Intrauterine Adhesion Formation Research Articles

Establishment and comparison of different procedures for modeling intrauterine adhesion in rats: A preliminary study

The establishment of a stable animal model for intrauterine adhesion (IUA) can significantly enhance research on the pathogenesis and pathological changes of this disease, as well as on the development of innovative therapeutic approaches. In this study, three different modeling methods, including phenol mucilage combined mechanical scraping, ethanol combined mechanical scraping and ethanol modeling alone were designed. The morphological characteristics of the models were evaluated. The underlying mechanisms and fertility capacity of the ethanol modeling group were analyzed and compared to those of the sham surgery group. All three methods resulted in severe intrauterine adhesions, with ethanol being identified as a reliable modeling agent and was subsequently subjected to further evaluation. Immunohistochemistry and RT-PCR results indicated that the ethanol modeling group exhibited an increase in the degree of fibrosis and inflammation, as well as a significant reduction in endometrial thickness, gland number, vascularization, and endometrial receptivity, ultimately resulting in the loss of fertility capacity. The aforementioned findings indicate that the intrauterine perfusion of 95 % ethanol is efficacious in inducing the development of intrauterine adhesions in rats. Given its cost-effectiveness, efficacy, and stability in IUA formation, the use of 95 % ethanol intrauterine perfusion may serve as a novel platform for evaluating innovative anti-adhesion materials and bioengineered therapies.

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 immediately 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.

#342 : Asherman’s Syndrome Attributed to Genital Tuberculosis: A Case Report

Background: Asherman’s syndrome is a rare pathology secondary to intrauterine adhesion formation characterized by menstrual disorders and reproductive dysfunction. Although the cause intrauterine adhesion is thought to be associated with vigorous curettage or previous uterine surgery, other causes such as tuberculosis or schistosomiasis leading to intrauterine adhesion, are particularly important in developing countries. Case Presentation: A 33-year-old, multiparous woman, has applied for care to our hospital after 6 months of secondary amenorrhea. Other than occasional untreated heavy vaginal discharge, she had no past medical history nor prior uterine surgical procedure. No one in her family was treated for tuberculosis. Previously she was given combination oral contraceptive pills for 2 months, with no desirable outcome. On June 2022, we conducted a transvaginal ultrasound, with several features suggestive of uterine synechiae i.e. interrupted endometrial line in sagittal plain, small focal cystic areas within endometrium, and hyperechoic lesion with and without posterior shadowing. We decided to perform a hysteroscopy, with findings of mottled endometrium across the fundus and corpus of the uterus. Adhesiolysis was performed. An intrauterine foley catheter was inserted to prevent the reformation of adhesions. The specimen from this procedure were collected for pathology testing, with positive result for endometrial tuberculosis with caseous necrosis. The patient was treated with anti-tuberculosis drugs for 9 months. Upon completion of her tuberculosis treatment, she received combination oral contraceptive pills for endometrial restoration. She had her first period on May 2022, but only scanty bleeding occurred. On July 2022, she had two days of period with heavier blood flow. She is still closely observed. Conclusion: Asherman’s syndrome attributed to genital tuberculosis may emerge in otherwise healthy individual especially in countries where tuberculosis is prevalent. Although the results of hysteroscopic adhesiolysis in Asherman’s syndrome are encouraging, unfortunately, women with Asherman’s syndrome due to genital tuberculosis have poorer prognosis for restoration of menstrual function as there is usually complete destruction of endometrium by the mycobacterial disease. Well-designed clinical trials are needed to determine the most appropriate diagnostic and therapeutic modalities.

Operative hysteroscopy versus ultrasound-guided electric vacuum aspiration for removal of retained products of conception: A prospective cohort study

ObjectivesTo compare intrauterine adhesion (IUA) formation after hysteroscopic removal (HR) of retained products of conception (RPOC) with IUA formation after ultrasound-guided electric vacuum aspiration (EVA) and externally validate the outcomes of an RCT. Study designThis prospective cohort study was conducted from April 2015 until June 2022 in 2 Dutch teaching hospitals and one Belgian university hospital. Women opting for EVA underwent the procedure as soon as possible. In the HR group, the therapeutic hysteroscopy was performed at least eight weeks after the end of pregnancy. Postoperatively, an office second-look hysteroscopy was offered to all patients. Women were included if they had been diagnosed with RPOC ranging from 1 to 4 cm on ultrasound and did not want to participate in the RCT. EVA was performed using a Karman cannula. Operative hysteroscopy consisted either of hysteroscopic morcellation with the TruClear™ System or the Intrauterine BIGATTI Shaver or cold loop resection with a bipolar resectoscope. ResultsOf 178 included women, 124 were treated with HR and 28 with EVA. Outcomes of HR and EVA did not differ significantly in terms of complications (5.6 % vs 3.6 %; p = 1.00). Second-look hysteroscopy showed IUAs in 14 of 91 women (15.4 %) after HR and in 1 of 16 (6.3 %) after EVA (p = .461). Completeness of removal was significantly higher (90.1 %) after HR than after EVA (68.8 %) (p = .035). Additional operative hysteroscopy was required in 14.3 % of the HR group versus 37.5 % in the EVA group (p = .036). ConclusionIn our cohort study, no significant differences in IUAs or complications were found. RPOC removal with HR was more often complete than removal with EVA, and additional therapeutic hysteroscopy was less frequently required after HR. These findings need to be correlated with those of RCTs. Clinical trial registrationThe study was registered in de Dutch Trial Register (NTR4923). Date of registration 23-11-2014. Date of first enrollment 01-01-2015. https://trialsearch.who.int/Trial2.aspx?TrialID=NTR4923

Surgical techniques for mini-laparotomy myomectomy

The prevalence of uterine fibroids is estimated to be approximately 80%. Fibroids can be associated with abnormal uterine bleeding, pressure symptoms, and infertility. Given this high prevalence, approximately 30,000 myomectomies are performed in the United States per year. Minimally invasive approaches are preferred, if feasible. The minimally invasive techniques include laparoscopic, robot-assisted, hysteroscopic, and mini-laparotomy. To discuss the multiple techniques for optimizing the use of mini-laparotomy in minimally invasive myomectomy. We use intraoperative surgical video to demonstrate techniques that optimize the use of the mini-laparotomy for myomectomy. Cleveland Clinic. Patient's undergoing fertility preserving, minimally invasive myomectomy at the Cleveland Clinic. The patient(s) included in this video gave consent for publication of the video and posting of the video online, including social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, and Scopus), and other applicable sites. After the surgeon has selected to proceed with mini-laparotomy myomectomy, different techniques can be employed to optimize management. We demonstrate and discuss these techniques to ensure that surgeons have a set of tools to tackle a fibroid uterus. These techniques include direct palpation of the fibroids, use of a uterine manipulator to visualize the endometrial cavity, use of the uterine manipulator to aid in repair of the cavity if entered, suturing technique that avoids the endometrial cavity and therefore limits foreign body exposure and decreases intrauterine adhesion formation, utilization of barbed suture in a layered fashion, in-situ debulking to avoid injury to fallopian tubes and other critical uterine structures, easy identification of the optimal enucleation plane, use of single hysterotomy for multiple fibroids, visualization of the "Tortuga" sign, and evaluation of the abdominal cavity using the mini-laparotomy site as a port site. To limit postoperative adhesion formation, the investigators place cellulose-based adhesion barriers with peritoneum closure. Although the need for prolonged postoperative observation can be made on a case-by-case basis, we consider this as an outpatient surgery and anticipate same-day discharge for our patients. In this video, we perform a mini-laparotomy myomectomy optimally and describe the techniques employed. Specific techniques employed in mini-laparotomy myomectomy make the case safe, effective, and can lead to same-day discharge. Mini-laparotomy myomectomy is a technique used to perform minimally invasive myomectomy. Following the discussed steps, surgeons can be more confident in performing this method of myomectomy.

Incidence of Intrauterine Adhesions After Hysteroscopic Myomectomy in Patients Seeking Fertility

To study the incidence of intrauterine adhesions (IUAs) after hysteroscopic myomectomy. Previous studies report a range of incidence for IUAs after hysteroscopic myomectomy. A retrospective review study. An academic community hospital in the Boston metropolitan area. Patients undergoing hysteroscopic myomectomy at our institution from January 2019 to February 2022. Patients were excluded if they did not have plans for future fertility or had a new diagnosis of cancer. All patients underwent hysteroscopic myomectomy using bipolar resectoscope without postoperative medical or barrier treatment. All procedures were performed by 1 of 4 fellowship-trained high-volume gynecologic surgeons with resident and fellow assistance. Incidence of postoperative IUAs was assessed and treated using second-look office hysteroscopy. A total of 44 patients without preoperative IUAs underwent hysteroscopic myomectomy during our study period, and 4 patients (9.1%) developed new IUAs. Among 9 patients who were found to have preoperative IUAs and underwent concurrent hysteroscopic myomectomy and lysis of adhesions, we found a recurrence of IUAs in 5 patients (55.6%). We found the number, size, and deepest type of myoma removed were not correlated to an increased risk of new IUA formation. In addition, removing myomas on opposing walls during the same operation did not increase the incidence of new IUAs. Formation of IUAs after hysteroscopic myomectomy is a well-documented consequence. Our reported incidence of 9.1% of new IUAs that are not affected by the number, size, deepest type of myoma resected, and resection of myomas on opposing uterine walls contributes to the current literature. In addition, our finding of 55.6% of recurrent IUAs in patients undergoing both hysteroscopic myomectomy and lysis of adhesions highlights a high-risk population requiring additional study.

Restoring Fertility of Patients with Severe Asherman's Syndrome in the Office Setting: A Step-by-Step Recipe for Success

To describe an effective in-office hysteroscopic strategy to restore fertility of patients with severe Asherman's syndrome. A step-by-step video demonstration of the technique with an emphasis on the key portions of the procedure. A detailed narrated description of the steps is provided. Tertiary care University Hospital. Three patients were managed by hysteroscopy performed in the office setting without anesthesia. Case 1 is a 34-year-old woman with obstetrical history of first-trimester incomplete abortion treated with Dilation and Curettage (D&C), followed by a tubal ectopic pregnancy treated with laparoscopic partial salpingectomy and a subsequent pregnancy on the tubal stump treated with uterine artery embolization. Case 2 is a 40-year-old woman with history of tubal ectopic pregnancy treated with salpingectomy, a surgical first-trimester voluntary termination of pregnancy with D&C and a full term vaginal delivery complicated with retained products of conception that were removed with D&C. Case 3 is a 35-year-old woman with two previous first-trimester spontaneous miscarriages both treated with D&C. Case 1 and 3 were treated using miniaturized mechanical instruments only; in case 2, miniaturized mechanical instruments and the 15 Fr bipolar mini-resectoscope were used. Preoperative 2D and 3D ultrasound were used to predict the complexity of the cases and to guide the surgeon during the procedure. Intrauterine lysis of adhesions was concluded when both tubal ostia were visualized, and the uterine cavity was determined to have adequate shape and volume. At the end of the procedures, hyaluronic acid-based gel was applied to prevent new intrauterine adhesion formation. Two weeks after the initial procedure, a second look diagnostic hysteroscopy was performed. Only one patient (#1) needed additional lysis of adhesions; in this case, at the end of the procedure, a Word catheter was inserted as a barrier method for the prevention of adhesion formation. Eight weeks later, the word catheter was removed, and additional lysis of adhesions was performed. All the surgical procedures were performed without complication, and a healthy endometrium was observed at the second look hysteroscopy, in all the three patients. All 3 patients conceived after the procedure. Pregnancy was achieved after one IVF cycle with the transfer of one frozen embryo in case 1 and spontaneously in cases 2 and 3. Patient 1 was delivered by elective caesarean section due to placenta previa, while the other two patients had normal vaginal deliveries. Patient 1 had Retained Products of Conception requiring hysteroscopic removal using a 27 Fr Resectoscope. When using innovative miniaturized instruments and adequate surgical technique, hysteroscopic lysis of adhesions is a feasible and effective in-office strategy to restore fertility in patients with severe Asherman's syndrome. The use of 2D and 3D ultrasound played an important role in the preoperative workup of the patient with Asherman's syndrome.

Разработка экспериментальной модели патологии эндометрия (синдрома Ашермана)

Introduction. One of the most challenging problems faced in gynecology is Asherman’s syndrome (AS), characterized by the formation of intrauterine adhesions, partial or complete obliteration of the uterine cavity with scar tissue, and the loss of the functional layer of the endometrium following intrauterine interventions. Treatments for AS are not always effective. This indicates a need to search and evaluate the effectiveness of new approaches to the prevention of fibrosis and stimulation of endometrial regeneration. According to ethical principles, this is possible only when simulating AS on laboratory animals. The aim of the work is to develop an etiologically adequate model of AS in Sprague Dawley rats. Materials and methods. We simulated AS in 18 female Sprague Dawley rats that were divided into 3 groups (6 rats in each). Operations were performed in the estrus phase. We made longitudinal incision of the right uterine horns, and the endometrium was scraped out to the inner layer of the myometrium with the scalpel. Groups 1 and 2 underwent only endometrial scraping. In group 3 abdominal cavities were opened on day 7 after curettage and intrauterine adhesions were destroyed with a needle inserted into the horn. Then, the standard procedure for suturing surgical wound was performed. The animals were removed from the experiment on days 7 (group 1) and 15 (groups 2 and 3) after the surgery with an overdose of ether anesthesia. The tissue samples of the operated and non-operated uterine horns were fixed with 10% buffered formalin and embedded in paraffin; the sections were stained with hematoxylin and eosin. Results. Macroscopic examination on day 7 after the surgery showed that all females had a compaction and contraction of the operated area of the uterine horn and uterine cavity fluid. On day 15, fluid collection was more pronounced. After the destruction of the uterine adhesions in rats from group 3, there was no fluid collection or it was less voluminous than in females of other groups. Histological examination showed that on days 7 and 15 after endometrial curettage, the uterine cavity and the luminal epithelium covering it were absent due to complete replacement by connective tissue. Uterine glands were not detected or were individual. On day 7 after the destruction of the adhesions and on day 15 after endometrial scraping the subjects developed a small stenosed uterine cavity lined with luminal epithelium or a larger uterine cavity containing single or multiple adhesions covered with epithelium. The number of glands was significantly smaller than in the non-operated horn. Conclusion. To simulate Asherman’s syndrome, female Sprague Dawley rats in the estrus phase were scraped out of the endometrial layer of the right uterine horn. On days 7 and 15 after surgery, the uterine cavity and luminal epithelium were absent due to complete replacement with connective tissue, which proves the formation of intrauterine adhesions and the adequacy of the obtained model. A significant difference of the original model was the destruction of the adhesions on day 7 after endometrial damage to remove excess fluid in the uterine cavity and restore uterine patency, which led to the formation of the uterine cavity and re-epithelialization on day 15. The developed model of Asherman’s syndrome can be used to develop new approaches to the prevention of adhesive process and the restoration of endometrial structure and functionality. Keywords: Asherman’s syndrome, experimental model, rat uterus, endometrial curettage, intrauterine adhesions

Intrauterine adhesion after hysteroscopic myomectomy of submucous myomas.

To evaluate the frequency of intrauterine adhesion (IUA) after hysteroscopic myomectomy, and to analyze the association of IUA and the location of submucous myomas and the use of postoperative barrier (POB). Hysteroscopic myomectomy was performed in 217 patients with submucous myomas. The retrospective investigation was performed, and the cases were divided into three groups: cases with solitary submucous myoma (SSM; group 1), cases with apposing submucous myomas (ASMs; group 2) and cases with submucous myomas that were far from each other or not in apposition to one another (not apposing submucous myomas: NASMs; group 3). As POB, intrauterine device with oxidized regenerated cellulose and silicon sheet was inserted immediately after surgery. IUA formation after hysteroscopic myomectomy was more frequent in group 2 than groups 1 and 3 (p=0.03 and 0.01, respectively), despite the higher rates of POB use (p=0.02). There was no significant difference in IUA formation in cases with POB between each group (p=0.06 and 0.21, respectively). But in cases without POB, group 2 showed higher rates of IUA formation than group 1 (p=0.04) and group 3 (p=0.03). Multivariable analysis for IUA formation demonstrated that ASMs were a risk factor of IUA (hazard ratio [HR]=27.9, p < 0.01), and the use of POB was a prognostic factor for reduction of IUA formation (HR=0.08, p < 0.01). ASMs appear to be a risk factor for IUA formation. The use of POB may be associated with preventing IUA formation after hysteroscopic myomectomy.

Hysteroscopic Resection of Early Pregnancy Loss

<h3>Study Objective</h3> 1. To report a case of early pregnancy loss successfully managed by hysteroscopic resection; 2. To review the literature comparing hysteroscopic resection to dilation and curettage for retained products of conception; and 3. To review potential advantages of hysteroscopic resection over dilation and curettage for management of early pregnancy loss. <h3>Design</h3> Case Report. <h3>Setting</h3> Academic affiliated private practice. <h3>Patients or Participants</h3> One woman with early pregnancy loss. <h3>Interventions</h3> Hysteroscopic resection using a mechanical morcellation device. <h3>Measurements and Main Results</h3> Complete uterine evacuation as demonstrated by normal transvaginal ultrasound and cessation of bleeding two weeks postoperatively after hysteroscopic resection. Hysteroscopic fluid deficit was 365ml with minimal blood loss. Products of conception were confirmed on pathologic examination. There were no intraoperative or postoperative complications. Saline infusion sonogram four months postoperatively demonstrated a normal endometrial cavity with no intrauterine adhesions. <h3>Conclusion</h3> Surgical management of early pregnancy loss may be complicated by retained products of conception (RPOC) or intrauterine adhesion formation (IUA), which can lead to adverse future fertility outcomes. Hysteroscopic resection has been associated with less intrauterine adhesions, more complete tissue removal, and earlier time to conception compared to dilation and curettage (D&C) in cases of retained products of conception. Early pregnancy loss can also be characterized as retained products of conception with potentially similar benefits from hysteroscopic resection. Thus, hysteroscopic resection can be considered an alternative surgical technique for management of early pregnancy loss. This case report demonstrates the successful application of hysteroscopic resection in a case of early pregnancy loss.

A LIGHT-HVEM/LTβR axis contributes to the fibrosis of intrauterine adhesion

Intrauterine adhesion (IUA) is a fibrotic disease, with complex and multifactorial process, causing menstrual disorders, pregnancy loss or infertility. LIGHT (also named TNFSF14), mainly expressed by immune cells, has been reported to be associated with tissue fibrosis. However, the features of immunocyte subsets, the expression and roles of LIGHT and its receptor HVEM (herpes virus entry mediator) and LTβR (lymphotoxin beta receptor) in IUA remain largely unknown. Compared with the control group, we observed increased ratios of CD45+ cells, neutrophils, T cells, macrophages and decreased natural killer cells proportion, and high LIGHT expression on CD4+ T cells and macrophages in IUA endometrium. Further analysis showed there was a positive correlation between upregulated profibrotic factors (e.g., ɑ-smooth muscle actin, transforming growth factor β1) and HVEM in IUA endometrial tissue. More importantly, recombinant human LIGHT protein directly up-regulated the expression of HVEM, LTβR, profibrotic and proinflammatory factors expression in human endometrial stromal cells. These findings reveal abnormal changes of immune cell subsets proportion and the overexpression of LIGHT-HVEM/LTβR axis in IUA endometrium, should contribute to inflammation and fibrosis formation of IUA.

Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine Treatment.

Intrauterine adhesions (IUAs) have caused serious harm to women’s reproductive health. Although emerging evidence has linked intrauterine microbiome to gynecological diseases, the association of intrauterine microbiome with IUA, remains unknown. We performed metagenome-wide association, metabolomics, and transcriptomics studies on IUA and non-IUA uteri of adult rats to identify IUA-associated microbial species, which affected uterine metabolites and endometrial transcriptions. A rat model was used with one side of the duplex uterus undergoing IUA and the other remaining as a non-IUA control. Both 16S rRNA sequencing and metagenome-wide association analysis revealed that instead of Mycoplasmopsis specie in genital tract, murine lung pathogen Mycoplasmopsis pulmonis markedly increased in IUA samples and displayed a distinct positive interaction with the host immune system. Moreover, most of the IUA-enriched 58 metabolites positively correlate with M. pulmonis, which inversely correlates with a mitotic progression inhibitor named 3-hydroxycapric acid. A comparison of metabolic profiles of intrauterine flushing fluids from human patients with IUA, endometritis, and fallopian tube obstruction suggested that rat IUA shared much similarity to human IUA. The endometrial gene Tenascin-N, which is responsible for extracellular matrix of wounds, was highly up-regulated, while the key genes encoding parvalbumin, trophectoderm Dkkl1 and telomerase involved in leydig cells, trophectoderm cells, activated T cells and monocytes were dramatically down-regulated in rat IUA endometria. Treatment for rat IUA with estrogen (E2), oxytetracycline (OTC), and a traditional Chinese patent medicine GongXueNing (GXN) did not reduce the incidence of IUA, though inflammatory factor IL-6 was dramatically down-regulated (96–86%) with all three. Instead, in both the E2 and OTC treated groups, IUA became worse with a highly up-regulated B cell receptor signaling pathway, which may be associated with the significantly increased proportions of Ulvibacter or Staphylococcus. Our results suggest an association between intrauterine microbiota alterations, certain uterine metabolites, characteristic changes in endometrial transcription, and IUA and the possibility to intervene in IUA formation by targeting the causal factors, microbial infection, and Tenascin-like proteins.

Hysteroembryoscopy and hysteroscopic uterine evacuation of early pregnancy loss: A feasible procedure in selected cases.

Hysteroscopic uterine evacuation of early pregnancy loss using tissue removal devices seems to be a safe and feasible procedure in selected cases. The hysteroscopic approach allows the precise localisation of the gestational sac inside the uterine cavity. The endoscopic approach allows one to perform hysteroembryoscopy before uterine evacuation and this technique appears to be more accurate than dilatation & curettage for fetal chromosome karyotyping, with lower maternal cell contamination. This "under vision" procedure may reduce retained products of conception rates and risk of intrauterine adhesions formation.

Endometrial ablation plus levonorgestrel releasing intrauterine system versus endometrial ablation alone in women with heavy menstrual bleeding: study protocol of a multicentre randomised controlled trial; MIRA2 trial

BackgroundIt is estimated that between 12 to 25% of women who undergo an endometrial ablation for heavy menstrual bleeding (HMB) are dissatisfied after two years because of recurrent menstrual bleeding and/or cyclical pelvic pain, with around 15% of these women ultimately having a hysterectomy. The insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) immediately after endometrial ablation may inactivate residual untreated endometrium and/or inhibit the regeneration of endometrial tissue. Furthermore, the LNG-IUS may prevent agglutination of the uterine walls preventing intrauterine adhesion formation associated with endometrial ablation. In these ways, insertion of an LNG-IUS immediately after endometrial ablation might prevent subsequent hysterectomies because of persisting uterine bleeding and cyclical pelvic pain or pain that arises de novo. Hence, we evaluate if the combination of endometrial ablation and an LNG-IUS is superior to endometrial ablation alone in terms of reducing subsequent rates of hysterectomy at two years following the initial ablative procedure.Methods/designWe perform a multicentre randomised controlled trial in 35 hospitals in the Netherlands. Women with heavy menstrual bleeding, who opt for treatment with endometrial ablation and without contraindication for an LNG-IUS are eligible. After informed consent, participants are randomly allocated to either endometrial ablation plus LNG-IUS or endometrial ablation alone. The primary outcome is the hysterectomy rate at 24 months following endometrial ablation. Secondary outcomes include women’s satisfaction, reinterventions, complications, side effects, menstrual bleeding patterns, quality of life, societal costs.DiscussionThe results of this study will help clinicians inform women with HMB who opt for treatment with endometrial ablation about whether concomitant use of the LNG-IUS is beneficial for reducing the need for hysterectomy due to ongoing bleeding and/or pain symptoms.Trial registration Dutch Trial registration: NL7817. Registered 20 June 2019, https://www.trialregister.nl/trial/7817.

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

ObjectiveTo 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 designA 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 resultsA 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. ConclusionsAccording 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.

Incidence and risk factors of intrauterine adhesions after myomectomy

ObjectiveTo determine the incidence and risk factors for intrauterine adhesions (IUAs) after minimally invasive and open myomectomy and hysteroscopic myomectomy (HM).DesignRetrospective cohort study.SettingUniversity-affiliated fertility center.Patient(s)Patients aged ≥18 years undergoing robotic-assisted or conventional laparoscopic minimally invasive myomectomy, abdominal myomectomy, or HM between January 2007 and January 2017. Only patients who underwent uterine cavity evaluation within 12 months of surgery via hysteroscopy or hysterosalpingography were included. Patients were excluded if they had a history of IUA before myomectomy.Intervention(s)Not applicable.Main Outcome Measure(s)The primary outcomes of this study were the presence and severity of IUA. The secondary outcomes were the identification of risk factors for IUA formation. The severity of IUAs was scored by 2 investigators using a previously published grading system by March et al.Result(s)Of 1,315 patients who underwent myomectomy, 173 (13.2%) met the inclusion criteria. Intrauterine adhesions were identified in 9.3% of all patients, 75.0% of which were classified as minimal. The incidence of IUA did not vary by modality: 8.6%, minimally invasive myomectomy; 7.8%, abdominal myomectomy; and 11.8%, HM. There were no differences in incidence of IUA by the number or size of fibroids removed. Of patients with IUA, 87.5% had submucosal fibroids resected compared with 58.6% without IUA.Conclusion(s)The incidence of postoperative IUA in women undergoing myomectomy of any modality is relatively low (9.3%) and does not vary by modality alone. Most IUAs are of minimal degree. The presence of submucosal fibroids is associated with an increased risk of IUA in all modalities.

Postsurgical Intrauterine Adhesions after Hysteroscopic Myomectomy Using the Myoma Pseudocapsule Preservation Technique Evaluated bv Second-look Hysteroscopy: A Retrospective Comparative Study

To analyze the frequency and risk factors of postsurgical intrauterine adhesions (IUAs) using second-look hysteroscopy (SLH) in patients undergoing hysteroscopic myomectomy performed using the myoma pseudocapsule preservation technique for submucosal myoma. Retrospective cohort study. University hospital from January 2017 to December 2019. A total of 124 patients underwent hysteroscopic myomectomy and SLH. None. Surgical duration, intraoperative blood loss, number of enucleated myomas, volume of specimen, and postsurgical IUA evaluated by SLH. Postsurgical IUA were found in 5 of 124 cases (4.0%) at SLH. There were no cases of IUA formation in cases in which a single myomas was resected (0 of 83 cases, 0%); all cases were multiple myomas (5 of 41 cases, 12.2%), and IUA significantly occurred more frequently in cases of multiple myoma (p=.003). Univariate analyses showed that the IUA group contained a significantly larger number of enucleated uterine myoma (p <.001), required a longer operation (p=.003), and displayed an increased volume of intraoperative bleeding (p=.007), and the heavier the specimen, the greater the number of patients that had inserted an intrauterine device than the group that did not display postsurgical IUA. Multivariate logistic regression analysis of the risk factors of postsurgical IUA showed that the number of enucleated myomas was strongly associated with IUA (odds ratio, 1.45; 95% confidence interval, 1.06-1.97). The frequency of postsurgical IUA after hysteroscopic myomectomy was high in cases of multiple myoma and may be a risk factor. SLH should be actively pursued in cases where the patient desires to bear children, and an informed consent should be attained before performing surgery.

Hysteroscopic resection for management of early pregnancy loss: a case report and literature review

ObjectiveTo report a case of early pregnancy loss successfully managed by hysteroscopic resection, review the literature comparing hysteroscopic resection to dilation and curettage for retained products of conception, and review potential advantages of hysteroscopic resection over dilation and curettage for management of early pregnancy loss.DesignCase report.SettingPrivate practice.Patient(s)One woman with early pregnancy loss.Intervention(s)Hysteroscopic resection using a mechanical morcellation device.Main Outcome Measure(s)Complete uterine evacuation after hysteroscopic resection as demonstrated by a normal transvaginal ultrasound and cessation of bleeding 2 weeks after surgery.Result(s)The hysteroscopic fluid deficit was 365 ml, with minimal blood loss. Products of conception were confirmed on pathologic examination. There were no intraoperative or postoperative complications. A saline infusion sonogram obtained 4 months after surgery demonstrated a normal endometrial cavity with no intrauterine adhesions.Conclusion(s)Surgical management of early pregnancy loss may be complicated by retained products of conception (RPOC) or intrauterine adhesion formation, which can lead to adverse fertility outcomes in the future. Hysteroscopic resection of RPOC has been associated with fewer cases of intrauterine adhesions, more cases of complete tissue removal, and earlier time to conception compared with dilation and curettage. Early pregnancy loss can also be characterized as RPOC with potentially similar benefits from hysteroscopic resection. Thus, hysteroscopic resection can be considered as an alternative surgical technique for management of early pregnancy loss. This case report demonstrates the successful application of hysteroscopic resection in a case of early pregnancy loss.

Prevalence of Intrauterine Adhesions after Myomectomy: A Prospective Multicenter Observational Study

Objectives: The aim of this study was to evaluate intrauterine adhesion formation after laparoscopic and laparotomic myomectomy. Design: This is a prospective, multicenter, observational study (ClinicalTrials.gov ID: NCT04030273). Methods: We included patients after laparotomic and laparoscopic myomectomy. All patients underwent postsurgical diagnostic hysteroscopy, after 3 months. The intrauterine adhesion rate and associated factors were investigated. Results: Between January 2020 and December 2020, 38 and 24 consecutive patients underwent laparoscopic and laparotomic myomectomy, respectively. All diagnostic hysteroscopies were performed in the office setting without complications. Intrauterine adhesions were identified in 19.4% of women (95% CI: of 9–29%). Factors univariately associated (p < 0.2) with the presence of intrauterine adhesions after myomectomy were previous uterine surgery, the surgical approach (laparoscopic or laparotomic), the number of removed fibroids, the type and diameter of the largest myoma, and the opening of the uterine cavity. In the multivariable analysis, only the opening of the uterine cavity (odds ratio [OR] 51.99; 95% confidence interval [CI]: 4.53–596.28) and the laparotomic approach (OR, 16.19; 95% CI: 1.66–158.35) were independently associated with the identification of intrauterine adhesions after myomectomy. Limitations: One of the main limitations of our study is that we used uterine manipulator only in the laparoscopic group; in addition, we did not perform a preoperative hysteroscopy to evaluate the rate of intrauterine adhesions potentially present even before the myomectomy. Conclusions: The prevalence of intrauterine adhesions after 3 months from surgery was significantly associated with the opening of the uterine cavity and the laparotomic approach.

Peptidome analysis of human intrauterine adhesion tissues and the identification of antifibrotic peptide.

Intrauterine adhesion (IUA) is a common clinical endometrial disease, which can severely damage the fertility and quality of life in women. This study aims to find the differentially expressed endogenous peptides and their possible roles in IUA. Liquid chromatography-mass spectrometry was used to identify the peptidomic profiling of IUA tissues, and the differentially expressed peptides were screened out. Using real-time quantitative PCR, Western blotting, and immunocytochemistry staining, the function of six endogenous peptides was verified in vitro. It was found that peptide 6 (T6) (peptide sequence: TFGGAPGFPLGSPLSSVFPR) could inhibit the expression of TGF-β1-induced cell fibrosis in human endometrial stromal cell line and primary human endometrial stromal cell at a concentration of 50 μmol/L. This study provides new targets for further clarifying the formation and prevention of IUA.