Fibroid-Associated Heavy Menstrual Bleeding: Correlation Between Clinical Features, Doppler Ultrasound Assessment of Vasculature, and Tissue Gene Expression Profiles

Abstract

Despite the prevalence of uterine fibroids (Fs), few studies have investigated the links between clinical features and the cellular or molecular mechanisms that drive F growth and development. Such knowledge will ultimately help to differentiate symptomatic from asymptomatic Fs and could result in the development of more effective and individualized treatments. The aim of this study was to investigate the relationship between ultrasound appearance, blood flow, and angiogenic gene expression in F, perifibroid (PM), and distant myometrial (DM) tissues. We hypothesized that angiogenic gene expression would be increased in tissues and participants that showed increased blood flow by Doppler ultrasound. The study was performed using Doppler ultrasound to measure blood flow prior to hysterectomy, with subsequent tissue samples from the F, PM, and DM being investigated for angiogenic gene expression. Overall, PM blood flow (measured as peak systolic velocity [PSV]) was higher than F blood flow, although significant heterogeneity was seen in vascularity and blood flow between different Fs and their surrounding myometrium. We did not find any correlation between PSV and any other clinical or molecular parameter in this study. We identified 19 angiogenesis pathway-related genes with significant differences in expression between F and DM, and 2 genes, matrix metalloproteinase 9 (MMP9) and Neuropilin 2 (NRP2), that were significantly different between F and PM. These results are consistent with subtle differences between PM and DM. Understanding the differences between symptomatic versus asymptomatic Fs may eventually lead to more effective treatments that directly target the source of heavy menstrual bleeding.

Fibroid vascularisation assessed with three‐dimensional power Doppler ultrasound is a predictor for uterine fibroid growth: a prospective cohort study

“…The capsule of the fibroid surrounds the fibroid and at the same time can be seen as a different entity. It has been a subject of interest and has been studied from different perspectives using different techniques (histopathological, immunohistochemical, [angiogenic] gene expression, growth factors, neurotransmitters, imaging techniques) . In this study no correlation was found between fibroid capsule vascularisation and fibroid growth.…”

Doppler sonography of perifibroid and intrafibroid arteries of uterine leiomyomas

“…Tsiligiannis et al [ 32 ] reported that the mean PSV was significantly higher in the perifibroid region than within the fibroids (30.2 vs. 12.0 cm/s; P <0.001). This is in agreement with our results though we recorded much higher PSV values (54 vs. 45 cm/s; P <0.001), presumably because the leiomyoma nodules in this study are larger.…”

Uterine myoma: еtiology and morphogenesis

“…Кроме того, ЛМ у одной и той же женщины растут различными темпами и обладают разной способностью к регрессу, несмотря на единообразную гормональную и паракринную среду [21]. Более того, такие характеристики, как размер, локализация и выраженность васкуляризации, определяемая ультрасонографически, не коррелируют с ростом миомы, маточным кровотечением или другой симптоматикой [21,22] ПАТОФИЗИОЛОГИЯ МИОМЫ В последние годы в качестве решающих факторов, контролирующих рост опухолей, рассматриваются ангиогенез и васкуляризация [24]. Классические исследования показывают, что миомы матки имеют аномальную сосудистую сеть и, как правило, гораздо менее васкуляризированы, чем окружающий миометрий [25,26,27].…”

“…Авторы предположили, что эта область сосудистой капсулы, вероятно, соответствует периферическому краю хорошо васкуляризированных сосудов, наблюдаемых при УЗИ, и используется как плоскость разграничения тканей при миомэктомии. Недавно также сообщалось, что область «псевдокапсулы» имеет увеличенный кровоток по сравнению с миомой, измеряемый доплеровским ультразвуком [52].…”