International Urogynecological Consultation (IUC): pathophysiology of pelvic organ prolapse (POP)

Jan A Deprest; Rufus Cartwright; Hans Peter Dietz; Luiz Gustavo Oliveira Brito; Marianne Koch; Kristina Allen-Brady; Jittima Manonai; Adi Y Weintraub; John W F Chua; Romana Cuffolo; Felice Sorrentino; Laura Cattani; Judith Decoene; Anne-Sophie Page; Natalie Weeg; Glaucia M Varella Pereira; Marina Gabriela M C Mori da Cunha de Carvalho; Katerina Mackova; Lucie Hajkova Hympanova; Pamela Moalli; Oksana Shynlova; Marianna Alperin; Maria Augusta T Bortolini

doi:10.1007/s00192-022-05081-0

International Urogynecological Consultation (IUC): pathophysiology of pelvic organ prolapse (POP)

Int Urogynecol J. 2022 Jul;33(7):1699-1710. doi: 10.1007/s00192-022-05081-0. Epub 2022 Mar 10.

Authors

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

Affiliations

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.

PMID: 35267063
DOI: 10.1007/s00192-022-05081-0

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.

Keywords: Age; Delivery; Genetics; Hormones; Labor; Menopause; Pathogenesis; Pelvic organ prolapse; Pregnancy; Risk factor.

Publication types

Review

MeSH terms

Delivery, Obstetric / adverse effects
Female
Humans
Parturition
Pelvic Organ Prolapse* / genetics
Pregnancy
Referral and Consultation
Vagina