Protocol for a longitudinal, prospective cohort study investigating the biology of uterine fibroids and endometriosis, and patients' quality of life: the FENOX study

Abstract

Introduction: Millions of women suffer from the consequences of endometriosis and uterine fibroids, with fibroids the cause for over 50% of hysterectomies in the USA, and direct costs for their treatment estimated at between US$4 and US$9 billion. Endometriosis commonly affects millions of women worldwide predominantly during reproductive age, with severe menstrual and non-menstrual pain and subfertility the main symptoms. Due to the 'unhappy triad' of endometriosis-lack of awareness, lack of clinically relevant biomarkers and the unspecific nature of symptoms-women wait on average for 8-12 years before the definitive endometriosis diagnosis is made. Treatment options for both conditions are not satisfactory at the moment, especially with a view to preserving fertility for the women and families affected. In the Fibroids and Endometriosis Oxford (FENOX) study, we combine the investigation of fibroids and endometriosis, and plan to collect high-quality tissue samples and medical data of participants over a time frame of 5 years after surgical intervention.

Methods and analysis: Biological samples such as blood, saliva, urine, fat, peritoneal fluid and-if found-endometrial tissue or fibroids as well as detailed clinical and intraoperative data will be collected from women undergoing surgery and participating in the study after informed consent. We plan to recruit up to 1200 participants per disease arm (ie, endometriosis and uterine fibroids) over 5 years. Participants will fill in detailed and validated questionnaires on their medical history and quality of life, with follow-ups for 5 years. Enrolment started on 2 April 2018, and FENOX will close on 31 March 2028. We will analyse the biological samples using state-of-the-art molecular biology methods and correlate the findings with the medical records and questionnaire data.

Ethics and dissemination: The findings will be published in high-ranking journals in the field and presented at national and international conferences.

Trial registration number: ISRCTN13560263.

Keywords: gynaecology; reproductive medicine; subfertility; surgery.

Figure 1

Participant groups and procedures. The participants will be allocated into case or control groups and tissues will be sourced according to the course of clinical intervention: Participants with fibroids treated by transcervical resection (TCRF) will not undergo abdominal surgery, while abdominal surgery is necessary if the fibroids are treated by laparoscopy, open myomectomy or hysterectomy. In these cases, peritoneal fluid can be obtained in addition to the tissue samples (fibroid, myometrium, endometrium). Endometriosis patients will undergo laparoscopy. If found without endometriosis, they will be grouped with the controls, who are women undergoing surgery for other, unrelated conditions (eg, tubular ligation).

Figure 2

Flow chart of participant data and tissue sampling. Consented participants of the different arms of the study donate pre-operative samples and fill in a baseline questionnaire. They can donate a range of tissue samples according to their condition and treatment mode (eg, fibroids or endometriotic tissue, peritoneal fluid), and are asked to repeatedly fill in follow-up questionnaires on their condition and quality of life, so that the clinical findings can be correlated with the outcome years later.