Objective <p>To evaluate the association between pretreatment with the glucagon-like peptide-1 receptor agonist semaglutide and reproductive outcomes in women with overweight and obesity with infertility.</p> Methods <p>This retrospective multicenter cohort study used real-world data from January 2021 to April 2024. A total of 1,936 women aged 20–40 years with infertility were included after 1:1 propensity score matching across three body mass index (BMI) categories. Women with prior bariatric surgery, pregnancy before the index date, incomplete weight data, or other weight-loss medication use were excluded. Semaglutide pretreatment within one year before fertility-related care was compared with matched controls. Primary outcomes were clinical pregnancy and live birth; miscarriage was secondary. Outcomes were analyzed using cross-sectional and time-to-event methods.</p> Results <p>Across all BMI categories, semaglutide pretreatment was associated with lower pregnancy and live birth rates compared with matched controls. Pregnancy rates were significantly lower in women with overweight and class I obesity, with a non-significant decrease in class II–III obesity. Live birth rates were significantly lower in women with class I and class II–III obesity. Time-to-event analyses showed lower cumulative probabilities of pregnancy and live birth among semaglutide users, although hazard ratios were not consistently significant. Miscarriage rates did not differ between groups.</p> Conclusions <p>In this large real-world cohort, semaglutide pretreatment before fertility-related care was associated with reduced and delayed pregnancy and live birth outcomes in women with overweight and obesity with infertility. These findings warrant confirmation in prospective and mechanistic studies to inform preconception counseling and treatment planning.</p>