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.

内容摘要

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. 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. 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. Human reproduction is shaped by the body’s internal clock and metabolism, but it is not yet clear how changes in these systems affect fertility, particularly in women with overweight or obesity, who are at higher risk of infertility. This study, part of the Healthy Early Life Moments in Singapore (HELMS) program, aims to better understand these links. A total of 283 women with a body mass index between 25 and 40 kg/m2 will be recruited at KK Women’s and Children’s Hospital, Singapore, and followed for one year while trying to conceive. At baseline and 3-month follow-up, participants’ daily routines, including the timing of eating and sleep, will be recorded using questionnaires, diaries, and wearable devices. Their metabolic health will be assessed through body fat, waist size, blood sugar control, and blood tests for biomarkers and gene activity. Researchers will analyze how changes in these patterns relate to the chances of becoming pregnant and the time it takes to conceive. This work is important because it may reveal lifestyle and health factors that can be modified to improve fertility. The findings will help shape new approaches to support women before pregnancy. By addressing daily routines such as meal timing and sleep, alongside metabolic health, this study may offer practical strategies for women struggling to conceive without a clear medical cause identified through standard reproductive investigations. In the long run, this approach could lead to more personalized and supportive fertility care that looks beyond medical treatment to the whole person.