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早期不利霍奇金淋巴瘤(HL)治疗后女性幸存者的生育能力和性腺功能。德国霍奇金研究组 HD14 试验。

Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial.

机构信息

First Department of Internal Medicine, University Hospital of Cologne, and Institute for Clinical Chemistry, University of Cologne, Cologne, Germany.

出版信息

Ann Oncol. 2012 Jul;23(7):1818-25. doi: 10.1093/annonc/mdr575. Epub 2012 Jan 6.

Abstract

BACKGROUND

In the HD14 trial, 2×BEACOPPescalated+2×ABVD (2+2) has improved the primary outcome. Compared with 4×ABVD, this benefit might be compromised by more infertility in women. Therefore, we analyzed gonadal function and fertility.

PATIENTS AND METHODS

Women≤45 years in ongoing remission at least 1 year after therapy were included. Hormone parameters, menopausal symptoms, measures to preserve fertility, menstrual cycle, pregnancies, and offspring were evaluated.

RESULTS

Three hundred and thirty one of 579 women addressed participated (57.2%) and 263 per-protocol treated patients qualified (A=ABVD: 137, B=2+2: 126, mean time after therapy 42 and 43 months, respectively). Regular menstrual cycle after treatment (A: 87%, B: 83%) and time to recovery (≤12 months) were not different. Follicle-stimulating hormone and anti-Muellerian hormone were significantly better in arm A. However, pregnancies after therapy favored arm B (A: 15%, B: 26%, P=0.043) and motherhood rates were equivalent to the German normal population. Multivariate analysis revealed prophylactic use of gonadotropin-releasing hormone (GnRH) analogues as highly significant prognostic factor for preservation of fertility (odds ratio=12.87, P=0.001). Severe menopausal symptoms were frequent in women≥30 years (A: 21%, B: 25%).

CONCLUSIONS

Hormonal levels after 2+2 indicate a reduced ovarian reserve. However, 2+2 in combination with GnRH analogues does not compromise fertility within the evaluated observation time.

摘要

背景

在 HD14 试验中,2×BEACOPP escalated+2×ABVD(2+2)改善了主要结局。与 4×ABVD 相比,这种益处可能因女性不孕不育率更高而受到影响。因此,我们分析了性腺功能和生育能力。

患者和方法

纳入缓解期至少 1 年的≤45 岁女性。评估了激素参数、更年期症状、生育力保存措施、月经周期、妊娠和后代。

结果

579 名女性中有 331 名符合条件(57.2%),263 名按方案治疗的患者符合要求(A=ABVD:137,B=2+2:126,治疗后平均时间分别为 42 和 43 个月)。治疗后月经周期恢复正常(A:87%,B:83%)和恢复时间(≤12 个月)无差异。促卵泡激素和抗苗勒管激素在 A 组显著更好。然而,治疗后妊娠率更倾向于 B 组(A:15%,B:26%,P=0.043),母亲率与德国正常人群相当。多变量分析显示,促性腺激素释放激素(GnRH)类似物的预防性使用是生育力保存的高度显著预后因素(优势比=12.87,P=0.001)。≥30 岁的女性中严重更年期症状较为常见(A:21%,B:25%)。

结论

2+2 后的激素水平表明卵巢储备减少。然而,在评估的观察时间内,2+2 联合 GnRH 类似物不会影响生育能力。

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