2.1 Recruitment of couples

Between October 2019 and January 2023, couples consulting the CMGG in the context of a future pregnancy were offered ECS, by means of BeGECS. After deciding, and regardless of accepting or declining the test, the couples were asked to fill out a self-administered questionnaire. The indications for consulting the CMGG were preconception counseling, initiating a PGT-M (for monogenic disorders)/PGT-SR (for structural chromosomal abnormalities) trajectory, or the specific request for ECS by the couple.

2.2 Counseling procedure

After offering the couples genetic counseling for the initial indication of their consultation, they received pre-test counseling on ECS. The pre-test counseling was always given by the same geneticist (SJ) and psychologist (AVT) and consisted of providing information on AR and X-linked inheritance, on the phenotype of the included conditions in the panel, as well as on the possible test results, the residual chance, the couples' reproductive decision-making options if the test would result in an increased risk of having a child with one of the tested conditions, and on how the results would be communicated. The clinical geneticist pointed out that ECS was offered to all couples planning a pregnancy, regardless of whether they already had a chance of having a child with a disorder or not. The turn-around-time of BeGECS was initially 4 months, but since mid-2022 this was reduced to 3 months. The date for result disclosure was scheduled at the time of the blood sampling. The couples were also informed about the cost of the ECS-panel (1.400 Euro or ± 1.528 USD), and the absence of any reimbursement by health insurance (out-of-pocket test). At the CMGG, we do not offer ECS to pregnant couples because of the 3-month turnaround time. Indeed, being informed at an advanced stage of pregnancy that there is an increased chance of having a child with a disorder can lead to making emotionally difficult decisions such as terminating a pregnancy. Moreover, couples evidently have fewer reproductive options when already pregnant.

2.3 Reporting the ECS results

Couples were informed about the two different results they would receive: a couple result and an individual result. The couple result shows whether or not there is an increased risk of having a child with an AR or X-linked disease. This is the case when both partners carry a variant in the same AR gene included in the ECS-panel or when a woman (or man) is a carrier of a variant in a gene responsible for an X-linked disease. Variants in genes with a carrier frequency of at least 1/50 (cystic fibrosis, GJB2-related hearing loss, phenylketonuria, Smith Lemli Opitz syndrome, hemoglobinopathy including thalassemia and sickle cell disease, medium-chain hydroxyacyl-CoA dehydrogenase deficiency, spinal muscular atrophy) are listed in the individual report of both partners. Carriership of these seven disorders is provided to enable cascade analysis of first-degree relatives planning a pregnancy. The results were communicated to the couples by SJ and AVT during a consultation, in person or by telephone (in accordance with the COVID-19 prophylaxis in our hospital).

2.4 Self-administered questionnaire

After providing verbal and written consent, the couples were instructed how to fill out the questionnaire. Each couple was asked to answer all questions individually, i.e., independently of their partner. Questions involved demographic information, prior experience with genetic testing, the indication for the consultation, and reasons for accepting or declining ECS. The respondents were allowed to select more than one reason for accepting or declining ECS. The couples declining ECS were asked in an additional question to indicate whether the cost of the test was an additional reason for declining the test.

2.5 Data analysis

Descriptive analysis was done to outline the characteristics of the respondents and the answers to each of the questions (Tables 1–5). In describing the characteristics of the respondents, they were either treated as couples or as individuals. In selecting the reasons for choosing ECS or not, they were considered as individuals, as they could have different motives. To ensure meaningful comparison across the two groups (‘accept BeGECS’ vs ‘decline BeGECS’) we classified all socio-demographic variables as follows: age (18–24 years; 25–32 years; ≥33 years), highest level of education (≤ secondary school; bachelor degree; master degree), relationship status (married; legally cohabiting; cohabiting) and number of children (none; ≥1). Because we confined our focus to the description of the characteristics of the cohort, and because almost all variables are categorical, we have limited ourselves to the use of chi-square and binomial tests (conducted in R) rather than logistic regression modeling followed by testing the regression parameters. A two-sided p-value <0.05 was considered statistically significant.

The study was approved by the ethics committee of the University Hospital Ghent (B.U.N.: B6702021000264, academic study). Informed consent was obtained from all patients for being included in the study.

3.1 Demographic information

Questionnaires from 814 individuals (407 couples) were collected and included in our analysis. Of the 407 participating couples in our study, 270 (66%) accepted ECS, whereas 137 (34%) declined the test. Table 1 represents the sociodemographic data of both groups.

The age of the 814 individuals varied between 19 and 50 years, with an average age of 31 years (SD 4.59). Mean age in the ‘accept BeGECS’ group was 31 years (range between 19 and 50, SD 4.55); in the ‘decline BeGECS’ group the mean age was also 31 years (range between 22 and 45, SD 4.63). Of all participating individuals, 34% (279/814) achieved a master's degree or higher as the highest level of education, 35% (282/814) a bachelor's degree and 31% (253/814) received at most a high school diploma. The Chi-Square test revealed that age and highest education level were statistically higher in the ‘accept BeGECS’ group compared to the ‘decline BeGECS’ group (p = 0.037). Sixty-five percent of the participants in the ‘accept BeGECS’ group were between 25 and 32 years of age and 3% were between 18 and 24 years of age. Furthermore, in the ‘accept BeGECS’ group, a higher percentage (41%) had a master's degree or higher, whereas in the ‘decline BeGECS’ group this was 20%. A lower percentage with a secondary school degree (24%) accepted BeGECS compared to 46% that declined the test.

Of the 407 couples, 128 (31%) were married, the remaining 279 couples (69%) were legally cohabiting (31%) or de facto cohabiting (38%).

The majority of all couples (76%) did not have children at the time of ECS offering. In the ‘accept BeGECS’ group 77% had no children, which is comparable to 75% in the ‘decline BeGECS’ group.

The vast majority of all participating couples (82%) consulted the CMGG in the context of initiating a PGT-M/SR procedure, 10% came for preconception counseling and 8% came with the specific request for BeGECS. In the ‘accept BeGECS’ group, 77% came for start-up of PGT-M/SR, 11% for preconception counseling and 12% specifically for BeGECS. It is an obvious finding that all couples who came to the consultation asking for BeGECS accepted the test at the time of pre-test counseling (32/32). Ninety-two percent of couples in the ‘decline BeGECS’ group consulted for PGT-M/SR, 8% came for preconception counseling (Table 1).

3.2 Reasons for accepting BeGECS

Of the 814 respondents in this survey, 540 (66%) chose to take ECS. Table 2 displays the reasons for electing BeGECS. The most common reason for taking the test was “in the context of prevention” (21%). Other frequently mentioned reasons were “I wish to obtain all possible information” (19%), “the information will facilitate future reproductive decision making” (16%), and “the information increases my sense of control” (16%). The couples who came to the consultation with the specific request for BeGECS had knowledge of the test's existence through various channels: the general practitioner (GP), a family member or a friend, or through media.

3.3 Reasons for declining BeGECS

137 couples in our survey (34%) decided not to have BeGECS. Table 3 shows the selected reasons for declining the test. The most frequent selected reason to decline the test was “too much information will cause fear and worry” (18%). Other reasons were “the information will not change the decision to have children” (17%), “I don't want to spend money on something that will not happen” (17%) and “I am not concerned about the family history” (16%). Nine percent indicated “I consider taking the test in the future.”. We did not explore further why people declined ECS now but considered it in the future.

3.4 The effect of the cost

A binomial test determined a statistically significant difference in the ‘decline BeGECS’ group between those for whom the cost was an additional factor to decline the test (68%), on top of the reasons they already selected, and those for whom the cost did not play an additional role in their decision to decline BeGECS (32%; p = 3.18e-09; Table 4). Table 5 shows that there is a difference, although not significant, in the ‘decline BeGECS’ group, between highest education level and cost of BeGECS as being an additional factor or not for declining the test: 49% of the participants who obtained at most a secondary school degree versus 16% of individuals holding a master's degree, indicated that the cost was an additional reason for declining ECS.

4.1 Uptake rate

Our results show that 66% of the couples (270/407) accepted out-of-pocket ECS after pre-test counseling. In previous studies, variable uptake rates were found on the actual uptake of preconception ECS. In a study by Gilmore et al. (2017), 34% of a cohort of women planning a pregnancy accepted to participate in a free of charge preconception ECS. A study by Larsen et al. (2019) showed an acceptance rate of almost 69% (46/67) among women after preconception counseling. Moreover, they found a higher acceptance rate in the group of patients that were in preparation for IVF (74.5%) compared to those who received genetic counseling for another reason (50%). In our study, we cannot make this comparison because most participating couples came to the consultation to start a PGT procedure (82%), which involves IVF treatment. In a survey by Plantinga et al. (2016), 56% of potential users responded that they would be interested in ECS and one-third planned to take the test if it was offered. A study by Nijmeijer et al. (2019), in which Dutch individuals aged 18–45 years were asked to complete a questionnaire on ECS, showed that 31% would accept the test. In these latter two studies, the uptake rate to desire ECS, hypothetically questioned, was lower than that of our participants. In a more recent Dutch paper by Schuurmans et al. (2020), 90% of couples who had attended pre-test counseling with their primary care physician accepted a free test offer of preconception expanded carrier screening. This acceptance rate is high, but the couples were offered a cost-free test, whereas the couples in our study had to pay for the test. The uptake rates of the different studies, including our study, vary, but comparison of the data is difficult given the different study designs and target groups.

4.2 Demographic characteristics

In our study sample, more participants between the age of 25 and 32 years accepted BeGECS, compared to the other age categories (18–24 years, ≥33). In addition, in the ‘accept BeGECS’ group more couples obtained a higher level of education (master's degree) and less couples got at the most a secondary school degree, compared to the ‘decline BeGECS’ group. Although we did not ask the annual income of the couples, we assume that both findings are related to a higher – or at least a more secure – income. This is in line with Gilmore et al. (2017) who found in their study that women who declined ECS were younger, less educated, and had a lower income. A paper from De Gregorio and Lee (2002) provided empirical evidence that education level plays a role in income distribution. We did not find a significant difference in the decision to accept or decline BeGECS between couples who already had children and who did not have children yet at the time of the ECS offer. This is in contrast with the findings of Gilmore et al. (2017), where women who already had children declined ECS more frequently. They also found that women were more likely to accept ECS when there was a genetic disorder in their family. From our study, we cannot however draw a conclusion about a correlation between experience with a genetic risk and choosing ECS, as our largest group of participants consulted in the context of PGT-M/SR startup (82%). Similarly, Nijmeijer et al., 2019 did not find an association between experience with genetic conditions and interest in carrier screening.

4.3 Reasons for accepting ECS

Our data showed that in the ‘accept BeGECS’ group (N = 540), the main reason for taking the test was prevention. Wanting to prevent the birth of a child with a severe hereditary disorder has also been reported in earlier studies (Nijmeijer et al. (2019) and Plantinga et al. (2016)). Even though prevention is not the primary aim of ECS, it suggests that the primary motivation for individuals to accept ECS is the desire to avoid having a child with a serious condition. van der Hout et al. (2019) addressed the reasons why the aim of ECS is presented in terms of ‘autonomy’ rather than ‘prevention’. When screening is conducted in the preconception period, carrier couples can avoid the birth of an affected child by making an autonomous decision, for instance PGT.

The other frequently selected reasons, “wanting to obtain all possible information,” “facilitating the future reproductive decision making process” and “increasing the feeling of control,” are also in line with the literature (Kauffman et al., 2017; Nijmeijer et al., 2019; Plantinga et al., 2016; Schuurmans et al., 2020). These arguments align with the primary objective of ECS in couples with no known chance of recessive disorders, which should be informing couples of a chance of genetic diseases in future offspring and of the available reproductive options in order to enable autonomous choices, rather than reducing the birth prevalence of affected children (Henneman et al., 2016).

4.4 Reasons for declining ECS

The most frequent selected reasons of our participants for declining ECS were “the information will cause fear and worry,” “information will not change the decision to have children,” “don't want to spend money on something that will not happen” and “not being concerned with the family history.” Gilmore et al. (2017) also assessed that potential anxiety was a major reason (17%) for declining ECS due to possible perceived implications of the testing being offered. Nijmeijer et al. (2019) found in their study that the most important reason for declining ECS was that participants did not have family members with one of the tested hereditary disorders. This corresponds to the reason that was quite frequently given by our participants, namely “not being concerned with the family history” (16%). It is remarkable that family history of a genetic condition was mentioned as an influencing factor on participants' decision to decline, even after pre-test genetic counseling on ECS. This indicates that the information on inheritance patterns of autosomal recessive diseases is sometimes misunderstood. This misconception about family history has previously been reported, more in particular regarding cystic fibrosis (CF) screening (McClaren et al., 2008). Participants in this study described their perception that a family history of CF would be a strong motivator for considering CF carrier screening. The other frequently selected argument of our participants for declining ECS, “not wanting to spend money on something that will not happen” (17%), is in line with the primary reason of the McClaren study for not accepting the offer of CF carrier screening, which is that CF and carrier screening “is not in my world.” These authors suggested that CF carrier screening programs require a strategy to bring CF and carrier screening into “people's world”. This may be possible with education initiatives that aim to increase public awareness and understanding of genetics and carrier screening (McClaren et al., 2008).

4.5 Cost of the test

Of the 274 individuals who declined BeGECS, 68% indicated that the cost of 1.400 Euro or ± 1.528 USD played an additional role in their decision to decline the test. If we look at the level of education of this group, we see that this was especially the case if they were less educated. Among the participants with a master's degree, cost of the test was less frequent mentioned as an additional factor for declining. In a study of Clarke et al. (2018) on willingness to pay for preconception expanded carrier screening, factors that were considered to promote willingness to pay included the current financial situation, whether there was a compelling reason to pay more (e.g., family history or health concern), and whether they felt their partner would be willing to pay this amount. The potential benefits considered to justify paying more included alleviation of anxiety in reproductive planning, the potential benefits of test knowledge and genetic counseling, and believing that learning about potentially medically actionable results for offspring or oneself is “priceless” (Clarke et al., 2018).