静脉注射环磷酰胺后卵巢功能衰竭和生育能力的风险。对84例患者的研究。

Risk of ovarian failure and fertility after intravenous cyclophosphamide. A study in 84 patients.

作者信息

Huong Du Le thi, Amoura Zahir, Duhaut Pierre, Sbai Abdallah, Costedoat Nathalie, Wechsler Bertrand, Piette Jean-Charles

机构信息

Department of Internal Medicine, Group Hospitalier Pitié-Salpêtrière, Paris, France.

出版信息

J Rheumatol. 2002 Dec;29(12):2571-6.

PMID:12465154

Abstract

OBJECTIVE

To compare the risk of ovarian failure and the fertility of women treated with intravenous cyclophosphamide (IVCY) according to the underlying inflammatory disease.

METHODS

Review of the data of 84 consecutive women: 56 with systemic lupus erythematosus (SLE), 28 with other diseases, mainly Wegener's granulomatosis and systemic vasculitides.

RESULTS

The mean age at IVCY initiation was 29 +/- 10 years (range 13-53). The mean dosage was 0.9 +/- 0.14 g per pulse (range 0.5-1), and the mean number of pulses 13 +/- 6.5 (range 3-42). With a mean followup of 5.1 +/- 3.7 years, 23 women developed amenorrhea, with a mean duration of 4 +/- 3.6 months between IVCY initiation and amenorrhea. Amenorrhea was sustained in 19 women (13 with SLE and 6 with other diseases, NS). The mean age at ovarian failure onset was 40 +/- 7.6 years. The risk of ovarian failure correlated with the age at IVCY institution (p < 0.0001), and was independent of underlying inflammatory disease. Eighteen women (13 with SLE and 5 with other diseases) became pregnant during or after CY therapy, with a total of 22 pregnancies. The mean age at IVCY initiation, and the mean number of IVCY (maximum 40 pulses) before pregnancy were similar in women with SLE and those with other diseases. Six pregnancies occurred during IVCY therapy, which ended in induced abortion (n = 3), spontaneous abortion (n = 1), and normal pregnancy after IVCY withdrawal (n = 2) in women who wished to keep their pregnancy despite the risk of teratogenicity. Sixteen pregnancies occurred 2.9 +/- 2.1 years (range 1-9) after IVCY withdrawal. They ended in: 3 induced abortions indicated for severe morphological anomalies (n = 2) and for SLE relapse (n = 1), 3 spontaneous miscarriages, and 10 deliveries of healthy newborns.

CONCLUSION

The risk of ovarian failure depends essentially on the age at IVCY initiation. Pregnancy may occur during IVCY therapy, and an efficient contraception is mandatory. After IVCY withdrawal, pregnancy is possible with a favorable outcome in two-thirds of the cases.

摘要

目的

根据潜在的炎症性疾病，比较接受静脉注射环磷酰胺（IVCY）治疗的女性发生卵巢功能衰竭的风险及生育能力。

方法

回顾84例连续女性的数据：56例患有系统性红斑狼疮（SLE），28例患有其他疾病，主要是韦格纳肉芽肿病和系统性血管炎。

结果

开始IVCY治疗时的平均年龄为29±10岁（范围13 - 53岁）。平均剂量为每次脉冲0.9±0.14 g（范围0.5 - 1 g），平均脉冲次数为13±6.5次（范围3 - 42次）。平均随访5.1±3.7年，23名女性出现闭经，从开始IVCY治疗到闭经的平均持续时间为4±3.6个月。19名女性闭经持续存在（13例SLE患者和6例其他疾病患者，无显著差异）。卵巢功能衰竭开始时的平均年龄为40±7.6岁。卵巢功能衰竭的风险与开始IVCY治疗时的年龄相关（p < 0.0001），且与潜在的炎症性疾病无关。18名女性（13例SLE患者和5例其他疾病患者）在CY治疗期间或之后怀孕，共22次妊娠。SLE患者和其他疾病患者开始IVCY治疗时的平均年龄以及怀孕前IVCY的平均次数（最多40次脉冲）相似。6次妊娠发生在IVCY治疗期间，其中3例因致畸风险而选择人工流产，1例自然流产，2例在停止IVCY治疗后继续妊娠并正常分娩。16次妊娠发生在停止IVCY治疗后2.9±2.1年（范围1 - 9年）。结局包括：2例因严重形态异常和1例因SLE复发而选择人工流产，3例自然流产，10例分娩出健康新生儿。