Social dimensions of preimplantation genetic diagnosis: a literature review

Abstract

The study provides a systematic overview of research on the social implications of preimplantation genetic diagnosis (PGD). The analysis focuses on empirical studies that provide insights into its heterogeneous fields of application and the concrete experiences of its users. The literature review shows that three areas of concern and controversial topics are particularly relevant for a social-scientific evaluation of PGD. Firstly, we present attitudes towards and assessments of PGD based on an ongoing expansion and transformation of its fields of application. This process includes not only more and more disorders and disease risks but also applications that are not disease-related. Secondly, there is evidence of significant gender asymmetries and financial concerns regarding the use of and access to PGD. Thirdly, the empirical studies point to a shift in normative expectations towards the idea of “genetic reproductive responsibility” and possible discriminatory consequences for individuals and families with diseases and disabilities.

Keywords:

• Preimplantation genetic diagnosis
• social implications
• risk
• inequality
• genetic responsibility
• discrimination

Notes

1 For the history of eugenics see Weingart, Kroll, and Bayertz (1992), Kevles (1995), Paul (1998), and Bashford and Levine (2010). For the relationship between classical eugenics and current practices in reproductive medicine and human genetics, see Lemke (2016).

2 The study was initiated by the Federal Office of Public Health of the Swiss Confederation. In the course of a revision of the Swiss Law on Reproductive Medicine (FMedG), in late 2015 the Federal Office commissioned – in addition to ethical and jurisprudential assessments – an expert opinion on the societal implications of preimplantation genetic diagnosis, which was completed in November 2016 (Lemke and Rüppel 2017). This article provides an overview of the key findings of this expertise.

3 It is worth stressing that the empirical studies reviewed in this paper are not entirely independent of regulatory regimes; on the contrary, attitudinal surveys and opinion polls in particular, which are often conducted under the label of “ethical, legal and social implications” (ELSI), form part of current styles of regulation in science and technology. These studies are often criticized on the grounds that they serve as source of legitimization and acceptance and a way of channeling potential public resistance (see Jasanoff 1995; Lopez and Robertson 2007; Rehmann-Sutter 2011).

4 In addition, PGD was also approved for sex chromosome-linked diseases, and, under certain conditions, for HLA typing.

5 “It is expected that PGD will be available only where there is a significant risk of a serious genetic condition being present in the embryo. […] The seriousness of the condition is expected to be a matter for discussion between the people seeking treatment and the clinical team.” (HFEA Guide CH(03)04); http://hfeaarchive.uksouth.cloudapp.azure.com/www.hfea.gov.uk/2686.html (last accessed 29 January 2018)

6 The list can be found on the following website: https://www.hfea.gov.uk/PGD-conditions?page=1 (Last accessed 29 January 2018).

7 The regulation of PGD in the United States is characterized by a “laissez-faire approach” (Bayefsky 2016, 42). It is also employed for highly controversial purposes such as non-medical (elective) sex selection (see Bayefsky 2015; Bayefsky and Jennings 2015, 11–12).

8 This number includes PGD and Preimplantation Genetic Screening (PGS) cycles (see 4.3.). When we refer here and in the following to the data of the ESHRE, the reference value is always the number of PGD cycles that have reached at least the stage of oocyte retrieval.

9 The first data set of the ESHRE (January 1997 to September 1998) documents 366 cycles (ESHRE PGD Consortium Steering Committee 1999); the latest data set (January 2011 to December 2012) documents 11,637 cycles (De Ryke et al. 2017). However, it has to be noted that the number of ART centers participating in the PGD Consortium increased from 16 to 71 during the same period.

10 They included adults affected by a genetic mutation associated with hereditary breast and ovarian cancer, Lynch syndrome, familial adenomatous polyposis, and multiple endocrine neoplasia type 1 or 2.

11 Rubin et al. (2014) traced the complex decision-making processes of women with a genetic risk for hereditary breast and ovarian cancer (BRCA 1/2) on the basis of qualitative interviews. It becomes clear that these cannot be understood without the specific family dynamics, the influence of experts, and contextual factors (see also Brüninghaus 2011; Heyen 2011; Hurley et al. 2012).

12 The structured questionnaire, however, did not record the genetic knowledge of respondents. The authors argue that individuals who were affected by or at risk for a single gene disorder might also accept a healthy carrier because they “value their own genetic status” (Katz et al. 2002, 1121).

13 IVF was initially established and is generally seen as an infertility treatment (Franklin 2013a). Approximately 186 million people, or rather between 8 and 12% of reproductive-aged couples worldwide, suffer from infertility, defined as “a disease characterized by the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse or due to an impairment of a person’s capacity to reproduce, either as an individual or with his/her partner” (Borght and Wyns 2018, 1).

14 Between 1997 and 2009 their share in the total number of PGD applications increased annually up to 58%; since then its proportion has decreased slightly to 52%. De Ryke et al. (2017, 1991) attribute this decrease to scientific doubts as to whether such screening is beneficial (see also Gianaroli et al. 2012, 1388–1389). According to a relevant meta-analysis (Checa et al. 2009), when compared to simple IVF a combination of IVF and PGD shows even a lower success rate (see also Mastenbroek et al. 2007). Proponents of screening counter this position by arguing that its failure is ultimately due to (until now) inadequate technology (see Harper et al. 1995; Vanneste et al. 2009; Munné, Grifo, and Wells 2016).

15 In the first ten years covered (1997–2007), the woman’s age was identified as an indication in almost 50% of cases (Harper et al. 2012, 241). An age of over 37 years is regarded as high (cf. Harper et al. 2010, 821).

16 Sex selection in the context of PGD can also be used to rule out the inheritance of a sex-related disease (e.g. an X-linked recessive inherited disorder such as Duchenne muscular dystrophy) (cf. Kollek 2000, 27–28).

17 In Israel, non-medical sex selection is prohibited in principle, but couples and single women can legally apply to the “Israeli National Committee for Sex Selection by PGD for Non-Medical Reasons” to grant an exception. This committee includes, among others, physicians, ethicists, a lawyer, a clergyman and a psychologist appointed by the Director General of the Ministry of Health. It can approve applications if the applicants are married, have at least four children of the same sex and none of the other and “there is real and immanent risk of significant damage to the mental health of one or both parents, or to the expected child, if the procedure is not conducted.” (Pessach et al. 2014, 2).

18 In a retrospective cohort study, Farra et al. (2014) documented 192 PGD cycles performed in Lebanon between 2004 and 2007. In 96.3% of these cases (185 cycles) non-medical sex selection was mentioned as indication. In 174 cycles the PGD users chose the male gender.

19 It should be noted, however, that a large part of the data came from a US-based center that offered PGD as well as sperm selection using the MicroSort^® method. The accuracy of this procedure is higher in determining an X chromosome than a Y chromosome. Accordingly, the selection of predominantly male embryos by PGD could also be attributed to the fact that couples who wanted a female child opted for the MicroSort^® method as an alternative, and thus dropped out of the statistics (cf. Harper et al. 2012, 243).

20 Another contentious issue is the use of PGD for the selection of embryos to which intersexuality is attributed at the chromosomal level. This also transcends the narrower medical framework, as in many cases no health restrictions exist (for this debate, see Gupta and Freeman 2013; Haramia 2013; Trafimow 2013; Sparrow 2013a, 2013b).

21 A social preference in reproductive decision-making for the male gender can be observed not only in India (Dey and Chaudhuri 2009; Malhi et al. 1999) and China (Chan et al. 2002; Chi et al. 2013); a few studies conducted in Western societies point in this direction as well (e.g. Van Balen 2006). In a US questionnaire study, Sensibaugh and Yarab (1997) found a tendency to favor a majority of boys in the case of an unbalanced gender relationship within a family. Data from the Israeli Ministry of Health show that PGD for sex selection is more in demand from couples who have already had several girls and want a son than vice versa (see Hashiloni-Dolev et al. 2010, 1024).

22 The assessment of the societal consequences of sex selection is also important because it is interpreted in public discourse as a precursor to other non-medical fields of application. Media articles often outline a future scenario in which PGD is used for the selection of further physical and psychological characteristics and is thus increasingly developing into a technology for the production of “designer babies” (e.g. Brandenburg 2011; see also Roberts 2002, 10–13; Jones and McMahon 2003, 271–274; Wüstner 2006, 93). Franklin and Roberts (Roberts and Franklin 2004; Franklin and Roberts 2006, 1–24) showed in an ethnographic study that the users of PGD are facing this scenario. They defended themselves against such ideas by emphasizing that they did not want to produce “designer babies”, but only to prevent serious illness or disability.

23 The reviewed studies focus on heterosexual couples to address the gender asymmetries, as legal access to PGD in many countries is restricted to this group of individuals (see 3.).

24 The study by Finck et al. (2006), however, did not find any clear correlation.

25 The item in question was: “PGD should be made compulsory for couples who are at risk to pass on gene abnormalities.” The average age of the two groups differed: 88% of the German students were between 21 and 30 years of age; 71.6% of the Japanese students were 20 years or younger (Wüstner and Heinze 2007, 8).

26 This sense of responsibility can also be found in couples affected by other genetic conditions. The study by Klitzman et al. (2007) focuses on individuals where Huntington’s disease (HD) had occurred in the family. The material documents how the idea of not only moral but also social responsibility materializes in the desire to prevent the birth of a child with the HD-typical genetic variation. As one respondent put it: “It seems unfair to ask people to forgo childbearing, but at the same time, you’re burdening society with people that are going to get sick.” (ibid., 358; see also Decruyenaere et al. 2007).

27 A significant proportion of respondents also feared that as a result of this technological selection option, the search for an effective therapy for breast and ovarian cancer would lose relevance and that necessary investments in corresponding medical research projects could decrease (Quinn et al. 2009a, 445).

28 No respondent voiced a preference for a child with deafness; 27.7% wished for a child without hearing impairment. In a British questionnaire study (Middleton, Hewison, and Mueller 2001), 644 deaf people were questioned about their attitudes towards a genetic test for hereditary deafness in the context of PND. It concluded that about 21% of those affected would seriously consider such a test; as many as two percent preferred a child with deafness and – should this attribute be absent – would consider abortion.

29 Another innovation boost in terms of the costs and duration of genetic analysis is so-called karyomapping, which was successfully performed for the first time in December 2015 (see Natesan et al. 2014; Thornhill et al. 2015).

30 For the use of PGD in healthy carriers, see Katz et al. (2002). In future, PGD could be used subsequent to an expanded carrier screening that is increasingly available (see Wehling 2014; Vaz-de-Macedo and Harper 2017).

Additional information

Funding

This work was supported by Federal Office of Public Health of the Swiss Confederation [grant number 604.0001-460].