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

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.

The role of angiogenic factors in the management of preeclampsia.

Preeclampsia is a pregnancy disorder causing substantial maternal and fetal morbidity and mortality. In the UK, its diagnosis currently depends upon new onset hypertension and proteinuria. There is a clinical need for enhanced screening to prevent unnecessary resource use and improve outcomes. Here, the current practice in preeclampsia diagnosis will be summarized, with assessment of the evidence that angiogenic factors could improve its management. Although the combination of new onset hypertension and proteinuria define and hence diagnose the disorder, separately they are poorly predictive. Preeclampsia is ultimately a placental disease caused by syncytiotrophoblast dysfunction. The angiogenic factors placental growth factor, soluble fms-like tyrosine kinase 1 and soluble endoglin, all originating at least in part from the syncytiotrophoblast, are biomarkers with predictive potential for preeclampsia and related adverse outcomes. Recent work with the soluble fms-like tyrosine kinase 1/placental growth factor ratio has identified key measurement cutoffs, with one having a high negative predictive value for preeclampsia. The soluble fms-like tyrosine kinase 1/placental growth factor ratio seems particularly promising as a screening measure, able to predict accurately the short-term absence of preeclampsia and suggest the likelihood of adverse events within 4 weeks. The ratio could be used to allocate specific management plans to patients according to risk. An understanding of angiogenic factors may also lead to new therapeutic options for a condition currently only curable by delivery, although it must be remembered that the factors are markers of underlying syncytiotrophoblast stress, which would not be resolved by targeting them.