Effect of Estradiol Pretreatment on Follicular Synchronization and IVF Outcomes in Women With Polycystic Ovary Syndrome Undergoing ICSI Using GnRH Antagonist Protocol

Effect of Estradiol Pretreatment on Follicular Synchronization and IVF Outcomes in Women With Polycystic Ovary Syndrome Undergoing ICSI Using GnRH Antagonist Protocol: A Randomized Clinical Trial

This randomized clinical trial included 60 infertile women diagnosed with PCOS undergoing ICSI cycles using a GnRH antagonist protocol. Participants were randomly allocated into two equal groups: the pretreatment (Cyclo) group (n = 30), which received oral estradiol valerate (Cycloprogynova) 4 mg/day during the luteal phase before stimulation, and the control group (n = 30), which did not receive pretreatment.

Primary outcomes included follicular synchronization, total gonadotropin dose, duration of stimulation, and ovarian response. Secondary outcomes included mature oocyte yield, fertilization rate, embryo quality, and pregnancy outcomes.

Study Overview

• Status: Completed
• Conditions: IVF Outcomes; PCOS GnRH Antagonist and GnRH Agonist IVF/ICSI Cycles
• Intervention / Treatment: Drug: GnRH Antagonist Protocol; Drug: Estradiol Valerate 4mg

Detailed Description

Controlled ovarian stimulation was initiated on day 2 of the menstrual cycle using individualized gonadotropin doses according to age, BMI, AMH, and AFC. GnRH antagonist was initiated once at least one follicle reached 13 mm diameter.

Ovulation trigger was administered when at least five follicles reached ≥17 mm. Add reference Oocyte retrieval was performed 36 hours after trigger under transvaginal ultrasound guidance.

Women in the pretreatment group received oral estradiol valerate (Cycloprogynova) 4 mg/day during the luteal phase from day 21 of prior cycle To day 2 of COH ovarian stimulation cycle while women in the control group underwent standard GnRH antagonist stimulation without estradiol pretreatment.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo Governorate
    • Cairo, Cairo Governorate, Egypt, 12111
      • Cairo University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• PCOS was defined by the presence of at least two of the following:

  1. oligo or anovulation,
  2. clinical or biochemical hyperandrogenism, and
  3. polycystic ovarian morphology on ultrasound (≥12 antral follicles 2-9 mm in diameter and/or ovarian volume >10 mL).

All participants had undergone failed ovulation induction or were candidates for IVF/ICSI due to male factor infertility.

Exclusion Criteria:

• previous ovarian surgery
• endometriosis
• known chromosomal abnormalities
• untreated thyroid disease
• body mass index (BMI) > 35 kg/m²
• basal FSH >12 IU/L
• use of hormonal medications within 3 months prior to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Estradiol group; received oral estradiol valerate (Cycloprogynova) 4 mg/day during the luteal phase from day 21 To day2 preceding ovarian stimulation cycle	Drug: GnRH Antagonist Protocol; Controlled ovarian stimulation was initiated on day 2 of the menstrual cycle using individualized gonadotropin doses according to age, BMI, AMH, and AFC. GnRH antagonist was initiated once at least one follicle reached 13 mm diameter.; Drug: Estradiol Valerate 4mg; oral estradiol valerate (Cycloprogynova) 4 mg/day during the luteal phase from day 21 To day 2 preceding ovarian stimulation cycle
Placebo Comparator: Control group; women in the control group underwent standard GnRH antagonist stimulation without estradiol pretreatment	Drug: GnRH Antagonist Protocol; Controlled ovarian stimulation was initiated on day 2 of the menstrual cycle using individualized gonadotropin doses according to age, BMI, AMH, and AFC. GnRH antagonist was initiated once at least one follicle reached 13 mm diameter.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Follicular synchronization	Mean follicle diameter and within patient standard deviation	at day 8 of stimulation

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Principal Investigator: Ahmed Maged, Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2024
• Primary Completion (Actual): February 17, 2026
• Study Completion (Actual): June 21, 2026

Study Registration Dates

• First Submitted: July 16, 2026
• First Submitted That Met QC Criteria: July 21, 2026
• First Posted (Actual): July 27, 2026

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Estradiol
• Other Study ID Numbers: 369

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