METHODS AND FINDINGS: Genetic instruments to proxy 12 risk factors were constructed by identifying single nucleotide polymorphisms (SNPs) that were robustly (P < 5 × 10-8) and independently associated with each respective risk factor in previously reported genome-wide association studies. These risk factors included genetic liability to 3 factors (endometriosis, polycystic ovary syndrome, type 2 diabetes) scaled to reflect a 50% higher odds liability to disease. We obtained summary statistics for the association of these SNPs with risk of overall and histotype-specific invasive epithelial ovarian cancer (22,406 cases; 40,941 controls) and low malignant potential tumours (3,103 cases; 40,941 controls) from the Ovarian Cancer Association Consortium (OCAC). The OCAC dataset comprises 63 genotyping project/case-control sets with participants of European ancestry recruited from 14 countries (US, Australia, Belarus, Germany, Belgium, Denmark, Finland, Norway, Canada, Poland, UK, Spain, Netherlands, and Sweden). SNPs were combined into multi-allelic inverse-variance-weighted fixed or random effects models to generate effect estimates and 95% confidence intervals (CIs). Three complementary sensitivity analyses were performed to examine violations of MR assumptions: MR-Egger regression and weighted median and mode estimators. A Bonferroni-corrected P value threshold was used to establish strong evidence (P < 0.0042) and suggestive evidence (0.0042 < P < 0.05) for associations. In MR analyses, there was strong or suggestive evidence that 2 of the 12 risk factors were associated with invasive epithelial ovarian cancer and 8 of the 12 were associated with 1 or more invasive epithelial ovarian cancer histotypes. There was strong evidence that genetic liability to endometriosis was associated with an increased risk of invasive epithelial ovarian cancer (odds ratio [OR] per 50% higher odds liability: 1.10, 95% CI 1.06-1.15; P = 6.94 × 10-7) and suggestive evidence that lifetime smoking exposure was associated with an increased risk of invasive epithelial ovarian cancer (OR per unit increase in smoking score: 1.36, 95% CI 1.04-1.78; P = 0.02). In analyses examining histotypes and low malignant potential tumours, the strongest associations found were between height and clear cell carcinoma (OR per SD increase: 1.36, 95% CI 1.15-1.61; P = 0.0003); age at natural menopause and endometrioid carcinoma (OR per year later onset: 1.09, 95% CI 1.02-1.16; P = 0.007); and genetic liability to polycystic ovary syndrome and endometrioid carcinoma (OR per 50% higher odds liability: 0.89, 95% CI 0.82-0.96; P = 0.002). There was little evidence for an association of genetic liability to type 2 diabetes, parity, or circulating levels of 25-hydroxyvitamin D and sex hormone binding globulin with ovarian cancer or its subtypes. The primary limitations of this analysis include the modest statistical power for analyses of risk factors in relation to some less common ovarian cancer histotypes (low grade serous, mucinous, and clear cell carcinomas), the inability to directly examine the association of some ovarian cancer risk factors that did not have robust genetic variants available to serve as proxies (e.g., oral contraceptive use, hormone replacement therapy), and the assumption of linear relationships between risk factors and ovarian cancer risk.
CONCLUSIONS: Our comprehensive examination of possible aetiological drivers of ovarian carcinogenesis using germline genetic variants to proxy risk factors supports a role for few of these factors in invasive epithelial ovarian cancer overall and suggests distinct aetiologies across histotypes. The identification of novel risk factors remains an important priority for the prevention of epithelial ovarian cancer.
METHODS: This retrospective observational study involved 1296 women seen in a urogynaecological centre. All had undergone an interview, clinical examination and 4D ultrasound (US) imaging supine and after voiding. Offline analysis of volume data was undertaken blinded against other data. Rectal ampulla position and rectocele depth were measured on Valsalva. A pocket depth of 10 mm was used as a cutoff to define rectocele on imaging.
RESULTS: Most women presented with prolapse (53%, n = 686); 810 (63%) complained of obstructed defecation (OD). Clinically, 53% (n = 690) had posterior-compartment prolapse with a mean Bp of -1 [standard deviation (SD)1.5; -3 to 9 cm]. Mean descent of the rectal ampulla was 10 mm below the symphysis (SD 15.8; -50 to 41). A rectocele on imaging was found in 48% (n = 618). On univariate analysis, OD symptoms were strongly associated with rectal descent, rectocele depth and rectocele on imaging (all P
METHODS: A 5-year (2011-2015) cross-sectional study was conducted using data from the Malaysian National Obstetrics Registry (NOR). A total of 608,747 deliveries were recorded from 11 tertiary state hospitals and 1 tertiary hospital from the Federal territory.
RESULTS: During the study period, there were 141,257 Caesarean sections (23.2%). Caesarean sections in Group 1 (nulliparous term pregnancy in spontaneous labour) and Group 3 (multiparous term pregnancy in spontaneous labour) had an increasing trend from 2011 to 2015. The group that contributed most to the overall caesarean section rates was Group 5 (multiparous, singleton, cephalic≥37 weeks with previous caesarean section) and the rates remained high during the 5-year study period. Groups 6, 7 and 9 had the highest caesarean section rates but they made the smallest contribution to the overall rates.
CONCLUSIONS: Like many countries, the rate of caesarean section has risen over time, and the rise is driven by caesarean section in low-risk groups. There was an important hospital to hospital variation. The rise in caesarean section rates reflects a globally disturbing trend, and changes in policy and training that creates a uniform standard across hospitals should be considered.
METHODOLOGY: A retrospective study on IOL using the CRB in women with previous caesarean section or grandmultiparity between January 2014 and March 2015. All cases were identified from the Sarawak General Hospital CRB request registry. Individual admission notes were traced and data extracted using a standardised proforma.
RESULTS: The overall success rate of vaginal delivery after IOL was 50%, although this increases to about two-thirds when sub analysis was performed in women with previous tested scars and the unscarred, grandmultiparous woman. There was a significant change in Bishop score prior to insertion and after removal of the CRB. The Bishop score increased by a score of 3.2 (95% CI 2.8-3.6), which was statistically significant (p<0.01) and occurred across both subgroups, not limited to the grandmultipara. There were no cases of hyperstimulation but one case of intrapartum fever and scar dehiscence each (1.4%). Notably, there were two cases of change in lie/presentation after CRB insertion.
CONCLUSION: CRB adds to the obstetricians' armamentarium and appears to provide a reasonable alternative for the IOL in women at high risk of uterine rupture. Rates of hyperstimulation, maternal infection and scar dehiscence are low and hence appeals to the user.