Jan A Deprest1, Rufus Cartwright2, Hans Peter Dietz3, Luiz Gustavo Oliveira Brito4, Marianne Koch5, Kristina Allen-Brady6, Jittima Manonai7, Adi Y Weintraub8, John W F Chua9, Romana Cuffolo10, Felice Sorrentino11, Laura Cattani12, Judith Decoene12, Anne-Sophie Page12, Natalie Weeg3, Glaucia M Varella Pereira4, Marina Gabriela M C Mori da Cunha de Carvalho12, Katerina Mackova12, Lucie Hajkova Hympanova12, Pamela Moalli13, Oksana Shynlova14, Marianna Alperin15, Maria Augusta T Bortolini16. 1. Department Development and Regeneration, Cluster Urogenital Surgery, Biomedical Sciences, and Clinical Department Obstetrics and Gynaecology, University Hospitals Leuven, KU Leuven, Herestraat 49, B-3000, Leuven, Belgium. jan.deprest@uzleuven.be. 2. Department of Epidemiology & Biostatistics, Imperial College London, Norfolk Place, London and Department of Urogynaecology, LNWH NHS Trust, London, UK. 3. Sydney Medical School Nepean, Nepean Hospital, Penrith, NSW, 2750, Australia. 4. Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil. 5. Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria. 6. Department of Internal Medicine, Genetic Epidemiology, University of Utah, Salt Lake City, UT, USA. 7. Department of Obstetrics and Gynaecology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 8. Department of Obstetrics and Gynecology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. 9. Department of Gynecology, Zhongshan Hospital, Fudan University, Shanghai, China. 10. Department of Obstetrics & Gynaecology, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK. 11. Department of Medical and Surgical Sciences, Institute of Obstetrics and Gynecology, University of Foggia, Foggia, Italy. 12. Department Development and Regeneration, Cluster Urogenital Surgery, Biomedical Sciences, and Clinical Department Obstetrics and Gynaecology, University Hospitals Leuven, KU Leuven, Herestraat 49, B-3000, Leuven, Belgium. 13. Division of Urogynecology & Pelvic Reconstructive Surgery, UPMC Magee-Womens Hospital, Pittsburgh, PA, USA. 14. Department of Obstetrics, Gynaecology and Physiology, Lunenfeld-Tanenbaum Research Institute, University of Toronto, Toronto, ON, Canada. 15. Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, School of Medicine, San Diego, CA, USA. 16. Department of Gynecology, Sector of Urogynecology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Abstract
INTRODUCTION AND HYPOTHESIS: This manuscript is the International Urogynecology Consultation (IUC) on pelvic organ prolapse (POP) chapter one, committee three, on the Pathophysiology of Pelvic Organ Prolapse assessing genetics, pregnancy, labor and delivery, age and menopause and animal models. MATERIALS AND METHODS: An international group of urogynecologists and basic scientists performed comprehensive literature searches using pre-specified terms in selected biomedical databases to summarize the current knowledge on the pathophysiology of the development of POP, exploring specifically factors including (1) genetics, (2) pregnancy, labor and delivery, (3) age and menopause and (4) non-genetic animal models. This manuscript represents the summary of three systematic reviews with meta-analyses and one narrative review, to which a basic scientific comment on the current understanding of pathophysiologic mechanisms was added. RESULTS: The original searches revealed over 15,000 manuscripts and abstracts which were screened, resulting in 202 manuscripts that were ultimately used. In the area of genetics the DNA polymorphisms rs2228480 at the ESR1 gene, rs12589592 at the FBLN5 gene, rs1036819 at the PGR gene and rs1800215 at the COL1A1 gene are significantly associated to POP. In the area of pregnancy, labor and delivery, the analysis confirmed a strong etiologic link between vaginal birth and symptoms of POP, with the first vaginal delivery (OR: 2.65; 95% CI: 1.81-3.88) and forceps delivery (OR: 2.51; 95% CI: 1.24-3.83) being the main determinants. Regarding age and menopause, only age was identified as a risk factor (OR : 1.102; 95% CI: 1.02-1.19) but current data do not identify postmenopausal status as being statistically associated with POP. In several animal models, there are measurable effects of pregnancy, delivery and iatrogenic menopause on the structure/function of vaginal support components, though not on the development of POP. CONCLUSIONS: Genetics, vaginal birth and age all have a strong etiologic link to the development of POP, to which other factors may add or protect against the risk.
INTRODUCTION AND HYPOTHESIS: This manuscript is the International Urogynecology Consultation (IUC) on pelvic organ prolapse (POP) chapter one, committee three, on the Pathophysiology of Pelvic Organ Prolapse assessing genetics, pregnancy, labor and delivery, age and menopause and animal models. MATERIALS AND METHODS: An international group of urogynecologists and basic scientists performed comprehensive literature searches using pre-specified terms in selected biomedical databases to summarize the current knowledge on the pathophysiology of the development of POP, exploring specifically factors including (1) genetics, (2) pregnancy, labor and delivery, (3) age and menopause and (4) non-genetic animal models. This manuscript represents the summary of three systematic reviews with meta-analyses and one narrative review, to which a basic scientific comment on the current understanding of pathophysiologic mechanisms was added. RESULTS: The original searches revealed over 15,000 manuscripts and abstracts which were screened, resulting in 202 manuscripts that were ultimately used. In the area of genetics the DNA polymorphisms rs2228480 at the ESR1 gene, rs12589592 at the FBLN5 gene, rs1036819 at the PGR gene and rs1800215 at the COL1A1 gene are significantly associated to POP. In the area of pregnancy, labor and delivery, the analysis confirmed a strong etiologic link between vaginal birth and symptoms of POP, with the first vaginal delivery (OR: 2.65; 95% CI: 1.81-3.88) and forceps delivery (OR: 2.51; 95% CI: 1.24-3.83) being the main determinants. Regarding age and menopause, only age was identified as a risk factor (OR : 1.102; 95% CI: 1.02-1.19) but current data do not identify postmenopausal status as being statistically associated with POP. In several animal models, there are measurable effects of pregnancy, delivery and iatrogenic menopause on the structure/function of vaginal support components, though not on the development of POP. CONCLUSIONS: Genetics, vaginal birth and age all have a strong etiologic link to the development of POP, to which other factors may add or protect against the risk.
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