Official Title

Case-Control Study II of Genomic Markers in Menstrual Blood for Diagnosis of Uterine Disorders

Purpose

This proposal will identify and evaluate genomic biomarkers found in menstrual fluid for the development of a non-invasive diagnostic test for uterine disorders such as endometriosis and adenomyosis, including staging and classification of disease. A non-invasive test for uterine disorders would fundamentally change how these diseases are diagnosed and treated, and it would greatly reduce the time to diagnosis, allowing for earlier interventions and better prognosis for patients with disease. In order to further identify and evaluate the performance of genomic markers in menstrual fluid, we will enroll patients with confirmed endometriosis/adenomyosis in order to ?1) Evaluate previously-identified biomarkers for the detection of endometriosis in menstrual fluid, 2) Identify and evaluate previously-identified and novel biomarkers that can be utilized to stage and classify endometriosis, 3) Determine sensitivity and specificity of the biomarkers for each indication in an independent cohort. 4) We will also collect a small cohort of samples that will be used to isolate specific cell types in menstrual fluid that will be used to culture cells for downstream therapeutic drug screening. We will provide informed consent / assent and enroll approximately 2,000 participants for this study from virtual consent / assents, private gynecological surgery clinics and university hospitals, where study staff personnel will recruit patients who may be going in for surgery for diagnosis of endometriosis. We will offer nominal compensation in the form of a gift card for each sample contribution to the study as a retention tool.?We will recruit patients who may be going in for laparoscopic surgery for diagnosis or treatment of endometriosis, or people with imaging confirmation of adenomyosis, fibroids, endometriomas or polycystic ovarian syndrome (PCOS) with primary symptoms being chronic pelvic pain and/or infertility. In addition to patients who are likely to have endometriosis, a negative control population will be recruited. This may include people who have had the classic symptoms such as pelvic pain, heavy menstrual bleeding, infertility, etc. and have had surgery where endometriosis was not found. It may also include those who have had surgical evaluation for a primary reason other than endometriosis (cysts, fibroids, PCOS, tubal ligation, etc), and endometrial tissue was not found. In addition to these surgery cohorts, people who have the above-mentioned symptoms, are not having surgery, and are likely to not have endometriosis may be recruited. For patients undergoing surgery, we will collect a minimum of 2 light absorbency tampons (1 pre- and 1 post-surgery). We may also collect a menstrual cup sample and a blood draw. For patients not undergoing surgery or with a diagnosis of one of the aforementioned conditions confirmed via imaging, we will collect at least 1 light absorbency tampon. We may also collect a menstrual cup sample and a blood draw. Patient will fill out a questionnaire and a post-surgical pathology report will be provided by the clinic. For tampon samples, we will use up to four sequencing approaches: methylation sequencing, RNA-transcriptional sequencing, miRNA sequencing, and 16s microbial sequencing. For menstrual cup samples, we will create and maintain cell cultures of isolated menstrual cell types for therapeutic drug screening in a cell culture model, as well as downstream transcriptional and small RNA sequencing to identify changes in gene expression by cell type. Using laparoscopy results, patient symptomology and biomarker measurements from this study, we will implement algorithms that combine biomarkers for diagnosis, disease sub-type classification, and staging.

Detailed Description

Eligibility Criteria

Inclusion Criteria

1.  Persons 14-17 years of age who can provide patient assent and guardian consent / assent. ; 2.  Persons over 18 years of age who can provide informed consent. ; 3.  Persons willing to undergo vaginal specimen collection with a tampon. ; 4.  Persons willing to adhere to study visit time requirements. ; 5.  Persons with chronic pelvic pain, abnormal uterine bleeding, infertility, or suspected of a reproductive disorder that has similar symptomology to endometriosis. ; 6.  Persons with a suspected uterine disorder as evaluated who may be scheduled for laparoscopic surgery or being evaluated for fertility treatment. ; 7.  Persons who undergo surgery for a primary reason other than endometriosis and are confirmed negative by either surgeon or pathology ; 8.  Persons with fibroids, endometriomas confirmed by either imaging, histology, or PCOS confirmed by a clinician

Exclusion Criteria

1.  Persons who cannot tolerate collection of vaginal specimens through use of a light absorbency tampon; 2.  Persons who are pregnant; 3.  Persons who are menopausal (those without a regular period) or post-menopausal.; 4.  Persons unable to provide informed consent / assent.; 5.  Persons on contraceptives that have stopped their period (those on contraceptives who still have their period are eligible).

Keywords and/or Specific Medical Conditions

Uterine Disorders

Endometriosis

Obstetrics and Gynecology

Sponsors

NextGenJane