Linzagolix in Adenomyosis and Recurrent Implantation Failure
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Linzagolix 200 mg (Yselty).
- Who it may be relevant to
- Registry conditions: Adenomyosis of Uterus, Implantation Failure, Infertility Female, Embryo Transfer. Basic parameters: 18 years — 50 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Spain
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Efficacy of Linzagolix 200 mg for 3 to 6 Months Prior to Embryo Transfer in Patients With Adenomyosis and Recurrent Implantation Failure: A Prospective Case Series
Overview
Adenomyosis is associated with impaired endometrial receptivity and reduced implantation rates in assisted reproduction, even when using high-quality embryos. Linzagolix (Yselty, 200 mg) is an oral GnRH receptor antagonist approved for uterine fibroids with a favourable tolerability profile and rapid elimination half-life (18-20 hours) compared to GnRH agonists. This prospective case series evaluates the efficacy of linzagolix 200 mg administered for 3 to 6 months prior to embryo transfer in patients with confirmed adenomyosis and recurrent implantation failure (RIF), defined as ≥2 failed transfers with high-quality blastocysts (≥BB Gardner in oocyte donation, or PGT-A confirmed euploid in autologous cycles). The primary endpoint is the live birth rate (LBR) per embryo transfer. Secondary endpoints include clinical pregnancy rate, miscarriage rate, morphological response of adenomyosis (uterine volume and junctional zone \[JZ\] thickness assessed by standardised transvaginal ultrasound), and tolerability profile. The study also explores the optimal treatment duration (3 vs 6 months) as a sub-analysis based on morphological response at the month-3 visit. The study is conducted at three centres of Vida Fertility Institute (Madrid, Alicante and San Sebastián, Spain). Sample size: n=35 patients. Study duration: 24 months.
Detailed description
BACKGROUND:
Current standard of care for adenomyosis prior to embryo transfer in RIF patients consists of GnRH agonist therapy (triptorelin depot) for 1-3 months, with or without letrozole. This approach requires intramuscular administration, is associated with intense vasomotor symptoms, and has a prolonged pharmacological residual effect (4-6 weeks) that complicates cycle planning. No prospective study has evaluated linzagolix in this specific clinical scenario.
DESIGN:
Prospective before-after case series. Each patient serves as her own historical control (prior failed transfers under standard care vs outcome after linzagolix treatment). Treatment duration (3 or 6 months) is determined by morphological response at the month-3 ultrasound visit. Endometrial preparation is initiated 7 days after the last dose of linzagolix.
ULTRASOUND PROTOCOL:
Standardised transvaginal ultrasound measurements at each visit: uterine volume (L x AP x T x 0.523 cm3), junctional zone maximum (mm), junctional zone minimum (mm) and junctional zone difference (mm). All measurements performed in strict sagittal plane with ≥7 MHz transvaginal probe.
VASOMOTOR SYMPTOM MANAGEMENT:
Standardised non-estrogenic supplementation protocol (Cimicifuga racemosa 20 mg, Remifemin) if EVA score ≥4 for hot flushes or insomnia. Suspended simultaneously with the last dose of linzagolix.
REGULATORY FRAMEWORK:
Observational study with medicinal products (EOMF) under Spanish Royal Decree 957/2020. Use of linzagolix in this indication is off-label. Study approved by CEIm del Hospital Clinico San Carlos, Madrid.
Interventions
- Drug Linzagolix 200 mg (Yselty)
Linzagolix 200 mg orally once daily for a minimum of 3 months, extendable to 6 months based on morphological response (uterine volume and junctional zone assessment) at the month-3 transvaginal ultrasound visit. Off-label use for adenomyosis prior to embryo transfer.
Primary outcome measures
- Live Birth Rate (LBR) per embryo transfer [Time frame: Up to 12 months after embryo transfer]
Secondary outcome measures (5)
- Clinical Pregnancy Rate [Time frame: 6-7 weeks after embryo transfer]
- Miscarriage Rate [Time frame: Up to 22 weeks of gestation]
- Change in Uterine Volume [Time frame: Baseline, month 3, month 6 (if applicable) and pre-transfer (approximately 3-7 months from baseline)]
- Change in Junctional Zone Maximum Thickness [Time frame: Baseline, month 3, month 6 (if applicable) and pre-transfer (approximately 3-7 months from baseline)]
- Incidence of Vasomotor Adverse Events [Time frame: Monthly during treatment period (up to 6 months)]
Eligibility criteria
Inclusion criteria
- Age 18 to 50 years
- Confirmed adenomyosis by transvaginal ultrasound or MRI
- Recurrent implantation failure defined as 2 or more failed embryo transfers with high-quality blastocysts: oocyte donation recipients (blastocyst grade BB or above, Gardner classification) OR autologous IVF cycles with PGT-A confirmed euploid blastocysts
- Normal uterine cavity with no submucosal distortion
- At least 1 suitable embryo available for transfer (blastocyst grade BB or above, or PGT-A euploid)
- Signed written informed consent including explicit acknowledgement of off-label use of linzagolix
Exclusion criteria
- Untreated hydrosalpinx
- Untreated stage III-IV endometriosis
- Major uterine anomaly (uterine septum, bicornuate uterus)
- Known contraindication to linzagolix including known hepatopathy
- Prior treatment with linzagolix
- GnRH analogue treatment within 6 months prior to enrolment
- BMI greater than 35 kg/m2
- Prior failed transfers exclusively with embryos below the quality threshold (below BB grade, non-euploid)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Spain · 3 centers
- Vida Fertility Alicante — Alicante
- Vida Fertility Donostia — San Sebastián
- Vida Fertility Institute Madrid — Madrid
Identifiers
NCT: NCT07698561 · VFI-LNZG-2025