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Background Ovarian carcinoma is not a single disease, but rather a collection of subtypes with differing molecular properties and risk profiles. The most common of these, and the subject of this work, is high-grade serous ovarian carcinoma (HGSC). Methods In this population-based study we identified a cohort of 441,382 women resident in Western Australia who had ever been admitted to hospital in the State. Of these, 454 were diagnosed with HGSC. We used Cox regression to derive hazard ratios (HRs) comparing the risk of disease in women who had each of a range of medical diagnoses and surgical procedures with women who did not. Results We found an increased risk of HGSC associated with a diagnosis of pelvic inflammatory disease (PID) (HR 1.47, 95% CI 1.04–2.07) but not with a diagnosis of infertility or endometriosis with HRs of 1.12 (95% CI 0.73–1.71) and 0.82 (95% CI 0.55–1.22) respectively. A personal history of breast cancer was associated with a three-fold increase in the rate of HGSC. Increased parity was associated with a reduced risk of HGSC in women without a personal history of breast cancer (HR 0.57; 95% CI 0.44-0.73), but not in women with a personal history of breast cancer (HR 1.48; 95% CI 0.74–2.95). Conclusions Our finding of an increased risk of HGSC associated with PID lends support to the hypothesis that inflammatory processes may be involved in the etiology of HGSC.

Background Hysterectomy is one of the most commonly performed gynecological surgeries, with an estimated 30% of women in Australia undergoing the procedure by age 70. In the USA, about 45% of women have a hysterectomy in their lifetime. Some studies have suggested this procedure increases the risk of premature mortality. With many women making the decision to have a hysterectomy for a benign indication each year, additional research is needed to clarify whether there are long-term health consequences of hysterectomy. Objective Our aim was to examine the association between hysterectomy for benign indications, with or without removal of the ovaries, and cause-specific and all-cause mortality. Study Design Our cohort of 666,588 women comprised the female population of Western Australia with linked hospital and health records from 1970 to 2015. We used Cox regression models to assess the association between hysterectomy and all-cause, cardiovascular disease, cancer and other mortality by oophorectomy type (categorized as none, unilateral and bilateral), with no hysterectomy or oophorectomy as the reference group. We repeated these analyses using hysterectomy without oophorectomy as the reference group. We also investigated whether associations varied by age at the time of surgery, although small sample size precluded this analysis in women who had a hysterectomy with unilateral salpingo-oophorectomy. In our main analysis, women who had hysterectomy and/or oophorectomy undertaken as part of treatment for cancer were retained in the analysis and considered unexposed to that surgery. As a sensitivity analysis, we censored procedures undertaken for cancer. Results Compared to no surgery, having a hysterectomy without oophorectomy before age 35 was associated with an increase in all-cause mortality (HR=1.29, 95% CI:1.19-1.40); for surgery after age 35, there was an inverse association (35-44 years: HR=0.93, 95%CI:0.89,0.97). Similarly, hysterectomy with bilateral salpingo-oophorectomy was associated with increased all-cause mortality when undertaken before age 45 (35-44 years: HR=1.15, 95%CI:1.04-1.27), but decreased mortality rates when surgery was undertaken after age 45. In our sensitivity analysis, censoring gynecological surgeries for cancer resulted in many cancer-related deaths being excluded for women who did not have surgery for benign indications, and thus increased the hazard ratios for the associations between both hysterectomy without oophorectomy and hysterectomy with bilateral salpingo-oophorectomy and risk of all-cause and cancer-specific mortality. The sensitivity analysis therefore potentially biased the results in favor of no surgery. Conclusion Among women having surgery for benign indications, hysterectomy without oophorectomy performed prior to 35 years and hysterectomy with bilateral salpingo-oophorectomy performed prior to 45 years were associated with an increase in all-cause mortality. These procedures are not associated with poorer long-term survival when performed at older ages.

Objectives To compare the risk of borderline ovarian tumours in women having in vitro fertilization (IVF) with women diagnosed with infertility but not having IVF. Methods This was a whole-population cohort study of women aged 20–44years seeking hospital infertility treatment or investigation in Western Australia in 1982–2002. Using Cox regression, we examined the effects of IVF treatment and potential confounders on the rate of borderline ovarian tumours. Potential confounders included parity, age, calendar year, socio-economic status, infertility diagnoses including pelvic inflammatory disorders and endometriosis and surgical procedures including hysterectomy and tubal ligation. Results Women undergoing IVF had an increased rate of borderline ovarian tumours with a hazard ratio (HR) of 2.46 (95% confidence interval [CI] 1.20–5.04). Unlike invasive epithelial ovarian cancer, neither birth (HR 0.89; 95% CI 0.43–1.88) nor hysterectomy (1.02; 0.24–4.37) nor sterilization (1.48; 0.63–3.48) appeared protective and the rate was not increased in women with a diagnosis of endometriosis (HR 0.31; 95% CI 0.04–2.29). Conclusions Women undergoing IVF treatment are at increased risk of being diagnosed with borderline ovarian tumours. Risk factors for borderline ovarian tumours appear different from those for invasive ovarian cancer.

Objective To examine the incidence rate of breast cancer in a cohort of women undergoing treatment for infertility, comparing the rate in women who had in vitro fertilization (IVF) with those who did not. Design Population-based cohort study using linked hospital and registry data. Setting Hospital. Patient(s) All women aged 20–44 years seeking hospital investigation and treatment for infertility in Western Australia during the period 1983–2002 (n = 21,025). Intervention(s) None. Main Outcome Measure(s) Hazard ratios (HRs) for breast cancer. Result(s) There was no overall increase in the rate of breast cancer in women who had IVF (HR 1.10, 95% confidence interval [CI] 0.88–1.36), but there was an increased rate in women who commenced IVF at a young age. Women who commenced hospital infertility treatment at 24 years and required IVF had an unadjusted HR of breast cancer of 1.59 (95% CI 1.05–2.42) compared with women of the same age who had infertility treatment but no IVF. When adjusted for late age at first delivery, which is associated with an increased rate of breast cancer, and delivery of twins and higher-order multiples, which is associated with a decreased rate of breast cancer, the HR remained elevated at 1.56 (95% CI 1.01–2.40). Hazard ratios were not elevated in women who commenced treatment at age 40 and required IVF (adjusted HR 0.87, 95% CI 0.62–1.22). Conclusion(s) Commencing IVF treatment at a young age is associated with an increased rate of breast cancer.

Objective To measure IVF effectiveness, which is defined as the cumulative incidence of live delivery over real time in women after commencing IVF treatment. Design Population-based retrospective cohort study. Setting IVF clinics in Western Australia (WA). Patient(s) All women ages 20–44 years inclusive at start of treatment, commencing IVF in 1982–1992 and 1993–2002 at clinics in WA (n = 8,275). Intervention(s) Data on IVF cycles were extracted from hospital records and a statutory reproductive technology register and linked to records of births. Main Outcome Measure(s) Cumulative incidence of an IVF-attributed live delivery and cumulative incidence of an IVF-attributed or IVF treatment-independent live delivery. Result(s) IVF effectiveness in the 1993–2002 cohort was 47% overall. It was highest in women ages 20–29 years at the start of treatment, measuring 58%; and 79% with the inclusion of IVF treatment-independent deliveries, and declined to 22% and 33%, respectively, in women ages 40–44 years. Couples underwent, on average, only three cycles, even though the cumulative probability of a live delivery increased with each successive cycle for at least the first five cycles. Conclusion(s) IVF effectiveness could be improved if women, particularly those over 35, underwent more cycles.