Department of Rheumatology, Einstein Medical Center, Philadelphia, PA, USA.
Department of Rheumatology, Emory University, Atlanta, GA, USA.
Lupus. 2021 Aug;30(9):1509-1514. doi: 10.1177/09612033211021163. Epub 2021 May 30.
Systemic lupus erythematosus (SLE) often affects females of reproductive age and Cyclophosphamide, an alkylating agent leading to premature ovarian insufficiency (POF) and labelled category D for pregnancy is used as induction therapy for severe manifestations of lupus. There have been multiple case series reflecting variable outcomes of pregnancies after cyclophosphamide use for cancers and autoimmune diseases. With increasing maternal age, we have an increasing population of lupus patients who may wish to conceive after having received cyclophosphamide therapy. The objective of our study was to improve our understanding of the impact of cyclophosphamide exposure on fertility and pregnancy outcomes in patients with SLE.We retrospectively reviewed the charts of all patients who had received intravenous cyclophosphamide at our academic institute in the time period from 2000-2018 and identified 440 patients which included 157 female patients of reproductive age. There were 37 documented pregnancies after the cyclophosphamide infusion, of which 23 patients had successful outcomes; 4 elective abortion and 10 miscarriages. There were 17 patients who developed POF, of which 7 also had end stage renal disease. The average cumulative dose of cyclophosphamide in the patients who had successful pregnancy was 4080.37 mg compared to 2806.25 mg in those who had a miscarriage (p 0.164) and 5526.47 mg in those who developed POF (p 0.046). Using multiple regressions to evaluate risk factors impacting pregnancy outcomes, when taken as a set, the predictors including race, serological profile, exposure to steroids and Mycophenolate mofetil, age at cyclophosphamide infusion, age at pregnancy, and cumulative cyclophosphamide dose accounted for 46.29% of the variance in outcome of pregnancy (p 0.23) and 39.58% of the variance in development of premature ovarian failure (p 0.008). We noted statistical significance in the impact of maternal age at time of pregnancy (p 0.04) and duration of time between the last infusions to subsequent pregnancy (p 0.02) to pregnancy outcome.Our findings suggest that a longer time interval between the last cyclophosphamide infusion and subsequent pregnancy was favorable for a successful outcome and higher cumulative cyclophosphamide dose is more likely to be associated with premature ovarian failure.
系统性红斑狼疮（SLE）常影响育龄女性，环磷酰胺是一种烷化剂，可导致卵巢早衰（POF），且被归类为妊娠 D 类药物，用于严重狼疮的诱导治疗。已有多项病例系列研究反映了癌症和自身免疫性疾病患者使用环磷酰胺后的妊娠结局存在差异。随着产妇年龄的增长，我们有越来越多的狼疮患者希望在接受环磷酰胺治疗后怀孕。我们研究的目的是提高我们对接受环磷酰胺治疗的 SLE 患者的生育和妊娠结局的影响的认识。我们回顾性地查阅了我们学术机构在 2000 年至 2018 年期间接受静脉内环磷酰胺治疗的所有患者的病历，并确定了 440 名患者，其中包括 157 名育龄女性。在环磷酰胺输注后有 37 例记录在案的妊娠，其中 23 例成功；4 例选择性流产和 10 例流产。有 17 名患者发生卵巢早衰，其中 7 名患者同时患有终末期肾病。在成功妊娠的患者中，环磷酰胺的累积剂量平均为 4080.37mg，而在流产的患者中为 2806.25mg（p 0.164），在发生卵巢早衰的患者中为 5526.47mg（p 0.046）。使用多元回归分析评估影响妊娠结局的危险因素，当作为一组因素时，包括种族、血清学特征、类固醇和霉酚酸酯暴露、环磷酰胺输注时的年龄、妊娠时的年龄以及累积环磷酰胺剂量等预测因素可解释妊娠结局（p 0.23）和卵巢早衰（p 0.008）的 46.29%和 39.58%的变异性。我们注意到，产妇妊娠时的年龄（p 0.04）和末次环磷酰胺输注与随后妊娠之间的时间间隔（p 0.02）对妊娠结局的影响具有统计学意义。我们的研究结果表明，末次环磷酰胺输注与随后妊娠之间的时间间隔较长有利于获得成功的妊娠结局，且较高的累积环磷酰胺剂量更可能与卵巢早衰有关。
