The Effect of the GM-CSF Gel on the Endometrial Thickness in Infertile Women With Thin Endometrium

A Randomized Controlled Trial of the Effect of the Granulocyte-macrophage Colony Stimulating Factor Gel on the Endometrial Thickness in Infertile Women With Thin Endometrium

The purpose of this study is to investigate the efficacy of the granulocyte-macrophage colony stimulating factor(GM-CSF) gel on the endometrial thickness in infertile women with thin endometrium.

Study Overview

• Status: Unknown
• Conditions: Thin Endometrium
• Intervention / Treatment: Drug: GM-CSF; Drug: 17-ß estradiol

Detailed Description

The thin endometrium is detrimental to embryo implantation, probability of clinical pregnancy for an endometrial thickness ≤ 7 mm was significantly lower compared with cases with endometrial thickness > 7 mm. It has been reported the granulocyte colony stimulating factor (G-CSF) increased the endometrial thickness and pregnancy rate of infertile women with thin endometrium during IVF cycle. However, most of the researches were retrospective and small sample size, and the results were conflicted among them. GM-CSF is another member of CSF superfamily, recalling more macrophage than G-CSF, which could be more effective in local homeostasis maintain and wound repair. GM-CSF has been widely used in skin repair after burn. It was also found the GM-CSF and its receptor in endometrium. In the past year, the investigators tried GM-CSF irrigation in 21 women with thin endometrium and most of them received GM-CSF after hysteroscopic examination or slight adhesion relaxing, and the preliminary data suggested that the GM-CSF may promote the endometrial growth. Does the GM-CSF gel can improve the endometrial thickness? Therefore, this study was conducted.

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310018
      • Sir Run Run Shaw Hospital
      • Contact: Minling Wei, Master; Phone Number: +8657186002222; Email: minling_wei@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Woman undergoes IVF treatment, 18-40 years old
2. The endometrial thickness <7mm on the day of human chorionic gonadotropin during IVF or after taking oral estradiol valerate 6mg/d for 14 days.
3. Embryo transfer is cancelled because of thin endometrium
4. No intrauterine adhesion according to the 3-D ultrasonography

Exclusion Criteria:

1. Systemic diseases unable to conceive
2. Chromasome abnormal
3. History of G-CSF or GM-CSF allergy or untoward effect
4. Thin endometrium related to clomid
5. Severe or moderate uterine adhesion
6. The influence factor of embryo implantation: hydrosalpinx, endometriosis, adenomyosis,myoma of uterus
7. Uterine malformation, adenomyosis, uterine leiomyoma sized more than 2cm.
8. Patients who is allergic to granulocyte-macrophage colony stimulating factor
9. Patients with inflammation of reproductive organs, pelvic cavity inflammation, malignant tumor of reproductive organs and other systemic diseases that could cause metrorrhagia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GM-CSF; Hysteroscopy will be arranged to confirm the uterine cavity is normal and there is no significant intrauterine adhesion. 3ml GM-CSF gel will be irrigated into the uterine cavity immediately when hysteroscopy is complete. Then same dose gel will be given every other day twice.	Drug: GM-CSF; 3ml GM-CSF gel will be irrigated into the uterine cavity immediately when hysteroscopy is complete. Then same dose gel will be given every other day twice; Other Names: granulocyte-macrophage colony stimulating factor; Drug: 17-ß estradiol; A hormone replace treatment by 17-ß estradiol (6mg per day) follows next cycle to prepare for embryo transfer; Other Names: Femoston
Experimental: Control; Hysteroscopy will be arranged to confirm the uterine cavity is normal and there is no significant intrauterine adhesion. After hysteroscopy examination, nothing was applied to the uterine cavity.	Drug: 17-ß estradiol; A hormone replace treatment by 17-ß estradiol (6mg per day) follows next cycle to prepare for embryo transfer; Other Names: Femoston

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the endometrial thickness	the endometrial thickness following the hormonal replacement treatment evaluated based on the ultrasound	1 months after hysteroscopy examination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
embryo transfer cancelation rate	according to the patients' wishes	2 months after hysteroscopy examination
uterine artery blood supply markers	uterine artery blood supply markers, such as PI, reflux index(RI) and S/D, evaluated based on the 3-D ultrasonography	1 months after hysteroscopy examination
pregnancy rate	pregnancy rate after frozen embryo transfer	3 months after hysteroscopy examination

Collaborators and Investigators

• Sponsor: Sir Run Run Shaw Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: September 3, 2019
• First Submitted That Met QC Criteria: September 20, 2019
• First Posted (Actual): September 24, 2019

Study Record Updates

• Last Update Posted (Actual): September 24, 2019
• Last Update Submitted That Met QC Criteria: September 20, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: GM-CSF; frozen embryo transfer
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol; Sargramostim; Molgramostim
• Other Study ID Numbers: SRRSH20190806-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No