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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 35
- 试验地点
- 3
- 主要终点
- Live Birth Rate (LBR) per embryo transfer
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
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.
干预措施: Linzagolix 200 mg (Yselty) (Drug)
结局指标
主要结局
Live Birth Rate (LBR) per embryo transfer
时间窗: 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.
次要结局
- 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))