Clinical outcomes and prognostic biomarkers among pregnant, post-partum and nulliparous women with breast cancer: a prospective cohort study.

PURPOSE: To compare clinical-pathologic characteristics and outcomes of pregnancy-associated, post-partum (PP) and nulliparous (NP) breast cancer (BC) patients and explore mediators of the poor prognosis associated with post-partum BC. METHODS: A prospective database of 233 women ≤ 40 years of age diagnosed with BC between February 2008 and January 2015 was analysed. Clinical-pathologic characteristics and outcomes among pregnant, PP and NP patients were compared using chi-square or Kruskal-Wallis tests. The Kaplan-Meier method was used to estimate disease-free survival (DFS), distant DFS and overall survival (OS). Survival curves were compared using the log-rank test. Univariable Cox proportional hazards regression models were used to evaluate factors that were potentially prognostic for the clinical outcomes of interest; a multivariable Cox model was constructed using a forward stepwise selection process. Androgen receptor (AR), GATA3, PDL1 status and the presence/absence of tumour-infiltrating lymphocytes (TILs) were assessed when possible. Pre-treatment neutrophil and lymphocyte counts were abstracted retrospectively. Statistical significance was defined as a p value ≤ 0.05. RESULTS: Women ≤ 2 years PP had a numerically higher incidence of lymph node-positive and high-grade disease and were significantly more likely to have estrogen receptor-negative BC compared to NP controls. With a median follow-up of 7.2 years, increasingly poor outcomes were observed among NP (longest OS), > 2 years PP, ≤ 2 years PP and pregnant (shortest OS) patients, but these differences were not statistically significant. The ≤ 2 years PP group had significantly lower AR expression, a strong trend toward higher PDL1 expression and a higher expression of stromal TILs compared to NP women. CONCLUSIONS: PPBC patients had numerically lower DFS and OS compared to NP controls. Higher PDL1 and stromal TILs in PPBC suggest that adjuvant immunotherapy may be effective in the post-partum BC subgroup.

Parenthood desire, childbearing plans and oocyte utilization among women who previously underwent planned oocyte cryopreservation.

RESEARCH QUESTION: To examine the motivations, life circumstances and parenthood aspirations of a cohort of women who underwent planned oocyte cryopreservation (POC) at a Canadian academic IVF centre. DESIGN: A single-site, cross-sectional, anonymous quantitative study using a study-specific questionnaire administrated via SurveyMonkey®. Of the 224 women who completed at least one POC cycle between 2012 and 2018, 198 were reached by email and invited to participate. RESULTS: Of the 98 (49.5%) questionnaires returned, 86 were fully completed and were analysed. Mean age at first POC cycle was 35.7 ± 2.4 (range 27-43) and at survey was 37.7 ± 2.5 years. At POC, 77% were single and 97.7% childless. At survey, 96% had not attempted to use their cryopreserved oocytes, yet 26 (30%) had tried natural conception or fertility treatments. Of these, three conceived naturally and two by assisted reproduction. Eighty-five per cent expressed a strong motherhood desire and 67.1% indicated that usage of their cryopreserved oocytes was mostly contingent on relationship status. Many expressed a desire for shared genetic parenthood within a committed relationship. Forty-seven per cent did not want to carry a pregnancy beyond the age of 46. CONCLUSION: The findings of this study confirm the central role of age and relationship status in influencing women's POC decisions and oocyte utilization plans. The late age at POC could be explained by women using it toward the end of their peak reproductive years to leverage their remaining chances of genetic motherhood. Surveying women at later points following POC would help to gain a more comprehensive picture of their oocyte utilization and disposition plans.

Assessing the quality of decision-making for planned oocyte cryopreservation.

PURPOSE: This survey study aims to examine the quality of planned oocyte cryopreservation (POC) decision-making in the domains of decision change, decision difficulty, decision regret and informed choice. METHODS: Of the 224 women who completed at least one POC cycle between 2012 and 2018 at a Canadian academic IVF centre, 198 were reachable by email for anonymous survey participation. RESULTS: Ninety-eight questionnaires were returned (response rate 49.5%). Of these, 86 fully completed questionnaires were analyzed for this study. Eighty-eight percent of respondents stated that it was a 'good decision' to cryopreserve oocytes, in retrospect. Despite this, 31% found the decision-making process to be 'difficult'. Three in five (61%) would have made 'exactly the same' decision without any change, yet slightly over a third (35%) would have made a 'similar' decision, but with option-related changes and process-related changes. A negative correlation between 'decision regret' and 'informed choice' was found (p < .005). Those who stated that they would have made exactly the 'same' POC decision were found to have a significantly higher 'informed choice' score compared to others who would have made a 'similar' or 'completely different' decision, in retrospect (p < .001). Respondents with lesser 'decision regret' were significantly more likely to appraise their decision as a well-informed choice (p < .001). CONCLUSIONS: Our findings show that high-quality POC decision-making is accompanied by the perception of being able to make an informed choice, which can be achieved by providing patients with adequate information and individualized counselling to help patients set realistic expectations of cycle outcomes.

Cost-effectiveness modelling of birth and infant dose vaccination against hepatitis B virus in Ontario from 2020 to 2050.

BACKGROUND: The World Health Organization recommends universal birth dose vaccination for hepatitis B virus (HBV), yet only 3 provinces and territories in Canada provide birth dose vaccination, and Canadian-born children in Ontario are acquiring HBV before adolescent vaccination. We sought to determine whether birth and/or infant HBV vaccination is cost-effective. METHODS: We used a dynamic HBV model that incorporates population by year, disease stage, sex and the influence of immigration to quantify the disease and economic burden of chronic HBV infection in Ontario from 2020 to 2050. We compared 4 vaccination scenarios, which included a birth dose vaccine and variations of the 2 subsequent doses (either alone or as a part of the hexavalent vaccine) and a hexavalent-only strategy in infancy with the current adolescent vaccination strategy. Our costing estimates were based on values from 2020. RESULTS: All 4 infant vaccination approaches prevented an additional 550-560 acute and 160 chronic pediatric HBV infections from 2020 to 2050 compared with adolescent vaccination. Whereas birth dose could be cost-effective, incorporating vaccination into a hexavalent vaccine was cost saving. By 2050, the hexavalent approach led to $428 000 in cost savings per disability-adjusted life years averted. INTERPRETATION: At the current prevalence in Ontario, a switch to birth dose or infant dose will be cost-effective or even cost saving. Introducing any form of infant HBV immunization in Ontario will prevent acute and chronic pediatric HBV infections.

Planned Oocyte Cryopreservation: Outcomes, Motivations, and Involvement of Primary Health Care Providers.

Background: With improvements in oocyte cryopreservation and widespread delays in childbearing, planned oocyte cryopreservation (POC) has become an increasingly attractive option. This study aimed to (1) review POC cycle outcomes at an academic in vitro fertilization (IVF) center and (2) examine POC users' motivations for pursuing POC, fertility knowledge, and the involvement of their primary health care providers (PHP). Materials and Methods: POC cycle outcomes were collected from IVF records of the 224 women who underwent ≥1 cycle from 2012 to 2018. The 198 who were reachable by e-mail were invited to complete an online survey. The study was approved by the University of Toronto Research Ethics Board (No. 32951). Results: Mean age of the 224 women at first cycle was 36.4 (range: 25-42), with a significant decrease in anti-Müllerian hormone level (p = 0.001) and mean number of oocytes retrieved (p = 0.006) and cryopreserved per cycle (p = 0.042) with increasing age. From those invited for survey participation, 98 (49.5%) questionnaires were returned, with 86 evaluable. Majority of respondents were Caucasian (66%), single (93%), and earned a gross annual income of >$70,000 (74%). Strongest motivation for pursuing POC was concern about age-related fertility decline in the absence of a partner. Respondents' annual income was positively correlated with the number of completed cycles (p = 0.032). Half the respondents correctly identified age of onset of marked fertility decline as ≥35 years. In only 19% of cases was the conversation PHP initiated, and 29% never discussed POC with their PHP. Conclusions: More than 50% of women underwent POC at an age when fertility has begun to markedly decline. It is important for PHPs to identify and discuss POC with appropriate patients and offer accurate preliminary information and timely referrals for those interested in exploring this option.