Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities

Background : Observational studies suggest higher pregnancy rates after the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions, which are present in 10% to 15% of women seeking treatment for subfertility. Objectives : To assess the effects of the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions suspected on ultrasound, hysterosalpingography, diagnostic hysteroscopy or any combination of these methods in women with otherwise unexplained subfertility or prior to intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Search methods : We searched the following databases from their inception to 16 April 2018; The Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Studies Online,; MEDLINE, Embase, CINAHL, and other electronic sources of trials including trial registers, sources of unpublished literature, and reference lists. We handsearched the American Society for Reproductive Medicine (ASRM) conference abstracts and proceedings (from 1 January 2014 to 12 May 2018) and we contacted experts in the field. Selection criteria : Randomised comparison between operative hysteroscopy versus control for unexplained subfertility associated with suspected major uterine cavity abnormalities. Randomised comparison between operative hysteroscopy versus control for suspected major uterine cavity abnormalities prior to medically assisted reproduction. Primary outcomes were live birth and hysteroscopy complications. Secondary outcomes were pregnancy and miscarriage. Data collection and analysis : Two review authors independently assessed studies for inclusion and risk of bias, and extracted data. We contacted study authors for additional information. Main results : Two studies met the inclusion criteria. 1. Randomised comparison between operative hysteroscopy versus control for unexplained subfertility associated with suspected major uterine cavity abnormalities. In women with otherwise unexplained subfertility and submucous fibroids, we were uncertain whether hysteroscopic myomectomy improved the clinical pregnancy rate compared to expectant management (odds ratio (OR) 2.44, 95% confidence interval (CI) 0.97 to 6.17; P = 0.06, 94 women; very low-quality evidence). We are uncertain whether hysteroscopic myomectomy improves the miscarriage rate compared to expectant management (OR 1.54, 95% CI 0.47 to 5.00; P = 0.47, 94 women; very low-quality evidence). We found no data on live birth or hysteroscopy complication rates. We found no studies in women with endometrial polyps, intrauterine adhesions or uterine septum for this randomised comparison. 2. Randomised comparison between operative hysteroscopy versus control for suspected major uterine cavity abnormalities prior to medically assisted reproduction. The hysteroscopic removal of polyps prior to IUI may have improved the clinical pregnancy rate compared to diagnostic hysteroscopy only: if 28% of women achieved a clinical pregnancy without polyp removal, the evidence suggested that 63% of women (95% CI 45% to 89%) achieved a clinical pregnancy after the hysteroscopic removal of the endometrial polyps (OR 4.41, 95% CI 2.45 to 7.96; P < 0.00001, 204 women; low-quality evidence). We found no data on live birth, hysteroscopy complication or miscarriage rates in women with endometrial polyps prior to IUI. We found no studies in women with submucous fibroids, intrauterine adhesions or uterine septum prior to IUI or in women with all types of suspected uterine cavity abnormalities prior to IVF/ICSI. Authors' conclusions : Uncertainty remains concerning an important benefit with the hysteroscopic removal of submucous fibroids for improving the clinical pregnancy rates in women with otherwise unexplained subfertility. The available low-quality evidence suggests that the hysteroscopic removal of endometrial polyps suspected on ultrasound in women prior to IUI may improve the clinical pregnancy rate compared to simple diagnostic hysteroscopy. More research is needed to measure the effectiveness of the hysteroscopic treatment of suspected major uterine cavity abnormalities in women with unexplained subfertility or prior to IUI, IVF or ICSI

The ENDOCARE questionnaire (ECQ): a valid and reliable instrument to measure the patient-centeredness of endometriosis care in Europe

BACKGROUND: Endometriosis is prevalent and women need high-quality care, which should be patient-centered. This study aimed to develop a valid and reliable patient-centeredness questionnaire, based on a defined concept of patient-centered endometriosis care (PCEC). METHODS: A literature review, focus groups (FGs) with patients and an expert panel defined PCEC with 10 dimensions. The ENDOCARE questionnaire (ECQ) was developed. FGs resulted in 43 specific statements covering the 10 dimensions of PCEC, for which the ECQ measured 'importance' and 'performance'. Medical and demographic questions and an open question were added. The Dutch ECQ questionnaire was piloted and reciprocally translated into English and Italian. Patients with endometriosis from Belgium, The Netherlands, Italy and the UK were invited to complete the ECQ online. Item analysis, inter-item analysis and confirmatory and exploratory factor analyses (EFA) and reliability analysis were performed. The theory-driven dimensions were adapted. RESULTS: The ECQ was completed by 541 patients. Based on item analysis, five statements were deleted. Factor analysis was performed on 322 questionnaires (only from respondents with a partner). Insights from the data-driven EFA suggested adaptations of the theory-driven dimensions. The reliability statistics of 9/10 adapted theory-driven dimensions were satisfactory and the root mean square error of approximation was good. CONCLUSIONS: This study resulted in a valid and reliable instrument to measure PCEC. For data presentation, the adapted theory-driven dimensions of PCEC are preferred over the data-driven factors. The ECQ may serve to benchmark patient-centeredness, conduct cross-cultural European research and set targets for improvement

Ectopic endometrium in human foetuses is a common event and sustains the theory of müllerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer

<p>Abstract</p> <p>Background</p> <p>Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Women with endometriosis have an increased risk of different types of malignancies, especially ovarian cancer and non-Hodgkin's lymphoma. Though there are several theories, researchers remain unsure as to the definitive cause of endometriosis. Our objective was to test the validity of the theory of müllerianosis for endometriosis, that is the misplacing of primitive endometrial tissue along the migratory pathway of foetal organogenesis</p> <p>Methods</p> <p>We have collected at autopsy 36 human female foetuses at different gestational age. We have performed a morphological and immunohistochemical study (expression of oestrogen receptor and CA125) on the pelvic organs of the 36 foetuses included en-block and totally analyzed.</p> <p>Results</p> <p>In 4 out of 36 foetuses we found presence of misplaced endometrium in five different ectopic sites: in the recto-vaginal septum, in the proximity of the Douglas pouch, in the mesenchimal tissue close to the posterior wall of the uterus, in the rectal tube at the level of muscularis propria, and in the wall of the uterus. All these sites are common location of endometriosis in women.</p> <p>Conclusion</p> <p>We propose that a cause of endometriosis is the dislocation of primitive endometrial tissue outside the uterine cavity during organogenesis.</p

Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?

Neurodegenerative disorders show an increasing prevalence in a number of highly developed countries. Often, these diseases require life-long treatment mostly with drugs which are costly and mostly accompanied by more or less serious side-effects. Their heterogeneous manifestation, severity and outcome pose the need for individualised treatment options. There is an intensive search for new strategies not only for treating but also for preventing these diseases. Green tea and green tea extracts seem to be such a promising and safe alternative. However, data regarding the beneficial effects and possible underlying mechanism, specifically in clinical trials, are rare and rather controversial or non-conclusive. This review outlines the existing evidence from preclinical studies (cell and tissue cultures and animal models) and clinical trials regarding preventive and therapeutic effects of epigallcatechin-3-gallate in neurodegenerative diseases and considers antioxidative vs. pro-oxidative properties of the tea catechin important for dosage recommendations

The Peritoneum Is Both a Source and Target of TGF-β in Women with Endometriosis

Transforming growth factor-β (TGF-β) is believed to play a major role in the aetiology of peritoneal endometriosis. We aimed to determine if the peritoneum is a source of TGF-β and if peritoneal TGF-β expression, reception or target genes are altered in women with endometriosis. Peritoneal fluid, peritoneal bushings and peritoneal biopsies were collected from women with and without endometriosis. TGF-β1, 2 and 3 protein concentrations were measured in the peritoneal fluid. TGF-β1 was measured in mesothelial cell conditioned media. Control peritoneum and peritoneum prone to endometriosis (within Pouch of Douglas) from women without disease (n = 16) and peritoneum distal and adjacent to endometriosis lesions in women with endometriosis (n = 15) and were analysed for TGF-β expression, reception and signalling by immunohistochemistry, qRT-PCR and a TGF-β signalling PCR array. TGF-β1 was increased in the peritoneal fluid of women with endometriosis compared to those without disease (P<0.05) and peritoneal mesothelial cells secrete TGF-β1 in-vitro. In women with endometriosis, peritoneum from sites adjacent to endometriosis lesions expressed higher levels of TGFB1 mRNA when compared to distal sites (P<0.05). The TGF-β-stimulated Smad 2/3 signalling pathway was active in the peritoneum and there were significant increases (P<0.05) in expression of genes associated with tumorigenesis (MAPK8, CDC6), epithelial-mesenchymal transition (NOTCH1), angiogenesis (ID1, ID3) and neurogenesis (CREB1) in the peritoneum of women with endometriosis. In conclusion, the peritoneum, and in particular, the peritoneal mesothelium, is a source of TGF-β1 and this is enhanced around endometriosis lesions. The expression of TGF-β-regulated genes is altered in the peritoneum of women with endometriosis and this may promote an environment favorable to lesion formation

Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities

BACKGROUND: Observational studies suggest higher pregnancy rates after the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions, which are present in 10% to 15% of women seeking treatment for subfertility. OBJECTIVES: To assess the effects of the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions suspected on ultrasound, hysterosalpingography, diagnostic hysteroscopy or any combination of these methods in women with otherwise unexplained subfertility or prior to intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). SEARCH METHODS: We searched the following databases from their inception to 16 April 2018; The Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Studies Online, ; MEDLINE, Embase , CINAHL , and other electronic sources of trials including trial registers, sources of unpublished literature, and reference lists. We handsearched the American Society for Reproductive Medicine (ASRM) conference abstracts and proceedings (from 1 January 2014 to 12 May 2018) and we contacted experts in the field. SELECTION CRITERIA: Randomised comparison between operative hysteroscopy versus control for unexplained subfertility associated with suspected major uterine cavity abnormalities.Randomised comparison between operative hysteroscopy versus control for suspected major uterine cavity abnormalities prior to medically assisted reproduction.Primary outcomes were live birth and hysteroscopy complications. Secondary outcomes were pregnancy and miscarriage. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and risk of bias, and extracted data. We contacted study authors for additional information. MAIN RESULTS: Two studies met the inclusion criteria.1. Randomised comparison between operative hysteroscopy versus control for unexplained subfertility associated with suspected major uterine cavity abnormalities.In women with otherwise unexplained subfertility and submucous fibroids, we were uncertain whether hysteroscopic myomectomy improved the clinical pregnancy rate compared to expectant management (odds ratio (OR) 2.44, 95% confidence interval (CI) 0.97 to 6.17; P = 0.06, 94 women; very low-quality evidence). We are uncertain whether hysteroscopic myomectomy improves the miscarriage rate compared to expectant management (OR 1.54, 95% CI 0.47 to 5.00; P = 0.47, 94 women; very low-quality evidence). We found no data on live birth or hysteroscopy complication rates. We found no studies in women with endometrial polyps, intrauterine adhesions or uterine septum for this randomised comparison.2. Randomised comparison between operative hysteroscopy versus control for suspected major uterine cavity abnormalities prior to medically assisted reproduction.The hysteroscopic removal of polyps prior to IUI may have improved the clinical pregnancy rate compared to diagnostic hysteroscopy only: if 28% of women achieved a clinical pregnancy without polyp removal, the evidence suggested that 63% of women (95% CI 45% to 89%) achieved a clinical pregnancy after the hysteroscopic removal of the endometrial polyps (OR 4.41, 95% CI 2.45 to 7.96; P < 0.00001, 204 women; low-quality evidence). We found no data on live birth, hysteroscopy complication or miscarriage rates in women with endometrial polyps prior to IUI. We found no studies in women with submucous fibroids, intrauterine adhesions or uterine septum prior to IUI or in women with all types of suspected uterine cavity abnormalities prior to IVF/ICSI. AUTHORS' CONCLUSIONS: Uncertainty remains concerning an important benefit with the hysteroscopic removal of submucous fibroids for improving the clinical pregnancy rates in women with otherwise unexplained subfertility. The available low-quality evidence suggests that the hysteroscopic removal of endometrial polyps suspected on ultrasound in women prior to IUI may improve the clinical pregnancy rate compared to simple diagnostic hysteroscopy. More research is needed to measure the effectiveness of the hysteroscopic treatment of suspected major uterine cavity abnormalities in women with unexplained subfertility or prior to IUI, IVF or ICSI.status: publishe

Priorities for endometriosis research: recommendations from an international consensus workshop.

Endometriosis is an estrogen-dependent disorder where endometrial tissue forms lesions outside the uterus. Endometriosis affects an estimated 10% of women in the reproductive-age group, rising to 30% to 50% in patients with infertility and/or pain, with significant impact on their physical, mental, and social well-being. There is no known cure, and most current medical treatments are not suitable long term due to their side-effect profiles. Endometriosis has an estimated annual cost in the United States of $18.8 to$22 billion (2002 figures). Although endometriosis was first described more than 100 years ago, current knowledge of its pathogenesis, spontaneous evolution, and the pathophysiology of the related infertility and pelvic pain, remain unclear. A consensus workshop was convened following the 10th World Congress on Endometriosis to establish recommendations for priorities in endometriosis research. One major issue identified as impacting on the capacity to undertake endometriosis research is the need for multidisciplinary expertise. A total of 25 recommendations for research have been developed, grouped under 5 subheadings: (1) diagnosis, (2) classification and prognosis, (3) treatment and outcome, (4) epidemiology, and (5) pathophysiology. Endometriosis research is underfunded relative to other diseases with high health care burdens. This may be due to the practical difficulties of developing competitive research proposals on a complex and poorly understood disease, which affects only women. By producing this consensus international research priorities statement it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis