Comparing the efficacy and pregnancy outcome of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis in infertile women: a prospective, randomized, controlled trial study.

STUDY OBJECTIVE: To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion. DESIGN: A prospective, randomized, controlled trial study. SETTING: A tertiary university hospital. PATIENTS: A total of 130 patients with moderate (American Fertility Society [AFS] score of 5-8) and severe (AFS score of 9-12) intrauterine adhesions were recruited. INTERVENTIONS: 86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD). MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased(P<0.05), whereas endometrial thickness was significantly increased across the three groups(P<0.001). Notably, the decline in the AFS score in the balloon group was greater than that in the IUD-1-month group and IUD-2-month group(P<0.01), with no significant difference between the IUD groups(P = 0.298). Lastly, In addition, the extent of the increase in endometrial thickness(P = 0.502) and the pregnancy outcomes(P = 0.803) in the three groups were not significantly different. CONCLUSION: Inserting a balloon or placing an IUD for one or two months can effectively lower the risk of adhesion recurrence and restore the shape of the uterine cavity. While the therapeutic effect of the balloon was superior to that of the IUD, no significant differences were observed in the one-month and two-month IUD groups. TRIAL REGISTRATION: This research was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/enIndex.aspx ); Clinical trial registry identification number: ChiCTR-IOR-17,011,943 ( http://www.chictr.org.cn/showprojen.aspx?proj=17979 ). Date of trial registration: July 11, 2017.

A cost-effectiveness analysis of intrauterine spacers used to prevent the formation of intrauterine adhesions following endometrial cavity surgery.

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.

Every year, women in the United States (US) undergo surgery to treat intrauterine abnormalities to maintain or improve the uterus' ability to support fetal development and result in a term delivery. Despite the benefits of these procedures, damage caused to the endometrium (uterine lining) is associated with a risk of adherence of the endometrial cavity surfaces with scar tissue known as intrauterine adhesions (IUAs).Damage to the endometrium and the resulting IUAs may be associated with infertility, light or absent menstruation, pregnancy loss, and other pregnancy-related complications. Treating these conditions within the US healthcare system consumes resources and adds costs for healthcare payers (public and private insurance providers).To facilitate endometrial repair and to reduce or prevent IUAs, researchers have developed materials to place within the endometrial cavity following surgery to separate the endometrial surfaces during the early healing period. These intrauterine "spacers" are intended to improve patients' subsequent clinical outcomes and save money for healthcare payers. It is unknown whether these improved clinical outcomes offset the cost of the routine use of spacers following "at-risk" procedures that involve the endometrial cavity.We developed a model designed to determine the cost-effectiveness of an intrauterine spacer by quantifying improvements in clinical outcomes and the resultant cost savings for patients undergoing uterine surgeries with or without spacers. Our model predicted that routinely using such spacers following at-risk procedures would improve patient outcomes and reduce costs to US payers.

Improvement of vaginal probiotics Lactobacillus crispatus on intrauterine adhesion in mice model and in clinical practice.

BACKGROUND: Intrauterine adhesion (IUA) is a frequent acquired endometrial condition, for which there is no effective preventive or treatment. Previous studies have found that vaginal microbiota dysregulation is closely related to endometrial fibrosis and IUA. Therefore, we wondered whether restoration of vaginal microbiota by vaginal administration of L. crispatus could prevent endometrial fibrosis and ameliorate IUA. RESULTS: First, we created a mechanically injured mouse model of IUA and restored the mice's vaginal microbiota by the addition of L. crispatus convolvulus. The observations suggested that intrauterine injections of L. crispatus significantly decreased the degree of uterine fibrosis, the levels of IL-1ß and TNF-α in blood, and downregulated the TGF-ß1/SMADs signaling pathway in IUA mice. A therapy with L. crispatus considerably raised the abundance of the helpful bacteria Lactobacillus and Oscillospira and restored the balance of the vaginal microbiota in IUA mice, according to high-throughput sequencing. Then we conducted a randomized controlled trial to compare the therapeutic effect of L. crispatus with estrogen after transcervical resection of adhesion (TCRA). And the results showed that vaginal probiotics had a better potential to prevent intrauterine adhesion than estrogen. CONCLUSIONS: This study confirmed that L. crispatus could restore vaginal microbiota after intrauterine surgery, inhibit endometrial fibrosis, and finally play a preventive and therapeutic role in IUA. At the same time, it is a new exploration for the treatment of gynecological diseases with vaginal probiotics. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/ , identifier (ChiCTR1900022522), registration time: 15/04/2019.

The effect of the combined use of an intrauterine device and a Foley balloon in the prevention of adhesion following hysteroscopic adhesiolysis.

The aim of this study was to determine whether intrauterine device (IUD) combined with Foley balloon could obtain better efficacy in preventing re-adhesion for patients with intrauterine adhesions (IUAs). The data of 89 patients with IUAs, who underwent transcervical resection of adhesion (TCRA) operation, were retrospectively collected. According to the method used for preventing re-adhesion of the uterine cavity after TCRA, the enrolled patients were divided into IUD group, Foley balloon group and the combined group. The second-look hysteroscopy was carried out at 3 months after TCRA surgery. The severity and extent of IUA were scored by American Fertility Society (AFS) scoring system. The endometrial thickness (EMT) was measured by ultrasound. Furthermore, the menstruation and pregnancy outcomes were also assessed. Our results showed that the postoperative decrease in AFS score was significantly greater in the combined group than in the IUD group or in the Foley balloon group. The increase in menstrual score among the 3 groups was not significantly different. The difference between preoperative and postoperative values of EMT was greater in the combined group than in the other 2 groups. In conclusion, the effect of a Foley balloon combined with IUD in preventing re-adhesion after TCRA might be better than that of IUD or Foley balloon alone.

Efficacy of autologous platelet-rich plasma in preventing adhesion reformation following hysteroscopic adhesiolysis: a randomized controlled trial.

RESEARCH QUESTION: What is the efficacy of platelet-rich plasma (PRP) in reducing adhesion reformation in women with moderate to severe intrauterine adhesions (IUA)? DESIGN: In this randomized controlled trial, women with moderate-to-severe IUA were recruited between November 2019 and June 2021 from a university hospital and randomized into the PRP or control group. The PRP group was treated using an intrauterine-suitable balloon combined with PRP infusion following hysteroscopic adhesiolysis, whereas the control group received only the former intervention. The reductions in adhesion scores from before to after surgery and the adhesion reformation rate were analysed. RESULTS: A total of 123 participants successfully completed the study (PRP group, 63; control group, 60). Age, pregnancy history, menstrual score and American Fertility Society score before surgery were not significantly different between the two groups. At the second-look hysteroscopy, the PRP group had a significantly greater reduction in adhesion score than the control group (7 versus 6, respectively; P = 0.027). The postoperative adhesion reformation rates in the PRP group and the control group were 20.6% and 30.0%, respectively (risk ratio 0.69, 95% confidence interval 0.27-1.38, P = 0.232; number needed to treat 10.6). CONCLUSIONS: Intrauterine PRP infusion seems to be beneficial in reducing postoperative adhesion reformation following hysteroscopic adhesiolysis.

To study the current status of uterine adhesions after fetal residue and the preventive effect of using estrogen and progesterone sequential therapy combined with Foley balloon.

To investigate the current status of uterine adhesions in patients with residual fetus and analyze the preventive effect of estrogen and progesterone sequential therapy combined with Foley balloon. Eighty-six patients with residual fetus were divided into control group and observation group. On the basis of the treatment plan of the control group, the observation group received estrogen and progesterone sequential therapy combined with Floey balloon treatment. Clinical efficacy, postoperative recovery status (abdominal pain duration, vaginal bleeding duration, vaginal bleeding volume, refluid time), the incidence of intrauterine adhesions, uterine hemodynamics (uterine artery systolic maximum blood flow rate [Vmax], end diastolic blood flow rate [Vmin], resistance index [RI]), and the probability of complications were evaluated. Compared with the control group, the observation group achieved higher curative effect (P < .05); the observation group had shorter duration of abdominal pain, vaginal bleeding and refluid time, and lower vaginal bleeding (P < .05); the probability of intrauterine adhesions is lower (P < .05); before treatment, there is little difference in the levels of Vmax, Vmin, RI, and other indicators between the 2 groups (P > .05). After treatment, compared with the control group, the observation group Vmax, Vmin, and other indicators, the level was significantly lower, and the RI level was significantly higher (P < .05); the observation group had a lower probability of complications (P < .05). The likelihood of uterine adhesions after fetal remains is increased. The use of estrogen and progesterone sequential therapy in conjunction with Foley balloon therapy can improve treatment efficacy, improve uterine adhesion prevention, and promote patient recovery after surgery.

Protective Effects of Engineered Lactobacillus crispatus on Intrauterine Adhesions in Mice via Delivering CXCL12.

Endometrial injury is the main cause of intrauterine adhesions (IUA), and there is currently no effective prevention and treatment. Immune cells play an important role in damage repair by sensing the change in the microenvironment. Exogenous CXCL12 can promote tissue regeneration and repair by recruiting immune cells, but its effect and possible mechanism on endometrial regeneration and repair have not been reported. In the present study, we constructed an engineered a Lactobacillus crispatus strain by transforming a pMG36e plasmid carrying a CXCL12 gene into the bacterium, and developed two animal models, the intrauterine adhesion mice with or without diabetes to evaluate the positive effects of this strain on the prevention of IUA after accepting intrauterine surgery in normal and diabetic mice. The results showed that vaginal application of L. crispatus-pMG36e-mCXCL12 strains significantly diminished the levels of pro-inflammatory factors interleukin-1ß (IL-1ß) and tumour necrosis factor-α (TNF-α) in serum and uterine tissues of IUA mice, and resulted in the inhibition of the inflammatory (toll-like receptor 4/nuclear factor-κb, TLR4/NF-κB) and fibrotic (transforming growth factor-ß1/smads, TGF-ß1/Smads) signalling pathways in the uterine tissues. The high-throughput sequencing results further indicated that treatment with L. crispatus-pMG36e-mCXCL12 strains greatly increased the abundance of Lactobacillus spp. and reduced that of the pathogenic Klebsiella spp. in IUA mice. Furthermore, among intrauterine adhesion mice with diabetes, we obtained similar results to non-diabetic mice, that is, L.crispatus-pMG36e-mCXCL12 significantly improved fibrosis and inflammation in the uterine cavity of diabetic mice, and restored the vaginal microbiota balance in diabetic mice. Therefore, we speculated that vaginal administration of L. crispatus-pMG36e-mCXCL12 strains can effectively alleviate intrauterine adhesions by restoring the microbial balance and reducing inflammation and fibrosis caused by surgery.

Hysteroscopic and ultrasound evaluation of a novel degradable polymer film for the prevention of intrauterine adhesion formation after hysteroscopic surgery.

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.

The efficacy of auto-cross-linked hyaluronic acid gel in addition to oestradiol and intrauterine balloon insertion in the prevention of adhesion reformation after hysteroscopic adhesiolysis.

RESEARCH QUESTION: What is the efficacy of auto-cross-linked hyaluronic acid gel use in preventing adhesion reformation after intrauterine adhesiolysis? DESIGN: This was a single-centre, double-blind randomized controlled trial. RESULTS: In total 171 participants successfully completed the study (84 in the treatment group and 87 in the control group). There was no significant difference in pre-operative variables between the two groups. The primary outcome measure was the adhesion reformation rate at second-look and third-look hysteroscopy. At second-look hysteroscopy, there was no significant difference in adhesion recurrence rate between the treatment group (20.2%, 17/84) and the control group (23.0%, 20/87; P = 0.662). At third-look hysteroscopy, there was also no significant difference in adhesion recurrence rate between the treatment group (9.5%, 8/84) and the control group (11.5%, 10/87; P = 0.675). The secondary outcome measure was the median American Fertility Society (AFS) score, which was not significantly different at second-look hysteroscopy 4 weeks after surgery between the treatment group (0, range 0-4.0) and the control group (0, range 0-4.0; P = 0.475), and at third-look hysteroscopy 8 weeks after surgery between the treatment group (0, range 0-3.5) and the control group (0, range 0-4.0; P = 0.965). Regarding the menstrual flow improvement rate 3 months post-operatively, there was no significant difference between the treatment and control groups (67.9% versus 64.4%; P = 0.630). CONCLUSIONS: The application of auto-cross-linked hyaluronic acid gel does not seem to reduce the incidence and severity of intrauterine adhesion recurrence or affect the menstrual pattern after hysteroscopic removal of mild to moderate intrauterine adhesions.

Short- and Long-term Outcomes of Postoperative Intrauterine Application of Hyaluronic Acid Gel: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To systematically evaluate the role of hyaluronic acid (HA) gel and its derivatives in the postoperative prevention of intrauterine adhesions (IUA) and to assess whether HA gel could improve the pregnancy rate. DATA SOURCES: A structured search was performed in PubMed, Cochrane, Scopus, Web of Science, and Embase on February 2, 2022. METHODS OF STUDY SELECTION: We chose medical subject headings and relevant terms from other articles for the database search. The following intervention was selected: HA gel or related derivatives vs placebo in randomized controlled trials (RCTs). The following outcomes were selected: the rate and severity of IUA after intrauterine operations and pregnancy rate. After the full-text screening, 12 articles were included in the final analysis. The study quality and risk of bias were assessed with the Cochrane tool (www.training.cochrane.org/handbook). TABULATION, INTEGRATION, AND RESULTS: Data from 12 articles on 1579 patients were extracted and analyzed by 2 independent reviewers. According to the meta-analysis, HA gel could decrease the risk of IUA (risk ratio [RR], 0.50; 95% confidence interval [CI], 0.37-0.67; p = .005; I2 = 59%) after intrauterine operations. Subgroup analysis revealed a significant positive impact of HA gel on both groups receiving dilatation and curettage (RR, 0.42; 95% CI, 0.30-0.59; p = .86; I2 = 0) or hysteroscopic surgery (RR, 0.55; 95% CI, 0.38-0.80; p = .007; I2 = 66%). The sensitivity analysis showed that heterogeneity could be improved significantly by removing one study. The severity of IUA (mean difference = -0.92; 95% CI, -1.49 to -0.34; p <.00; I2 = 89%) was lower in the intervention group. Subgroup and sensitivity analyses did not significantly improve the heterogeneity. When the studies are classified by the volume of HA gel, 10 mL (RR, 0.40; 95% CI, 0.27-0.60; p = .96; I2 = 0) and 5 mL (RR, 0.34; 95% CI, 0.14-0.82; p = .36; I2 = 0) were effective in treating IUA. In contrast, HA gel <5 mL was not sufficient to prevent IUA (RR, 0.66; 95% CI, 0.43-1.01; p = .02; I2 = 71%; p = .05). The pregnancy rate was also improved by the use of HA gel (RR, 1.39; 95% CI, 1.13-1.72; p = .37, I2 = 0). CONCLUSION: HA gel helps prevent IUA and decreases the severity of IUA after intrauterine surgery. A greater volume (≥5 mL) of HA gel is recommended to prevent IUA, according to this analysis. Moreover, HA gel can increase the pregnancy rate after intrauterine surgery. However, these conclusions should be interpreted with caution because of the inadequate quality of some RCTs with relatively small sample sizes and sample heterogeneity. Large RCTs are required to verify these conclusions in the future.

Efficacy of hyaluronic acid on the prevention of intrauterine adhesion and the improvement of fertility: A meta-analysis of randomized trials.

BACKGROUND: and purpose:Intrauterine adhesion (IUA) and re-adhesion were common problems in women of childbearing age. The aim of our research was to evaluate the efficacy of hyaluronic acid gel on preventing IUA and improving the fertility. METHODS: A systematic search for randomized controlled trial (RCT) articles that tested the effectiveness of using hyaluronic acid gel during intrauterine surgery in prevention of IUA and improvement of fertility was performed in PubMed, Medline, Embase, the Cochrane Library and clinicaltrials.gov until December 2020. Data were extracted independently and analyzed using RevMan statistical software version 5.3. RESULTS: Twelve articles (11 studies) were deemed eligible for inclusion. There was a significantly reduced proportion of IUA after using hyaluronic acid gel during intrauterine operation (OR 0.39, 95% CI 0.29 to 0.52). It has significantly reduced the incidence of moderate-to-severe IUA after using hyaluronic acid gel, but no effect on the mild IUA. In addition, our analysis showed that the hyaluronic acid gel group was associated with a significant increased incidence of pregnancy (OR 1.64, 95% CI 1.08 to 2.50). CONCLUSION: Our analysis confirmed that using hyaluronic acid gel during intrauterine operation seemed to be more helpful for patients with high risk of IUA. However, larger and well-designed studies would be desired in the future to confirm its efficacy and safety in protecting fertility.

Bioactive NIR-II Light-Responsive Shape Memory Composite Based on Cuprorivaite Nanosheets for Endometrial Regeneration.

Intrauterine adhesions (IUAs) caused by mechanical damage or infection increase the risk of infertility in women. Although numerous physical barriers such as balloon or hydrogel are developed for the prevention of IUAs, the therapeutic efficacy is barely satisfactory due to limited endometrial healing, which may lead to recurrence. Herein, a second near-infrared (NIR-II) light-responsive shape memory composite based on the combination of cuprorivaite (CaCuSi4 O10 ) nanosheets (CUP NSs) as photothermal conversion agents and polymer poly(d,l-lactide-co-trimethylene carbonate) (PT) as shape memory building blocks is developed. The as-prepared CUP/PT composite possesses excellent shape memory performance under NIR-II light, and the improved operational feasibility as an antiadhesion barrier for the treatment of IUAs. Moreover, the released ions (Cu, Si) can stimulate the endometrial regeneration due to the angiogenic bioactivity. This study provides a new strategy to prevent IUA and restore the injured endometrium relied on shape memory composite with enhanced tissues reconstruction ability.

Arrowhead Composite Microneedle Patches with Anisotropic Surface Adhesion for Preventing Intrauterine Adhesions.

Biomedical patches are considered as a promising strategy to help tissue repair and regeneration, prevent tissue adhesion, and reduce neighboring friction. Here, novel arrowhead composite microneedle patches (MNPs) are presented with anisotropic surface adhesion and growth factor encapsulation using a heterogeneous template replication approach for endometrium repair and intrauterine adhesions (IUAs) prevention. The arrowhead structures bring about interlocking between the microneedle (MN) tips and tissues, allowing these MNPs to steadily adhere to the tissues. Besides, benefitting from the cytoadhesive needle-tip material and the antiadhesive base material, these MNPs possess anisotropic surface adhesion and can facilitate cell adhesion on one surface to repair damaged tissues while restrain tissue contact on the other to prevent adverse adhesion. In the meanwhile, the encapsulated growth factor can be delivered through the MNs to the deep tissue, further accelerating tissue repair. Additionally, as the bases are soft and their patterns are highly tunable, the MNPs can change their shapes flexibly to adjust to the irregular morphology of uteri. It is demonstrated that these MNPs show good performances in treating injured endometrium and preventing IUAs of a rat model, indicating their great potential in versatile postoperative adhesion prevention and other clinical applications.

Postsurgical barrier strategies to avoid the recurrence of intrauterine adhesion formation after hysteroscopic adhesiolysis: a network meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy of mechanical strategies to avoid the recurrence of intrauterine adhesions, to evaluate the impact on subsequent fertility after hysteroscopic adhesiolysis and to rank the available antiadhesive options. DATA SOURCES: MEDLINE, Scopus, ClinicalTrials.gov, CINAHL, Scielo, EMBASE, PROSPERO, Cochrane Library, conference proceedings, and international controlled trials registries were searched without temporal, geographic, and language restrictions. STUDY ELIGIBILITY CRITERIA: Randomized trials that analyzed the recurrence, reproductive outcomes, or both in women undergoing hysteroscopic adhesiolysis followed by mechanical prevention of intrauterine adhesions were included. The exclusion criteria included the following: quasi-randomized trials and trials without randomization and studies including patients undergoing hysteroscopic surgery that was different from adhesiolysis. STUDY APPRAISAL AND SYNTHESIS METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension statement for network meta-analyses guidelines were followed. We performed a network meta-analysis based on the random effects model for mixed multiple treatment comparisons to rank the antiadhesive strategies by surface under the cumulative ranking curve area. Quality assessment was performed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was the recurrent presence of intrauterine adhesions. RESULTS: Eleven studies with data for 1596 women were identified as applicable. A copper intrauterine device together with an intrauterine balloon (surface under the cumulative ranking curve area=46.4%) or with cross-linked hyaluronic acid gel (surface under the cumulative ranking curve area=21.3%) seemed effective in preventing adhesions recurrence. Regarding the fecundity, hyaluronic acid gel demonstrated the highest pregnancy rates (surface under the cumulative ranking curve area=79.8%). The greatest degrees of change in the mean adhesions scores were found with the use of hyaluronic acid gel plus an intrauterine device (surface under the cumulative ranking curve area=38.9%). For postsurgical adhesion severity, hyaluronic acid gel plus intrauterine device (surface under the cumulative ranking curve area=49.9%) followed by intrauterine device alone (surface under the cumulative ranking curve area=30.8%) was ranked the highest. Dried amnion graft (surface under the cumulative ranking curve area=53.8%) and uterine balloon (surface under the cumulative ranking curve area=45%) showed the greatest menstrual pattern improvement. CONCLUSION: Cross-linked hyaluronic acid gel, with or without insertion of a copper intrauterine device, seems to be the most effective approach. However, the lack of a clear best therapy suggests the need for further studies to draw firm conclusions.

Focus on the Primary Prevention of Intrauterine Adhesions: Current Concept and Vision.

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.

A randomized controlled study on an integrated approach to prevent and treat re-adhesion after transcervical resection of moderate-to-severe intrauterine adhesions.

OBJECTIVES: This study aims to compare the clinical efficacy of an integrated approach to prevent and treat the recurrence of moderate-to-severe intrauterine adhesions (IUA) after hysteroscopic transcervical resection of adhesion (TCRA). METHODS: The study included a total of 70 patients with moderate-to-severe IUAs who underwent TCRA. Patients were randomly divided into two groups: treatment group (n=35) and control group n=35). In the treatment group, patients underwent balloon uterine stent placement and artificial cycle as well as received intrauterine perfusion of Danshen injection and oral Chinese medicine. In the control group, patients underwent balloon uterine stent placement and artificial cycle as well as received hyaluronic acid sodium and intrauterine device (IUD). Follow-up was performed after treatment of uterine cavity, menstruation and pregnancy. RESULTS: After 3 months of treatment, we observed a significantly lower rate of intrauterine re-adhesion (45.71% versus 77.14%, p=0.044) and significantly higher clinical efficiency (82.86% versus 77.14%, p=0.025) in the treatment group than those in the control group. After 6 months of treatment, we observed a significantly higher clinical efficiency in the treatment group than that in the control group (88.57% versus 68.57%, p=0.039). During the follow-up period, the pregnancy rate was 45.71% and 37.14% in the treatment group and control group, respectively, although the difference was not statistically significant (p=0.628). CONCLUSIONS: After surgical management of IUA, the integrated treatment combining a uterus stent placement and artificial cycle with Danshen injection and oral Chinese medicine can improve the condition of menstruation, and prevent and treat recurrence of IUA.

The Effect of Disulfiram in the Prevention of Postoperative Adhesion Formation in an Experimental Rat Uterine Horn Model.

Postoperative adhesions can cause serious complications, including intestinal obstruction, chronic abdominopelvic pain, and infertility in women. Here we investigate the effects of disulfiram on the postoperative adhesion model. Female Wistar rats were used (n = 72). The animals were separated into six groups (12 rats per group): group 1 (control), group 2 (300 mg/kg disulfiram administered for 3 days preoperatively), group 3 (50 mg/kg disulfiram administered for 3 days preoperatively and 14 days postoperatively), group 4 (300 mg/kg disulfiram administered for 3 days preoperatively and 14 days postoperatively), group 5 (50 mg/kg disulfiram administered 14 days postoperatively only), and group 6 (300 mg/kg disulfiram administered 14 days postoperatively only). A histopathologic examination was performed. Immunohistochemical stainings for matrix metalloproteinase-2 and 9 (MMP-2, and MMP-9) and vascular endothelial growth factor (VEGF) were evaluated. The macroscopic adhesion scores were significantly lower in the disulfiram groups (groups 3, 4, and 6) compared to the control group (p < 0.05). Inflammation scores were lower in all groups receiving disulfiram, but only reached statistical significance in group 4 (p < 0.05). In the immunohistochemical evaluation of the groups, MMP-9 was significantly lower in group 5 than group 4 (p < 0.05). There was no significant difference between the groups for MMP-2 and VEGF. We found that disulfiram reduced postoperative adhesion formation. Disulfiram becomes more effective (by directly reducing inflammation) when initiated during the preoperative period at high doses.

Effect of Gloriosa superba linn (EEGS) on mPT and monosodium glutamate-induced proliferative disorder using rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperplasia, Tumors and cancers are various forms of proliferative disorders affecting humans. Surgery is the main treatment approach while other options are also associated with adverse effects. There is therefore a need for the development of better alternative therapy that is cost effective and readily available with little or no adverse effect. Some bioactive agents in medicinal plants exhibit their anti-proliferative potential by induction of mitochondrial permeability transition pore (mPT) opening. Gloriosa superba, a medicinal plant, is folklorically used in the treatment of tumors and cancers. AIM OF THE STUDY: This study therefore aimed at investigating the effect of ethanol leaf extract of Gloriosa superba (EEGS) on mPT and monosodium glutamate-induced proliferative disorder in some specific tissues using rat model. MATERIALS AND METHODS: Isolated rat liver mitochondria were exposed to different concentrations (10, 30, 50, 70 and 90 µg/ml) of EEGS. The mPT pore opening, cytochrome c release, mitochondrial ATPase activity and lipid peroxidation were assessed spectrophotometrically. Caspases 9 and 3 activities were carried out using ELISA technique. Histological assessment of the liver, prostate and uterus of normal and monosodium glutamate (MSG)-treated rats were carried out. RESULTS: The results showed significant induction of mPT pore opening, release of cytochrome c, enhancement of mitochondrial ATPase activity, inhibition of lipid peroxidation and activation of caspases 9 and 3 activities by EEGS. The histological assessment revealed the presence of MSG-induced hepato-cellular damage, benign prostate hyperplasia and uterine hyperplasia which were ameliorated by EEGS co-administration. CONCLUSIONS: These findings suggest that EEGS contains putative agents that can induce apoptosis via induction of mPT pore opening and as well protect against MSG-induced hepato-cellular damage and proliferative disorder in prostate and uterus.

In Vivo Evaluation of the Efficacy and Safety of a Novel Degradable Polymeric Film for the Prevention of Intrauterine Adhesions.

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.

A randomized controlled study on an integrated approach to prevent and treat re-adhesion after transcervical resection of moderate-to-severe intrauterine adhesions

OBJECTIVES: This study aims to compare the clinical efficacy of an integrated approach to prevent and treat the recurrence of moderate-to-severe intrauterine adhesions (IUA) after hysteroscopic transcervical resection of adhesion (TCRA). METHODS: The study included a total of 70 patients with moderate-to-severe IUAs who underwent TCRA. Patients were randomly divided into two groups: treatment group (n=35) and control group n=35). In the treatment group, patients underwent balloon uterine stent placement and artificial cycle as well as received intrauterine perfusion of Danshen injection and oral Chinese medicine. In the control group, patients underwent balloon uterine stent placement and artificial cycle as well as received hyaluronic acid sodium and intrauterine device (IUD). Follow-up was performed after treatment of uterine cavity, menstruation and pregnancy. RESULTS: After 3 months of treatment, we observed a significantly lower rate of intrauterine re-adhesion (45.71% versus 77.14%, p=0.044) and significantly higher clinical efficiency (82.86% versus 77.14%, p=0.025) in the treatment group than those in the control group. After 6 months of treatment, we observed a significantly higher clinical efficiency in the treatment group than that in the control group (88.57% versus 68.57%, p=0.039). During the follow-up period, the pregnancy rate was 45.71% and 37.14% in the treatment group and control group, respectively, although the difference was not statistically significant (p=0.628). CONCLUSIONS: After surgical management of IUA, the integrated treatment combining a uterus stent placement and artificial cycle with Danshen injection and oral Chinese medicine can improve the condition of menstruation, and prevent and treat recurrence of IUA.