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Preimplantation genetic diagnosis (PGD) is now well established and provided in many European countries. However, regulations, professional standards and accreditation requirements can differ notably. Furthermore, no comprehensive independent data exist either about practice and provision in Europe or about the quality assurance practices and proce...
Context in source publication
Context 1
... PGD providers to be certified or accredited, 3,4 the uptake of formal systems of quality management or of their different elements remains low (Table 3). Only 77/141 centres (55%) have a designated quality manager, an essential early step in implementing a quality system, and just 46/141 (33%) have achieved or are preparing for accreditation or certification. ...
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ABSTRACT
Background: Couples who are at risk of having an infant with a serious genetic disorder can benefit from
pre-implantation genetic diagnosis (PGD), but many couples still opt for the riskier pre-natal diagnosis (PND).
Although couples make this decision together, the male and the female in the couple may have different
attitudes toward choo...
Citations
... While no explicit regulation for PGT existed, discarding embryos was not permitted under the 1990 Embryo Protection Act, thereby disallowing selective transfer of embryos (1990). While direct testing of embryos (including cleavage stage embryos and blastocysts) was not allowed, an exception was made for the analysis of polar bodies, which is conducted in the oocytes and is thus not considered testing of embryos (Soini et al., 2006;Corveleyn et al., 2007Corveleyn et al., , 2008. As polar body biopsy only gives information about the egg cell, PGT via polar body testing is not possible for conditions inherited via the father (Corveleyn et al., 2007;Bock von Wulfingen, 2016). ...
STUDY QUESTION: Would the different regulatory approaches for preimplantation genetic testing (PGT) in Europe permit the implementation of preimplantation genetic testing using polygenic risk scores (PGT-P)?
SUMMARY ANSWER: While the regulatory approaches for PGT differ between countries, the space provided for potential implementation of PGT-P seems limited in all three regulatory models.
WHAT IS KNOWN ALREADY: PGT is a reproductive genetic technology that allows the testing for hereditary genetic disorders and chromosome abnormalities in embryos before implantation. Throughout its history, PGT has largely been regarded as an ethically sensitive technology. For example, ethical questions have been raised regarding the use of PGT for adult-onset conditions, non-medical sex selection, and human leukocyte antigen typing for the benefit of existing siblings. Countries in which PGT is offered each have their own approach of regulating the clinical application of PGT, and a clear overview of legal and practical regulation of PGT in Europe is lacking. An emerging development within the field of PGT, namely PGT-P, is currently bringing new ethical tensions to the forefront. It is unclear whether PGT-P may be applied within the current regulatory frameworks in Europe. Therefore, it is important to investigate current regulatory frameworks in Europe and determine whether PGT-P fits within these frameworks.
STUDY DESIGN, SIZE, DURATION: The aim of this study was to provide an overview of the legal and practical regulation of the use of PGT in seven selected European countries (Belgium, France, Germany, Italy, the Netherlands, Spain and the United Kingdom) and critically analyse the different approaches with regards to regulatory possibilities for PGT-P. Between July and September 2023, we performed a thorough and extensive search of websites of governments and governmental agencies, websites of scientific and professional organisations, and academic articles in which laws and regulations are described.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We investigated the legal and regulatory aspects of PGT by analysing legal documents, regulatory frameworks, scientific articles, and guidelines from scientific organizations and regulatory bodies to gather relevant information about each included country. The main sources of information were national laws relating to PGT.
MAIN RESULTS AND THE ROLE OF CHANCE: We divided the PGT regulation approaches into three models. The regulation of PGT differs per country, with some countries requiring central approval of PGT for each new indication (the medical indication model: the United Kingdom, the Netherlands), other countries evaluating each individual PGT request at the local level (the individual requests model: France, Germany), and countries largely leaving decision-making about clinical application of PGT to healthcare professionals (the clinical assessment model: Belgium, Italy, Spain). In the countries surveyed that use the medical indication model and the individual requests model, current legal frameworks and PGT criteria seem to exclude PGT-P. Even in countries using the clinical assessment model, the fact that healthcare professionals and scientific organizations in Europe are generally negative about implementation of PGT-P due to scientific and socio-ethical concerns, implies that, even if it were legally possible, the chance that PGT-P would be offered in the near future might be low.
LIMITATIONS, REASONS FOR CAUTION: The results are based on our interpretation of publicly available written information and documents, therefore not all potential discrepancies between law and practice might have been identified. In addition, our analysis focuses on seven – and not all – European countries. However, since these countries are relevant players within PGT in Europe and since they have distinct PGT regulations, the insights gathered give relevant insights into diverse ways of PGT regulation.
WIDER IMPLICATIONS OF THE FINDINGS: To the best of our knowledge, this is the first paper that provides a thorough overview of the legal and practical regulation of PGT in Europe. Our analysis of how PGT-P fits within current regulation models provides guidance for healthcare professionals and policymakers in navigating the possible future implementation of PGT-P within Europe.
STUDY FUNDING/COMPETING INTERESTS: This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 813707. The authors declare no conflict of interest.
TRIAL REGISTRATION NUMBER: Not applicable.
... European IVF clinics participating in preimplantation genetic diagnosis (PGD) found about 1/3 of patients were referred internationally due to legal reasons, followed by PGD availability in home country [59]. In Dubai, clinicians promoted family balancing through gender selection with one clinician emphasizing, "If the father died, there needs to be a son," and another stating, "You need to have a boy," in reference to inheritance traditionally being given to the boy [60]. ...
Objectives
This review analyzes the experiences of patients and clinicians with regards to international cross border reproductive care (CBRC) for the purpose of conception
Methods
Electronic databases PubMed, Embase, Web of Science, and Scopus were searched using ‘medical tourism’ AND ‘assisted reproductive technology’ from 1978-2020.
Results
Predominant patient motivators for CBRC were cost and legality of assisted reproduction technology (ART) in one's home country, followed by cultural factors like shared language, religion, and cultural familiarity. Clinicians suggested global laws for CBRC would reduce the potential for exploitation of vulnerable populations but believed the enactment of international regulations unlikely and, even if enacted, difficult to enforce
Conclusions
While patient and clinician experiences with CBRC varied, patients frequently cited financial and legal reasons for pursuing CBRC, while many providers had concern for the patient’s safety.
Clinical practice implications
This review recommends clinicians involved in family planning counsel patients seeking treatment abroad by: (i) informing patients of the risks and benefits of treatment abroad, (ii) establishing guidelines and standards for clinicians on resuming patient care post-CBRC, and (iii) creating a directory of reputable CBRC clinicians and experts.
... When we look at the answers for when should screening take place, we see divided opinions; however, "at birth" seem to reunite most of the responses (12). ...
... [11]. POs in Czech Republic, Denmark, Italy, Luxembourg, North Macedonia, Poland, Serbia and Switzerland are unaware of the possibility of PGD in their country however it is available in, the Czech Republic, Denmark, Italy and Switzerland [10,12,13]. The discrepancies we have observed in the answers might also be due to the modalities (public or private services) of PGD offer in each country. ...
Background
The development of new genetic testing methods and the approval of the first treatments raises questions regarding when and how to perform screening for inherited neuromuscular conditions. Screening directives and access to the different techniques is not uniform across Europe. The patient advisory board of the European reference network for rare neuromuscular diseases (NMD) conducted a qualitative study to understand the state of play of screening for inherited NMD in Europe and patients’ needs.
Results
We collected answers from 30 patient organisations (POs) from 18 European countries. Fifteen acknowledge the existence of pre-implantation genetic diagnosis in their country. Regarding prenatal screening, we had 25 positive answers and 5 negative ones. Twenty-four POs mentioned that newborn screening was available in their country. We had some contradictory answers from POs from the same country and in some cases; diseases said to be part of the screening programmes were not hereditary disorders. Twenty-eight organisations were in favour of screening tests. The reasons for the two negative answers were lack of reimbursement and treatment, religious beliefs and eventual insurance constrains. Most POs (21) were in favour of systematic screening with the option to opt-out. Regarding the timing for screening, “at birth”, was the most consensual response. The main priority to perform screening for NMDs was early access to treatment, followed by shorter time to diagnostic, preventive care and genetic counselling.
Conclusions
This is the first study to assess knowledge and needs of POs concerning screening for NMDs. The knowledge of POs regarding screening techniques is quite uneven. This implies that, even in communities highly motivated and knowledgeable of the conditions they advocate for, there is a need for better information. Differences in the responses to the questions “how and when to screen” shows that the screening path depends on the disease and the presence of a disease modifying treatment. The unmet need for screening inherited NMDs should follow an adaptive pathway related to the fast moving medical landscape of NMDs. International coordination leading to a common policy would certainly be a precious asset tending to harmonize the situation amongst European countries.
... HbE/βthal disease is the most common consultation in each center, following by alpha thalassemia and Duchenne muscular dystrophy. In European countries, there are several centers that perform PGT-M as their main or sole activity and approximately 50 centers offer PGT-M in addition to their ART service [30]. In these centers, the most common referral is for cystic fibrosis, which is consistent with the high carrier rate in people of north European descent [25]. ...
Thalassemia and hemoglobinopathy is a group of hereditary blood disorder with diverse clinical manifestation inherited by autosomal recessive manner. The Beta thalassemia/Hemoglobin E disease (HbE/βthal) causes a variable degree of hemolysis and the most severe form of HbE/βthal disease develop a lifelong transfusion-dependent anemia. Preimplantation genetic testing (PGT) is an established procedure of embryo genetic analysis to avoid the risk of passing on this particular condition from the carrier parents to their offspring. Preimplantation genetic testing for chromosomal aneuploidy (PGT-A) also facilitates the selection of embryos without chromosomal aberration resulting in the successful embryo implantation rate. Herein, we study the clinical outcome of using combined PGT-M and PGT-A in couples at risk of passing on HbE/βthal disease. The study was performed from January 2016 to December 2017. PGT-M was developed using short tandem repeat linkage analysis around the beta globin gene cluster and direct mutation testing using primer extension-based mini-sequencing. Thereafter, we recruited 15 couples at risk of passing on HbE/βthal disease who underwent a combined total of 22 IVF cycles. PGT was performed in 106 embryos with a 3.89% allele drop-out rate. Using combined PGT-M and PGT-A methods, 80% of women obtained satisfactory genetic testing results and were able to undergo embryo transfer within the first two cycles. The successful implantation rate was 64.29%. PGT accuracy was evaluated by prenatal and postnatal genetic confirmation and 100% had a genetic status consistent with PGT results. The overall clinical outcome of successful live birth for couples at risk of producing offspring with HbE/βthal was 53.33%. Conclusively, combined PGT-M and PGT-A is a useful technology to prevent HbE/βthal disease in the offspring of recessive carriers.
... Von den 53 europäischen PID-Zentren waren 2008 nur 33 % akkreditiert bzw. bereiteten sich auf eine Akkreditierung vor [2]. Die Ergebnisse einer Befragung im Jahr 2014 zeigen eine erhebliche Erhöhung des Anteils akkreditierter Labors. ...
Zusammenfassung
Seit 25 Jahren gibt es die Präimplantationsdiagnostik (PID) als Alternative zur Pränataldiagnostik monogener, mitochondrialer und chromosomaler Erkrankungen. Nach In-vitro-Fertilisation (IVF) oder (meist) Intrazytoplasmatischer Spermieninjektion (ICSI) werden entweder Polkörperchen, Blastomere oder Ektodermzellen aus den Oozyten bzw. dem Präimplantationsembryo gewonnen, um sie einer molekularen Diagnostik zu unterziehen. Nichtbetroffene Embryonen werden ausgewählt, um sie in die Gebärmutter einzusetzen, um dadurch einen Schwangerschaftsabbruch zu verhindern.
1997 wurde das ESHRE (European Society of Human Reproduction and Embryology) PGD Consortium als Teil der ESHRE-Arbeitsgruppe für Reproduktionsgenetik mit dem Ziel gegründet, in einer Langzeitbeobachtung Effizienz und klinische Ergebnisse der PID zu erfassen. Im Dezember 1999 wurde der erste von inzwischen insgesamt 13 PID-Konsortiumsberichten veröffentlicht. Darüber hinaus wurden in den letzten Jahren (2013–2015) unpublizierte Daten von der Hälfte aller 121 Mitglieder (darunter 89 europäische) des PID-Konsortiums gesammelt.
Auch wenn die Unterschiede nicht mehr so groß sind wie früher, ist die Bandbreite der PID-Gesetzgebung, -Regelwerke und -Angebote in den einzelnen europäischen Ländern noch relativ groß. Dies hat dazu geführt, dass Patienten über die nationalen Grenzen hinweg nach medizinischer Hilfe suchen.
Zu Beginn entsprach das Indikationsspektrum mehr oder weniger demjenigen der Pränataldiagnostik. Interessanterweise wird in einigen Ländern eine zunehmende Anzahl von Tests für spätmanifeste Erkrankungen angeboten, was darauf hinweist, dass für diese Fälle die PID eher akzeptiert wird als die Pränataldiagnostik.
Die wichtigsten chromosomalen Indikationen für PID stellen die reziproken Translokationen dar (sowohl für männliche als auch für weibliche Translokationsträger).
Es ist zu beobachten, dass die Biopsie eines Embryos in sehr frühen Furchungsstadien langsam durch die Blastozystenbiopsie ersetzt wird. Die Fehlgeburtenrate ist nicht erhöht. Die Anzahl der Schwangerschaftsabbrüche ist extrem niedrig. Eine von 6 Schwangerschaften führt zur Geburt von Zwillingen und die Zahl von höheren Mehrlingsschwangerschaften ist sehr begrenzt. In einzelnen Fällen wurde von Fehldiagnosen berichtet.
... Although CBRS poses difficult medical, social and normative issues, for the moment, there is no literature review covering this topic. Only few studies limited to the European situation have addressed the specific medical nature and social implications of reprogenetics in cross-border settings (10,11). Evidences are scattered and call for a synthesis in order to understand the larger picture. ...
... After discarding affected embryos, one to three unaffected embryos are implanted depending on the medical indications and IVF protocol (15). Cross-border PGD have been observed in many parts of the world for conditions of variable severity, penetrance, and time of manifestation (10,(18)(19)(20). The international offer on the Internet of PGD services has also been noticed (21) as well as cross-border traveling for non-directive genetic counseling, an important feature of PGD services (22). ...
... In many cases, both IVF clinics and laboratories were in the same institutions. One of their conclusions is that foreign patients represent 'a large part of the total PGD activity in Europe' (10). They reported that the international flow for PGD was expanding and accounts for one-third of all PGD activities. ...
The purpose of this review is to synthesize the current knowledge on the international movement of patients and biopsied embryo cells for preimplantation genetic diagnosis and its different applications. Thus far, few attempts have been made to identify the specific nature of this phenomenon called “cross-border reprogenetic services”. There is scattered evidence, both empirical and speculative, suggesting that these services raise major issues in terms of service provision, risks for patients and the children-to-come, the legal liabilities of physicians, as well as social justice. To compile this evidence, this review uses the narrative overview protocol combined with thematic analysis. Five major themes have emerged from the literature at the conjunction of cross-border treatments and reprogenetics: “scope”, “scale”, “motivations”, “concerns”, and “governance”. Similar themes have already been observed in the case of other medical tourism activities, but this review highlights their singularity with reprogenetic services. It emphasizes the diagnostic and autologous feature of reprogenetics, the constant risk of misdiagnosis, the restriction on certain tests for medically controversial conditions, and the uncertain accessibility of genetic counseling in cross-border settings.
... In 2009, PGD for single gene disorders and translocations was allowed after an Italian Supreme Court decision that the restrictions were unconstitutional [19]. For a further discussion of European regulation of PGD, see Corveleyn, et al. [20,21]. ...
Preimplantation genetic diagnosis was developed nearly a quarter-century ago as an alternative form of prenatal diagnosis that is carried out on embryos. Initially offered for diagnosis in couples at-risk for single gene genetic disorders, such as cystic fibrosis, spinal muscular atrophy and Huntington disease, preimplantation genetic diagnosis (PGD) has most frequently been employed in assisted reproduction for detection of chromosome aneuploidy from advancing maternal age or structural chromosome rearrangements. Major improvements have been seen in PGD analysis with movement away from older, less effective technologies, such as fluorescence in situ hybridization (FISH), to newer molecular tools, such as DNA microarrays and next generation sequencing. Improved results have also started to be seen with decreasing use of Day 3 blastomere biopsy in favor of polar body or Day 5 trophectoderm biopsy. Discussions regarding the scientific, ethical, legal and social issues surrounding the use of sequence data from embryo biopsy have begun and must continue to avoid concern regarding eugenic or inappropriate use of this technology.
... The survey of QA practices in 53 European PGD laboratories revealed that only 33% of laboratories described themselves as 'accredited, certified or preparing for accreditation' , and 66% as not participating in EQA, a problem which was exacerbated at that time by the absence of existing PGD-specific schemes. 179 The ESHRE PGD Consortium reacted rapidly to develop and encourage better QA, with a network of partner organisations: (a) PGD-specific EQA schemes are now available, (b) training workshops addressing the accreditation of PGD laboratories are held regularly, (c) the Consortium has formally recommended that all PGD laboratories should be accredited or working actively towards accreditation (ISO 15189) and (d) a guidance document has been published. 150 A more recent survey by the EuroGentest2 consortium of molecular genetic testing laboratories in Europe revealed that only 23% of responding laboratories were accredited, and that 22% did not participate in any genetics EQA schemes. ...
Study question:
How has the interface between genetics and assisted reproduction technology (ART) evolved since 2005?
Summary answer:
The interface between ART and genetics has become more entwined as we increase our understanding about the genetics of infertility and we are able to perform more comprehensive genetic testing.
What is known already:
In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and ART and published an extended background paper, recommendations and two Editorials.
Study design, size, duration:
An interdisciplinary workshop was held, involving representatives of both professional societies and experts from the European Union Eurogentest2 Coordination Action Project.
Participants/materials, setting, methods:
In March 2012, a group of experts from the European Society of Human Genetics, the European Society of Human Reproduction and Embryology and the EuroGentest2 Coordination Action Project met to discuss developments at the interface between clinical genetics and ART.
Main results and the role of chance:
As more genetic causes of reproductive failure are now recognized and an increasing number of patients undergo testing of their genome prior to conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and PGD may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from RCTs to substantiate that the technique is both effective and efficient. Whole genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo.
Limitations, reasons for caution:
The legal landscape regarding assisted reproduction is evolving, but still remains very heterogeneous and often contradictory. The lack of legal harmonization and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe, and beyond.
Wider implications of the findings:
This continually evolving field requires communication between the clinical genetics and IVF teams and patients to ensure that they are fully informed and can make well-considered choices.
Study funding/competing interests:
Funding was received from ESHRE, ESHG and EuroGentest2 European Union Coordination Action project (FP7 - HEALTH-F4-2010-26146) to support attendance at this meeting.
... The contribution of a doctor could be minimized by not forcing him or her to refer to a specific clinic but by asking him or her to distribute a leaflet that contains all the information needed to find a clinic. In a number of countries, such as Germany, Switzerland and Ireland, referral to a doctor or clinic abroad is prohibited (Corveleyn et al., 2008). Although this rule has never been put to the test in court, it seems to be a fairly strong deterrent in practice. ...
Since the development of assisted reproduction technologies, there has been discussion on which people should have access to these technologies and which treatments and techniques are morally acceptable. However, national legislation can no longer determine what citizens do. Some countries react to their citizens going abroad to evade restrictions by implementing even more restrictive laws. Turkey has recently become the first state to ban reproductive travel in pursuit of donor gametes. Several states in Australia have enacted or are considering laws that prohibit international commercial surrogacy. This article investigates the consistency and morality of several state reactions to cross-border reproductive care (CBRC), including extraterritorial regulation. The only widespread existing extraterritorial regulation of private life concerns female genital cutting (FGC), sex with children and (largely in the past) abortion. This discussion develops an analogy with these cross-border crimes to evaluate the morality of similar legislation in cases of CBRC. The dissimilarity in these analogies shows that extraterritoriality is a radical position that is generally inappropriate in the case of CBRC. Subsequently, several potential state reactions to CBRC for law evasion are considered. It is concluded that legislation of CBRC should be modest, tolerant and nuanced.
... For example with respect to genetic testing, there is evidence that it falls short of the desired quality with substantial numbers of errors in both the EU and the USA [4]. Throughout the EU, regulations, professional standards and accreditation requirements can differ substantially with respect, for example, to preimplantation genetic diagnosis [5]. ...
Views on pharmacogenetics and gene therapy systematically differ across European countries. But despite a complex regulatory regime there is a balance of support, albeit laced with considerable uncertainty.
