Bridging ideal studies and real-world practice: the potential role of real-world evidence in reproductive medicine

Abstract

Evidence-based medicine is central to reproductive health care, guiding interventions such as ovarian stimulation protocols and fertility preservation strategies. While randomized controlled trials (RCT) remain the gold standard for providing evidence and for establishing causality, their limitations, including restricted generalizability and high costs, highlight the need for complementary methodologies. Real-world evidence (RWE), derived from real-world data (RWD) such as electronic health records and assisted reproductive technology (ART) registries, has the potential to bridge the gap between controlled research settings and routine clinical practice, particularly for evaluating long-term and rare outcomes. However, RWE faces considerable challenges, including bias, variability in data quality, and difficulties in establishing causality. This paper explores the role of RWE in ART. Despite its promise, RWE cannot replace RCT, particularly in scenarios where the signal-to-noise ratio is low, such as detecting small effect differences in ovarian stimulation protocols or treatment add-ons. Instead, in most instances, RWE is positioned to complement RCT, supported by emerging regulatory frameworks such as the guidelines of the European Medicine Agency and the European Union's tissue directives, which emphasize the generation of RWE from ART practice to strengthen patient follow-up and safety monitoring. For ART stakeholders, a comprehensive understanding of the strengths and limitations of RWE is essential, as is the target trial emulation framework on RWD, for advancing the field and improving patient outcomes.