Prevention of intrauterine adhesions.

Intrauterine adhesions are a serious complication that occurs after intrauterine procedures, most often in connection with pregnancy. Manifestations such as amenorrhea, pelvic pain, and infertility for a woman, especially in reproductive age, are serious and together with intrauterine adhesions we call them Asherman's syndrome. Primary prevention after intrauterine procedures is important. Published studies show that the use of hyaluronic acid gel, especially after abortions, leads to the prevention of moderate and severe intrauterine adhesions and also increases the pregnancy rate.

A Network Meta-Analysis of Efficacy of Different Interventions in the Prevention of Postoperative Intrauterine Adhesions.

This network meta-analysis was conducted to compare the efficacy of six interventions, including anti-blocking agents, intrauterine contraceptive devices (IUDs), estrogens, intrauterine balloon, Foley catheter, and amnion graft for the prevention of intrauterine adhesions (IUAs). We searched PubMed, Embase, and Cochrane Library from inception to December 2016. Cohort studies meeting these six interventions in the prevention of IUAs were included. The combination of direct and indirect evidence was conducted to assess the odds ratio (OR) or weighted mean differences and surface under the cumulative ranking curves of the six interventions in the prevention of postoperative IUAs. Finally, 12 eligible cohort studies were included in this network meta-analysis. The results of this network meta-analysis demonstrated that during 1 to 2 months after operation, compared with the surgical group, anti-blocking agent, and estrogens presented with relatively low ratios of postoperative IUAs (OR = 0.30 95% confidence interval (CI) = 0.10-0.67; OR = 0.12, 95% CI = 0.01-0.78, respectively). Compared with IUDs, estrogens exerted comparatively low ratio of postoperative IUAs (OR = 0.10, 95% CI = 0.01-0.90), which indicated that anti-blocking agent and estrogens had relatively better prevention efficacy. The cluster analysis showed that estrogens had relatively better efficacy in the prevention postoperative IUAs. Overall, our findings support that estrogens had relatively better efficacy in the prevention of postoperative IUAs.

Antifibrotic Effects of Decellularized and Lyophilized Human Amniotic Membrane Transplant on the Formation of Intrauterine Adhesion.

OBJECTIVES: Intrauterine adhesion is a disease involving endometrial fibrosis that arises from injury to the basal layer of the endometrium. Here, we aimed to explore the preventive effects of decellularized and lyophilized amniotic membrane on endometrial fibrosis in a rat model of intrauterine adhesion. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 2 groups. For the intrauterine adhesion group, endometria of left uteri were scraped without treatment. For the intrauterine adhesion plus decellularized and lyophilized amniotic membrane transplant group, decellularized and lyophilized amniotic membrane was sutured onto the scraped wound of left uteri. Right uteri were kept as the control group. At 3, 7, 14, and 28 days after transplant, uteri were sampled for histologic and immunohistochemical evaluation. RESULTS: Histology examination revealed extensive fibrosis with significantly reduced numbers of endometrial glands in uteri in the intrauterine adhesion group. Immunohistochemical staining showed a remarked increase in expression of transforming growth factor ß1 (P < .01) and decreased expression of matrix metalloproteinase-9 (P < .01) in the intrauterine adhesion group. In rats with transplant of decellularized and lyophilized amniotic membrane, endometrial fibrosis apparently improved (P < .05) with reduced expression of transforming growth factor ß1 and increased matrix metalloproteinase-9 expression (P < .05). However, there were no significant differences in the number of endometrial glands or endometrial thickness between the 2 groups (P > .05). CONCLUSIONS: Development of intrauterine adhesion was prevented with transplant of decellularized and lyophilized amniotic membrane via suppression of transforming growth factor ß1 and increased production of matrix metalloproteinase-9 in a rat model.

Metformin Promotes Regeneration of the Injured Endometrium Via Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis.

Intrauterine adhesion (IUA) is now recognized as one of the most common diseases in reproductive-age women. Metformin, a well-known frontline oral antidiabetic drug, has been found effective in numerous different diseases. The aim of this study was to determine the effect of metformin on reducing adhesions in an animal model of IUA. Sprague-Dawley rats were randomized into 4 groups: sham operation, control, metformin-treated for 7 days, and metformin-treated for 14 days. To establish the IUA model, mechanical injury to the endometria of rats was induced with a mini curette. Metformin was injected intraperitoneally after surgery. A significant amelioration in both the number of glands and the fibrotic area, compared to those of the control group, was detected 14 days after metformin intervention. The expression levels of antigen KI-67 and vascular endothelial growth factor were increased at 7 and 14 days after treatment. However, the transforming growth factor-ß expression was decreased at 14 days after treatment. Endoplasmic reticulum stress-related apoptosis proteins (glucose-regulated protein 78, caspase-12, and CCAAT/enhancer binding protein (EBP) homologous protein) were downregulated after metformin treatment. Moreover, we determined that the effect of metformin was related to the inhibition of endoplasmic reticulum stress-induced apoptosis via the Phosphatidylinositol 3 kinase (PI3K)/Protein kinase B (AKT) and Extracellular regulated protein kinases1/2 pathways. In conclusion, metformin can attenuate the adhesion and promote the regeneration of the endometrium of the IUA rat, and metformin may serve as a novel therapeutic strategy for IUA patients.

Meta-analysis of the use of amniotic membrane to prevent recurrence of intrauterine adhesion after hysteroscopic adhesiolysis.

BACKGROUND: Various adjuvant therapies have failed to improve clinical symptoms and pregnancy rates among patients with moderate-to-severe intrauterine adhesion. OBJECTIVES: To evaluate the ability of amniotic membrane to prevent the recurrence of intrauterine adhesion after hysteroscopic adhesiolysis. SEARCH STRATEGY: The Cochrane Library, Embase, and PubMed databases were searched for articles published before December 31, 2017, using the terms: ("amnion") and ("intrauterine adhesions" or "Asherman syndrome" or "IUA" or "endometrial injury" or "uterine adhesion" or "hysteroscopic" or "hysteroscopic adhesiolysis"). SELECTION CRITERIA: Randomized controlled trials of amniotic membrane therapy after hysteroscopic adhesiolysis. DATA COLLECTION AND ANALYSIS: Four studies were included in the meta-analysis (300 patients in total). Dichotomous outcomes were expressed as relative risk (RR) with 95% confidence intervals (CIs). Continuous variables were expressed as mean difference. MAIN RESULTS: Amniotic membrane increased menstrual blood volume after hysteroscopic adhesiolysis (mean difference 6.15, 95% CI 4.20-8.11; P<0.001). By contrast, this treatment did not affect the rates of intrauterine adhesion recurrence (RR 0.84, 95% CI 0.61-1.16; P=0.290); pregnancy (RR 1.40, 95% CI 0.78-2.50; P=0.260); or spontaneous abortion (RR 0.88, 95% CI 0.38-1.99; P=0.750). CONCLUSIONS: The use of amniotic membrane increased menstrual blood volume but failed to improve other measures assessed in the current meta-analysis.

Asherman's Syndrome: it may not be all our fault.

Asherman's Syndrome (AS) is an acquired condition defined by the presence of intrauterine adhesions (IUA) that cause symptoms such as menstrual abnormalities, pelvic pain, infertility, recurrent miscarriage, abnormal placentation and attendant psychological distress. Classically, AS is considered an iatrogenic disease triggered by trauma to the pregnant uterus. Different factors can cause the destruction of the endometrium, thus affecting the endometrial stem cell niche and creating IUAs. Curettage of the pregnant uterus appears to be the most common source of this destruction. Nevertheless, some AS cases have been associated with congenital uterine abnormalities and infections, and there are some idiopathic cases without any prior surgical procedures, suggesting a putative constitutional predisposition to IUA. Factors reported to cause AS share an underlying inflammatory mechanism leading to defective endometrial healing and vascularization. Interestingly, distinct genetic profiles have been observed in the endometrium of AS patients. These data suggest that AS might not just be an iatrogenic complication, but also the result of a genetic predisposition. Elucidating the possible physiopathological processes that contribute to AS will help to identify patients at risk for this condition, providing an opportunity for prevention.

The Effect of Adjuvant Treatment to Prevent and Treat Intrauterine Adhesions: A Network Meta-Analysis of Randomized Controlled Trials.

Intrauterine adhesions (IUAs) can lead to partial or complete closure of the uterine cavity, which may result in symptoms including abnormal menstruation, infertility, and pelvic pain. A network meta-analysis was performed to assess the effect of adjuvant therapy on the prevention and treatment of IUAs. We searched electronic databases, including PubMed, Embase, and the Cochrane Library, up to May 5, 2017, without language restrictions. The primary outcomes in the present analysis were the rate of IUAs for prevention and the rate of IUA recurrence for treatment. The secondary outcomes included the IUA score and the rate of severity of IUAs. The treatments were then ranked by the surface under the cumulative ranking curve (SUCRA). We included 20 articles that involved a total of 1891 patients in our analysis. In the outcomes of prevention-related studies, an alginate hyaluronate-carboxymethylcellulose membrane (ACH) (n = 10, SUCRA score = 93.3%) was the adjuvant treatment that most effectively reduced IUA incidence. It was followed by intercoat (n = 10, SUCRA score = 74.7%) and misoprostol (n = 10, SUCRA score = 68.6%). In addition, auto-cross-linked hyaluronic acid (ACP) (n = 3, SUCRA score = 83.2%) and intercoat (n = 3, SUCRA score = 66.4%) each corresponded to a relatively high preventive effect against severe IUAs. In the treatment-related studies, ACP plus a balloon (n = 4, SUCRA score = 96.3%) and a freeze-dried amnion graft plus a balloon (n = 4, SUCRA score = 62.7%) most effectively reduced IUA recurrence and had a high probability of most effectively reducing IUA scores. Therefore, according to the prophylactic analysis, ACH and intercoat were most likely to prevent IUA development. In our analysis of agents used to prevent severe IUAs, we found that ACP and intercoat provided significant advantages and had high reliability. In our analysis of treatments, ACP plus a balloon and freeze-dried amniotic agents plus a balloon were most likely to reduce IUA recurrence and IUA scores after adhesiolysis.

Efficacy of freeze-dried amnion graft following hysteroscopic adhesiolysis of severe intrauterine adhesions.

OBJECTIVE: To evaluate the efficacy of freeze-dried amnion graft for prevention of intrauterine adhesion (IUA) reformation after hysteroscopic adhesiolysis. METHODS: A prospective randomized controlled trial was conducted among 88 women with severe IUAs who underwent hysteroscopic adhesiolysis at Beijing Obstetrics and Gynecology Hospital between July 15, 2015, and July 1, 2016. All participants had a balloon inserted into the uterine cavity for 1 week. Sterilized freeze-dried amnion graft covered the balloon portion of the Foley catheter among patients allocated to the amnion group (n=44), whereas patients in the control group (n=44) did not receive the graft. Follow-up hysteroscopy was performed 3 months after surgery. Preoperative and postoperative IUA scores, menstruation scores, and pregnancy rates were assessed. RESULTS: Both groups exhibited reductions in IUA scores and improvements in menstruation scores following treatment (P<0.001 for each measure). Compared with the control group, the amnion group had a lower IUA score (P=0.032) and a higher menstruation score (P<0.001) at follow-up. By contrast, the rates of IUA reformation and pregnancy were not significantly different between the two groups. CONCLUSION: Use of freeze-dried amnion graft was effective in reducing IUA reformation and improving menstruation (according to pictorial blood-loss assessment chart) following hysteroscopic adhesiolysis of severe IUAs. ClinicalTrials.gov: (NCT02496052).

Effectiveness of estrogen treatment before transcervical resection of adhesions on moderate and severe uterine adhesion patients.

Intrauterine adhesion (IUA), also known as Asherman's syndrome, is a common disease for among women. The extent of adhesion and pre-surgery hormone therapy greatly affects the function of uterine cavity. This current study investigates the association of different doses of estrogen before transcervical resection of adhesions (TCRA) surgery and clinical outcome in serious IUA. About 120 newly diagnostic serious IUA patients who underwent TCRA were randomly divided into three study groups: Estradiol valerate (progynova) 3 or 9 mg per diet before surgery and the control group. Follow-up hysteroscopy checkups were taken in 1- and 3-month post-operation. The effective power of 9 mg group was significantly higher than other groups. The 9 mg group achieved the best menstrual recovery rate in all study groups compared with the other two groups in 6 months post-operatively (p < 0.05). Our results confirmed estradiol valerateas an alternative effective drug for the prevention of IUAs before and after hysteroscopic surgery.

A comparison of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of adhesion reformation following hysteroscopic surgery for Asherman syndrome: a cohort study.

OBJECTIVE: To compare the efficacy of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of the adhesion reformation after hysteroscopic adhesiolysis for Asherman's syndrome. STUDY DESIGN: Retrospective cohort study of 107 women with Asherman's syndrome who were treated with hysteroscopic division of intrauterine adhesions. After hysteroscopic adhesiolysis, 20 patients had intrauterine balloon inserted, 28 patients had intrauterine contraceptive device (IUD) fitted, 18 patients had hyaluronic acid gel instilled into the uterine cavity, and 41 control subjects did not have any of the three additional treatment measures. A second-look hysteroscopy was performed in all cases, and the effect of hysteroscopic adhesiolysis was scored by the American Fertility Society classification system. RESULTS: Both the intrauterine balloon group and the IUD group achieved significantly (P<0.001) greater reduction in the adhesion score than that of the hyaluronic acid gel group and control group. The efficacy of the balloon was greater than that of the IUD (P<0.001). There was no significant difference in results between the hyaluronic acid gel group and the control groups. CONCLUSION: The insertion of an intrauterine balloon or intrauterine device is more effective than the use of hyaluronic acid gel in the prevention of intra-uterine adhesion reformation.

[Asherman's syndrome II--therapy, methods of guidance, prevention of readhesion processs, complications and results of therapy]. / Ashermanuv syndrom II--terapie, asistencní metody, prevence readhezí, komplikace a výsledky lécby.

OBJECTIVE: To describe the current knowledge about Asherman's syndrome: methods of therapy and guidance, preventions of readhesion process, complications and results of therapy. DESIGN: Review article. RESULTS: There are presented historic and recent methods for therapy of Asherman's syndrome and their postoperative results. The hysteroscopy is the gold standard in diagnostics and therapy in this time. For prevention of perforation there are used several methods of guidance. The most frequent methods are laparoscopic and ultrasound asistence. The most actual question in this time is using of antiadhesion products for preventing of readhesion process. Between described complications belong peroperative complications and complications of consecutive pregnancy. Every patient is endangered by abortion, premature delivery, IUGR and placenta accreta or increta. The results of therapy depend on degree of intrauterine finding and previous pregnancy anamnesis. CONCLUSION: The Asherman's syndrome is very complicated and severe disease that can significantly influence a possibility of woman conceive and give birth to a healthy child.

Asherman syndrome--one century later.

OBJECTIVE: To provide an update on the current knowledge of Asherman syndrome. DESIGN: Literature review. SETTING: The worldwide reports of this disease. PATIENT(S): Patients with Asherman syndrome who presented with amenorrhea or hypomenorrhea, infertility, or recurrent pregnancy loss. INTERVENTION(S): Hysteroscopy and hysteroscopic surgery have been the gold standard of diagnosis and treatment respectively for this condition. MAIN OUTCOME MEASURE(S): The etiology, pathology, symptomatology, diagnosis, treatment, and reproductive outcomes were analyzed. RESULT(S): This syndrome occurs mainly as a result of trauma to the gravid uterine cavity, which leads to the formation of intrauterine and/or intracervical adhesions. Despite the advances in hysteroscopic surgery, the treatment of moderate to severe Asherman syndrome still presents a challenge. Furthermore, pregnancy after treatment remains high risk with complications including spontaneous abortion, preterm delivery, intrauterine growth restriction, placenta accrete or praevia, or even uterine rupture. CONCLUSION(S): The management of moderate to severe disease still poses a challenge, and the prognosis of severe disease remains poor. Close antenatal surveillance and monitoring are necessary for women who conceive after treatment.

Síndrome de asherman. Factores asociados. Diagnóstico y manejo, Profamilia Medellín. 1983–1989 / Asherman Syndrome. Associated factors. Diagnosis and handling. Profamilia, Medellín 1983 – 1989

El síndrome de Adherencias Intrauterinas (Síndrome de Asherman) es una entidad que no ha sido estudiada en nuestro medio y por lo tanto no existen protocolos para diagnóstico y manejo ante un paciente con factores de riesgo para desarrollar la enfermedad. Se realizó un estudio descriptivo retrospectivo para evaluar incidencia, factores de riesgo, hallazgos histeroscópicos, tratamientos y resultados en pacientes con síndrome de Asherman en Profanilla Medellín desde enero de 1983 hasta abril de 1989. Se presentaron 68 casos, pero sólo fue posible recolectar datos en 55 pacientes. Los dos principales motivos de consulta o de remisión fueron amenorrea e infertilidad, presentándose en el 92 por ciento de las pacientes. El principal factor de riesgo encontrado fue el traumatismo intrauterino, de origen obstétrico o ginecológico encontrándose en el 81.8 por ciento de los casos. Todas las pacientes fueron evaluadas mediante histeroscopia, encontrándose en la mayoría de ellas (67.27) adherencias corporales, siguiendo en importancia adherencias combinadas, atrepsia total y adherencias ístmicas. Para el tratamiento se utilizaron procedimientos histeroscópicos, inserción de dispositivo intrauterino y terapia hormonal en la gran mayoría de las pacientes. En el 64.8 por ciento de las pacientes se documentó reaparición de la menstruación y en el 43 por ciento de las pacientes que deseaban embarazo se logró este objetivo. Al comparar la respuesta al tratamiento se vio que hubo una respuesta más favorable cuando se realizó ruptura con instrumento romo de las adherencias e inserción del dispositivo intrauterino, siendo esta diferencia estadísticamente significativa. Once pacientes lograron 16 embarazos de los cuales 7 fueron a término, 5 presentaron ruptura prematura de membranas y parto prematuro y 4 abortos del primer trimestre. Los factores de riesgo encontrados, los resultados y dificultades en el tratamiento, nos obligan a replantear tanto la indicación como la técnica p.