Adenomyosis of UterusLINZA-RIFNCT07698561
Linzagolix in Adenomyosis and Recurrent Implantation Failure
An observational study of Adenomyosis of Uterus and Implantation Failure, run by Vida Fertility Institute at 3 sites in Spain.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Adenomyosis of Uterus, Implantation Failure, Infertility Female
- What is being tested?
- Linzagolix 200 mg (Yselty)
- Type of treatment
- Pill or oral medicine
- How many people
- 30 participants
- Where
- 3 sitesSpain
- Study dates
- 1 Jan 2027to 1 Sep 2028
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Study population: Women aged 18 to 50 years with confirmed adenomyosis (transvaginal ultrasound or MRI) and recurrent implantation failure, defined as 2 or more failed embryo transfers with high-quality blastocysts (grade BB or above in oocyte donation cycles, or PGT-A confirmed euploid blastocysts in autologous cycles), attending Vida Fertility Institute centres in Madrid, Alicante and San Sebastian, Spain.
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Spain3 sites
Vida Fertility Alicante
Alicante, 03008
Sergio Rogel, MD, +34 669657631, rogel.s@vidafertility.com
Alejandra García Villalba, MD, +34 605920083, garciavillalba.a@vidafertility.com
Vida Fertility Institute Madrid
Madrid, 28043
Elena De Santiago Romero, MD, +34 679211353, santiago.e@vidafertility.com
Irene Hervas, PhD, +34 697766609, hervas.i@vidafertility.com
Vida Fertility Donostia
San Sebastián, Gipuzkoa, 20018
Estefanía Rodriguez, MD, +34 653733284, rodriguez.e@vidafertility.com
About this study
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
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).
Read more
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=30 patients. Study duration: 24 months.
Read the 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. Treatment extension to 6 months is indicated if any of the following criteria are met at month 3: uterine volume reduction <20% from baseline, JZ maximum ≥12 mm, JZ difference ≥5 mm, or serum estradiol >40 pg/ml indicating incomplete hypothalamic-pituitary-ovarian axis suppression. 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 (ref. 26/769-O_M_SP, October 13, 2026)."
- Being tested
- Linzagolix 200 mg (Yselty)
- Keywords
- Linzagolix, Yselty, adenomyosis, recurrent implantation failure, junctional zone, live birth rate, oocyte donation, PGT-A, GnRH antagonist, endometrial receptivity
- Medical subject headings
- Adenomyosis, Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Linzagolix 200 mg (Yselty)Drug
Also called Yselty, GnRH receptor antagonist
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) and serum estradiol levels (>40 pg/ml) at the month-3 visit.O ff-label use for adenomyosis prior to embryo transfer.
| Study group | Role | What they receive |
|---|---|---|
| Linzagolix 200 mg - Adenomyosis and RIF | Patients with confirmed adenomyosis and recurrent implantation failure (2 or more failed embryo transfers with high-quality blastocysts: grade BB or above in oocyte donation cycles, or PGT-A confirmed euploid in autologous cycles) receiving linzagolix 200 mg orally once daily for 3 to 6 months prior to embryo transfer. Treatment duration is determined at the month-3 visit based on morphological response (uterine volume reduction, junctional zone measurements) and serum estradiol levels (>40 pg/ml indicating incomplete axis suppression). Endometrial preparation is initiated 7 days after the last dose of linzagolix. Receives: Drug: Linzagolix 200 mg (Yselty) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live Birth Rate (LBR) per embryo transfer
Proportion of embryo transfers resulting in the birth of a live neonate at or beyond 24 weeks of gestation.
Measured: Up to 12 months after embryo transfer
Secondary outcomes (7)
Clinical Pregnancy Rate
Proportion of embryo transfers resulting in the presence of an intrauterine gestational sac with fetal heartbeat on transvaginal ultrasound at 6-7 weeks of gestation.
Measured: 6-7 weeks after embryo transfer
Miscarriage Rate
Proportion of clinical pregnancies ending in spontaneous pregnancy loss before 22 weeks of gestation.
Measured: Up to 22 weeks of gestation
Change in Uterine Volume
Change in uterine volume (cm3) measured by transvaginal ultrasound using the ellipsoid formula (L x AP x T x 0.523) from baseline to post-treatment.
Measured: Baseline, month 3, month 6 (if applicable) and pre-transfer (approximately 3-7 months from baseline)
Change in Junctional Zone Maximum Thickness
Change in junctional zone (JZ) maximum thickness (mm) measured by standardised transvaginal ultrasound in strict sagittal plane from baseline to post-treatment.
Measured: Baseline, month 3, month 6 (if applicable) and pre-transfer (approximately 3-7 months from baseline)
Incidence of Vasomotor Adverse Events
Proportion of patients reporting hot flushes, insomnia or other vasomotor symptoms, assessed using a visual analogue scale (EVA 0-10) at each visit.
Measured: Monthly during treatment period (up to 6 months)
Serum estradiol levels
Serum estradiol levels (pg/ml) measured at baseline, month 1, month 3 and month 6 to assess degree of hypothalamic-pituitary-ovarian axis suppression during linzagolix treatment.
Measured: Baseline, month 1, month 3, month 6 (if applicable).
Hepatic safety
Hepatic function parameters (ALT, AST, GGT and total bilirubin) measured at baseline, month 3 and month 6 to assess liver safety during linzagolix treatment.
Measured: Baseline, month 3, month 6 (if applicable).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2026
- Study start1 Jan 2027 (estimated)
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adenomyosis of UterusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Vida Fertility Institute
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07698561
- Sponsor's protocol ID
- VFI-LNZG-2025
- Acronym
- LINZA-RIF
- Status last verified
- Oct 2026
- First submitted
- 6 Jul 2026
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Individual participant data will not be shared at this stage due to the small sample size and the need to protect patient privacy in accordance with the General Data Protection Regulation (GDPR, EU 2016/679) and Spanish Organic Law 3/2018 on Personal Data Protection. Anonymised aggregate data may be made available upon reasonable request following publication of the primary results.
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07698561
- Acronym / sponsor ID
- LINZA-RIF / VFI-LNZG-2025
- Keywords
- Linzagolix, Yselty, adenomyosis, recurrent implantation failure, junctional zone, live birth rate, oocyte donation, PGT-A
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Vida Fertility InstituteIndustry (pharma, biotech, devices)
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 1 Jul 2028 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 13 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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=30 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. Treatment extension to 6 months is indicated if any of the following criteria are met at month 3: uterine volume reduction <20% from baseline, JZ maximum ≥12 mm, JZ difference ≥5 mm, or serum estradiol >40 pg/ml indicating incomplete hypothalamic-pituitary-ovarian axis suppression. 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 (ref. 26/769-O_M_SP, October 13, 2026)."
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Linzagolix 200 mg - Adenomyosis and RIF | – | Drug: Linzagolix 200 mg (Yselty)Patients with confirmed adenomyosis and recurrent implantation failure (2 or more failed embryo transfers with high-quality blastocysts: grade BB or above in oocyte donation cycles, or PGT-A confirmed euploid in autologous cycles) receiving linzagolix 200 mg orally once daily for 3 to 6 months prior to embryo transfer. Treatment duration is determined at the month-3 visit based on morphological response (uterine volume reduction, junctional zone measurements) and serum estradiol levels (>40 pg/ml indicating incomplete axis suppression). Endometrial preparation is initiated 7 days after the last dose of linzagolix. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Women aged 18 to 50 years with confirmed adenomyosis (transvaginal ultrasound or MRI) and recurrent implantation failure, defined as 2 or more failed embryo transfers with high-quality blastocysts (grade BB or above in oocyte donation cycles, or PGT-A confirmed euploid blastocysts in autologous cycles), attending Vida Fertility Institute centres in Madrid, Alicante and San Sebastian, Spain.
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Linzagolix 200 mg (Yselty)Also: Yselty, GnRH receptor antagonistLinzagolix 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) and serum estradiol levels (>40 pg/ml) at the month-3 visit.O ff-label use for adenomyosis prior to embryo transfer. | Drug | Linzagolix 200 mg - Adenomyosis and RIF |
Primary outcome
Live Birth Rate (LBR) per embryo transfer
Time frame: Up to 12 months after embryo transfer
Proportion of embryo transfers resulting in the birth of a live neonate at or beyond 24 weeks of gestation.
7 secondary outcomes
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)
Serum estradiol levels
Time frame: Baseline, month 1, month 3, month 6 (if applicable).
Hepatic safety
Time frame: Baseline, month 3, month 6 (if applicable).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Individual participant dataSharing planned: Undecided. Individual participant data will not be shared at this stage due to the small sample size and the need to protect patient privacy in accordance with the General Data Protection Regulation (GDPR, EU 2016/679) and Spanish Organic Law 3/2018 on Personal Data Protection. Anonymised aggregate data may be made available upon reasonable request following publication of the primary results.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Adenomyosis of Uterus and Implantation Failure, run by Vida Fertility Institute at 3 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elena De Santiago Romero, MD (+34 679211353, santiago.e@vidafertility.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live Birth Rate (LBR) per embryo transfer (time frame: Up to 12 months after embryo transfer). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.