Menstrual Cup for Early Endometrial Cancer Detection in Lynch Syndrome

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.

• Menstrual cup use (Device): Menstrual cup use in menstruating women to collect menstrual fluid with the aim to 1) compare the histology to endometrial biopsy samples from the same patient, to 2) investigate the feasibility and clinical utility of a menstrual cup use as a screening method for endometrial cancer and to 3) generate organoids from the menstrual cup samples

Primary outcomes

• Proportion of samples considered adequate for pathologic evaluation [Postprocedural (7-14 days after study visit #2)]: A pathologist will evaluate the menstrual cup-based sample and record its adequacy for pathological evaluation using a questionnaire with binary responses.

Secondary outcomes

• Overall participant satisfaction with menstrual cup collection for endometrial screening. [Periprocedural (on day of study visit #2)]: Participants self-report to questions on overall participant satisfaction with menstrual cup collection for endometrial screening with 5 answer possibilities ranging from "very satisfied" to "very dissatisfied".
• Successful endometrial organoid generation from menstrual cup sample [Postprocedural (5-7 days after study visit #2)]: Successful organoid generation from menstrual cup samples will be assessed by viability assays after 5 days of culture and immunofluorescence imaging to compare cell composition.
• Successful endometrial organoid generation from endometrial biopsy sample (EMB). [Postprocedural (5-7 days after study visit #2)]: Successful organoid generation from EMB samples will be assessed by viability assays after 5 days of culture and immunofluorescence imaging to compare cell composition.
• Provider satisfaction of menstrual cup collection for endometrial cancer screening within this study setting [Through study completion, an average of 1 year.]: Provider self-report on question regarding satisfaction of menstrual cup collection for endometrial cancer screening within this study setting with 5 answer possiblities ranging from "very satisfied" to "very dissatisfied".

Sex: Female, ages: 18 Years to any, accepts healthy volunteers

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)

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• Hewitt SC, Dickson MJ, Edwards N, Hampton K, Garantziotis S, DeMayo FJ. From cup to dish: how to make and use endometrial organoid and stromal cultures derived from menstrual fluid. Front Endocrinol (Lausanne). 2023 Sep 21;14:1220622. doi: 10.3389/fendo.2023.1220622. eCollection 2023. PMID 37810883

• Jessica D St. Laurent, MD, Principal investigator, Brigham and Women's Hospital