Study design

A qualitative study design using semi-structured interviews was applied for this study. The Medical Ethical Committee of the Amsterdam University Medical Center (location AMC) approved the study protocol and exempted this study from ethical review (W18_054).

Theoretical framework

Two theoretical models, the Constellation Perspective and the Network of Actors model, were used for the study design and the interpretation of findings. The Constellation Perspective [23] argues that a (healthcare) system can be seen as a constellation of interrelated practices and relevant structuring elements, and can be described by its (i) structure (organizational and power structures), (ii) culture (values and thinking) and (iii) practice (actions and implementation) (Fig 1). According to this model, actors (stakeholders) determine structure and culture. Actors are known to generally be hesitant to change, for example to adopt a new technology that is (not yet) concordant with the structure or culture of the existing system. When new technologies are developed and implemented in an existing (healthcare) system, transition occurs when fundamental changes in all three aspects of the system happen. Key actors in the field can either hinder or facilitate change, and act as change agents [3,24].

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Fig 1. The existing system of reproductive medicine: Operationalization of the constellation concept into structure, culture and practice, adapted from Rigter [25] and van Raak [23].

https://doi.org/10.1371/journal.pone.0269719.g001

The Network of Actors model can be used to identify and describe the key actors involved in the process of development and implementation of new technologies [26]. Moreover, this model is helpful to gain in depth understanding of technology development and implementation by focusing on the roles of stakeholders and their interactions. According to this model the different actors are divided in four categories: (i) the scientists who develop and do research into the technology, (ii) policymakers and ethicists who decide whether a technology is acceptable and should be made available, (iii) the healthcare providers who organise implementation of a technology in the actual healthcare system and offer it to recipients, and, last but not least, (iv) the citizens and patients who may use or demand a technology (Fig 2). The existing model does not include the industry; however, we believe this stakeholder group is of importance when discussing new technologies, both for development and implementation in health care and therefore we have invited someone from that field. The Network of Actors model facilitates exploring expectations and actions of the various stakeholders when attuning the use of technologies in a changing field. It should be noted that, in practice, stakeholders may have different roles to fulfil at the same time, e.g. working as a healthcare provider and policy adviser to the government. The sources of dynamics and roles/categories of actors involved are interrelated and merged in Fig 2 [3,26].

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Fig 2. Network of Actors model, adapted from Achterbergh et al. [26].

The numbers of interviewees per stakeholder group are indicated with N = x.

https://doi.org/10.1371/journal.pone.0269719.g002

Participants and procedure

A total number of 28 key stakeholders were identified with purposive sampling strategy using the Network of Actors model and 21 stakeholders were interviewed. Representing healthcare professionals included gynaecologists (n = 1), midwives (n = 1), clinical geneticists (n = 5) and clinical embryologists (n = 1), researchers included laboratory (n = 3) and clinical (n = 2) scientists; professionals from industry (n = 1), institutions included governmental (n = 2) and health insurance institutions (n = 1), ethicists (n = 2), legal experts (n = 1), and representatives from patient organisations (n = 1) (Fig 2). To achieve a spread of participants throughout the country, stakeholders working in different (academic) hospitals and institutions were invited. It should be noted that participants had different expertise and knowledge concerning the discussed technologies (i.e. some participants work solely in the field of PGT). The perspectives of couples who face an increased risk of having affected offspring, representing the stakeholders that may voice “demand” for these techniques, have been published elsewhere [27]. For this study, patient perspectives were therefore represented by contacting an alliance organisation for patients with rare and genetic diseases. Relevant stakeholders were contacted through email with an invitation letter, four stakeholders, among which three were healthcare professionals and one government employee replied that they did not consider themselves suitable for participation in this interview study, and three stakeholders, working for institutions and in healthcare, did not reply. From December 2019 until February 2021, twenty-one interviews of approximately 45 minutes were conducted (n = 5 face-to face and n = 16 online due to the COVID-19 pandemic) by one researcher (I.D.) who is trained in conducting interviews. Respondents gave verbal consent to participate which was recorded. All respondents were based in the Netherlands and/or affiliated with Dutch institutions.

Interview guide

The following topics were discussed in the interviews: (i) Stakeholders’ own role, their current activities, their responsibilities and observed demand for these developments, (ii) expectations regarding the impact of the technologies on the existing field and current practice, and (iii) expectations regarding the dynamics between current and future technologies (i.e. ECS, NIPD/NIPT, PND, PGT, GGE).

Data analysis

All interviews were recorded, using a recording device, after participants’ verbal consent and transcribed verbatim. For collecting and analysing qualitative data, we adhered to the COREQ checklist [28], supplemental material. The qualitative data software Atlas.ti 8 was used for analysis. First, open coding was performed and the perceived relevant items of the data were marked in the transcripts. Second, thematic content analysis was conducted. To increase validity, five transcripts were coded by two researchers independently [C.E. and I.D.]. The codes were compared, discussed and adapted until agreement was reached. All other transcripts were coded by one researcher [I.D.]. Themes and topics were selected for several reasons: most expressive, repeatedly identified, or remarkable cases. The quotes that were considered most relevant for illustration of the results were translated into English. When relevant, we tried to indicate which group particularly hold certain views. The stakeholder group and the interview number (participant; P1, 2, 3…) are indicated with the quotes.

Theme 1: The typical Dutch approach

Participants framed the dynamics of new technologies within a cultural background. The typical Dutch approach emerged as a theme from discussing previous examples and experiences and looking forward on the new technologies discussing ECS, NIPD and GGE. The Dutch approach can be characterised as including careful consideration and restrictive legislation. Important values of the Dutch approach are the importance of an egalitarian society, autonomy and support for people with disabilities. It was mentioned that the Netherlands acts carefully, but as a consequence is not a pioneer in reproductive technology worldwide. They argued that technologies tend to be implemented only under certain conditions imposed by the government. Legislation, such as the Dutch Population Screening Act, contributes to accurate implementation of screening and aims to protect people against potential harm [29]. Several respondents called this a “conservative approach” when it comes to research and implementation of new (reproductive) technologies:

“We have a government that handles the changes it wishes to pursue very responsibly. In the Netherlands, change is never immediate and even the smallest decisions get weighed and measured for pros and cons. (…) Look, we don’t usually lead the way: we like rules, laws and discussion too much for that, but we are never really behind the curve. But we’re not forerunners.” P9, institution.

This sometimes frustrates stakeholders as they believe that certain legislation is too strict, hindering research and innovation and risking progress within the country:

“I don’t understand why some processes here are so slow, it frustrates me. I contact a colleague abroad and hear that some techniques or tests are already being offered on a structural basis. We [referring to the Dutch government] are sometimes too strict.” P4, healthcare provider.

In terms of actors influencing the reproductive healthcare system, some interviewees believed that professionals working in the field, especially healthcare providers, have an important role in the organization and implementation of new technologies, with the support of government policy. Stakeholders explain professional groups and consortia working in the field see it as their responsibility to develop guidelines based on state-of-the-art knowledge, in order to ensure people receive the best available care.

Participants believed that the political landscape has some influence as well. After elections, the Dutch government changes every four years and, according to some participants, this heavily influences the healthcare system. For example, if more conservative parties are elected, the availability or progress of implementing certain reproductive technologies may be affected. One respondent argued that once benefits of a certain technology are proven, it should be available to people, regardless of the political nature of the government:

“It seems to me that a government which is unable to call upon Christian or other conservative beliefs would have a hard time stopping such change(s). So, I assume that all these developments, when safe and effective, would in some way manage to find a spot in the healthcare system.” P13, healthcare provider

Some stakeholders were somewhat hesitant describing their own role in the implementation of new technologies. However, all believed that participating in research was an important societal responsibility when working in the field of reproductive and genetic care.

Cultural background

Implementation of new genetic technologies are greatly influenced by the cultural background, as was mentioned by participants. Several norms and values were mentioned that are characteristic of Dutch culture: (i) An egalitarian society, (ii) Concern about medicalisation of pregnancy and autonomous decisions, and (iii) Support for people living with disabilities.

(i) The importance of an egalitarian society. It was considered important by stakeholders to maintain healthcare services that are accessible for all. Some described this as an “Egalitarian society”:

“In the Netherlands, we have a pretty egalitarian society, causing people to quickly call out: ‘Hey, but this shouldn’t just be for the happy few?” P14, institution.

An example listed by some of the participants was that the Netherlands was one of the first countries to integrate NIPT into routine prenatal care, making it widely available for all pregnant women, albeit with a fee that may deter a proportion of women (Table 1). Another example mentioned by healthcare providers was the three IVF/ICSI cycles within the PGT process that are reimbursed for most couples who face no medical, personal (e.g. age, obesity) and/or social contraindications. A member from an institution mentioned that this egalitarian approach sometimes creates difficulties for the government, for example, in a possible scenario where ECS is offered to everyone and fully reimbursed by the government:

“On what grounds do you decide that a technique should be collectively offered?” P12, institution.

(ii) Concern about medicalisation of pregnancy and autonomous decisions. Stakeholders brought up the societal discussions and concerns about (over)medicalization, this involves situations where more medical care is applied to a health condition than is required or recommended to achieve better health. Earlier discussions about the medicalisation of pregnancy have been central to, for example, a cautious implementation of prenatal screening in the Netherlands. Some stakeholders argued couples have ‘the right not to know’ and should be able to opt out of screening. An important related concept in reproductive decision making is autonomy. Stakeholders agreed that everyone should be able to make their own autonomous decisions, and in the Netherlands, this includes declining tests or information about tests. Current policy and counselling guidelines in the Netherlands are organized to support this. For instance, in prenatal screening, women are asked if they want to receive information about screening rather than being offered the screening directly. Moreover, feelings of any pressure to opt for certain technologies should be avoided, a member of an institution stated:

“I do think that it is very important that people receive proper support in this selection process [of opting for a specific technology] and that they do not experience any pressure. It is important to pay attention to the benefits as well as the potential harms.” P16, institution.

(iii) Support for people living with disabilities. All stakeholders agreed that the support for people living with disabilities is well established in the Dutch culture and healthcare. Some stakeholders thought this support could be threatened by the implementation of new technologies. When one can avoid having an affected child, treatments would still need to remain accessible.

“I really believe in prevention. But if people do not want that, the facilities should remain available to take care of people with certain conditions. We have to ensure the continued existence of services.” P4, healthcare provider.

Noticeably, respect for people with disabilities was often mentioned as another reason why the Dutch government is hesitant and careful in implementing preventative technologies like preconception carrier screening for the general public. In contrast, some others thought the attitude towards disabilities is sometimes ‘romanticized’ by favourable portrayal in the media, and this may lead to the general public underestimating the seriousness of some conditions.

Theme 2: Moving forward with new technologies

The expectations of stakeholders concerning ECS, NIPD and GGE are structured according to the three elements of the Constellation Perspective model; practice, structure and culture. In general, stakeholders mentioned that attention should be paid to the costs of emerging technologies. In the preconception context, stakeholders pointed to the lack of genetic literacy in the general public and the need to reach and inform couples that are not pregnant yet about for example the availability of ECS. The growing number of available reproductive technologies was said to possibly hinder autonomous decision making, highlighting the need to provide counselling to support the process.

Expectations of expanded carrier screening (ECS)

Expectations of Non-invasive prenatal diagnosis (NIPD)

Expectations of germline genome editing (GGE)

Expected implementation of ECS, NIPD and GGE

Stakeholders envisioned different scenarios for the implementation of the three reproductive technologies reviewed here. For ECS, several structural changes may be necessary in order to become established in preconception care. More professionals will have to be trained to provide counselling, and reimbursement of the test will be needed to safeguard equal access, among others. Concerning NIPD, some stakeholders were surprised that this technology is not yet embedded in care as in other countries and all expected it will be as a matter of due course. In the prenatal context, few structural hurdles were identified for NIPD implementation, and availability for couples with a known increased risk seemed feasible on the short term. Expectations and views on GGE varied widely among stakeholders, but all believed that this technology is still far from clinical implementation. For GGE, structural changes were needed in the legal context to shape good governance.

The Dutch approach: Slow but steady?

The results of this study show that the Dutch cultural background heavily influences the course of new technology implementation. The “Dutch approach” can be characterized by several aspects such as the value of inclusive dialogues and the importance of a learning phase. Although it is sometimes perceived as unnecessarily viscous, this Dutch approach also has advantages such as building public support and opportunities to learn from small-scale implementation. These aspects have specific advantages and disadvantages that are weighed differently among interviewed stakeholders. The insights gained from this method can also inspire and educate other countries.

Recently, the World Health Organization published recommendations for governance and oversight of human genome editing [30] and one of their recommendations was to facilitate an inclusive global dialogue. The ethical committees of the WHO and the European Commission furthermore recommended establishing a GGE-registry platform, where GGE research knowledge can be shared and used to help create oversight. As Turocy et al [31] suggested, in their review on the progress and considerations of GGE, the way in which mitochondrial replacement therapy was handled in the United Kingdom could serve as a model. In implementing that technology, regulatory and ethical discussions involving stakeholders proved crucial for public acceptance of this therapy. Such a national dialogue on GGE has taken place in the Netherlands in 2019–2020, funded by the government [21]. Soliciting societal input and reaching consensus through public dialogue fits readily within the careful and reasoned Dutch approach. Indeed, the traditional “polder model” was founded on the involvement of all stakeholders to make decisions how to safeguard reclaimed land against flooding [32]. This method of consensus decision-making and cooperation despite differences continues to serve as an example for policy making internationally. Because GGE affects subsequent generations, GGE would benefit from a strong governance model with international oversight and cooperation. “Poldering”, the slow decision-making process where all parties need to be heard, could be perceived justified or, alternatively, as a waste of time or harmful, e.g. when consensus is unfeasible or it unnecessarily delays safe implementation.

Introduction of new technologies in an existing system could benefit from a learning phase, as brought forward by professionals in this study and previously described by van Schendel et al. for NIPT implementation [33]. Especially in the reproductive context, a careful implementation of potentially risky technologies that includes a pilot study and a learning period with suitable follow-up is important to determine adverse effects and establish safety. Unfortunately, history shows that some technologies were implemented prematurely, such as preimplantation genetic screening (PCS): a technology used to screen IVF derived embryos for aneuploidies. Eventually PCS was also offered in clinica to increase the IVF success rate, however this was not properly evaluated with thorough effectiveness studies beforehand, as previously argued [1]. A collective learning phase is considered valuable because participants can gain experience and anticipate structural changes. From the field of transition management and innovation science, we know that emerging innovations often first take place in a ‘niche’. Those niche developments are described by Rotmans et al. as involving individual actors or technologies that can change the current practice of the social-technological landscape [34]. Successful niche developments need scaling up to gradually expand. The two currently available ECS initiatives in the Netherlands can serve as examples of a learning phase and evaluation might provide key insights to consider for potentially scaling up implementation [35,36]. It was expected by professionals in this study that the use of ECS will increase in the future, although currently carrier screening is not widely available and public awareness is low [37]. Lessons learned from global initiatives could be shared, such as ‘Mackenzie’s mission’ in Australia [38]. The Australian federal government funds this pilot study that aims to screen 10,000 couples for 1,200 severe, childhood-onset genetic conditions in a research setting for three years.

International context: Structural and cultural differences, variable offers

Technologies are embedded in local practice, and are shaped by a national context where culture and structure define the reproductive healthcare system [23]. The core values of the “Dutch approach” shape the implementation of technologies, and this in particular distinguishes the Netherlands from many other countries where healthcare is often, to a larger extent, provided by commercial and private parties. Variability between countries was previously described in studies involving NIPT and ECS [11,18]. An example is the high number of commercial providers in the United States that offer carrier screening [39]. Once high throughput sequencing was available at a reasonable price, commercial companies seized the opportunity to offer large screening panels to the general public [18]. The difference in healthcare systems could also be an explanation for the variability of ECS between countries [40,41]. The Belgian reproductive healthcare system, for example, is differently organised compared to the Netherlands. Belgian women visit a gynaecologist on a regular basis, which simplifies opportunities for preconception counselling and increases awareness of the availability of ECS. Since 2017, the Belgian Superior Health Council recommended to offer ECS for the general population and currently this is available from the clinical genetic centres for all couples at their own cost [42]. Given the difference between healthcare systems in countries it is not possible to simply implement elements a reproductive genetic healthcare system from one country in another country. It is important to understand the contexts of innovation, by unravelling the culture, structure and practice.

Important policy challenges

The main challenges of current policy seem to be the balance between accessible care for all, while keeping healthcare affordable. The careful consideration of evolving technologies and the egalitarian approach with a strong emphasis on equal access were mentioned in this study as important core values of the “Dutch approach”. Previous evaluation studies of ECS in the Netherlands showed that a large number of participants considered the costs of the test too high and believed that it should be reimbursed by health insurance companies [43,44]. The egalitarian approach favoured by the government is not achieved when out-of-pocket costs hamper equity in access. Whether reimbursement for all could be feasible was discussed by experts at a workshop held at the ESHG in 2015 on ECS [45]. Those experts agreed that equity of access was important, however, they also expressed doubts whether it was feasible because of the high cost of healthcare. The goal of an egalitarian society to avoid unequal access could delay implementation and scaling up innovative discoveries from niches. Another challenge could be in defining the right actors for the implementation process, especially key stakeholders and/or so-called change-agents. Stakeholders often said it was the government’s job to attune roles and responsibilities, and not many participants mentioned their own potential role in the process of responsible implementation. Conversely, the government also expects experts from the field to initiate and orchestrate these matters, which is a discrepancy that hides a potential structural problem.

Strengths and limitations

This qualitative research enabled rich and in-depth insights into the perspectives of various stakeholders involved in the field of genetic and reproductive health. Insights in what stakeholders view as prerequisites for responsible implementation of technologies in reproductive healthcare in a national context could also be relevant for developments in other countries. A broad range of professional stakeholders were included, which provided an extensive overview of expectations towards the technologies and the changing field. However, completeness of perspectives cannot be assured: general practitioners were approached several times per email but did not respond, and other perspective, e.g. the perspectives of health insurance companies, are missing, which we believe could have contributed valuable insights for the current discussion. All interviewed stakeholders are operating within the ‘Dutch approach’, perhaps a majority has the opinion the system they are supporting is doing things the right way. It would be informative to ask an expert perspective on the ‘Dutch approach’ from professionals in, for example, the United Kingdom, Iceland, or culturally more distinct country for example in Southeast Asia.