Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy.

STUDY QUESTION: How has the interface between genetics and assisted reproduction technology (ART) evolved since 2005? SUMMARY ANSWER: The interface between ART and genetics has become more entwined as we increase our understanding about the genetics of infertility and we are able to perform more comprehensive genetic testing. WHAT IS KNOWN ALREADY: In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and ART and published an extended background paper, recommendations and two Editorials. STUDY DESIGN, SIZE, DURATION: An interdisciplinary workshop was held, involving representatives of both professional societies and experts from the European Union Eurogentest2 Coordination Action Project. PARTICIPANTS/MATERIALS, SETTING, METHODS: In March 2012, a group of experts from the European Society of Human Genetics, the European Society of Human Reproduction and Embryology and the EuroGentest2 Coordination Action Project met to discuss developments at the interface between clinical genetics and ART. MAIN RESULTS AND THE ROLE OF CHANCE: As more genetic causes of reproductive failure are now recognized and an increasing number of patients undergo testing of their genome prior to conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and PGD may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from RCTs to substantiate that the technique is both effective and efficient. Whole genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. LIMITATIONS, REASONS FOR CAUTION: The legal landscape regarding assisted reproduction is evolving, but still remains very heterogeneous and often contradictory. The lack of legal harmonization and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe, and beyond. WIDER IMPLICATIONS OF THE FINDINGS: This continually evolving field requires communication between the clinical genetics and IVF teams and patients to ensure that they are fully informed and can make well-considered choices. STUDY FUNDING/COMPETING INTERESTS: Funding was received from ESHRE, ESHG and EuroGentest2 European Union Coordination Action project (FP7 - HEALTH-F4-2010-26146) to support attendance at this meeting.

Reaching for Precision Healthcare in Finland via Use of Genomic Data.

Concerns over future healthcare capacity along with continuing demands for sustainability call for novel solutions to improve citizens' health and wellbeing through effective prevention and improved diagnosis and treatment. Part of the solution to tackle the challenge could be making the most of the exploitation of genomic data in personalized risk assessment, creating new opportunities for data-driven precision prevention and public health. Presently, the utilization of genomic data in the Finnish healthcare system is limited to a few medical specialty areas. To successfully extend the use of genomic information in everyday healthcare, evidence-based and feasible strategies are needed. The national actions that Finland is taking towards this goal are 1) providing scientific evidence for the utility of genomic information for healthcare purposes; 2) evaluating the potential health-economic impact of implementing precision healthcare in Finland; 3) developing a relevant legal framework and infrastructures for the utilization of genomic information; 4) building a national multidisciplinary expert network bringing together relevant professionals and initiatives to achieve consensus among the different stakeholders on specific issues vital for translating genomic data into precision healthcare; 5) building competence and genomic literacy skills among various target groups; and 6) public engagement (informing and educating the public). Taken together, these actions will enable building a roadmap towards the expedient application of genomic data in Finnish healthcare and promoting the health of our citizens.

Successful weight loss maintenance: A systematic review of weight control registries.

Weight loss maintenance is a major challenge for obesity treatment. Weight control registries can be useful in identifying psychological and behavioural factors that could contribute to better long-term success. The objective of this study is to describe the existing weight control registries and their participants and identify correlates of weight loss maintenance. A comprehensive search of peer-reviewed articles published until November 2018 was conducted in PubMed, Web of Science, and Scopus. Studies that reported results from weight control registries were considered. Fifty-two articles, corresponding to five registries (the United States, Portugal, Germany, Finland, and Greece), were included. Registries differed in inclusion criteria and procedures. Of 51 identified weight loss and maintenance strategies, grouped in 14 domains of the Oxford Food and Activity Behaviors taxonomy, the following were the most frequently reported: having healthy foods available at home, regular breakfast intake, increasing vegetable consumption, decreasing sugary and fatty foods, limiting certain foods, and reducing fat in meals. Increased physical activity was the most consistent positive correlate of weight loss maintenance. To our knowledge, this is the first systematic review of information about successful weight loss maintenance obtained from weight control registries. Key common influential characteristics of success were identified, which can inform future prospective studies and weight management initiatives.

Transnational access to large prospective cohorts in Europe: Current trends and unmet needs.

Biobank samples and data from studies of large prospective cohorts (LPC) represent an invaluable resource for health research. Efficient sharing and pooling of samples and data is a central pre-requisite for new advances in biomedical science. This requirement, however, is not compatible with the present scattered and traditional access governance structures, where legal and ethical frameworks often form an obstacle for effective sharing. Moreover, the EU General Data Protection Regulation (GDPR) is demanding increasingly rigorous administration from all those organisations processing personal data. The BBMRI-LPC project (Biobanking and Biomolecular Research Infrastructure - Large Prospective Cohorts) assembled 21 LPCs from 10 countries and two EU-wide multinational cohort networks with a key objective to promote collaborative innovative transnational research proposed by external researchers on the broad field of common chronic diseases, and analyze the gaps and needs involved. BBMRI-LPC organized three scientific calls to offer European investigators an opportunity to gain free of charge transnational access to research material available in the participating cohorts. A total of 11 high-quality research proposals involving multiple prospective cohorts were granted, and the access process in the individual projects carefully monitored. Divergent access governance structures, complex legal and ethical frameworks and heterogeneous procedures were identified as currently constituting substantial obstacles for sample and data transfer in Europe. To optimize the scientific value and use of these research resources, practical solutions for more streamlined access governance in collaborative projects are urgently needed. A number of infrastructure developments could be made to improve time-efficiency in access provision.

Long-term Weight Maintenance after Successful Weight Loss: Motivational Factors, Support, Difficulties, and Success Factors.

OBJECTIVES: The main aims of this study were to assess motivational factors for weight loss, and support and difficulties during the weight loss and weight maintenance phase. METHODS: This study was based upon findings from the Finnish Weight Control Registry (FWCR), including 158 formerly obese persons, who lost at least 10% of their initial weight and maintained it for at least 2 years. Data have been collected through electronic forms. RESULTS: The 2 most commonly reported motivational factors for weight loss were health- and appearance-related factors. Women reported dissatisfaction with their body more commonly than men (p = .023), whereas men reported health-related reasons (p = .008) more often. The majority (58%) reported losing weight alone, without any outside support, men more commonly than women (p = .006). Persons reported fewer difficulties during the maintenance than during the weight loss phase. CONCLUSIONS: Various motivational factors for losing weight may lead to successful weight loss and long-term weight maintenance. Marked sex differences were reported in relation to difficul- ties and need for support.

Personality Traits Associated with Weight Maintenance among Successful Weight Losers.

Objective The influence of personality traits on successful weight loss has been studied previously with conflicting findings. Much less is known about the influence of personality traits on weight maintenance after weight loss. The aims of this study were to assess how personality traits were associated with motivational factors, dietary habits, self-weighing frequency, need for support, and difficulties encountered during the weight loss process in formerly successful weight maintainers. MethodsThis study was based upon findings from the Finnish Weight Control Registry, including 158 (100 women and 58 men, age 18-60 years) formerly obese participants with ≥10% weight loss and who maintained it ≥ 2 years. Data were collected through electronic forms and personality traits were assessed according to the Five Factor Model with the Finnish version of the Ten Item Personality Inventory. ResultsPersonality traits neuroticism, agreeableness, and conscientiousness were associated with motivational factors, self-weighing frequency, dietary habits, support, and difficulties during the weight loss process. Sex differences were observed. ConclusionsPersonality traits may be important in successful long-term weight maintenance after weight loss. Our results might not be generalizable in other populations because only Caucasians were included. The small sample size needs to be considered.

Perceptions of legislation relating to the sharing of genomic biobank results with donors-a survey of BBMRI-ERIC biobanks.

Biobanks accumulate huge amounts of research findings, including participants' genomic data. Increasingly this leads to biobanks receiving research results that could be of clinical significance to biobank participants. The EU Horizon 2020 Project 'Genetics Clinic of the Future' surveyed European biobanks' perceptions of the legal and regulatory requirements for communicating individual research results to donors. The goal was to gain background knowledge for possible future guidelines, especially relating to the consent process. The Survey was implemented using a web-based Webropol tool. The questionnaire was sent at the end of 2015 to 351 European biobanks in 13 countries that are members of BBMRI-ERIC (Biobanking and Biomolecular Resources Research Infrastructure-European Research Infrastructure Consortium). Seventy-two biobanks responded to the survey, representing each of the 13 BBMRI Member States. Respondents were mainly individuals responsible for the governance of biobanks. The replies indicate that the majority of the respondents thought that their national legislation allowed them to contact participants to communicate results, and that research participants had the right to request their results. However, respondents' understanding of their national legislation varied even within member states. Our results indicate that legislation applied to biobanks in many countries may be scattered and difficult to interpret. In BBMRI-ERIC, there is an ongoing discussion about the need for European recommendations on sharing genomic biobank results with donors, which may pave the way for more coherent global guidelines. Our results form a basis for this work.

The interface between assisted reproductive technologies and genetics: technical, social, ethical and legal issues.

The interface between assisted reproductive technologies (ART) and genetics comprises several sensitive and important issues that affect infertile couples, families with severe genetic diseases, potential children, professionals in ART and genetics, health care, researchers and the society in general. Genetic causes have a considerable involvement in infertility. Genetic conditions may also be transmitted to the offspring and hence create transgenerational infertility or other serious health problems. Several studies also suggest a slightly elevated risk of birth defects in children born following ART. Preimplantation genetic diagnosis (PGD) has become widely practiced throughout the world for various medical indications, but its limits are being debated. The attitudes towards ART and PGD vary substantially within Europe. The purpose of the present paper was to outline a framework for development of guidelines to be issued jointly by European Society of Human Genetics and European Society of Human Reproduction and Embryology for the interface between genetics and ART. Technical, social, ethical and legal issues of ART and genetics will be reviewed.

Biobanks as a Central Part of the Finnish Growth and Genomic Strategies: How to Balance Privacy in an Innovation Ecosystem?

Finland has aimed to make itself an international leader in genomic research and related business and, in working towards that goal, has enacted biobank legislation. The Biobank Act requires biobanks to gain approval, be supervised, and register at the national level. Numerous other laws may also apply in any given research setting, such as the Personal Data Act, the Medical Research Act, and the Act on Medical Use of Human Organs and Tissues.In terms of privacy protection, anonymization is generally not permitted under Finnish law and therefore most biobanks pseudonomize data and samples. However, the broad understanding of what is identifiable data in Finland has created difficulties in sharing with non-EU countries. Furthermore, consent to biobank research is only applicable to the sample and related data, not to data stored in other health-related registries, and consent is only to the field of research for that particular biobank. These restrictions impede the sharing of samples and data for research.

Weight loss methods and changes in eating habits among successful weight losers.

BACKGROUND: Changes in several lifestyle related factors are required for successful long-term weight loss. Identification of these factors is of major importance from a public health point of view. METHODS/SUBJECTS: This study was based upon findings from the Finnish Weight Control Registry (FWCR), a web-based registry. In total, 316 people were recruited and 184 met the study inclusion criteria. The aims of this study were to assess means and typical changes in eating habits associated with successful long-term weight loss. RESULTS: Half of the participants (48%) reported that they lost weight slowly primarily with dietary changes. Self-weighing frequency was high, 92% was weighing themselves at least once a week during the weight loss phase, and 75% during the maintenance phase. Dietary aspects associated with successful weight loss and weight maintenance included an increase in intake of vegetables, a reduction in frequency of eating candies and fast food, regular meal frequency and application of the Plate model. CONCLUSIONS: Both slow and fast weight loss may lead to successful long-term results and weight maintenance. A decrease in energy intake was achieved by reducing intake of energy-dense food, applying the Plate model and by regular meal frequency. Key messages Successful long-term weight loss is associated with a reduction in intake of energy-dense food. A more regular meal frequency and a high frequency of self-weighing seem to be helpful.

Consent for Biobanking: The Legal Frameworks of Countries in the BioSHaRE-EU Project.

Currently, there is no single, Europe-wide regulation of biomedical research using human samples and data. Instead, the law that applies spans a number of areas of law, such as data protection, clinical trials, and tissue regulation. In the absence of harmonized regulation, there is considerable scope for national legal variation. This article analyzes the legislative frameworks that apply to biobanking activities to identify differences in legal requirements between the BioSHaRE-EU project countries: Finland, France, Germany, the Netherlands, Norway, and the United Kingdom. This article highlights the primary role of consent and accompanying governance mechanisms, such as research ethics committee oversight, which enable consent exemptions in the context of research. Our analysis identifies a complicated legal landscape, whereby broadly similar provisions are contained in varied sources of law in each jurisdiction. The challenge for researchers is locating the applicable legal provisions within each national legal framework.

Feedback of Individual Genetic Results to Research Participants: Is It Feasible in Europe?

BACKGROUND: There is growing consensus that individual genetic research results that are scientifically robust, analytically valid, and clinically actionable should be offered to research participants. However, the general practice in European research projects is that results are usually not provided to research participants for many reasons. This article reports on the views of European experts and scholars who are members of the European COST Action CHIP ME IS1303 (Citizen's Health through public-private Initiatives: Public health, Market and Ethical perspectives) regarding challenges to the feedback of individual genetic results to research participants in Europe and potential strategies to address these challenges. MATERIALS AND METHODS: A consultation of the COST Action members was conducted through an email survey and a workshop. The results from the consultation were analyzed following a conventional content analysis approach. RESULTS: Legal frameworks, professional guidelines, and financial, organizational, and human resources to support the feedback of results are largely missing in Europe. Necessary steps to facilitate the feedback process include clarifying legal requirements to the feedback of results, developing harmonized European best practices, promoting interdisciplinary and cross-institutional collaboration, designing educational programs and cost-efficient IT-based platforms, involving research ethics committees, and documenting the health benefits and risks of the feedback process. CONCLUSIONS: Coordinated efforts at pan-European level are needed to enable equitable, scientifically sound, and socially robust feedback of results to research participants.

Lifestyle-related factors associated with successful weight loss.

BACKGROUND: Short-term weight loss is often successful, but the obtained results are difficult to maintain. Therefore, a study focusing on obese people who successfully lost weight, with special emphasis upon methods applied and background factors, is of major importance. METHODS/SUBJECTS: This study was based upon a web-based questionnaire, which the participants filled in after registration. Altogether 316 people were recruited through articles in newspapers all over Finland, and of them 184 met the inclusion criteria: age 18-60 years, body mass index (BMI) ≥ 30 kg/m(2) before weight loss, a weight loss of at least 10%, and maintaining it for a minimum of 2 years. RESULTS: A total of 158 participants (100 women and 58 men) were included in the final analyses. The mean age was 44.5 years, average BMI before weight loss 35.9 kg/m(2) and after weight loss 26.1 kg/m(2), average weight loss was 26.5% or 32.4 kg. Compared with the general Finnish population the participants smoked less (P = 0.009), used less alcohol (P ≤ 0.001), and were physically more active (P ≤ 0.001). CONCLUSIONS: People who were successful in long-term weight loss have a much healthier lifestyle than the general Finnish population. Increased physical activity seems to be a major determinant of successful long-term results.

Finland on a road towards a modern legal biobanking infrastructure.

Finland has enacted a Biobank Act that will come into force on 1 September 2013. Finland is regarded as a highly successful environment for medical research using population samples and data for many reasons. One of the rationales behind the new legislation was to solve the problems due to the overly strict informed consent doctrine hindering access to old samples and data and asking for multi-purpose consents. Yet although consent is the primary justification to use biobank samples and data, the Biobank Act allows asking for a consent for several unspecified future research purposes. The guiding principles of the Biobank Act are promotion of trust, equal access to data and samples, protection of privacy, acceleration of innovation activities, and bringing biobank activities under public scrutiny. To the author's knowledge, this is the first "all purpose" Biobank Act in Europe applied to all biobanks in one country.

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005.