A prospective randomized clinical trial is needed to confirm our findings but in women with RIF a hysteroscopic evaluation of the uterine cavity to exclude CE should be considered and appropriate antibiotic treatment should be given before submitting the patient to a further IVF attempt.

Endometriosis is one of the most common gynaecologic diseases in women of reproductive age. It is characterized by the presence of endometrial tissue outside the uterine cavity. The women affected suffer from pelvic pain and infertility. The complex etiology is still unclear and it is based on three main theories: retrograde menstruation, coelomic metaplasia, and induction theory. Genetics and epigenetics also play a role in the development of endometriosis. Recent studies have put the attention on the role of oxidative stress, defined as an imbalance between reactive oxygen species (ROS) and antioxidants, which may be implicated in the pathophysiology of endometriosis causing a general inflammatory response in the peritoneal cavity. Reactive oxygen species are intermediaries produced by normal oxygen metabolism and are inflammatory mediators known to modulate cell proliferation and to have deleterious effects. A systematic review was performed in order to clarify the different roles of oxidative stress and its role in the development of endometriosis. Several issues have been investigated: iron metabolism, oxidative stress markers (in the serum, peritoneal fluid, follicular fluid, peritoneal environment, ovarian cortex, and eutopic and ectopic endometrial tissue), genes involved in oxidative stress, endometriosis-associated infertility, and cancer development.

ObjectiveOvarian senescence affects many tissues and produces a variety of symptoms and signs. We hypothesized that estrogens may also influence circulating redox balance by regulating activity of the cellular antioxidative enzyme system. We aimed to explore the impact of surgical estrogen deprivation and replacement (ERT) on the glutathione balance and antioxidant enzymes expression in fertile women.Study designNineteen healthy premenopausal women who underwent total hysterectomy with bilateral salpingo-oophorectomy were evaluated at baseline, 30 days after surgery without ERT and 30 days after ERT. Redox balance was determined by measuring blood reduced (GSH) and oxidized (GSSG) glutathione, as well as the GSSG/GSH ratio. Antioxidant status was evaluated by measuring serum estrogen (E2) levels and mRNA expression of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST) in peripheral blood mononuclear cells.ResultsSerum E2 significantly lowered after surgery, and increased in 12 out of 19 patients after 30 days of ERT (Responders). In such patients, an increase in oxidative stress was observed after surgery that resolved after ERT. Oxidative stress was sustained by reduction in the mRNA expression of both SOD and GSH-Px, that recovered after 30 days of therapy in responders. CAT and GST mRNA expression were not modified by surgery and replacement therapy.ConclusionsMenopause is associated with significant change in antioxidant gene expression that in turn affects circulating redox state. Estrogens replacement therapy is able to prevent and counteract such modifications by acting as regulators of key antioxidant gene expression. These findings suggest that antioxidant genes are, almost in part, under the control of sex hormones, and that pathophysiology of the difference in gender disease may depend on the redox biology.

Distant metastases are unusual at presentation and during the course of ovarian carcinoma. The aim of the present study was to determine the incidence and prognostic factors of distant metastases consistent with stage IV disease in ovarian cancer patients. A retrospective chart review was conducted on 162 patients with epithelial ovarian carcinoma treated at our Unit between 1991 and 2000. Pertinent clinical information, pathologic data, treatment, and prognostic factors for survival following documentation of distant metastatic disease were collected. The significance of the association between metastatic status and various clinical variables was assessed using the standard chi-square test. Survival time was calculated from the time of diagnosis of ovarian cancer and from the time of diagnosis of the distant metastases. A logistic regression procedure was used to estimate the odds of metastatic status given the presence of certain clinical variables. A total of 67 metastatic sites were diagnosed in 50 patients. Thirteen patients (8%) had distant metastatic disease at the time of diagnosis, 37 patients (22%) had distant metastases at the time of recurrent of progressive disease. Site of metastases were: liver, 21; pleura, 11; lung, 8; central nervous system and skin, 7 each; extra-abdominal lymph nodes and spleen, 5 each; bone, 2; and breast, 1. Significant risk factors for the development of distant metastases were stage, grade, and lymph node involvement. Median interval time between diagnosis of ovarian cancer and documentation of metastatic disease was 44 months (range 3-105), and at the time of diagnosis of distant disease, 36 of 50 patients (72%) had other sites of disease (intra-abdominal or extra-abdominal). Median survival from diagnosis of distant disease was 12 months (range 1-58). In univariate analysis performance status (P = 0.03), the presence of other sites of disease (P = 0.04) and interval time between diagnosis of ovarian cancer and documentation of distant metases (P = 0.03) were the only factors significantly associated with survival. Long interval time remained significant for prognosis in multivariate analysis also (P = 0.04). Distant metastasis consistent with stage IV disease is a late complication that occurs in about one third of ovarian cancer patients. Prognosis after documentation of distant metastases is poor. We conclude the most important prognostic factor associated with survival is the interval time between diagnosis of ovarian cancer and documentation of distant metastases.