Vascularisation in Deep Endometriosis: A Systematic Review with Narrative Outcomes

Cells. 2023 May 5;12(9):1318. doi: 10.3390/cells12091318.


Deep endometriosis (DE) is the most severe subtype of endometriosis, with the hallmark of lesions infiltrating adjacent tissue. Abnormal vascularisation has been implicated in contributing to endometriosis lesion development in general, and how vascularisation influences the pathogenesis of DE, in particular, is of interest. This systematic review followed the PRISMA guidelines to elucidate and examine the evidence for DE-specific vascularisation. A literature search was performed using MEDLINE, Embase, PubMed, Scopus, Cochrane CENTRAL Library and Europe PubMed Central databases. The databases were searched from inception to the 13 March 2023. A total of 15 studies with 1125 patients were included in the review. The DE lesions were highly vascularised, with a higher microvessel density (MVD) than other types of endometriotic lesions, eutopic endometrium from women with endometriosis and control tissue. Vascular endothelial growth factor, its major subtype (VEGF-A) and associated receptor (VEGFR-2) were significantly increased in the DE lesions compared to superficial endometriosis, eutopic endometrium and control tissue. Progestin therapy was associated with a significant decrease in the MVD of the DE lesions, explaining their therapeutic effect. This review comprehensively summarises the available literature, reporting abnormal vascularisation to be intimately related to the pathogenesis of DE and presents potentially preferential therapeutic targets for the medical management of DE.

Keywords: HIF-1A; VEGF-A; deep endometriosis; endometriosis; microvessel density; systematic review; vascularisation.

Publication types

  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endometriosis* / metabolism
  • Endometrium / metabolism
  • Female
  • Humans
  • Neovascularization, Pathologic / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factors / metabolism


  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Grants and funding

The authors would like to acknowledge Royal Liverpool University Hospital’s support for SGP and JW’s clinical research fellowship; DKH is supported by the Wellbeing of Women’s Project grant (RG2137).