' gestation of the first frozen embryo transfer	12 weeks' gestation
number of oocytes retrieved	number of oocytes retrieved	1 day after oocyte retrieval
OHSS（ovarian hyperstimulation syndrome）	Moderate or severe ovarian hyperstimulation syndrome.Ovarian hyperstimulation syndrome (OHSS) is diagnosed and classified according to the Royal College of Obstetricians and Gynaecologists guideline. Green-top guideline No.5. Ovarian hyperstimulation syndrome. https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg5/ (accessed 26 Feb 2016).	1 month after ovarian stimulation
birthweight of newborns	birthweight of newborns	1 year after embryo transfer

Collaborators and Investigators

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

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.
• 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.
• 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.
• Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN; PCOS/Troglitazone Study Group. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006 Jan;91(1):48-53. doi: 10.1210/jc.2005-1329. Epub 2005 Oct 25.
• Lee E, Illingworth P, Wilton L, Chambers GM. The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review. Hum Reprod. 2015 Feb;30(2):473-83. doi: 10.1093/humrep/deu303. Epub 2014 Nov 28.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 28, 2022
• First Submitted That Met QC Criteria: April 9, 2022
• First Posted (Actual): April 13, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Polycystic Ovary Syndrome; Syndrome; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Cetrorelix
• Other Study ID Numbers: JIAI 2022-03

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