Study Goal:

This pilot study wants to find out if using a menstrual cup can be a good, non-invasive way to collect samples from the lining of the uterus (called the endometrium) to help screen for endometrial cancer. This is especially important for women who have a higher chance of getting this cancer, such as those with a genetic condition called Lynch syndrome.

Main Questions the Study Will Answer:

1. Can a menstrual cup collect enough uterine lining (endometrial tissue) for doctors to examine under a microscope?
2. Are the samples from the menstrual cup as useful for diagnosis as samples taken using the usual method (called an endometrial biopsy or EMB)?
3. Is using a menstrual cup at home easy, effective, and comfortable for participants?
4. Can scientists grow small lab models of the uterus (called organoids) from the menstrual cup samples and from biopsy samples?

What Will Happen in the Study:

• Participants will use a menstrual cup at home to collect menstrual blood.
• They will also have a standard endometrial biopsy done by a healthcare provider.
• After both collections, participants will fill out a short survey about how comfortable and easy it was to use the menstrual cup.

What the Study Will Measure:

• Feasibility: How well participants are able to use the menstrual cup and send in the sample.
• Sample Quality: Whether the menstrual cup collects enough good-quality tissue for testing, and how it compares to biopsy samples.
• Participant Experience: How women feel about using the menstrual cup, based on the survey.
• Lab Testing: Whether researchers can successfully grow endometrial organoids from both types of samples.

Why This Study Matters: If this method works, it could offer a gentler, more convenient way for women to get checked for endometrial cancer-especially those who need regular screening. It could also make it easier to collect samples for research and improve early detection of cancer.

Menstrual Cup for Early Endometrial Cancer Detection in Lynch Syndrome (SCREEN-CUP) The study entails two parts that will be conducted one after each other.

1. Pre-pilot study Pre-pilot study including 5 menstruating females who will provide a one-time menstrual cup-based endometrial collection for the generation of organoids and for a pathological evaluation of endometrial specimen from menstrual fluid.

   After optimizing the study protocol in the pre-pilot study period, the main study will be conducted.

2. Main pilot study Prospective feasibility study including 20 female Lynch syndrome (LS) carriers undergoing annual endometrial biopsy for endometrial cancer surveillance or suspected endometrial pathology will provide a one-time menstrual cup-based endometrial collection and endometrial biopsy specimen. One study aim is to evaluate the comparability and quality of the menstrual cup-based endometrial collection with the EMB sample from the same patient. For the second study aim, endometrial sample collected with the menstrual cup and EMB will be used and compared for organoid generation. Patient satisfaction and feasibility will be monitored through patient and provider questionnaires.

Pre-pilot study

Inclusion criteria:

• Individuals over the age of 18
• Menstruating

Exclusion criteria:

• Levonorgestrel intrauterine device (IUD) in situ or removed within the last 30 days prior to sample collection
• Patients with prior endometrial ablation
• Prior history of endometrial cancer or endometrial intraepithelial neoplasia
• History of germline pathologic germline variant in MLH1, MSH2, MSH6, PMS2, or EPCAM
• Known allergy against menstrual cup material (silicone)

Main Study Inclusion criteria

• LS carrier with a pathogenic or likely pathogenic germline variant in MLH1, MSH2, MSH6, PMS2, or EPCAM
• Individuals over the age of 18
• Planned screening EMB
• Menstruating
• Ability to give consent

Exclusion criteria:

• Current pregnancy
• Levonorgestrel IUD in situ or removed within the last 30 days prior to sample collection
• Patients with prior endometrial ablation
• Prior history of endometrial cancer
• Known allergy against menstrual cup material (silicone)

De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a data use agreement. The protocol and statistical analysis plan will be made available to on clinicaltrials.gov only as required by federal regulations or as a condition of awards and agreements supporting research.

Beginning 12 months after publication of the primary results, for a period of up to 3 years.

Researchers must submit a methodologically sound proposal and demonstrate an IRB-approved protocol. Requests maybe directed to the sponsor investigator or designee. A formal data use agreement will be required prior to access.

Only one part of the outcome assessor will be masked: the pathologist evaluating the EMB specimen and menstrual cup-collected specimen.