Vaginal birth confers an 8-fold increase in the risk for a woman developing prolapse, a condition that results in 200,000 operations per year and carries up to a 25% reoperation rate at 10 years. Two primary causes for prolapse have emerged: 1) descent of the cervix and upper vagina (apical descent) involving the cardinal/uterosacral ligaments, and 2) neuromuscular damage to the levator ani muscles during vaginal birth. The relationship between these factors is unknown. It is the overall goal of our research to discover the basic mechanism whereby muscle and ligament failure interact producing prolapse. Our theoretical work suggests the working hypothesis that levator damage leads to opening of the levator urogenital hiatus and results in exposure of the vaginal wall to a pressure differential that pulls downward on the apical supports. Lack of data concerning ligament stiffness prevents a quantitative understanding of these relationships. We will recruit and test 50 asymptomatic volunteers and 50 women with pelvic organ prolapse to accomplish the following aims.
Aim 1 will use a new servoactuator device to measure the in vivo ligament force-displacement behavior ("stiffness") to determine the role of different ligament properties in prolapse.
Aim 2 will make static and dynamic MRI images and clinical pelvic floor measurements to establish the relative contribution to apical descent by a) muscle impairment b) ligament properties.
Aim 3 will create subject-specific 3D models of the cardinal and uterosacral ligaments, which will be used to and determine the measurement differences in cardinal and uterosacral elongation in apical descent. The results of this study will provide data that can lead to clinically relevant tests to, for example, identify which patients need an operation to support the apex. It will also provide the much needed data, validating an overall disease model concerning interactions between ligament support and muscle damage. This research will be helpful in developing strategies for improved prevention and treatment selection and a better understanding of why muscle damage at birth causes prolapse later in life.

Public Health Relevance

Pelvic floor disorders represent a hidden epidemic of distressing problems women suffer due to their unique sex-differences in reproduction. The mechanistic insights from this proposed research will help to define the relationship between injuries that occur at birth and how they play a role in pelvic organ prolapse. These insights are needed to help prevent these disabling conditions and to open new avenues to personalized treatment and improved prevention.

Agency
National Institute of Health (NIH)
Type
Specialized Center (P50)
Project #
5P50HD044406-13
Application #
8720542
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
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