OBJECTIVES: To summarise the evidence of colchicine's effects on fertility, pregnancy, and lactation in the treatment of patients with familial Mediterranean fever (FMF). METHODS: Two reviewers and a methodologist conducted the systematic review. Together with an expert in FMF, they established the protocol and the PICOt questions. Medline via PubMed, Embase, and the Cochrane Library were searched from inception until August 23, 2023. All clinical trials, cohort studies, or case series focused on the safety of colchicine in FMF, concerning reproductive issues or breastfeeding, and involving at least 5 patients were eligible. The risk of bias in the studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was planned for at least 2 homogeneous studies with fixed-effect models using the Mantel-Haenszel method to obtain the pooled risk ratio (RR) and 95% CI. RESULTS: Twenty-five studies were included overall of moderate to low quality. The RR of miscarriage or foetal loss with colchicine in FMF was 0.87 (95% CI, 0.67-1.12), showing a heterogeneity of 31%. The percentage of birth defects in the exposed group ranged from 0.6% to 4.0%, not very different, comparable to the rates of women with FMF without exposure to colchicine. Regarding fertility, there were no apparent differences between colchicine-exposed and nonexposed groups, neither among women nor men (sperm assessment). Only 1 study reported breastfeeding data, showing no growth differences among exposed and nonexposed babies. CONCLUSIONS: Colchicine appears to have a good risk-benefit profile regarding reproductive safety. Ideally, higher-quality studies should be performed, especially regarding male fertility.