GnRH Agonist Pretreatment Duration and Letrozole Supplementation in Frozen Embryo Transfer for Adenomyosis Patients

Официальное название

The Impact of Duration of Gonadotropin-Releasing Hormone Agonist Pretreatment and Letrozole Supplementation on Pregnancy Outcomes in Frozen-Thawed Embryo Transfer Cycles for Patients With Adenomyosis: A 2 by 2 Factorial Multicenter, Randomized Controlled Trial

Обзор

This randomized clinical trial aims to assess the comparative effectiveness of different pre-treatment protocols prior to frozen embryo transfer (FET) among women with adenomyosis, providing evidence-based guidance for clinical decision-making. The main questions it aims to answer are: Does the protocol involving two doses of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment result in a higher live birth rate compared to one dose of GnRH-a pretreatment in women with adenomyosis undergoing frozen embryo transfer? Does the protocol involving GnRH-a with letrozole supplementation result in a higher live birth rate compared to GnRH-a monotherapy in women with adenomyosis undergoing frozen embryo transfer? Eligible participants will undergo screening before endometrial preparation for FET, following which they will be randomly assigned to one of four groups: GnRH-a-1M, GnRH-a-2M, GnRH-a+LE-1M or GnRH-a+LE-2M. In the GnRH-a-1M group, participants will be pre-treated with one dose GnRH agonist before endometrial preparation. In the GnRH-a-2M group, participants will be pre-treated with two doses GnRH agonist before endometrial preparation. In the GnRH-a+LE-1M group, participants will be pre-treated with one dose GnRH agonist and letrozole 28 days before endometrial preparation. In the GnRH-a+LE-2M group, participants will be pre-treated with two doses GnRH agonist, along with daily 2.5 mg letrozole for 28 days since the first injection of GnRH agonist before endometrial preparation. After pre-treament, all participants will return for endometrial preparation in artificial cycles.

Вмешательства

• Препарат GnRH-a-1M
  Pre-treatment with one dose GnRH agonist before endometrial preparation.
• Препарат GnRH-a-2M
  Pre-treatment with two doses GnRH agonist before endometrial preparation.
• Препарат GnRH-a+LE-1M
  Pre-treatment with one dose GnRH agonist, along with daily 2.5 mg letrozole for 28 days before endometrial preparation.
• Препарат GnRH-a+LE-2M
  Pre-treatment with two doses GnRH agonist, along with daily 2.5 mg letrozole for 28 days since the first injection of GnRH agonist before endometrial preparation.

Первичные конечные точки

• Live birth rate [Срок оценки: 40 weeks after embryo transfer]

Вторичные конечные точки (12)

• Cycle Cancellation Rate [Срок оценки: 3 weeks after initiating artificial cycle]
• Hypoestrogenic Adverse Event Rate [Срок оценки: 4 weeks after 3.75mg GnRH-a intramuscular injection]
• Positive Pregnancy Test Rate [Срок оценки: 2 weeks post embryo transfer]
• Embryo Implantation Rate [Срок оценки: 3 weeks post embryo transfer]
• Clinical Pregnancy Rate [Срок оценки: 5 weeks post embryo transfer]
• Ectopic Pregnancy Rate [Срок оценки: 7 weeks' gestation]
• Ongoing Pregnancy Rate [Срок оценки: 10 weeks post embryo transfer]
• Miscarriage Rate [Срок оценки: Prior to 28 weeks' gestation]
• Drug-Related Venous Thromboembolism (VTE) Rate [Срок оценки: Treatment initiation until 10 weeks' gestation]
• Preterm Birth Rate [Срок оценки: 22, 28, 32, 37 weeks' gestation]
• Gestational Diabetes Mellitus (GDM) Incidence [Срок оценки: 24-28 weeks' gestation]
• Rate of Hypertension in Pregnancy [Срок оценки: 20 weeks' gestation to delivery]

Критерии участия

Критерии включения

• Sonographically diagnosed adenomyosis via transvaginal ultrasound;
• Candidates scheduled for frozen single blastocyst (Day5, Day6) transfer
• Age 20-38 years
• Previous embryo transfer attempts: ≤2 cycles

Критерии исключения

• Patients diagnosed with Recurrent pregnancy loss, Autoimmune disorders (e.g., systemic lupus erythematosus), Uterine fibroids ≥5 cm, Cervical incompetence, Cesarean scar niche
• History of Myomectomy and/or adenomyosis lesion excision, Cervical conization
• Patients presenting with Congenital Müllerian anomalies (unicornuate uterus, septate uterus, etc.), Endometrial atypical hyperplasia, malignancy or defects
• Sperm retrieval method: Micro-TESE (microdissection testicular sperm extraction)
• Fertilization method: Rescue ICSI
• Endometrial thickness <7 mm, Intrauterine adhesions, Intrauterine fluid
• Contraindications to exogenous hormone administration
• Use of GnRH within 3 months prior to enrollment

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Факторный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Reproductive Medical Center, the First Af liated Hospital of Sun Yat-sen University, Zhong — Гуанчжоу

Публикации

• Badawy AM, Elnashar AM, Mosbah AA. Aromatase inhibitors or gonadotropin-releasing hormone agonists for the management of uterine adenomyosis: a randomized controlled trial. Acta Obstet Gynecol Scand. 2012 Apr;91(4):489-95. doi: 10.1111/j.1600-0412.2012.01350.x. PMID 22229256
• Duhan N, Madaan S, Sen J. Role of the aromatase inhibitor letrozole in the management of uterine leiomyomas in premenopausal women. Eur J Obstet Gynecol Reprod Biol. 2013 Dec;171(2):329-32. doi: 10.1016/j.ejogrb.2013.09.010. Epub 2013 Sep 20. PMID 24103533
• Harmsen MJ, Van den Bosch T, de Leeuw RA, Dueholm M, Exacoustos C, Valentin L, Hehenkamp WJK, Groenman F, De Bruyn C, Rasmussen C, Lazzeri L, Jokubkiene L, Jurkovic D, Naftalin J, Tellum T, Bourne T, Timmerman D, Huirne JAF. Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: results of modified Delphi procedure. Ultrasound Obstet Gynecol PMID 34587658
• Selntigia A, Molinaro P, Tartaglia S, Pellicer A, Galliano D, Cozzolino M. Adenomyosis: An Update Concerning Diagnosis, Treatment, and Fertility. J Clin Med. 2024 Sep 3;13(17):5224. doi: 10.3390/jcm13175224. PMID 39274438
• Struble J, Reid S, Bedaiwy MA. Adenomyosis: A Clinical Review of a Challenging Gynecologic Condition. J Minim Invasive Gynecol. 2016 Feb 1;23(2):164-85. doi: 10.1016/j.jmig.2015.09.018. Epub 2015 Sep 30. PMID 26427702
• Xiong Y, Gu F, Du L, Gu J, Ke Z, Xu Y, Mol BW, Zheng B, Lin X, Xu Y. Gonadotropin-releasing hormone agonist (GnRH-a) pretreatment duration and letrozole supplementation for optimizing live birth rates in women with adenomyosis undergoing frozen-thawed embryo transfer (GOLD-FET): study protocol for a multicenter, 2 x 2 factorial randomized controlled trial in China. Trials. 2026 Apr 24;27(1):421. d PMID 42032741

Идентификаторы

NCT: NCT07065539 · 2025012-5010

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗