Although it has been known for millennia that many young women who give birth vaginally will suffer from disabling pelvic organ prolapse later in their lifespan, the factors linking these two events remain a mystery. Of the 3 million women who deliver vaginally each year 300,000 or 1 in 10 will later require surgery for pelvic floor dysfunction due to their unique sex-determined role in reproduction. Our discovery of birth-induced levator ani muscle injury and its strong relationship to prolapse has identified a key connection between birth and prolapse. Ignorance of how birth-induced injury occurs and how it produces subsequent prolapse has blocked efforts to improve prevention and treatment. In this application we seek to continue SCOR support for our broadly interdisciplinary sex-differences research group representing 4 schools and 2 institutes. The group has won 10 awards in the last 4 years for our discoveries and now seeks funding to begin to translate these insights into improved prevention at birth and strategies for better treatment. Project I """"""""Birth Biomechanics"""""""" will test hypotheses concerning basic mechanisms of levator ani injury during vaginal birth to identify specific situations that may increase or decrease injury risk. Project II """"""""Injury Extensio"""""""" will determine whether minor clinically insignificant levator injury after first birth extends to a clinically significant tear during second birth. Because a second birth doubles the risk of genital prolapse, this event offers the opportunity of preventing injury and their sequelae later in life. Project III """"""""Muscle-Ligament Dynamics"""""""" will establish the interaction between birth-related levator muscle injury and the properties of the uterovaginal supporting ligaments associated with prolapse. Core A """"""""Administrative/Human Subjects"""""""" integrates and supports the interdisciplinary team and provides project support by recruiting subjects, compiling and analyzing data and protecting subject safety. Core B """"""""Biostatistics/Measurements"""""""" provides statistical and technical support for the projects along with integrated analysis for 2- and 3-dimensional spatial data gathered across projects. It will prepare data for presentation, publication, subject safety analysis and eventually public use. Core C """"""""Translation/Mentorship""""""""w foster insight dissemination and drive investigator development. This SCOR will produce translational insights to reduce the sex-determined consequences women suffer from their unique role in reproduction. It will establish the scientific basis for new strategies to improve treatment, identify important prevention opportunities, and train a new generation of researchers.

Public Health Relevance

Of the 3 million women that give birth each year in the US, three hundred thousand or 1 in 10 will need surgery later in life for the debilitating conditions o prolapsed and incontinence collectively known as pelvic floor dysfunction. Coordinated interdisciplinary sex-differences research can lay the foundation for rational prevention and reduced disease burden and lessen the 5 to 30% treatment failure rate.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center (P50)
Project #
5P50HD044406-12
Application #
8549843
Study Section
Special Emphasis Panel (ZRG1-EMNR-Q (50))
Program Officer
Parrott, Estella C
Project Start
2002-09-25
Project End
2017-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
12
Fiscal Year
2013
Total Cost
$1,014,439
Indirect Cost
$511,668
Name
University of Michigan Ann Arbor
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Berger, Mitchell B; Khandwala, Nikhila; Fenner, Dee E et al. (2016) Colovaginal Fistulas: Presentation, Evaluation, and Management. Female Pelvic Med Reconstr Surg 22:355-8
Miller, Janis M; Garcia, Caroline E; Hortsch, Sarah Becker et al. (2016) Does Instruction to Eliminate Coffee, Tea, Alcohol, Carbonated, and Artificially Sweetened Beverages Improve Lower Urinary Tract Symptoms?: A Prospective Trial. J Wound Ostomy Continence Nurs 43:69-79
Luo, Jiajia; Betschart, Cornelia; Ashton-Miller, James A et al. (2016) Quantitative analyses of variability in normal vaginal shape and dimension on MR images. Int Urogynecol J 27:1087-95
Swenson, Carolyn W; Smith, Tovia M; Luo, Jiajia et al. (2016) Intraoperative cervix location and apical support stiffness in women with and without pelvic organ prolapse. Am J Obstet Gynecol :
Chen, Luyun; Lisse, Sean; Larson, Kindra et al. (2016) Structural Failure Sites in Anterior Vaginal Wall Prolapse: Identification of a Collinear Triad. Obstet Gynecol 128:853-62
Tracy, Paige V; DeLancey, John O; Ashton-Miller, James A (2016) A Geometric Capacity-Demand Analysis of Maternal Levator Muscle Stretch Required for Vaginal Delivery. J Biomech Eng 138:021001
Brown, Lindsay K; Fenner, Dee E; DeLancey, John O L et al. (2016) Defining Patient Knowledge and Perceptions of Vaginal Pessaries for Prolapse and Incontinence. Female Pelvic Med Reconstr Surg 22:93-7
Swenson, Carolyn W; Luo, Jiajia; Chen, Luyun et al. (2016) Traction force needed to reproduce physiologically observed uterine movement: technique development, feasibility assessment, and preliminary findings. Int Urogynecol J 27:1227-34
Cameron, Anne P; Suskind, Anne M; Neer, Charlene et al. (2015) Functional and anatomical differences between continent and incontinent men post radical prostatectomy on urodynamics and 3T MRI: a pilot study. Neurourol Urodyn 34:527-32
Kim, Jinyong; Betschart, Cornelia; Ramanah, Rajeev et al. (2015) Anatomy of the pubovisceral muscle origin: Macroscopic and microscopic findings within the injury zone. Neurourol Urodyn 34:774-80

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