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


CONCLUSIONS
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.
Huong
Du Le thi
DL
Department of Internal Medicine, Group Hospitalier Pitié-Salpêtrière, Paris, France. du.boutin@wanadoo.fr
Amoura
Zahir
Z
Duhaut
Pierre
P
Sbai
Abdallah
A
Costedoat
Nathalie
N
Wechsler
Bertrand
B
Piette
Jean-Charles
JC
D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D010053:Ovary / Q000187:drug effects; D017697:Premenopause / Q000502:physiology; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced*; D012189:Retrospective Studies
D018501:Antirheumatic Agents; D003520:Cyclophosphamide