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 #
5P50HD044406-13
Application #
8720539
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Parrott, Estella C
Project Start
2002-09-25
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
13
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Swenson, Carolyn W; Morgan, Daniel M; George, Jenny et al. (2018) Effect of Cystocele Repair on Cervix Location in Women With Uterus In Situ. Female Pelvic Med Reconstr Surg 24:56-59
Huebner, Markus; DeLancey, John O L; Reisenauer, Christl et al. (2018) Magnetic resonance imaging of vaginal support structure before and after Vecchietti procedure in women with Mayer-Rokitansky-K├╝ster-Hauser syndrome. Acta Obstet Gynecol Scand 97:830-837
Masteling, Mariana; Ashton-Miller, James A; DeLancey, John O L (2018) Technique development and measurement of cross-sectional area of the pubovisceral muscle on MRI scans of living women. Int Urogynecol J :
Tracy, Paige V; Wadhwani, Shreya; Triebwasser, Jourdan et al. (2018) On the variation in maternal birth canal in vivo viscoelastic properties and their effect on the predicted length of active second stage and levator ani tears. J Biomech 74:64-71
Sammarco, Anne G; Swenson, Carolyn W; Kamdar, Neil S et al. (2018) Rate of Pelvic Organ Prolapse Surgery Among Privately Insured Women in the United States, 2010-2013. Obstet Gynecol 131:484-492
Berger, Mitchell B; Kolenic, Giselle E; Fenner, Dee E et al. (2018) Structural, functional, and symptomatic differences between women with rectocele versus cystocele and normal support. Am J Obstet Gynecol 218:510.e1-510.e8
Tracy, Paige V; Wineman, Alan S; Orejuela, Francisco J et al. (2018) A constitutive model description of the in vivo material properties of lower birth canal tissue during the first stage of labor. J Mech Behav Biomed Mater 79:213-218
Sammarco, Anne G; Nandikanti, Lahari; Kobernik, Emily K et al. (2017) Interactions among pelvic organ protrusion, levator ani descent, and hiatal enlargement in women with and without prolapse. Am J Obstet Gynecol 217:614.e1-614.e7
Harris, John A; Sammarco, Anne G; Swenson, Carolyn W et al. (2017) Are perioperative bundles associated with reduced postoperative morbidity in women undergoing benign hysterectomy? Retrospective cohort analysis of 16,286 cases in Michigan. Am J Obstet Gynecol 216:502.e1-502.e11
DeLancey, John O L (2017) ""Mommy, how will the baby get out of your tummy? Will it hurt you?"" Am J Obstet Gynecol 217:110-111

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