Initiation of Ovarian Stimulation With Recombinant-human FSH (Bemfola®) in the Late Follicular Phase

Initiation of Ovarian Stimulation With Recombinant-human FSH (Bemfola®) in the Late Follicular Phase, a Randomised Controlled Pilot Study.

A randomised controlled open-label clinical trial to compare the outcome parameters after ovarian stimulation using recombinant-human FSH (follicle stimulating hormone), starting on day 2 of the cycle versus start in the late follicular phase of the cycle.

Study Overview

• Status: Completed
• Conditions: Infertility, Female
• Intervention / Treatment: Combination product: Early follicular phase stimulation with recombinant-human FSH; Combination product: Late follicular phase stimulation with recombinant-human FSH

Detailed Description

Objective: To determine whether late follicular stimulation using recombinant-human FSH has comparable outcomes to treatment using recombinant-human FSH in early follicular phase in a flexible GnRH (Gonadotropin-releasing hormone) antagonist protocol, in oocyte donor patients.

Design: Open label, phase 3 randomized trial using a two-arm design with 1:1 allocation ratio

Patients: Oocyte donors (aged 18-36 years)

Intervention(s): Reference group: Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from day 2 of follicular phase onwards. Initiation of GnRH antagonist (ganirelix, 0.25mg/day) on stimulation day 6 till day of trigger.

Investigational group: Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from the late follicular phase of the menstrual cycle (evaluation trough ultrasound and hormonal assessment) onwards. Start of GnRH antagonist (ganirelix 0.25mg/day) when serum LH (Luteinizing Hormone) > 10 IU/L, till day of trigger.

Oocyte maturation trigger with GnRH agonist (0.2mg Gonapeptyl) in both groups.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1090
    • Universitair Ziekenhuis Brussel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 36 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• oocyte donor patients
• Age from 18 to 36 years
• BMI 19 to 35
• Regular menstrual cycle length i.e. 24-35 days

Exclusion Criteria:

• Patients with AMH <1.1 ng/ml and/or AFC<7
• Patients with FNPO (Follicle Number Per Ovary) ≥ 19 and/ord AMH >5ng/ml
• Endometriosis grade 3-4
• Oligo-amenorrhea
• Any untreated endocrine abnormality

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: Early follicular phase stimulation with recombinant-human FSH; Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from day 2 of follicular phase onwards. Initiation of GnRH antagonist (ganirelix, 0.25mg/day) on stimulation day 6 till day of trigger.	Combination product: Early follicular phase stimulation with recombinant-human FSH; Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from day 2 of follicular phase onwards. Initiation of GnRH antagonist (ganirelix, 0.25mg/day) on stimulation day 6 till day of trigger.
Experimental: Late follicular phase stimulation with recombinant-human FSH; Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from the late follicular phase of the menstrual cycle onwards. Start of GnRH antagonist (ganirelix 0.25mg/day) when serum LH > 10 IU/L, till day of trigger.	Combination product: Late follicular phase stimulation with recombinant-human FSH; Start of ovarian stimulation with recombinant-human FSH (Bemfola 225 IU daily) from the late follicular phase of the menstrual cycle onwards. Start of GnRH antagonist (ganirelix 0.25mg/day) when serum LH > 10 IU/L, till day of trigger.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
total amount of COC (cumulus-oocyte-complex)	at oocyte aspiration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endocrine profile	LH (Luteinising hormone) level	on menstrual cycle day 2 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group
Endocrine profile	FSH level	on menstrual cycle day 2 and 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group
Endocrine profile	Progesterone level	on menstrual cycle day 2 and 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group
Endocrine profile	Estradiol level	on menstrual cycle day 2 and 9, (extra days as per site protocol) and day of oocyte maturation trigger in reference group. On menstrual cycle day 2 and 12, (extra days as per site protocol) and day of oocyte maturation trigger in investigational group
Consumption of gonadotrophins	totaal amount of IU (international units) used	during the ovarian stimulation
Number of days needed for ovarian stimulation		during the ovarian stimulation
Days of GnRH antagonist use		during the ovarian stimulation
Total number of mature oocytes		at day of oocyte aspiration
Total medication cost		during the ovarian stimulation

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): May 27, 2022
• Study Completion (Actual): November 25, 2022

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (Actual): December 6, 2018

Study Record Updates

• Last Update Posted (Actual): May 16, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Ovarian stimulation; Oocyte donor
• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone
• Other Study ID Numbers: D2.D12.Bemfola

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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