Senescent Endometrial Cells in Patients with Thin Endometrial Lining

Is Thin Endometrial Lining Associated with Senescent Endometrial Cells

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

Study Overview

• Status: Recruiting
• Conditions: Asherman's Syndrome; Thin Endometrial Lining; Cell Senescence
• Intervention / Treatment: Procedure: Endometrial Biopsy

Detailed Description

The investigators hypothesized that senescent cells in the endometrium may be the cause of the failure of thin endometrium to respond to normal growth stimuli such as estrogen.

The outcome that research team anticipate to measure is the percentage of senescent cells in the endometrial biopsies of women with thin endometrium compared to the control group biopsies.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2K4
      • Recruiting
      • Trio Fertility
      • Contact: Yasaman Sadeghi, M.Sc.; Phone Number: 2268 416-506-0804; Email: yasamans@triofertility.com
      • Contact: Robert. F. Casper, Dr.; Phone Number: 3228 416-506-0804; Email: casper@lunenfeld.ca
      • Contact: Robert. F. Casper, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• 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.

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; 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; 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; 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).
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; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: Trio Fertility

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: May 28, 2024
• First Submitted That Met QC Criteria: June 3, 2024
• First Posted (Actual): June 10, 2024

Study Record Updates

• Last Update Posted (Estimated): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 18, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Gynatresia
• Other Study ID Numbers: 3533

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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