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This article reviews the history of research guidelines in pregnancy and illustrates ongoing challenges, as seen in the development of vaccines and therapies during the coronavirus disease 2019 pandemic and investigation of statins for preeclampsia prevention. It explores new approaches that may be used to improve therapeutic research in pregnancy. A major cultural shift is needed to balance potential maternal and\/or fetal risks with potential benefits from participation in research, as well as harm from withholding treatment or providing one that is not evidence\u2010based. 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