Follicular Long GnRH Agonist Versus Antagonist Protocol in PCOS Women Undergoing in Vitro Fertilization

Follicular Long GnRH Agonist Versus Antagonist Protocol in PCOS Women Undergoing in Vitro Fertilization: a Prospective Randomized Controlled Trial

Pituitary down regulation is widely used during in vitro fertilization (IVF) procedures. It can suppress the spontaneous luteinizing hormone (LH) surge, and can also make follicles growth evenly.

At present, standard gonadotropin releasing hormone analogue (GnRH-a) long protocol is used in arou Long term GnRH-a, which is usually used in patients with endometriosis,has been shown to increase IVF outcome by altering endometrial receptivity. Moreover, it is also very convenient because patients do not have to inject GnRH-a daily. In order to make patients feel more comfortable during IVF treatment, the investigators have used a new ovarian stimulation protocol since the beginning of 2015. The investigators give patients long term GnRH-a (3.75mg) once at menstrual cycle D2, and begin the use of Gn to stimulate follicle growth around 30 days later based on the hormone levels and follicle size. In the pilot observational study of several patients, no LH surge occurred during ovarian stimulation.

The aim of this randomized controlled study is to compare the efficiency of this new protocol and standard GnRH-a long protocol in the investigator's center.

Study Overview

• Status: Completed
• Conditions: IVF; Ovulation Induction; Clinical Pregnancy Rate
• Intervention / Treatment: Drug: GnRH-a; Drug: GnRH-anta

Detailed Description

The primary outcome is clinical prengancy rate. Secondary outcome is cumulative live birth rate. Other parameters include number of oocytes retrieved, 2 pronucleus (2PN) fertilization rate, high quality embryo formation rate, implantation rate, spontaneous abortion rate, and ectopic pregnancy rate.

• Study Type: Interventional
• Enrollment (Actual): 1266
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Reproductive Medical Center, 1st Affiliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 38 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• First IVF cycle;
• With normal ovarian reserve(FSH < 10 mIU/mL; antral follicle count>5);
• With normal uterine.
• PCOS women according to Rotterdam criteria

Exclusion Criteria:

• Pre-implantation genetic diagnosis cycles;
• Oocyte donation or sperm donation cycles.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: New protocol group; Use long term GnRH-a 3.75mg at day 2 of menstrual cycle. Around 30 days later, controlled ovarian hyperstimulation using gonadotropins is initiated.	Drug: GnRH-a; In experimental group, patients use long term GnRH-a; Patients' serum or follicle fluid will be collected if needed.
Active Comparator: GnRH-antagonist; In the GnRH antagonist protocol, Gn was injected from day 2-3 of the menstrual cycle and GnRH antagonist (Cetrotide; 0.25 mg) was added daily from day 6 of stimulation. When 2 dominant follicle ≥ 18 mm or three follicles ≥ 17 mm, recombinant human chorionic gonadotropin (hCG) was injected.	Drug: GnRH-anta; In control group, patients use GnRH-antagonist. Patients' serum or follicle fluid will be collected if needed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical pregnancy rate	5 weeks after embryo transfer, gestational sac with fetal heart present inside uterus	5 weeks after embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of oocytes retrieved		1 day at oocyte retrieved day
2 pronucleus (2PN) fertilization rate	Number of 2PN/Matured oocytes	48 hours after oocyte retrieved day
cumulative live birth rate		2 years after oocyte retrivial

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University
• Investigators: Principal Investigator: Yingpu Sun, M.D, Zhengzhou University

Publications and helpful links

General Publications

• Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006 Jan 25;2006(1):CD004635. doi: 10.1002/14651858.CD004635.pub2.
• Niu Z, Chen Q, Sun Y, Feng Y. Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis. Gynecol Endocrinol. 2013 Dec;29(12):1026-30. doi: 10.3109/09513590.2013.824960. Epub 2013 Sep 5.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: July 8, 2015
• First Submitted That Met QC Criteria: July 13, 2015
• First Posted (Estimated): July 14, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 2, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: RMCZZU-New protocol

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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.: No