Department of Obstetrics and Gynecology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
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Abstract |
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Key words: chemotherapy/gestational trophoblastic tumour/subsequent pregnancy outcome
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Introduction |
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In this paper, we studied the subsequent pregnancy outcome and recurrence in patients with persistent GTT who achieved remission after receiving methotrexate (MTX), actinomycin D (Act-D), etoposide and several combination chemotherapy regimens.
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Materials and methods |
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All patients were monitored for at least 1 year. The median follow-up duration was 14.8 ± 6.9 years. Forty-two (11.1%) patients could not be traced. For women with definite foci of GTT in the uterus who had no desire to preserve fertility, we recommended adjuvant hysterectomy to reduce the total dose of drugs needed to achieve remission (Suzuka et al., 2001). Surgical removal of drug resistant foci in the uterus and metastatic sites was also performed in patients with high-risk GTT.
Remission was diagnosed when three consecutive weekly HCG levels were within the normal range, and after an additional one or two cycles for low-risk GTT or seven cycles for high-risk GTT. After remission, HCG levels were determined monthly for 6 months, every other month for another 6 months, and then every 3 or 4 months for the next 12 months. Patients were strongly advised not to become pregnant for at least 1 year after completing chemotherapy.
Statistical analyses were performed by Welch's t-test, analysis of variance followed by Scheffe's F-test, and the 2 test.
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Results |
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Discussion |
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Patients with treated persistent GTT may express fears related to future pregnancies, especially the possibility of GTT recurrence or fetal anomalies. Therefore, data related to subsequent pregnancy outcome after chemotherapy for persistent GTT are essential to counsel patients and their partners concerning the potential risks of subsequent pregnancies. Many previous studies have reported that patients with persistent GTT can be assured that they may anticipate a normal reproductive outcome. In our series, the rates of term live birth, stillbirth, premature delivery, spontaneous abortion and congenital anomaly in patients who had been treated for persistent GTT were similar to the rates in the general Japanese population (Ministry of Health and Welfare, 1998) and those reported in the literature (Goldstein et al., 1984
; Rustin et al., 1984
; Ngan et al., 1988
; Berkowitz et al., 1994
; Kim et al., 1998
; Woolas et al., 1998
).
The other fear concerning future pregnancy, expressed by patients and their partners, is secondary development of GTT in subsequent pregnancies. The incidence of repeat molar pregnancy (2.1%) was apparently higher than that in the general population, while it was comparable with that in patients with spontaneous resolution of HCG after evacuation of their first molar pregnancy (Matsui et al., 2001). In the present series, recurrence of GTT was observed in three (2.3%) patients who conceived after remission and in six (7.7%) patients who did not conceive. There was no significant difference in relapse rate in patients who had subsequent pregnancies and those who did not (P = 0.084; Fisher's exact test).
Recently, Tuncer et al. addressed the specific problem of pregnancy in patients who conceive before completion of the conventionally mandated waiting period of 12 months after chemotherapy (Tuncer et al., 1999). They reported that maternal age, parity, antecedent pregnancy, International Federation of Gynecology and Obstetrics (FIGO) stage, World Health Organization score, number of chemotherapy cycles, and interval from remission to new pregnancy had no effect on subsequent pregnancy outcome. Furthermore, they stated that pregnancy within the mandated follow-up period of 12 months was reasonably safe and therapeutic abortion was not required.
We also strongly advise patients who are treated for persistent GTT to use reliable contraception for 12 months following completion of chemotherapy, due to the anxiety and fear of fetal anomalies resulting from anti-cancer drugs. Nevertheless, 19 patients (14.7%) and 15 patients (11.6%) conceived between 612 months and within 6 months respectively, after the completion of chemotherapy. The cumulative spontaneous abortion rate in those patients who conceived within the standard waiting period of 1 year was 17.6% (6/34). This rate was slightly higher than that in patients who conceived after 12 months, while no significant difference was observed compared with the report of Tuncer et al. (P = 0.08) (Tuncer et al., 1999). However, the spontaneous abortion rate in those patients who conceived within 6 months (33.3%) was significantly higher than that in patients who conceived after 12 months. Furthermore, excluding three therapeutic abortions, the spontaneous abortion rate in the patients who conceived within 6 months was significantly higher than that in patients who conceived between 612 months. The mean maternal age, regimen and numbers of chemotherapy treatment were not related to the unfavourable pregnancy outcomes (data not shown). Although our study was small and retrospective, these findings suggest that it may be safer to avoid conception within 6 months after the completion of chemotherapy.
Folliculogenesis appears to be a very long process in normal women. Gougeon reported that the full span of growth from the primordial to Graafian follicle was in the order of 612 months (Gougeon, 1996). If anti-cancer drugs do affect the developing pre-antral follicles, ovulatory oocytes that develop within a short interval after completion of chemotherapy may be subjected to genetic damages or teratogenic effects induced by the anti-cancer drugs. Meirow et al. reported that fertilization shortly after cyclophosphamide chemotherapy could result in a high rate of pregnancy failure and high malformation rate in mice (Meirow et al., 2001
). It will become vital for anti-cancer chemotherapy to define the safety period between cessation of chemotherapy and fertilization.
In conclusion, patients with treated persistent GTT may anticipate normal future reproductive outcome. As pregnancies occurring within 6 months following remission are likely to result in a more unfavourable outcome, a waiting period of at least 6 months after chemotherapy for persistent GTT is needed. Repeat molar pregnancy is also an unfavourable event in subsequent pregnancy in patients with persistent GTT, and the incidence is increased seven times compared with the general population. However, subsequent pregnancy after chemotherapy for GTT does not increase the recurrence of GTT.
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Notes |
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References |
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Submitted on May 8, 2001; accepted on October 6, 2001.