Protocol of the Temporality, Eating and Metabolic health during PreconceptiOn (TEMPO) study in females with overweight and obesity: a prospective observational cohort nested within a preconception lifestyle intervention program

Journal article

Introduction: Human reproduction is tightly regulated by circadian and metabolic signals. However, the extent to which alterations in these systems affect fertility, especially in females with overweight or obesity who are at increased risk of infertility, remains poorly understood. This study, nested within the Healthy Early Life Moments in Singapore (HELMS) integrated lifestyle intervention program, aims to: (i) examine the associations between changes in circadian behavior and metabolic health indicators over a 3-month period and subsequent reproductive outcomes during a year of conception attempts, (ii) identify risk factors associated with these changes, and (iii) elucidate the biological mechanisms underpinning these relationships in females attempting to conceive. Methods: This prospective observational cohort study will enroll 283 females with a BMI of 25–40 kg/m² participating in the HELMS program at KK Women’s and Children’s Hospital, Singapore. Participants will be followed for one year as they attempt to conceive. At baseline and at the 3-month mark, circadian behavior will be assessed using validated questionnaires, tracking diaries, and digital wearables. Metabolic health will be evaluated through anthropometry, body fat composition, a metabolic syndrome score, and an insulin resistance index. Blood samples will be collected to analyze metabolic biomarkers and gene expression levels. We will use modified Poisson regression models to examine associations with the clinical pregnancy rate (primary outcome) and discrete-time proportional hazards models to estimate associations with fecundability (secondary outcome) within one year of conception attempts. Discussion: This study is pivotal for identifying potential novel modifiable risk factors to address low fertility rates. Insights from this research will generate hypotheses for interventions designed to enhance preconception care. By screening and managing circadian behaviors and metabolic profiles among females with overweight and obesity, these strategies may benefit those experiencing unexplained infertility. Ultimately, this approach could foster a shift towards a more holistic and patient-centered model of reproductive healthcare.

Authors: Loy, SL; Ku, CW; Pek, JW; Cheung, YB; Leow, MKS

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BioMed Central
• Journal: Reproductive Health
• Volume: 23
• Issue: 1
• Article number: 123
• Publication date: 2026-04-30
• Acceptance date: 2026-04-25
• DOI: 10.1186/s12978-026-02347-4
• EISSN: 1742-4755
• ISSN: 1742-4755
• Language: English
• Keywords: Chrononutrition; Preconception; Female reproductive health; Sleep; Meal timing; Clock gene; Behavior; Chronobiology