Senescent Endometrial Cells in Patients with Thin Endometrial Lining

NCT06450301 | Recruiting

• 1 other identifier: 3533
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to determine if thin endometrial lining that is unresponsive to estrogen might be associated with the presence of senescent cells in patients following long-term use of oral contraceptives. The main question it aims to answer is: Are there any senescent cells present in thin endometrial lining? During the luteal phase of the cycle, participants will will undergo:

• Gynecologic US to measure the endometrial lining thickness and pattern.
• Endometrial biopsy with Pipelle catheter

Conditions

Asherman's Syndrome; Thin Endometrial Lining; Cell Senescence

Outcome Measures

Primary Outcomes (1)

• Senescent cells presence

  Percentage of senescent cells in the endometrial biopsies of women with thin endometrium compared to the control group biopsies.

  Through study completion, an average of 3 years.

Study Arms (3)

Thin endometrial lining

Patients following long-term use of oral contraceptives with known thin endometrial lining (less than 7mm, confirmed in at least two cycles and unresponsive to estrogen-induced growth). We will ask each woman to undergo an endometrial biopsy as part of the study during their luteal phase.

Procedure: Endometrial Biopsy

Asherman's syndrome

Patients with Asherman's syndrome following Dilation and curettage (D\&C). We will ask each woman to undergo an endometrial biopsy as part of the study during their luteal phase.

Procedure: Endometrial Biopsy

Control

Patients already scheduled to undergo an endometrial biopsy for infertility management. We will ask each woman to undergo an endometrial biopsy as part of the study during their luteal phase. In some cases, we may be able to access archived endometrial samples from women in the control group who agree to participate and who have already had an endometrial biopsy.

Procedure: Endometrial Biopsy

Interventions

Endometrial Biopsy PROCEDURE

An endometrial biopsy is the removal of a small piece of tissue from the endometrium, which is the lining of the uterus. Endometrial biopsies are commonly done to check for the window of implantation, to determine ovulation or for enhancing implantation (procedure called endometrial scratching). For this purpose, we will use a "Pipelle" catheter. This procedure is very common in gynecologic practice and generally considered safe. In most of the cases this procedure is indicated for evaluation of irregular vaginal bleeding, vaginal bleeding in post-menopausal women and for infertility related problems (recurrent implantation failures for example).

Asherman's syndrome; Control; Thin endometrial lining

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

We intend to recruit 30 patients following long-term use of oral contraceptives with known thin endometrial lining (less than 7mm, confirmed in at least two cycles and unresponsive to estrogen-induced growth). We will also recruit 20 women with Asherman's syndrome following D\&C. We will ask each woman to undergo an endometrial biopsy as part of the study. As a control group, we will recruit 50 patients already scheduled to undergo an endometrial biopsy for infertility management (EMMA testing, endometrial scratching for IVF cycles). Endometrial biopsies are standard procedures during infertility investigations. In some cases, we may be able to access archived endometrial samples from women in the control group who agree to participate and who have already had an endometrial biopsy.

You may qualify if:

• Age 18-39
• BMI - up to 35
• Thin endometrium after OCP use
• Asherman's syndrome
• Women already undergoing endometrial biopsy for infertility testing (eg. EMMA testing)
• Women with archived endometrial biopsy samples

You may not qualify if:

• Women with systemic disease (Rheumatic disease, DM)
• Women with coagulopathies
• Women with active pelvic inflammatory process
• Uterine anomalies
• Pregnant women
• Any hormonal contraception use or IUD

Sponsors & Collaborators

• Trio Fertility: lead

Study Sites (1)

Trio Fertility

Toronto, Ontario, M5G 2K4, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

We will measure the percentage of senescent cells in endometrial biopsies by Sudan Black-B (SBB) immunohistochemistry, since this is a specific marker of cell senescence and can be performed on formalin fixed, paraffin-embedded tissue. This assay also allows us to test archived samples for women in the control group who have already had an endometrial biopsy. We will also freeze part of the endometrial biopsy sample for RNA extraction for senescent biomarker expression (BMI-1, p16lnka4, p14ARF, Cyclin-D1, and CDK4 by RT-PCR) and protein determination (western blotting) for confirmation of the SBB staining results

MeSH Terms

Conditions

Gynatresia

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientific Director, MD, FRCSC, REI

Study Record Dates

• First Submitted: May 28, 2024
• First Posted: June 10, 2024
• Study Start: September 11, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: November 21, 2024

Record last verified: 2024-11

Locations

CA (1)