Mechanisms for pelvic organ prolapse after obstetrical levator muscle injury

描述（由申请人提供）：女性盆腔器官脱垂（POP）是一种致残的慢性疾病，子宫和阴道壁突出阴道，引起不适以及膀胱和肠道功能障碍。女性一生中接受POP手术的风险为19%。预防策略尚未确定，因为持久性有机污染物的生物学机制尚不确定。除了年龄，唯一已知的POP风险因素是阴道分娩。具体来说，该团队先前的研究表明，阴道分娩与POP的几率增加5倍有关。然而，这种关联的机制尚不清楚。本研究将探讨产科提肛肌损伤（LAMI）是否通过改变提肛肌的结构和/或功能而导致POP。LAMI发生在20%的阴道分娩后，可以通过三维超声成像检测到。该建议的中心假设是LAMI通过两种离散的机制导致POP：提提肌裂孔的慢性扩大（结构改变）和提提肌复合体的无力（功能改变）。本提案的具体目的是：(1)比较有和没有LAMI的女性之间提肛肌的结构和功能，通过3D超声识别；(2)确定LAMI、提肛肌结构和功能对POP的相对贡献。为了实现这些目标，该团队建立的纵向队列研究（R01HD056275）中的460名顺产妇女将在分娩后5-15年进行评估。评估将包括盆腔器官支持的定量评估，提提肌复合体的3D成像和提提肌力量的客观测量。3D超声是一种令人兴奋的工具，它提供了提肌的动态、实时视图，使我们能够检测LAMI，并区分有和没有LAMI的人之间的结构和功能差异。因此，拟议的研究不仅将考虑LAMI在POP发展中的作用，还将考虑LAMI的长期后遗症（如提肌裂孔的慢性改变）。LAMI已成为一种重要的产科并发症，目前无法预防，除非通过选择性剖宫产。这项研究将具有重要意义，因为在病理生理学被阐明和POP风险标记物被确定之前，预防POP是不可能的。本申请书中提出的研究预计将提供标记，以确定POP风险最大的妇女，并将作为制定有效预防战略的平台。鉴于持久性有机污染物的高流行率，预防对于减轻公共卫生负担至关重要。

DESCRIPTION (provided by applicant): Female pelvic organ prolapse (POP) is a disabling, chronic condition in which the uterus and vaginal walls protrude through the vagina, causing discomfort as well as bladder and bowel dysfunction. A woman's lifetime risk of POP surgery is 19%. Prevention strategies have not been identified because the biological mechanisms underlying POP are uncertain. Other than aging, the only known risk factor for POP is vaginal childbirth. Specifically, prior research by this team demonstrated that vaginal delivery is associated with a 5-fold increase in the odds of POP. However, the mechanisms for this association remain unknown. Studies proposed in this application will investigate whether obstetrical levator ani muscle injury (LAMI) contributes to POP through alterations in the structure and/or the function of the levator muscles. LAMI, which occurs after 20% of vaginal births, can be detected with 3-dimensional ultrasound imaging. The central hypothesis of this proposal is that LAMI leads to POP through two discrete mechanisms: chronic widening of the levator hiatus (change in structure) and weakness of the levator muscle complex (change in function). The specific aims of this proposal are: (1) to compare levator ani muscle structure and function between women with and without LAMI, as identified on 3D ultrasound; (2) to determine the relative contributions of LAMI, levator ani muscle structure and function to POP. To accomplish these aims, 460 vaginally parous women from this team's established longitudinal cohort study (R01HD056275) will be evaluated 5-15 years from delivery. Evaluation will include quantitative assessment of pelvic organ support, 3D imaging of the levator muscle complex, and objective measures of levator strength. 3D ultrasound is an exciting tool that provides dynamic, real time views of the levator muscle and will enable us to detect LAMI and to distinguish structural and functional differences between those with and without LAMI. Thus, the proposed studies will consider not only the role of LAMI in the development of POP, but also the long term sequelae of LAMI (such as chronic changes to the levator hiatus). LAMI has emerged as an important obstetrical complication that is currently not preventable, except by elective cesarean birth. This research will be significant because POP prevention will not be possible until the pathophysiology is elucidated and markers for POP risk are identified. The studies proposed in this application are expected to provide markers that will identify women at greatest risk for POP and will serve as a platform for developing effective prevention strategies. Given the high prevalence of POP, prevention is critical to reduce the public health burden.