CTLA4-Linked Autoimmunity in the Pathogenesis of Endometriosis and Related Infertility: A Systematic Review.

Several studies, although with conflicting results, have sought to determine the concentration of soluble CTLA4 antigens in peripheral blood plasma and peritoneal fluid in patients with endometriosis-related infertility. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) through a search of the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database and Web of Science, and Clinical Trials research register. We included observational or prospective human and animal studies with any features related to endometriosis and/or infertility studies involving CTLA4-related pathogenesis published in English. The results of studies in which the size and characteristics of the observed groups were not stated were excluded. From the initial pool of 73 publications identified and screened, we finally included 5 articles to summarize the most recent knowledge about CTLA4-linked autoimmunity in the pathogenesis of endometriosis and related infertility. Evidence from clinical studies shows that CTLA4-based autoimmunity is involved in the maintenance of chronic inflammation in the peritoneal environment, with pre-clinical evidence of anti-CTLA antibodies as a potential novel target therapy for endometriosis. However, CTLA4 gene analyses do not support findings of CTLA4-linked autoimmunity as a primary determinant of the pathogenesis of endometriosis. These findings underlie the role of complex interactions within the family of immune checkpoint molecules involved. Further studies are needed to investigate the clinical relevance of anti-CTLA target therapy, taking into account the potential adverse events and repercussions of novel immunologic therapy modalities. However, with the general scarcity of studies investigating this topic, the clinical importance of CTLA4 autoimmunity still remains unclear.

HISTOPATHOLOGIC FINDINGS IN WOMEN UNDERGOING HYSTEROSCOPIC RESECTION OF ENDOMETRIAL POLYPS AND UTERINE MYOMAS.

The aim of our study was to determine the prevalence of endometrial premalignant and malignant lesions in women undergoing hysteroscopy and to identify anthropologic factors related to the presence of malignancy. Data on 3470 women with submucosal myomas or endometrial polyps suspected on ultrasound were retrospectively analyzed. Hysteroscopy was performed in all these women in order to make a more precise diagnosis. Histologic analysis of endometrial samples obtained during hysteroscopy was used to confirm the diagnosis. Statistical analysis was performed using the SPSS 20.0.0 software. The mean age of study women was 49.1±13.3 years. The number of procedures performed due to the referral diagnosis of endometrial or submucosal myoma significantly increased over the 16-year study period. A significantly higher number of women had a benign histopathologic diagnosis. Histologic analysis revealed malignancy in 67 women. The youngest woman and oldest woman with malignant findings was aged 32 and 75, respectively. A significantly higher number of women with atypical hyperplasia and malignancy were in menopause. A comparable number of women with different histologic findings lived in urban and rural areas. There were a significantly larger proportion of widows among women with the histologic diagnosis of atypical hyperplasia or malignancy. The prevalence rate of malignancy in women having undergone hysteroscopy for polyps and myoma found by ultrasound was 1.93%. Postmenopausal status and older age were associated with an increased risk of malignancies, but premalignant changes and malignancies were also found in young and premenopausal women. Therefore, diagnostic hysteroscopy can be recommended in women of all age groups.