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临床研究
子宫性不孕的多参数MRI、MR-HSG及临床特征分析
王洁 段娜 王绍娟 胡旭宇 任帅 殷燕云 王中秋

Cite this article as: WANG J, DUAN N, WANG S J, et al. Multiparametric MRI, MR-HSG and clinical characteristics of uterine factor infertility[J]. Chin J Magn Reson Imaging, 2024, 15(3): 122-129.本文引用格式王洁, 段娜, 王绍娟, 等. 子宫性不孕的多参数MRI、MR-HSG及临床特征分析[J]. 磁共振成像, 2024, 15(3): 122-129. DOI:10.12015/issn.1674-8034.2024.03.020.


[摘要] 目的 探讨子宫性不孕(uterine factor infertility, UFI)多参数磁共振成像(magnetic resonance imaging, MRI)、磁共振子宫输卵管造影(magnetic resonance hysterosalpingography, MR-HSG)及临床特征,并建立预测UFI模型。材料与方法 回顾性分析312例仅有UFI患者临床、MRI与MR-HSG影像资料,并随访中西医治疗后的妊娠结果。统计比较随访后不孕及已孕两组患者临床指标(年龄、饮食、月经周期等)、性激素及子宫异常(子宫肌瘤、宫腔粘连、瘢痕子宫、子宫腺肌症、子宫内膜息肉、宫颈纳氏囊肿等)差异。先后通过单、多因素logistic回归分析,筛选UFI的风险因素,采用logistic回归输入法构建临床参数模型、临床联合MRI及MR-HSG预测模型。受试者工作特征(receiver operating characteristic, ROC)曲线下面积(area under the curve, AUC)评估模型效能,并采用DeLong检验比较模型间AUC值差异。结果 经治疗后随访不孕组86例,已孕组226例,两组间年龄、月经周期不规律、子宫多发肌瘤、瘢痕子宫及宫腔粘连差异有统计学意义(P<0.05);多因素logistic回归分析证实年龄(OR=0.822,P<0.001)、子宫多发肌瘤(OR=0.540,P=0.002)及宫腔粘连(OR=0.367,P=0.036)是UFI的独立危险因素;联合模型(年龄+子宫多发肌瘤+宫腔粘连)预测UFI的AUC为0.809,显著高于单独年龄模型(P<0.05),与年龄+宫腔粘连、年龄+子宫多发肌瘤模型差异无统计学意义(P>0.05)。结论 年龄、子宫多发肌瘤、宫腔粘连是UFI的危险因素,联合模型预测妊娠结果具有临床价值。
[Abstract] Objective To investigate multiparametric magnetic resonance imaging (MRI), magnetic resonance hysterosalpingography (MR-HSG) and clinical characteristics of uterine factor infertility (UFI) and to develop a model for predicting UFI.Materials and Methods The clinical characteristics, MRI and MR-HSG imaging data of 312 patients with UFI only were analyzed retrospectively. The pregnancy results were followed up after treatment and divided into the infertile group and the pregnant group. The differences were compared including clinical indexes (age, diet, menstrual cycle, etc), sex hormones, and uterine abnormalities (such as uterine fibroids, intrauterine adhesions, scarred uterus, adenomyosis, endometrial polyps, Nabothian cyst, etc) between the two groups. Risk factors for UFI were then identified through univariate and multivariate logistic regression analysis. The enter method was performed to construct the clinical parameter model, the combination of clinical and MRI and MR-HSG parameter prediction models. The performance of the model was evaluated by the area under the curve (AUC) of receiver operating characteristic (ROC), and the AUCs were compared using the DeLong test.Results The differences in age, menstrual cycle irregularity, uterine fibroids, cesarean scar diverticulum, and intrauterine adhesions between the infertility group of 86 cases and pregnant group of 226 cases were statistically significant (all P<0.05). Multivariate logistic regression analysis confirmed that age (OR=0.822, P<0.001)、multiple uterine fibroids (OR=0.540, P=0.002) and intrauterine adhesion (OR=0.367, P=0.036) were independent risk factors for UFI. The AUC for the combined model (age + multiple uterine fibroids + intrauterine adhesion) was 0.809, which was significantly higher than the age model (P<0.05). The combined model did not show a statistically significant difference compared to the age + intrauterine adhesion model and the age + multiple fibroids model (all P>0.05).Conclusions Age, multiple uterine fibroids, and intrauterine adhesion are identified as risk factors for UFI, and the combined model has clinical value in predicting pregnancy.
[关键词] 不孕症;子宫肌瘤;宫腔粘连;磁共振子宫输卵管造影;磁共振成像
[Keywords] infertility;uterine fibroids;intrauterine adhesion;magnetic resonance hysterosalpingography;magnetic resonance imaging

王洁 1   段娜 1   王绍娟 1   胡旭宇 1   任帅 1   殷燕云 2   王中秋 1*  

1 南京中医药大学附属医院放射科,南京 210029

2 南京中医药大学附属医院生殖医学中心,南京 210029

通信作者:王中秋,E-mail:zhq2001us@163.com

作者贡献声明:王中秋设计本研究的方案,对稿件重要内容进行了修改;王洁起草和撰写稿件,获取、分析和解释本研究的数据;段娜、王绍娟、胡旭宇、任帅、殷燕云获取、分析或解释本研究数据,对稿件重要内容进行了修改,其中段娜获得了江苏省中医院院级课题面上项目资助;全体作者都同意发表最后的修改稿,同意对本研究的所有方面负责,确保本研究的准确性和诚信。


基金项目: 江苏省中医院院级课题面上项目 Y22026
收稿日期:2023-11-10
接受日期:2024-02-05
中图分类号:R445.2  R711.6 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2024.03.020
本文引用格式王洁, 段娜, 王绍娟, 等. 子宫性不孕的多参数MRI、MR-HSG及临床特征分析[J]. 磁共振成像, 2024, 15(3): 122-129. DOI:10.12015/issn.1674-8034.2024.03.020.

0 引言

       不孕症指1年及以上无保护规律性生活后未能成功怀孕,其中35岁及以上女性超过6个月未孕即可诊断[1]。女性不孕症常见病因有输卵管疾病(约40%)、卵巢排卵障碍(20%~30%)、子宫异常(15%~20%)及不明原因不孕(10%)等[2, 3, 4, 5]。子宫是胚胎着床及维持妊娠至足月的关键器官,而生育年龄的推迟、反复刮宫流产后子宫内膜的损伤、剖宫产盛行后的瘢痕子宫形成、受雌激素影响的子宫肌瘤等改变正损害育龄女性的生育潜力[6, 7]。近年来子宫性不孕(uterine factor infertility, UFI)呈上升趋势[8]。因此,明确诊断有生育能力风险,甚至是不孕唯一原因的子宫疾病,及早采取临床干预措施,对不孕症患者的妊娠结局至关重要。

       临床常用诊断子宫的方法有超声、MRI、腹腔镜或宫腔镜等。传统X线子宫输卵管造影不能检查宫腔轮廓外及卵巢的病变,且有辐射;子宫输卵管超声造影从二维发展至四维,尽管可辨别不孕相关的宫腔病变,但是受限于对比剂及图像分辨率,且一定程度上依赖操作者的经验;而磁共振子宫输卵管造影(magnetic resonance hysterosalpingography, MR-HSG)一站式检查能准确评价子宫、输卵管及卵巢异常,而且安全无创、观察者依赖性小,在女性不孕症诊断中有良好的应用前景[9, 10]。课题组前期研究表明MR-HSG技术对输卵管及卵巢性不孕有明确的诊断价值,但对不孕症相关子宫疾病的评价未予总结[2, 3, 10, 11]。此外,目前文献多应用MR-HSG技术聚焦输卵管的通畅性,对于不孕症相关的子宫异常缺乏深度研究[12, 13, 14]。而MRI联合MR-HSG既能多角度可视化子宫腔内异常如宫腔粘连、子宫内膜息肉、黏膜下肌瘤等,又能识别子宫外部轮廓及子宫肌层病变,尤其对先天性子宫畸形的鉴别诊断具有显著优势,是诊断器质性UFI病因最准确的影像学检查技术[15, 16]。因此,本研究应用多参数MRI及MR-HSG技术,随访UFI患者经中西医治疗1年后的妊娠情况,分析UFI相关的风险因素并建立妊娠预测模型,为临床诊疗提供影像学依据。

1 材料与方法

1.1 一般资料

       本研究严格遵循《赫尔辛基宣言》,并经江苏省中医院(南京中医药大学附属医院)伦理委员会批准,免除受试者知情同意,批件号:2016NL-005-02。回顾性分析自2016年9月至2022年8月于江苏省中医院(南京中医药大学附属医院)行MRI及MR-HSG检查的1 835例女性不孕症患者的临床及影像资料,排除卵巢、输卵管异常及不明原因不孕等病例后有312例子宫器质性病变患者,经中西医治疗后1年内随访妊娠结局,分析比较已孕组和未孕组患者的临床基线资料、性激素及影像资料。

       纳入标准:(1)年龄20~45岁;(2)规律且无保护性生活≥1年无孕,≥35岁女性超过6个月未孕。排除标准:(1)男性伴侣不育;(2)生殖激素异常;(3)图像质量不合格即因推注对比剂患者疼痛产生运动伪影,影响图像观察及诊断;(4)卵巢性不孕(包括多囊卵巢综合征、卵巢子宫内膜异位症、卵巢萎缩、卵巢术后、卵巢良恶性肿瘤等);(5)MRI及MR-HSG排除输卵管不孕(包括输卵管阻塞、积水、宫外孕史)、不明原因不孕及子宫先天畸形;(6)失访病例。UFI的多参数MRI、MRI-HSG表现及临床特征分析研究流程图见图1图2。随访临床妊娠定义为人绒毛膜促性腺激素升高、超声检查宫内妊娠3个月以上。

图1  UFI的多参数MRI、MR-HSG及临床特征分析研究流程图。UFI:子宫性不孕;MR-HSG:磁共振子宫输卵管造影。
Fig. 1  Flowchart of multiparametric MRI, MR-HSG and clinical characteristics of UFI. UFI: uterine factor infertility; MR-HSG: magnetic resonance hysterosalpingography.
图2  UFI患者纳入、排除的MRI及MR-HSG具体表现。2A~2D:25岁,原发性不孕1年。MR-HSG(2A)示双侧输卵管通畅,重建后多角度旋转示宫腔局部充盈缺损(2B,箭);冠状位T2-FS(2C)示双侧卵巢显示清晰,右侧卵巢见优势卵泡;轴位T2-FS(2D)示宫腔内低信号影(箭);经宫腔镜确诊左侧宫角息肉。本例仅有子宫异常,纳入研究。2E~2H:28岁,原发性不孕1年,3年前行右侧卵巢囊肿剥除术。MR-HSG(2E)示右侧输卵管通畅,左侧输卵管通而欠畅;2F~2H示左侧卵巢、子宫直肠窝、子宫后壁浆膜下异常信号影(箭),冠状位T2WI可见左侧卵巢高信号影(箭),子宫扭曲(2F),轴位T2-FS(2G)呈高信号,部分病灶内见阴影征(箭),轴位T1-FS(2H)呈均匀高信号(箭),提示左侧卵巢、子宫直肠窝、子宫后壁浆膜下多发子宫内膜异位灶。本例输卵管、卵巢、子宫均有异常,予以排除。2I~2L,34岁,继发性不孕1年余,备孕二胎,自诉近1年下腹疼痛间作。MR-HSG(2I)示右侧输卵管积水呈管状扩张(白箭),左侧输卵管近端堵塞(红箭);轴位T2-FS(2J)示右侧输卵管扩张积水扭曲(箭);2K~2L示右侧卵巢类圆形异常信号影,轴位T1-FS(2K)呈高信号(箭),轴位T2-FS(2L)呈低信号(箭),提示右侧卵巢子宫内膜异位囊肿。本例输卵管、卵巢均有异常,子宫无器质性异常,予以排除。UFI:子宫性不孕;MR-HSG:磁共振子宫输卵管造影;FS:脂肪抑制。
Fig. 2  Manifestations of MRI and MR-HSG in inclusion and exclusion of UFI patients. 2A-2D: A 25-year-old woman with primary infertility for 1 year. MR-HSG (2A) shows patent bilateral fallopian tubes, with a local filling defect in the uterine cavity after reconstruction (2B, arrow); coronal T2-FS image (2C) reveals clear visualization of both ovaries, with a dominant follicle on the right ovary; axial T2-FS image (2D) shows a low signal shadow in the uterine cavity (arrow); which is a polyp in the left uterine horn confirmed by hysteroscopy. The case is included in the study because only the uterus is abnormal. 2E-2H: A 28-year-old woman with primary infertility for 1 year and a history of right ovarian cyst removal 3 years ago. MR-HSG (2E) shows a patent right fallopian tube and a patent but not smooth left fallopian tube; 2F-2H: There are multiple abnormal signal shadows on the left ovary, recto-uterine pouch, and the serosa of the uterus (arrows), coronal T2WI (2F) displays a high signal shadow in the left ovary (arrow) and the morphology of uterine cavity distortion, the shading sign is visible in some lesions on the axial T2-FS (2G, arrow) and all lesions show a uniform high signal on the axial T1-FS (2H, arrow), which suggest multiple endometriotic foci on the left ovary, recto-uterine pouch, and the serosa of the uterus. This case involves the fallopian tubes, ovaries, and uterus, and is therefore excluded. 2I-2L: A 34-year-old woman with secondary infertility for more than 1 year, preparing for a second child, and complaining of intermittent lower abdominal pain for the last year. MR-HSG (2I) shows hydrosalpinx with tubal dilation in the right fallopian tube (white arrow) and proximal obstruction in the left fallopian tube (red arrow); axial T2-FS (2J) shows dilated and distorted right fallopian tube (arrow); 2K-2L: There is a circular abnormal signal on the right ovary, with high signal on T1-FS (2K, arrow) and low signal on T2-FS (2L, arrow), indicating an endometriotic cyst on the right ovary. The findings suggest abnormalities on the fallopian tubes and ovaries, while the uterus shows no organic abnormalities, leading to exclusion. MR-HSG: magnetic resonance hysterosalpingography; UFI: uterine factor infertility; FS: fat suppression.

1.2 临床病史及性激素检查

       收集子宫异常不孕患者临床病史资料包括年龄、身体质量指数(body mass index, BMI)、不孕时间及类型(原发或继发不孕)、月经相关情况及性激素结果(MRI检查当月),包括卵泡刺激素(follicle-stimulating hormone, FSH)、黄体生成素(luteinizing hormone, LH)、雌二醇(estradiol, E2)、睾酮(testosterone, T)、孕酮(progesterone, P)、泌乳素(prolactin, PRL)、抗苗勒氏管激素(anti-Müllerian hormone, AMH)。

1.3 MRI检查方法

       所有研究对象均于月经结束后3~7 d内完成3.0 T盆腔MRI及MR-HSG检查,技术规范参照输卵管造影中国专家共识(2022版)[17]。采用德国西门子(Siemens Magnetom Verio)3.0 T MRI扫描仪,6通道躯干相控阵列表面线圈。患者取仰卧位,行常规盆腔扫描,包括轴位T1WI(TR 712 ms,TE 12 ms,层厚4 mm)、轴位T2WI(TR 5 810 ms,TE 94 ms,层厚4 mm)、矢状位脂肪抑制T2WI(TR 3 000 ms、TE 85 ms,层厚3 mm)。后常规外阴消毒引入内窥器暴露宫颈,置输卵管造影导管于宫腔并注射生理盐水2~3 mL固定。采用三维脂肪抑制T1WI梯度回波动态增强序列扫描(TR 3.25 ms,TE 1.22 ms,层厚0.7 mm),共扫描4期,每期16 s,同时手动注射20 mL MR-HSG对比剂钆喷酸葡胺(马根维显,拜耳公司),每期注射5 mL,重建生成减影和最大信号投影图像。2 min后采用快速T1WI脂肪抑制轴位序列(TR 3.96 ms,TE 1.39 ms,层厚3 mm)评估对比剂盆腔弥散情况。

1.4 图像分析

       图像由两名10年以上妇科影像诊断经验的副高级职称医师独立阅片。MR-HSG排除输卵管相关异常,多参数MRI及临床病史排除卵巢性不孕、不明原因不孕及子宫先天畸形。UFI因素包括子宫内膜厚度异常(<5 mm或>10 mm),子宫肌瘤(单发或多发、大小及位置),子宫腺肌症(局灶或弥漫),子宫内膜息肉、瘢痕子宫、宫腔粘连、子宫颈管多发囊肿等,诊断结果有异议通过讨论达成一致。

1.5 统计学分析

       采用SPSS 26.0软件分析数据。计量资料用Kolmogorov-Smirnov方法进行正态性检验,符合正态分布的计量资料以均值±标准差表示,两组间比较采用独立样本t检验;非正态分布计量资料以中位数(四分位数间距)表示,两组间比较采用Mann-Whitney U检验。计数资料用n(%)表示,组间比较采用χ2检验或Fisher确切概率法。先后采用单因素、多因素logistic回归分析UFI的风险因素。根据单因素分析结果,将所有P<0.1的参数纳入多因素分析,差异有统计学意义的参数采用logistic回归输入法构建临床参数模型、临床与MRI及MR-HSG联合模型,进一步绘制受试者工作特征(receiver operating characteristic, ROC)曲线,计算曲线下面积(area under the curve, AUC)、敏感度和特异度。采用DeLong检验比较模型间的预测效能。P<0.05为差异有统计学意义。

2 结果

2.1 UFI患者治疗后已孕组与不孕组临床表现、性激素比较分析

       本研究共纳入病例312例,年龄21~43(31.60±3.58)岁,MRI诊断黏膜下肌瘤、宫腔粘连及子宫内膜息肉均于本院行宫腔镜手术并病理证实。其余病例经药物调理治疗。一年后随访不孕组86例(27.6%),已孕组226例(72.4%)。两组间的年龄、月经周期不规律差异有统计学意义(P<0.05),年龄与妊娠结局呈负相关,不孕组的年龄高于已孕组(34.00±4.24 vs. 30.00±2.65),30岁以上不孕组比例高于已孕组,其中>35岁组尤为明显(27.91% vs. 4.42%);不孕组月经周期不规律的比例高于已孕组(94.19% vs. 83.19%);其他临床资料如BMI、不孕时间、月经期长、原发继发不孕及性激素检查(FSH、LH、E2、T、P、PRL、AMH)结果两组间差异均无统计学意义(P>0.05)(表1)。

表1  UFI治疗后不孕组与已孕组临床表现、性激素比较分析
Tab. 1  Comparison of clinical data and sex hormones between the infertile group and the pregnant group after treatment of UFI patients

2.2 UFI患者治疗后不孕组与已孕组影像资料比较分析

       两组间子宫肌瘤的数量和位置、瘢痕子宫及宫腔粘连差异有统计学意义(P<0.05,表2)。子宫多发肌瘤不孕组的比例(17.44%,15/86)显著高于已孕组(4.87%,11/226);仅位于黏膜下的肌瘤均在不孕组(4.65%,4/86),仅位于肌壁间或浆膜下肌瘤的比例两组相近,两个位置同时出现肌瘤的不孕组显著高于已孕组。瘢痕子宫不孕组的比例(22.09%,19/86)高于已孕组(9.29%,21/226)。瘢痕残余肌层厚度不孕组[(0.53±0.09)mm]和已孕组[(0.62±0.15)mm]差异无统计学意义(P>0.05)。宫腔粘连比例不孕组(13.95%,12/86)高于已孕组(6.64%,15/226)。其他如子宫内膜厚度、子宫肌瘤大小、子宫腺肌症(局灶或弥漫)、子宫内膜息肉、子宫颈管纳氏囊肿两组间差异均无统计学意义(P>0.05,表2)。

表2  UFI患者治疗后不孕组与已孕组影像资料比较分析
Tab. 2  Comparison of imaging data between the infertile group and the pregnant group after treatment of UFI patients

2.3 UFI危险因素的logistic回归分析

       单因素分析显示不孕与年龄、月经周期不规律、子宫肌瘤(肌瘤位置及肌瘤数量)、瘢痕子宫及宫腔粘连密切相关(P<0.05)。多因素分析证实年龄、子宫多发肌瘤、宫腔粘连差异有统计学意义,年龄[OR=0.822,95% 置信区间(confidence interval, CI):0.759~0.891;P<0.001]、子宫多发肌瘤[OR=0.540(95% CI:0.375~0.777);P=0.002]、宫腔粘连[OR=0.367(95% CI:0.144~0.938);P=0.036]是UFI的独立危险因素(表3图3)。

图3  UFI患者多参数MRI、MR-HSG影像及宫腔镜表现。3A~3D:27岁,原发性不孕1年。MR-HSG(3A)示双侧输卵管通畅,右侧宫角充盈缺损;轴位(3B)及矢状位(3C)T2-FS示子宫多发黏膜下及肌壁间多发低信号影,突向宫腔,提示为子宫多发黏膜下及肌壁间肌瘤;宫腔镜(3D)下肌瘤切除术所见,随访未孕。3E~3H:33岁,继发性不孕3年,3年前行清宫术。MR-HSG(3E)示双侧输卵管通畅;轴位T2-FS(3F)示双侧卵巢显示清晰,轴位T2-FS(3G)示左侧宫角条状低信号影;宫腔镜(3H)确诊宫腔粘连并行粘连松解术,随访未孕。3I~3L:34岁,继发性不孕1年余,备孕二胎。经间期点滴出血,MR-HSG(3I)示双侧输卵管通畅;轴位T2-FS(3J)示双侧卵巢显示清晰;矢状位T2-FS(3K~3L)示子宫前壁肌层不连续,部分缺如(3K),提示为子宫瘢痕憩室,残余肌层最薄处厚约5 mm(3L),随访已孕。3M~3N:32岁,原发性不孕1年。矢状位T2-FS(3M)示子宫底后壁类圆形低信号,内见囊状高信号,其内高信号灶轴位T1-FS(3N)亦呈高信号,提示子宫底后壁腺肌瘤,随访已孕。3O:29岁,继发性不孕2年。矢状位T2-FS示宫腔内低信号,宫腔镜证实为子宫内膜息肉并切除,随访已孕。3P:34岁,继发性不孕1年。矢状位T2-FS示宫颈内口多发囊状高信号,提示纳氏囊肿,随访已孕。UFI:子宫性不孕;MR-HSG:磁共振子宫输卵管造影;FS:脂肪抑制。
Fig. 3  Multiparametric MRI, MR-HSG images and hysteroscopic presentation of UFI patients. 3A-3D: A 27-year-old with primary infertility for 1 year. MR-HSG (3A) shows patent bilateral fallopian tubes, with filling defect in the right uterine horn. There are multiple low-signal shadows protruding into the uterine cavity between the submucosa and the muscle layer of the uterus on axial T2-FS (3B) and sagittal T2-FS (3C), suggesting multiple submucosal and intramural fibroids in the uterus. The patient is still infertile after hysteroscopic myomectomy performed (3D). 3E-3H: A 33-year-old with secondary infertility for 3 years, who underwent a hysterectomy 3 years ago. MR-HSG (3E) shows patent bilateral fallopian tubes; axial T2-FS image (3F) shows clear bilateral ovaries; axial T2-FS image (3G) shows linear low signal in the left uterine horn; intrauterine adhesion is confirmed by hysteroscopy (3H) and adhesion release is performed, but pregnancy does not occur on follow-up. 3I-3L: A 34-year-old with secondary infertility for more than 1 year, preparing for the second child, experiencing intermenstrual spotting bleeding. MR-HSG (3I) shows patent bilateral fallopian tubes; axial T2-FS image (3J) shows clear bilateral ovaries; sagittal T2-FS image (3K) shows the discontinuity of the anterior wall muscle layer of the uterus, with partial absence, suggesting a uterine scar diverticulum, with the thinnest residual muscle layer measuring approximately 5 mm (3L). Despite this, the patient achieves a pregnancy on follow-up. 3M-3N: A 32-year-old with primary infertility for 1 year. Sagittal T2-FS image (3M) shows a round low-signal lesion in the posterior wall of the uterine fundus, with cystic high-signal areas inside; the inside high signal areas also show high signal on the axial T1-FS (3N), suggesting adenomyoma. The patient achieves a pregnancy on follow-up. 3O: A 29-year-old with secondary infertility for 2 years. Sagittal T2-FS image shows low signal within the uterine cavity. Hysteroscopy confirms endometrial polyp and resection. The patient achieves a pregnancy on follow-up. 3P: A 34-year-old with secondary infertility for 1 year. Sagittal T2-FS image shows multiple high signal cysts in the endocervix, suggesting Nabothian cysts. The patient achieves a pregnancy on follow-up. UFI: uterine factor infertility; MR-HSG: magnetic resonance hysterosalpingography; FS: fat suppression.
表3  UFI相关的危险因素logistic回归结果
Tab. 3  Logistic regression analysis to predict risk factors associated with UFI

2.4 各模型预测UFI的ROC结果

       ROC分析显示年龄预测模型AUC为0.694(95% CI:0.592~0.795);年龄+宫腔粘连预测模型AUC为0.745(95% CI:0.656~0.845);年龄+子宫多发肌瘤预测模型AUC为0.796(95% CI:0.714~0.876);年龄+子宫多发肌瘤+宫腔粘连联合预测模型AUC为0.809(95% CI:0.728~0.889)(图4)。多参数联合模型AUC值超过0.8(为0.809),结果有一定准确性,DeLong检验比较多参数联合模型与其余模型的AUC值,与年龄模型差异具有统计学意义(P<0.05),而与年龄+宫腔粘连预测模型、年龄+子宫多发肌瘤预测模型差异无统计学意义(P>0.05)。

图4  各模型预测UFI的受试者工作特征曲线。UFI:子宫性不孕;AUC:曲线下面积。
Fig. 4  The receiver operating characteristic curves of each model for predicting UFI. UFI: uterine factor infertility; AUC: area under the curve.

3 讨论

       多参数MRI及MR-HSG技术安全无创、患者疼痛感轻、并发症少,有助于临床医生对育龄期女性不孕原因进行详细评估,在准确、有效可视化输卵管通畅性的同时,还能精准诊断宫腔内外及卵巢的器质性异常,尤其是不孕相关的子宫异常,敏感度、特异度可达腹腔镜标准[18, 19]。本研究收集1 835例不孕症患者的临床资料、生化检查指标、多参数MRI及MR-HSG特征,着眼其中312例仅有子宫异常的不孕患者,通过治疗后的怀孕情况,比较已孕组和不孕组的临床指标及子宫异常差异,分析子宫疾患与不孕的相关性,建立妊娠预测模型。本研究发现较大年龄、子宫多发肌瘤及宫腔粘连是女性UFI的风险因素,进一步细化了影响女性不孕的子宫因素,为临床制订个体化的诊疗方案作参考,联合模型对UFI患者预测妊娠有较高价值。

3.1 年龄与UFI

       不孕组女性年龄明显大于已孕组,年龄与妊娠结局呈明显负相关,与既往研究一致[20]。本研究中30岁以上不孕组比例高于已孕组,>35岁不孕组尤为明显,而随着年龄减小,经治疗1年后怀孕比例明显增高。女性的生育能力在22~26岁之间达到顶峰,与年龄相关的生育能力下降在35岁尤为明显,妊娠几率随着年龄的增长明显降低[21, 22]。此外,随着年龄增长女性更易罹患子宫疾病如子宫肌瘤、子宫腺肌症、子宫内膜息肉等损害生育能力的疾患。因此,从优生优育层面,适龄婚育尤为重要。

3.2 子宫肌瘤与UFI

       子宫肌瘤是导致女性不孕及反复流产的常见原因,MRI诊断肌瘤的准确率高达92%[23, 24]。目前有研究认为肌壁间肌瘤和黏膜下肌瘤影响生育,黏膜下肌瘤与大于4 cm的扭曲宫腔的肌壁间肌瘤对胚胎植入有不利影响,而浆膜下肌瘤对生育无明显影响[8, 25]。另一项研究表明,不侵犯子宫内膜腔的小肌瘤不影响女性的生育能力[26]。本研究中子宫多发肌瘤是UFI的独立危险因素。子宫多发肌瘤可能通过导致子宫内膜腔扭曲、子宫收缩力异常、子宫内膜血供减少和子宫内膜容受性改变,从而影响生育力,导致不孕,该观点也见于其他研究报导[27]。本研究中黏膜下肌瘤经宫腔镜摘除,肌壁间肌瘤较小,无扭曲宫腔的改变,不影响受精卵着床,故子宫肌瘤的大小、位置在已孕组和不孕组间无显著性差异。

3.3 宫腔粘连与UFI

       宫腔粘连与继发性不孕风险增加有关,MRI具有较高的准确度(94.57%)、敏感度(98.8%)和特异度(42.9%)[28]。本研究中宫腔粘连是UFI的独立危险因素。宫腔粘连常继发于反复的宫腔操作,病理上以子宫内膜纤维化即子宫内膜明显变薄、宫腔缩短、结合带异常增厚为特征,子宫内膜基底层被破坏,即使行手术粘连松解后,仍然对生殖结果产生不利影响[29, 30]。本组病例均接受宫腔镜粘连松解术,术后1年随访宫腔粘连患者仍然不孕,宫腔粘连是UFI的独立风险因素。MRI及MR-HSG对宫腔粘连诊断的准确性较高,现有部分研究通过体素内不相干运动(intravoxel incoherent motion, IVIM)及扩散峰度成像(diffusion kurtosis imaging, DKI)评估宫腔粘连的细节特征[31, 32],后期功能MRI技术有望能更精准评价宫腔粘连对生育力的影响。

3.4 其他因素与UFI

       瘢痕子宫致女性不孕的风险可高达19%[33]。瘢痕内经血残留,血红蛋白降解后可能致胚胎毒性或影响其着床[34]。瘢痕子宫生育率低和瘢痕处残余肌层的厚度有关,修复瘢痕憩室后生育能力有明显改善[35]。残余肌层厚度是不孕症治疗中一个重要的观察指标,若残余肌层厚度<3 mm,行宫腔镜下肌层修复是非常有必要的[36]。本组瘢痕子宫残余肌层厚度均值为6.0 mm,对妊娠结局无明显影响。子宫内膜息肉在不孕症中发病率高达32%[37]。息肉导致甘油三酯、芳香化酶、炎症标志物水平升高以及与子宫内膜容受性相关的分子标志物(HOXA10、HOXA11)水平下调,对精子运输或胚胎植入产生不利影响[38, 39]。此外,息肉还可通过机械干扰对生育能力产生不利影响,相较于简单的诊断性宫腔镜检查,宫腔镜下子宫内膜息肉切除后可能会提高受试者临床妊娠率[40]。本组MRI诊断为内膜息肉的患者均接受了宫腔镜切除,随访结果显示息肉切除后患者获益。腺肌症对生育有负面影响,尤其是辅助生殖技术的妊娠结局[41]。腺肌症病灶局部血小板聚集和缺氧,产生细胞因子、前列腺素并增加雌激素的合成,导致子宫内膜容受性下降及子宫蠕动过度,破坏精子运输和胚胎植入[42]。然而,有些研究中无症状腺肌症女性的妊娠结局与无腺肌症女性相似[43, 44]。内生型腺肌症源于内膜基底层,不受月经周期及激素调节影响。外生型腺肌症源于内膜功能层,和卵巢子宫内膜异位症、腹膜型子宫内膜异位症及深部子宫内膜异位症相伴存在,受月经周期及激素调节[45]。本研究发现不伴有卵巢、输卵管及深部子宫内膜异位症的子宫腺肌症不是妊娠的风险因素。子宫腺肌症的表现多样,发生位置、累及范围、有无症状等都可能影响妊娠结局,值得进一步探索研究。

3.5 联合模型对预测UFI的效能分析

       MRI联合MR-HSG评估致生育力低下的子宫器质性病变具有显著优势,本研究基于临床资料、MRI及MR-HSG所示的子宫异常,建立年龄、子宫多发肌瘤、宫腔粘连多参数联合模型,AUC值达0.809,明显优于单个年龄参数模型,联合模型预测效能优于年龄单参数模型。尽管多参数联合模型与年龄+宫腔粘连模型、年龄+子宫多发肌瘤模型差异无统计学意义,但多因素联合模型AUC值较后两者有所提升。多参数联合模型对UFI预测效能较好,提供精准的诊断信息以及进一步的治疗方向,有助于临床制订规范的个体化治疗方案及助孕措施。

3.6 本研究的局限和展望

       尽管MRI、MR-HSG检查耗时较长、费用偏高,但是MR-HSG一站式检查能较明确诊断不孕的可能原因,提高现有不孕症的诊疗水平。本研究也存在一些局限性:首先,单中心回顾性研究存在一定的选择偏倚;其次,本研究仅分析影响不孕症的重要子宫病变,合并输卵管、卵巢异常及不明原因不孕的病例未纳入分析,研究适用于不孕症仅有子宫疾病的评价,后期将对子宫和/或输卵管和/或卵巢疾病患者的妊娠结局进一步综合分析;最后,治疗方法是影响怀孕的关键因素之一,虽然本研究所有病例均严格按照临床规范进行标准化治疗,但纳入患者治疗方案间存在个体化差异,因此未对治疗方法进行深入分析。

4 结论

       综上所述,多参数MRI及MR-HSG可以全面、细致地分析影响不孕的子宫疾病。较大年龄、子宫多发肌瘤及宫腔粘连是UFI的危险因素,建立的多因素联合预测妊娠模型对辅助临床决策、制订个体化诊疗方案具有一定价值。

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