Scholarly article on topic 'Comparative preimplantation genetic diagnosis policy in Europe and the USA and its implications for reproductive tourism'

Comparative preimplantation genetic diagnosis policy in Europe and the USA and its implications for reproductive tourism Academic research paper on "Law"

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Abstract of research paper on Law, author of scientific article — Michelle J Bayefsky

Abstract Unlike many European nations, the USA has no regulations concerning the use of preimplantation genetic diagnosis (PGD), a technique employed during some fertility treatments to select embryos based on their genes. As such, PGD can and is used for a variety of controversial purposes, including sex selection, selection for children with disabilities such as deafness, and selection for ‘saviour siblings’ who can serve as tissue donors for sick relatives. The lack of regulation, which is due to particular features of the US political and economic landscape, has ethical and practical implications for patients seeking PGD around the world. This paper contrasts the absence of PGD oversight in the USA with existing PGD policies in Switzerland, Italy, France and the UK. The primary reasons why PGD is not regulated in the USA are addressed, with consideration of factors such as funding for assisted reproductive technology treatmemt and the proximity of PGD to the contentious abortion debate. The obstacles that would need to be overcome in the USA for PGD to be regulated in the future are outlined. Then, the significance of the current divergence in PGD policy for patients around the world are discussed. Regulatory differences create opportunities for reproductive tourism, which result in legal, health and moral challenges. The paper concludes with comments on the need for policymakers around the world to balance respect for the characters and constitutions of their individual countries with appreciation of the needs of infertile patients across the globe.

Academic research paper on topic "Comparative preimplantation genetic diagnosis policy in Europe and the USA and its implications for reproductive tourism"

RBMS-00042; No of Pages 7 Reproductive BioMedicine and Society Online (2017) xx, xxx-xxx

REPRODUCTIVE BIOMEDICINE SOC.ETY

www.sciencedirect.com www.rbmsociety.com

BROCHER SYMPOSIUM: PERSPECTIVES ON ACCESS TO REPRODUCTIVE HEALTHCARE

Comparative preimplantation genetic diagnosis policy in Europe and the USA and its implications for reproductive tourism ☆

Michelle J Bayefsky

Bioethics Department, National Institutes of Health, 10 Center Drive, Building 10, Room 1C118, Bethesda, Maryland, USA 20892 E-mail address: michelle.bayefsky@gmail.com.

Michelle Bayefsky is a pre-doctoral fellow in the Bioethics Department of the National Institutes of Health (NIH). She Mm graduated summa cum laude from Yale University in 2014 with a Bachelor of Arts in Ethics, Politics and Economics. She

IP ^ has published a book (Palgrave Macmillan 2015), co-authored with Bruce Jennings, entitled Regulating Preimplan-

JH f tation Genetic Diagnosis in the United States: The Limits of Unlimited Selection. At the NIH, Bayefsky conducts

bioethics research primarily in the areas of clinical genomics and reproductive medicine.

Abstract Unlike many European nations, the USA has no regulations concerning the use of preimplantation genetic diagnosis (PGD), a technique employed during some fertility treatments to select embryos based on their genes. As such, PGD can and is used for a variety of controversial purposes, including sex selection, selection for children with disabilities such as deafness, and selection for 'saviour siblings' who can serve as tissue donors for sick relatives. The lack of regulation, which is due to particular features of the US political and economic landscape, has ethical and practical implications for patients seeking PGD around the world. This paper contrasts the absence of PGD oversight in the USA with existing PGD policies in Switzerland, Italy, France and the UK. The primary reasons why PGD is not regulated in the USA are addressed, with consideration of factors such as funding for assisted reproductive technology treatmemt and the proximity of PGD to the contentious abortion debate. The obstacles that would need to be overcome in the USA for PGD to be regulated in the future are outlined. Then, the significance of the current divergence in PGD policy for patients around the world are discussed. Regulatory differences create opportunities for reproductive tourism, which result in legal, health and moral challenges. The paper concludes with comments on the need for policymakers around the world to balance respect for the characters and constitutions of their individual countries with appreciation of the needs of infertile patients across the globe.

■ ■ 1 HBM

Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). KEYWORDS: comparative policy, embryo, preimplantation genetic diagnosis, reproductive tourism, selection

☆ This paper was presented at the Brocher Symposium 'Between Policy and Practice: Interdisciplinary Perspectives on Assisted Reproductive Technologies and Equitable Access to Health Care,' held at the Brocher Foundation, Hermance, Switzerland in July 2015. The Brocher Foundation's mission is to encourage research on the ethical, legal and social implications of new medical technologies. Its main activities are to host visiting researchers and to organize symposia, workshops and summer academies. More information on the Brocher foundation program is available at www.brocher.ch. R^ffiM

BROCHER

http://dx.doi.org/10.1016/j.rbms.2017.01.001

2405-6618 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

25 Introduction

26 Preimplantation genetic diagnosis (PGD) is a technique

27 which can be employed during fertility treatment to test

28 an embryo's genes before deciding whether to transfer the

29 embryo to a woman's uterus. The technique is primarily used

30 to detect serious heritable disorders, such as Tay-Sachs or

31 cystic fibrosis, which the parents wish to avoid passing on to

32 their children. It can also be used for more controversial

33 purposes, however, such as selecting for a child who can

34 serve as a tissue donor for a sick sibling, selecting for a child

35 with a certain condition, such as deafness, and selecting for

36 a child of a particular sex. In nearly all countries with

37 advanced fertility clinics carrying out PGD, the technique is

38 limited by legal restrictions on its acceptable use. The USA

39 stands apart in its laissez-faire approach towards the use of

40 PGD. Elective sex selection is reported to account for 9% of

41 PGD uses in the USA, and a small number of clinics offer

42 PGD to select for conditions such as deafness and dwarfism

43 (Baruch et al., 2008).

44 This paper compares the lack of regulatory oversight

45 of PGD in the USA with the regulations in place in Italy,

46 Switzerland, France and the UK. It aims to answer two

47 related questions: what is different about the USA, and what

48 implications does the US approach have for PGD patients

49 globally? To address these questions, this paper analyses the

50 similarities and differences among the national laws in the

51 selected countries and examines medical professional

52 guidelines in the USA. Factors such as the absence of public

53 funding for fertility treatment, the contentiousness of the

54 abortion debate and the relative independence of physicians

55 in the USA are discussed. It also draws upon the scholarly

56 literature on cross-border reproductive care (CBRC) to argue

57 that the lack of regulation in the USA, like other very lenient

58 or stringent policies, helps to foster global reproductive

59 tourism, which poses well-documented health and legal risks

60 for patients and their offspring. Ultimately, it concludes that

61 when creating rules for the use of PGD, policymakers around

62 the world should consider not only the need for laws to

63 reflect the desires and beliefs of their citizenry, but also the

64 very real impact of policies - particularly extremely permis-

65 sive or strict policies - on patients within their country and

66 abroad.

67 PGD policy in Europe

68 There is wide variation in PGD policy in Europe, but a

69 majority of European countries restrict the use of PGD in

70 some way (Soini, 2007). Italy, Switzerland, France and the

71 UK were selected as case studies in order to demonstrate the

72 variation in PGD policy in Europe and the range and types of

73 forces at play in the development of regulations on the

74 acceptable use of PGD.

75 Italy

76 In 2004, taking advantage of its unprecedented majority, the

77 Italian Parliament's conservative coalition passed one of the

78 most restrictive laws on assisted reproduction in Europe,

79 Italian Law 40 (Biondi, 2013). The law limited the number of

embryos created during IVF to a maximum of three and 80 required that all viable embryos be transferred into the 81 patient's uterus so no embryos would be stored or destroyed. 82 The law also banned the use of PGD and restricted access to 83 assisted reproductive technology to only those with a diagnosis 84 of infertility (Gianaroli et al., 2014) rather than also allowing 85 access to fertile patients with a hereditary condition who 86 need assisted reproductive technology to ensure the birth of 87 unaffected children. Under the restrictive law, PGD was not 88 performed in Italy and Italian couples in need of PGD had to 89 travel abroad for treatment. 90

Many patients, scientists and members of the general 91 public were opposed to the controversial law, but when a 92 referendum was called in 2005 to have it repealed, only 25.9% 93 of eligible citizens voted, falling short of the 50% needed to 94 meet the quorum. Patient advocates also challenged the law 95 in court and in January 2008 the Regional Administrative Court 96 of Latium declared the ban on PGD unconstitutional (Gianaroli 97 et al., 2014). However, as all embryos, regardless of whether 98 they test positive for the unwanted genetic condition, have to 99 be transferred to the woman's uterus, in practice PGD still 100 could not be carried out. Finally, in May 2009, the Italian 101 Constitutional Court declared that the rule that only three 102 embryos could be created and that all must be transferred was 103 unconstitutional (Molinelli et al., 2012) and PGD began to be 104 performed in Italy once more. 105

PGD can now be carried out in Italy for purposes aimed at 106 protecting the health and development of the embryo itself 107 - in other words, to prevent the transmission of a hereditary 108 disease. What remains of Law 40 bans 'any form of eugenic 109 selection' or 'breeding techniques ... intended to alter the 110 genetic heritage of the embryo or gamete or to predeter- 111 mine genetic characteristics, except interventions with 112 diagnostic or therapeutic purposes' (L. 40/2004). There is 113 no formal mechanism for determining what constitutes a 114 sufficiently serious disease to merit PGD, but social uses of 115 PGD, such as sex selection, are prohibited. 116

Switzerland 117

From January 2001, Switzerland's legal environment was 118 much like Italy's under Italian Law 40. PGD was prohibited, 119 only three embryos could be created during IVF, and all 120 needed to be transferred. As with Italy, fertility treatment 121 success rates declined and rates of multiple pregnancies 122 increased under the restrictive law (De Geyter, 2012). 123 Switzerland then changed its law, however. In June 2013, 124 the Federal Counsel sent to Parliament proposed changes 125 that included allowing PGD for serious heritable disorders, 126 allowing eight, rather than three, embryos to be created, 127 and allowing embryo freezing so that not all viable embryos 128 need to be transferred. In December of 2014, Parliament 129 considered the proposed changes and decided to allow the 130 screening of embryos for chromosomal abnormalities (PGS) 131 in addition to PGD for serious heritable conditions. In order 132 for the proposed changes to come into effect, the Swiss 133 needed to amend their Constitution, which required a 134 popular vote. The vote for modifying Switzerland's assisted 135 reproductive technology law took place on June 14, 2015, 136 and 62% of voters decided to allow PGD and PGS (Wurz, 137 2015). Now in Switzerland, as in Italy, PGD is legal, but the 138

139 particular set of conditions for which PGD is be permitted is

140 not specified.

141 France

142 France, in contrast, has a more detailed regulatory framework

143 for PGD. National law stipulates that PGD can only be

144 performed by a specially certified fertility specialist and can

145 only be used to select against a serious, incurable disease (Loi

146 no. 2011-814). Beyond these general requirements, the 2004

147 Loi relative à la bioéthique created the Agence de la

148 Biomédecine, which is charged with overseeing assisted

149 reproductive technology and PGD, among other areas (Loi

150 no. 2004-800). The Agence has the power to extend the

151 uses of PGD laid out in France's bioethics laws (Conseil

152 D'Orientation, 2013a). In 2013, following recommendations

153 from a multidisciplinary Advisory Board, the Director of the

154 Agence decided to permit the use of PGD for human leukocyte

155 antigen (HLA) tissue matching, to select for siblings who can

156 serve as tissue donors, on a trial, case-by-case basis (Conseil

157 D'Orientation, 2013b). Aside from cases of HLA matching,

158 each request to use PGD is reviewed by a Centre

159 Pluridisciplinaire de Diagnostic Prénatal (CPDPN) comprised

160 of physicians, biologists and others. CPDPN decisions to allow

161 PGD are based on an evaluation of whether conditions are

162 sufficiently severe and whether the relevant genetic informa-

163 tion is sufficiently prognostic (Le Diagnostic Preimplantatoire

164 et Vous, 2012).

165 The United Kingdom

166 In the UK, a statutory body called the Human Fertilization

167 and Embryology Authority (HFEA) regulates what assisted

168 reproductive technology may be offered. The HFEA receives

169 its authority from the Human Fertilization and Embryology

170 Acts of 1990 and 2008. These bills allow for the use of PGD

171 only for medical purposes, including HLA matching, and the

172 HFEA maintains a detailed list of disorders for which PGD is

173 permitted (PGD Conditions Licensed by the HFEA, 2015).

174 License committees determine whether new conditions

175 qualify as appropriate medical uses of PGD after reviewing

176 an application submitted by a fertility clinic on behalf of a

177 patient. Before it is considered by a License Committee, the

178 application is sent to clinical geneticists and is posted on the

179 HFEA website for public comment. Licenses may be given

180 when there is a significant risk that an embryo will have 'a. a

181 serious physical or mental disability; b. a serious illness; or c.

182 any other serious medical condition' (Human Fertilization

183 and Embryology Act, 1990). For lower penetrance and later

184 onset conditions, the HFEA has conducted wider policy

185 reviews that involved public consultation. Like France, the

186 UK regulates precisely the conditions for which PGD can be

187 used and has concluded that PGD can be used to select

188 against serious medical conditions or to select for an HLA

189 match for a sick relative.

190 PGD policy (or lack thereof) in the USA

191 In the USA, no agency such as the HFEA or the Agence de la

192 Biomédecine exists and there are no state or federal laws on

the acceptable use of PGD. The genetic testing process itself 193 (i.e. the analytic quality of the tests and the qualifications of 194 the technicians who carry them out) are subject to the Clinical 195 Laboratory Improvement Amendments (CLIA), and the Food 196 and Drug Administration may soon begin ensuring that all 197 laboratory-developed tests, including most genetic tests, are 198 clinically valid, but the use of the tests - the reason for which 199 they are carried out - is left to doctors' discretion and the 200 recommendations of professional organizations. 201

However, professional guidance relevant to the use of PGD 202 is scant and insufficient. Society guidelines are not legally 203 binding, and many guidelines state that they are educational 204 resources, not requirements (Bayefsky and Jennings, 2015). 205 Furthermore, none of the relevant professional societies have 206 promulgated conclusive guidelines aimed at restricting PGD to 207 a set of ethically acceptable uses. For instance, in 1999, the 208 American Society for Reproductive Medicine (ASRM) published 209 a document on sex selection discouraging the use of PGD for 210 non-medical sex selection, but the subsequently revised ASRM 211 Ethics Committee document on sex selection states that 212 'there are reasoned differences of opinion about the permis- 213 sibility' of non-medical sex selection, and therefore practi- 214 tioners 'are under no ethical obligation to provide or refuse to 215 provide non-medically indicated methods of sex selection' 216 (Ethics Committee of the American Society for Reproductive 217 Medicine, 2015). Furthermore, a 2013 ASRM Ethics Committee 218 opinion considers PGD for adult-onset conditions 'ethically 219 justifiable' when the condition is serious and there are no 220 known, or only extremely burdensome, interventions avail- 221 able. For less serious or lower penetrance conditions, though, 222 the opinion states that PGD is 'ethically acceptable as a 223 matter of reproductive liberty' (Ethics Committee of the 224 American Society for Reproductive Medicine, 2013a). Thus, 225 while ASRM addresses some uses of PGD, their guidelines do 226 not draw a clear line between acceptable and unacceptable 227 uses. 228

The American Congress of Obstetricians and Gynecologists 229 (ACOG) draws a clearer line regarding the use of assisted 230 reproductive technology for sex selection, recommending 231 against elective sex selection for any reason (Committee 232 on Ethics of the American Congress of Obstetricians and 233 Gynecologists, 2007). However, their guidelines are not 234 binding and sex selection is performed nonetheless. ACOG 235 does not directly address other uses of PGD. 236

The American College of Medical Genetics (ACMG) does 237 not have a policy specifically on PGD, but its policy on 238 prenatal and preconception screening states there must be 239 validated associations between a mutation and the severity 240 of a disorder (Grody et al., 2013). However, the ACMG also 241 suggests that for adult-onset disorders and disorders with 242 mild phenotypes, variable expression and low penetrance, 243 parents should be able to decide whether to learn this 244 information (Grody et al., 2013). It is left up to the parents, 245 therefore, whether they want to receive and act upon 246 information about less serious genetic conditions regarding 247 their future child. 248

What explains the lack of regulation of PGD in the USA, as 249 compared with Italy, Switzerland, France and the UK? The 250 USA, like the other countries discussed in this paper, is a 251 Western liberal democracy with high-quality fertility centres 252 offering advanced reproductive care. A combination of 253 interrelated factors contributes to the unusual dearth of 254

regulation. In the following segments, this paper will describe the most salient economic, political and social features of the USA that bear on the current regulatory landscape for PGD, and the factors that would need to shift in order for PGD to be regulated in the USA. The lack of regulation in the USA effects patients around the world because it makes the country a destination for reproductive tourism for patients from countries with more restrictive laws.

Lack of government-sponsored healthcare

Italy, France and the UK all have healthcare systems that are largely or nearly entirely funded through the government. Since the government plays a major role in financing healthcare, government officials must consider the applications of medical treatments in order to determine what to cover. In France, for example, government-sponsored insurance funds up to four IVF cycles, but only for heterosexual couples. In the UK, the National Health Service (NHS) funds three cycles of IVF for women between ages 23 and 39, one cycle for women between 40 and 42, and coverage is not restricted to heterosexuals or couples. (In practice, coverage for IVF depends in part on the funding available in a given NHS locality. Thus, depending on her postcode, a woman may receive one, two or three three cycles of IVF funded by the NHS.) Italy does not specify to what extent assisted reproductive technology will be funded, but allocates a certain amount of funding for assisted reproductive technology (White and Case LLP, 2009). In the USA, in contrast, most people are covered by private insurance - government-funded care (through Medicare, Medicaid and the Veterans Health Administration) does not cover advanced fertility treatment such as IVF and PGD, although 15 states in the USA have insurance mandates that require some coverage of fertility treatment by private insurers (coverage requirements and eligibility criteria vary widely and several of the mandates specifically do not require coverage for IVF). Since the US government does not directly fund assisted reproductive technology, it is not forced to stipulate when assisted reproductive technology, including PGD, is permissible. While it is possible for a government to regulate medical practice without subsidizing medical care, regulation by such a government is not necessary or inevitable as it is in places where the government also funds care. Though it has not been required to regulate PGD, it remains an interesting question why the US government has not opted to do so. This question is at least partially explained by the other pressures discussed below.

Switzerland also has no government-sponsored healthcare, but unlike the USA, it has developed PGD regulations nonetheless. (Like the USA after the passage of the Affordable Care Act, Switzerland requires individuals to purchase private health insurance.) In Switzerland, other factors - notably the history of eugenics in Germany, and the large portion of culturally-German Swiss people - have contributed to their relatively strict laws (Ehrensperger, 2015). The old Swiss reproductive law was developed as a counter-proposal to a popular initiative entitled 'Against the misuse of reproductive technologies and genetic manipulation to the human species', which was launched in 1985 by a German-language newspaper.

In the parliamentary debate surrounding the law, the issue of 314 eugenics was raised repeatedly (Parliamentary Debate on the 315 'Federal Law on Medically Assisted Procreation", 1998). 316 Furthermore, a study on the attitudes of Swiss couples 317 concerning the fate of supernumary IVF embryos found that 318 couples from German-speaking areas were less comfortable 319 with research on embryos, suggesting that German-speaking 320 Swiss may have distinct 'cultural factors' that influence 321 their attitudes towards the manipulation of human embryos 322 (Mohler-Kuo et al., 2009). In the USA, while the spectre of 323 eugenics is occasionally invoked in the context of PGD (see, for 324 example, Sparrow, 2013), there is not the same widespread 325 public concern about a resurgence of eugenic beliefs. 326

Independence of medical professionals 327

The lack of government-funded healthcare is both a product 328 of and contributor to the attitudes of physicians towards 329 government regulation of medical practice. Without a 330 single-payer system, medicine in the USA is largely-market 331 driven (Hartzband and Groopman, 2009), and the field of 332 assisted reproduction in particular is directed by market 333 forces rather than a top-down regulatory approach (Spar, 334 2006). The market system provides considerable leeway to 335 physicians to offer the services they want to provide and 336 charge the fees they deem appropriate, within certain limits 337 (Spar, 2006). Many physicians have come to value their 338 relative independence - sometimes called 'physician 339 sovereignty' (Starr, 1982) or 'physician autonomy' (Emanuel 340 and Pearson, 2012) - especially their fiscal independence 341 (Kirch and Vernon, 2009), and therefore have a strong 342 motivation to resist government regulation. 343

In a paper written by past presidents of the ASRM on the 344 regulation of PGD, the authors state that they 'espouse 345 self-regulation, eschewing legislative mandates' (Simpson 346 et al., 2006) They concede that they 'might feel differently 347 if assisted reproductive technology were funded entirely by 348 the government' since 'If the US government or a state were 349 to fund IVF and PGD fully, one could agree that the right to 350 regulate would increase proportionally'. The ASRM leaders 351 believe that as the government does not provide any 352 funding, it lacks the right to regulate their practice. In the 353 UK, by contrast, the NHS directly employs most physicians, 354 and as the employer, the right of the NHS to regulate 355 medical practice is taken somewhat for granted (see, for 356 example, Nettleton et al., 2007). Physicians in the USA 357 continue to hold political capital (Timmermans and Oh, 358 2012), and their resistance to government regulation creates 359 a significant obstacle in this area. 360

Embryo politics 361

Fertility treatment often involves the destruction of excess 362 embryos, and PGD involves the added dimension that 363 discarded embryos contain an 'undesired' genetic feature 364 (Bayefsky, 2015). The destruction of embryos is a conten- 365 tious topic in many places due to the proximity to the 366 abortion debate, but in the USA, intense controversy has 367 resulted in the federal government, for the most part, 368 distancing itself from the issue. The 1995 Dickey-Wicker 369 Amendment prohibits the use of federal funds for research 370

that involves the creation or destruction of human embryos. The prohibition covers funding allocated to the National Institutes of Health's (NIH) intramural and extramural research, and even the medical care provided by the NIH Clinical Centre's fertility programme. In addition, a 1992 law (106 STAT. 4943. Public Law 102-585) prohibits the Veterans Administration from paying for IVF. Rather than adopting a hands-on regulatory approach, as in Italy, the government reached a compromise in which research on embryos and IVF treatment is not banned but also is not publicly funded. It remains an open question whether this compromise was reached due to greater disagreement in the USA, a different balance of political force or other factors. The greater diversity of the USA as compared with most Western European countries (Morin, 2013) may also have contributed, since it is more difficult to design regulations on divisive topics such as the destruction of embryos and the appropriate use of PGD in an extremely diverse representative democracy (Bayefsky, 2015). In order to delineate when PGD is acceptable, the government would need to stake a position on the controversial question of how to handle excess embryos with harmful genetic conditions. As bioethics scholar Thomas Murray writes, 'Persistent passionate conflicts over the legal and moral status of embryos and fetuses have discouraged American legislators from proposing sensible regulation, lest they be drawn into the abortion debate' (Murray, 2014). Legislating on contentious issues is particularly difficult during election years, and in Congress, deep divisions on issues related to abortion regularly cause major pieces of legislation to be stalled or blocked (see, for example, Reuters, 2015). States within the USA have adopted a smattering of laws regarding assisted reproductive technology-related issues such as cloning, surrogacy and insurance coverage for IVF, but none have addressed the question of the appropriate uses of PGD. Any state that wished to do so would have to tackle the contentiousness of embryo politics.

The lack of government involvement in funding IVF or PGD, the independence of medical professionals, and the controversial nature of embryos politics in such a diverse country have all contributed to the lack of regulation of PGD in the USA as compared with other Western nations. Other factors, including governmental structure and the moral complexity of when PGD should be allowed, have no doubt also contributed to the dearth of regulation on the topic in the USA, but these will not be discussed in the present paper.

Divergent laws and reproductive tourism

A variety of internal political, economic and cultural factors have contributed to the development, or lack thereof, of PGD regulations in Europe and the USA. While it is reasonable for countries to have laws that reflect the views of the majority of their populace, there are well-documented consequences of divergent laws on assisted reproductive technology one of which is that patients travel abroad to receive care that is not permitted or difficult to access in their home country (Ferraretti et al., 2010). CRBC is a relatively common phenomenon, accounting for 5% of all European fertility care and 4% of US fertility treatment (Ethics Committee of the American Society for Reproductive Medicine, 2013b). 'Law

evasion' is a primary driver of CBRC (Inhornand Patrizio, 2012) 430 and laws on PGD have directly impacted the number of 431 patients seeking treatment from countries with restrictive 432 rules (Gianaroli et al., 2014; Shenfield et al., 2010). Patients 433 are prepared to travel great distances for reproductive care, 434 including PGD, that they cannot receive in their home country 435 (Preimplantation Genetic Diagnosis in Europe, 2007; Spar, 436 2005), indicating that for some couples, geographic barriers 437 are smaller than legal barriers. 438

While CBRC can be viewed as a useful option for patients 439 seeking access to treatments prohibited at home, the 440 practice also poses a number of health risks to patients and 441 the resulting offspring. It can be difficult for foreigners to 442 identify high-quality fertility centres where they can access 443 standard-of-care treatment. Furthermore, patients who 444 have travelled to receive care may feel pressured to transfer 445 multiple embryos at once, exposing the patient and offspring 446 to the greater risks of morbidity and mortality associated 447 with multiple pregnancy (Ethics Committee of the American 448 Society for Reproductive Medicine, 2013b). Moreover, some 449 clinics may be reluctant to treat patients who become 450 pregnant abroad as a result of a prohibited treatment, 451 making it difficult to perform monitoring and follow-up after 452 IVF and PGD to ensure a healthy pregnancy and live birth 453 (Preimplantation Genetic Diagnosis in Europe, 2007). These 454 potential health risks are concerning and more data is 455 needed to determine the probability and severity of the 456 risks, as well as which patients are most vulnerable. 457

Patients seeking also CBRC expose themselves and others to 458 legal risks. It may be illegal to travel abroad for assisted 459 reproductive technology prohibited at home, or illegal to 460 advise or assist patients seeking treatment elsewhere (Storrow, 461 2011). Furthermore, countries may refuse to recognize the 462 legal parental status of those who have crossed borders to 463 illegally have a child (Storrow, 2011). While this risk applies 464 mainly to surrogacy, it is possible for a country, in theory, to 465 deny parental status following PGD obtained abroad because 466 the parents achieved the pregnancy illegally. Patients could, at 467 minimum, feel pressured to withhold medical information 468 about their child's conception from their doctors to protect 469 themselves from legal trouble and physicians from complicity 470 in illegal behaviour. To minimize the health and legal risks of 471 CBRC, laws could specifically protect physicians who provide 472 recommendations for where to obtain treatment abroad and 473 care for patients upon their return. 474

Finally, CBRC may also foster inequalities in access to 475 assisted reproductive technology due to the expense of 476 travel and out-of-pocket care (Ferraretti, 2010), which may Q2 be exacerbated for such a specialized and costly treatment 478 as PGD. For a foreign couple to undergo IVF and PGD in the 479 USA, they must pay approximately $16,000 out-of-pocket 480 per cycle (RESOLVE, 2015), in addition to travel expenses 481 and the costs of multiple cycles. This cost will be prohibitive 482 to many European couples, even if they decide that they are 483 willing to expose themselves to the medical and legal risks. 484 Only those who are relatively wealthy will be able to obtain 485 PGD abroad from a high-quality clinic. 486

While CBRC may appear to be a practical solution for 487 patients seeking fertility treatments forbidden in their home 488 countries, it will only be available to patients of sufficient 489 means and is associated with significant medical and legal 490 challenges. 491

Conclusion

493 Assisted reproductive technology, and PGD in particular,

494 raise profound ethical questions about which reasonable

495 people, and different cultures and societies, can disagree. It

496 is therefore understandable and morally appropriate for PGD

497 policy to vary in different countries around the world.

498 Distinct societies develop standards that are suited to their

499 histories, circumstances and the beliefs of their respective

500 populations. Nonetheless, in the process of devising these

501 standards, the risks of CBRC should give policymakers pause

502 for thought when designing national regulation on PGD,

503 particularly at the two extremes of banning PGD and

504 permitting all uses. If both very lenient and very restrictive

505 policies were tempered, patients would have a diminished

506 incentive to seek CBRC. In the USA, policymakers have

507 largely avoided the controversial issue, failing to recognize

508 that not regulating PGD involves taking a moral position too

509 (Pennings, 2004); it means allowing patients with sufficient

510 financial resources to obtain whatever service they desire and

511 helping to foster global reproductive tourism. Legislators in

512 the USA and around the world should consider the negative

513 effects of CBRC when reviewing and designing national

514 regulations on PGD. While the significance of national

515 autonomy should not be undervalued, policymakers should

516 nonetheless acknowledge and consider the impact of diver-

517 gent national legal frameworks on the behaviour of patients

518 internationally.

Q3 Uncited references

520 Human Fertilisation and Embryology Bill, 2007

521 Loi relative à la bioéthique, 2004

Loi relative à la bioéthique, 2011 Veterans Health Care Act of 1992,

524 Acknowledgements

525 The author wishes to thank Benjamin E. Berkman in the Department

526 of Bioethics, National Institutes of Health and National Human

527 Genome Research Institute for his helpful comments and advice.

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Declaration: The author reports no financial or commercial 671 conflicts of interest. The opinions expressed herein are the author's 672 and do not reflect the policies and positions of the National 673 Institutes of Health, the US Public Health Service or the US 674 Department of Health and Human Services. 675

Received 30 November 2015; refereed 27 July 2016; accepted 23 676 January 2017. 677