Intranasal Nafarelin For Triggering Oocyte Maturation (INFORM)

Intranasal Nafarelin Compared to Subcutaneous Triptorelin for Triggering Final Oocyte Maturation in Ovarian Stimulation: a Non-inferiority Randomised Controlled Clinical Trial

This is a non-inferiority randomised, controlled clinical trial comparing subcutaneous triptorelin to intranasal nafarelin for the final maturation of oocytes in women undergoing fertility preservation cycles with oocyte cryopreservation undergoing ovarian stimulation.

Study Overview

• Status: Not yet recruiting
• Conditions: Fertility Preservation
• Intervention / Treatment: Drug: Subcutaneous Triptorelin; Drug: Intranasal nafarelin

Detailed Description

Women meeting the inclusion criteria will be randomised to receive triggering for final oocyte maturation with 200 micrograms of subcutaneous triptorelin (control group) or 800 micrograms of intranasal nafarelin (experimental group). The primary outcome is the number of mature (metaphase 2 (MII)) oocytes collected.

The study has been designed with a non-inferiority limit of a difference of 2 mature oocytes, with 80% power and two-sided alpha of 0.05.

• Study Type: Interventional
• Enrollment (Estimated): 154
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ignacio Rodríguez, MSc; Phone Number: 22029 0034932274700; Email: nacrod@dexeus.com
• Study Contact Backup: Name: Nikolaos P Polyzos, MD, PhD; Phone Number: 0034932274700; Email: nikpol@dexeus.com

Study Locations

• Spain
  • Barcelona, Spain, 08037
    • Departamento de Ginecología Obstetricia y Reproducción. Hospital Universitari Dexeus
  • Tarragona, Spain, 43206
    • Dexeus Mujer Tarragona
    • Contact: Josep Gonzalo, MD
    • Sub-Investigator: Josep Gonzalo, MD
  • Barcelona
    • Sabadell, Barcelona, Spain, 08203
      • Dexeus Mujer Sabadell
      • Contact: Silvia Grau, MD
      • Sub-Investigator: Silvia Grau, MD
    • Sant Cugat del Vallès, Barcelona, Spain, 08190
      • Dexeus Mujer Sant Cugat
      • Contact: Silvia Grau, MD
      • Principal Investigator: Silvia Grau
  • Tarragona
    • Reus, Tarragona, Spain, 43202
      • Dexeus Mujer Reus
      • Sub-Investigator: Josep Gonzalo
      • Contact: Josep Gonzalo, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Women undergoing fertility preservation cycles with oocyte cryopreservation
• Undergoing a progesterone-primed ovarian stimulation cycle (PPOS) with any commercially available gonadotropin preparation(s)
• BMI 18 - 30 kg/m2

Exclusion Criteria:

• Allergy or hypersensitivity to either of the study drugs
• Hypopituitarism
• Known pituitary tumour
• Contraindication to intranasal medication administration
• Previous poor response to agonist trigger

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: Subcutaneous Triptorelin; 200 mcg subcutaneous triptorelin 34-36 hours prior to planned oocyte collection	Drug: Subcutaneous Triptorelin; Women undergoing fertility preservation will undergo progesterone-primed ovarian stimulation according to the standard operating protocol for the clinical unit.. For participants taking oral contraceptives before the treatment, the pill-free interval before starting ovarian stimulation will be 5 days. Participants will administer exogenous gonadotropins (recombinant or urinary), along with 200mg oral micronized progesterone per day for pituitary suppression. Participants using any commercially available gonadotropin preparation will be eligible for inclusion. Once 3 follicles ≥18mm are observed, participants will be randomised to one of the study arms. n the control group, 200 mcg subcutaneous triptorelin will be administered 34-36 hours prior to planned oocyte collection.
Active Comparator: Intranasal Nafarelin; 800 mcg intranasal nafarelin 36 hours prior to planned oocyte collection	Drug: Intranasal nafarelin; Women undergoing fertility preservation will undergo progesterone-primed ovarian stimulation according to the standard operating protocol for the clinical unit. For participants taking oral contraceptives before the treatment, the pill-free interval before starting ovarian stimulation will be 5 days. Participants will administer exogenous gonadotropins (recombinant or urinary), along with 200mg oral micronized progesterone per day for pituitary suppression. Participants using any commercially available gonadotropin preparation will be eligible for inclusion. Once 3 follicles ≥18mm are observed, participants will be randomised to one of the study arms.In the experimental group, 800 mcg intranasal nafarelin will be administered 34-36 hours prior to planned oocyte collection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of MII (metaphase 2) oocyte retrieved	Until study completion - average of 10-20 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of oocytes retrieved		Until study completion - average of 10-20 days
Incidence of ovarian hyperstimulation syndrome		Until study completion - average of 10-20 days
Serum FSH levels 10-14 hours after trigger		1 day after study medication
Serum LH levels at time of oocyte collection		2 days after study medication
Serum FSH levels at time of oocyte collection		2 days after study medication
Serum progesterone levels at time of oocyte collection		2 days after study medication
Participant-reported pain	. Participant-reported pain (measured using a visual analogue scale from 0 (no pain) to 10 (severe pain))	Until study completion - average of 10-20 days
Medication ease of use	Medication ease of use (measured using a visual analogue scale from 0 (very easy) to 10 (very difficult))	Until study completion - average of 10-20 days
Medication preference	Medication preference (measured using a 5-point Likert scale from (a) "I would strongly prefer the nasal spray" to (e) "I would strongly prefer the injection")	Until study completion - average of 10-20 days
Adverse events		Until study completion - average of 10-20 days

Collaborators and Investigators

• Sponsor: Fundacion Dexeus
• Investigators: Principal Investigator: Nikolaos P Polyzos, MD, PhD, Dexeus Fertility

Publications and helpful links

General Publications

• Bar-Hava I, Mizrachi Y, Karfunkel-Doron D, Omer Y, Sheena L, Carmon N, Ben-David G. Intranasal gonadotropin-releasing hormone agonist (GnRHa) for luteal-phase support following GnRHa triggering, a novel approach to avoid ovarian hyperstimulation syndrome in high responders. Fertil Steril. 2016 Aug;106(2):330-3. doi: 10.1016/j.fertnstert.2016.04.004. Epub 2016 Apr 22.
• Golan A, Weissman A. Symposium: Update on prediction and management of OHSS. A modern classification of OHSS. Reprod Biomed Online. 2009 Jul;19(1):28-32. doi: 10.1016/s1472-6483(10)60042-9.
• Youssef MA, Van der Veen F, Al-Inany HG, Mochtar MH, Griesinger G, Nagi Mohesen M, Aboulfoutouh I, van Wely M. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev. 2014 Oct 31;2014(10):CD008046. doi: 10.1002/14651858.CD008046.pub4.
• V. Donno, A. R. Neves, S. Garcia Martinez, N. P. Polyzos. O-074 Dual trigger is not superior to GnRH Agonist alone for final oocyte maturation in elective fertility preservation. A Randomized Controlled Trial. Hum Reprod. 2024;39(Supp 1).
• Davenport MJ, MacLachlan VB, Vollenhoven BJ, Talmor AJ, Healey M. How we trigger matters: intranasal GnRH-agonist trigger may reduce oocyte maturation compared to subcutaneous administration in ICSI cycles. Fertility and Sterility. 2019
• Bar Hava I, Yafee H, Omer Y, Humaidan P, Ganer Herman H. GnRHa for trigger and luteal phase support in natural cycle frozen embryo transfer - A proof of concept study. Reprod Biol. 2020 Sep;20(3):282-287. doi: 10.1016/j.repbio.2020.07.009. Epub 2020 Jul 30.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): January 15, 2028

Study Registration Dates

• First Submitted: December 17, 2024
• First Submitted That Met QC Criteria: January 2, 2025
• First Posted (Actual): January 8, 2025

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: IVF; GnRH agonist
• Additional Relevant MeSH Terms: Contraceptive Agents, Hormonal; Antineoplastic Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Luteolytic Agents; Contraceptive Agents, Female; Contraceptive Agents; Triptorelin Pamoate; Nafarelin
• Other Study ID Numbers: FSD-NAF-2024-11; 2024-516621-31-00 (Ctis)

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