Intranasal Nafarelin For Triggering Oocyte Maturation

Official title

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

Overview

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.

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.

Interventions

• 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 a
• 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 av

Primary outcome measures

• Number of MII (metaphase 2) oocyte retrieved [Time frame: Until study completion - average of 10-20 days]

Secondary outcome measures (10)

• Total number of oocytes retrieved [Time frame: Until study completion - average of 10-20 days]
• Incidence of ovarian hyperstimulation syndrome [Time frame: Until study completion - average of 10-20 days]
• Serum FSH levels 10-14 hours after trigger [Time frame: 1 day after study medication]
• Serum LH levels at time of oocyte collection [Time frame: 2 days after study medication]
• Serum FSH levels at time of oocyte collection [Time frame: 2 days after study medication]
• Serum progesterone levels at time of oocyte collection [Time frame: 2 days after study medication]
• Participant-reported pain [Time frame: Until study completion - average of 10-20 days]
• Medication ease of use [Time frame: Until study completion - average of 10-20 days]
• Medication preference [Time frame: Until study completion - average of 10-20 days]
• Adverse events [Time frame: Until study completion - average of 10-20 days]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 5 centers

• Dexeus Mujer Sabadell — Sabadell
• Dexeus Mujer Sant Cugat — Sant Cugat del Vallès
• Dexeus Mujer Reus — Reus
• Departamento de Ginecología Obstetricia y Reproducción. Hospital Universitari Dexeus — Barcelona
• Dexeus Mujer Tarragona — Tarragona

Publications

• 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. PMID 25358904
• 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. PMID 32741721
• 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. PMID 27114332
• 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. PMID 19573287

Identifiers

NCT: NCT06763926 · FSD-NAF-2024-11 · 2024-516621-31-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗