Abstract:
BACKGROUND:Pelvic organ prolapse is common, but the underlying etiologies are poorly understood, which limits our current prevention and treatment options. OBJECTIVE:Our primary objective was to compare the uterosacral ligament histologic features in women with and without prolapse using the novel pelvic organ prolapse histologic quantification system. Our secondary aim was to determine whether composite histologic findings in uterosacral ligaments are associated with prolapse risk factors. STUDY DESIGN:This was a prospective cohort study in which paracervical uterosacral ligament biopsies were performed at the time of hysterectomy for primary prolapse or other benign gynecologic indications and processed for histologic evaluation. The pelvic organ prolapse quantification system was used to determine the prolapse stage. In this study, 9 prominent histologic features were semiquantitatively scored using the pelvic organ prolapse histologic quantification system in a blinded fashion and compared between prolapse and control groups. Unbiased principal component analysis of these scores was independently performed to identify potential relationships between histologic measures and prolapse risk factors. RESULTS:The histologic scores of 81 prolapse and 33 control ligaments were analyzed. Compared with the control group, women in the prolapse group were significantly older and more likely to be in the menopausal phase. There was no difference in the number of vaginal deliveries, body mass index, hormone use, or smoking status between the groups. To control for baseline differences, patients were also stratified by age over 40 years and menopausal status. Compared with the control group, the prolapse ligaments in the premenopausal group had significantly more loss of smooth muscle fibers within the fascicles (P<.001), increased inflammatory infiltrates of neutrophils within the tissue and perineural inflammatory cells (P<.01 and P=.04, respectively), and reduced neointimal hyperplasia (P=.02). Prolapse ligaments in the postmenopausal group exhibited elevated adipose content compared with that of the control group (P=.05). Amount of fibrillar collagen, total nonvascular smooth muscle, and muscle fiber vesicles of prolapse ligaments did not differ in either the premenopausal or postmenopausal group compared with that of the control group. Unbiased principal component analysis of the histologic scores separated the prolapse ligaments into 3 phenotypes: (1) increased adipose accumulation, (2) increased inflammation, and (3) abnormal vasculature, with variable overlap with controls. Posthoc analysis of these subgroups demonstrated a positive correlation between increasing number of vaginal deliveries and body mass index with increasing adipose content in the adipocyte accumulation and inflammatory phenotype and increasing neointimal hyperplasia in the vascular phenotype. However, only the relationship between vaginal delivery and adipocytes was significant in the adipose phenotype (R2=0.13; P=.04). CONCLUSION:Histologic phenotypes exist in pelvic support ligaments that can be distinguished using the pelvic organ prolapse histologic quantification system and principle component analysis. Vaginal delivery is associated with aberrant adipose accumulation in uterosacral ligaments. Our findings support a multifactorial etiology for pelvic organ prolapse contributing to altered smooth muscle, vasculature, and connective tissue content in crucial pelvic support structures. To confirm these associations and evaluate the biomechanical properties of histologic phenotypes of prolapse, larger studies are warranted. Closing this gap in knowledge will help optimize personalized medicine and help identify targets for prevention and treatment of this complex condition.
journal_name
Am J Obstet Gynecoljournal_title
American journal of obstetrics and gynecologyauthors
Orlicky DJ,Guess MK,Bales ES,Rascoff LG,Arruda JS,Hutchinson-Colas JA,Johnson J,Connell KAdoi
10.1016/j.ajog.2020.10.040subject
Has Abstractpub_date
2021-01-01 00:00:00pages
67.e1-67.e18issue
1eissn
0002-9378issn
1097-6868pii
S0002-9378(20)31270-9journal_volume
224pub_type
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journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(97)70299-0
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abstract:OBJECTIVE:To determine maternal and perinatal outcome in women with severe preeclampsia at <26 weeks according to gestational age at the onset of expectant management and the presence of severe fetal growth restriction (<5th percentile). STUDY DESIGN:Fifty-one patients (53 fetuses; 2 twins) were retrospectively studie...
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doi:10.1016/j.ajog.2015.10.931
更新日期:2016-04-01 00:00:00
abstract::Reductions in publicly funded prenatal care programs in 1981 to 1984 resulted in an increase in unregistered patient deliveries from 7.8% to 14.9% of births at University of California San Diego Medical Center. To assess the economic and perinatal impact of the increasing number of deliveries of women without prenatal...
journal_title:American journal of obstetrics and gynecology
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doi:10.1016/0002-9378(86)90387-x
更新日期:1986-01-01 00:00:00
abstract:OBJECTIVE:We characterized US women's preferred and usual sources of reproductive health care. STUDY DESIGN:Data were drawn from the Women's Health Care Experiences and Preferences Study, an Internet survey of 1078 women aged 18-55 years randomly sampled from a national probability panel. We described and compared wom...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2015.04.025
更新日期:2015-09-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
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journal_title:American journal of obstetrics and gynecology
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更新日期:1985-02-01 00:00:00
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doi:10.1016/0002-9378(75)90500-1
更新日期:1975-12-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
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更新日期:1973-06-15 00:00:00
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更新日期:1991-10-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2009.07.049
更新日期:2010-01-01 00:00:00
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doi:10.1067/mob.2001.117969
更新日期:2001-10-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
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更新日期:2009-04-01 00:00:00
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更新日期:1993-02-01 00:00:00
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doi:10.1016/j.ajog.2011.01.056
更新日期:2011-06-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2007-06-01 00:00:00
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更新日期:2000-01-01 00:00:00
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更新日期:1979-05-15 00:00:00
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更新日期:1986-11-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2004-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:1986-06-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
pub_type: 临床试验,杂志文章
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更新日期:1975-12-15 00:00:00