(3)子宮体癌における高単位プロゲステロンによる妊孕性温存療法 : 治療効果および安全性,その後の妊娠について,長期観察結果(<特集>第62回学術講演会 シンポジウム1 婦人科癌における妊孕性温存治療(手術および薬物療法))

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  • Fertility Sparing Treatment with High Dose Progesterone for Endometrial Carcinoma and Atypical Hyperplasia in Young Women : Five Years Observation of the Effect, Safety, and Following Pregnancy

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As the number of younger women with endometrial carcinoma has increased, fertility-sparing treatment has received much attention. Progestin has been a major role of this treatment. Nevertheless, the clinical benefit of fertility-sparing treatment with progestin is still uncertain. To clarify the efficacy of fertility-sparing treatment using medroxyprogesterone acetate (MPA) for endometrial carcinoma (EC) and atypical hyperplasia (AH) in young women, we conducted multicenter prospective study for this issue at 16 institutions in Japan. Twenty-eight patients having EC at presumed stage I a and 17 patients with AH at less than 40 years of age were enrolled. All patients were given a daily oral dose of 600mg MPA with low dose aspirin. This treatment continued for 26 weeks, as long as the patients responded. Either estrogenprogestin therapy or fertility treatment was provided for the responders after MPA therapy. CR was found in 55% of EC cases and 82% of AH cases. The overall CR rate was 67%. Neither therapeutic death nor irreversible toxicities were observed. During the 5-year follow-up period, among 20 patients with wish for baby, fifteen pregnancies in 12 patients and 9 normal deliveries were achieved after MPA therapy. Eleven of 15 pregnancies were brought about by fertility treatment, and 8 of them were achieved by in-vitro fertilization and embryo-transfer program. Fifteen recurrences were found between 7 and 58 months including 9 of 14 EC (64%) and 6 of 16 AH (38%). Recurrence was seen in 72% of patients having treatment free period and in 86% of patients without conception in spite of fertility treatment. Four cases of ovarian malignancies (10.2%) was found in this series. In EC patients of our institution, the more incidence of ovarian cancer in EC patients of less than 40 years of age (15.0%) than those of more than 40 years of age (6.6%) was shown. Also, high incidence of clonality difference between endometrium and ovary was f ound in younger patients. In conclusion, the efficacy of fertility-sparing treatment by high-dose MPA for EC and AH was proved by this first prospective trial. The indication of MPA therapy should be restricted to stagela disease. Even in the responders, close follow up with continuous Estrogen-Progesterone administration or immediate infertility treatment is required because of their substantial recurrence rate. Longer-term hormonal treatment or ovarian preservation at hysterectomy is not recommended, because these patients have high incidence of synchronous ovarian cancer. Close communication and corroboration between gynecologic oncologist and reproductive endocrinologist is indispensable for the safety and achievement to the goal of fertility-sparing treatment.

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