Involvement of inflammation in early-stage peritoneal endometriosis

Endometriosis is one of the most frequently encountered benign diseases in gynecology, being the cause of dysmenorrhea, chronic pelvic pain and infertility in more than 35% of women of reproductive age. Decreased quality of life may result not only from symptoms of pelvic pain and infertility, but also from side effects of various medical and surgical treatments. For women with pain, surgery commonly provides temporary relief, but symptoms recur in up to 75% of women within 2 years, and further surgery is needed in many cases. The most widely accepted hypothesis on the origin of peritoneal endometriosis is Sampson’s theory of retrograde menstruation. According to this theory, endometriosis originates from endometrial cells regurgitated through the fallopian tubes, which have the ability to survive, adhere to peritoneum, invade tissues, create a blood supply and proliferate outside their eutopic location. Endometriosis is nowadays considered to be a multifactorial and enigmatic disease. Anatomic, genetic, environmental, hormonal, immunologic and oxidative stress factors have been implicated in the establishment, development, maintenance and progression of endometriotic lesions. Peritoneal endometriosis is a chronic pelvic inflammatory disease, characterized by increased numbers of peritoneal macrophages and their secreted products, such as cytokines, growth and angiogenic factors in peritoneal fluid. Inflammation plays a major role in pain and infertility associated with endometriosis, but is also extensively involved in molecular and cellular processes that lead to peritoneal endometriotic lesion development. The aim of this research project was to better characterize endometriosis-associated inflammation and its involvement in early-stage endometriosis development. In the first part of our study, we focused on three inflammatory pathways implicated in the pathogenesis of endometriosis, highlighting the involvement of peritoneal macrophages: peritoneal iron metabolism, NF-κB activation and prostaglandin biosynthesis. According to available data from our studies and the literature, these three pathways may be linked and potential molecular interactions are considered. The second part of our project was designed to evaluate the impact of treating endometrial cells by proinflammatory cytokines on the adhesion process to mesothelial cells. The establishment and validation of an original in vitro experimental model are also described. A fundamental understanding of the inflammatory response is essential to better target the development of new therapeutic approaches in endometriosis, as well as in other pathogenic processes involving cellular adhesion and inflammation.(MED 3) -- UCL, 201

Laparoscopic observation of spontaneous human ovulation.

We report laparoscopic observation of spontaneous human ovulation, illustrated by protrusion of the mature follicle and oocyte release into the peritoneal cavity

Laparoscopic management of endometriomas using a combined technique of excisional (cystectomy) and ablative surgery.

OBJECTIVE: To describe and evaluate a new technique of laparoscopic treatment of endometriomas that combines excisional and ablative surgery. DESIGN: Descriptive and prospective study. SETTING: Gynecology research unit in a university hospital. PATIENT(S): Fifty-two women under 35 years of age presenting for infertility and/or pelvic pain with endometriomas larger than 3 cm were included in the study. None had undergone any surgery for endometriosis. INTERVENTION(S): A large part of the endometrioma wall was first excised according to the cystectomy technique. After this first step, CO(2) laser was used to vaporize the remaining 10%-20% of the endometrioma wall close to the hilus. MAIN OUTCOME MEASURE(S): The feasibility of this new technique was assessed. Ovarian volume and antral follicle count (AFC) were compared between operated ovaries and nonoperated ovaries of patients with endometriosis and controls (women with male factor infertility). RESULT(S): The combined technique was possible in all cases. The volume of the ovary after the combined technique was similar to that of the contralateral normal ovary, as well as to that observed in infertile women without endometriosis presenting for male factor infertility. The AFC on day 2-5 showed the same number of antral follicles in all subgroups. Histopathology of the excised part of the endometrioma revealed the presence of follicles in only one case (2%). The pregnancy rate was 41% at a mean follow-up of 8.3 months. Recurrence of a small endometrioma was observed in only one case (2%). CONCLUSION(S): The combined technique (stripping and ablation) has proved not to be deleterious to the ovary

Luminescence as a Tool to Assess Pelvic Endometriosis Development in Murine Models.

Classic murine endometriosis models may be insufficient to evaluate the effect of therapeutic agents on endometriosis development, because the process of identification and measurement of induced lesions is often impeded, as implants are small and embedded in murine tissue. In this context, as summarized in the current review, luminescence techniques have proved useful for identifying and visualizing or quantifying endometriotic transplants. They are also a valuable tool for endometrial cell tracking in live animals, yielding further information by adding spatial and temporal dimensions to biological processes in vivo. Such approaches involve transplanting luminescently labeled murine or human endometrium into animals. Two main strategies are applied to label endometrium before injection: use of genetically modified tissue or tissue labeled with a fluorescent dye. Each model has its advantages and disadvantages, the choice of model depends on the study objectives/design (long- or short-term studies, homologous or heterologous model)

Expression of eicosanoid biosynthetic and catabolic enzymes in peritoneal endometriosis.

BACKGROUND Increased peritoneal eicosanoid concentrations have been reported in endometriosis patients and might be important in disease-associated pain and inflammation. Here, we evaluated the expression of key biosynthetic and catabolic enzymes involved in this abnormal eicosanoid production in peritoneal macrophages and endometriotic lesions. METHODS Peritoneal macrophages, endometriotic lesions and matched eutopic endometrium were collected from endometriosis patients (n = 40). Peritoneal macrophages and eutopic endometrium samples were also collected from disease-free women (n = 25). Expression of type IIA secretory phospholipase A(2) (sPLA(2)-IIA), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and 5-lipoxygenase (5-LO) was quantified by real-time PCR, and these five key enzymes were localized by immunohistochemistry. RESULTS sPLA(2)-IIA, COX-2 and mPGES-1 mRNA was significantly increased in peritoneal macrophages of endometriosis patients compared with controls (P = 0.006, P = 0.016 and P = 0.025, respectively). In endometriosis patients, sPLA(2)-IIA, mPGES-1 and 15-PGDH mRNA was significantly enhanced in peritoneal lesions compared with matched eutopic endometrium (P < 0.001, P < 0.001 and P = 0.005, respectively). In eutopic endometrium, a significant decrease in 15-PGDH mRNA was found in the endometriosis group compared with controls (P = 0.023). Finally, sPLA(2)-IIA, COX-2, mPGES-1 and 15-PGDH immunostaining was found mainly in endometrial glands, whereas 5-LO was distributed throughout the glands and stroma. CONCLUSIONS Our study highlights an imbalance between eicosanoid biosynthesis and degradation in endometriosis patients. Both peritoneal macrophages and endometriotic lesions may be involved. Research into new molecules inhibiting biosynthetic enzymes (such as sPLA(2)-IIA and mPGES-1) and/or activating catabolic enzymes (such as 15-PGDH) may prove to be a major field of investigation in the development of targeted medical therapies

Suspicious myometrial mass on ultrasonography and MRI does not necessarily mean a sarcoma on histology

We report an unusual ultrasonographic and magnetic resonance imaging (MRI) presentation of a myometrial mass in a 38-year-old woman hoping to conceive. Hysterectomy had been proposed elsewhere because of the suspicious nature of the mass, but the patient was seeking a second opinion. This atypical formation looked consistent with either hydropic degeneration of a uterine myoma or leiomyosarcoma, but preoperative differential diagnosis was impossible. Laparoscopic tumorectomy was performed and histology confirmed a degenerating uterine myoma. We, therefore, show that unusual ultrasonographic and MRI findings do not necessarily require radical surgery, even if sarcoma cannot be excluded preoperatively, especially in patients who wish to conceiv

Tumor necrosis factor-α and interleukin-1β treatment of endometrial stromal cells does not promote their adhesion to peritoneal mesothelial cells in an in vitro model of early-stage endometriosis

In the present study, we developed an original and reproducible quantitative in vitro model of endometrial cell adhesion to peritoneal mesothelial cells in order to better assess the impact of pro-inflammatory cytokines on early-stage endometriosis development. We demonstrated that pre-treatment with TNF-α and IL-1β does not promote endometrial stromal cell adhesion to peritoneal mesothelial cells

Fertility preservation in women with ovarian endometriosis

Endometriosis is one of the most frequently encountered benign diseases in gynecology. Complete resolution of endometriosis is not yet possible, but therapy has essentially three main objectives: (1) to preserve and improve fertility, (2) to reduce pain, and (3) to delay recurrence for as long as possible. The aim of this paper is to focus on fertility preservation in women with severe endometriosis. In moderate and severe endometriosis, a medico-surgical approach remains the gold standard, but more and more papers are reporting a low ovarian reserve after laparoscopic cystectomy for endometriomas. Indeed, very frequently, normal ovarian tissue is excised together with the endometrioma wall. Ovarian surgery in endometriosis patients should therefore be performed by experienced surgeons in order to both preserve and improve fertility. Preservation of ovarian tissue should be considered in all patients at serious risk of future fertility impairment, particularly before any treatment likely to result in ovarian endometriosis recurrence and/or premature ovarian failure