卵巢缺如：系统文献综述和病例系列报告

卵巢缺失是一种罕见的疾病，最常见于单侧。 已经提出了该病症的几种病因，包括扭转、血管意外和胚胎缺陷。 通过系统检索 Cochrane Library、ClinicalTrials.gov、Google Scholar、Ovid Embase、Ovid Medline、PubMed、Scopus 和 科学网。 排除标准包括怀疑性别发育差异、缺乏经手术证实的卵巢缺失的病例以及除 46XX 以外的核型。 的检索产生了 12,120 次引用，其中纳入了 79 项研究。 通过引用追踪发现了另外 10 项研究，总计 113 个案例，其中包括本综述中提出的两个未发表的案例。 腹部/盆腔疼痛（30%）和不孕/生育能力低下（19%）是最常见的症状。 28% 的术前卵巢成像结果未发现卵巢异常。 大约 17% 的病例伴有子宫异常，22% 的病例伴有肾脏异常。 子宫异常的患者更容易出现肾脏异常（p<0.005）。 扭转或血管病因是卵巢缺如最常怀疑的病因（52%），其次是不确定病因（27%）和胚胎学病因（21%）。 尽管文献中许多人将这种情况称为“发育不全”，但大多数卵巢缺如的病例可能归因于扭转或血管意外。 影像学可能无法正确诊断卵巢缺失，在许多情况下诊断性腹腔镜检查可能更可取，因为可以在手术过程中评估泌尿生殖解剖和生育能力。 单侧卵巢缺失的女性的生育能力可能受到最小程度的影响或不受影响。

单侧卵巢缺如 (UOA) 是一种罕见的发现，之前报道的患病率为 1:11,241。 这种情况涉及单个卵巢的缺失，通常伴有同侧输卵管和/或附件的部分或完全缺失，以及偶尔伴随的异常。 卵巢缺如 (OA) 的各种提出的病因可分为胚胎学、血管或扭转相关假说。 胚胎学观点认为，UOA是性腺胚胎发生缺陷造成的，导致先天性缺失一侧卵巢。 血管假说认为，血管意外继发的缺血是 UOA 和邻近附件结构发育不全的原因。 最后，扭转假说指出，卵巢扭转会导致附件自动截肢。 尽管扭转或血管意外可能发生在任何年龄，但子宫内或早期发育中的事件可能分别是临床沉默或错误归因的（例如婴儿绞痛）。 所有这三种机制都可能导致先前病例报告中详述的 UOA 实例。

在人类中，泌尿生殖 (GU) 系统源自中间中胚层——位于轴旁板和侧板中胚层之间的胚层的一个组成部分。 性腺发育在妊娠第四周左右开始，此时中间中胚层的体腔上皮增殖，在发育中的胚胎的两侧形成生殖脊。 这些生殖脊是性腺的体细胞组成部分，在第六周左右，来自后内胚层的原始生殖细胞将在其中定居，形成后肠。 在此阶段，性腺未分化或具有双潜能，并且将根据遗传线索发育成睾丸或卵巢。 双能性腺中表达的几个基因在中间中胚层的稳定和性腺原基内细胞的增殖中发挥重要作用。 其中包括同源盒基因 Emx2 和 Lhx1/9、维尔姆斯肿瘤基因 Wt1 和类固醇生成因子 1（Nr5a1 或 Sf1），这些基因在小鼠体内的消融会导致性腺形成的严重破坏。

性别决定发生在妊娠 6-8 周左右，取决于 Y 连锁基因 SRY 及其下游靶标 SOX9 的表达，SOX9 可激活睾丸发育。 卵巢发育曾经被认为是默认发生的，需要包括 Foxl2、Wnt4 和 Rspo1 在内的几个基因的作用。 动物研究表明Foxl2和Wnt4通过下调Sox9表达来调节卵巢发育。 此外，Foxl2通过拮抗Wt1来抑制Nr5a1表达。 Rspo1 上调 Wnt4 表达并与 Wnt4 信号传导配合。 发育后，卵巢在妊娠第三个月左右在引带的引导下从后腹部下降到卵巢窝。 卵巢下降不良虽然不常见，但可以沿着从椎旁后腹壁到骨盆边缘的下降线发现。

子宫单独发育。 在第七周至第九周之间，副中肾管在颅端融合形成子宫，在尾部融合形成阴道的上三分之二。 颅管的侧面（未融合）部分最终发育成输卵管。 因此，伴随卵巢异常在苗勒氏管发育不全中很少见。 WNT4 突变与少数苗勒管异常病例相关，小鼠体内 Wnt4 的消融会破坏苗勒管发育和性别决定，但不会导致性腺发育不全。

UOA 的发病率为 11,241 分之一，这是基于马来西亚一家机构在 22,483 例妇科和产科手术中观察到的两个病例。 由于 UOA 通常无症状，因此这个数字可能被低估。 该评估假设在电子病历广泛使用之前，对数千次手术中的偶然发现进行了完美记录。 过去几十年的大量病例报告可能代表了妇科领域腹腔镜检查的采用（从而增加了偶然发现），而不是 UOA 真实发病率的变化。 尽管 UOA 已成为多个文献综述的主题，但尚未对该主题进行系统综述。 努力通过对卵巢缺如的系统回顾，为围绕 UOA 病因学的讨论提供信息，并提高临床认识，同时介绍相关机构的两例 UOA 病例。

卵巢缺如：系统文献综述和病例系列报告

图 1
病例1的术中腹腔镜骨盆视图。U=子宫，R-O=右侧卵巢，箭头指向部分左侧输卵管，左侧卵巢缺失

卵巢缺如：系统文献综述和病例系列报告

图 2
PRISMA 流程图。 有关筛选方法和排除研究的更多信息可以在补充材料中找到。 改编自：Page MJ、McKenzie JE、Bossuyt PM、Boutron I、Hoffmann TC、Mulrow CD 等人。 PRISMA 2020 声明：系统评价报告更新指南。 BMJ 2021；372：n71。 https://doi.org/10.1136/bmj.n71。 欲了解更多信息，请访问：http://www.prisma-statement.org/

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