Linzagolix in Adenomyosis and Recurrent Implantation Failure

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.

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)