Social disparities in the use of ART treatment: a national register-based cross-sectional study among women in Denmark.

STUDY QUESTION: How are educational level, labor market attachment and income associated with receiving a first ART treatment in either the public or private healthcare sector among women in Denmark? SUMMARY ANSWER: Higher educational level and income as well as labor market attachment were associated with higher probability of initiating ART treatment at public and private fertility clinics among women in Denmark. WHAT IS KNOWN ALREADY: Infertility is common in populations worldwide, and the approach to this issue differs between societies and healthcare systems. In the public Danish healthcare system, ART treatment is free of charge, and the direct cost for patients is therefore low. In the private healthcare sector in Denmark, ART treatment is self-financed. There is limited knowledge about the association between socioeconomic factors and seeking ART treatment, although previous studies have indicated that higher socioeconomic status is associated with seeking ART treatment. STUDY DESIGN, SIZE, DURATION: Women undergoing ART treatment during 1994-2016 registered in the Danish IVF register were individually linked with data from sociodemographic population registers using the Danish Personal Identification number. The study population consisted of 69 018 women treated with ART and 670 713 age-matched comparison women from the background population with no previous history of ART treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: The women included in the analyses were aged 18-45 years. The associations between attained educational level, labor market attachment and income and receiving a first ART treatment attempt were investigated for women either initiating treatment in the public sector or in the private sector, respectively. Information on age and origin was included as potential confounders, and odds ratios (ORs) were estimated in logistic regression models. In addition, analyses were stratified by age group to investigate potential differences across the age span. MAIN RESULTS AND THE ROLE OF CHANCE: Adjusted results showed increased odds of receiving a first ART treatment in either the public or private sector among women with a higher educational level. Furthermore, women in employment were more likely to receive a first ART treatment in the public or private sector compared to women outside the workforce. The odds of receiving a first ART treatment increased with increasing income level. Surprisingly, income level had a greater impact on the odds of receiving a first ART treatment in the public sector than in the private sector. Women in the highest income group had 10 times higher odds of receiving a first ART treatment in the public sector (OR: 10.53 95% CI: 10.13, 10.95) compared to women in the lowest income group. Sub-analyses in different age groups showed significant associations between ART treatment and income level and labor market attachment in all age groups. LIMITATIONS, REASONS FOR CAUTION: Our study does not include non-ART treatments, as the national IVF register did not register these types of fertility treatments before 2007. WIDER IMPLICATIONS OF THE FINDINGS: In Denmark, there is equal access to medically assisted reproduction treatment in the publicly funded healthcare system, and since there is no social inequality in the prevalence of infertility, social inequality in the use of ART treatment would not be expected as such. However, our results show that social inequality is found for a first ART treatment attempt across publicly and privately funded ART treatment across the socioeconomic indicators, educational level, labor market attachment and income. STUDY FUNDING/COMPETING INTEREST(S): The funding for the establishment of the Danish National ART-Couple II Cohort (DANAC II Cohort) was obtained from the Rosa Ebba Hansen Foundation. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Infertility, pregnancy loss and assisted reproduction in women with asthma: a population-based cohort study.

STUDY QUESTION: Is the chance of childbirth, and risk of infertility, pregnancy loss and need for assisted reproduction different for women with asthma compared to women without asthma? SUMMARY ANSWER: Women with asthma had comparable chances of giving birth compared to the reference population, however, their risk of both infertility and pregnancy loss, as well their need for medically assisted reproduction, was higher. WHAT IS KNOWN ALREADY: Reproductive dysfunction has been reported among women with asthma, including longer time to pregnancy, increased risk of pregnancy loss and a higher need of medically assisted reproduction, but their risk of clinical infertility is unknown. STUDY DESIGN, SIZE, DURATION: This longitudinal register-based cohort study included all women with a healthcare visit for delivery, infertility, pregnancy loss or induced abortion in the southernmost county in Sweden, over the last 20 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the Skåne Healthcare Register, we identified all women aged 15-45 between 1998 and 2019, who received a diagnosis of asthma before their first reproductive outcome (n = 6445). Chance of childbirth and risk of infertility, pregnancy loss and assisted reproduction were compared to a healthcare seeking population of women without any asthma (n = 200 248), using modified Poisson regressions. MAIN RESULTS AND THE ROLE OF CHANCE: The chance of childbirth was not different between women with asthma versus those without, adjusted risk ratio (aRR) = 1.02, 95% CI: 1.01-1.03. The risk of seeking care for infertility was increased, aRR = 1.29, 95% CI: 1.21-1.39, and women with asthma more often needed assisted reproduction aRR = 1.34 95% CI: 1.18-1.52. The risk of suffering a pregnancy loss was higher, aRR = 1.21, 95% CI: 1.15-1.28, and induced abortions were more common, aRR = 1.15, 95% CI: 1.11-1.20, among women with asthma. LIMITATIONS, REASONS FOR CAUTION: The study was an observational study based on healthcare visits and lacked detailed anthropometric data, thus residual confounding cannot be excluded. Only women with a healthcare visit for a reproductive outcome were included, which cannot be translated into pregnancy intention. A misclassification, presumed to be non-differential, may arise from an incorrect or missing diagnosis of asthma or female infertility, biasing the results towards the null. WIDER IMPLICATIONS OF THE FINDINGS: This study points towards reproductive dysfunction associated with asthma, specifically in regards to the ability to maintain a pregnancy and the risk of needing medically assisted reproduction following clinical infertility, but reassuringly the chance of subsequently giving birth was not lower for these women. STUDY FUNDING/COMPETING INTEREST(S): This article is part of the ReproUnion collaborative study, co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne and Ferring Pharmaceuticals. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Infertility-related stress and the risk of antidepressants prescription in women: a 10-year register study.

STUDY QUESTION: Is the first-time redeemed prescription of antidepressants predicted by the level of infertility-related stress in women seeking ART treatment? SUMMARY ANSWER: Infertility-related stress in the personal and marital domains and general physical stress reactions were significant predictors of a first redeemed prescription of antidepressants after ART treatment in this 10-year follow-up cohort study. WHAT IS KNOWN ALREADY: The literature has found inconsistent findings regarding the association between infertility-related stress and later psychological adjustment in fertility patients. The association between infertility-related stress and later prescription of antidepressants had never been explored in long-term cohort studies. STUDY DESIGN, SIZE, DURATION: All women (n = 1169) who participated in the Copenhagen Cohort Multi-centre Psychosocial Infertility (COMPI) cohort study in the year 2000 (questionnaire data) were linked with the register-based Danish National ART-Couple (DANAC) I cohort, which includes women and their partners having received ART treatment from 1 January 1994 to 30 September 2009. The study population were among other national health and sociodemographic registers further linked with the Danish National Prescription Registry. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women initiating ART treatment were followed until they had redeemed the first prescription of antidepressants or until 31 December 2009. Logistic regression analyses were conducted to test the association between general physical stress reactions and infertility-related stress in the personal, marital and social domains, respectively, and a future redeemed prescription of antidepressants. Age, education level, marital status, number of fertility treatments prior to study inclusion and female infertility diagnosis were included as covariates in the adjusted analyses. Further, the analysis was stratified according to childbirth or no childbirth during follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: The final sample consisted of 1009 women with a mean age of 31.8 years. At study inclusion, women had tried to conceive for an average of 3.45 years. At 10-year follow-up, a total of 13.7% of women had a first redeemed prescription of antidepressant medication. The adjusted odds ratio (OR) showed that high general physical stress predicted the later prescription of antidepressants (adjusted (adj) OR = 2.85, 95% confidence interval (CI) 1.96-4.16). Regarding infertility-related stress domains, high personal stress (adj OR = 2.14, 95% CI 1.46-3.13) and high marital stress (adj OR = 1.80, 95% CI 1.23-2.64) were significantly associated with the later prescription of antidepressants. Social stress was not significantly associated with the future redeemed prescription of antidepressants (adj OR = 1.10, 95% CI 0.76-1.61). Among women not having achieved childbirth during follow-up, the risk of a first-time prescription of antidepressants associated with infertility-specific stress was higher compared to the risk among women having childbirth during follow-up. LIMITATIONS, REASONS FOR CAUTION: This study did not account for potential mediating factors, such as negative life events, which could be associated with the prescription of antidepressants. Second, we are not able to know if these women had sought psychological support during follow-up. Additionally, antidepressants might be prescribed for other health conditions than depressive disorders. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that women presenting high infertility-related stress in the personal and marital domains were at higher risk of redeemed first-time prescription of antidepressants after ART, independently of having delivered a child or not after initiation of ART treatment. Women would benefit from an initial screening specifically for high infertility-related stress. The COMPI Fertility Problem Stress Scales can be used by clinical staff in order to identify women in need of psychological support before starting ART treatments. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Portuguese Foundation for Science and Technology (FCT) under an individual doctoral grant attributed to the first author (SFRH/BD/103234/2014). The establishment of the DANAC I cohort was funded by Rosa Ebba Hansen's Fund. The COMPI Infertility Cohort project was supported by The Danish Health Insurance Fund (J.nr. 11/097-97), the Else and Mogens Wedell-Wedellsborgs Fund, the manager E. Danielsens and Wife's Fund, the merchant L.F. Foghts Fund, the Jacob Madsen and Wife Olga Madsens Fund. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: NA.

Male factor infertility and risk of death: a nationwide record-linkage study.

STUDY QUESTION: What is the risk of death among men with oligospermia, unspecified male factor and azoospermia in the years following fertility treatment? SUMMARY ANSWER: No significantly elevated risk was observed among men with oligospermia and unspecified male factor, while an increased risk was found among men with azoospermia. WHAT IS KNOWN ALREADY: Previous studies have shown associations between male factor infertility and risk of death, but these studies have relied on internal reference groups and the risk of death according to type of male infertility is not well characterized. STUDY DESIGN, SIZE, DURATION: In this prospective record-linkage cohort study, we identified men who had undergone medically assisted reproduction (MAR) between 1994 and 2015. Data was linked to the Danish causes of death register and sociodemographic registers through personal identification numbers assigned to all Danish citizens at birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men that had undergone MAR in Denmark (MAR Cohort; n = 64 563) were identified from the Danish IVF register, which includes data on whether infertility was due to male factor. For each man in the MAR cohort, five age-matched men who became fathers without fertility treatment were selected from the general population (non-MAR fathers; n = 322 108). Men that could not adequately be tracked in the Danish CPR register (n = 1259) and those that were censored prior to study entry (n = 993) were excluded, leaving a final population of 384 419 men. Risk of death was calculated by Cox regression analysis with age as an underlying timeline and adjustments for educational attainment, civil status and year of study entry. The risk of death was compared among men with and without male factor infertility identified from the IVF register (internal comparisons) as well as to the non-MAR fathers (external comparison). MAIN RESULTS AND THE ROLE OF CHANCE: The risk of death between the MAR cohort (all men, regardless of infertility) and the non-MAR fathers was comparable [hazard ratio (HR), 1.07; 95% CI, 0.98-1.15]. When the MAR cohort was limited to infertile men, these men were at increased risk of death [HR, 1.27; 95% CI, 1.12-1.44]. However, when stratified by type of male factor infertility, men with azoospermia had the highest risk of death, which persisted when in both the internal [HR, 2.30; 95% CI, 1.54-3.41] and external comparison [HR, 3.32; 95% CI, 2.02-5.40]. No significantly elevated risk of death was observed among men with oligospermia [HR, 1.14; 95% CI, 0.87-1.50] and unspecified male factor [HR, 1.10; 95% CI, 0.75-1.61] compared with the non-MAR fathers. The same trends were observed for the internal comparison. LIMITATIONS, REASONS FOR CAUTION: Duration of the follow-up was limited and there is limited generalizability to infertile men who do not seek fertility treatment. WIDER IMPLICATIONS OF THE FINDINGS: Using national health registers, we found an increased risk of death among azoospermic men while no increased risk was found among men with other types of infertility. For the azoospermic men, further insight into causal pathways is needed to identify options for monitoring and prevention. STUDY FUNDING/COMPETING INTEREST(S): This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. C.G.'s research stay at Stanford was funded by grants from the University of Copenhagen, Kong Christian den Tiendes Fond, Torben og Alice Frimodt Fond and Julie Von Müllen Fond. M.E. is an advisor for Sandstone and Dadi. All other authors declare no conflict of interests. TRIAL REGISTRATION NUMBER: Not relevant.

Parental socioeconomic position and risk of ADHD in offspring: a cohort study of 9648 individuals in Denmark 1976-2013.

The strength of the association between parental socioeconomic position (SEP) and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring is found to vary substantially, perhaps due to the negligence of possible changes in parental life course SEP. The present study investigated the association between parental SEP in adulthood and risk of ADHD diagnosis in offspring and whether parental childhood SEP modified this association. The study population included 9648 live-born singletons followed in the Psychiatric Central Register from birth in 1976-1996 until 2013. Cox regression was used to estimate hazard ratios for ADHD diagnosis according to parental SEP in adulthood. The results showed that low parental SEP in adulthood was associated with higher risk of ADHD diagnosis in offspring, also after adjustment for possible confounders. Thus, offspring of parents with low SEP in adulthood had 4.52 (95% CI 2.81-7.26) times higher hazard of ADHD diagnosis compared with offspring of parents with high SEP in adulthood. Further, parental childhood SEP was found to modify the observed association. Thus, offspring of parents with downward social mobility from childhood to adulthood and offspring of parents with stable low SEP experienced the highest risk of ADHD diagnosis, followed by offspring of parents with upward social mobility, compared with offspring of parents with stable high SEP. The results suggest that it is important to take into account the possibility of social mobility as changes in parental life course SEP from childhood to adulthood seem to influence the risk of ADHD diagnosis in offspring.

Concerns on future fertility among users and past-users of combined oral contraceptives: a questionnaire survey.

Objective: The combined oral contraceptive pill is the most preferred contraceptive method worldwide. Despite high life-time prevalence of infertility of 16-26%, scarce data about concerns of future fertility among COC users are available. We aimed to study whether COC usage induces concerns about fertility. Methods: Online questionnaire-based survey included 1283 current COC users and 1006 past users. The questionnaire covered knowledge and concerns of various aspects of fertility with respect to COC usage. Results: Significantly, more current users (66%) than past users (52%) had considered whether or not COC usage could affect future fertility (OR = 1.6, 95% CI 1.3-1.9). Nearly 50% of both groups believed COC usage could impair conception rates after discontinuation. Furthermore, 28% current vs. 19% past users believed COC could diminish the ovarian reserve more permanently. Conversely, 14% current and 11% past users believed that lack of ovulation could 'spare' the eggs (OR = 0.9, 95% CI 0.7-1.3). Significantly fewer current users (22%) vs. past users (35%) had heard, primarily by female friends, that a short break of 1-2 months during long-term COC usage was healthy, (OR 0.72, 95%CI = 0.56-0.92). Conclusions: Health care professionals prescribing hormonal contraception should be aware of misapprehensions and concerns of fertility among users of COC.

Mortality in Women Treated With Assisted Reproductive Technology-Addressing the Healthy Patient Effect.

In previous studies, investigators have reported reduced mortality among women undergoing assisted reproductive technology (ART) treatment, possibly related to selection of healthy women into ART treatment. Our aim in this study was to explore the impact of relevant selection factors on the association between ART treatment and mortality and to explore effect modification by parity. Women treated with ART in fertility clinics in Denmark during 1994-2009 (n = 42,897) were age-matched with untreated women from the background population (n = 204,514) and followed until December 31, 2010. With adjustment for relevant confounders, the risk of death was lower among ART-treated women during the first 2 years after ART treatment (hazard ratio (HR) = 0.68, 95% confidence interval (CI): 0.63, 0.74), but there was no apparent difference after 10 years (HR = 0.92, 95% CI: 0.79, 1.07). Having children prior to ART treatment was associated with markedly reduced mortality (HR = 0.45, 95% CI: 0.38, 0.53), possibly due to better health among fertile women. While the frequencies of previous medical and psychiatric diagnoses among ART-treated and untreated women were similar, differences in disease severity could explain the reduced mortality among ART-treated women, as poor prognosis would make initiation of ART treatment unlikely. The survival advantage among ART-treated women is likely a selection phenomenon rather than a biological phenomenon.

The impact of ART on union dissolution: a register-based study in Denmark 1994-2010.

STUDY QUESTION: Are couples initiating ART treatment at higher risk for future union dissolution compared to other couples? SUMMARY ANSWER: There is no effect of ART treatments in future marital dissolution over a period of 16 years when adjusting for all confounders. WHAT IS KNOWN ALREADY: Findings regarding marital stability and infertility treatments have been sparse and controversial. While there is data showing higher divorce rates among women who go through infertility treatments, there is also some evidence of this experience bringing couples closer by forcing them to communicate more and to deal with the surrounding stigma. Using a population-based study and couple-level data, we investigated the extent to which ART treatment increases the risk for divorce/marital dissolution during up to 16 years of follow-up. STUDY DESIGN SIZE, DURATION: Register-based national cohort study including all women registered with ART treatment in Denmark between 1 January 1994 and 30 September 2009 (n = 42 845). Marital/cohabiting status was confirmed by matching these women to partners who they were married to or shared an address with. To account for having a significant relationship at baseline (2 years), marital/cohabiting status was confirmed by accessing this variable before the establishment of the cohort back to 1 January 1992. PARTICIPANTS/MATERIALS, SETTING, METHODS: A comparison group from the background population including five controls per case and matched to female age at baseline was prospectively sampled. Participants could change status during follow-up if they entered ART. The final sample had 148 972 couples, followed until marital dissolution, death of self/spouse, migration or until 31 December 2010. We used Cox regression models adjusting for female and male age, education, marriage, common child at baseline and live-born child during follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, the majority of couples were married (69%). More non-ART couples opted for marriage (70% versus 64%; P < 0.0001) and already had common children at study entry (43% versus 9%; P < 0.0001). During the 16 years of follow-up the majority of couples had children with their baseline partners (56% non-ART versus 65% ART), and 22% ended up separated or divorced (20% ART versus 22% non-ART). Findings revealed a lower risk of break-up among ART couples (crude HR 0.84, 95% CI 0.82-0.86), even after adjusting for both partners' age, education, partnership status and having a common child at baseline (adj HR 0.83, 95% CI 0.80-0.86). However, when subsequent common children (time-dependent) was added to the model, no difference in the risk of dissolution was found (adj HR 1.00, 95% CI 0.99-1.01). A significant interaction between ART status and common children showed that the risk of break-up was attributed to childlessness regardless of having gone through ART treatment. LIMITATIONS REASON FOR CAUTION: This study did not control for involuntary childlessness, non-ART fertility care (ovulation induction, IUI) and biological parenthood. Additionally, there are important predictors of divorce that were not considered. We were unable to adjust for religion, existence of previous marital relationships, income, employment, health status of parents and child(ren), and quality of relationship. WIDER IMPLICATION OF FINDINGS: The finding that going through ART does not increase the risk of break up per se is reassuring for couples who underwent ART and have children or are contemplating to start ART. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by FCT (Portuguese Foundation for Science and Technology), grant ref. SFRH/BPD/85789/2012. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Male factor infertility and risk of multiple sclerosis: A register-based cohort study.

BACKGROUND: Gender, possibly due to the influence of gonadal hormones, is presumed to play a role in the pathogenesis of multiple sclerosis (MS), but no studies have evaluated whether male infertility is associated with MS. OBJECTIVE: To study the association between male factor infertility and prevalent as well as incident MS. METHOD: Our cohort was established by linkage of the Danish National in vitro fertilization (IVF) registry to The Danish Multiple Sclerosis Registry and consisted of 51,063 men whose partners had undergone fertility treatment in all public and private fertility clinics in Denmark between 1994 and 2015. RESULTS: With a median age of 34 years at baseline, 24,011 men were diagnosed with male factor infertility and 27,052 did not have male factor infertility and made up the reference group. Men diagnosed with male factor infertility had a higher risk of prevalent (odds ratio (OR) = 1.61, 95% confidence interval (95% CI) 1.04-2.51) and incident MS (hazard ratio (HR) = 1.28, 95% CI 0.76-2.17) when compared to the reference group. CONCLUSION: This nationwide cohort study has shown, for the first time, an association between male infertility and MS which may be due to underlying common etiologies such as hypogonadism, shared genetics, or a joint autoimmune component.

Risk of diabetes according to male factor infertility: a register-based cohort study.

STUDY QUESTION: Is male factor infertility associated with an increased risk of developing diabetes? SUMMARY ANSWER: The study provides evidence that male factor infertility may predict later occurrence of diabetes mellitus with the risk being related to the severity of the underlying fertility problem. WHAT IS KNOWN ALREADY: Previous cross-sectional studies have shown an increased prevalence of comorbidities among infertile men when compared to controls. STUDY DESIGN, SIZE, DURATION: In this prospective cohort study, 39 516 men who had since 1994 undergone fertility treatment with their female partner were identified from the Danish national IVF register, which includes data on assumed cause of couple infertility (male/female factor, mixed and unexplained infertility) and type of fertility treatment. With a median follow-up time of 5.6 years, each man was followed for diabetes occurrence from enrollment until 31 December 2012 using the National Diabetes Register (NDR). Men with a history of diabetes prior to their fertility diagnosis were excluded. Hazard ratios (HR) were estimated by Cox proportional hazard models with age as the underlying time scale. In addition to analyzing the data for the entire IVF registration period (1994-2012), separate analyses were performed for men identified from the first (1994-2005) and second (2006-2012) IVF registration period owing to heterogeneity in the reporting of male factor infertility in these two time periods, because the reason for male factor infertility was not available from the first register. PARTICIPANTS/MATERIALS, SETTING, METHODS: Male factor infertility was identified from the variable 'yes' or 'no' from the first IVF register and through a diagnosis code (e.g. oligospermia, azoospermia) from the second IVF register. The reference group was men with male factor infertility (='no') and those with normal semen quality or sterilized men. Of the included men, 18 499 (46.8%) had male factor infertility and 21 017 (53.2%) made up the reference group. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 651 (1.6%) diabetes cases were identified during the follow-up period. The adjusted HR's for diabetes risk among men with male factor infertility when compared to the reference group were HR = 1.08 (95% CI: 0.89, 1.31) and HR = 1.45 (95% CI: 1.06, 1.97) for the first and second IVF registration period, respectively. When assessing the effects of individual causes of male factor infertility, the adjusted HR's for men with oligospermia, azoospermia and aspermia were HR = 1.44 (95% CI: 1.01, 2.06), HR = 2.10 (95% 1.25, 3.56) and HR = 3.20 (95% CI 1.00, 10.31), respectively. LIMITATIONS, REASONS FOR CAUTION: We found no increased risk among men identified from the first IVF register, which may be related to exposure misclassification as the reason for male factor infertility was not available from this time period. The NDR does not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: These findings support previous studies that a man's reproductive and somatic health are closely intertwined and highlight the importance for further monitoring of these men. Further, implementation of diabetes screening may be especially relevant among aspermic and azoospermic men. STUDY FUNDING/COMPETING INTERESTS: This article is part of the ReproUnion collaborative study, co-financed by the European Union, Intereg V Öresund-Kattegat-Skagerrak. None of the authors declare any conflict of interest. TRIAL REGISTRATION NUMBER: None.

Medical and social egg freezing: internet-based survey of knowledge and attitudes among women in Denmark and the UK.

INTRODUCTION: Until recently, limited options for preserving fertility in order to delay childbearing were available. Although egg freezing and successful thawing is now possible, it remains unclear to what extent women are aware of the availability of this technique, their attitudes towards its use, or the circumstances under which this technique may be considered. MATERIAL AND METHODS: An online cross-sectional survey was designed to investigate knowledge and attitudes of women in Denmark and the UK on egg freezing and their potential intentions regarding the procedure. RESULTS: Data was collected from September 2012 to September 2013 and the responses of 973 women were analyzed. In total, 83% of women reported having heard of egg freezing, and nearly all considered it acceptable for medical indications, whilst 89% considered it acceptable for social reasons. Overall, 19% expressed active interest in the procedure, and 27% expressed possible interest. Key factors found to positively influence attitudes to accepting the procedure were reassurance that it would not affect future fertility and greater than 50% chance of achieving a live birth. Characteristics significantly associated with intention to freeze eggs were being single, age under 35 years, childlessness, and a history of infertility. In this group, risk and cost were less important considerations. CONCLUSIONS: This study indicates that there is widespread awareness and support of the availability of eggs freezing for reproductive planning. Reassurance regarding its efficacy appears more important than its potential adverse effects on their health or that of future children, or the costs of the procedure.

Use and Preference of Advice on Small Children's Food: Differences Between Parents From Ethnic Minority, Ethnic Majority, and Mixed Households.

The authors analyzed the influence of acculturation on parental attitudes to, and use of, different sources of health advice about young children's food in Denmark. Using combined ethnic position of the children's parents as a proxy for household acculturation, the authors conducted a postal survey of 2,511 households with young children (6 months to 3.5 years) occupying ethnic minority, ethnic majority, or ethnic mixed position. The analysis showed that the use of advice differed in the 3 groups. Households with ethnic minority status were more likely to use the child's grandparents, general practitioners, and hospital staff as information sources, while households with ethnic majority status were more likely to use mothers' peer groups and written material. In all types of household municipal public health nurses were relied on as a source of advice on young children's food, but households with ethnic minority status were more likely to find the advice obtained in this way incompatible with their family eating habits. Although existing dietary health communication strategies delivered by public health nurses appear to work well in all household types, parents from minority households seem to experience dilemmas. These may be related to their cultural and generational status at the time of receiving the advice. Adjustments to current communication strategies on young children's food are suggested.

Cancer in children and young adults born after assisted reproductive technology: a Nordic cohort study from the Committee of Nordic ART and Safety (CoNARTaS).

STUDY QUESTION: Do children and young adults born after assisted reproductive technology (ART) have an increased risk of cancer? SUMMARY ANSWER: Children born after ART showed no overall increase in the rate of cancer when compared with children born as a result of spontaneous conception. WHAT IS KNOWN ALREADY: Children born after ART have more adverse perinatal outcomes, i.e. preterm births, low birthweights and birth defects. Previous studies have shown divergent results regarding the risk of cancer among children born after ART. STUDY DESIGN, SIZE, DURATION: A retrospective Nordic population-based cohort study was performed, comprising all children born after ART in Sweden, Denmark, Finland and Norway between 1982 and 2007. The mean (±standard deviation) follow-up time was 9.5 (4.8) years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Children born after ART (n = 91 796) were compared with a control group of children born after spontaneous conception. This control group was almost 4-fold the size of the ART group (n = 358 419) and matched for parity, year of birth and country. Data on perinatal outcomes and cancer were obtained from the National Medical Birth Registries, the Cancer Registries, the Patient Registries and the Cause of Death Registries. The cancer diagnoses were divided into 12 main groups. Hazard ratios (HRs) and adjusted HR were calculated. Adjustments were carried out for country, maternal age, parity, sex, gestational age and birth defects. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant increase in overall cancer rates among children born after ART when compared with children born after spontaneous conception (adjusted HR 1.08; 95% CI 0.91-1.27). Cancer, of any form, was found among 181 children born after ART (2.0/1000 children, 21.0/100 000 person-years) compared with 638 children born after spontaneous conception (1.8/1000 children, 18.8/100 000 person-years). Leukaemia was the most common type of cancer (n = 278, 0.62/1000 children) but no significantly increased incidence was found among children born after ART. An increased risk was observed for 2 of 12 cancer groups. They were central nervous system tumours (adjusted HR 1.44; 95% CI 1.01-2.05) and malignant epithelial neoplasms (adjusted HR 2.03; 95% CI 1.06-3.89); the absolute risks were 0.46/1000 and 0.15/1000 children, respectively, corresponding to an absolute increased risk of 0.14/1000 and 0.08/1000 children, respectively. LIMITATIONS, REASONS FOR CAUTION: As this is an observational study, the main limitation is the fact that it is not possible to adjust for all potential confounders. We were not able to control for confounders such as socio-economic status and perinatal factors, such as Apgar score, which other studies have suggested affect cancer rates. WIDER IMPLICATIONS OF THE FINDINGS: The results of this large population-based cohort study are in agreement with most previously published studies. The main findings are reassuring for couples undergoing ART, children born after ART and clinicians working with ART. STUDY FUNDING/COMPETING INTERESTS: No conflict of interest was reported. The study was supported by grants from The European Society for Human Reproduction and Embryology (ESHRE), Sahlgrenska University Hospital, Gothenburg, Sweden, the University of Copenhagen, Denmark, the Danish Agency of Science, Technology and Innovation and the Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

Opportunities for healthier child feeding. Does ethnic position matter? - self-reported evaluation of family diet and impediments to change among parents with majority and minority status in Denmark.

Health inequality between ethnic groups is expressed in differences in the prevalence of diet related diseases. The aim of the study was to investigate and compare barriers toward eating healthier among ethnic majority and minority parents in Denmark. A postal survey was carried out among 2511 parents with either Danish or non-western ethnic minority descendant background, investigating barriers on cultural, structural, social, individual, and practical levels. The results showed that compared with parents of Danish origin, ethnic minority parents were more likely to evaluate their own diets negatively (OR 3.0, CI 1.7-5.3), and to evaluate their children's diets negatively (OR 4.6, CI 2.5-8.4). In addition, ethnic minority parents to a higher degree experienced barriers to eating healthier than Danish parents did. Most salient was ethnic minority parents' expression of a lack of control over their own food intake and the food given to their children in everyday life. Such a lack of control was identified on practical, social, structural and individual levels. Young age of the parents was found to explain some of the differences between ethnic groups. It is concluded that dietary interventions directed at parents of small children should address not only cultural background but also barriers operating on practical, social, structural, and individual levels, as some of these influence ethnic minorities and the majority population differently. Further exploration of the importance of young age and the interplay between structural and cultural factors in the lives of ethnic minority families is needed.

Do psychotic experiences act as effect modifiers in youths with common mental health problems allocated to transdiagnostic cognitive behavioural therapy versus management as usual? Secondary analyses of the Mind-My-Mind randomized trial.

BACKGROUND: Psychotic experiences (PEs) are common in help-seeking youths with non-psychotic mental health problems, yet the clinical importance of PEs as potential effect modifiers of psychotherapy interventions has been scarcely examined. We examined if PEs were associated with a differential response to transdiagnostic cognitive behavioural therapy (CBT) aimed at common emotional and behavioural problems. METHODS: We present secondary analyses from the Mind My Mind (MMM) trial that randomized 396, 6-16-year-old youths to either 9-13 sessions of transdiagnostic modular community-based CBT (MMM) or community-based management as usual (MAU). MMM was superior to MAU in reducing parent-reported impact of mental health problems according to the Strengths and Difficulties Questionnaire (SDQ). PEs were assessed by semi-structured screening interviews at baseline. The contrast between subgroups (presence/absence of PEs) was calculated to test if PEs are potential effect modifiers regarding the change in parent-reported SDQ-impact (primary outcome, rated 0[low]-10[high]) and other SDQ-related outcomes. RESULTS: Baseline PEs were present in 74 (19%) of youths. The superior effect of MMM on changes in SDQ-impact from baseline to week 18 was not effect modified by the presence of PEs (PEs[yes] -0.89 [95%CI -1.77;-0.01] vs. PEs[no] -1.10 [95%CI -1.52;-0.68], p-value for interaction .68). For secondary outcomes similar patterns were observed. Limitations Statistical power was limited to show if PEs modified treatment response. Replication and meta-analytic evidence are needed. CONCLUSIONS: The beneficial effects of MMM transdiagnostic CBT did not differ by PE-status, indicating that youths with emotional and behavioural problems could be offered such psychotherapy irrespective of co-occurring PEs.

Influence of the COVID-19 pandemic on births and induced abortions in Southern Sweden: a register-based study.

BACKGROUND: Pandemics are linked with declining birth rates, but little is known about how the COVID-19 pandemic has influenced childbearing decisions. We aimed to investigate the associations between the COVID-19 pandemic and reproductive decisions, specifically to identify potential changes in the frequency of deliveries and induced abortions in Skåne, Sweden. METHODS: Using the Skåne Healthcare Register, we identified women aged 15-45 years who had at least one pregnancy-related care visit registered between 1 January 2013 and 11 November 11 2021. Deliveries and induced abortions were identified, and changes in weekly delivery and abortion counts were assessed using an interrupted time series design. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated from a Poisson regression model. RESULTS: During the study period we identified 129 131 deliveries and 38 591 abortions. Compared with the counterfactual (exposed interval assuming COVID-19 had not occurred), pandemic exposure was associated with fewer deliveries (RR 0.93; 95% CI 0.89 to 0.98). For abortions, pandemic exposure appeared to be associated with fewer abortions (RR 0.95; 95% CI 0.90 to 1.00); however, age-related differences were found. Among women aged 25 years and over, pandemic exposure was more strongly associated with fewer abortions. Contrastingly, among women aged under 25 years, abortions appeared to increase. CONCLUSIONS: The COVID-19 pandemic seemed to have contributed to a decline in births in Southern Sweden. During the same period, abortions declined in women in the older age range, but contrastingly increased among younger women.

The risk of Type 1 diabetes in children born after ART: a Nordic cohort study from the CoNARTaS group.

STUDY QUESTION: Do children born after ART have a higher risk of developing Type 1 diabetes (DM1) than children conceived without ART? SUMMARY ANSWER: The risk of DM1 was similar for children conceived with and without ART, and there were no clear differences in risk according to method of fertility treatment. WHAT IS KNOWN ALREADY: ART is associated with a higher risk of adverse perinatal outcomes, and the risk depends on the method of ART. The Developmental Origins of Health and Disease theory proposes that prenatal stress can provoke changes in endocrine processes which impact health later in life. STUDY DESIGN SIZE DURATION: A Nordic register-based cohort study was carried out, including all children born in Denmark (birth years 1994-2014), Finland (1990-2014), and Norway (1984-2015). The study included 76 184 liveborn singletons born after ART and 4 403 419 born without ART. Median follow-up was 8.3 and 13.7 years in the ART and non-ART group, respectively. PARTICIPANTS/MATERIALS SETTING METHODS: The cohort, initiated by the Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS), was established by linking national registry data from the medical birth registries and national patient registries available in the Nordic countries. We performed multivariable logistic regression analyses for the birth year intervals 1984-1990, 1991-1995, 1996-2000, 2001-2005, 2006-2010, and 2011-2015, while adjusting for year of birth within each interval, sex of the child, parity, maternal age, maternal diabetes, and maternal smoking during pregnancy as potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: During follow-up, 259 (3.4‰) children born after ART were diagnosed with DM1, while this was the case for 22 209 (5.0‰) born without ART, corresponding to an adjusted odds ratio of 0.98 (95% CI: 0.861.11). Within the different birth year intervals, no significant difference in risk of DM1 between the two groups was found, except for the youngest cohort of children born 2011-2015 where ART was associated with a higher risk of DM1. We found no significant differences in risk of DM1 when comparing children born after IVF versus ICSI or fresh versus frozen embryo transfer, but with only few cases in each group. LIMITATIONS REASONS FOR CAUTION: The main limitation of the study is the relatively short follow-up time. The incidence rate of DM1 peaks during ages 10-14 years, hence a longer follow-up would benefit all analyses and, in particular, the subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGS: Overall, our findings are reassuring especially considering the concomitantly increasing number of children born from ART and the increasing incidence of DM1 globally. STUDY FUNDING/COMPETING INTERESTS: This Nordic registry study has been supported by the Nordic Trial Alliance/NORDFORSK and Rigshospitalets Research Foundation. The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. None of the authors has any conflicts of interest to declare regarding this study. TRIAL REGISTRATION NUMBER: ISRCTN11780826.

Effect modification of an effective transdiagnostic cognitive behavioral psychotherapy in youths with common mental health problems: Secondary analyses of the randomized mind-my-mind trial.

Mind My Mind (MMM) cognitive behavioral therapy (CBT) manualized treatment is effective in the management of common emotional and behavioral mental health problems in youth, yet not all individuals respond satisfactorily to treatment. This study explored potential effect modifiers, i.e., baseline factors associated with a differential treatment effect. We conducted secondary effect modifier analyses with MMM trial data, which involved randomization of 396 youths aged 6-16 years to either MMM CBT treatment (9-13 sessions) or management as usual in local community settings. We examined sociodemographic- (sex, age, family composition, ethnicity, parental education, and income) and clinical variables (mental disorders and duration of mental health problems) as potential effect modifiers of the a) change in parent-rated impact of mental health problems measured by the Strengths and Difficulties Questionnaire (SDQ) or b) response (reduction of ≥1 on SDQ-impact). In intention-to-treat analyses, superior treatment (net) benefits from the MMM intervention were found among youths who met criteria for any mental disorder at baseline (-1.25 [95%CI: -1.67;-0.82]) compared to youths that did not meet diagnostic criteria (-0.22 [95%CI:-1.09;0.65]). Comorbidity vs no comorbidity (-1.84 [95%CI:-2.58;-1.10] vs -0.72 [95%CI:-1.15;-0.29]) and longer duration of untreated mental health problems, i.e., more vs less than 6 months (-1.16 [95%CI:-1.55;-0.78] vs 0.43 [95%CI:-1.01;1.86]) were also associated with superior treatment benefits. The sociodemographic factors were not associated with differential treatment effects in the intention-to-treat analyses. These findings suggest that community-based programs like the MMM are well-suited for youths with substantial mental health problems. Clinical Trials Identifier: NCT03535805.

The impact of social relations among men and women in fertility treatment on the decision to terminate treatment.

STUDY QUESTION: Do social support and social strain from social relations have an impact on the decision to terminate fertility treatment among men and women after 1 year of unsuccessful treatment? SUMMARY ANSWER: Several functional aspects of social relations show an impact on the probability to terminate treatment; social support from family significantly decreases the probability to terminate and experience of conflicts or problematic communication with the partner significantly increases the probability to terminate treatment. WHAT IS KNOWN ALREADY: Fertility patients can experience psychological, physical and economical strain as consequences of infertility and fertility treatment, and previous studies have shown that these pressures increase the probability of deciding to terminate treatment before the treatment options are exhausted. Some studies have indicated that social relations can also have an effect. STUDY DESIGN, SIZE, DURATION: This study is part of the prospective Infertility Cohort from the Copenhagen Multi-centre Psychosocial Infertility Research Programme. Baseline data were collected during January 2000-August 2001 among patients recruited at five Danish fertility clinics during their initial visit and follow-up data were collected after 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study group (n = 777; 427 women, 350 men) consisted of patients who did not achieve a live birth or an ongoing pregnancy during follow-up. Social support and strain from the patients' partner, family, family-in-law, friends and colleagues were measured at baseline and the decision to terminate treatment while treatment options were not yet exhausted was measured as the outcome at the 1-year follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: At the 1-year follow-up, 23% of the study group had decided to terminate treatment. For women, low levels of family support, specifically with regard to infertility, were associated with the termination of treatment after 1 year [odds ratio (OR) 6.1, 95% confidence interval (CI) 2.2-16.8] and, for men, low levels of general family support had a similar impact (OR 2.6, 95% CI 1.0-7.0). For men, difficulties in communicating with their partner about the infertility increased the probability of terminating the treatment (OR 2.3, 95% CI 1.2-4.1) and, for women, frequent conflicts with their partner increased the probability of terminating the treatment (OR 12.4, 95% CI 2.9-54.1). For women, conflicts with friends were also a predictor of treatment termination (OR 2.2, 95% CI 1.2-4.2). WIDER IMPLICATIONS OF THE FINDINGS: Functional aspects of social relations have an impact on the decision to terminate fertility treatment among men and women. The findings in this study provide new insights into how the close social environment can have implications for men and women going through fertility treatment. FUNDING: This study has received support from the Danish Health Insurance Fund (J.nr. 11/097-97), the Else and Mogens Wedell-Wedellsborgs Fund, the manager E. Danielsens and Wife's Fund, the merchant L.F. Foghts Fund, the Jacob Madsen and Wife Olga Madsen's Fund, and the Engineer K.A. Rohde and Wife's Fund. The authors have no conflicts of interest to declare.

Design of the OPUS School Meal Study: a randomised controlled trial assessing the impact of serving school meals based on the New Nordic Diet.

INTRODUCTION: Danish children consume too much sugar and not enough whole grain, fish, fruit, and vegetables. The Nordic region is rich in such foods with a strong health-promoting potential. We lack randomised controlled trials that investigate the developmental and health impact of serving school meals based on Nordic foods. AIM: This paper describes the rationale, design, study population, and potential implications of the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. METHODS: In a cluster-randomised cross-over design, 1021 children from 3rd and 4th grades (8-11 years old) at nine Danish municipal schools were invited to participate. Classes were assigned to two 3-month periods with free school meals based on the New Nordic Diet (NND) or their usual packed lunch (control). Dietary intake, nutrient status, physical activity, cardiorespiratory fitness, sleep, growth, body composition, early metabolic and cardiovascular risk markers, illness, absence from school, wellbeing, cognitive function, social and cultural features, food acceptance, waste, and cost were assessed. RESULTS: In total, 834 children (82% of those invited) participated. Although their parents were slightly better educated than the background population, children from various socioeconomic backgrounds were included. The proportion of overweight and obese children (14%) resembled that of earlier examinations of Danish school children. Drop out was 8.3%. CONCLUSIONS: A high inclusion rate and low drop out rate was achieved. This study will be the first to determine whether school meals based on the NND improve children's diet, health, growth, cognitive performance, and early disease risk markers.