title: Potential consequences of clinical application of artificial gametes: a systematic review of stakeholder views.
abstract: BACKGROUND
  Recent progress in the formation of artificial gametes, i.e. gametes generated from progenitors or somatic cells, has led to scientific and societal discussion about their use in medically assisted reproduction. In animals, live births have already been achieved using artificial gametes of varying (cell type) sources and biological research seems to be progressing steadily toward clinical application in humans. Artificial gametes could potentially help not only infertile heterosexual couples of reproductive age of which one or both partners lacks functional gametes, but also post-menopausal women and same-sex couples, to conceive a child who will be genetically related to them. But as clinical application of these new technologies may have wider societal consequences, a proactive consideration of the possible impact seems timely and important. This review aims to contribute to this by providing a systematic overview of the potential consequences of clinical application of artificial gametes anticipated by different stakeholders.
  
  
  METHODS
  The electronic database 'Medline/Pubmed' was systematically searched with medical subject heading terms (MesH) for articles published in English between January 1970 and December 2013. Articles were selected based on eligibility and reference lists of eligible studies were hand searched. The reported potential consequences of clinical application of artificial gametes were extracted from the articles and were grouped into categories by content analysis. Per category, we noted which stakeholders referred to which potential consequences, based on author affiliations and, if applicable, study participants.
  
  
  RESULTS
  The systematic search yielded 2424 articles, and 84 studies were included after screening. Nine positive consequences, 21 specific consequences requiring consideration and 22 recommendations referring to clinical application of artificial gametes were documented. All positive consequences, consequences requiring consideration and recommendations could be categorized under the following eight objectives to be safeguarded during clinical application of artificial gametes: (i) timing the implementation of new treatments correctly, (ii) meeting 'plausible demands of patients', (iii) improving and safeguarding public health, (iv) promoting the progress of medical science in the interest of future patients, (v) providing treatments that are morally acceptable for the general public, (vi) controlling medical practice, (vii) offering treatments that allow acquisition of informed consent and (viii) funding treatments fairly. Professionals specialized in biomedical science, science journalists and professionals specialized in ethics all addressed these eight objectives on artificial gametes, whereas professionals specialized in law or political science addressed seven objectives. Although one study reported on the perspective of parents of under-aged patients on three objectives, the perspectives of patients themselves were not reported by the reviewed literature.
  
  
  CONCLUSIONS
  Of course, clinical introduction of artificial gametes should only be considered on the basis of reassuring outcomes of appropriate preclinical effectiveness and safety studies. In addition, potential users' views on the desirability and acceptability of artificial gametes should be studied before clinical introduction. A societal debate including all stakeholders is needed to determine the relative importance of all arguments in favor of and against the introduction of artificial gametes into clinical practice. More broadly, establishing pre-implementation processes for new medical techniques is relevant for all fields of medicine.
authors.affiliation: Center for Reproductive Medicine, Women's and Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Hendriks
authors.affiliation: Department of Health, Ethics and Society, Research Schools GROW and CAPHRI, Maastricht University, Maastricht, The Netherlands.
authors.forename: Wybo
authors.initials: W
authors.lastname: Dondorp
authors.affiliation: Department of Health, Ethics and Society, Research Schools GROW and CAPHRI, Maastricht University, Maastricht, The Netherlands.
authors.forename: Guido
authors.initials: G
authors.lastname: de Wert
authors.affiliation: Center for Reproductive Medicine, Women's and Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: Hamer
authors.affiliation: Center for Reproductive Medicine, Women's and Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Repping
authors.affiliation: Center for Reproductive Medicine, Women's and Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Leuven University Fertility Centre, Leuven University Hospital, Leuven, Belgium e.a.dancet@amc.uva.nl.
authors.forename: Eline A F
authors.initials: EA
authors.lastname: Dancet
mesh_terms: D053595:Embryonic Stem Cells / Q000166:cytology; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D008297:Male; D008846:Micromanipulation / Q000379:methods*; D009865:Oocytes / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology; D027724:Reproductive Techniques, Assisted / Q000941:ethics*; D013094:Spermatozoa / Q000166:cytology*
keywords: artificial gametes; assisted reproductive technologies; ethics; gametogenesis