Ovarian Stimulation With FSH Alone Versus FSH Plus GnRH Antagonist in an Oocyte Donor/Recipient Programme

Ovarian Stimulation With FSH Alone Versus FSH Plus a GnRH Antagonist in an Oocyte Donor/Recipient Programme: a Protocol for a Non-randomised Multicenter Study

The aim of this study is to compare the efficacy of a protocol using FSH alone with that of a protocol using FSH plus a GnRH antagonist for controlled ovarian hyperstimulation in cycles of elective freezing in the context of a donor/recipient programme.

Study Overview

• Status: Not yet recruiting
• Conditions: Premature Luteinisation; Progesterone Elevation
• Intervention / Treatment: Other: GnRH antagonist

Detailed Description

The hypothesis to be tested is that an ovarian stimulation protocol that includes FSH alone without any LH surge prevention regimens is not inferior to a protocol including FSH plus a GnRH antagonist in terms of clinical outcome in a donor/recipient model.

The formal sample size is calculated as follows:

If there is a true difference in favour of the experimental treatment of 5% (20% vs 15%), then 160 patients (80 per group in case of 1:1 enrolment) are required to be 80% sure that the upper limit of a one-sided 95% confidence interval (or equivalently a 90% two-sided confidence interval) will exclude a difference in favour of the standard/control group of more than 10%.

In the context of the present pilot study (as a first stage), the investigators intend to study 50 patients (25 per group in case of 1:1 enrolment). At a second stage the above mentioned sample size will be used.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ioannis Messinis, Prof; Phone Number: 0030 6944370627; Email: messinis.io@gmail.com
• Study Contact Backup: Name: Charalampos Siristatidis, Prof; Phone Number: 0030 2107286306; Email: harrysiri@yahoo.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 32 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• healthy women 21-32 years old with a BMI of 21 to 29 kg/m2 who wish to donate their oocytes
• normal ovarian reserve tests
• normal menstrual cycles of 26-32 days

• the women would not have received any hormonal treatment during the last three months before entering the study.

  • absence of coagulation and/or autoimmune disorders.

Exclusion Criteria:

1. Use of other protocols towards oocyte retrieval, such as natural, or modified natural cycles
2. Poor ovarian response according to the Bologna criteria [22],
3. History of endocrine or metabolic disorders, ovarian cystectomy or oophorectomy,
4. Women with the diagnosis of polycystic ovary syndrome

5. Clinical and/or laboratory markers of hereditary or acquired thrombophilia that complied to the standard protocols of each Unit.

   • Non-hormonal medication for a serious medical condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FSH only (no GnRH antagonist); Women receive only FSH starting on day 2 of the cycle. The starting dose of FSH is 225-300 IU s.c. for the first 4 days adjusted thereafter according to the ovarian response.	Other: GnRH antagonist; The GnRH antagonist in the control group (standard therapy) is administered from day 6 of FSH treatment at the dose of 0.25 mg per day until the triggering day and is injected each time immediately after the injection of FSH.
Active Comparator: FSH + GnRH antagonist; Women receive 225-300 IU s.c. FSH, and a GnRH antagonist from day 6 of FSH treatment at the dose of 0.25 mg per day until the triggering day. The GnRH antagonist in group 2 is injected each time immediately after the injection of FSH.	Other: GnRH antagonist; The GnRH antagonist in the control group (standard therapy) is administered from day 6 of FSH treatment at the dose of 0.25 mg per day until the triggering day and is injected each time immediately after the injection of FSH.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of LH secretory peaks	A secretory peak of LH is defined as the increase at levels ≥10 IU/l.	3 weeks after start of ovarian stimulation.
Rate of concentration of progesterone >1 ng/ml	Concentration of progesterone elevation >1 ng/ml	At any time within 3 weeks after start of ovarian stimulation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of ongoing clinical pregnancy	Clinical pregnancy (fetal heart beat) at ultrasound	12 weeks after last menstrual period
Rate of miscarriage	Miscarriage / Loss of the embryo	Within 20 weeks after last menstrual period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total dose of gonadotrophins (rFSH)	Dose of rFSH administered	2 weeks after last menstrual period
Number of retrieved cumulus oocytes complexes (COCs)	Number of retrieved cumulus oocytes complexes (COCs) at oocyte retrieval	3 weeks after last menstrual period / and start of ovarian stimulation

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Collaborators: Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece; Embryoland, Athens, Greece; Embryolab IVF Unit, Thessaloniki, Greece; Assisting Nature IVF Unit, Thessaloniki, Greece; HYGEIA IVF - Embryogenesis A.R.T. Unit, Athens, Greece; Institute of Fertility, Athens, Greece; Mitosis IVF Centre, Pireas, Greece

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.
• Wang HL, Lai HH, Chuang TH, Shih YW, Huang SC, Lee MJ, Chen SU. A Patient Friendly Corifollitropin Alfa Protocol without Routine Pituitary Suppression in Normal Responders. PLoS One. 2016 Apr 21;11(4):e0154123. doi: 10.1371/journal.pone.0154123. eCollection 2016.
• Yangyang Zhang et al. Effect of a premature luteinizing hormone surge on cumulative live birth rate during a flexible GnRH antagonist protocol: a retrospective study. https://doi.org/10.21203/rs.3.rs-1361146/v1
• Messinis IE, Messini CI, Anifandis G, Daponte A. Exogenous progesterone for LH surge prevention is redundant in ovarian stimulation protocols. Reprod Biomed Online. 2021 Apr;42(4):694-697. doi: 10.1016/j.rbmo.2021.01.017. Epub 2021 Jan 30.
• Messinis IE, Templeton A, Baird DT. Endogenous luteinizing hormone surge in women during induction of multiple follicular development with pulsatile follicle stimulating hormone. Clin Endocrinol (Oxf). 1986 Feb;24(2):193-201. doi: 10.1111/j.1365-2265.1986.tb00762.x.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: February 9, 2023
• First Submitted That Met QC Criteria: February 26, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: oocyte donation; GnRH antagonist; Controlled ovarian stimulation; LH surge
• Other Study ID Numbers: Non-anta-D

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