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Preserving the option to conceive through egg freezing (oocyte cryopreservation) is surrounded by value conflicts and diverse viewpoints, particularly when non-medical or so-called ‘social’ reasons are involved. The debate is controversial and shaped by normative perceptions of the life course, including concepts regarding reproductive ageing, gender, motherhood and biomedicalization. To unravel the controversy and systematically identify the variety of viewpoints on egg freezing, a Q-methodology study was conducted in The Netherlands between December 2018 and October 2019. Thirty-four women of reproductive age participated in the study. They ranked 40 statements according to their level of agreement, and explained their ranking during follow-up interviews. Data were analysed using by-person factor analysis and interpreted using both quantitative and qualitative data. Four viewpoints, of which the fourth was bipolar, were identified: (1) cautious about egg freezing technology; (2) my body, my choice; (3) egg freezing is unnatural; and (4) have children and have them early. The distinct viewpoints illustrate different prioritizations of values and normative dimensions of biomedical innovations. By knowing more about the prevalent opinions on egg freezing and the surrounding controversy, policy makers and practitioners can make better informed decisions in terms of promoti

Contains fulltext : 232410.pdf (Publisher’s version ) (Open Access), BACKGROUND: Decision making regarding future fertility can be very difficult for female cancer patients. To support patients in decision making, fertility preservation decision aids (DAs) are being developed. However, to make a well-informed decision, patients need personalized information tailored to their cancer type and treatment. Tailored cancer-specific DAs are not available yet. METHODS: Our DA was systematically developed by a multidisciplinary steering group (n = 21) in an iterative process of draft development, three rounds of alpha testing, and revisions. The drafts were based on current guidelines, literature, and patients' and professionals' needs. RESULTS: In total, 24 cancer-specific DAs were developed. In alpha testing, cancer survivors and professionals considered the DA very helpful in decision making, and scored an 8.5 (scale 1-10). In particular, the cancer-specific information and the tool for recognizing personal values were of great value. Revisions were made to increase readability, personalization, usability, and be more careful in giving any false hope. CONCLUSIONS: A fertility preservation DA containing cancer-specific information is important in the daily care of female cancer patients and should be broadly available. Our final Dutch version is highly appraised, valid, and usable in decision making. After evaluating its effectiveness with newly diagnosed patients, the DA can be translated and adjusted according to (inter)national guidelines.

Contains fulltext : 237733.pdf (Publisher’s version ) (Open Access), BACKGROUND: Female childhood cancer survivors (CCSs) carry a risk of therapy-related gonadal dysfunction. Alkylating agents (AA) are well-established risk factors, yet inter-individual variability in ovarian function is observed. Polymorphisms in CYP450 enzymes may explain this variability in AA-induced ovarian damage. We aimed to evaluate associations between previously identified genetic polymorphisms in CYP450 enzymes and AA-related ovarian function among adult CCSs. METHODS: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function in a discovery cohort of adult female CCSs, from the pan-European PanCareLIFE cohort (n = 743; age (years): median 25.8, interquartile range (IQR) 22.1-30.6). Using two additive genetic models in linear and logistic regression, nine genetic variants in three CYP450 enzymes were analyzed in relation to cyclophosphamide equivalent dose (CED) score and their impact on AMH levels. The main model evaluated the effect of the variant on AMH and the interaction model evaluated the modifying effect of the variant on the impact of CED score on log-transformed AMH levels. Results were validated, and meta-analysis performed, using the USA-based St. Jude Lifetime Cohort (n = 391; age (years): median 31.3, IQR 26.6-37.4). RESULTS: CYP3A4*3 was significantly associated with AMH levels in the discovery and replication cohort. Meta-analysis revealed a significant main deleterious effect (Beta (95% CI): -0.706 (-1.11--0.298), p-value = 7 × 10(-4)) of CYP3A4*3 (rs4986910) on log-transformed AMH levels. CYP2B6*2 (rs8192709) showed a significant protective interaction effect (Beta (95% CI): 0.527 (0.126-0.928), p-value = 0.01) on log-transformed AMH levels in CCSs receiving more than 8000 mg/m(2) CED. CONCLUSIONS: Female CCSs CYP3A4*3 carriers had significantly lower AMH levels, and CYP2B6*2 may have a protective effect on AMH levels. Identification of risk-contributing variants may improve individualized counselling regarding the treatme

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We study collusion in an infinitely repeated prisoners' dilemma when firms' discount factor is private information. If tacit collusion is not feasible, firms that are capable of sustaining high prices may still be willing and able to collude explicitly. Firms eager to collude may signal their intentions when forming the agreement is costly, but not too costly. As antitrust makes explicit collusion costly in expected terms, it may in fact function as a signaling device. We show that there always exists a cost level for which explicit collusion is viable. Moreover, our analysis suggests that antitrust enforcement is unable to fully deter collusion.

This paper examines endogenous cartel formation in the presence of a competition authority. Competition policy makes the most inclusive stable cartels less inclusive. In particular, small firms that might have been cartel members in the absence of a competition authority are no longer members. Regarding the least inclusive stable cartels, competition policy can either increase or decrease their inclusiveness. Highly inelastic market demand is sufficient for the presence of a competition authority to cause the least inclusive stable cartels to increase in size.

Item does not contain fulltext, BACKGROUND: Chemotherapy for breast cancer may have a negative impact on reproductive function due to gonadotoxicity. Fertility preservation via banking of oocytes or embryos after ovarian stimulation with FSH can increase the likelihood of a future live birth. It has been hypothesized that elevated serum estrogen levels during ovarian stimulation may induce breast tumour growth. This has led to the use of alternative stimulation protocols with addition of tamoxifen or letrozole. The effectiveness of these stimulation protocols in terms of oocyte yield is unknown. METHODS/DESIGN: Randomized open-label trial comparing ovarian stimulation plus tamoxifen and ovarian stimulation plus letrozole with standard ovarian stimulation in the course of fertility preservation. The study population consists of women with breast cancer who opt for banking of oocytes or embryos, aged 18-43years at randomisation. Primary outcome is the number of oocytes retrieved at follicle aspiration. Secondary outcomes are number of mature oocytes retrieved, number of oocytes or embryos banked and peak E2 levels during ovarian stimulation. DISCUSSION: Concerning the lack of evidence on which stimulation protocol should be used in women with breast cancer and the growing demand for fertility preservation, there is an urgent need to undertake this study. By performing this study, we will be able to closely monitor the effects of various stimulation protocols in women with breast cancer and pave the way for long term follow up on the safety of this procedure in terms of breast cancer prognosis. TRIAL REGISTRATION: NTR4108.

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Contains fulltext : 171486.pdf (publisher's version ) (Closed access), STUDY QUESTION: Do BRCA1/2 mutation carriers have a compromised ovarian reserve compared to proven non-carriers, based on serum anti-Mullerian hormone (AMH) levels? SUMMARY ANSWER: BRCA1/2 mutation carriers do not show a lower serum AMH level in comparison to proven non-carriers, after adjustment for potential confounders. WHAT IS KNOWN ALREADY: It has been suggested that the BRCA genes play a role in the process of ovarian reserve depletion, although previous studies have shown inconsistent results regarding the association between serum AMH levels and BRCA mutation status. Hence, it is yet unclear whether BRCA1/2 mutation carriers may indeed be at risk of a reduced reproductive lifespan. STUDY DESIGN, SIZE, DURATION: A multicenter, cross-sectional study was performed between January 2012 and February 2015 in 255 women. We needed to include 120 BRCA1/2 mutation carriers and 120 proven non-carriers to demonstrate a difference in AMH levels of 0.40 microg/l (SD +/- 0.12 microg/l, two-sided alpha-error 0.05, power 80%). PARTICIPANTS/MATERIALS, SETTING, METHOD: Healthy women aged 18-45 years who were referred to the Clinical Genetics Department and applied for predictive BRCA1/2 testing because of a familial BRCA1/2 mutation were asked to participate. A cross-sectional assessment was performed by measuring serum AMH levels and filling out a questionnaire. Multivariate linear regression analyses adjusted for age, current smoking and current hormonal contraceptive use were performed on log-transformed serum AMH levels. MAIN RESULTS AND THE ROLE OF CHANCE: Out of 823 potentially eligible women, 421 (51.2%) were willing to participate, and of those, 166 (39%) did not meet our inclusion criteria. Two hundred and fifty-five women were available for analyses; 124 BRCA1/2 mutation carriers and 131 proven non-carriers. The median [range] AMH level in carriers was 1.90 microg/l [0.11-19.00] compared to 1.80 microg/l [0.11-10.00] in non-carriers (P = 0.34). Adjusted linear regres

Support for climate change policies is crucial in the quest of limiting climate change. However, the success of the traditional method, highlighting the environmental benefits of policies, has stalled (Bain et al., 2015). The traditional method is especially ineffective in gathering policy support for people who do not (fully) believe in the problem of climate change (climate change critics). In a recent study, Bain et al. (2015) find a new method to engage people in environmentally friendly behaviour. Bain et al. (2015) state that this method is effective for both climate change critics and non-critics. In this method, policy information gets framed in terms of personal benefits called co-benefits. Examples are: saving money by using green energy and health benefits due to cleaner air. Informing people through the use of co-benefits is called a gain frame. If a gain frame is indeed effective for both climate change critics and non-critics, the use of a gain frame could potentially lead to a substantial increase in climate change policy support. Up until now, this has not been tested. Furthermore, several studies suggest that negative information has a stronger psychological effect than positive information (Baumeister et al., 2001). Therefore, the use of a loss frame, which highlights personal costs of climate change, may have a stronger effect on policy support. However, Bain et al. (2015) have not taken this into account. In this study, I test and extend the theory of Bain et al. (2015) in four ways: (1) I test the external validity by examining the effect of a gain frame on climate change non-critics, (2) I add a loss frame, (3) I look at the possible different effects of health and financial co-benefits and co-costs, and (4) I connect the ‘values-belief-norms’ (VBN) theory with the theory of framing by looking at the effect of gain and loss frames on people with different levels of egoistic and altruistic values. I find that the use of a gain and loss frame is

Contains fulltext : 168797.pdf (publisher's version ) (Closed access), OBJECTIVE: It has been hypothesized that BRCA1/2 mutation carriers have an earlier age at natural menopause (ANM), although to date findings are inconclusive. This study assessed the influence of BRCA mutation status on ANM, and aimed to explore the reasons of inconsistency in the literature. METHODS: Cross-sectional assessment from an ongoing nationwide cohort study among members of BRCA1/2 mutated families. Information was obtained by a standardized questionnaire. Kaplan-Meier curves were constructed, and Cox regression was used to assess the association between BRCA1/2 mutation status and ANM. Adjustments were made for birth cohort, family, smoking, use of hormonal contraceptives, and parity. RESULTS: A total of 1,208 BRCA1/2 mutation carriers and 2,211 proven noncarriers were included. Overall, no association was found between BRCA1/2 mutation status and ANM (adjusted hazard ratio [HR] = 1.06 [95% CI, 0.87-1.30]). We examined if the null finding was due to informative censoring by uptake of risk-reducing salpingo-oophorectomy. Indeed, within the oldest birth cohort, in which the percentage of surgical menopause events was lowest and comparable between carriers and noncarriers, the HR for earlier natural menopause in carriers was 1.45 (95% CI, 1.09-1.94). The second oldest birth cohort, however, demonstrated a decreased HR (0.67 [95% CI, 0.46-0.98]), and thus no trend over birth cohorts was found. CONCLUSIONS: Various types of selection bias hamper the comparison of ANM between BRCA1/2 mutation carriers and noncarriers, genetically tested in the clinic.