ABSTRACTObjectiveTo assess safety of fertility treatments in women with systemic lupus erythematosus (SLE).DesignData from the multicentre French observational GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) study (2014‐ongoing).SettingSeventy‐six centres in France.PopulationAll pregnancies in women with SLE enrolled in the GR2 study, conceived before 1 August 2022, with available end‐of‐pregnancy data and known conception type, were included; that is, 577 spontaneous and 53 assisted pregnancies.MethodsA comparative analysis of spontaneous and assisted pregnancies was conducted. Logistic regression was used to determine if fertility treatments were independently associated with live birth prognosis, adjusting for confounders (e.g., maternal age). Kaplan–Meier analysis compared cumulative incidences of disease flares and adverse pregnancy outcomes (APOs), with confounding factors adjusted using a Cox regression model.Main Outcome MeasuresLive birth, disease flares, and APOs.ResultsThe mean age was older (35.8 vs. 32.3 years, p < 1 × 10−4), and twins were more frequent in assisted pregnancies (5/50, 10.0% vs. 20/554, 3.6%; p = 0.047). Lupus disease was clinically inactive at baseline in 51 (96.2%) assisted pregnancies (vs. n = 511, 89.6%; p = 0.15), with 35 of 45 (77.8%) having no chronic damage (vs. 448/513, 87.3%; p = 0.07). The live birth rate was similar between assisted and spontaneous pregnancies (n = 46, 86.8% vs. n = 505, 87.5%; p = 0.83), with no statistical difference in the incidence of lupus flares and APOs. These results remained consistent after adjusting for confounding factors.ConclusionsFertility treatments in women with mostly well‐controlled SLE did not appear to increase risks of maternal and neonatal complications, supporting current recommendations.Trial RegistrationClinicalTrials.gov identifier: NCT02450396