子宫内膜非典型增生及子宫内膜癌患者保留生育功能治疗的临床研究

doi:10.19723/j.issn.1671-167X.2022.05.021

北京大学学报（医学版） ›› 2022, Vol. 54 ›› Issue (5): 936-942. doi: 10.19723/j.issn.1671-167X.2022.05.021

子宫内膜非典型增生及子宫内膜癌患者保留生育功能治疗的临床研究

森本智惠子,王益勤,周蓉,王建六*()

北京大学人民医院妇产科, 北京 100044

收稿日期:2022-06-15 出版日期:2022-10-18 发布日期:2022-10-14
通讯作者: 王建六 E-mail:wangjianliu@pkuph.edu.cn
作者简介:王建六，妇产科教授，博士生导师，北京大学人民医院副院长、党委委员，北京大学妇产科学系主任，北京大学人民医院妇产科教研室主任，北京市女性盆底疾病防治重点实验室主任。担任中华医学会妇产科学分会常务委员，中华医学会妇科肿瘤分会常务委员，中国研究型医院学会妇产科学专业委员会主任委员，北京医学会妇产科学分会主任委员，北京市医师协会妇产科专科医师分会会长，Gynecology and Obstetrics Clinical Medicine (GOCM), Journal of Gynecological Surgery, Journal of Gynecological Oncology等杂志主编及编委，《中华妇产科杂志》编委，《现代妇产进展》副主编，《中国妇产科临床杂志》副主编。
主要研究领域：妇科肿瘤和盆底疾病。在妇科肿瘤方面，对常见妇科恶性肿瘤宫颈癌、卵巢癌和子宫内膜癌进行了系列研究，特别是子宫内膜癌的发病机制和分子分型研究，研究成果发表在Advanced Science及Science(suppl)等国内外学术期刊，主编科技部重点图书《子宫内膜癌》；在盆底疾病方面，建立了盆底功能障碍性疾病多学科联合诊疗模式，推广盆底功能障碍性疾病的诊疗规范，探索新型补片在盆腔器官脱垂手术中的应用，牵头编写国内外首部专著《盆底医学》，促进了我国盆底疾病诊疗的发展。
承担科技部“十三五”规划项目、国家自然科学基金、卫生部优秀人才基金等科研项目。曾获霍英东基金会教师奖、吴阶平-杨森医学药学奖(2013)，荣获卫生部优秀科研人才、科学中国人(2016)、国家名医(2018)等称号
基金资助:
国家重点研发计划(2019YFC1005200);国家重点研发计划(2019YFC1005204)

Clinical analysis of fertility-sparing therapy of patients with complex atypical hyperplasia and endometrial cancer

Chieko MORIMOTO,Yi-qin WANG,Rong ZHOU,Jian-liu WANG*()

Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China

Received:2022-06-15 Online:2022-10-18 Published:2022-10-14
Contact: Jian-liu WANG E-mail:wangjianliu@pkuph.edu.cn
Supported by:
the National Key Technology Research and Development Program of China(2019YFC1005200);the National Key Technology Research and Development Program of China(2019YFC1005204)

摘要/Abstract

摘要：

目的: 探讨子宫内膜非典型增生(complex atypical hyperplasia, CAH)及子宫内膜癌(endometrial cancer, EC)患者保留生育功能治疗的效果及妊娠结局。方法: 回顾性分析2009年1月至2021年9月北京大学人民医院进行保留生育功能治疗的EC患者及CAH患者共191例, 对患者的肿瘤缓解、复发及妊娠情况进行分析。结果: (1) 疗效及相关因素: 总体完全缓解(complete response, CR)率为86.1%(161/187例), CAH组的CR率显著高于EC组(92.7% vs. 79.1%, P=0.007), Logistic回归分析显示, CAH组的CR率更高(OR=2.786, P=0.035);(2)复发率: 总体复发率为19.3%(31/161例), EC组显著高于CAH组(26.4% vs. 13.5%, P=0.039), 中位复发时间为22.5(9.0, 50.0)个月; (3)复发相关因素: 病理类型为EC(χ²=4.880, P=0.027)、未使用二甲双胍(χ²=7.075, P=0.008)、治疗达CR的时间>7个月(χ²=6.204, P=0.013)及未妊娠(χ²=6.765, P=0.009)患者的累积复发率显著更高; (4)妊娠结局及相关因素: 达到CR的患者中共有108例有生育意愿, 妊娠率为41.7%(45/108例), 生育率为34.3%(37/108), EC组的生育率显著低于CAH组(28.6% vs. 42.4%, P=0.045), 中位妊娠时间为10.50(5.75, 33.25)个月。既往有妊娠史(OR=9.468, P < 0.001)和接受辅助生殖治疗(OR=7.809, P < 0.001)患者的妊娠率更高。结论: EC及CAH患者进行保留生育功能治疗的疗效肯定, 可以获得较高的疾病缓解率和一定的妊娠分娩率, 但仍存在复发率高及生育率低的问题。

关键词: 子宫内膜非典型增生, 子宫内膜癌, 保留生育功能, 复发, 妊娠

Abstract:

Objective: To analyze the efficacy and prognosis of fertility-sparing therapy of the patient with complex atypical hyperplasia (CAH) and endometrial cancer (EC). Methods: Clinical data of 191 EC and CAH patients who received fertility-sparing therapy in Peking University People's Hospital between January 2009 and September 2021 were recruited retrospectively. Outcomes of remission, recurrence and pregnancy were analyzed. Results: (1) Efficacy and efficacy-related factors: The complete response (CR) rate was 86.1% (161/187) for all the patients, and the CR rate of the CAH patients were higher than that of the EC patients (92.7% vs. 79.1%, P=0.007), the CR rate was significant higher in the CAH patients (OR=2.786, P=0.035). (2) The recurrence rate was 19.3% (31/161), and the recurrence rate of the EC patients were much higher than that of the CAH patients (26.4% vs. 13.5%, P=0.039). The median recurrence time was 22.5 (9.0, 50.0) months. (3) The high risk factors of recurrence were pathological type of EC (χ²=4.880, P=0.027), without the use of metfor-min (χ²=7.075, P=0.008), longer time to complete remission (>7 months) (χ²=6.204, P=0.013), and no pregnancy (χ²=6.765, P=0.009). (4) Results of pregnancy and related factors: Among the patients who achieved CR, 108 patients had fertility willing with the pregnancy rate of 41.7% (45/108), and the live birth rate was 34.3% (37/108). The live birth rate was lower in EC than that in the CAH patients (28.6% vs. 42.4%, P=0.045). The median time to achieve pregnancy was 10.50 (5.75, 33.25) months. The pregnancy rate was significant higher in the patients with pregnancy history (OR=9.468, P < 0.001) and in those who received assisted reproductive therapy (OR=7.809, P < 0.001). Conclusion: Fertility-sparing therapy of CAH and EC patients is effective resulting in high disease remission and certain pregnancy. However, the high recurrence rate and low pregnancy rate are still key problems for EC and CAH patients, therefore close monitoring and follow-up are indicated.

Key words: Complex atypical hyperplasia, Endometrial carcinoma, Fertility preservation, Recurrence, Pregnancy

中图分类号:

R737.33

森本智惠子,王益勤,周蓉,王建六. 子宫内膜非典型增生及子宫内膜癌患者保留生育功能治疗的临床研究[J]. 北京大学学报（医学版）, 2022, 54(5): 936-942.

Chieko MORIMOTO,Yi-qin WANG,Rong ZHOU,Jian-liu WANG. Clinical analysis of fertility-sparing therapy of patients with complex atypical hyperplasia and endometrial cancer[J]. Journal of Peking University (Health Sciences), 2022, 54(5): 936-942.

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参考文献 21

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Items	Total (n=191)	EC (n=92)	CAH (n=99)	P value
Age/years	33.0±5.7	32.5±5.4	33.4±5.9	0.244
Number of times of pregnancy
0	121 (63.4)	59 (64.1)	62 (62.6)	0.829
≥1	70 (36.6)	33 (35.9)	37 (37.4)
Number of times of delivery
0	157 (82.2)	78 (84.8)	79 (79.8)	0.368
≥1	34 (17.8)	14 (15.2)	20 (20.2)
BMI/(kg/m ²)	27.5±5.1	27.5±5.2	27.6±5.1	0.973
Complications
Type Ⅱ diabetes	22 (11.5)	12 (13.0)	10 (10.1)	0.524
PCOS	23 (12.0)	11 (12.0)	12 (12.1)	0.972
Thyroid disease	11 (5.8)	6 (0.7)	5 (0.5)	0.663

Items		One factor analysis		Multiple factors analysis
Items		OR (95% CI)	P value	OR (95% CI)	P value
Age/years	≥30	1.833 (0.653-5.147)	0.25	2.256 (0.717-7.100)	0.164
	< 30	1		1
BMI/(kg/m²)	≥25	1.774 (0.664-4.738)	0.253	1.729 (0.631-4.733)	0.287
	< 25	1		1
Pathology	CAH	3.355 (1.336-8.424)	0.01	2.786 (1.073-7.235)	0.035
	EC	1		1
Complication with PCOS	Yes	0.588 (0.129-2.677)	0.492
	No	1
Complication with diabetes	Yes	1.036 (0.283-3.799)	0.957
	No	1
Types of progesterone	MPA	0.916 (0.194-4.330)	0.912
	MA	1
Using metformin	Yes	1.361 (0.582-3.180)	0.477
	No	1

Items		One factor analysis		Multiple factors analysis
Items		OR (95% CI)	P value	OR (95% CI)	P value
Age/years	≥30	0.844 (0.361-1.973)	0.696
	< 30	1
BMI/(kg/m²)	≥25	0.960 (0.416-2.218)	0.924
	< 25	1
Pathology	CAH	2.300 (1.031-5.134)	0.042	1.779 (0.729-4.343)	0.206
	EC	1		1
Complication with PCOS	Yes	0.712 (0.195-2.601)	0.608
	No	1
Complication with diabetes	Yes	0.821 (0.222-3.034)	0.768
	No	1
Complication with thyroid disease	Yes	0.689 (0.080-5.939)	0.735
	No	1
Types of progesterone	MPA	2.800 (0.845-9.283)	0.092	2.288 (0.653-8.014)	0.196
	MA	1		1
Using metformin	Yes	2.036 (0.890-4.660)	0.092	1.662 (0.691-3.994)	0.256
	No	1		1
Using GnRHa	Yes	1.960 (0.870-4.415)	0.104	1.667 (0.675-4.117)	0.268
	No	1		1
Maintenance treatment	Yes	0.734 (0.297-1.812)	0.502
	No	1
Pregnancy	Yes	1.024 (0.358-2.933)	0.964
	No	1
Delivery	Yes	2.13 (0.333-13.666)	0.424
	No	1

Items	Total	CAH (n=89)	EC (n=72)	P value
Patients with fertility intention	108	59	49
Patients with assisted human reproduction	34	19	15
Patients with pregnancy (pregnancy times)	45 (50)	26 (29)	19 (21)
Patients with delivery (delivery times)	39 (37)	27 (25)	12 (12)
Pregnancy rate/%	41.7	44.1	38.8	0.579
Fertility rate/%	34.3	42.4	28.6	0.045
Pregnancy duration/months, M (P₂₅, P₇₅)	10.50 (5.75, 33.25)	9.00 (2.50, 29.50)	13.00 (7.00, 46.50)	0.196

Items		One factor analysis		Multiple factors analysis
Items		OR (95% CI)	P value	OR (95% CI)	P value
Age/years	≥30	0.773 (0.338-1.772)	0.543
	< 30	1
Pregnancy history	Yes	10.711 (4.206-27.271)	< 0.001	9.468 (2.928-30.618)	< 0.001
	No	1		1
BMI/(kg/m²)	≥25	0.731 (0.324-1.647)	0.45
	< 25	1
Complication with PCOS	Yes	2.508 (0.762-8.253)	0.13	2.209 (0.374-13.046)	0.382
	No	1		1
Complication with diabetes	Yes	0.247 (0.051-1.186)	0.081	0.627 (0.061-6.432)	0.695
	No	1		1
Complication with thyroid disease	Yes		0.999
	No
Pathology	CAH	0.804 (0.372-1.738)	0.579
	EC	1
Using metformin	Yes	0.822 (0.379-1.785)	0.621
	No	1
Using GnRHa	Yes	1.099 (0.469-2.576)	0.828
	No	1
Assisted human reproduction	Yes	12.768 (4.763-34.244)	< 0.001	7.809 (2.600-23.457)	< 0.001
	No	1
Recurrence	Yes	1.024 (0.358-2.933)	0.964
	No	1

子宫内膜非典型增生及子宫内膜癌患者保留生育功能治疗的临床研究

Clinical analysis of fertility-sparing therapy of patients with complex atypical hyperplasia and endometrial cancer

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