The hidden burden of infertility: multimorbidity patterns and longitudinal disease trajectories in a population-based cohort of 2 million women

Infertility is increasingly recognized not only as a reproductive concern but also as a potential sentinel of systemic health vulnerability in women. Yet, the broader multimorbidity patterns and temporal progression of diseases surrounding infertility remain poorly understood. In this large-scale retrospective cohort study, we analyzed electronic health records from 2,064,482 women in Tianjin, China, diagnosed with infertility and infertility-related gynecological disorders between 2014 and 2023. We constructed multimorbidity networks using partial correlation and multimorbidity coefficients (MMC), and applied disease trajectory modeling to map temporal patterns before and after infertility diagnosis. Among all patients, 94.6% exhibited multimorbidity, with the number of distinct diagnoses peaking at age 40 and rising sharply after 50. Non-random disease clusters emerged across gynecological and systemic conditions, including gastrointestinal, musculoskeletal, cardiovascular, and endocrine disorders. We identified a sequential progression from pelvic inflammatory disorders (N70) to structural ovarian abnormalities (N83) and then to benign ovarian neoplasms (D27), indicating a reproductive-to-systemic transition. Notably, inflammatory diseases of the vagina and vulva (N76, MMC=1.17) and oligomenorrhea (N91, MMC=0.78) were associated with the highest multimorbidity burden. Infertility significantly elevated the risk of subsequent hyperlipidemia (E78), heart failure (I50), and pregnancy-related complications (O24), with antecedent diagnoses occurring on average 0.6 years before and downstream conditions appearing one year after infertility diagnosis. This study provides the first comprehensive mapping of multimorbidity and disease progression in women with infertility, positioning infertility as an early-life marker of multisystem dysregulation. These findings underscore the need for life course-oriented, integrated care strategies in women’s health that bridge reproductive and systemic medicine.