|
1
|
Ouyang Y, Peng Y, Zheng M, Mao Y, Gong F, Li Y, Chen H, Li X. The impact of intrauterine adhesions on endometrial receptivity in patients undergoing in vitro fertilization-embryo transfer. Front Endocrinol (Lausanne) 2025; 15:1489839. [PMID: 39906037 PMCID: PMC11790458 DOI: 10.3389/fendo.2024.1489839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 12/27/2024] [Indexed: 02/06/2025] Open
Abstract
Objective To clarify whether intrauterine adhesions (IUAs) affect endometrial receptivity (ER) on the day of ovulation and to compare patients with mild and moderate-severe adhesions. Methods This prospective cohort study included 592 infertile women with IUAs who underwent frozen-thawed embryo transfer (FET). Patients were divided into groups with or without IUAs; and pregnant and nonpregnant populations based on whether a clinical pregnancy was achieved. The ultrasound ER parameters on the ovulation day were compared. Patients with IUAs were then divided into mild or moderate-severe IUA subgroups according to IUA degree. Results The proportions of patients with Type B plus Type C endometrial morphology (94% vs. 75%, P<0.001), an endometrial thickness≥8mm (97% vs. 81%, P<0.001), an endometrial volume≥2ml (94% vs. 67%, P<0.001), a frequency of endometrial peristalsis≥2 times/min (84% vs. 53%, P<0.001), low subendometrial volume (11.54 ± 2.94 vs. 9.57 ± 2.35, P<0.001) and subendometrial vascularization flow index (VFI) values (2.70 ± 3.10 vs. 2.23 ± 2.23, P=0.033) and a low live birth rate (65% vs. 56%, P=0.039) were significantly higher in the group without IUAs than in the group with IUAs. The group with moderate-severe IUAs had lower proportion of patients with an endometrial thickness≥8mm (73% vs. 89%, P=0.008) and an endometrial volume ≥2ml (58% vs. 78%, P=0.005), a lower frequency of endometrial peristalsis≥2 times/min (42% vs. 65%, P=0.003), and low subendometrial volume (9.22 ± 2.29 vs. 9.97 ± 2.36, P=0.023) and subendometrial flow index (FI) (31.48 ± 3.64 vs. 33.43 ± 4.17, P=0.002) values than the group with mild IUAs; a high antral follicle count (AFC), basal follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH) levels and an endometrial thickness≥8mm were independent predictors of clinical pregnancy. Conclusion IUAs can affect ER on the ovulation day and the live birth rate during natural cycles. Moderate-severe IUAs have a greater impact on ER than mild adhesions do; however, if these adhesions are treated properly, they do not have adverse effects on the clinical pregnancy rate. A high AFC, basal FSH and AMH levels and an endometrial thickness ≥8 mm were found to be independent predictors of clinical pregnancy.
Collapse
Affiliation(s)
- Yan Ouyang
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
| | - Yangqin Peng
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- College of Information Science and Engineering, Hunan University, Changsha, China
| | - Mingxiang Zheng
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
| | - Yuyao Mao
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
| | - Fei Gong
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Sciences, Central South University, Hunan University, Changsha, China
| | - Yuan Li
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
| | - Hui Chen
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
| | - Xihong Li
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China
| |
Collapse
|
|
2
|
Hong W, Wu Z, Li L, Wang B, Li X. Intrauterine adhesions treated with hysteroscopic adhesiolysis and subsequent obstetric outcome: A retrospective matched cohort study. BJOG 2025; 132:155-164. [PMID: 38418403 DOI: 10.1111/1471-0528.17793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 12/12/2023] [Accepted: 02/06/2024] [Indexed: 03/01/2024]
Abstract
OBJECTIVE To examine whether a history of hysteroscopic adhesiolysis (HA)-treated intrauterine adhesions (IUAs) was associated with an increased risk of adverse obstetrical outcomes in subsequent pregnancies. DESIGN Retrospective cohort study. SETTING A tertiary-care hospital in Shanghai, China. POPULATION A cohort of 114 142 pregnant women who were issued an antenatal card and received routine antenatal care in Shanghai First Maternity and Infant Hospital, between January 2016 and October 2021. METHODS From the cohort of 114 142 pregnant women, each woman with a history of HA-treated IUA prior to the current pregnancy (n = 780) was matched with four women without a history of IUAs (n = 3010) using propensity score matching. The matching variables were maternal age and parity, mode of conception, pre-pregnancy body mass index and prior history of abortion. MAIN OUTCOME MEASURES Pregnancy complications, placental abnormalities, postpartum haemorrhage and adverse birth outcomes. RESULTS Compared with women with no history of IUAs, women with a history of HA-treated IUAs were at higher risk of pre-eclampsia (RR 1.69, 95% CI 1.23-2.33), placenta accreta spectrum (RR 4.72, 95% CI 3.9-5.73), placenta praevia (RR 4.23, 95% CI 2.85-6.30), postpartum haemorrhage (RR 2.86, 95% CI 1.94-4.23), preterm premature rupture of membranes (RR 3.02, 95% CI 1.97-4.64) and iatrogenic preterm birth (RR 2.86, 95% CI 2.14-3.81). Those women were also more likely to receive cervical cerclage (RR 5.63, 95% CI 3.95-8.02) during pregnancy and haemostatic therapies after delivery (RR 2.17, 95% CI 1.75-2.69). Moreover, we observed that the RRs of those adverse obstetrical outcomes increased with the increasing number of hysteroscopic surgeries. CONCLUSIONS This study found that a history of HA-treated IUAs, especially a history of repeated HAs, was associated with an increased risk of adverse obstetrical outcomes.
Collapse
Affiliation(s)
- Wei Hong
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Zhiping Wu
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Li Li
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Beiying Wang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xiaocui Li
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| |
Collapse
|
|
3
|
Luo Y, Sun Y, Huang B, Chen J, Xu B, Li H. Effects and safety of hyaluronic acid gel on intrauterine adhesion and fertility after intrauterine surgery: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials. Am J Obstet Gynecol 2024; 231:36-50.35. [PMID: 38191020 DOI: 10.1016/j.ajog.2023.12.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 12/19/2023] [Accepted: 12/28/2023] [Indexed: 01/10/2024]
Abstract
OBJECTIVE This study aimed to determine the efficacy and safety of hyaluronic acid gel for the prevention of intrauterine adhesions and improved fertility after intrauterine surgery. DATA SOURCES PubMed, EMBASE, Cochrane Library, Web of science, and ClinicalTrials.gov were searched up to November 1, 2023. STUDY ELIGIBILITY CRITERIA Randomized controlled trials that reported intrauterine adhesion and fertility outcomes among women who used hyaluronic acid after intrauterine surgery. METHODS The risk of bias was assessed using criteria of the Cochrane Handbook, and the quality of the evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A trial sequential analysis was conducted to assess the outcomes, and Stata 14 was used for sensitivity analyses and publication bias analyses. RESULTS Data from 16 randomized controlled trials involving 2359 patients were extracted and analyzed. The analysis revealed that hyaluronic acid reduced the incidence of intrauterine adhesion (risk ratio, 0.53; 95% confidence interval, 0.42-0.67; I2=48%) and improve pregnancy rates (risk ratio, 1.24; 95% confidence interval, 1.02-1.50; I2=0%). A subgroup analysis was conducted to evaluate factors that influence the effect of hyaluronic acid on the incidence of intrauterine adhesion. It was found that a small volume of hyaluronic acid reduced the incidence of intrauterine adhesions. Hyaluronic acid exhibited a protective effect among patients who underwent various intrauterine surgeries and who had different gynecologic medical histories. The protective effect was statistically significant after a follow-up of 6 to 12 weeks. The results of the trial sequential analysis indicated that the effect of hyaluronic acid on the incidence of mild intrauterine adhesions, pregnancy rates, live birth rates, and miscarriage rates after intrauterine surgery may be inconclusive and thus further evaluation is required in the form of additional clinical trials. However, the remaining effects were found to be verifiable and did not require more clinical trials for confirmation. CONCLUSION Hyaluronic acid can safely and effectively reduce the incidence of intrauterine adhesions and may improve fertility outcomes.
Collapse
Affiliation(s)
- Yan Luo
- Department of Reproductive Medicine, Xiangya Hospital, Central South University, Changsha, China; Clinical Medicine Eight-Year Program, Xiangya Hospital, Central South University, Changsha, China
| | - Yuanyuan Sun
- Department of Reproductive Medicine, Xiangya Hospital, Central South University, Changsha, China; Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha, China
| | - Bixia Huang
- Department of Reproductive Medicine, Xiangya Hospital, Central South University, Changsha, China; Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha, China
| | - Jingjing Chen
- Department of Reproductive Medicine, Xiangya Hospital, Central South University, Changsha, China; Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha, China
| | - Bin Xu
- Department of Reproductive Medicine, Xiangya Hospital, Central South University, Changsha, China; Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha, China.
| | - Hui Li
- Department of Reproductive Medicine, Xiangya Hospital, Central South University, Changsha, China; Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha, China; Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
| |
Collapse
|
|
4
|
Schmerold L, Martin C, Mehta A, Sobti D, Jaiswal AK, Kumar J, Feldberg I, Munro MG, Lee WC. A cost-effectiveness analysis of intrauterine spacers used to prevent the formation of intrauterine adhesions following endometrial cavity surgery. J Med Econ 2024; 27:170-183. [PMID: 38131367 DOI: 10.1080/13696998.2023.2298584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 12/20/2023] [Indexed: 12/23/2023]
Abstract
AIM To assess, from a United States (US) payer's perspective, the cost-effectiveness of gels designed to separate the endometrial surfaces (intrauterine spacers) placed following intrauterine surgery. MATERIALS AND METHODS A decision tree model was developed to estimate the cost-effectiveness of intrauterine spacers used to facilitate endometrial repair and prevent the formation (primary prevention) and reformation (secondary prevention) of intrauterine adhesions (IUAs) and associated pregnancy- and birth-related adverse outcomes. Event rates and costs were extrapolated from data available in the existing literature. Sensitivity analyses were conducted to corroborate the base case results. RESULTS In this model, using intrauterine spacers for adhesion prevention led to net cost savings for US payers of $2,905 per patient over a 3.5-year time horizon. These savings were driven by the direct benefit of preventing procedures associated with IUA formation ($2,162 net savings) and the indirect benefit of preventing pregnancy-related complications often associated with IUA formation ($3,002). These factors offset the incremental cost of intrauterine spacer use of $1,539 based on an assumed price of $1,800 and the related increase in normal deliveries of $931. Model outcomes were sensitive to the probability of preterm and normal deliveries. Budget impact analyses show overall cost savings of $19.96 per initial member within a US healthcare plan, translating to $20 million over a 5-year time horizon for a one-million-member plan. LIMITATIONS There are no available data on the effects of intrauterine spacers or IUAs on patients' quality of life. Resultingly, the model could not evaluate patients' utility related to treatment with or without intrauterine spacers and instead focused on costs and events avoided. CONCLUSION This analysis robustly demonstrated that intrauterine spacers would be cost-saving to healthcare payers, including both per-patient and per-plan member, through a reduction in IUAs and improvements to patients' pregnancy-related outcomes.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Malcolm G Munro
- Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | | |
Collapse
|
|
5
|
Zhao F, Wei W, Huang D, Guo Y. Knockdown of miR-27a reduces TGFβ-induced EMT and H 2O 2-induced oxidative stress through regulating mitochondrial autophagy. Am J Transl Res 2023; 15:6071-6082. [PMID: 37969181 PMCID: PMC10641347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 09/22/2023] [Indexed: 11/17/2023]
Abstract
OBJECTIVES The present research aimed at clarifying the role played by miR-27a in the context of intrauterine adhesion (IUA) by focusing on its impact on TGFβ1-induced epithelial-mesenchymal transition (EMT), migration, oxidative stress, and mitochondrial autophagy in endometrial stromal cells (ESCs). METHODS We employed the Cell Counting Kit CCK-8/WST-8 assay to assess ESC proliferation, flow cytometric analysis and an Annexin-V-FITCV-FITC Apoptosis Detection kit to determine cell apoptosis, and wound healing and transwell assays to evaluate cell migration. Besides, intracellular reactive oxygen species (ROS) levels measured by the Reactive Oxygen Species Assay Kit were analyzed by flow cytometry, and protein expression levels were quantified by Western blotting analysis. RESULTS Knockdown of miR-27a inhibited TGFβ1-induced EMT and H2O2-induced oxidative stress in ESCs. H2O2-induced miR-27a suppressed PINK1 expression, leading to inhibition of mitophagy. MiR-27a promoted TGFβ1 or H2O2-induced EMT through PINK1. CONCLUSIONS miR-27a plays a crucial role in endometrial fibrosis. It regulates TGFβ1-induced EMT, migration, oxidative stress, and apoptosis in ESCs. Additionally, miR-27a impacts mitophagy through PINK1 suppression upon H2O2 induction. Our findings highlight miR-27a as a potential therapeutic target for IUA treatment, shedding light on its multifaceted involvement in the mechanism of intrauterine adhesion fibrosis.
Collapse
Affiliation(s)
- Fangfang Zhao
- Department of Gynaecology, The First Affiliated Hospital of Guangxi Medical UniversityNanning 530022, Guangxi, P. R. China
| | - Wei Wei
- Department of Gynaecology, The First Affiliated Hospital of Guangxi Medical UniversityNanning 530022, Guangxi, P. R. China
| | - Dongping Huang
- School of Public Health, Guangxi Medical UniversityNanning 530020, Guangxi, P. R. China
| | - Yi Guo
- Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical UniversityNanning 530022, Guangxi, P. R. China
| |
Collapse
|
|
6
|
Guangwei W, Ling M, Qing Y, Yue Y, Yanqiu Y, Silei C, Xiaohan C, Yaoxing R, Zhe C, Yu W. Comparison of the efficacy of autologous platelet gel and medical chitosan in the prevention of recurrence of intrauterine adhesions after transcervical resection of adhesion: a prospective, randomized, controlled trial. Arch Gynecol Obstet 2023; 308:1369-1378. [PMID: 37552284 DOI: 10.1007/s00404-023-07175-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 07/23/2023] [Indexed: 08/09/2023]
Abstract
PURPOSE Intrauterine adhesion (IUAs) in women is a debatable topic and there is no clear consensus in its management and treatment strategies. Previous treatment measures have limitations which necessitates to consider effective measures for prevention of recurrence of IUAs. Hence, the aim of this study to explore the efficacy and safety of intrauterine infusion of autologous platelet gel (APG) and medical chitosan in preventing recurrence of IUAs in females after transcervical resection of adhesion (TCRA). METHODS A prospective, randomized controlled trial was conducted among 80 patients presented with moderate to severe IUAs. Patients were randomized into two groups, APG group (n = 40) and medical chitosan group (n = 40). All patients were injected with either APG or medical chitosan after TCRA. RESULTS The postoperative recurrence rate of adhesions in APG group was significantly lower than those in medical chitosan group (21% vs 49%). The median AFS score during the second-look hysteroscopy was significantly lower in APG group than in medical chitosan group (P = 0.008). The median AFS score reduction after TCRA surgery was significantly higher in APG group than in medical chitosan group (median, 95% CI 7.000, 6.0 to 8.3 vs. 6.000, 5.0 to 7.0, P = 0.004). Subgroup analysis of platelet concentration (1000 as cut-off value) into high- and low-dose subgroups reported no significant correlation existed between APG and baseline characteristics, recurrence rate and postoperative AFS reduction score except for previous intrauterine operation (P < 0.05). CONCLUSION Thus, after TCRA, intrauterine injections of APG provides better efficacy and safety compared with intrauterine injections of medical chitosan in preventing recurrence of intrauterine adhesions.
Collapse
Affiliation(s)
- Wang Guangwei
- Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004, China
| | - Ma Ling
- Department of Pathophysiology, China Medical University, Taichung, China
| | - Yang Qing
- Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004, China
| | - You Yue
- Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004, China
| | - Yu Yanqiu
- Department of Pathophysiology, China Medical University, Taichung, China
- Shenyang Cell Therapy Engineering Technology R&D Center Co., Ltd., Jiading, China
| | - Chen Silei
- Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004, China
| | - Chang Xiaohan
- Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004, China
| | - Rong Yaoxing
- Shenyang Cell Therapy Engineering Technology R&D Center Co., Ltd., Jiading, China
| | - Chen Zhe
- Shenyang Cell Therapy Engineering Technology R&D Center Co., Ltd., Jiading, China
| | - Wang Yu
- Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004, China.
| |
Collapse
|
|
7
|
Khan Z. Etiology, Risk Factors, and Management of Asherman Syndrome. Obstet Gynecol 2023; 142:543-554. [PMID: 37490750 DOI: 10.1097/aog.0000000000005309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 06/20/2023] [Indexed: 07/27/2023]
Abstract
Asherman syndrome is characterized by a triad of symptoms including pain, menstrual abnormalities, and infertility and is a result of intrauterine scar tissue after instrumentation of a gravid uterus. Saline sonohysterogram is typically the most sensitive diagnostic tool; however, hysteroscopy is the criterion standard for diagnosis. Treatment includes hysteroscopic-guided lysis of adhesion, with restoration of the anatomy of the uterine cavity. Several modalities are used in an attempt to reduce the reformation of scar tissue after surgery; however, there is no consensus on the ideal method. Stem cells and platelet-rich plasma are being explored as means of regenerative therapy for the endometrium, but data remain limited. At present, most individuals can have restoration of menstrual function; however, lower pregnancy rates and obstetric complications are not uncommon. These complications are worse for patients with a higher grade of disease. Efforts are needed in standardizing classification, reducing uterine instrumentation of the gravid uterus, and referring patients to health care professionals with clinical expertise in this area.
Collapse
Affiliation(s)
- Zaraq Khan
- Division of Reproductive Endocrinology & Infertility and the Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics & Gynecology, Mayo Clinic, Rochester, Minnesota
| |
Collapse
|
|
8
|
Hooker AB, de Leeuw RA, Emanuel MH, Mijatovic V, Brolmann HAM, Huirne JA. The link between intrauterine adhesions and impaired reproductive performance: a systematic review of the literature. BMC Pregnancy Childbirth 2022; 22:837. [PMID: 36376829 PMCID: PMC9664654 DOI: 10.1186/s12884-022-05164-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 10/29/2022] [Indexed: 11/16/2022] Open
Abstract
Background Intrauterine adhesions (IUAs) are one of the main reproductive system diseases in women worldwide. Fusion between the injured opposing walls leads to partial-to-complete obliteration of the cavity and/or cervical canal. The main clinical manifestations in case of IUAs are menstrual disturbances, cyclic pain and reproductive disorders. The reproductive outcomes of women with IUAs remain limited and inefficient compared to women without IUAs, even after adhesiolysis. An exact understanding of the underlying mechanisms and processes to explain the compromised reproductive performance and outcomes in case of IUAs are lacking. Methods A systematic literature review of MEDLINE-PubMed (1966 to January 2022) and EMBASE (1974 to January 2022) was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if they reported underlying causes, related mechanisms and processes to explain the association between IUAs and impaired reproductive performance, pregnancy and obstetric complications. Results After an extensive review of the literature, 58 articles were identified reporting underlying mechanisms to explain the association between IUAs and impaired fertility. Intrauterine scarring influences the process of fertilization, reproductive performance and ultimately reproductive outcome. IUAs can disturb the cervico-utero-tubal sperm transport and result in an avascular and unresponsive endometrium with decreased receptivity and thickness. Abnormal decidualization and abnormal trophoblastic infiltration leads to placental attachment disorders. Moreover, the risk for premature delivery, intrauterine fetal growth restriction and fetal anomalies is increased in case of IUAs. Conclusion The impact of IUAs on reproductive performance, even after adhesiolysis, is becoming more apparent. The postulated mechanisms to explain the association are related to sperm transport, embryo implantation and placentation. Prevention, by preserving the basal layer of the endometrium is essential. Effective and evidence-based strategies for the prevention of endometrial injury and formation of IUAs, are urgently needed. Supplementary Information The online version contains supplementary material available at 10.1186/s12884-022-05164-2.
Collapse
|
|
9
|
Yang H, Jiang X, Chen T, Yao Z, Xu X, Wu L, Zhu X. A novel technique for moderate to severe intrauterine adhesions: A historical cohort study. Medicine (Baltimore) 2022; 101:e30480. [PMID: 36086753 PMCID: PMC10980481 DOI: 10.1097/md.0000000000030480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 08/02/2022] [Indexed: 11/25/2022] Open
Abstract
To evaluate the feasibility and efficiency of our novel technique, ultrasound guided hysteroscopic catheter dilation (US-HCD), for the treatment of moderate to severe intrauterine adhesion (IUA). A total of 126 patients diagnosed with IUA and met the enrollment criteria were admitted in this historical cohort study from June 1, 2016 to December 31, 2018. All patients were divided into 2 groups according to the surgical techniques used. Group A (n = 68) were treated with traditional hysteroscopic adhesiolysis with scissors (THA) and Group B (n = 58) were treated with US-HCD. Their data for the next 2 years following the initial surgery were analyzed. Safety and feasibility (operation time, surgical complications and the third-look hysteroscopic surgery rate), and post-operation efficacy (reduction of American Fertility Society [AFS] scores, pregnancy and live birth rates) were evaluated between groups. Between the groups, there was no statistically significant differences in basic preoperative information and AFS scores (P > .05). While there were significant differences in the operation time of the initial surgery (P < .05) and reduction of AFS scores (P < .05). No surgical complications were recorded and only 3 patients (5.2%) received a third-look hysteroscopy in Group B, while there were 6 cases of complications and 13 cases (19.1%) of third-look hysteroscopy in Group A, indicating significant differences between Groups (P < .05). Both groups exhibited comparable pregnancy rate, live birth rate and obstetric complications (P > .05). Our new technique is a safe, feasible and effective procedure for moderate to severe IUA patients, which can be mastered more quickly and easily by surgeons and applied in areas with less affluent economy and without hysteroscopic scissors, thus worthy of further study.
Collapse
Affiliation(s)
- Huadi Yang
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Xuelu Jiang
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Ting Chen
- Department of Ultrasonography, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Zhitao Yao
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Xuqun Xu
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Li Wu
- Department of Center of Clinical Evaluation, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Xiaojing Zhu
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| |
Collapse
|
|
10
|
Zizolfi B, Saccone G, Cancelliere E, Carugno J, Gallo A, De Angelis MC, Di Spiezio Sardo A. Hysteroscopic and ultrasound evaluation of a novel degradable polymer film for the prevention of intrauterine adhesion formation after hysteroscopic surgery. Eur J Obstet Gynecol Reprod Biol 2022; 275:54-58. [PMID: 35728489 DOI: 10.1016/j.ejogrb.2022.06.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 06/03/2022] [Accepted: 06/12/2022] [Indexed: 11/17/2022]
Abstract
OBJECTIVE To collect information on the application and behavior of a novel degradable polymeric film (DPF) developed to prevent intra-uterine adhesions (IUAs) after hysteroscopic surgery. STUDY DESIGN A prospective observational study conducted in a university hospital in Naples, Italy. Women undergoing hysteroscopic myomectomy, metroplasty or adhesiolysis, were eligible for the study. Women had their uterine cavity assessed by transvaginal ultrasound scan before their hysteroscopic surgery, which was followed by the DPF insertion. Ultrasonographic and hysteroscopic assessments were undertaken immediately after insertion then at 2 h, 2-5 days, and 6 weeks postoperative. The main outcome of interest was to assess the behavior of the DPF, from insertion to degradation, by ultrasound and hysteroscopy. Other outcomes included ease of DPF insertion, any patient reported adverse events and the presence of IUAs at 6 weeks. MEASUREMENTS AND MAIN RESULTS A total of 15 patients were enrolled into the study. The DPF insertion was reported to be very easy in almost all the cases and was visualized immediately and 2 h after insertion in all patients. At the 2-5 day follow-up 5 and 2 of the 15 participants still had the entire or partially hydrolyzed film respectively. By 6 weeks there was no evidence of the DPF in all women. No adverse events were reported at the time of insertion or follow-up. None of the study participants had IUAs at the 6-week assessment. CONCLUSIONS According to this pilot study, the solid degradable polymer film, Womed Leaf, is a promising, easy to apply and well tolerated novel option for the prevention of intrauterine adhesion formation after hysteroscopic surgery.
Collapse
Affiliation(s)
- Brunella Zizolfi
- Department of Public Health, School of Medicine, University of Naples Federico II, Naples, Italy.
| | - Gabriele Saccone
- Department of Neuroscience, Reproductive Science, and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Elena Cancelliere
- Department of Neuroscience, Reproductive Science, and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Jose Carugno
- Obstetrics, Gynecology and Reproductive Science Department, Minimally Invasive Gynecology Division, University of Miami, Miller School of Medicine, Miami, FL USA
| | - Alessandra Gallo
- Department of Neuroscience, Reproductive Science, and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Maria Chiara De Angelis
- Department of Neuroscience, Reproductive Science, and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Attilio Di Spiezio Sardo
- Department of Public Health, School of Medicine, University of Naples Federico II, Naples, Italy
| |
Collapse
|
|
11
|
Sroussi J, Lecurieux-Lafayette C, Benifla JL. First Use Of A Novel Barrier Film In An Infertile Woman With Severe Asherman Syndrome. J Minim Invasive Gynecol 2022; 29:1129-1130. [PMID: 35705163 DOI: 10.1016/j.jmig.2022.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/06/2022] [Accepted: 06/08/2022] [Indexed: 10/18/2022]
Affiliation(s)
- Jeremy Sroussi
- Lariboisière hospital, Department of Obstetrics and Gynaecology, Paris, France..
| | | | - Jean Louis Benifla
- Lariboisière hospital, Department of Obstetrics and Gynaecology, Paris, France
| |
Collapse
|
|
12
|
Bark HS, Maeng I, Kim JU, Kim KD, Na JH, Min J, Byun J, Song Y, Cha BY, Oh SJ, Ji YB. Terahertz Spectral Properties of PEO-Based Anti-Adhesion Films Cross-Linked by Electron Beam Irradiation. Polymers (Basel) 2022; 14:polym14102008. [PMID: 35631892 PMCID: PMC9147511 DOI: 10.3390/polym14102008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/09/2022] [Accepted: 05/11/2022] [Indexed: 01/27/2023] Open
Abstract
We investigated the spectral property changes in anti-adhesion films, which were cross-linked and surface-modified through electron beam irradiation, using terahertz time-domain spectroscopy (THz-TDS). Polyethylene oxide (PEO), which is a biocompatible and biodegradable polymer, was the main component of these anti-adhesion films being manufactured for testing. The terahertz characteristics of the films were affected by the porosity generated during the freeze-drying and compression processes of sample preparation, and this was confirmed using optical coherence tomography (OCT) imaging. An anti-adhesion polymer film made without porosity was measured by using the THz-TDS method, and it was confirmed that the refractive index and absorption coefficient were dependent on the crosslinking state. To our knowledge, this is the first experiment on the feasibility of monitoring cross-linking states using terahertz waves. The THz-TDS method has potential as a useful nondestructive technique for polymer inspection and analysis.
Collapse
Affiliation(s)
- Hyeon Sang Bark
- Radiation Center for Ultrafast Science, Korea Atomic Energy Research Institute (KAERI), Deajeon 34057, Korea;
| | - Inhee Maeng
- YUHS-KRIBB Medical Convergence Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea;
| | - Jin Un Kim
- HW Tech, Yangsan 50585, Korea; (J.U.K.); (K.D.K.)
| | | | - Jae Hun Na
- Gimhae Biomedical Center, Gimhae Biomedical Industry Promotion Agency (GBIA), Gimhae 50969, Korea; (J.H.N.); (J.M.); (J.B.); (Y.S.); (B.-y.C.)
| | - Junki Min
- Gimhae Biomedical Center, Gimhae Biomedical Industry Promotion Agency (GBIA), Gimhae 50969, Korea; (J.H.N.); (J.M.); (J.B.); (Y.S.); (B.-y.C.)
| | - Jungsup Byun
- Gimhae Biomedical Center, Gimhae Biomedical Industry Promotion Agency (GBIA), Gimhae 50969, Korea; (J.H.N.); (J.M.); (J.B.); (Y.S.); (B.-y.C.)
| | - Yongkeun Song
- Gimhae Biomedical Center, Gimhae Biomedical Industry Promotion Agency (GBIA), Gimhae 50969, Korea; (J.H.N.); (J.M.); (J.B.); (Y.S.); (B.-y.C.)
| | - Byung-youl Cha
- Gimhae Biomedical Center, Gimhae Biomedical Industry Promotion Agency (GBIA), Gimhae 50969, Korea; (J.H.N.); (J.M.); (J.B.); (Y.S.); (B.-y.C.)
| | - Seung Jae Oh
- YUHS-KRIBB Medical Convergence Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea;
- Correspondence: (S.J.O.); (Y.B.J.)
| | - Young Bin Ji
- Gimhae Biomedical Center, Gimhae Biomedical Industry Promotion Agency (GBIA), Gimhae 50969, Korea; (J.H.N.); (J.M.); (J.B.); (Y.S.); (B.-y.C.)
- Correspondence: (S.J.O.); (Y.B.J.)
| |
Collapse
|
|
13
|
Short-and long-term outcomes of postoperative intrauterine application of hyaluronic acid gel: a meta-analysis of randomized controlled trials. J Minim Invasive Gynecol 2022; 29:934-942. [DOI: 10.1016/j.jmig.2022.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/03/2022] [Accepted: 05/09/2022] [Indexed: 11/20/2022]
|
|
14
|
Xu X, Kong DS, Tian YP, Xie YL, Zhang JK, Huang XH. Autocross-linked hyaluronic acid gel and adipose-derived mesenchymal stem cell composites for the treatment intrauterine adhesions. Taiwan J Obstet Gynecol 2021; 60:1031-1037. [PMID: 34794733 DOI: 10.1016/j.tjog.2021.09.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/08/2021] [Indexed: 10/19/2022] Open
Abstract
OBJECTIVE To evaluate the effect of adding adipose-derived mesenchymal stem cells (ASCs) to autocross-linked hyaluronic acid (HA) gel for intrauterine adhesion (IUA) treatment. METHODS A rat IUA model was established by mechanical curettage and infection, and then different treatments were administered to the rats on day 7 after modeling. Ninety-six rats were randomly divided into the following groups: IUA model group, gel therapy group, and combination therapy group (HA gel combined with ASCs). Eight rats per group were sacrificed on days 7, 10, 14 and 21 for the subsequent experiments. Morphological changes were determined by hematoxylin-eosin staining and Masson staining. Smad3 and leukocyte inhibitory factor (LIF) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry. RESULTS The endometrial lines in the gel therapy group and the combination therapy group were more complete than those in the model group. Masson staining showed that fibrosis area rates in the gel therapy group and the combination therapy group were significantly lower than those in the model group on day 7(P < 0.05). During the observation period, the fibrosis area rates in the combination therapy group remained lower than those in the model group (P < 0.05). The mRNA expression of Smad3 in the combination therapy group was lower than that in the model group and gel therapy group during the observation period (P < 0.05). The mRNA expression level of LIF in the combination therapy group was higher than that in the model group and the gel therapy group throughout the observation period (P < 0.05). CONCLUSIONS HA gel was effective in preventing the IUA adhesion formation at the early stage of the observation period, while ASC enhanced this effect throughout the observation period. Gel and ASC composites helped to improve endometrial receptivity.
Collapse
Affiliation(s)
- Xin Xu
- Department of Gynecology and Obstetrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - De-Sheng Kong
- Department of Gynecology and Obstetrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yan-Peng Tian
- Department of Gynecology and Obstetrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yan-Ling Xie
- Department of Gynecology and Obstetrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jing-Kun Zhang
- Department of Gynecology and Obstetrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiang-Hua Huang
- Department of Gynecology and Obstetrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
| |
Collapse
|
|
15
|
Taylor C, Ellett L, Hiscock R, Mooney S. Hysteroscopic management of retained products of conception: A systematic review. Aust N Z J Obstet Gynaecol 2021; 62:22-32. [PMID: 34751942 DOI: 10.1111/ajo.13455] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 10/16/2021] [Accepted: 10/20/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND The management of retained products of conception (RPOC) is not well standardised due to a lack of evidence-based guidelines. Hysteroscopic resection has been proven to be safe and is hypothesised to have lower risk than dilation and curettage, but data comparing the two directly are limited. AIM The aim of this study is to evaluate the outcomes for hysteroscopic resection for the management of RPOC in comparison to current standard management techniques. METHODS A literature search was conducted in September 2019 using MEDLINE, Scopus, The Cochrane Library and Web of Science. The key search terms were 'hysteroscopy'/'hysteroscopic resection' and 'retained products of conception'/'RPOC'. Both prospective and retrospective studies were included. A total of 19 studies were included (n = 2314). Due to a critical risk of bias in all studies with a comparison arm, a meta-analysis was not performed. Meta-analysis techniques were still used to provide summary estimates for primary and secondary outcomes, including conception rate, time to conception, live birth rate, intrauterine adhesions (IUAs), surgical complications and future pregnancy complications. RESULTS The overall conception rate for hysteroscopic resection was 81.1% (live birth rate 87.3%) compared to 65.4% for non-hysteroscopic management (live birth rate 93.8%). After hysteroscopic resection the overall complication rate was 1.9% and the IUA rate was 6.8%. CONCLUSIONS Due to the poor quality and overall scarcity of comparative data, the question whether hysteroscopic resection is superior to traditional curettage for the management of RPOC remains unanswered. This review provides summary data, which will enable the design of adequately powered future studies.
Collapse
Affiliation(s)
- Cassandra Taylor
- Department of Obstetrics and Gynaecology, Mercy Hospital for Women, Melbourne, Victoria, Australia.,Department of Obstetrics and Gynaecology, Joan Kirner Women's and Children's Hospital, Western Health, Melbourne, Victoria, Australia
| | - Lenore Ellett
- Department of Obstetrics and Gynaecology, Mercy Hospital for Women, Melbourne, Victoria, Australia
| | - Richard Hiscock
- Mercy Perinatal at Mercy Hospital for Women, Melbourne, Victoria, Australia
| | - Samantha Mooney
- Department of Obstetrics and Gynaecology, Mercy Hospital for Women, Melbourne, Victoria, Australia
| |
Collapse
|
|
16
|
Effectiveness of Hyaluronic Acid Gel and Intrauterine Devices in Prevention of Intrauterine Adhesions after Hysteroscopic Adhesiolysis in Infertile Women. J Minim Invasive Gynecol 2021; 29:284-290. [PMID: 34433103 DOI: 10.1016/j.jmig.2021.08.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 08/13/2021] [Accepted: 08/14/2021] [Indexed: 11/21/2022]
Abstract
STUDY OBJECTIVE To compare the recurrence rate, post-treatment American Fertility Society (AFS) score, ongoing pregnancy rate, and endometrial thickness of 3 secondary prevention therapies in preventing recurrent intrauterine adhesions (IUAs) and increasing pregnancy rates in infertile women after hysteroscopic adhesiolysis. DESIGN A retrospective study. SETTING A private fertility hospital. PATIENTS A total of 200 consecutive infertile women, with the desire to have a baby and were diagnosed as having IUAs detected by hysterosalpingogram, who underwent hysteroscopic adhesiolysis for IUAs from January, 2018 to May, 2020. INTERVENTIONS Women who underwent hysteroscopic adhesiolysis received hormone therapy, and one of the 3 secondary preventions: hyaluronic acid (HA) gel alone, intrauterine devices (IUDs) alone, or HA gel + IUD. MEASUREMENTS AND MAIN RESULTS Of the 200 women included in the final analysis, 121 received HA alone, 59 were treated with IUD alone, and 20 received HA gel + IUD combination. The mean post-treatment AFS score for IUAs was significantly lower in the HA gel + IUD group than the HA alone or the IUD alone groups (adjusted p = .01 and p = .02, respectively). Multivariable analysis revealed a significantly lower recurrence rate in the women after treatment with HA gel + IUD than HA alone (adjusted odds ratio, 0.19; 95% credible interval [CreI], 0.03-0.88). Women treated with HA gel + IUD also had reduced post-treatment AFS scores compared with HA alone (β coefficients, -0.83; 95% CreI, -1.64 to -0.01). For ongoing pregnancy rates after in vitro fertilization, the adjusted odds ratio for HA gel + IUD vs HA alone was 2.03 (95% CreI, 0.44-11.00) and for IUD alone vs HA alone was 1.13 (95% CreI, 0.41-3.29), indicating nonsignificant differences. There were no differences observed in endometrial thickness on the day of embryo transfer among the 3 groups. CONCLUSION The investigation of the primary outcome in reducing the recurrence rate IUA after treatment demonstrated that a combination of HA gel + IUD provides greater prevention of recurrent IUAs and may decrease post-treatment AFS scores for infertile women undergoing hysteroscopic adhesiolysis. However, for the secondary outcome of increasing pregnancy rates, there was no improvement in the ongoing pregnancy rates after in vitro fertilization.
Collapse
|
|
17
|
Lee WL, Liu CH, Cheng M, Chang WH, Liu WM, Wang PH. Focus on the Primary Prevention of Intrauterine Adhesions: Current Concept and Vision. Int J Mol Sci 2021; 22:ijms22105175. [PMID: 34068335 PMCID: PMC8153321 DOI: 10.3390/ijms22105175] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/11/2021] [Accepted: 05/12/2021] [Indexed: 02/07/2023] Open
Abstract
Intrauterine adhesion (IUA), and its severe form Asherman syndrome (Asherman’s syndrome), is a mysterious disease, often accompanied with severe clinical problems contributing to a significant impairment of reproductive function, such as menstrual disturbance (amenorrhea), infertility or recurrent pregnancy loss. Among these, its correlated infertility may be one of the most challenging problems. Although there are many etiologies for the development of IUA, uterine instrumentation is the main cause of IUA. Additionally, more complicated intrauterine surgeries can be performed by advanced technology, further increasing the risk of IUA. Strategies attempting to minimize the risk and reducing its severity are urgently needed. The current review will expand the level of our knowledge required to face the troublesome disease of IUA. It is separated into six sections, addressing the introduction of the normal cyclic endometrial repairing process and its abruption causing the formation of IUA; the etiology and prevalence of IUA; the diagnosis of IUA; the classification of IUA; the pathophysiology of IUA; and the primary prevention of IUA, including (1) delicate surgical techniques, such as the use of surgical instruments, energy systems, and pre-hysteroscopic management, (2) barrier methods, such as gels, intrauterine devices, intrauterine balloons, as well as membrane structures containing hyaluronate–carboxymethylcellulose or polyethylene oxide–sodium carboxymethylcellulose as anti-adhesive barrier.
Collapse
Affiliation(s)
- Wen-Ling Lee
- Department of Medicine, Cheng-Hsin General Hospital, Taipei 112, Taiwan;
- Department of Nursing, Oriental Institute of Technology, Taipei 220, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; (C.-H.L.); (M.C.); (W.-H.C.)
| | - Chia-Hao Liu
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; (C.-H.L.); (M.C.); (W.-H.C.)
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan
| | - Min Cheng
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; (C.-H.L.); (M.C.); (W.-H.C.)
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan
| | - Wen-Hsun Chang
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; (C.-H.L.); (M.C.); (W.-H.C.)
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan
- Department of Nursing, Taipei Veterans General Hospital, Taipei 112, Taiwan
| | - Wei-Min Liu
- Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei 110, Taiwan;
| | - Peng-Hui Wang
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; (C.-H.L.); (M.C.); (W.-H.C.)
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan
- Female Cancer Foundation, Taipei 104, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan
- Correspondence: ; Tel.: +886-2-28757566
| |
Collapse
|
|
18
|
Wu C, Dong Y, Li Y, Liu H. The efficacy of amniotic membrane-mediated sequential double-barrier therapy for the treatment of postoperative intrauterine adhesions. Medicine (Baltimore) 2021; 100:e25416. [PMID: 33847639 PMCID: PMC8051972 DOI: 10.1097/md.0000000000025416] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 03/10/2021] [Indexed: 01/04/2023] Open
Abstract
To study the efficacy of using amniotic membrane, balloon and intrauterine device (IUD) as barrier therapy to prevent re-adhesion after hysteroscopic adhesiolysis.A total of 45 patients diagnosed with intrauterine adhesions in Changzhou Maternal and Child Health Hospital from June 2014 to December 2017 were included in this retrospective case control study. According to different postoperative isolation barrier methods, the patients were divided into group A (Foley balloon + fresh amniotic membrane Day1 + IUD Day7) (22 cases) and group B (Foley balloon Day1 + IUD Day7) (23 cases). Three months after the surgery, the second hysteroscopy was performed to observe the condition of the uterine cavity and the improvement of menstruation, and to monitor the thickness of the endometrium.The efficacy of hysteroscopic procedure in group A was significantly higher than that of group B (P < .05). After 3 months of treatment, the improvement rate of menstruation was significantly higher in group A than in group B (P < .05). Endometrial thickness in both group A and B was significantly increased compared with that before the surgery (P < .05). The postoperative endometrium of group A was significantly thicker than that of group B (P < .05).Amniotic membrane-mediated sequential double-barrier method is clinically feasible for preventing recurrent intrauterine adhesions.
Collapse
|
|
19
|
Introduction of Female Reproductive Processes and Reproductive Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1300:23-38. [PMID: 33523428 DOI: 10.1007/978-981-33-4187-6_2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The female reproductive process is very complicated, including multiple processes. Each process is different and plays a vital role in reproduction. If some reproductive diseases occur, these processes will be abnormal, causing infertility problem. In this Chapter, we will describe the female reproductive process and their corresponding reproductive diseases.
Collapse
|
|
20
|
Hooker AB, de Leeuw RA, Twisk JWR, Brölmann HAM, Huirne JAF. Reproductive performance of women with and without intrauterine adhesions following recurrent dilatation and curettage for miscarriage: long-term follow-up of a randomized controlled trial. Hum Reprod 2021; 36:70-81. [PMID: 33320197 PMCID: PMC7801791 DOI: 10.1093/humrep/deaa289] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 08/04/2020] [Indexed: 01/22/2023] Open
Abstract
STUDY QUESTION Are the long-term reproductive outcomes following recurrent dilatation and curettage (D&C) for miscarriage in women with identified and treated intrauterine adhesions (IUAs) comparable to women without IUAs. SUMMARY ANSWER Reproductive outcomes in women with identified and treated IUAs following recurrent D&C for miscarriage are impaired compared to women without IUAs; fewer ongoing pregnancies and live births are achieved with a prolonged time to a live birth. WHAT IS KNOWN ALREADY The Prevention of Adhesions Post Abortion (PAPA) study showed that application of auto-crosslinked hyaluronic acid (ACP) gel, an absorbable barrier in women undergoing recurrent D&C for miscarriage resulted in a lower rate of IUAs, 13% versus 31% (relative risk 0.43, 95% CI 0.22 to 0.83), lower mean adhesion score and significant less moderate to severe IUAs. It is unclear what the impact is of IUAs on long-term reproductive performance. STUDY DESIGN, SIZE, DURATION This was a follow-up of the PAPA study, a multicenter randomized controlled trial evaluating the application of ACP gel in women undergoing recurrent D&C for miscarriage. All included women received a diagnostic hysteroscopy 8-12 weeks after randomization to evaluate the uterine cavity and for adhesiolysis if IUAs were present. Here, we present the reproductive outcomes in women with identified and treated IUAs versus women without IUAs, 46 months after randomization. PARTICIPANTS/MATERIALS, SETTING, METHODS Between December 2011 and July 2015, 152 women with a first-trimester miscarriage with at least one previous D&C, were randomized for D&C alone or D&C with immediate intrauterine application of ACP gel. Participants were approached at least 30 months after randomization to evaluate reproductive performance, obstetric and neonatal outcomes and cycle characteristics. Additionally, the medical files of all participants were reviewed. Main outcome was ongoing pregnancy. Outcomes of subsequent pregnancies, time to conception and time to live birth were also recorded. MAIN RESULTS AND THE ROLE OF CHANCE In women pursuing a pregnancy, 14/24 (58%) ongoing pregnancies were recorded in women with identified and treated IUAs versus 80/89 (90%) ongoing pregnancies in women without IUAs odds ratio (OR) 0.18 (95% CI 0.06 to 0.50, P-value <0.001). Documented live birth was also lower in women with IUAs; 13/24 (54%) with versus 75/89 (84%) without IUAs, OR 0.22 (95% CI: 0.08 to-0.59, P-value 0.004). The median time to conception was 7 months in women with identified and treated IUAs versus 5 months in women without IUAs (hazard ratio (HR) 0.84 (95% CI 0.54 to 1.33)) and time to conception leading to a live birth 15 months versus 5.0 months (HR 0.54 (95% CI: 0.30 to 0.97)). In women with identified and treated IUAs, premature deliveries were recorded in 3/16 (19%) versus 4/88 (5%) in women without IUAs, P-value 0.01. Complications were recorded in respectively 12/16 (75%) versus 26/88 (30%), P-value 0.001. No differences were recorded in mean birth weight between the groups. LIMITATIONS, REASONS FOR CAUTION In the original PAPA study, randomization was applied for ACP gel application. Comparing women with and without IUAs is not in line with the randomization and therefore confounding of the results cannot be excluded. IUAs, if visible during routine hysteroscopy after randomization were removed as part of the study protocol; the influence of IUAs on reproductive outcome may therefore be underestimated. Women undergoing a recurrent D&C for miscarriage were included, a specific group likely to generate clinically significant adhesions. The findings should therefore not be generalized to all women undergoing D&C for miscarriage. WIDER IMPLICATIONS OF THE FINDINGS As IUAs have an impact on reproductive performance, even after hysteroscopic adhesiolysis, primary prevention is essential. Expectative and medical management should therefore be considered as serious alternatives for D&C in women with a miscarriage. In case D&C is necessary, application of ACP gel should be considered. STUDY FUNDING/COMPETING INTEREST(S) The original PAPA study (NTR 3120) was an investigator initiated study that was funded by the Foundation for scientific investigation in Obstetrics and Gynaecology of the Saint Lucas Andreas Hospital (currently renamed OLVG Oost), SWOGA. The syringes containing ACP gel were received from Anika Therapeutics, the manufacturer of Hyalobarrier® Gel Endo. The current follow-up study was also an investigator-initiated study without funding. The funder and sponsor had no role in the design of this follow-up study, data collection, data analysis, data interpretation, trial design, patient recruitment, writing of the report or any aspect pertinent to the study. ABH, RAL, JAFH and JWRT have no conflict to declare. HAMB reports being a member of safety board research Womed. TRIAL REGISTRATION NUMBER Netherlands Trial Register NTR 3120.
Collapse
Affiliation(s)
- Angelo B Hooker
- Department of Obstetrics and Gynecology, Zaans Medical Center, Zaandam, the Netherlands
- Department of Obstetrics and Gynecology, Amsterdam UMC, Location VU University Medical Center, Amsterdam, the Netherlands
| | - Robert A de Leeuw
- Department of Obstetrics and Gynecology, Amsterdam UMC, Location VU University Medical Center, Amsterdam, the Netherlands
| | - Jos W R Twisk
- Department of Epidemiology and Biostatistics, Amsterdam UMC, Location VU University Medical Center, Amsterdam, the Netherlands
| | - Hans A M Brölmann
- Department of Obstetrics and Gynecology, Amsterdam UMC, Location VU University Medical Center, Amsterdam, the Netherlands
| | - Judith A F Huirne
- Department of Obstetrics and Gynecology, Amsterdam UMC, Location VU University Medical Center, Amsterdam, the Netherlands
| |
Collapse
|
|
21
|
Chiu CSC, Hwu YM, Lee RKK, Lin MH. Intrauterine adhesion prevention with Malecot catheter after hysteroscopic myomectomy: A novel approach. Taiwan J Obstet Gynecol 2020; 59:56-60. [PMID: 32039801 DOI: 10.1016/j.tjog.2019.11.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/05/2019] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVE Intrauterine adhesion after hysteroscopic myomectomy contributes to infertility, recurrent miscarriages, menstrual irregularities, and hinders pregnancy outcomes. The aim of this study was to apply the indwelling Malecot catheter in prevention of intrauterine adhesion after hysteroscopic myomectomy and to further evaluate the effectiveness of this approach with reported live birth rates in infertile patients who underwent subsequent infertility treatment. MATERIALS AND METHODS Seventeen patients with FIGO Classification System PALM-COIEN Type 0 or 1 submucous myoma that received hysteroscopic myomectomy were recruited in this retrospective analysis. Post-operative insertion of the Malecot catheter via the aid of the uterine sound was performed and the catheter was left in place for seven days. RESULTS The mean duration of TTP (time to pregnancy) was 15.6 months after hysteroscopy. Within three years after the operation, 10 out of 17 infertility patients achieved ongoing pregnancy over 12 weeks. Ongoing pregnancy rate was 58.8% (10/17). Eight patients achieved live birth (seven singletons, one twin pregnancy) with mean gestational age of 38 weeks. Live birth rate was 47.1% (8/17). CONCLUSION The Malecot catheter is an inexpensive, easy-to-operate, and effective physical barrier method for preventing IUA in infertile patients undergoing hysteroscopic myomectomy with high live birth rate and no obvious visible post-operative adhesions.
Collapse
Affiliation(s)
| | - Yuh-Ming Hwu
- Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan; Mackay Medical College, New Taipei City, Taiwan.
| | - Robert Kuo-Kuang Lee
- Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, Taipei Medical University, Taipei, Taiwan
| | - Ming-Huei Lin
- Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan; Mackay Medical College, New Taipei City, Taiwan
| |
Collapse
|
|
22
|
Wang B, Feng C, Dang J, Zhu Y, Yang X, Zhang T, Zhang R, Li J, Tang J, Shen C, Shen L, Dong J, Zhang X. Preparation of Fibroblast Suppressive Poly(ethylene glycol)- b-poly(l-phenylalanine)/Poly(ethylene glycol) Hydrogel and Its Application in Intrauterine Fibrosis Prevention. ACS Biomater Sci Eng 2020; 7:311-321. [PMID: 33455202 DOI: 10.1021/acsbiomaterials.0c01390] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Intrauterine adhesions (IUA) often occur as a result of trauma to the basal layer after curettage, postpartum hemorrhage, or surgical miscarriage. Endometrial fibrosis is the primary pathological feature of IUA. The characteristic features of IUA include excessive deposition and reorganization of the extracellular matrix, replacing the normal endometrium. To prevent uterine fibrosis after injury, we prepared and evaluated a type of fibroblast suppressive hydrogel. Poly(ethylene glycol)-b-poly(l-phenylalanine) (PEBP) copolymers were successfully synthesized by ring opening polymerization of l-Phenylalanine N-carboxyanhydride, initiated by methoxy-poly(ethylene glycol)-amine. Injectable PEBP/PEG hydrogels were subsequently formed through π-π accumulations between PEBP macromolecules and hydrogen bonds among PEBP, PEG, and H2O molecules. PEBP/PEG hydrogel could suppress the proliferation of fibroblasts due to the action of l-Phe, released sustainably from PEBP/PEG gels. Lastly, the in vivo preventive effect of PEBP/PEG hydrogel on fibrosis was evaluated in a rat uterine curettage model. It was found that PEBP/PEG hydrogel suppressed uterine fibrosis caused by curettage and promoted embryo implantation in injured uterine by regulating the expression and interactions of transforming growth factor beta 1 (TGF-β1) and Muc-4. PEBP/PEG hydrogels have the potential for application in uterine adhesion prevention owing to their fibrosis preventive and pregnancy promotiing effects on uterine tissue after injury.
Collapse
Affiliation(s)
- Bing Wang
- Medical Imaging Key Laboratory of Sichuan Province & Department of Chemistry, School of Preclinical Medicine, North Sichuan Medical College, Nanchong 637000, P. R. China
| | - Chengmin Feng
- Otorhinolaryngology, Department of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, P. R. China
| | - Jiafeng Dang
- Gynecology and Obstetrics, Department of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, P. R. China
| | - Yanghui Zhu
- School of Pharmacy, North Sichuan Medical College, 637000 Nanchong, P. R. China
| | - Xiaomei Yang
- Department of Clinical Medicine, North Sichuan Medical College, Nanchong, P. R. China
| | - Ting Zhang
- Department of Clinical Medicine, North Sichuan Medical College, Nanchong, P. R. China
| | - Ruqin Zhang
- Department of Clinical Medicine, North Sichuan Medical College, Nanchong, P. R. China
| | - Jiawen Li
- Department of Clinical Medicine, North Sichuan Medical College, Nanchong, P. R. China
| | - Jing Tang
- Department of Clinical Medicine, North Sichuan Medical College, Nanchong, P. R. China
| | - Chengyi Shen
- Medical Imaging Key Laboratory of Sichuan Province & Institute of Morphological Research, North Sichuan Medical College, Nanchong, P. R. China
| | - Lunhua Shen
- Department of Gynecology and Obstetrics, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, P. R. China
| | - Jun Dong
- Department of Chemistry, School of Preclinical Medicine, North Sichuan Medical College, Nanchong 637000, P. R. China
| | - Xiaoming Zhang
- Medical Imaging Key Laboratory of Sichuan Province & Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, P. R. China
| |
Collapse
|
|
23
|
Cheng M, Chang WH, Yang ST, Huang HY, Tsui KH, Chang CP, Lee WL, Wang PH. Efficacy of Applying Hyaluronic Acid Gels in the Primary Prevention of Intrauterine Adhesion after Hysteroscopic Myomectomy: A Meta-Analysis of Randomized Controlled Trials. Life (Basel) 2020; 10:life10110285. [PMID: 33203159 PMCID: PMC7697815 DOI: 10.3390/life10110285] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/12/2020] [Accepted: 11/13/2020] [Indexed: 12/15/2022] Open
Abstract
Intrauterine adhesion (IUA), which mainly occurs after intrauterine surgery or an inflammatory process, is an important but often neglected condition in women of reproductive age. The presentation of IUA varies greatly, ranging from symptom-free to severe, with amenorrhea or infertility. With much advanced development of intrauterine instruments, more intrauterine diseases can be successfully cured by hysteroscopic surgery. Among these, submucosal myoma is one of the best examples. Submucosal myomas are often related to abnormal bleeding, anemia, and possible infertility or miscarriage. However, submucosal myoma after hysteroscopic myomectomy may be complicated by IUA in various grades of severity, and its incidence and prevalence might be nearly one-quarter to one-third of patients, suggesting an urgent need for efforts to decrease the risk of developing IUA after hysteroscopic myomectomy. Many strategies have been reported to be useful for this purpose, and intrauterine application of anti-adhesive gels, such as polyethylene oxide–sodium carboxymethylcellulose (PEO-NaCMC) or auto-crosslinked hyaluronic acid (ACHA), has become increasingly popular in routine clinical practice. This meta-analysis is aimed at investigating the effect of ACHA on the primary prevention of IUA formation after hysteroscopic myomectomy. A pooled analysis of three studies (hysteroscopic surgeries for fibroids, polyps, and septum) including 242 women showed that using PEO-NaCMC or ACHA gel decreased the IUA rate with an odds ratio (OR) of 0.364 (95% confidence interval (CI) 0.189–0.703, p = 0.03). Pooled analysis of two studies that limited the use of ACHA in 119 women showed that the application of ACHA gel for the primary prevention of IUA in patients after hysteroscopic myomectomy led to a statistically significant reduction of the development of IUA postoperatively (OR 0.285, 95% CI 0.116–0.701, p = 0.006). All of this suggests that the use of ACHA gel in patients after hysteroscopic myomectomy could significantly reduce de novo IUA, although more evidence is needed.
Collapse
Affiliation(s)
- Min Cheng
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan; (M.C.); (W.-H.C.); (S.-T.Y.); (C.-P.C.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
- Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei 112, Taiwan
| | - Wen-Hsun Chang
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan; (M.C.); (W.-H.C.); (S.-T.Y.); (C.-P.C.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
- Department of Nursing, Taipei Veterans General Hospital, Taipei 112, Taiwan
| | - Szu-Ting Yang
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan; (M.C.); (W.-H.C.); (S.-T.Y.); (C.-P.C.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
- Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei 112, Taiwan
| | - Hsin-Yi Huang
- Biostatics Task Force, Taipei Veterans General Hospital, Taipei 112, Taiwan;
| | - Kuan-Hao Tsui
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
- Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei 112, Taiwan
- Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
- Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung County 907, Taiwan
| | - Chia-Pei Chang
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan; (M.C.); (W.-H.C.); (S.-T.Y.); (C.-P.C.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
- Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei 112, Taiwan
| | - Wen-Ling Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
- Department of Medicine, Cheng-Hsin General Hospital, Taipei 112, Taiwan
- Department of Nursing, Oriental Institute of Technology, New Taipei City 220, Taiwan
- Correspondence: (W.-L.L.); (P.-H.W.); Tel.: +886-2-2873-4400 (W.-L.L.); +886-2-2875-7566 (P.-H.W.)
| | - Peng-Hui Wang
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan; (M.C.); (W.-H.C.); (S.-T.Y.); (C.-P.C.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
- Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei 112, Taiwan
- Cancer Female Foundation, Taipei 104, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan
- Correspondence: (W.-L.L.); (P.-H.W.); Tel.: +886-2-2873-4400 (W.-L.L.); +886-2-2875-7566 (P.-H.W.)
| |
Collapse
|
|
24
|
Huberlant S, Leprince S, Allegre L, Warembourg S, Leteuff I, Taillades H, Garric X, de Tayrac R, Letouzey V. In Vivo Evaluation of the Efficacy and Safety of a Novel Degradable Polymeric Film for the Prevention of Intrauterine Adhesions. J Minim Invasive Gynecol 2020; 28:1384-1390. [PMID: 33152532 DOI: 10.1016/j.jmig.2020.10.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/27/2020] [Accepted: 10/28/2020] [Indexed: 12/16/2022]
Abstract
STUDY OBJECTIVE To study the safety of a degradable polymeric film (DPF) and its efficacy on reducing the risk of intrauterine-adhesion (IUA) formation in a rat model. DESIGN A series of case-control studies relying on random allocation, where feasible. SETTING University and good practice animal laboratories. ANIMALS The animal models comprised female and male Oncins France Strain A and female Wistar rats. INTERVENTION(S) AND MEASUREMENTS The Oncins France Strain A rats were used for in vivo evaluation of the impact of the DPF on endometrial thickness and its effect on fertility. For in vivo evaluation of the biologic response, 40 Wistar rats were randomly allocated to intervention and control groups, with matched sampling time after surgery. Finally, for the in vivo evaluation of the DPF's efficacy on IUA prevention, a total of 24 Wistar rats were divided into 3 groups: 1 treated with the DPF, 1 treated with hyaluronic acid gel, and a sham group. MAIN RESULTS The DPF did not have a significant impact on endometrial thickness, and there were no significant differences in the number of conceived or prematurely terminated pregnancies, confirming its noninferiority to no treatment. The DPF did not induce irritation at 5 days and 28 days. Finally, the DPF significantly reduced the likelihood of complete IUA formation compared with hyaluronic acid gel- and sham-implanted animals, where only 27% of the animals had their uterine cavity obliterated compared with 80% and 100%, respectively. CONCLUSION The DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.
Collapse
Affiliation(s)
- Stéphanie Huberlant
- Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université Montpellier, ENSCM (Drs. Huberlant, Leprince, Allegre, Warembourg, Leteuff, Garric, de Tayrac, and Letouzey); Experimental Department, University of Montpellier (Mr. Taillades), Montpellier; Department of Gynecology and Obstetrics, CHU Nîmes, University of Montpellier, Nîmes (Drs. Huberlant, Allegre, de Tayrac, and Letouzey); Gynecology Department, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon (Dr. Warembourg), France.
| | - Salome Leprince
- Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université Montpellier, ENSCM (Drs. Huberlant, Leprince, Allegre, Warembourg, Leteuff, Garric, de Tayrac, and Letouzey); Experimental Department, University of Montpellier (Mr. Taillades), Montpellier; Department of Gynecology and Obstetrics, CHU Nîmes, University of Montpellier, Nîmes (Drs. Huberlant, Allegre, de Tayrac, and Letouzey); Gynecology Department, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon (Dr. Warembourg), France
| | - Lucie Allegre
- Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université Montpellier, ENSCM (Drs. Huberlant, Leprince, Allegre, Warembourg, Leteuff, Garric, de Tayrac, and Letouzey); Experimental Department, University of Montpellier (Mr. Taillades), Montpellier; Department of Gynecology and Obstetrics, CHU Nîmes, University of Montpellier, Nîmes (Drs. Huberlant, Allegre, de Tayrac, and Letouzey); Gynecology Department, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon (Dr. Warembourg), France
| | - Sophie Warembourg
- Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université Montpellier, ENSCM (Drs. Huberlant, Leprince, Allegre, Warembourg, Leteuff, Garric, de Tayrac, and Letouzey); Experimental Department, University of Montpellier (Mr. Taillades), Montpellier; Department of Gynecology and Obstetrics, CHU Nîmes, University of Montpellier, Nîmes (Drs. Huberlant, Allegre, de Tayrac, and Letouzey); Gynecology Department, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon (Dr. Warembourg), France
| | - Isabelle Leteuff
- Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université Montpellier, ENSCM (Drs. Huberlant, Leprince, Allegre, Warembourg, Leteuff, Garric, de Tayrac, and Letouzey); Experimental Department, University of Montpellier (Mr. Taillades), Montpellier; Department of Gynecology and Obstetrics, CHU Nîmes, University of Montpellier, Nîmes (Drs. Huberlant, Allegre, de Tayrac, and Letouzey); Gynecology Department, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon (Dr. Warembourg), France
| | - Hubert Taillades
- Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université Montpellier, ENSCM (Drs. Huberlant, Leprince, Allegre, Warembourg, Leteuff, Garric, de Tayrac, and Letouzey); Experimental Department, University of Montpellier (Mr. Taillades), Montpellier; Department of Gynecology and Obstetrics, CHU Nîmes, University of Montpellier, Nîmes (Drs. Huberlant, Allegre, de Tayrac, and Letouzey); Gynecology Department, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon (Dr. Warembourg), France
| | - Xavier Garric
- Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université Montpellier, ENSCM (Drs. Huberlant, Leprince, Allegre, Warembourg, Leteuff, Garric, de Tayrac, and Letouzey); Experimental Department, University of Montpellier (Mr. Taillades), Montpellier; Department of Gynecology and Obstetrics, CHU Nîmes, University of Montpellier, Nîmes (Drs. Huberlant, Allegre, de Tayrac, and Letouzey); Gynecology Department, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon (Dr. Warembourg), France
| | - Renaud de Tayrac
- Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université Montpellier, ENSCM (Drs. Huberlant, Leprince, Allegre, Warembourg, Leteuff, Garric, de Tayrac, and Letouzey); Experimental Department, University of Montpellier (Mr. Taillades), Montpellier; Department of Gynecology and Obstetrics, CHU Nîmes, University of Montpellier, Nîmes (Drs. Huberlant, Allegre, de Tayrac, and Letouzey); Gynecology Department, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon (Dr. Warembourg), France
| | - Vincent Letouzey
- Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université Montpellier, ENSCM (Drs. Huberlant, Leprince, Allegre, Warembourg, Leteuff, Garric, de Tayrac, and Letouzey); Experimental Department, University of Montpellier (Mr. Taillades), Montpellier; Department of Gynecology and Obstetrics, CHU Nîmes, University of Montpellier, Nîmes (Drs. Huberlant, Allegre, de Tayrac, and Letouzey); Gynecology Department, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon (Dr. Warembourg), France
| |
Collapse
|
|
25
|
Recent Advances in Understandings Towards Pathogenesis and Treatment for Intrauterine Adhesion and Disruptive Insights from Single-Cell Analysis. Reprod Sci 2020; 28:1812-1826. [PMID: 33125685 PMCID: PMC8189970 DOI: 10.1007/s43032-020-00343-y] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 10/01/2020] [Indexed: 12/22/2022]
Abstract
Intrauterine adhesion is a major cause of menstrual irregularities, infertility, and recurrent pregnancy losses and the progress towards its amelioration and therapy is slow and unsatisfactory. We aim to summarize and evaluate the current treatment progress and research methods for intrauterine adhesion. We conducted literature review in January 2020 by searching articles at PubMed on prevention and treatment, pathogenesis, the repair of other tissues/organs, cell plasticity, and the stem cell–related therapies for intrauterine adhesion. A total of 110 articles were selected for review. Uterine cell heterogeneity, expression profile, and cell-cell interaction were investigated based on scRNA-seq of uterus provided by Human Cell Landscape (HCL) project. Previous knowledge on intrauterine adhesion (IUA) pathogenesis was mostly derived from correlation studies by differentially expressed genes between endometrial tissue of intrauterine adhesion patients/animal models and normal endometrial tissue. Although the TGF-β1/SMAD pathway was suggested as the key driver for IUA pathogenesis, uterine cell heterogeneity and distinct expression profile among different cell types highlighted the importance of single-cell investigations. Cell-cell interaction in the uterus revealed the central hub of endothelial cells interacting with other cells, with endothelial cells in endothelial to mesenchymal transition and fibroblasts as the strongest interaction partners. The potential of stem cell–related therapies appeared promising, yet suffers from largely animal studies and nonstandard study design. The need to dissect the roles of endometrial cells, endothelial cells, and fibroblasts and their interaction is evident in order to elucidate the molecular and cellular mechanisms in both intrauterine adhesion pathogenesis and treatment.
Collapse
|
|
26
|
Doroftei B, Dabuleanu AM, Ilie OD, Maftei R, Anton E, Simionescu G, Matei T, Armeanu T. Mini-Review of the New Therapeutic Possibilities in Asherman Syndrome-Where Are We after One Hundred and Twenty-Six Years? Diagnostics (Basel) 2020; 10:diagnostics10090706. [PMID: 32957624 PMCID: PMC7554703 DOI: 10.3390/diagnostics10090706] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 09/08/2020] [Accepted: 09/16/2020] [Indexed: 02/03/2023] Open
Abstract
Asherman syndrome is a multifaceted condition describing the partial or complete removal of the uterine cavity and/or cervical canal. It is a highly debatable topic because of its pronounced influence on both reproductive outcomes and gynaecologic symptoms. The latest reports demonstrated that trauma to the endometrium is the main cause of intrauterine adhesion formation. Left untreated, such adhesions gradually lead to a range of repercussions ranging from mild to severe. Considering the lack of non-invasive approaches, the advent of hysteroscopy has revolutionized the entire field, being otherwise considered the most efficient tool offering new directions and amplifying the chances of treating the Asherman syndrome.
Collapse
Affiliation(s)
- Bogdan Doroftei
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; (B.D.); (A.-M.D.); (R.M.); (E.A); (G.S.)
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania; (T.M.); (T.A.)
- Origyn Fertility Center, Palace Street, No. 3C, 700032 Iasi, Romania
| | - Ana-Maria Dabuleanu
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; (B.D.); (A.-M.D.); (R.M.); (E.A); (G.S.)
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania; (T.M.); (T.A.)
- Origyn Fertility Center, Palace Street, No. 3C, 700032 Iasi, Romania
| | - Ovidiu-Dumitru Ilie
- Department of Research, Faculty of Biology, Alexandru Ioan Cuza University, Carol I Avenue, No. 20A, 700505 Iasi, Romania
- Correspondence:
| | - Radu Maftei
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; (B.D.); (A.-M.D.); (R.M.); (E.A); (G.S.)
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania; (T.M.); (T.A.)
- Origyn Fertility Center, Palace Street, No. 3C, 700032 Iasi, Romania
| | - Emil Anton
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; (B.D.); (A.-M.D.); (R.M.); (E.A); (G.S.)
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania; (T.M.); (T.A.)
- Origyn Fertility Center, Palace Street, No. 3C, 700032 Iasi, Romania
| | - Gabriela Simionescu
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, No. 16, 700115 Iasi, Romania; (B.D.); (A.-M.D.); (R.M.); (E.A); (G.S.)
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania; (T.M.); (T.A.)
- Origyn Fertility Center, Palace Street, No. 3C, 700032 Iasi, Romania
| | - Theodor Matei
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania; (T.M.); (T.A.)
- Origyn Fertility Center, Palace Street, No. 3C, 700032 Iasi, Romania
| | - Theodora Armeanu
- Clinical Hospital of Obstetrics and Gynecology “Cuza Voda”, Cuza Voda Street, No. 34, 700038 Iasi, Romania; (T.M.); (T.A.)
- Origyn Fertility Center, Palace Street, No. 3C, 700032 Iasi, Romania
| |
Collapse
|
|
27
|
Chang QY, Zhang SW, Li PP, Yuan ZW, Tan JC. Safety of menstrual blood-derived stromal cell transplantation in treatment of intrauterine adhesion. World J Stem Cells 2020; 12:368-380. [PMID: 32547685 PMCID: PMC7280865 DOI: 10.4252/wjsc.v12.i5.368] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 04/03/2020] [Accepted: 04/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Intrauterine adhesion (IUA) can cause serious damage to women's reproductive health, yet current treatment methods are difficult to achieve satisfactory results. In our previous studies, we demonstrated that menstrual-derived stromal stem cells (MenSCs), with high proliferative capacity and self-renewal ability, have a powerful therapeutic effect in patients with severe IUA. However, safety assessment of MenSCs transplantation is essential for its further application.
AIM To evaluate the short-, medium-, and long-term biosafety of MenSCs via intrauterine transplantation in a rat model of IUA, with a focus on toxicity and tumorigenicity.
METHODS MenSCs were injected into the sub-serosal layer of the uterus in an IUA rat model, for 3 d, 3 mo, and 6 mo separately, to monitor the corresponding acute, sub-chronic, and chronic effects. Healthy rats of the same age served as negative controls. Toxicity effects were evaluated by body weight, organ weight, histopathology, hematology, and biochemistry tests. Tumorigenicity of MenSCs was investigated in Balb/c-nu mice in vivo and by colony formation assays in vitro.
RESULTS Compared with the same week-old control group, all of the IUA rats receiving MenSC transplantation demonstrated no obvious changes in body weight, main organ weight, or blood cell composition during the acute, sub-chronic, and chronic observation periods. At the same time, serum biochemical tests showed no adverse effects on metabolism or liver and kidney function. After 4 wk of subcutaneous injection of MenSCs in Balb/c-nu nude mice, no tumor formation or cell metastasis was observed. Moreover, there was no tumor colony formation of MenSCs during soft agar culture in vitro.
CONCLUSION There is no acute, sub-chronic, or chronic poisoning, infection, tumorigenesis, or endometriosis in rats with IUA after MenSC transplantation. The above results suggest that intrauterine transplantation of MenSCs is safe for endometrial treatment.
Collapse
Affiliation(s)
- Qi-Yuan Chang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
- Key Laboratory of Reproductive Dysfunction Diseases and Fertility Remodeling of Liaoning Province, Shenyang 110004, Liaoning Province, China
| | - Si-Wen Zhang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
- Key Laboratory of Reproductive Dysfunction Diseases and Fertility Remodeling of Liaoning Province, Shenyang 110004, Liaoning Province, China
| | - Ping-Ping Li
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
- Key Laboratory of Reproductive Dysfunction Diseases and Fertility Remodeling of Liaoning Province, Shenyang 110004, Liaoning Province, China
| | - Zheng-Wei Yuan
- Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital of China Medical University, Benxi 117004, Liaoning Province, China
| | - Ji-Chun Tan
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
- Key Laboratory of Reproductive Dysfunction Diseases and Fertility Remodeling of Liaoning Province, Shenyang 110004, Liaoning Province, China
| |
Collapse
|
|
28
|
Di Spiezio Sardo A, Campo R, Zizolfi B, Santangelo F, Meier Furst R, Di Cesare C, Bettocchi S, Vitagliano A, Ombelet W. Long-Term Reproductive Outcomes after Hysteroscopic Treatment of Dysmorphic Uteri in Women with Reproductive Failure: An European Multicenter Study. J Minim Invasive Gynecol 2020; 27:755-762. [DOI: 10.1016/j.jmig.2019.05.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 04/18/2019] [Accepted: 05/17/2019] [Indexed: 01/09/2023]
|
|
29
|
Zhang Z, Li S, Deng J, Yang S, Xiang Z, Guo H, Xi H, Sang M, Zhang W. Aspirin inhibits endometrial fibrosis by suppressing the TGF‑β1‑Smad2/Smad3 pathway in intrauterine adhesions. Int J Mol Med 2020; 45:1351-1360. [PMID: 32323728 PMCID: PMC7138280 DOI: 10.3892/ijmm.2020.4506] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 01/24/2020] [Indexed: 01/07/2023] Open
Abstract
Intrauterine adhesions (IUAs) represent one of the most common diseases in women of reproductive age. Patients with moderate‑to‑severe IUA can experience a decrease in normal menstrual patterns, amenorrhea and even infertility. At present, the first‑line treatment strategies for IUAs in the clinical practice are hysteroscopic transuterine resection of adhesion and postoperative adjuvant therapy, including oestrogen. However, a high recurrence rate of IUAs remains. In recent years, studies have demonstrated that aspirin combined with oestrogen may significantly prevent the postoperative disease recurrence rate, improve endometrial receptivity and improve the conception rate by increasing endometrial blood supply and angiogenesis more effectively. The TGF‑β1‑Smad2/Smad3 pathway is one of the important mechanisms involved in endometrial fibrosis. However, whether aspirin can inhibit endometrial fibrosis through the TGF‑β1‑Smad2/Smad3 pathway to prevent postoperative re‑adhesion remains to be elucidated. The results of the present study suggested that aspirin inhibits endometrial fibrosis by suppressing the TGF‑β1‑Smad2/Smad3 pathway, which may provide new hypotheses for the mechanism of action of aspirin in the treatment of IUAs.
Collapse
Affiliation(s)
- Zihui Zhang
- Department of Obstetrics and Gynaecology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Shuang Li
- Department of Obstetrics and Gynaecology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Jie Deng
- Department of Obstetrics and Gynaecology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Shaorong Yang
- Department of Pathology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Ziwu Xiang
- Department of Pathology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Hongyan Guo
- Department of Obstetrics and Gynaecology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Hongli Xi
- Department of Obstetrics and Gynaecology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Ming Sang
- Department of Obstetrics and Gynaecology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Wei Zhang
- Department of Obstetrics and Gynaecology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| |
Collapse
|
|
30
|
Sebbag L, Even M, Fay S, Naoura I, Revaux A, Carbonnel M, Pirtea P, de Ziegler D, Ayoubi JM. Early Second-Look Hysteroscopy: Prevention and Treatment of Intrauterine Post-surgical Adhesions. Front Surg 2019; 6:50. [PMID: 31475154 PMCID: PMC6706867 DOI: 10.3389/fsurg.2019.00050] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 07/30/2019] [Indexed: 12/19/2022] Open
Abstract
Introduction: Intra-uterine adhesion (IUA) is one of the main causes of secondary infertility. The aim of this study was to evaluate the prevalence of IUA developing in women undergoing hysteroscopic resection for submucous myomas, polyps, and intrauterine synechiae and test the efficacy of second look hysteroscopy for diagnosing and treating post-surgical adhesions. Materials and Methods: We retrospectively collected data from reproductive age women who had a second look office hysteroscopy following hysteroscopic resection for myoma, polyp, or IUA at Foch hospital (Suresnes, France) between 2009 and 2017. Results: Six hundred and twenty two reproductive-age women underwent hysteroscopic resection for myoma, polyp, and/or IUA. Among them, 155 women had a second look hysteroscopy. In this group, 29/155 (18.7%) had IUA formation: 17/83 (20.5%) women who underwent hysteroscopic myomectomy, 5/46 (10.9%) women who underwent hysteroscopic polypectomy, and 7/26 (26.9%) women who underwent hysteroscopic lysis of adhesions. These IUA have been lysed by the office hysteroscopy procedure in 16/29 (55.2%) patients: 11/17 (64.7%), 2/5 (40%), and 3/7 (42.9%) in women who underwent hysteroscopic myomectomy, polypectomy and lysis of adhesion, respectively. Conclusion: IUA is a common complication of hysteroscopic surgery. Second look office hysteroscopy is an easy and effective procedure for diagnosing and removing newly formed IUA. It should be recommended for all women undergoing hysteroscopic resection for myomas, polyps, or IUA.
Collapse
Affiliation(s)
- Lauren Sebbag
- Department of Obstetrics, Gynecology and Reproductive Sciences, Foch Hospital, Suresnes, France
| | - Marc Even
- Department of Obstetrics, Gynecology and Reproductive Sciences, Foch Hospital, Suresnes, France
| | - Stéphanie Fay
- Department of Obstetrics, Gynecology and Reproductive Sciences, Foch Hospital, Suresnes, France
| | - Iptissem Naoura
- Department of Obstetrics, Gynecology and Reproductive Sciences, Foch Hospital, Suresnes, France
| | - Aurélie Revaux
- Department of Obstetrics, Gynecology and Reproductive Sciences, Foch Hospital, Suresnes, France
| | - Marie Carbonnel
- Department of Obstetrics, Gynecology and Reproductive Sciences, Foch Hospital, Suresnes, France
| | - Paul Pirtea
- Department of Obstetrics, Gynecology and Reproductive Sciences, Foch Hospital, Suresnes, France
| | - Dominique de Ziegler
- Department of Obstetrics, Gynecology and Reproductive Sciences, Foch Hospital, Suresnes, France
| | - Jean-Marc Ayoubi
- Department of Obstetrics, Gynecology and Reproductive Sciences, Foch Hospital, Suresnes, France
| |
Collapse
|
|
31
|
Torres-De La Roche LA, Campo R, Devassy R, Di Spiezio Sardo A, Hooker A, Koninckx P, Urman B, Wallwiener M, De Wilde RL. Adhesions and Anti-Adhesion Systems Highlights. Facts Views Vis Obgyn 2019; 11:137-149. [PMID: 31824635 PMCID: PMC6897521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The peritoneal and intrauterine cavities are lined by fragile membranes with a high-wound healing capacity, e.g. repairing the endometrium in its cyclical "injury and scar-free repair process" during menstruation. However, peritoneal and intrauterine fibrosis and adhesions can develop after surgical trauma through activation of molecular, immune and genetic mechanisms. During procedures with a high-risk of adhesions, the use of new peritoneal and intrauterine conditions in combination with anti-adhesion substances are promising measures to preserve peritoneal and endometrial function and avoid the most common complication of gynecological surgery. Highlights of adhesions and anti-adhesion prevention techniques in laparoscopic, laparotomic and hysteroscopic surgeries are discussed in this paper. Unfortunately, evidence is lacking to prove the superiority of one technique over its counterparts in terms of postoperative adhesions, such as instrumentation, type of energy, distending media, and intracavitary pressure. Additionally, there is limited evidence about the efficacy and outcomes of techniques and adjuvant measures used during adhesiolysis. The definition of a universal intrauterine adhesions classification scheme as well as a prognostic scoring system to identify women at high risk of postoperative adhesions are necessary for advising those who could benefit the most of the use of antiadhesion barriers.
Collapse
Affiliation(s)
- LA Torres-De La Roche
- University Hospital for Gynecology, Pius Hospital, University Medicine Oldenburg, Carl von Ossietzky University Oldenburg, 26121, Germany
| | - R Campo
- Leuven Institute for Fertility and Embryology, Tiensevest, 3000, Leuven
| | - R Devassy
- Dubai London Clinic and Speciality Hospital, Dubai, 3371500, UAE
| | | | - A Hooker
- Zaans Medical Centre, Zaandam, 1502, Netherlands
| | - P Koninckx
- UZ Leuven Campus Gasthuisberg, Leuven, 3000, Belgium
| | - B Urman
- Koç University Faculty of Medicine, Department of Obstetrics and Gynecology, Istanbul, Turkey, 34330, Turkey
| | - M Wallwiener
- Heidelberg University Women's Hospital, Heidelberg, 69115, Germany
| | - RL De Wilde
- University Hospital for Gynecology, Pius Hospital, University Medicine Oldenburg, Carl von Ossietzky University Oldenburg, 26121, Germany
| |
Collapse
|
|
32
|
Kim JK, Park JY, Lee DW, Ro DH, Lee MC, Han HS. Temperature-sensitive anti-adhesive poloxamer hydrogel decreases fascial adhesion in total knee arthroplasty: A prospective randomized controlled study. J Biomater Appl 2019; 34:386-395. [DOI: 10.1177/0885328219852890] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
| | - Jae-Young Park
- Seoul National University Hospital, Seoul, Republic of Korea
| | - Do Weon Lee
- Seoul National University Hospital, Seoul, Republic of Korea
| | - Du Hyun Ro
- Seoul National University Hospital, Seoul, Republic of Korea
| | - Myung Chul Lee
- Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyuk-Soo Han
- Seoul National University Hospital, Seoul, Republic of Korea
| |
Collapse
|
|
33
|
Leprince S, Huberlant S, Allegre L, Warembourg S, Leteuff I, Bethry A, Paniagua C, Taillades H, De Tayrac R, Coudane J, Letouzey V, Garric X. Preliminary design of a new degradable medical device to prevent the formation and recurrence of intrauterine adhesions. Commun Biol 2019; 2:196. [PMID: 31123719 PMCID: PMC6531438 DOI: 10.1038/s42003-019-0447-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 04/26/2019] [Indexed: 01/22/2023] Open
Abstract
Intrauterine adhesions lead to partial or complete obliteration of the uterine cavity and have life-changing consequences for women. The leading cause of adhesions is believed to be loss of stroma resulting from trauma to the endometrium after surgery. Adhesions are formed when lost stroma is replaced by fibrous tissue that join the uterine walls. Few effective intrauterine anti-adhesion barriers for gynecological surgery exist. We designed a degradable anti-adhesion medical device prototype to prevent adhesion formation and recurrence and restore uterine morphology. We focused on ideal degradation time for complete uterine re-epithelialization for optimal anti-adhesion effect and clinical usability. We developed a triblock copolymer prototype [poly(lactide) combined with high molecular mass poly(ethylene oxide)]. Comparative pre-clinical studies demonstrated in vivo anti-adhesion efficacy. Ease of introduction and optimal deployment in a human uterus confirmed clinical usability. This article provides preliminary data to develop an intrauterine medical device and conduct a clinical trial.
Collapse
Affiliation(s)
- Salome Leprince
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier, 34093 France
| | - Stéphanie Huberlant
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier, 34093 France
- Department of Gynecology and Obstetrics, University Hospital, Nîmes, 30900 France
| | - Lucie Allegre
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier, 34093 France
- Department of Gynecology and Obstetrics, University Hospital, Nîmes, 30900 France
| | - Sophie Warembourg
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier, 34093 France
- Department of Gynecology and Obstetrics, University Hospital, Nîmes, 30900 France
| | - Isabelle Leteuff
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier, 34093 France
- Department of Gynecology and Obstetrics, University Hospital, Nîmes, 30900 France
| | - Audrey Bethry
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier, 34093 France
| | - Cedric Paniagua
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier, 34093 France
| | - Hubert Taillades
- Experimental Department, University of Montpellier, Montpellier, 34000 France
| | - Renaud De Tayrac
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier, 34093 France
- Department of Gynecology and Obstetrics, University Hospital, Nîmes, 30900 France
| | - Jean Coudane
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier, 34093 France
| | - Vincent Letouzey
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier, 34093 France
- Department of Gynecology and Obstetrics, University Hospital, Nîmes, 30900 France
| | - Xavier Garric
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Montpellier, 34093 France
| |
Collapse
|
|
34
|
Hooker AB, de Leeuw RA, van de Ven PM, Brölmann HAM, Huirne JAF. Reproductive performance after the application of hyaluronic acid gel after dilation and curettage in women who have experienced at least one previous curettage: long-term results of a multicenter prospective randomized trial. Fertil Steril 2019; 110:1231-1238. [PMID: 30503111 DOI: 10.1016/j.fertnstert.2018.07.021] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 07/24/2018] [Accepted: 07/25/2018] [Indexed: 11/17/2022]
Abstract
OBJECTIVE To examine whether intrauterine application of auto-cross-linked hyaluronic acid (ACP) gel after dilation and curettage (D&C) improves reproductive performance. DESIGN Multicenter prospective randomized trial. SETTING One university and seven university-affiliated teaching hospitals. PATIENT(S) A total of 149 women who have experienced a miscarriage at <14 weeks of gestation, with at least one previous D&C for miscarriage or termination of pregnancy, were randomly assigned to either D&C plus ACP gel (intervention group) or D&C alone (control group). A hysteroscopy was performed 8-12 weeks after the procedure. Where intrauterine adhesions (IUAs) were found, adhesiolysis was executed. INTERVENTION(S) Participants received questionnaires 3, 6, and 12 months after the initial D&C procedure with questions regarding menstrual pattern, conception, and reproductive outcome. MAIN OUTCOME MEASURE(S) Reproductive outcomes during the 12 months after the D&C procedure. RESULT(S) Outcomes were available for 149 women: 77 in the intervention group and 72 in the control group. The conception rates were, respectively, 71% (46/64) and 59.7% (40/67). There was no significant difference in the miscarriage, ongoing pregnancy, and live birth rates. The median times to conception were 5.5 and 7.1 months, respectively. CONCLUSION(S) Reproductive performance was similar in both groups although there was a significant difference in the prevalence of IUAs. Given the favorable reproductive outcome in this underpowered study and the fact that adhesiolysis was executed, no solid conclusion can be drawn. Future studies are needed to evaluate the effect of ACP gel on fertility and reproductive outcomes. CLINICAL TRIAL REGISTRATION NUMBER NTR 3120.
Collapse
Affiliation(s)
- Angelo B Hooker
- Department of Obstetrics and Gynecology, Zaans Medical Center, Zaandam, The Netherlands; Department of Obstetrics and Gynecology, Free University Medical Center, Amsterdam, The Netherlands.
| | - Robert A de Leeuw
- Department of Obstetrics and Gynecology, Free University Medical Center, Amsterdam, The Netherlands
| | - Peter M van de Ven
- Department of Epidemiology and Biostatistics, Free University Medical Center, Amsterdam, the Netherlands
| | - Hans A M Brölmann
- Department of Obstetrics and Gynecology, Free University Medical Center, Amsterdam, The Netherlands
| | - Judith A F Huirne
- Department of Obstetrics and Gynecology, Free University Medical Center, Amsterdam, The Netherlands
| |
Collapse
|
|
35
|
Dong L, Zheng X, Wang G. Peritoneal adhesions induce T h17/Treg imbalance in mice. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2018; 11:4352-4362. [PMID: 31949832 PMCID: PMC6962961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 02/10/2018] [Indexed: 06/10/2023]
Abstract
Naïve CD4+ T cells differentiate to a distinct subset to mount specific inflammatory responses while minimizing self-reactivity. Recent work has identified that an imbalance between T helper (Th) 17 cell and regulatory T (Treg) cells is involved in the pathophysiology of tumor immune responses. The factors that modulate the development of Th17 and Treg cells are variable but still unclear. Peritoneal adhesion is a common complication of surgery and peritonitis, which can lead to abdominal pain, intestinal obstruction, and infertility. In this study, we examined the role of peritoneal adhesions in development of Th17 and Treg cells and discovered that adhesions reduced proliferation of Th17 cells and promoted the Tregs. in particular we found that adhesion modulated the activity of signal transducers and activators of transcription (STAT) 5 which was critical for the development of Th17 and Treg cells.
Collapse
Affiliation(s)
- Linlin Dong
- Department of Anesthesiology, Qi Lu Hospital of Shan Dong UniversityJinan, Shandong, China
| | - Xiaoyu Zheng
- Department of Anesthesiology, Harbin Medical University Cancer HospitalHeilongjiang, China
| | - Guonian Wang
- Department of Anesthesiology, Harbin Medical University Cancer HospitalHeilongjiang, China
- Department of Pain Research Institute of Heilongjiang Academy of Medical SciencesHeilongjiang, China
| |
Collapse
|
|
36
|
A comprehensive review of Asherman's syndrome: causes, symptoms and treatment options. Curr Opin Obstet Gynecol 2018; 29:249-256. [PMID: 28582327 DOI: 10.1097/gco.0000000000000378] [Citation(s) in RCA: 125] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
PURPOSE OF REVIEW Intrauterine adhesions, also known as Asherman's syndrome, can have an impact on both reproductive outcomes and gynaecologic symptoms. Understanding the cause of intrauterine adhesions and the common clinical presentation will increase awareness of the condition and guide the patient to appropriate therapy. Surgical management offers favourable fertility outcomes and is often successful in restoring menstruation. RECENT FINDINGS Surgical management with hysteroscopic lysis of adhesions is the gold standard for treatment and adopting an office-based approach offers several advantages. Prevention of reformation of adhesions remains challenging and no single method for preventing recurrence has shown superiority. Cell-based therapies using endometrial stem/progenitor cells hold promise for future use in regenerating inadequate endometrium. SUMMARY Increased awareness of the symptoms suggestive of intrauterine adhesive disease, as well as recognition of common causes and preceding events, is crucial for early diagnosis, patient counselling and treatment. VIDEO ABSTRACT: http://links.lww.com/COOG/A36.
Collapse
|
|
37
|
The sticky business of adhesion prevention in minimally invasive gynecologic surgery. Curr Opin Obstet Gynecol 2018; 29:266-275. [PMID: 28582326 DOI: 10.1097/gco.0000000000000372] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW The negative impact of postoperative adhesions has long been recognized, but available options for prevention remain limited. Minimally invasive surgery is associated with decreased adhesion formation due to meticulous dissection with gentile tissue handling, improved hemostasis, and limiting exposure to reactive foreign material; however, there is conflicting evidence on the clinical significance of adhesion-related disease when compared to open surgery. Laparoscopic surgery does not guarantee the prevention of adhesions because longer operative times and high insufflation pressure can promote adhesion formation. Adhesion barriers have been available since the 1980s, but uptake among surgeons remains low and there is no clear evidence that they reduce clinically significant outcomes such as chronic pain or infertility. In this article, we review the ongoing magnitude of adhesion-related complications in gynecologic surgery, currently available interventions and new research toward more effective adhesion prevention. RECENT FINDINGS Recent literature provides updated epidemiologic data and estimates of healthcare costs associated with adhesion-related complications. There have been important advances in our understanding of normal peritoneal healing and the pathophysiology of adhesions. Adhesion barriers continue to be tested for safety and effectiveness and new agents have shown promise in clinical studies. Finally, there are many experimental studies of new materials and pharmacologic and biologic prevention agents. SUMMARY There is great interest in new adhesion prevention technologies, but new agents are unlikely to be available for clinical use for many years. High-quality effectiveness and outcomes-related research is still needed.
Collapse
|
|
38
|
Capmas P, Pourcelot AG, Fernandez H. Are synechiae a complication of laparotomic myomectomy? Reprod Biomed Online 2018; 36:450-454. [DOI: 10.1016/j.rbmo.2018.01.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Revised: 01/10/2018] [Accepted: 01/11/2018] [Indexed: 11/16/2022]
|
|
39
|
Xu W, Zhang Y, Yang Y, Zhang S, Lin X. Effect of early second-look hysteroscopy on reproductive outcomes after hysteroscopic adhesiolysis in patients with intrauterine adhesion, a retrospective study in China. Int J Surg 2017; 50:49-54. [PMID: 29203342 DOI: 10.1016/j.ijsu.2017.11.040] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Revised: 11/19/2017] [Accepted: 11/27/2017] [Indexed: 10/18/2022]
Abstract
OBJECTIVE The aim of this study was to assess the effect of early second-look hysteroscopy after hysteroscopic adhesiolysis for intrauterine adhesions (IUAs) on the pregnancy rate (PR) and live birth rate (LBR). STUDY DESIGN It is a retrospective, observational study of 151 women were referred to our institution from January 2010 to January 2016. Operative hysteroscopy for treatment of IUAs and office hysteroscopic follow-up to assess IUAs. We investigated demographic characteristics, menstrual pattern, previous intrauterine surgery, reproductive history, ovarian preservation assessment, tubal patency examination, husband's semen test, obstetric parameters, and surgical variables to evaluate the effect of early second-look hysteroscopy after hysteroscopic adhesiolysis on the PR and LBR. RESULTS Of 151 women treated for IUAs, the general PR was 71.5% and LBR was 53.0%. The PR and LBR were higher in the earlier second-look group (compared with second hysteroscopy later than 2 months group) and the group which received less than three times adhesiolysis (p < 0.05). The PR was higher in the amenorrhea group (compared with normal menses group) and recurrent miscarriage group (compared with infertility group) (p < 0.05). Logistic regression showed that the second-look time interval, times of operation to relieve adhesion, and pregnancy history were associated with the PR, while age and the second-look time interval were associated with the LBR. CONCLUSIONS Early second-look hysteroscopic examinations within 2 months may increase the cumulative PR and LBR.
Collapse
Affiliation(s)
- Wenzhi Xu
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No.3 East Qing Chun Road, Hangzhou, 310016, PR China
| | - Yuxue Zhang
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No.3 East Qing Chun Road, Hangzhou, 310016, PR China
| | - Yang Yang
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No.3 East Qing Chun Road, Hangzhou, 310016, PR China
| | - Songying Zhang
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No.3 East Qing Chun Road, Hangzhou, 310016, PR China
| | - Xiaona Lin
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No.3 East Qing Chun Road, Hangzhou, 310016, PR China.
| |
Collapse
|
|
40
|
Bosteels J, Weyers S, D'Hooghe TM, Torrance H, Broekmans FJ, Chua SJ, Mol BWJ. Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility. Cochrane Database Syst Rev 2017; 11:CD011110. [PMID: 29178172 PMCID: PMC6486292 DOI: 10.1002/14651858.cd011110.pub3] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Observational evidence suggests a potential benefit with several anti-adhesion therapies in women undergoing operative hysteroscopy (e.g. insertion of an intrauterine device or balloon, hormonal treatment, barrier gels or human amniotic membrane grafting) for decreasing intrauterine adhesions (IUAs). OBJECTIVES To assess the effectiveness of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy, following operative hysteroscopy for treatment of female subfertility. SEARCH METHODS We searched the following databases from inception to June 2017: the Cochrane Gynaecology and Fertility Group Specialised Register; the Cochrane Central Register of Studies (CRSO); MEDLINE; Embase; CINAHL and other electronic sources of trials, including trial registers, sources of unpublished literature and reference lists. We handsearched the Journal of Minimally Invasive Gynecology, and we contacted experts in the field. We also searched reference lists of appropriate papers. SELECTION CRITERIA Randomised controlled trials (RCTs) of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy in subfertile women. The primary outcome was live birth. Secondary outcomes were clinical pregnancy, miscarriage and IUAs present at second-look hysteroscopy, along with mean adhesion scores and severity of IUAs. DATA COLLECTION AND ANALYSIS Two review authors independently selected studies, assessed risk of bias, extracted data and evaluated quality of evidence using the GRADE method. MAIN RESULTS The overall quality of the evidence was low to very low. The main limitations were serious risk of bias related to blinding of participants and personnel, indirectness and imprecision. We identified 16 RCTs comparing a device versus no treatment (two studies; 90 women), hormonal treatment versus no treatment or placebo (two studies; 136 women), device combined with hormonal treatment versus no treatment (one study; 20 women), barrier gel versus no treatment (five studies; 464 women), device with graft versus device without graft (three studies; 190 women), one type of device versus another device (one study; 201 women), gel combined with hormonal treatment and antibiotics versus hormonal treatment with antibiotics (one study; 52 women) and device combined with gel versus device (one study; 120 women). The total number of participants was 1273, but data on 1133 women were available for analysis. Only two of 16 studies included 100% infertile women; in all other studies, the proportion was variable or unknown.No study reported live birth, but some (five studies) reported outcomes that were used as surrogate outcomes for live birth (term delivery or ongoing pregnancy). Anti-adhesion therapy versus placebo or no treatment following operative hysteroscopy.There was insufficient evidence to determine whether there was a difference between the use of a device or hormonal treatment compared to no treatment or placebo with respect to term delivery or ongoing pregnancy rates (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.42 to 2.12; 107 women; 2 studies; I² = 0%; very-low-quality evidence).There were fewer IUAs at second-look hysteroscopy using a device with or without hormonal treatment or hormonal treatment or barrier gels compared with no treatment or placebo (OR 0.35, 95% CI 0.21 to 0.60; 560 women; 8 studies; I² = 0%; low-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) was 9 (95% CI 5 to 17). Comparisons of different anti-adhesion therapies following operative hysteroscopyIt was unclear whether there was a difference between the use of a device combined with graft versus device only for the outcome of ongoing pregnancy (OR 1.48, 95% CI 0.57 to 3.83; 180 women; 3 studies; I² = 0%; low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without graft/gel or gel combined with hormonal treatment and antibiotics compared with using a device only or hormonal treatment combined with antibiotics, but the findings of this meta-analysis were affected by evidence quality (OR 0.55, 95% CI 0.36 to 0.83; 451 women; 5 studies; I² = 0%; low-quality evidence). AUTHORS' CONCLUSIONS Implications for clinical practiceThe quality of the evidence ranged from very low to low. The effectiveness of anti-adhesion treatment for improving key reproductive outcomes or for decreasing IUAs following operative hysteroscopy in subfertile women remains uncertain. Implications for researchMore research is needed to assess the comparative safety and (cost-)effectiveness of different anti-adhesion treatments compared to no treatment or other interventions for improving key reproductive outcomes in subfertile women.
Collapse
Affiliation(s)
- Jan Bosteels
- Cochrane BelgiumAcademic Centre for General PracticeKapucijnenvoer 33blok J bus 7001LeuvenBelgium3000
- University Hospital GhentObstetrics and GynaecologyDe Pintelaan 185GhentBelgium9000
| | - Steven Weyers
- University Hospital GhentObstetrics and GynaecologyDe Pintelaan 185GhentBelgium9000
| | - Thomas M D'Hooghe
- University Hospital GasthuisbergLeuven University Fertility CentreHerestraat 49LeuvenBelgium3000
| | - Helen Torrance
- University Medical CenterDepartment of Reproductive Medicine and GynecologyHeidelberglaan 100UtrechtNetherlands3584 CX
| | - Frank J Broekmans
- University Medical CenterDepartment of Reproductive Medicine and GynecologyHeidelberglaan 100UtrechtNetherlands3584 CX
| | - Su Jen Chua
- The University of AdelaideAdelaideAustraliaSA5005
| | - Ben Willem J Mol
- The University of AdelaideDiscipline of Obstetrics and Gynaecology, School of Medicine, Robinson Research InstituteLevel 3, Medical School South BuildingFrome RoadAdelaideSouth AustraliaAustraliaSA 5005
| | | |
Collapse
|
|
41
|
Xu Q, Duan H, Gan L, Liu X, Chen F, Shen X, Tang YQ, Wang S. MicroRNA-1291 promotes endometrial fibrosis by regulating the ArhGAP29-RhoA/ROCK1 signaling pathway in a murine model. Mol Med Rep 2017; 16:4501-4510. [PMID: 28849001 PMCID: PMC5647010 DOI: 10.3892/mmr.2017.7210] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Accepted: 06/08/2017] [Indexed: 12/17/2022] Open
Abstract
Intrauterine adhesions (IUAs) are caused by endometrial damage and are associated with a poor pregnancy prognosis including infertility, oligomenorrhea and recurrent pregnancy loss. Understanding the pathogenesis of IUAs may help prevent and treat this condition more effectively. The aim of the current study was to investigate the function of microRNA-1291 (miR-1291) during the development of IUAs following endometrial damage and elucidate the potential molecular mechanisms involved. The expression of Rho GTPase activating protein 29 (ArhGAP29), a putative target mRNA of miR-1291, was determined by immunohistochemical staining of human endometrial tissue from patients with IUAs and compared with normal endometrial tissues. ArhGAP29 expression was significantly decreased in endometrial tissues with IUAs compared with normal endometrium. Additionally, a murine IUAs model was developed and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) demonstrated that miR-1291 levels were significantly increased in the uterine tissue and plasma of the IUAs group compared with the normal mice. Furthermore, an miR-1291 antagomir was injected into the uterine cavity of experimental IUAs mice to block miR-1291. Hematoxylin and eosin and Masson's stain revealed that blocking miR-1291 significantly ameliorated endometrial fibrosis. Furthermore, levels of epithelial mesenchymal transition (EMT)-associated proteins, and ArhGAP29-RhoA/Rho-associated coiled coil containing protein kinase 1 (ROCK1) were measured in uterine tissue by western blot, RT-qPCR analysis and immunofluorescence staining. Levels of the mesenchymal marker proteins, vimentin and N-cadherin, were increased in the IUAs group mice, accompanied by a relative decrease in the epithelial marker proteins, cytokeratin and E-cadherin compared with normal murine endometrium. miR-1291 inhibition decreased RhoA/ROCK1 expression in the EMT pathway, but increased ArhGAP29 expression. Taken together, the findings indicate that miR-1291 acts upstream of ArhGAP29 to negatively regulate the RhoA/ROCK1 EMT pathway, ultimately leading to endometrial fibrosis. These studies may provide new potential therapeutic options and pave the way to use circulating miR-1291 as a clinical biomarker of endometrial fibrosis.
Collapse
Affiliation(s)
- Qian Xu
- Department of Gynecology Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Dong Cheng, Beijing 100006, P.R. China
| | - Hua Duan
- Department of Gynecology Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Dong Cheng, Beijing 100006, P.R. China
| | - Lu Gan
- Department of Gynecology Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Dong Cheng, Beijing 100006, P.R. China
| | - Xin Liu
- Department of Gynecology Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Dong Cheng, Beijing 100006, P.R. China
| | - Fang Chen
- Department of Gynecology Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Dong Cheng, Beijing 100006, P.R. China
| | - Xue Shen
- Department of Gynecology Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Dong Cheng, Beijing 100006, P.R. China
| | - Yi-Qun Tang
- Department of Gynecology Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Dong Cheng, Beijing 100006, P.R. China
| | - Sha Wang
- Department of Gynecology Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Dong Cheng, Beijing 100006, P.R. China
| |
Collapse
|
|
42
|
AAGL Practice Report: Practice Guidelines on Intrauterine Adhesions Developed in Collaboration With the European Society of Gynaecological Endoscopy (ESGE). J Minim Invasive Gynecol 2017; 24:695-705. [PMID: 28473177 DOI: 10.1016/j.jmig.2016.11.008] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Accepted: 11/15/2016] [Indexed: 11/15/2022]
|
|
43
|
AAGL practice report: practice guidelines on intrauterine adhesions developed in collaboration with the European Society of Gynaecological Endoscopy (ESGE). ACTA ACUST UNITED AC 2017; 14:6. [PMID: 28603474 PMCID: PMC5440524 DOI: 10.1186/s10397-017-1007-3] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 03/23/2017] [Indexed: 11/22/2022]
|
|
44
|
Prevalence of intrauterine adhesions after the application of hyaluronic acid gel after dilatation and curettage in women with at least one previous curettage: short-term outcomes of a multicenter, prospective randomized controlled trial. Fertil Steril 2017; 107:1223-1231.e3. [PMID: 28390688 DOI: 10.1016/j.fertnstert.2017.02.113] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Revised: 02/04/2017] [Accepted: 02/26/2017] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To examine whether intrauterine application of auto-crosslinked hyaluronic acid (ACP) gel, after dilatation and curettage (D&C), reduces the incidence of intrauterine adhesions (IUAs). DESIGN Multicenter; women and assessors blinded prospective randomized trial. SETTING University and university-affiliated teaching hospitals. PATIENT(S) A total of 152 women with a miscarriage of <14 weeks with at least one previous D&C for miscarriage or termination of pregnancy. INTERVENTION(S) Women were randomly assigned to either D&C plus ACP gel (intervention group) or D&C alone (control group). A follow-up diagnostic hysteroscopy was scheduled 8-12 weeks after the D&C procedure. MAIN OUTCOME MEASURE(S) The primary outcome was the number of women with IUAs and the secondary outcome was the severity of IUAs. RESULT(S) Outcomes were available for 149 women: 77 in the intervention group and 72 in the control group. The IUAs were observed in 10 (13.0%) and 22 women (30.6%), respectively (relative risk, 0.43; 95% confidence interval 0.22-0.83). Mean adhesion score and the amount of moderate-to-severe IUAs were significantly lower in the intervention group according to the American Fertility Society (AFS) and European Society of Gynecological Endoscopy classifications systems of adhesions. CONCLUSION(S) Intrauterine application of ACP gel after D&C for miscarriage in women with at least one previous D&C seems to reduce the incidence and severity of IUAs but does not eliminate the process of adhesion formation completely. Future studies are needed to confirm our findings and to evaluate the effect of ACP gel on fertility and reproductive outcomes. CLINICAL TRIAL REGISTRATION NUMBER NTR 3120.
Collapse
|
|
45
|
Effects of Aspirin and Intrauterine Balloon on Endometrial Repair and Reproductive Prognosis in Patients with Severe Intrauterine Adhesion: A Prospective Cohort Study. BIOMED RESEARCH INTERNATIONAL 2017; 2017:8526104. [PMID: 28251159 PMCID: PMC5303840 DOI: 10.1155/2017/8526104] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Revised: 01/05/2017] [Accepted: 01/10/2017] [Indexed: 12/19/2022]
Abstract
This study aimed to investigate the effects of estrogen in combination with aspirin and intrauterine balloon on the uterine endometrial repair and reproductive prognosis in patients after surgery for severe intrauterine adhesion (sIUA). We prospectively recruited 114 patients with sIUA. Intrauterine device (IUD) was placed and oral estrogen was administered after surgery. Patients were divided into control group and aspirin group. In addition, patients in aspirin group were subdivided into nonballoon group and balloon group. Results showed that, after therapy, the increase in endometrial thickness of aspirin groups was superior to control group (P < 0.05). The scores of intrauterine adhesion and menstruation were significantly improved in balloon group as compared to nonballoon group and control group, and significant differences were also observed between nonballoon group and control group (P < 0.05). Of 97 patients, 44.3% became pregnant after surgery, the live birth rate was 27.8%, and the miscarriage rate was 37.2%, but there were no significant differences among three groups (P > 0.05). Thus, aspirin may promote the uterine endometrial growth and repair after surgery for sIUA, and IUD in combination with intrauterine balloon may reduce the recurrence of intrauterine adhesion, but their effect on the reproductive prognosis is required to be further studied.
Collapse
|
|
46
|
Cheong Y, Bailey S, Forbes J. Randomized Controlled Trial of Hyalobarrier ® Versus No Hyalobarrier ® on the Ovulatory Status of Women with Periovarian Adhesions: A Pilot Study. Adv Ther 2017; 34:199-206. [PMID: 27900662 PMCID: PMC5216085 DOI: 10.1007/s12325-016-0453-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Indexed: 01/18/2023]
Abstract
Introduction Periadnexal adhesions are known to contribute to subfertility. The restoration of the tubo-ovarian anatomy is one the key principles in reproductive surgery, and this involves adhesiolysis. However, adhesion formation/reformation is very common after periovarian adhesiolysis. It is not known if the application of Hyalobarrier®, an anti-adhesion gel, around the adnexal region postsurgery influences ovulatory status. The study is a pilot randomized controlled trial (RCT) randomizing women into the application of Hyalobarrier® versus no Hyalobarrier® at the time of laparoscopy, where postsurgical ovulatory status and pregnancy rates were evaluated. Methods This was a pilot RCT where women were recruited from the gynecological and subfertility clinic who were deemed to require an operative laparoscopy. If intraoperatively they were found to have periovarian adhesions, they were randomized into having adhesiolysis with and without usage of Hyalobarrier®. Demographic details and intraoperative details including the severity, extent, and the ease of use of Hyalobarrier® were recorded. Prior to the surgery and postoperatively, the participants had their serum hormonal status (day 2 FSH, LH and day 21 progesterone) evaluated. Postoperatively, they underwent a follicular tracking cycle at 3 months. Results Fifteen women were randomized into use of Hyalobarrier® (study group) and 15 into the no Hyalobarrier® group (control group) between December 2011 and January 2014. There was no difference in the patient characteristics in terms of age, BMI, the number of previous pregnancies, or the extent, site, and severity of adhesions between the two groups. There was no significant difference between the study versus control groups in terms of the hormonal profile (day 2 FSH and day 21 progesterone) before or after surgery. The 3-month postoperative day 10–12 follicular tracking findings and endometrial thickness were similar between the study and control groups. Four women were pregnant in the study group (24%) and one in the control group (7%) cumulatively over 2 years. Conclusion The use of Hyalobarrier® post salpingo-ovariolysis did not influence follicular development as inferred from the results of the day 21 progesterone and folliculogram on day 10–12 3-month postsurgery. Trial Registration ISRCTN number, ISRCTN1833588. Funding Nordic Pharma.
Collapse
Affiliation(s)
- Ying Cheong
- Southampton University Hospital Foundation NHS Trust, Southampton, UK.
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
| | - Sarah Bailey
- Southampton University Hospital Foundation NHS Trust, Southampton, UK
- Faculty of Health Sciences, University of Southampton, Southampton, UK
| | - Jane Forbes
- Southampton University Hospital Foundation NHS Trust, Southampton, UK
| |
Collapse
|
|
47
|
Chen Y, Liu L, Luo Y, Chen M, Huan Y, Fang R. Prevalence and Impact of Chronic Endometritis in Patients With Intrauterine Adhesions: A Prospective Cohort Study. J Minim Invasive Gynecol 2016; 24:74-79. [PMID: 27773811 DOI: 10.1016/j.jmig.2016.09.022] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Revised: 09/20/2016] [Accepted: 09/22/2016] [Indexed: 11/28/2022]
Abstract
STUDY OBJECTIVE To evaluate the prevalence and impact of chronic endometritis (CE) in patients with intrauterine adhesions (IUAs). DESIGN Prospective cohort study (Canadian Task Force classification II-2). SETTING University-affiliated hospital. PATIENTS Eighty-two women with moderate to severe IUAs. INTERVENTIONS Transcervical resection of adhesions (TCRA) and endometrial biopsy were performed in all patients. According to results of the endometrial biopsy, participants were classified into 2 groups: 29 patients with CE (CE group) and 53 women without CE (NCE group). Second-look hysteroscopy assessed the impact of TCRA using the American Fertility Society classification system. MEASUREMENTS AND MAIN RESULTS Prevalence of CE, reformation of adhesions, and reduction of adhesion score were studied. Thirty-one women (37.8%) presented with visual signs of CE at hysteroscopy, confirmed by histology in 29 of 82 patients (35.4%). In hysteroscopic diagnosis of CE, sensitivity and specificity were 79.3% (23/29) and 84.9% (45/53), respectively. At second-look hysteroscopy, the recurrence of adhesions in the CE group was significantly higher than in the NCE group (44.8% vs 20.8%, respectively; p = .022). The median reduction of adhesion score was significantly greater in the NCE group (median, 8; range, 0-12) than in the CE group (median, 5; range, 0-10). CONCLUSION CE in women with IUAs may be a contributing factor in higher adhesion recurrence, indicating chronic inflammation may play a role in IUA recurrence. (Clinical Trial Registration No.: NCT02744807.).
Collapse
Affiliation(s)
- Yuqing Chen
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China.
| | - Lixiang Liu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China
| | - Yuanna Luo
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China
| | - Minghui Chen
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China
| | - Yang Huan
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China
| | - Ruili Fang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China
| |
Collapse
|
|
48
|
Review of nonsurgical/minimally invasive treatments and open myomectomy for uterine fibroids. Curr Opin Obstet Gynecol 2016; 27:391-7. [PMID: 26536205 DOI: 10.1097/gco.0000000000000223] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW The main purpose of this review is to collect the most recent evidence with regards to safety and effectiveness of the nonsurgical and minimally invasive treatment options for uterine fibroids. RECENT FINDINGS Among the nonsurgical options, uterine artery embolization (UAE), and in eligible patients, magnetic resonance-guided high-intensity focused ultrasound (MRgFUS) are emerging as effective alternatives to surgical options for treatment of symptomatic fibroids. MRgFUS is comparable to UAE, and appears to be a cost effective treatment option, especially in older women, although long-term data are awaited. The transvaginal route for radiofrequency ablation is a promising new nonsurgical alternative, which needs to be studied in larger trials to establish its safety and efficacy.The laparoscopic myomectomy results in less postoperative pain, reduced febrile morbidity, and shorter hospital stay when compared with open laparotomy. The newer robotic approach is comparable to traditional laparoscopic technique in short surgical outcomes but is associated with higher costs. Hysteroscopic myoma resection is an effective surgical intervention for submucous fibroids and prior misoprostol use can help in reducing cervical lacerations. SUMMARY UAE and MRgFUS can be offered as an alternative nonsurgical option for eligible women with symptomatic fibroids. Laparoscopic myomectomy remains a safe and effective surgical option with advantage of less postoperative pain and faster recovery compared with open laparotomy for women who wish to retain their fertility options.
Collapse
|
|
49
|
Abstract
Adverse events associated with hysteroscopic procedures are generally rare, but, with increasing operative complexity, it is now apparent that they are experienced more often. There exists a spectrum of complications that relate to generic components of procedures, such as patient positioning, anesthesia, and analgesia, to a number that are specific to intraluminal endoscopic surgery that largely comprise perforation and injuries to surrounding structures and blood vessels. Whereas a number of endoscopic procedures require the use of distending media, the response of premenopausal women to excessive absorption of nonionic fluids used for hysteroscopy is somewhat unique, and deserves special attention on the part the surgeon. There is also an increasing awareness of uncommon but problematic sequelae related to the use of monopolar radiofrequency uterine resectoscopes that involve thermal injury to the vulva and vagina. Furthermore, the uterus that has previously undergone hysteroscopic surgery may behave in unusual ways, at least in premenopausal women who experience menstruation or who become pregnant. Fortunately, better understanding of the mechanisms involved in these adverse events, as well as the use or development of a number of innovative devices, have collectively provided the opportunity to perform hysteroscopic and resectoscopic surgery in a manner that minimizes risk to the patient.
Collapse
|
|
50
|
Surgical treatment: Myomectomy and hysterectomy; Endoscopy: A major advancement. Best Pract Res Clin Obstet Gynaecol 2016; 34:104-21. [DOI: 10.1016/j.bpobgyn.2015.11.021] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 11/26/2015] [Indexed: 12/12/2022]
|