Aspirin-loaded thermo-sensitive chitosan-sodium alginate hydrogel for the prevention of intrauterine adhesions

Ultrasound and intrauterine adhesions: a novel structured approach to diagnosis and management.

Pregnancy-related intrauterine adhesion treatment: new insights

Effects of Operative Hysteroscopy with Antiadhesion Solution in the Patients Who Have Abnormal Uterine Bleeding or Intrauterine Lesions

Objective To compare the curative effects of three methods in the prevention of adhesion reformation after transcervical resection of adhesion (TCRA). Methods A total of 495 patients were involved, who were diagnosed as intrauterine adhesions (IUA) by hysteroscopy and received TCRA treatment in the Northwest Women and Children′s Hospital from January 2010 to January 2016. The 495 patients were randomly divided into A, B and C 3 groups by drawing lots. There were 180 IUA patients in group A, who were placed foley catheter ballon combined with absorbable anti-adhesion materials in uterine cavity to prevent adhesion reformation after TCRA. There were 168 IUA patients in group B, who were only placed foley catheter ballon in uterine cavity after TCRA. And there were 147 IUA patients in group C, who were placed intra-uterine device (IUD) in uterine cavity after TCRA. Meanwhile, three groups of patients were treated with estrogen-progestogen sequential therapy to repair endometrium. All patients were followed up after TCRA, and hysteroscopic examination was conducted at the third month after TCRA. Then according to IUA score criteria and the judgment of degree based on the 1988 American Society for Fertility (AFS) on hysteroscopic examination and clinical manifestations of patients with IUA, the IUA situation which included the total scores and the scores of scope of IUA, type of adhesions and menstrual status of three groups of patients, were evaluated again to evaluate efficacy of each method. The following items were statistically compared by the randomized controlled clinical trial: the general situation of patients, the IUA score by AFS and each item′s score before TCRA among three groups were compared. The effective rate, IUA score by AFS and each item′s score at the third month after TCRA among three groups were compared. Informed consent was signed with each patient before this study was implemented. Results ①According to the data collected before TCRA, there were no significant differences among three groups in the general situation of patients′s age, body mass index (BMI), the frequency of artificial termination of pregnancy or curettage, the IUA score by AFS and the each item′s score of scope of IUA, the type of adhesions and menstruation status (P>0.05). ②At the third month after TCRA, the effective rate of group A (88.3%, 159/180) was higher than that of group C(60.5%, 89/147), and the difference was statistically significant (χ2=16.000, P<0.001). ③At the third month after TCRA, the menstruation status score of group A was significantly lower than that of group C, and the difference was statistically significant (P<0.001). The scores of IUA scope, adhesions type and IUA score by AFS of group A were lower than those of group B and C, respectively; similarly, those of group B was lower than those of group C, and all the differences were statistically significant (P<0.05). Conclusions Among these three methods in the prevention of adhesion reformation after TCRA, the placement of the foley catheter ballon combined with absorbable anti-adhesion materials in uterine cavity has better curative effect than the placement of foley catheter ballon or IUD in uterine cavity. Key words: Gynatresia; Intrauterine devices; Comparative study; Female

To evaluate the efficacy and safety of auto-crosslinked hyaluronic acid (HA) gel for preventing intrauterine adhesion (IUA) after hysteroscopic adhesiolysis. A prospective, randomized, double blinded and controlled clinical trial (level I) was performed. According to American Fertility Society (AFS) scoring system, 120 patients (treatment group: 60 cases, control group: 60 cases) with moderate to severe IUA were enrolled. Upon completion of adhesiolysis, a Foley balloon catheter was first introduced into the uterine cavity and then 3 ml of auto-crosslinked HA gel for patients in the treatment group; patients in the control group, however, only received Foley balloon catheter. Second-look hysteroscopic examination was performed to all patients at 3 months postoperatively for evaluation of IUA. Primary endpoint was the reduction rate of IUA at 3 months after surgery. The secondary endpoints include total AFS score, score of each individual AFS category. At 3 months after surgery, auto-crosslinked HA gel resulted in significantly higher effective rate for reduction of adhesion, the effective rate were 76% (42/55) and 48% (27/56) respectively (P = 0.000 9); the total AFS score of treatment group was 2.1 ± 1.1, and significantly lower than that of control group (3.7 ± 2.5, P = 0.000 8). Application of auto-crosslinked HA gel after surgery significantly enhanced the improvement for each individual patient with regard to their adhesive type and menstrual pattern (P = 0.037 8, P = 0.000 4). The treatment group had significantly lower proportion of patients with moderate to severe adhesive stages than that of control group [13% (7/55) versus 38% (21/56), P = 0.000 6]. No adverse events and complications were observed. Auto-crosslinked HA gel coule be able to reduce IUA, decrease adhesion severity, and improve menopause postoperatively. This absorbable auto-crosslinked HA gel is proposed as a barrier for preventing IUA after intrauterine procedures.

Intrauterine adhesion prevention after hysteroscopy: a systematic review and meta-analysis

Objective To explore the clinical effects of sodium hyaluronate gel for preventing recurrence of moderate intrauterine adhesion (IUA). Methods From January 2013 to January 2014, a total of 72 patients with moderate IUA who underwent transcervical resection of adhesion (TCRA) by hysteroscopy in Department of Gynecology, Guangdong Maternal and Child Health Hospital were selected as research subjects. According to the prevention methods of IUA recurrence after TCRA, they were divided into study group (n=32) and control group (n=40). Patients in study group were given sodium hyaluronate gel in uterine cavity, placement of intrauterine device (IUD) and oral estradiol valerate and dydrogesterone after TCRA. Patients in control group were given placement of IUD and oral estradiol valerate and dydrogesterone after TCRA. Three months after TCRA treatment, the menstruation recoveries of two groups were observed, and re-examinations of hysteroscopy were performed on all patients in two groups to assess the effective rate of measures taken after TCRA treatment for preventing recurrence of IUA. Six months after TCRA treatment, clinical pregnancies of two groups were observed. The effective rates of measures taken after TCRA treatment for preventing recurrence of IUA and clinical pregnancy of two groups were compared by chi-square test. This study was approved by the Ethics Committee of Human Beings in Guangdong Maternal and Child Health Hospital and every subject signed informed consent of clinical research. Results ①There were no statistical differences between two groups in the aspects of age, times of artificial termination and so on (P>0.05). ②The effective rate of measures taken after TCRA treatment for preventing recurrence of IUA in study group was 71.9% (23/32), which was statistically higher than that of control group 15.0% (6/40), and the difference was statistically significant (χ2=5.237, P=0.022). After 6-month of treatment by TCRA, the clinical pregnancy rate in study group was 34.4% (11/32), and 15.0% (6/40) in control group, but there was no statistical difference between two groups in the clinical pregnancy rate (χ2=3.700, P=0.054). Conclusions As to moderate IUA patients, the use of sodium hyaluronate gel in uterine cavity, placement of IUD and oral estrin after TCRA treatment can promote menstrual recovery and improve uterine morphology, and effectively prevent the recurrence of IUA. As the sample size in this study is relatively small, whether this method is worthy of clinical application in preventing recurrence of IUA after TCRA treatment in patients with moderate IUA, it remains to be confirmed by large sample, multicenter, and randomized controlled trials. Key words: Sodium hyaluronate; Intrauterine adhesion; Treatment outcome; Recurrence; Transcervical resection of adhesion; Women

Ultrasound‐guided treatment of intrauterine adhesions in the outpatient setting

Objective To investigate the clinical effect of different methods of postoperative intrauterine adhesions in patients with uterine septum and intrauterine adhesions. Methods Fifty-four patients with uterine septum and 36 cases of intrauterine adhesions were randomly selected from voluntarily participated in this study in January 2015 to February 2016 and were underwent hysteroscopic surgery. They were divided into A group (n=14 cases, take IUD scheme of estradiol valerate combined with intrauterine), B group (n=22 cases, do not take any measures), C group (n=36 cases, take intrauterine contraceptive device scheme) and D group (n=18 cases, take estradiol valerate therapy) four groups according to the surgical procedures, compared the treatment effect. Results Forty-two cases of patients with fertility requirements of living birth rate increased significantly compared with the preoperative (P 0.05); A group had the lowest incidence of intrauterine adhesions, intrauterine adhesions in group A was lower than that of group B (P 0.05). Conclusions The hysteroscopic surgery, to complete mediastinum with severe intrauterine adhesions in patients with estradiol valerate is an ideal drug for prevention of intrauterine adhesions, and combined with intrauterine contraceptive therapy can effectively prevent the occurrence of uterine mediastinum and severe intrauterine adhesions. Key words: Hysteroscopy; Uterine septum; Intrauterine adhesion; Intrauterine device

The endometrial–myometrial junction: a fresh look at a busy crossing

It has recently been proposed that local tissue renin-angiotensin system activation has a role in post-surgical adhesion. Intrauterine adhesions are scar tissues that form in the endometrial cavity causing the walls of the uterine to adhere together. Women, undergoing major gynecological surgery, are exposed to a high risk of adhesion formation. Post-operative uterine adhesion is associated with chronic pain and infertility that are important problems following post-operation uterine adhesion. A local renin-angiotensin system has been found in the organs of the female reproductive system, for example in the endometrium. Data about the physiological roles of local RAS in the gynecological tract are largely unknown, but dysfunctional local RAS in the endometrium may contribute to this pathological condition. Local AngII/AT1R may be over-activated after surgical injury or hypoxia leading to an up-regulation of the molecular mechanisms that may lead to a chronic immune response, oxidative stress, and increase the expression of fibrotic molecules like TGF-β to induce the risk of connective fibrotic tissues. Based on AngII/AT1R pathological potential to induce pelvic and uterine adhesions, using angiotensin receptor blockers could be a therapeutic strategy for the prevention and treatment of post-surgical adhesions. IMPACT STATEMENT What is already known on this subject? Intrauterine adhesions are described as fibrotic scar tissues following gynecological surgeries. It’s reported that 55–100% of women are at risk of intrauterine adhesion after gynecological surgeries. Injury to tissues and hypoxia during the surgery, promote molecular mechanisms to contribute post-surgical adhesion. Recently evidence supports the existence of renin-angiotensin system components in the gynecological tract. Abnormal expression of local angiotensin II and AT1R in uterus tissue following gynecological surgeries up-regulate molecular mechanisms to induce post-operative adhesions. What do the results of this study add? Recently there has been an increased focus on the role of the local renin-angiotensin system in organ fibrosis. The results of this Mini-review article refer to the pathological roles of the local renin-angiotensin system in fibrotic bands formation after gynecological operations. Over-activation of local renin-angiotensin systems up-regulate molecular mechanisms such as inflammation and the TGF-β1 signalling pathway. TGF-β as a profibrotic molecule strongly induces the expression of some fibrotic molecules such as PAI and TIMP to increase the risk of intrauterine adhesions. What are the implications of these findings for clinical practice and/or further research? According to the biological roles of local renin-angiotensin system and AT1R following injuries to develop post-operative adhesion, the administration of ARBs may be considered as a new therapeutic strategy for the prevention of IUA.

Intrauterine adhesions (IUAs) can occur following an invasive intrauterine procedure as a result of the normal healing process of the damaged endometrium/myometrium1. Although several interventions have been proposed for preventing the occurrence of IUAs, such as use of hyaluronic acid gel or polyethylene oxide-sodium carboxymethylcellulose gel, estrogen therapy and use of an intrauterine balloon or intrauterine device, their effectiveness is still uncertain2. The idea of using intrauterine pressure, through injection of saline solution into the uterine cavity, under ultrasound guidance for treating IUAs was first introduced in 20013. Subsequently, the potential therapeutic effect on mild adhesions of intrauterine insertion of a balloon and infusion of a distending medium was reported in 20144. More recently, ultrasound-guided balloon therapy for the treatment of mild IUAs in the outpatient setting was described5, 6. Here, we present a technique for adhesion prophylaxis following intrauterine surgery, based on the hypothesis that use of a balloon for dilatation of the uterine cavity and/or adhesiolysis might be effective using short repeated sequences in the most pivotal period. Before introducing the intrauterine balloon approach, we used hyaluronic acid gel routinely for prevention of IUAs. In our experience, repeat intrauterine balloon therapy can achieve better anatomic results and reduce the need for repeat intervention compared with use of hyaluronic acid gel (Figure 3 and Figure S2). The main disadvantages of the technique are the need for additional appointments and the pain associated with uterine-cavity distension. Although we are optimistic about the value of the method, well-designed studies are needed to evaluate its effectiveness and safety. A randomized controlled trial (RCT) completed recently found that intermittent intrauterine balloon therapy can prevent reformation of IUAs after hysteroscopic adhesiolysis8. Another RCT from the same group, evaluating the efficacy of intrauterine balloon dilatation therapy in adhesion prevention following hysteroscopic myomectomy, is ongoing9. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Intrauterine adhesions (IUA), which is characterized by endometrial fibrosis, continue to be the most common cause of uterine infertility globally. Our work revealed that 3 fibrotic progression markers (Vimentin, COL5A2, and COL1A1) were significantly increased in the endometrium of IUA patients. Mesenchymal stem cell-derived exosomes (EXOs) have been recently revealed as a cell-free therapy for fibrosis diseases. Nevertheless, the application of EXOs is restricted by the short residency duration in the target tissue. To overcome this limitation, herein, we reported an exosome-based regimen (EXOs-HP) that thermosensitive poloxamer hydrogel possessed the ability to efficiently promote the residency duration of EXOs in the uterine cavity. By downregulating fibrotic progression markers (Vimentin, COL5A2, and COL1A1), EXOs-HP could significantly restore the function and structure of the injured endometrium in the IUA model. Our work provides the theoretical and experimental foundation of EXOs-HP in treating IUA, highlighting the clinical potential of topical EXOs-HP delivery system in IUA patients.

Analysis of factors affecting the prognosis of patients with intrauterine adhesions after transcervical resection of adhesions

Predisposing Factors and Treatment Outcome of Different Stages of Intrauterine Adhesions