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

NCT07065539 | Not Yet Recruiting DMC

• 1 other identifier: 2025012-5010
• Study Type: interventional
• Target: 432
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Adenomyosis of Uterus; Frozen Embryo Transfer (FET)

Keywords

adenomyosis; embryo transfer; GnRH-a; letrozole; pre-treament

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  40 weeks after embryo transfer

Secondary Outcomes (20)

• Cycle Cancellation Rate

  3 weeks after initiating artificial cycle

• Hypoestrogenic Adverse Event Rate

  4 weeks after 3.75mg GnRH-a intramuscular injection

• Positive Pregnancy Test Rate

  2 weeks post embryo transfer

• Embryo Implantation Rate

  3 weeks post embryo transfer

• Clinical Pregnancy Rate

  5 weeks post embryo transfer

Study Arms (4)

GnRH-a-1M

ACTIVE COMPARATOR

Drug: GnRH-a-1M

GnRH-a-2M

ACTIVE COMPARATOR

Drug: GnRH-a-2M

GnRH-a+LE-1M

ACTIVE COMPARATOR

Drug: GnRH-a+LE-1M

GnRH-a+LE-2M

ACTIVE COMPARATOR

Drug: GnRH-a+LE-2M

Interventions

GnRH-a-1M DRUG

Pre-treatment with one dose GnRH agonist before endometrial preparation.

GnRH-a-1M

GnRH-a-2M DRUG

Pre-treatment with two doses GnRH agonist before endometrial preparation.

GnRH-a-2M

GnRH-a+LE-1M DRUG

Pre-treatment with one dose GnRH agonist, along with daily 2.5 mg letrozole for 28 days before endometrial preparation.

GnRH-a+LE-1M

GnRH-a+LE-2M DRUG

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.

GnRH-a+LE-2M

Eligibility Criteria

• Age: 20 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• First Affiliated Hospital, Sun Yat-Sen University: lead
• Women and Children's Hospital of Fujian Province: collaborator
• BoAi Hospital of Zhongshan: collaborator

Study Sites (1)

Reproductive Medical Center, the First Af liated Hospital of Sun Yat-sen University, Zhongshan 2nd Road, Number 1

Guangzhou, Guangdong, 510000, China

Location

Related Publications (5)

• 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 BACKGROUND

• 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 BACKGROUND

• 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. 2022 Jul;60(1):118-131. doi: 10.1002/uog.24786.

  PMID: 34587658 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Adenomyosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Yanwen Xu

  Center for Reproductive Medicine, The First Affiliated Hospital of Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanwen Xu

CONTACT

+8613682213000; xuyanwen@mail.sysu.edu.cn

Yujing Xiong

CONTACT

+8618816899615; xiongyj3@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Reproductive Medical Center, the First Affliated Hospital of Sun Yat-sen University

Study Record Dates

• First Submitted: June 13, 2025
• First Posted: July 15, 2025
• Study Start: July 20, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)