ENDO-REAL: Endometriosis and Reproductive Enhancement with Letrozole

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Brussel

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Phenomena and Processes [G] - Reproductive and Urinary Physiological Phenomena [G08]

Decision date (initial)

2026-05-13

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The primary objective of this study is to determine whether letrozole co-administration during ovarian stimulation for IVF/ICSI can improve the occurrence of a live birth following embryo transfer(s) in patients diagnosed with endometriosis +/- adenomyosis. Primary outcome will focus on cumulative live birth per stimulation cycle, including fresh and frozen embryo transfers resulting from the same oocyte aspiration and transferred within 1 year (52 weeks) of randomization. Live birth following fresh embryo transfer and number of ETs needed for successful pregnancy will also be evaluated as an important outcome.

Secondary objectives 7

1. To compare other reproductive outcomes including implantation, clinical pregnancy, ectopic pregnancy and miscarriage rates between the intervention and control group.
2. To compare pregnancy related complications, neonatal outcomes and congenital abnormalities between the intervention and the control group for women achieving a pregnancy > 24 weeks.
3. To compare total recFSH dose administered and number of stimulation days between the intervention and control group
4. To compare endometrial thickness and estradiol levels on day of trigger, serum progesterone levels on day of trigger and of ET, number of stimulation days, cumulus oocyte complexes and mature M2 oocytes retrieved, fertilization rates and total number of good quality (EQ 1-2) blastocysts obtained.
5. To compare pain scores following OPU in both groups.
6. To compare patient QOL between both groups measured at 5 days post OPU and compared to baseline (screening).
7. To compare evaluate the occurrence of side effects related to letrozole and patient tolerability

Conditions and MedDRA coding

Women with endometriosis undergoing IVF/ICSI

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Sub/infertile women with a diagnosis of endometriosis (all types/ stages) either by TVUS/ MRI or surgically and an indication for treatment with IVF/ICSI (based on existing guidelines) are eligible for the study.
2. Planned fresh ET following oocyte retrieval
3. Patient with and without concomitant adenomyosis will be included
4. The patient must have undergone not more than three consecutive unsuccessful IVF/ICSI cycles since the last ongoing pregnancy (whether fresh and/or several frozen ET resulted from these attempts). Each patient may only participate once.
5. Age ≥ 18 years and < 40 years
6. Body mass Index (BMI) < 35kg/m
7. Participant should be capable of giving informed consent

Exclusion criteria 7

1. Anti-müllerian hormone (AMH) < 0.5 ng/mL (dosage in the 1 year preceding randomization)
2. Abnormal uterine cavity (known mullerian duct anomalies, intra-uterine adhesions or other untreated intra-uterine pathology)
3. Untreated tubal factor (hydrosalpinx)
4. Any untreated endocrine abnormality
5. Surgically obtained sperm
6. Ovarian stimulation for pre-implantation genetic testing (PGT-A/M)
7. Severe OHSS in previous treatment cycle or patients planned in forehand for a freeze-all strategy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is cumulative live birth per stimulation (or IVF/ICSI) cycle, including fresh ET and frozen ETs resulting from the same oocyte aspiration and transferred within 1 year of randomization.

Secondary endpoints 9

1. LBR per fresh ET cycle (excluding freeze-all), defined as live birth at ≥ 24 weeks of gestation.
2. Number of ETs needed for successful pregnancy
3. Miscarriage rate (defined as pregnancy loss prior to viability scan and including those confirmed on ultrasound scan up to ≤ 23 weeks 6 days gestation) for fresh and frozen ETs.
4. Implantation rate (positive serum βhCG 10-15 days after transfer) for fresh and frozen ETs.
5. Clinical pregnancy rate (at least one gestational sac 4-6 weeks after transfer) for fresh and frozen ETs.
6. Rate of ectopic pregnancy or pregnancy of unknown location for fresh and frozen ETs.
7. For women achieving a pregnancy > 24 weeks:  Pregnancy related complications: pre-eclampsia and pregnancy-induced hypertension, preterm birth, intrauterine growth restriction, caesarean delivery and obstetric hemorrhage.  Extreme preterm birth (24-28 weeks of gestation)  Still birth and termination of pregnancy  Gestational age at delivery, Birthweight  Neonatal admission and mortality  Major congenital abnormalities
8. Pain score: NRS 1-10 one to four hours after OPU
9. Patient QOL measured at the day of fresh embryo transfer (OPU +5) and compared to baseline (FertiQOL)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Brussel

Sponsor organisation

UZ Brussel

Address

Laarbeeklaan 101

City

Jette

Postcode

1090

Country

Belgium

Scientific contact point

Organisation

UZ Brussel

Contact name

Michelle Soares

Public contact point

Organisation

UZ Brussel

Contact name

Michelle Soares

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications