Intrauterine G-CSF Infusion for Thin Endometrium

Официальное название

A Single-Center Randomized Controlled Trial of Intrauterine G-CSF Infusion for Improving Pregnancy Outcomes in Patients With Thin Endometrium

Обзор

Thin endometrium is a condition in which the lining of the uterus is too thin during preparation for embryo transfer. This may reduce the chance of pregnancy and live birth in patients undergoing frozen-thawed embryo transfer. This study will evaluate whether intrauterine infusion of granulocyte colony-stimulating factor, also called G-CSF, can improve pregnancy outcomes in patients with thin endometrium. Participants will be randomly assigned to one of two groups. The experimental group will receive mild endometrial stimulation followed by intrauterine infusion of G-CSF 300 μg. The control group will receive the same mild endometrial stimulation followed by intrauterine infusion of normal saline. Both groups will then continue standard endometrial preparation for frozen-thawed embryo transfer. The main outcome of the study is the live birth rate. The study will also assess endometrial thickness, endometrial blood flow, clinical pregnancy rate, miscarriage rate, and safety outcomes, including adverse events, pregnancy complications, fetal malformations, and neonatal birth defects. Participants will be followed from enrollment through embryo transfer, pregnancy assessment, and delivery. This is a single-center, prospective, randomized controlled trial conducted at Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School. The planned sample size is 620 participants.

Подробное описание

Thin endometrium remains a clinical challenge in assisted reproductive technology because it may reduce endometrial receptivity and the chance of successful embryo implantation and live birth. Several treatment strategies have been used for thin endometrium, including hormonal treatment, medications to improve blood flow, endometrial stimulation, and intrauterine infusion of granulocyte colony-stimulating factor (G-CSF). However, the clinical benefit of intrauterine G-CSF infusion remains uncertain, partly because previous studies have differed in patient populations, timing of administration, dose, and study design.

This study is designed to evaluate whether intrauterine infusion of G-CSF during the endometrial preparation phase can improve reproductive outcomes in patients with thin endometrium undergoing frozen-thawed embryo transfer. The study uses a prospective, single-center, randomized, parallel-group, blinded, superiority design. Eligible participants will be randomly assigned in a 1:1 ratio to receive either mild endometrial stimulation with intrauterine G-CSF infusion or mild endometrial stimulation with intrauterine normal saline infusion. Randomization will be performed using an interactive web response system.

All participants will receive routine endometrial preparation for frozen-thawed embryo transfer according to local clinical practice. In the intervention group, participants will undergo mild endometrial stimulation followed by intrauterine infusion of G-CSF 300 μg. In the control group, participants will undergo the same mild endometrial stimulation procedure followed by intrauterine infusion of an equal volume of normal saline. Participants, outcome assessors, and statistical analysts will be blinded to group assignment, while the physician performing the intrauterine procedure will not be blinded.

After the intrauterine procedure, endometrial development will be monitored by ultrasound. Embryo transfer will be performed after endometrial transformation according to the frozen-thawed embryo transfer protocol. Participants will be followed for pregnancy outcomes, delivery outcomes, and safety events. The study aims to determine whether the addition of intrauterine G-CSF to mild endometrial stimulation provides a clinically meaningful benefit compared with mild endometrial stimulation and saline control.

Вмешательства

• Биопрепарат Granulocyte Colony-Stimulating Factor(G-CSF)
  Participants in the experimental arm will receive a single intrauterine infusion of G-CSF 300 μg after mild endometrial stimulation during the endometrial preparation cycle for frozen-thawed embryo transfer.
• Препарат Normal Saline
  Participants in the control arm will receive a single intrauterine infusion of an equal volume of normal saline after the same mild endometrial stimulation procedure during the endometrial preparation cycle for frozen-thawed embryo transfer.

Первичные конечные точки

• Live Birth Rate [Срок оценки: From embryo transfer to delivery, approximately 40 weeks after embryo transfer]

Вторичные конечные точки (4)

• Endometrial Thickness [Срок оценки: On the day 1 of endometrial transformation]
• Endometrial and Sub-endometrial Blood Flow [Срок оценки: On the day 1 of endometrial transformation]
• Clinical Pregnancy Rate [Срок оценки: 4 to 6 weeks after embryo transfer]
• Early Miscarriage Rate [Срок оценки: From confirmation of clinical pregnancy to 12 weeks of gestation]

Критерии участия

Критерии включения

• Female patients aged 18 to <40 years.
• Patients with normal ovarian function.
• History of endometrial thickness ≤7 mm in at least one previous endometrial preparation cycle.
• At least two good-quality embryos remaining.
• Fewer than 3 previous embryo transfer cycles.
• Willing and able to provide written informed consent.

Критерии исключения

• Uterine diseases or conditions that may affect the uterine cavity, including intramural uterine fibroids affecting the uterine cavity, severe adenomyosis, endometriosis, uterine malformation, endometrial tuberculosis, or severe untreated intrauterine adhesions.
• Endometrial lesions, history of pelvic tumors, or previous radiotherapy or chemotherapy.
• Known allergy to G-CSF.
• Current participation in another clinical study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Lian R, Wang X, Lin R, Zeng H, Zeng Y, Liu S. Evaluation of granulocyte colony-stimulating factor on the treatment of thin endometrium during frozen-thawed embryo transfer cycles: a retrospective cohort study. Gynecol Endocrinol. 2020 Apr;36(4):370-374. doi: 10.1080/09513590.2019.1658187. Epub 2019 Aug 29. PMID 31464150
• Zhu YC, Sun YX, Shen XY, Jiang Y, Liu JY. Effect of intrauterine perfusion of granular leukocyte-colony stimulating factor on the outcome of frozen embryo transfer. World J Clin Cases. 2021 Oct 26;9(30):9038-9049. doi: 10.12998/wjcc.v9.i30.9038. PMID 34786386
• Liu KE, Hartman M, Hartman A. Management of thin endometrium in assisted reproduction: a clinical practice guideline from the Canadian Fertility and Andrology Society. Reprod Biomed Online. 2019 Jul;39(1):49-62. doi: 10.1016/j.rbmo.2019.02.013. Epub 2019 Mar 20. PMID 31029557

Идентификаторы

NCT: NCT07692672 · 2026-0087-04

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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