ABSTRACT Genomic research in the reproductive context is shifting from screening and diagnosis to interventions: identifying ways to alter the human genome, epigenome, or microbiome in order to improve obstetric, neonatal, and pediatric outcomes. Already, questions abound regarding the health of children born following experimental CRISPR genetic modification. However, another critically important factor has received far less attention: the involvement of pregnant and potentially-pregnant women in studies of reproductive genomic interventions. At the core of research on genomic interventions is a fundamental question: whether and how to involve women with the intention that they will carry a genetically modified embryo or embryonic environment within their bodies, ultimately becoming pregnant and giving birth to what, is hoped, will be a healthy, live infant. It is problematic that there has been so little discussion about the pregnant women who serve as research participants in reproductive genomics (reprogenomics) trials such as these, and about protections that must be in place for them—either in the short term while they are pregnant or in the long term, well after the pregnancy. At the core of these questions is how to achieve the full potential of reprogenomics research to improve outcomes for children and mothers without causing immediate or generational harms, not just for children but also for women as individuals and members of families. Building on the Second Wave Initiative, which outlined an ethical framework for inclusion of women in pharmacologic clinical trials, this project will build a framework to ethically and socially guide research in reprogenomics, with particular concern for the interests of women participants along with their potential children. Study aims will (1) characterize the ethical challenges of reprogenomics research, including strengths and gaps, through a systematic review of the literature and interviews with key stakeholders; (2) build an ethical framework for reprogenomics research through analyzing stakeholder interview data and holding a deliberative meeting with key stakeholders; and (3) develop a stakeholder-informed toolkit to guide IRBs and researchers who are developing, reviewing and implementing protocols for reprogenomics research. By engaging key stakeholders in reproductive science and medicine, including researchers, IRB members, bioethicists, and patient advocates, this project will develop robust, anticipatory guidance for addressing the ethical challenges of reprogenomics research, along with a toolkit to provide concrete guidance for IRBs, researchers, and research institutions. This work will dovetail with existing efforts to develop ethical guidance for genome editing among scientific and medical professional societies and organizations, while drawing particular attention to the interests of women as research participants (during studies) and patients (after study participation has ended). These strategies will create a pathway for more concerted attention to research ethics in reprogenomics and a broadened consensus on these technologies among key professional bodies.

PROJECT NARRATIVE Research in reproductive genomics is shifting, from diagnostics to interventions in the human genome, epigenome, and microbiome. But we lack ethical guidance about how to conduct these human trials without causing undue harm, especially in regard to the women participants who are a necessary part of such trials. By building an ethical framework and a toolkit to guide researchers and institutional review boards, this project will create robust guidance for research in reprogenomics and a broadened consensus on these technologies among key professional bodies.