Ultra-Long GnRH-a Pretreatment for FET Outcomes in Patients With Deep Infiltrating Endometriosis

NCT07696351 | Recruiting Phase 4

• 2 other identifiers: DIE-GnRHa-FET-RCT-2025-012025-0564
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Deep infiltrating endometriosis is a severe form of endometriosis that may reduce fertility and negatively affect pregnancy outcomes after assisted reproductive treatment. Gonadotropin-releasing hormone agonist pretreatment may suppress endometriotic lesions, reduce inflammation, and improve endometrial receptivity, but its benefit before frozen-thawed embryo transfer remains uncertain. This randomized controlled study will evaluate whether ultra-long GnRH-a pretreatment before hormone replacement therapy improves clinical pregnancy outcomes in patients with deep infiltrating endometriosis undergoing their first frozen-thawed embryo transfer cycle. Eligible participants will be randomly assigned to either the GnRH-a pretreatment group or the control group. Participants in the GnRH-a group will receive two injections of long-acting GnRH-a before hormone replacement therapy for endometrial preparation, while participants in the control group will receive routine hormone replacement therapy alone. The primary outcome is clinical pregnancy rate, defined as the presence of a gestational sac on transvaginal ultrasound 30 ± 3 days after embryo transfer. Secondary outcomes include implantation rate, ectopic pregnancy rate, early spontaneous abortion rate, ongoing pregnancy rate at 12 weeks of gestation, and delivery rate. Safety will be evaluated by recording adverse events after GnRH-a injection. The planned enrollment is 120 participants.

Conditions

Deep Infiltrating Endometriosis (DIE); Infertility

Keywords

Deep infiltrating endometriosis; GnRH-a; Triptorelin; Frozen-thawed embryo transfer; Hormone replacement therapy; Clinical pregnancy rate; Infertility

Outcome Measures

Primary Outcomes (1)

• Clinical Pregnancy Rate

  Clinical pregnancy is defined as the presence of a gestational sac detected by transvaginal ultrasound 30 ± 3 days after embryo transfer. Clinical pregnancy rate will be calculated as the number of clinical pregnancy cycles divided by the total number of embryo transfer cycles.

  30 ± 3 days after embryo transfer

Secondary Outcomes (5)

• Implantation Rate

  30 ± 3 days after embryo transfer

• Ectopic Pregnancy Rate

  Up to 49 ± 7 days after embryo transfer

• Early Spontaneous Abortion Rate

  Up to 12 weeks of gestation

• Ongoing Pregnancy Rate at 12 Weeks of Gestation

  12 weeks of gestation

• Delivery Rate

  At delivery, up to study completion

Other Outcomes (1)

• Incidence of Adverse Events After GnRH-a Injection

  From first GnRH-a injection to embryo transfer

Study Arms (2)

Ultra-Long GnRH-a Pretreatment Group

EXPERIMENTAL

Participants in this group will receive ultra-long GnRH-a pretreatment before frozen-thawed embryo transfer. Long-acting GnRH-a will be administered on menstrual cycle days 2 to 4, followed by a second injection 28 to 30 days later. Hormone replacement therapy for endometrial preparation will begin 28 to 30 days after the second GnRH-a injection, followed by frozen-thawed embryo transfer according to routine clinical practice.

Drug: Triptorelin (GnRH agonists)

Routine HRT Group

ACTIVE COMPARATOR

Participants in this group will undergo routine hormone replacement therapy for endometrial preparation before frozen-thawed embryo transfer without GnRH-a pretreatment.

Other: Hormone Replacement Therapy (HRT)

Interventions

Triptorelin (GnRH agonists) DRUG

Long-acting GnRH-a pretreatment will be administered before hormone replacement therapy for endometrial preparation. Participants will receive two injections of triptorelin 3.75 mg: the first on menstrual cycle days 2 to 4 and the second 28 to 30 days later.

Also known as: GnRHa

Ultra-Long GnRH-a Pretreatment Group

Hormone Replacement Therapy (HRT) OTHER

Routine hormone replacement therapy will be used for endometrial preparation before frozen-thawed embryo transfer.

Also known as: HRT

Routine HRT Group

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female patients aged 18 to 39 years.
• Diagnosed with deep infiltrating endometriosis by ultrasound at the study center.
• Undergoing the first frozen-thawed embryo transfer cycle with hormone replacement therapy for endometrial preparation.
• Having at least one good-quality frozen embryo.
• Willing to participate in this randomized controlled study of GnRH-a pretreatment for deep infiltrating endometriosis and able to personally sign the written informed consent form.

You may not qualify if:

• Abnormal chromosomal karyotype.
• Other uterine diseases or conditions that may affect uterine cavity morphology or pregnancy outcomes, including intrauterine adhesions affecting the uterine cavity, intramural uterine fibroids, moderate to severe adenomyosis, congenital uterine malformation, endometrial tuberculosis, or endometrial thickness less than 8 mm on the transformation day.
• Recurrent implantation failure.
• Contraindications to hormone replacement therapy or long-acting GnRH-a treatment.
• Osteoporosis or depressed mood.
• Currently participating in another clinical study.
• Unable to adhere to study visits and follow-up, or planning to receive other treatment during the follow-up period.

Sponsors & Collaborators

• Li-jun Ding: lead

Study Sites (1)

The Affiliated Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 216000, China

RECRUITING

Related Publications (3)

• Surrey ES, Katz-Jaffe M, Kondapalli LV, Gustofson RL, Schoolcraft WB. GnRH agonist administration prior to embryo transfer in freeze-all cycles of patients with endometriosis or aberrant endometrial integrin expression. Reprod Biomed Online. 2017 Aug;35(2):145-151. doi: 10.1016/j.rbmo.2017.05.004. Epub 2017 May 17.

  PMID: 28601378 RESULT

• Tamura H, Takasaki A, Nakamura Y, Numa F, Sugino N. A pilot study to search possible mechanisms of ultralong gonadotropin-releasing hormone agonist therapy in IVF-ET patients with endometriosis. J Ovarian Res. 2014 Oct 21;7:100. doi: 10.1186/s13048-014-0100-8.

  PMID: 25331066 RESULT

• Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022 Nov 14;379:e070750. doi: 10.1136/bmj-2022-070750.

  PMID: 36375827 RESULT

MeSH Terms

Conditions

Infertility

Interventions

Triptorelin Pamoate; Hormone Replacement Therapy

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Drug Therapy; Therapeutics

Study Officials

• Jie Mei

  Department of Reproductive Medicine, Nanjing Drum Tower Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jie Mei, PhD

CONTACT

+86 15051839536 Email; meijie560@163.com

Yuan Yan

CONTACT

+86 15950526117

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Professor

Model Details: Participants will be randomly assigned in a 1:1 ratio to either the ultra-long GnRH-a pretreatment group or the routine hormone replacement therapy control group. The two groups will be compared in parallel to evaluate the effect of GnRH-a pretreatment on frozen-thawed embryo transfer outcomes.

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 10, 2026
• Study Start: August 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)