The etiopathogenesis of endometriosis is a multifactorial process resulting in a heterogeneous disease. Considering that endometriosis etiology and pathogenesis are still far from being fully elucidated, the current review aims to offer a comprehensive summary of the available evidence. We performed a narrative review synthesizing the findings of the English literature retrieved from computerized databases from inception to June 2019, using the Medical Subject Headings (MeSH) unique ID term “Endometriosis” (ID:D004715) with “Etiology” (ID:Q000209), “Immunology” (ID:Q000276), “Genetics” (ID:D005823) and “Epigenesis, Genetic” (ID:D044127). Endometriosis may origin from Müllerian or non-Müllerian stem cells including those from the endometrial basal layer, Müllerian remnants, bone marrow, or the peritoneum. The innate ability of endometrial stem cells to regenerate cyclically seems to play a key role, as well as the dysregulated hormonal pathways. The presence of such cells in the peritoneal cavity and what leads to the development of endometriosis is a complex process with a large number of interconnected factors, potentially both inherited and acquired. Genetic predisposition is complex and related to the combined action of several genes with limited influence. The epigenetic mechanisms control many of the processes involved in the immunologic, immunohistochemical, histological, and biological aberrations that characterize the eutopic and ectopic endometrium in affected patients. However, what triggers such alterations is not clear and may be both genetically and epigenetically inherited, or it may be acquired by the particular combination of several elements such as the persistent peritoneal menstrual reflux as well as exogenous factors. The heterogeneity of endometriosis and the different contexts in which it develops suggest that a single etiopathogenetic model is not sufficient to explain its complex pathobiology.

BACKGROUND: Adhesion-related readmissions are frequent sequelae to gynaecological surgery. Attempts to prevent adhesions by separating healing peritoneal surfaces include site-specific barriers and hydroflotation by instilled solutions. Rapid absorption limits the effectiveness of solutions such as Ringer's lactated saline (RLS). This pilot study assessed the safety, tolerability and preliminary effectiveness of a non-viscous, iso-osmolar solution of 4% icodextrin, an α-1,4 glucose polymer with prolonged intraperitoneal residence, in reducing adhesions after laparoscopic gynaecological surgery. METHODS: Women aged │18 years, requiring laparoscopic adnexal surgery (n = 62), were entered into a randomized, open-label, assessor-blinded, multicentre study to compare 4% icodextrin with RLS. Treatments were coded in blocks of four with equal randomization to each group, and pre-allocated to consecutively numbered patients. At least 100 ml per 30 min was used for intra-operative lavage, with 1 l instilled post-operatively. Per protocol analysis included all eligible patients (n = 53); reformation analysis required one or more baseline adhesion (n = 42). Incidence, extent and severity of post-operative adhesions were assessed at second-look laparoscopy after 6–12 weeks. Procedures were video-taped for third party, blinded assessment. RESULTS: Safety and tolerability (laboratory variables, adverse events, clinical follow-up) were good with no difference between treatments. A shift analysis of incidence-ranked adhesions (n = 53) showed apparent improvements in more patients with icodextrin than RLS (37 versus 15%; not significant). Adhesion score reduction (n = 42) was more frequent in icodextrin- than RLS-treated patients: incidence (52 versus 32%), extent (52 versus 47%), and severity (65 versus 37%). Despite greater baseline adhesions, median reformation was less after icodextrin (24%) than RLS (60%). The pilot study group sizes were not powered for statistical significance. CONCLUSIONS: In this preliminary study, 4% icodextrin lavage plus instillation was well tolerated and reduced adhesion formation and reformation following laparoscopic gynaecological surgery. A Phase III pivotal study is currently in progress.

Deep endometriosis has been defined as endometriosis infiltrating deeper than 5 mm under the peritoneum. A model for the development and propagation of endometriosis is presented. Subtle and non-pigmented lesions are suggested to occur intermittently in all women. Infiltration occurs generally to a few millimeters of depth only, and these lesions become typical, burnt out lesions. In some 20% of women, severe endometriosis develops either as deeply infiltrating disease or as cystic ovarian disease. Arguments are given to consider deep endometriosis and cystic ovarian endometriosis as two specific entities of endometriotic disease. A possible causal relationship with dioxin pollution is discussed. Diagnosis of deep endometriosis is made by clinical examination and palpation during surgery. Clinical examination during menstruation and CA-125 concentrations in plasma are useful to help in the diagnosis of smaller deep lesions. Surgical excision can be carried out by laparoscopy, laparotomy or vaginally using sharp dissection, electrosurgery or with the use of a CO₂ laser. Excision is the treatment of choice because of a high pregnancy rate, a complete cure of pain in most women, and a low recurrence rate. Medical treatment is probably less effective to treat infertility, but highly effective in relieving pelvic pain. Medical therapy, by luteinizing hormone-releasing hormone agonists, danazol, or gestrinone, also seems useful as a pretreatment for surgery. The choice of treatment will therefore depend on the local expertise with minimal invasive surgery, certainly if a first excision has been incomplete and pain symptoms recur.