Diet, lifestyle factors, and human fertility: what we know, what we wish we knew, and what we may never know.

Persistent downward trends in birth rates and semen quality across the globe have understandably raised interest in understanding the key drivers of human fertility. Among these, interest in factors that are potentially modifiable and subject to an important degree of volitional control, such as diet, exercise, or substance use, has been considerable. Unfortunately for those interested in this topic, either to guide their own behavior or to provide medical advice to those seeking care, the level of detail sought is often misaligned with the level of evidence available at any point in time. Further, the very nature of lifestyle factors is such that for some specific questions patients may pose, there will never be an answer that matches the highest standards of evidence-based medicine. Nevertheless, it is possible to outline rational and robust recommendations that simultaneously balance what is known with the outstanding knowledge gaps. This review addressed three broad topics in their relation to human fertility: diet, including the use of dietary supplements, specific foods, and dietary patterns; energy balance, covering the role of weight management and physical activity; and substance use. Throughout, we identified questions for which the state of the literature allows for strong recommendations; questions that remain open today but are answerable, and addressing them is likely to advance the practice of reproductive medicine; and questions that may never be fully answered without this uncertainty being a barrier for robust action.