Risk of Ovarian Failure and Pregnancy Outcome in Patients With Lupus Nephritis Treated With Intravenous Cyclophosphamide Pulse Therapy

Abstract

ABSTRACT

Ovarian failure resulting from treatment with cyclophosphamide (CY) has become an increasing concern in patients with systemic lupus erythematosus (SLE) as survival has improved. It is a risk factor for significant morbidity in premenopausal women. This study examined the risk of ovarian failure and outcomes of pregnancy in 67 women having SLE and renal biopsy findings of class III or class IV proliferative lupus nephritis. The women were to receive intravenous CYC (IVCYC) pulse therapy in a dose of 0.5 to 0.75 mg/m2 monthly for 6 months, followed by a pulse every 3 months for 18 months longer. All the women received more than 2 IVCYC treatments. The mean number of IVCYC pulses was 8.8, and the mean dose administered was 988 mg per pulse.

Ovarian failure was defined as sustained amenorrhea without resumption of menstruation. Follow up averaged 74.4 months, or slightly longer than 6 years.

Amenorrhea developed in 25 women, 37% of the total, and 10 of them (15%) had sustained, presumably permanent amenorrhea. Women with ovarian failure were significantly older than the others and received higher cumulative doses of CYC. On logistic regression analysis, both older age at the start of treatment and the cumulative dose of CYC were independent risk factors for ovarian failure. Fifteen women had a total of 19 pregnancies. The mean interval between withdrawal of IVCYC pulse treatment and pregnancy was 46 months. Abortion was induced in 2 instances, once because the patient did not want to have a child and once because of a disease flare 9 weeks after conception. The remaining 17 pregnancies were uncomplicated and culminated in the delivery of healthy infants, none of whom had congenital anomalies or perinatal illness. After excluding women with ovarian failure and those using contraception, the occurrence of amenorrhea, apart from its duration, was a risk factor for pregnancy failure.

Unless amenorrhea develops, successful pregnancies clearly are possible in women with proliferative lupus nephritis after IVCYC pulse treatment is withdrawn.