Linzagolix in Adenomyosis and Recurrent Implantation Failure

NCT07698561 | Not Yet Recruiting

• 1 other identifier: VFI-LNZG-2025
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 3

Brief 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 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.

Conditions

Adenomyosis of Uterus; Implantation Failure; Infertility Female; Embryo Transfer

Keywords

Linzagolix; Yselty; adenomyosis; recurrent implantation failure; junctional zone; live birth rate; oocyte donation; PGT-A; GnRH antagonist; endometrial receptivity

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 12 months after embryo transfer

Secondary Outcomes (5)

• Clinical Pregnancy Rate

  6-7 weeks after embryo transfer

• Miscarriage Rate

  Up to 22 weeks of gestation

• Change in Uterine Volume

  Baseline, month 3, month 6 (if applicable) and pre-transfer (approximately 3-7 months from baseline)

• Change in Junctional Zone Maximum Thickness

  Baseline, month 3, month 6 (if applicable) and pre-transfer (approximately 3-7 months from baseline)

• Incidence of Vasomotor Adverse Events

  Monthly during treatment period (up to 6 months)

Study Arms (1)

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 by morphological response assessed at the month-3 transvaginal ultrasound visit. Endometrial preparation is initiated 7 days after the last dose of linzagolix.

Drug: Linzagolix 200 mg (Yselty)

Interventions

Linzagolix 200 mg (Yselty) DRUG

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.

Also known as: Yselty, GnRH receptor antagonist

Linzagolix 200 mg - Adenomyosis and RIF

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Female only. The study population consists exclusively of women undergoing assisted reproduction treatment for infertility associated with adenomyosis.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Vida Fertility Institute: lead

Study Sites (3)

Vida Fertility Alicante

Alicante, Alicante, 03008, Spain

Location

Vida Fertility Donostia

San Sebastián, Gipuzkoa, 20018, Spain

Location

Vida Fertility Institute Madrid

Madrid, Madrid, 28043, Spain

Location

MeSH Terms

Conditions

Adenomyosis; Infertility, Female

Interventions

linzagolix

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Elena De Santiago Romero, MD

CONTACT

+34 679211353; santiago.e@vidafertility.com

Irene Hervas, PhD

CONTACT

+34 697766609; hervas.i@vidafertility.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 13, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: July 13, 2026

Record last verified: 2026-07

Locations

ES (3)