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The World Health Organisation has defined infertility as the inability to become pregnant after 12 months of regular unprotected vaginal sexual intercourse. Primary infertility refers to couples that have never conceived, whereas secondary infertility refers to couples that have failed to conceive despite previous pregnancy. In the general population, 80% of couples are expected to be able to conceive within a year and 90% by the end of 2 years. With the rising trend for increasing maternal age at time of first pregnancy and the obesity epidemic, the incidence of infertility is likely to increase. Couples unable to conceive will seek help and advice from their GP. Infertility is highly emotive, and patients and their partners subject to investigation and management for infertility are likely to experience anxiety. Although primarily managed in secondary care, a robust understanding of investigation and treatment options for infertility can enable GPs to educate and support patients, as well as manage expectations.

Obesity and hyperinsulinemia are known risk factors for endometrial cancer, yet thebiological pathways underlying this relationship are incompletely understood. Thisstudy investigated protein expression in endometrial cancer and benign tissue andits correlation with obesity and insulin resistance.One hundred and seven women undergoing hysterectomy for endometrial canceror benign conditions provided a fasting blood sample and endometrial tissue. Weperformed proteomic expression according to body mass index, insulin resistance,and serum marker levels. We used linear regression and independentttest for statis-tical analysis. Proteomic data from 560 endometrial cancer cases from The CancerGenome Atlas (TCGA) databank were used to assess reproducibility of results.One hundred and twenty seven proteins were significantly differentially expressedbetween 66 cancer and 26 benign patients. Protein expression involved in cellcycle progression, impacting cytoskeletal dynamics (PAK1) and cell survival (Rab25), were most significantly altered. Obese women with cancer had increasedPRAS40_pT246; a downstream marker of increased PI3K-AKT signaling. Obesewomen without cancer had increased mitogenic and antiapoptotic signaling byway of upregulation of Mcl-1, DUSP4, and Insulin Receptor-b.This exploratory study identified a number of candidate proteins specific to endo-metrioid endometrial cancer and benign endometrial tissues. Obesity and insulinresistance in women with benign endometrium leads to specific upregulation ofproteins involved in insulin and driver oncogenic signaling pathways such as thePI3K-AKT-mTOR and growth factor signaling pathways which are mitogenic andalso disruptive to metabolism. (Translational Research 2020; 000:1 16)

BackgroundObesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here, we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery.MethodsVaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery.ResultsThe bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of aLactobacillus-dominant VMB and higher prevalence of a high diversity (Lactobacillusspp., andGardnerella- spp. depleted) VMB, compared with non-obese subjects (pDialisterspecies (pAnaerococcus vaginalis(p=0.021), andPrevotella timonensis(p=0.020) and decreased relative abundance ofLactobacillus crispatus(p=0.014). Local vaginal IL-1β, IL-4, IL-6, IL-8, IFNγ, MIP-1α and TNFα levels were all higher among obese women, however, only IL-1β and IL-8 correlated with VMB species diversity. In a subset of obese women undergoing bariatric surgery, there were no significant overall differences in VMB following surgery; however, 75% of these women remained obese at 6 months. Prior to surgery, there was no relationship between body mass index (BMI) and VMB structure; however, post-surgery women with aLactobacillus-dominant VMB had a significantly lower BMI than those with a high diversity VMB.ConclusionsObese women have a significantly different vaginal microbiota composition with increased levels of local inflammation compared to non-obese women. Bariatric surgery does not change the VMB; however, those with the greatest weight loss 6-month post-surgery are most likely to have aLactobacillus-dominant VMB.

Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia&mdash, the early recognition of which may allow fertility sparing management and cancer prevention.

We performed a systematic review and meta-analysis to explore the optimum management strategy for women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intra-epithelial lesions (LSIL/mild dyskaryosis) cytological abnormalities at primary screening in the absence of HPV DNA test. We searched MEDLINE, EMBASE and CENTRAL and included randomised controlled trials comparing immediate colposcopy to cytological surveillance in women with ASCUS/LSIL. The outcomes of interest were occurrence of different histological grades of cervical intraepithelial neoplasia (CIN) and default rates during follow-up. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effect model and with inverse variance weighting. Interstudy heterogeneity was assessed using I2 statistics. Six RCTs were included. Immediate colposcopy significantly increased detection of unimportant abnormalities as opposed to repeat cytology (koilocytosis: 32 vs. 21%, RR: 1.49, 95% CI = 1.17–1.90); CIN1: 21 vs. 8%, RR: 2.58, 95% CI = 1.69–3.94). Although immediate colposcopy detected CIN2, CIN2+, and CIN3+ earlier than cytology, the differences were no longer observed at 24 months (CIN3+: 10.3 vs.11.9%, RR: 1.02, 95% CI = 0.53–1.97), with significant interstudy heterogeneity (p