Endometriosis and adenomyosis are chronic gynaecological conditions that can cause pain and reduce fertility. Women with these conditions often have lower pregnancy and live birth rates after fertility treatments like IVF or ICSI, especially if they suffer from a more severe form of the disease. Endometriosis and adenomyosis are very common, yet affected patients often receive standard fertility treatments that do not account for the unique challenges posed by these conditions. A key factor in both endometriosis and adenomyosis is an increased level of oestrogen in the uterus, leading to progesterone resistance which can negatively affect women’s ability to conceive.
Letrozole, a medication that temporarily reduces oestrogen levels, is already used safely to induce ovulation and also during ovarian stimulation in patients with hormone-sensitive cancers. It may also help improve IVF outcomes in women with endometriosis or adenomyosis by lowering oestrogen exposure during stimulation and increasing progesterone values during the last phase of the menstrual cycle (luteal phase).
The ENDO-REAL trial is a large, multicentre randomized controlled study conducted in several Belgian fertility centres. It will compare the standard ovarian stimulation protocol with and without letrozole as a co-treatment.
A total of 854 women under 40 years old with endometriosis (with or without adenomyosis) and an indication for IVF/ICSI will be included. Participants will be randomly assigned to receive either the standard stimulation or the standard stimulation with letrozole (5mg daily during stimulation).
The main objective is to determine whether adding letrozole increases the cumulative (total) live birth rate per IVF/ICSI cycle, including all embryos from that cycle transferred within one year. Secondary outcomes include pregnancy and miscarriage rates, obstetrical outcomes, hormone levels, medication use, side effects, and patient well-being.
If successful, this study could provide an inexpensive, widely available, and safe strategy to improve IVF success for thousands of women affected by endometriosis.
| Title | Reproductive outcomes with letrozole co-treatment during ovarian stimulation in women with endometriosis undergoing IVF/ICSI: a randomised, multicentre, parallel group pragmatic trial |
| Participants (P) | Women below the age of 40 years with a surgical or imaging diagnosis of endometriosis (rASRM stages 1- 4) and an indication for IVF/ICSI based on existing guidelines. Patients with and without concomitant adenomyosis will be included. |
| Intervention (I) | Use of letrozole as co-treatment during an ovarian stimulation cycle (i.e an average of 10-12 days) in an GnRH antagonist protocol for IVF/ICSI. Letrozole will be administered 5 mg daily from the start of the ovarian stimulation with gonadotropines until the day of trigger of final oocyte maturation. |
| Control (C) | Standard GnRH antagonist ovarian stimulation protocol with recFSH, without letrozole and without placebo or any other additional medication – or ‘add-ons’. |
| Outcome (O) | Cumulative live birth rate per IVF/ICSI stimulation cycle, including fresh embryo transfer and frozen embryo transfers (of embryos from the same oocyte aspiration) performed within 52 weeks after stimulation start (SD1). |
| Trial Design | Open labelled parallel group multicentre randomized controlled trial in several Belgian fertility centres |
| Sample Size | 854 randomized patients |
| Trial duration | 60 months from FPI to CSR |
| Budget | 2,530,000 € |
| Sponsor | UZ Brussel |
| Chief Investigator | Dr Michelle SOARES |
| External partners | |
| Number of participating sites | 11 sites: UZ Brussel |
EU Clinical Trials: https://clinicaltrials.eu/trial/letrozole-during-ivf-icsi-for-women-with-endometriosis/
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