Transvaginal Ultrasound-guided Culdocentesis for Peritoneal Fluid Cytokines in Patients With Possible Superficial Endometriosis But no Ultrasound-diagnosed Ovarian or Deep Endometriosis (SPG)

Introduction Endometriosis is a common benign disease characterized by the growth of uterine cells outside of the uterus, causing various forms of pelvic pain and/or difficulty with conceiving a pregnancy, amongst other symptoms. Endometriosis most commonly occurs in the forms of Superficial Endometriosis (SE), Deep Endometriosis and Ovarian Endometriosis (Endometrioma) (OE). Ultrasound diagnosis of DE and OE has become more reliable with advances in ultrasound technology, technique and expertise leading to decreased diagnosis time for patients and allowing for better optimization of surgeries if required. SE, however, lacks any reliable non-invasive diagnosis methods.

SE is the most common form of endometriosis and is defined as a disease that lines the peritoneum and is small and superficial in nature, leading to chronic inflammation, infertility, and pain. SE is difficult to visualize on ultrasound due to its size and alignment with tissue, requiring fluid in order expand the pelvis and partially suspend these small lesions, allowing them to be diagnosed through ultrasound. Leonardi et al. observed that in some patients, a physiologic change occurs whereby fluid fills the pouch of Douglas (POD) allowing increased visualizing during ultrasound. This led to the development of Saline-infused sonoPODgraphy (SPG), a novel method utilizing modified commonly used ultrasound techniques called saline-infusion sonohysterography (SIS) and hysterosalpingo-contrast-sonography (HyCoSy), to reliably visualize the POD. The ability to visualize the POD is important as SE is often deposited in the POD.

Biomarkers are also an active area of research in endometriosis diagnosis. There are possible biomarkers that have been identified in the peritoneal fluid of people with endometriosis, including Tumour Necrosis Factor (TNF) and interleukin-6 (IL-6). Indeed, a landmark biomarker study in 2002 demonstrated that TNF in peritoneal fluid had a 100% sensitivity for identifying women with endometriosis. However, this finding has never been further evaluated or validated, even though there is evidence of TNF involvement in endometriosis development. Recently, insulin-like growth factor 1 (IGF-1) has been noted to be elevated in the peritoneal fluid of people with endometriosis compared to those without. Further, IGF-1 has also been found to contribute to the development of abnormal nerves, which may explain the link between endometriosis and pain.

The previous work with POD imaging combined with the knowledge of endometriosis biomarkers leads to the question: Can these non-invasive diagnostic methods be combined to diagnose superficial endometriosis accurately and consistently. We hypothesize that using a combined approach of SPG and biomarker analysis to diagnose superficial endometriosis will provide sufficient evidence to support a large multi-centre international diagnostic accuracy trial.

Technical Study Summary