Does The Addition Of Letrozole To Ultra-Long GnRH Agonists Help Adenomyosis Patients in ART? The AURA Trial

NCT06985186 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: AURA Trial
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

Brief Summary

The AURA Trial seeks to improve fertility treatment for women affected by a condition known as adenomyosis. Adenomyosis often leads to heavy menstrual bleeding, pelvic pain, dyspareunia and can make it more difficult to achieve and maintain a healthy pregnancy. In this randomized controlled trial participating women ≥ 18 years of age with a confirmed imaging diagnosis of adenomyosis according to Morphological Uterus Sonographic Assessment (MUSA) consensus will first undergo a thorough assessment. This initial workup includes reviewing medical history, assessing the characteristics of the uterus (volume, myometrial architecture, shape of the uterine cavity, stiffness, etc.) via 2D/3D transvaginal ultrasound, and obtaining blood tests to establish baseline hormone levels. Once enrolled, each participant will be assigned at random-without prior knowledge by either the woman or her care team-to one of two 90-day pre-treatment regimens. The first group will receive monthly injections of a GnRH agonist, a medication that temporarily suppresses ovarian function and lowers estrogen levels. The second group will follow the same injection schedule but will also take daily letrozole tablets, an aromatase inhibitor that further reduces estrogen production. The hope is that this combined approach will calm the inflammatory environment caused by adenomyosis, promote a more receptive uterus, and ultimately increase the likelihood of an embryo developing beyond the critical 12-week mark. At the end of the 90-day protocol, and after repeating all evaluations carried out during the enrolment phase, all women will proceed with the planned assisted reproductive technology cycle with the usual careful monitoring until the day of emrbyo transfer. To ensure correct interpretation of the results and to minimise the potential effect of any incompetent oocytes, only euploid embryos evaluated by pre-implantation genetic test or embryos derived from donated oocytes will be transferred. Pregnancy will be assessed first with a blood test, followed by an ultrasound scan at approximately six or seven weeks to confirm a clinical pregnancy. An ongoing pregnancy, defined by the detection of the fetal heartbeat beyond the 12th week, is the main measure of success. By participating in AURA, women and their families not only gain access to cutting-edge clinical care but also contribute valuable knowledge that could shape future standard treatments for adenomyosis-related infertility. For further information or to explore participation, please reach out to the Instituto Bernebu Assisted Reproduction Center, where our team is ready to guide you through every step of this important study.

Conditions

Adenomyosis of Uterus; Infertility Assisted Reproductive Technology

Keywords

adenomyosis; infertility; Ultra-Long GnRH Agonists; Aromatase inhibitor; IVF outcomes; assisted reproductive technology; egg-donation

Outcome Measures

Primary Outcomes (1)

• Ongoing pregnancy rate

  An ongoing pregnancy was defined as each pregnancy showing a positive heartbeat at ultrasound after 12 weeks of gestation

  12 weeks after embryo transfer

Secondary Outcomes (2)

• Implantation rate

  6 to 7 weeks after transfer

• Miscarriage rate

  22 weeks after embryo transfer

Study Arms (2)

Ultra-Long GnRH Agonists

ACTIVE COMPARATOR

All patients will receive a depot injection of the long-acting GnRH agonist, intramuscularly, once (11.25mg) or every 28 days (3.75mg) for at least 3 months prior to embryo transfer. The first injection of GnRH agonist will be administered during the menstrual phase of the cycle.

Drug: Ultra-Long GnRH Agonists

Ultra-Long GnRH Agonists + Letrozole

EXPERIMENTAL

All patients will receive a depot injection of the long-acting GnRH agonist, intramuscularly, once (11.25mg) or every 28 days (3.75mg) for at least 3 months prior to embryo transfer. Upon initiation of the GnRH agonist, patients will also receive 2.5mg of Letrozole every 12h for 60 days. The start of therapy will be during the menstrual phase of the cycle.

Drug: Ultra-Long GnRH Agonists + Letrozole

Interventions

Ultra-Long GnRH Agonists + Letrozole DRUG

All patients will receive a depot injection of the long-acting GnRH agonist, intramuscularly, once (11.25mg) or every 28 days (3.75mg) for at least 3 months prior to embryo transfer. Upon initiation of the GnRH agonist, patients will also receive 2.5mg of Letrozole every 12h for 60 days. The start of therapy will be during the menstrual phase of the cycle.

Ultra-Long GnRH Agonists + Letrozole

Ultra-Long GnRH Agonists DRUG

All patients will receive a depot injection of the long-acting GnRH agonist, intramuscularly, once (11.25mg) or every 28 days (3.75mg) for at least 3 months prior to embryo transfer. The first injection of GnRH agonist will be administered during the menstrual phase of the cycle.

Ultra-Long GnRH Agonists

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \- Infertile patients affected by adenomyosis diagnosed by 2D-3D transvaginal ultrasound according to revised Morphological Uterus Sonographic Assessment consensus.

You may not qualify if:

• concomitant uterine fibroids,
• Müllerian malformations,
• endometrial pathology,
• thin endometrium,
• hydrosalpinx,
• mucometra,
• previous surgery except for previous cesarean section,
• coagulation disorders,
• untreated endocrinopathies,
• severe seminal pathologies,
• double ET,
• ET different from the first one after adenomyosis treatment.

Sponsors & Collaborators

• University of Palermo: lead

Study Sites (1)

Instituto Bernabeu

Alicante, Alicante, 03016, Spain

Location

MeSH Terms

Conditions

Adenomyosis; Infertility

Interventions

Letrozole

Condition Hierarchy (Ancestors)

Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Andrea Etrusco, M.D.

CONTACT

+39 3381614122; auratrial.ib@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: May 22, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

ES (1)