An international team of experts in embryology and bioethics has published the first white paper on the use of embryonic models based on stem cells in the field of reproductive biology. The document, coordinated by UPF researcher Alfonso Martínez-Arias, offers an integrated view of developmental biology, bioethics and legislation, and proposes guidelines for the correct implementation of these models in research and in the regulation and development of technologies related to human reproduction. This text should facilitate the use of models to study embryo development beyond the 14-day legal barrier, hopefully leading to understanding some of the conditions that cause infertility.
It is estimated that one in six people of reproductive age experiences fertility problems at some point in their lives. Worldwide, infertility affects 48 million couples. Despite the fact that in the last 30 years assisted reproduction techniques have enabled the birth of more than 10 million babies worldwide, much remains to be understood about why, in humans, only one in three fertilized eggs progresses beyond the third week of development.
“We are very knowledgeable of what happens during the first seven days of embryonic development; we know much less about what happens during the following week in which the embryo becomes implanted in the uterus and, for ethical and legal reasons, we cannot take our research further”. In particular, exploring the third week is crucial in our study, explains Alfonso Martínez-Arias , an ICREA researcher, professor emeritus at Pompeu Fabra University in Barcelona and project leader. “This limitation prevents us from seeing how, at the end of the third week, the embryo has transformed, it is organized and primed for organogenesis”. According to Martínez-Arias, during this process, known as gastrulation, “many of the cardiovascular and metabolic disorders or even limb malformations that are detected after birth originate”.
The so-called ‘14-day rule’ prohibits the cultivation of human embryos in the laboratory beyond this period. In addition, the embryos that are used for research are surplus ones donated by assisted reproduction clinics. The supply is limited supply and subject to ethical restrictions that do not allow the investigation of gastrulation.
Embryonic models based on stem cells, that is, copies of embryos generated in the laboratory from cells that can become any cell in the body, are, conversely, a good alternative. Although in humans it has not yet been possible to go beyond the early stages of gastrulation, in monkeys they can already be used to mimic it.
To answer the biological, ethical and legal questions involved in the use of these models in research and in the regulation and development of technologies related to human reproduction, a white paper has been published in Human Reproduction . Coordinated by biologist Alfonso Martínez-Arias, the work includes the opinion of experts from different fields who during a meeting at the Institut Pasteur in Paris, in November 2024, discussed the requirements to use these models properly.
“If we want embryonic models based on stem cells to be useful for research and the treatment of infertility, we must have reliable, reproducible models with a legal framework that allows us to use them”, the development expert states.
In the document, the experts advocate the need to standardize the models, at the highest level, so that they can be used for clinical practice and the development of devices that can improve assisted reproduction techniques. “The disparity of methodologies and cell lines used to create the models means that the results are not yet comparable to human embryos”. Nevertheless, the experts hope to break this barrier in the not-too-distant future.
In their opinion, nowadays embryos and models should not be subject to the same regulations. “We agree that an embryo should not be cultured beyond 14 days, but it is important to explain the value of stem cell models as an extraordinary resource to understand this period, when many human diseases originate, as a replacement for embryos”, Martínez-Arias adds.
Precisely because it is not the same, the white paper makes the red lines clear: the models must never be transferred to the uterus of any animal or human, and must be cultivated only for the time necessary for each study. These limits, they suggest, must always be overseen by ethics committees and must be communicated responsibly and transparently.
Human Reproduction
Systematic review
Human embryos
Human stem cell-based embryo models: innovation, ethics, and policy
1-Jun-2026
P.R.-G. is a named inventor on a patent application filed by the Babraham Institute on embryo implantation models. N.R. is an inventor on the patents ‘Blastoid, cell line based artificial blastocyst’ (EP2986711) and ‘Blastocyst-like cell aggregate and methods’ (EP21151455.9) and is a share-holder in Dawn-bio, a company holding licenses for these patents. A.W. is a cofounder of and holds equity in Simbryo Technologies. V.P., through The KU Leuven, Belgium, has filed a patent application PCT/EP2023/073949. V.P. is one of the inventors on this patent. A.M.A. and N.M. are inventor of two patents on Human Polarised Three-dimensional Cellular Aggregates PCT/GB2019/052670 and Polarised Three-dimensional Cellular Aggregates PCT/GB2019/052668. J.H.H. has submitted patent applications relevant to the findings reported herein on naive pluripotency, synthetic embryo models, and ex utero embryogenesis and is a founding member and chief scientific advisor to Renewal Bio Ltd. M.M. is an ISSCR Board member since 2023; Clerk since 2025; ISSCR Committee member throughout last 36 months and role in developing ISSCR Guidelines the executive committee of the International Society for Stem Cell Research and declares that her institute was reimbursed for travel costs to attend ISSCR Board meetings (biannual over last 3 years); board member and Clerk of International Society for Stem Cell Research; and Member of ISSCR Ethics and Public Policy Committees. K.K.N. is a member of the Board of managers of the ISSCR. E.C. receives Consulting fees—Nuffield Council on Bioethics—and chaired the NCoB working group on SCBEMs in 2024 for which she received a small honorarium. O.P. has paid employment and is a co-founder and shareholder for Cellular Intelligence. V.P. has a patent pending with KU Leuven related to human PSCs to create extraembryonic mesoserm. T.T. is an inventor on patent applications related to naïve hPSCs and human embryo models. No specifications or comments included. N.d.G. is an unpaid member of the ISSCR Ethics committee. N.d.G. is supported by the Dutch Organization for Health Research and Development (ZonMW PSIDER, project number: 10250022120002); reNEW, the Novo Nordisk Foundation Center for Stem Cell Medicine (NNF21CC0073729). E.C. acknowledges travel support—Nuffield Council on Bioethics—chairing the NCoB working group on SCBEMs in 2024 and received travel expenses for meetings. K.S. is a past member and current immediate past chair of ESHRE. The rest of the authors declare that they do not have any conflict of interests in relation to this article.