Preimplantation genetic testing for more than one genetic condition: clinical and ethical considerations and dilemmas

Autor: V. van der Schoot, Aimee D C Paulussen, G. de Wert, Edith Coonen, C. E. M. De Die-Smulders, Joseph C F M Dreesen, Wybo Dondorp
Přispěvatelé: MUMC+: DA KG Polikliniek (9), Metamedica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), Obstetrie & Gynaecologie, MUMC+: VMK IVF Lab (9), Klinische Genetica
Rok vydání: 2019
Předmět:
Counseling
medicine.medical_specialty
media_common.quotation_subject
Fertilization in Vitro
combination PGT
DIAGNOSIS
Genetic Condition
Preimplantation genetic diagnosis
Choice Behavior
Consanguinity
03 medical and health sciences
0302 clinical medicine
Quality of life (healthcare)
Pregnancy
ESHRE PGD CONSORTIUM
medicine
Humans
Quality (business)
Genetic Testing
Prospective Studies
Duration (project management)
Preimplantation Diagnosis
Netherlands
Retrospective Studies
Genetic testing
media_common
Ivf treatment
Fertility Clinics
indications
030219 obstetrics & reproductive medicine
medicine.diagnostic_test
Rehabilitation
Genetic Diseases
Inborn
Obstetrics and Gynecology
Embryo Transfer
ethics
transfer decisions
Reproductive Medicine
PRACTICE GUIDELINES
Family medicine
Practice Guidelines as Topic
Quality of Life
Female
Long term safety
preimplantation genetic testing
Psychology
Zdroj: Human Reproduction, 34(6), 1146-1154. Oxford University Press
ISSN: 1460-2350
0268-1161
DOI: 10.1093/humrep/dez059
Popis: STUDY QUESTION Which clinical and ethical aspects of preimplantation genetic testing for monogenic disorders or structural rearrangements (PGT-M, PGT-SR) should be considered when accepting requests and counselling couples for PGT when applied for more than one condition (combination-PGT; cPGT-M/SR)? SUMMARY ANSWER cPGT is a feasible extension of the practice of PGT-M/SR that may require adapting the criteria many countries have in place with regard to indications-setting for PGT-M/SR, while leading to complex choices that require timely counselling and information. WHAT IS KNOWN ALREADY Although PGT-M/SR is usually performed to prevent transmission of one disorder, requests for PGT-M/SR for more than one condition (cPGT-M/SR) are becoming less exceptional. However, knowledge about implications for a responsible application of such treatments is lacking. STUDY DESIGN, SIZE, DURATION Retrospective review of all (40) PGT-M/SR applications concerning more than one genetic condition over the period 1995-2018 in the files of the Dutch national PGT centre. This comprises all relevant national data since the start of PGT in the Netherlands. PARTICIPANTS/MATERIALS, SETTING AND METHODS Data regarding cPGT-M/SR cases were collected by means of reviewing medical files of couples applying for cPGT-M/SR. Ethical challenges arising with cPGT-M/SR were explored against the background of PGT-M/SR regulations in several European countries, as well as of relevant ESHRE-guidance regarding both indications-setting and transfer-decisions. MAIN RESULTS AND THE ROLE OF CHANCE We report 40 couples applying for cPGT-M/SR of which 16 couples started their IVF treatment. Together they underwent 39 IVF cycles leading to the birth of five healthy children. Of the couples applying for cPGT, 45% differentiated between a primary and secondary condition in terms of perceived severity. In the light of an altered balance of benefits and drawbacks, we argue the 'high risk of a serious condition' standard that many countries uphold as governing indications-setting, should be lowered for secondary conditions in couples who already have an indication for PGT-M/SR. As a consequence of cPGT, professionals will more often be confronted with requests for transferring embryos known to be affected with a condition that they were tested for. In line with ESHRE guidance, such transfers may well be acceptable, on the condition of avoiding a high risk of a child with a seriously diminished quality of life. LIMITATIONS, REASONS FOR CAUTION We are the first to give an overview of cPGT-M/SR treatments. Retrospective analysis was performed using national data, possibly not reflecting current trends worldwide. WIDER IMPLICATIONS OF THE FINDINGS Our observations have led to recommendations for cPGT-M/SR that may add to centre policy making and to the formulation of professional guidelines. Given that the introduction of generic methods for genomic analysis in PGT will regularly yield incidental findings leading to transfer requests with these same challenges, the importance of our discussion exceeds the present discussion of cPGT. STUDY FUNDING/COMPETING INTEREST(S) The research for this publication was funded by the Dutch Organization for Health Research and Development (ZonMw), project number: 141111002 (Long term safety, quality and ethics of Preimplantation Genetic Diagnosis). None of the authors has any competing interests to declare.
Databáze: OpenAIRE
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