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Originally published as JCO Early Release 10.1200/JCO.2009.23.5366 on August 17 2009 © 2009 American Society of Clinical Oncology.
Reproduction Rates After Cytotoxic TherapyFertility and Cancer Unit, Leuven Cancer Institute, University Hospitals Leuven, Leuven; and St Rembert Hospital, Torhout, Belgium
Fertility and Cancer Unit, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium
Fertility and Cancer Unit, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium To the Editor: In the January 20, 2009, issue of Journal of Clinical Oncology, Cvancarova et al1 described the results of a Norwegian monocentric retrospective analysis of reproduction rates after cytotoxic cancer treatment. Although their findings are interesting, an important shortcoming of their study is that the desire to become pregnant after such therapy was not considered. We believe this is a crucial aspect when looking into reproduction after cytotoxic cancer treatment. We recently sent out a questionnaire, approved by our ethics committee, and report here the results, which contained some complementary aspects on this issue not covered by the Norwegian study. Our data represent relevant complementary information (not included in the Norwegian study) with respect to desire to become pregnant before and after chemotherapy, time to pregnancy interval, time interval to resumption of menstrual cyclicity, and regularity of menstrual cycles after chemotherapy. The main goal of the questionnaire was to assess the effect of cytotoxic therapy on menstrual status, desire to become pregnant, and pregnancy rate in women age 15 to 35 years (highly relevant with respect to desire to become pregnant after chemotherapy) who had been treated for breast cancer or lymphoma (both Hodgkin's lymphoma [HL] and non-Hodgkin's lymphoma [NHL]), which represent the most commonly observed cancers in women with fertility problems after chemotherapy. We only considered patients who did not experience relapse until 2007 and identified 126 eligible female patients who had previously received chemotherapy at our institution during the period from 1999 to 2005. The questionnaire together with a patient information form was sent out to all such patients; the forms were completed and sent back for analysis. The response rate was 78% (98 of 126 patients). The mean age of our patients at time of diagnosis was 29 years (range, 15 to 35 years; median, 30 years; standard deviation [SD], 5.6 years), and they were affected by breast cancer (64.3% compared with 11% in the Norwegian study1), HL (27.5%), and NHL (8.2%). Chemotherapy administered for breast cancer included cyclophosphamide, methotrexate, and fluorouracil (23.8%); anthracycline-based chemotherapy (61.9%); and an anthracycline plus taxane–based regimen (14.3%). For HL, a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine was administered, and patients with NHL received cyclophosphamide, doxorubicin, vincristine, and prednisone–like chemotherapy. Overall, our results are in agreement with those of the Norwegian study.1 Looking at prediagnosis parenthood, 45 (45.9%) of the 98 patients in our study were childless at diagnosis (compared with 34% in the Norwegian study). Fifty three (54.1%) of 98 had been pregnant before, with a mean of 1.7 living births (range, zero to four living births; median, two living births; SD, 0.8 living births). Mean age at first pregnancy before therapy was 25.9 years (range, 18 to 32 years; median, 26 years; SD, 3 years). For patients who had been pregnant before diagnosis, mean number of months between last birth and cancer diagnosis was 38.3 (range, 0 to 132 months; median, 23.5 months; SD, 34.7 months). The pregnancy rate after therapy in our study was slightly less than that in the whole group in the study by Cvancarova et al1 (9.2% v 13% of female patients). Mean age at diagnosis of our patients who became pregnant after therapy was 27.9 years (range, 16 to 33 years; median, 30 years; SD, 5.5 years). With regard to postdiagnosis reproduction (ie, reproduction rate after cancer diagnosis), we compared the Norwegian results1 in the 1988+ group with those in our group of patients. Two patient groups were defined: patients who were childless at moment of diagnosis and patients who had already had one or more children at diagnosis. Our postdiagnosis reproduction rates were 11% (compared with 19% in the 1988+ group) and 7% (compared with 4% in the 1988+ group), respectively. In our study, data concerning desire to become pregnant before and after cytotoxic treatment were analyzed. The results of our questionnaire showed that 26 (26.5%) of 98 patients had a desire to become pregnant before therapy, whereas only nine (9.2%) of 98 patients wanted to become pregnant after therapy. In seven (7.1%) of 98 patients who had a desire to become pregnant before therapy, there were fertility problems before diagnosis. After therapy, there were fertility problems in four (44.4%) of the nine patients who wanted to become pregnant. Only four (44.4%) of the nine patients with a clear, active desire to become pregnant actually did so after therapy. One of our patients had a successful pregnancy after therapy despite having not self-reported an active desire to become pregnant. In the report by Cvancarova et al,1 no information was provided about the desire to become pregnant before or after therapy. In our study, eight (88.9%) of nine patients who became pregnant after therapy had uncomplicated pregnancies (compared with 98% in the Norwegian study), and all births were live births (12 births among eight patients). One patient had an abortion after therapy, in accordance with her wishes. In seven (77.8%) of the nine patients, no major health problems were observed in the newborns. No patient underwent in vitro fertilization treatment in the first postdiagnosis pregnancy (compared with 2% in the Norwegian study). We also obtained information about mean time between start of active desire to become pregnant and successful pregnancy. Before therapy, this was 5.9 months (range, 0 to 48 months; median, 3 months; SD, 9.3 months). After therapy, mean time until successful pregnancy was 10.2 months (range, 0 to 36 months; median, 8 months; SD, 11.5 months). Part of our questionnaire was about menses before, during, and after therapy. During chemotherapy, 34 (34.7%) of 98 patients maintained spontaneous menses without oral contraception. Spontaneous resumption of menstruation was observed 5.5 months (range, 0 to 61 months; median, 9.5 months; SD, 2 months) after cessation of cytotoxic therapy in 68 (69.4%) of 98 patients whose menses had stopped during chemotherapy. In 44 (63.4%) of these 68 patients, menses were regular. Seventy (71.4%) of our 98 patients started contraception after cytotoxic therapy, with a mean interval of 4.7 months after end of therapy (range, 0 to 36 months; median, 0 months; SD, 8.4 months). We conclude that in young female patients treated for breast cancer or lymphoma with cytotoxic therapy, there is a clear increase in fertility problems after end of therapy. Our main observation was that only a few patients wanted to become pregnant after cytotoxic therapy. But in patients with an active desire to become pregnant after therapy, nearly half did not become pregnant. Mean time between start of active desire to become pregnant and successful pregnancy seemed longer after cytotoxic therapy. There were no major health problems in the newborns who were born after their mothers received cytotoxic therapy. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCE
1. Cvancarova M, Samuelsen S, Magelssen H, et al: Reproduction rates after cancer treatment: Experience from the Norwegian Radium Hospital. J Clin Oncol 27:334–343, 2009.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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