Chronic Endometritis and Benefits of Antibiotics in Women With Recurrent Miscarriage

The Prevalence of Chronic Endometritis and Therapeutic Benefits of Antibiotics in Women With Unexplained Recurrent Miscarriage

The aim of the study is to estimate the incidence of CE, evaluate the endometrial microorganism of CE, and investigate the therapeutic benefits of antibiotics for women with unexplained recurrent miscarriage and CE.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Miscarriage
• Intervention / Treatment: Other

Detailed Description

Eligible women, based on the inclusion and exclusion criteria, will be recruited from the miscarriage clinic in the Prince of Wales Hospital. Endometrial sampling (ES) will alternatively be conducted during mid-luteal phase. In natural cycles, all the subjects will have a daily urine test from day 9 of the menstrual cycle to identify the Luteinizing Hormone (LH) surge. The ES will be obtained precisely 7 days after LH surge. Endometrial samples will be obtained using a Pipelle sampler as an outpatient procedure. The endometrium will be divided into three aliquots. One will be fixed in 4% formalin for 24 hours, routinely processed and embedded in paraffin wax. One will be investigated by microbial culture for infectious agents and one will be sequenced to reveal the endometrial microbiota.

CE will be diagnosed either by the presence of plasma cells and changes in endometrial stromal cells identified using HE and IHC, or by the finding of infectious agents using microbial culture. The selection of antibiotics will be based on the type of infectious agents or empirical, doxycycline 100mg BD po. for 14 days, for women with negative microbial culture. Endometrial biopsy will be repeated at the same time point after antibiotic treatment for women with CE. For persistent subjects with negative culturing, ciprofloxacin 500mg, BD po., and metronidazole 400mg TDS po. for 14 days will be used. The treatment will be repeated for three courses at maximum for women with persistent CE according to their willingness.

• Study Type: Observational
• Enrollment (Estimated): 175

Contacts and Locations

• Study Contact: Name: Stacey Wong, Bsc; Phone Number: 35051764; Email: staceywong@cuhk.edu.hk
• Study Contact Backup: Name: Jacqueline Pui Wah Chung, MBBS; Phone Number: 35051764; Email: jacquelinechung@cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • The Chinese University of Hong Kong
    • Contact: PUI WAH JACQUELINE CHUNG, MBBS; Phone Number: +852 35051537; Email: jacquelinechung@cuhk.edu.hk
    • Contact: Stacey Wong, Bsc; Phone Number: +852 35051764; Email: staceywong@cuhk.edu.hk
    • Principal Investigator: PUI WAH JACQUELINE CHUNG, MBBS
    • Sub-Investigator: TAO ZHANG, MBBS
    • Sub-Investigator: JING XI JOSHUA LI, MBBS
    • Sub-Investigator: WAI YIN NG, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects will be identified and recruited from the miscarriage clinic by clinicians and research assistants and research nurse.

Description

Inclusion Criteria:

• Women with a history of 2 or more consecutive miscarriages before 24 weeks of gestation
• Women aged 20-45 years old

Exclusion Criteria:

• Uncorrected uterine anomalies, such as the septate or bicornuate uterus, fibroids (submucous/intramural)
• Untreated hydrosalpinx
• Antiphospholipid syndrome
• Known clinical autoimmune disease
• Undergoing immunotherapy
• Abnormal thyroid function
• Abnormal karyotyping of couples
• Known immunodeficiency pathologies such as diabetes or HIV
• Currently taking other antibiotics or other trial medications or TCM;
• Currently or previously involved in other clinical trials with medication intake;
• Those with active pelvic inflammatory disease or suspicion of infection etc.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Observational study; Women with recurrent miscarriage would be invited to do endometrial sampling (ES) procedure. The ES will be conducted precisely 7 days after LH surge. It will be obtained using a Pipelle sampler as an outpatient procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of chronic endometritis in local women with unexplained recurrent miscarriage	the incidence of chronic endometritis in local women with unexplained recurrent miscarriage	31 January 2027

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate the spectrum of endometrial microorganisms associated with chronic endometritis in this population	Investigate the spectrum of endometrial microorganisms associated with chronic endometritis in this population	31 January 2027
Assess the clinical pregnancy outcomes between cured CE group and non-CE group	Assess the clinical pregnancy outcomes in both cured CE group and non-CE group	31 January 2027

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Jacqueline Pui Wah CHUNG, MBBS, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: November 30, 2023
• First Submitted That Met QC Criteria: November 30, 2023
• First Posted (Actual): December 8, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 18, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: antibiotics; chronic endometritis; unexplained recurrent miscarriage women
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Adnexal Diseases; Pelvic Inflammatory Disease; Recurrence; Abortion, Spontaneous; Abortion, Habitual; Endometritis
• Other Study ID Numbers: 2023.526

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