Confounding Factors of Chronic Endometritis in Women With Reproductive Failure

The aim of the study is to investigate the confounding factors of chronic endometritis and therapeutic benefits of antibodies targeting plasma cells in women with reproductive failure.

Study Overview

• Status: Recruiting
• Conditions: IVF
• Intervention / Treatment: Other

Detailed Description

Eligible women, based on the inclusion and exclusion criteria, will be recruited from the IVF and/ or miscarriage clinic in the Prince of Wales Hospital/ CUHK medical centre (CUMC). 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. In artificial cycles, 6mg estradiol will be given daily orally from day 2 of the menstrual cycle for 14+/-1-2 days. Transvaginal ultrasound will be performed on day 14 of the estrogen therapy to assess the endometrial thickness and to exclude ovarian activity. If endometrial thickness is ≥8 mm, plasma progesterone level is < 4nmol/L, progesterone will be commenced using either Endometrin (Ferring, Saint-Prex, Switzerland) 100 mg TDS vaginally. ES will be obtained using a Pipelle sampler as an outpatient procedure. The ES will be obtained precisely 5 days after progesterone supplementation.

Immunohistochemical staining will be used to determine plasma cells by using a mouse antihuman monoclonal primary anti-CD138 antibody and anti-CD38 antibody. The total number of plasma cell present in the stroma of the entire specimen will be determined and expressed as plasma cell count per unit area of the specimen. If CE is present, antibiotics will be given following the guideline from the Hospital Authority (HA). Then ES will be taken again to be re-examined by histology and microbiology.

• Study Type: Observational
• Enrollment (Estimated): 720

Contacts and Locations

• Study Contact: Name: Stacey Wong, Bsc; Phone Number: 35051764; Email: staceywong@cuhk.edu.hk
• Study Contact Backup: Name: JacquelinePui 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
    • Sub-Investigator: Karen NG, MBBS
    • Contact: Stacey Wong, Bsc; Phone Number: +852 35051764; Email: staceywong@cuhk.edu.hk
    • Principal Investigator: PUI WAH JACQUELINE CHUNG, MBBS
    • Sub-Investigator: NGA PING PATRICIA IP, MBBS
    • Sub-Investigator: CHI CHIU RONALD WANG, MBBS
    • Sub-Investigator: TAO ZHANG, MBBS
    • Sub-Investigator: JING XI JOSHUA LI, MBBS
    • Sub-Investigator: LAI PING CHEUNG, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

Inclusion criteria:

1. Age 20-45 years;
2. Women with a history of 2 or more consecutive miscarriages before 24 weeks of gestation12; or
3. Women who failed to conceive after unprotected intercourse for one year; or
4. Women who failed failure to achieve a clinical pregnancy after two consecutive cycles of IVF, ICSI or frozen embryo replacement cycles where the cumulative number of transferred embryos is no less than four for day-2 embryos and no less than 2 for day-5 embryos (blastocysts), with all embryos being of good quality.

Exclusion criteria

1. Uncorrected uterine anomalies, such as the septate or bicornuate uterus, fibroids (submucous/intramural);
2. Untreated hydrosalpinx;
3. History of antiphospholipid syndrome;
4. Known clinical autoimmune disease;
5. Undergoing immunotherapy;
6. Abnormal thyroid function;
7. Abnormal karyotyping.
8. Those with active pelvic inflammatory disease or suspicion of infection etc.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Observational group; Patients have 2 or more miscarriage or repeated implantation failure (RIF), or infertile women would be invited to do endometrial sampling (ES) procedure. The ES will be conducted randomly or when women undergo hysteroscopy or obtained 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
Live birth rate	compare the brith rate between the group and cohort	31 December 2027

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the pregnancy rate between groups	compare the general pregnancy rate in women with or without CE	31 March 2028
Compare the miscarriage rate between groups	compare the miscarriage rate in women with or without CE	31 March 2028
Compare the implantation rate between groups	Compare the implantation successful rate in women with or without CE	31 March 2028

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): January 26, 2023
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: November 3, 2022
• First Submitted That Met QC Criteria: November 10, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 27, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: IVF; infertility; confounding factors; chronic endometritis; reproductive failure; infertility women
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Adnexal Diseases; Pelvic Inflammatory Disease; Endometritis
• Other Study ID Numbers: 2022.339

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
• product manufactured in and exported from the U.S.: No