Review of Asherman syndrome and its hysteroscopic treatment outcomes: experience in a low-resource setting.

BACKGROUND: Asherman syndrome is one of the endometrial factors that influence a woman's reproductive capacity. However, in our context, it needs to be well-documented. This study aimed to evaluate the clinical characteristics and hysteroscopic treatment outcomes of Asherman syndrome. METHOD: A retrospective follow-up study from January 1, 2019, to December 31, 2022, was conducted on cases of Asherman syndrome after hysteroscopic adhesiolysis at St.Paul's Hospital in Addis Ababa, Ethiopia. Clinical data were collected via telephone survey and checklist. Epidata-4.2 and SPSS-26 were employed for data entry and analysis, respectively. RESULT: A total of 177 study participants were included in the final analysis. The mean patient age was 31 years (range: 21-39) at the initial presentation, and 32.3 years (range: 22-40) during the phone interview. The majority of the patients (97.7%) had infertility, followed by menstrual abnormalities (73.5%). Among them, nearly half (47.5%) had severe, 38.4% had moderate, and 14.1% had mild Asherman syndrome. The review identified no factor for 51.4% of the participants. Endometrial tuberculosis affected 42 patients (23.7%). It was also the most frequent factor in both moderate and severe cases of Asherman syndrome. Only 14.7% of patients reported menstrual correction. Overall, 11% of women conceived. Nine patients miscarried, three delivered viable babies, and six were still pregnant. The overall rate of adhesion reformation was 36.2%. Four individuals had complications (3 uterine perforations and one fluid overload) making a complication rate of 2.3%. CONCLUSION: Our study revealed that severe forms of Asherman syndrome, which are marked by amenorrhea and infertility, were more common, leading to incredibly low rates of conception and the resumption of regular menstruation, as well as high recurrence rates. A high index of suspicion for Asherman syndrome, quick and sensitive diagnostic testing, and the development of a special algorithm to identify endometrial tuberculosis are therefore essential. Future multi-centered studies should focus on adhesion preventive techniques.

A retrospective cohort study to examine factors affecting live birth after hysteroscopic treatment of intrauterine adhesions.

OBJECTIVE: To evaluate independent factors that affect the chance of live birth (LB) after hysteroscopic adhesiolysis in patients with intrauterine adhesions. DESIGN: Retrospective cohort study. SETTING: Hysteroscopic center of Fuxing Hospital in Beijing, China. PATIENT(S): Patients diagnosed with Asherman syndrome between June 2020, and February 2022. INTERVENTION(S): Hysteroscopic adhesiolysis is followed by a second look hysteroscopy to assess the outcome and follow-up for a year. MAIN OUTCOME MEASURE(S): Live birth rate (LBR) without the use of assisted reproductive technologies at 12-month follow-up. RESULT(S): Of the 544 women included in the cohort, the pregnancy rate at the end of 1 year of follow-up was 47.6% (95% confidence interval [CI] 45.5%-49.7%), and the LBR was 41.0% (95% CI 38.9%-43.1%). Stepwise multiple logistic regression analysis identified three independent predictors of LB in decreasing order of significance: increase in menstrual flow after surgery (odds ratio [OR] 3.69, 95% CI 1.77-8.21), postoperative endometrial thickness in the midluteal phase (OR 1.53, 95% CI 1.31-1.80), and the severity of recurred adhesion at second-look hysteroscopy (OR 0.62, 95% CI 0.50-0.76). Among subjects with good independent prognostic factors, namely, increased menstrual flow after surgery, postoperative endometrial thickness in the midluteal phase >6 mm, and no or minimal recurrence of adhesions at second-look hysteroscopy, the LBR was 69.0% (95% CI 65.4%-72.6%). On the other hand, in women (n = 26) without any of the three good prognostic factors, none had a successful LB (0). CONCLUSION(S): Overall, the LBR after treatment for Asherman syndrome was 41.0%. The prognosis is dependent on three outcome measures after surgery, namely, improvement in menstrual flow, postoperative endometrial thickness, and the minimal degree of recurrent adhesions at second-look hysteroscopy.

Hysteroscopic Lysis of Complex Uterine Adhesions After Interventional Radiology-Guided Access.

OBJECTIVE: To demonstrate a novel surgical technique using hysteroscopic lysis of adhesions after interventional radiology (IR)-guided access in patients with severe intrauterine adhesions and challenging uterine access. DESIGN: This video illustrates the technique of the safe division of intrauterine adhesions after IR-guided access. SETTING: Conventional hysteroscopic adhesiolysis might be inadequate or risky in cases of severely narrowed or obstructed uterine flow tract, possibly resulting in incomplete adhesiolysis, false passages, or uterine perforation. This video presents 2 cases from a tertiary center involving a multidisciplinary team of a reproductive surgeon and an interventional radiologist. The first case involves a 38-year-old with severe Asherman syndrome, who experienced unsuccessful attempt to treat adhesions that was complicated by a false passage. The second case involves a 39-year-old with recurrent severe Asherman syndrome and a history of unsuccessful attempts at hysterosalpingogram and conventional hysteroscopic lysis of adhesions. INTERVENTIONS: In the IR suite, the patient was put in a lithotomy position on the fluoroscopy table. A vaginal speculum was inserted exposing the cervix. The procedure was performed using intravenous sedation and topical anesthetic spray applied to the cervix. Using fluoroscopy, a balloon cannula was inserted through the cervix, followed by contrast injection to assess uterine access. If there is no route, transvaginal ultrasound-guided needle cannulation of the main portion of the uterine cavity would be performed, approximating as closely as possible to the expected route of the cervical canal. A guidewire followed by a locked loop catheter was advanced through adhesions into the uterine cavity. The catheter was left protruding from the cervix to guide the hysteroscope. The patient was then transferred to the operating room for the hysteroscopic procedure. Under the guidance of the intrauterine catheter, the adhesions were carefully lysed using cold scissors. The endometrial cavity and tubal openings were inspected to ensure complete adhesiolysis and exclusion of any other copathologies. CONCLUSION: IR guidance can provide a safe and effective approach to hysteroscopic lysis of adhesions in patients with challenging intrauterine adhesions and difficult uterine access, such as patients with severe Asherman syndrome, intractable cervical stenosis, uterine wall agglutination, previous adhesiolysis failure, marked fixed retroverted retroflexed uteri, and previous false passage or uterine perforation.

A Patient with Partial 17α-Hydroxylase Deficiency Initially Diagnosed with Asherman Syndrome and Pheochromocytoma.

This study present a case of a 49-year-old woman who suffered from resistant hypertension, hypokalemia, hypomenorrhea, and infertility. She was hospitalized 6 years earlier for hypomenorrhea and abdominal pain at the Xiamen Maternity and Child Health Hospital, where she was diagnosed with Asherman syndrome. During hospitalization, a computed tomography examination revealed an adrenal mass. She was referred to Xiamen University Affiliated Zhongshan Hospital for pheochromocytoma and underwent surgical resection of the left adrenal gland. The adrenal cortex adenoma was confirmed by pathological biopsy. Six years later, the patient also presented with hypertension and hypokalemia to our emergency department. A diagnosis of 17α-hydroxylase deficiency was established through the analysis of clinical and laboratory characteristics. The genetic analysis of CYP17A1 revealed compound heterozygous mutations, 1 of which was a mutation of c.1226 C>G, and the other c.297+2T>C.

Multi-Lineage Human Endometrial Organoids on Acellular Amniotic Membrane for Endometrium Regeneration.

Asherman's syndrome is an endometrial regeneration disorder resulting from injury to the endometrial basal layer, causing the formation of scar tissue in the uterus and cervix. This usually leads to uterine infertility, menstrual disorders, and placental abnormalities. While stem cell therapy has shown extensive progress in repairing the damaged endometrium and preventing intrauterine adhesion, issues of low engraftment rates, rapid senescence, and the risk of tumorigenesis remain to be resolved for efficient and effective application of this technology in endometrial repair. This study addressed these challenges by developing a co-culture system to generate multi-lineage endometrial organoids (MLEOs) comprising endometrial epithelium organoids (EEOs) and endometrial mesenchymal stem cells (eMSCs). The efficacy of these MLEOs was investigated by seeding them on a biocompatible scaffold, the human acellular amniotic membrane (HAAM), to create a biological graft patch, which was subsequently transplanted into an injury model of the endometrium in rats. The results indicated that the MLEOs on the HAAM patch facilitated endometrial angiogenesis, regeneration, and improved pregnancy outcomes. The MLEOs on the HAAM patch could serve as a promising strategy for treating endometrial injury and preventing Asherman's syndrome.

Association of intrauterine synechiae with pituitary gonadotrophin pulse patterns: A pilot study.

BACKGROUND: Intrauterine synechiae (IS) is an acquired uterine condition that occurs when scar tissues (adhesions) form within the uterus and/or cervix, causing menstrual disturbance. However, approximately 50% of patients with IS are refractory to treatment. Therefore, other endocrine disturbances, such as gonadotropin disturbance, may affect treatment success. STUDY AIM: To analyze gonadotropin levels in women with and without IS. METHODS: Ten women with refractory IS experiencing amenorrhea since at least 6 months and nine with normal menstrual cycles (control group) were included in this study. Blood sample were collected every 10 minutes during a 4-h period. The serial ultrasound was performed in both groups for evaluating the cycle phase. Blood was collected when the follicles size was between 5-10 mm. Serum LH, FSH, progesterone and estradiol concentrations were measured. To detect LH and FSH pulses, the technique proposed by Santen and Bardin was adopted; therefore, one pulse was defined as a 20% increase in the concentrations as to the preceding point, followed by an important decrease. RESULTS: No differences were observed between the study groups at baseline. Estradiol levels were lower in the IS group than in the control group, but the difference was not statistically significant. During the first hour of monitoring, cumulative FSH pulsatile frequency of IS group was lower than one of control. CONCLUSION: Our data suggest that the estradiol levels of IS participants are lower than those of women with normal menstrual cycle. The role of this finding in the physiology of uterine synechiae requires further investigation.

Adjuvants to prevent reformation of adhesions following adhesiolysis for Asherman syndrome: a systematic review and meta-analysis.

Two international guidelines published on the management of Asherman syndrome (AS) have made recommendations on various adjuvant methods to prevent intrauterine reformation. Nevertheless, the effectiveness of these methods when used in primary or secondary prevention settings is different. Our aim is to assess the effectiveness of various adjuvant methods for the secondary prevention of intrauterine adhesions (IUAs). Articles were considered eligible if they included subjects with AS before surgery and compared a chosen method with either a control or a comparison group (using another method). The primary outcome was the IUA reformation rate at follow-up hysteroscopy. A total of 29 studies [15 randomised controlled trials (RCTs) and 14 cohort studies] were included. Adhesion reformation with various methods to prevented IUA reformation when compared with controls were: second-look hysteroscopy: [risk ratio (RR): 0.21, 95% confidence interval (CI): 0.05-0.90 (p = 0.02)]; intrauterine contraceptive device: RR: 0.64, 95% CI: 0.36-1.12 (p = 0.12); continuous intrauterine balloon: RR: 0.18, 95% CI: 0.05-0.68 (p = 0.01); intermittent intrauterine balloon: RR: 0.50, 95% CI: 0.31-0.80 (p = 0.004); anti-adhesion gel: RR: 0.80, 95% CI: 0.58-1.10 (p = 0.17); amnion graft: RR: 0.63, 95% CI: 0.44-0.91 (p = 0.01).

Decoding the endometrial niche of Asherman's Syndrome at single-cell resolution.

Asherman's Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman's Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman's Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.

MicroRNA-122-5p alleviates endometrial fibrosis via inhibiting the TGF-ß/SMAD pathway in Asherman's syndrome.

RESEARCH QUESTION: What is the effect of miR-122 on the progression and recovery of fibrosis in Asherman's syndrome? DESIGN: Endometrial tissue was collected from 21 patients, 11 with intrauterine adhesion (IUA) and 10 without IUA. Quantitative real-time polymerase chain reaction, immunofluorescence and Western blot were applied to observe the expression of mRNAs/miRNAs and protein, respectively. The endometrial physical injury was carried out in C57BL/6 mice to create an endometrial fibrosis model, with intrauterine injection of adenovirus to compare the antifibrosis and repair function of miR-122 on endometrium. The morphology of the uterus was observed using haematoxylin and eosin staining, and fibrosis markers were detected by immunohistochemistry. RESULTS: miR-122 expression was reduced in patients with IUAs, accompanied by fibrosis. MiR-122 overexpression reduced the degree of fibrosis in endometrial stromal cells. Further molecular analyses demonstrated that miR-122 inhibited fibrosis through the TGF-ß/SMAD pathway by directly targeting the 3' untranslated region of SMAD family member 3, suppressing its expression. Notably, miR-122 promoted endometrial regeneration and recovery of pregnancy capacity in a mouse endometrial injury model. CONCLUSIONS: miR-122 is a critical regulator for repair of endometrial fibrosis and provided new insight for the clinical treatment of intrauterine adhesions.

Etiology, Risk Factors, and Management of Asherman Syndrome.

Asherman syndrome is characterized by a triad of symptoms including pain, menstrual abnormalities, and infertility and is a result of intrauterine scar tissue after instrumentation of a gravid uterus. Saline sonohysterogram is typically the most sensitive diagnostic tool; however, hysteroscopy is the criterion standard for diagnosis. Treatment includes hysteroscopic-guided lysis of adhesion, with restoration of the anatomy of the uterine cavity. Several modalities are used in an attempt to reduce the reformation of scar tissue after surgery; however, there is no consensus on the ideal method. Stem cells and platelet-rich plasma are being explored as means of regenerative therapy for the endometrium, but data remain limited. At present, most individuals can have restoration of menstrual function; however, lower pregnancy rates and obstetric complications are not uncommon. These complications are worse for patients with a higher grade of disease. Efforts are needed in standardizing classification, reducing uterine instrumentation of the gravid uterus, and referring patients to health care professionals with clinical expertise in this area.

MRI for Diagnosing Intrauterine Adhesions.

OBJECTIVES: To prospectively assess the diagnostic accuracy of MRI and transvaginal ultrasound (TVS) as well as the prognostic value of MRI for intrauterine adhesions (IUAs), using hysteroscopy as the reference standard. DESIGN: Prospective observational study. SETTING: Tertiary medical centre. PATIENT(S): Ninety-two women with amenorrhea, hypomenorrhea, subfertility, or recurrent pregnancy loss who underwent MRI and in whom Asherman's syndrome was suspected upon TVS. INTERVENTION(S): MRI and TVS were conducted approximately 1 week before hysteroscopy. METHODS: Ninety-two patients suspected of having Asherman's syndrome were examined by MRI and TVS within 7 days of an upcoming hysteroscopy. All hysteroscopy procedures were performed during the early proliferative phase of the menstrual cycle. All hysteroscopic diagnoses were performed by an experienced expert. All MRIs were read by 2 experienced, blinded radiologists. RESULTS: MRI was highly accurate (94.57%), sensitive (98.8%), and specific (42.9%) for diagnosing IUAs with a positive predictive value of 95.5% and a negative predictive value of 75%. The diagnostic values of MRI and TVS were significantly different according to McNemar tests. Junctional zone signal and junctional zone alterations correlated with the stage of IUAs. CONCLUSION: MRI is markedly superior to TVS in terms of diagnostic accuracy for IUAs, with total agreement with hysteroscopic findings. However, the main advantage of MRI is that, unlike TVS and hysterosalpingography, it can be used to assess the risk of hysteroscopy and to predict postoperative recovery and future pregnancy based on the uterine junctional zone.

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.

The perinatal outcomes of women treated for Asherman syndrome: a propensity score-matched cohort study.

STUDY QUESTION: Do the perinatal outcomes of patients following hysteroscopic treatment for Asherman syndrome (AS) differ from that of a control population? SUMMARY ANSWER: Perinatal complications including placental issues, high blood loss, and prematurity in women after treatment for AS should be considered as moderate to high risk, especially in patients who have undergone more than one hysteroscopy (HS) or repeated postpartum instrumental revisions of the uterine cavity (Dilation and Curettage; D&C). WHAT IS KNOWN ALREADY: The detrimental impact of AS on obstetrics outcomes is commonly recognized. However, prospective studies evaluating perinatal/neonatal outcomes in women with AS history are sparse, and the characteristics accounting for the respective morbidity of AS patients remain to be elucidated. STUDY DESIGN, SIZE, DURATION: We conducted a prospective cohort study utilizing data from patients who underwent HS treatment for moderate to severe AS in a single tertiary University-affiliated hospital (enrolled between 01 January 2009 and March 2021), and who consequently conceived and progressed to at least 22nd gestational week of pregnancy. Perinatal outcomes were compared to a control population without an AS history, retrospectively enrolled concomitantly at the time of delivery for each patient with AS. Maternal and neonatal morbidity was assessed as well as the characteristics-related risk factors of AS patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our analytic cohort included a total of 198 patients, 66 prospectively enrolled patients with moderate to severe AS and 132 controls. We used multivariable logistic regression to calculate a propensity score to match 1-1 women with and without AS history based on demographic and clinical factors. After matching, 60 pairs of patients were analysed. Chi-square test was used to compare perinatal outcomes between the pairs. Spearman's correlation analysis was utilized to investigate the correlation between perinatal/neonatal morbidity and the characteristics-related factors of AS patients. The odds ratio (OR) for the associations was calculated by logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 60 propensity matched pairs, the AS group more frequently experienced overall perinatal morbidity, including abnormally invasive placenta (41.7% vs 0%; P < 0.001), retained placenta requiring manual or surgical removal (46.7% vs 6.7%; P < 0.001), and peripartum haemorrhage occurrence (31.7% vs 3.3%; P < 0.001). Premature delivery (<37 gestational weeks) was reported more frequently also for patients with AS (28.3% vs 5.0%; P < 0.001). However, no increased frequency of intra-uterine growth restriction or worsened neonatal outcomes were observed in AS group. Univariable analysis of risk factors for AS group morbidity outcomes revealed that the main factor related to abnormally invasive placenta was two or more HS procedures (OR 11.0; 95% CI: 1.33-91.23), followed by two or more D&Cs preceding AS treatment (OR 5.11; 95% CI: 1.69-15.45), and D&C performed postpartum as compared to post abortion (OR 3.0; 95% CI: 1.03-8.71). Similarly, two or more HS procedures were observed as the most important factor for retained placenta (OR 13.75; 95% CI: 1.66-114.14), followed by two or more preceding D&Cs (OR 5.16; 95% CI: 1.67-15.9). Premature birth was significantly associated with the number of preceding D&Cs (OR for two or more, 4.29; 95% CI: 1.12-14.91). LIMITATIONS, REASONS FOR CAUTION: Although the cohort of patients with AS was enrolled prospectively, a baseline imbalance was intrinsically involved in the retrospective enrolment of the control group. However, to reduce the risk of bias, confounding factors were adjusted for using propensity score matching. The limitation to the generalization of our reported results is the single institution design in which all patients were treated for AS in one tertiary medical centre. WIDER IMPLICATIONS OF THE FINDINGS: Within our search scope, our study represents one of the first and largest prospective studies of perinatal and neonatal outcomes in moderate to severe AS patients with a prospectively analysis of the risks factors of characteristics significantly influencing reported morbidities among patients with AS. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Charles University in Prague [UNCE 204065] and by the institutional grant of The General Faculty Hospital in Prague [00064165]. No competing interests were declared. TRIAL REGISTRATION NUMBER: N/A.

E. faecalis Sepsis and Asherman's Syndrome as Complications of Sonata System Transcervical Fibroid Ablation.

The Sonata System is a minimally invasive, ultrasound-guided transcervical fibroid ablation procedure for the management of symptomatic uterine fibroids. Since its approval by the US Food and Drug Administration in 2018, this procedure has demonstrated an excellent safety profile and postprocedure satisfaction rate. We present the case of a patient treated with Sonata, who subsequently developed bacterial sepsis and Asherman's syndrome-serious complications with long-term sequelae and implications for fertility. A nulligravid woman in her 40s presented in the outpatient setting with dysmenorrhea and bulk symptoms, with imaging showing an enlarged myomatous uterus compressing the urinary bladder. She desired minimally invasive, fertility-preserving management and underwent the Sonata procedure at an outside hospital. On postoperative day 3, she was admitted to our institution with abdominal pain, fever, tachycardia, and Enterococcus faecalis bacteremia. Despite 6 days of culture-directed antibiotic therapy, the patient remained septic with worsening symptoms and imaging findings and with persistent bacteremia. On hospital day 7, the patient underwent laparoscopic myomectomy and excision of hemorrhagic, infected myometrium. She recovered appropriately after surgery and was discharged home on hospital day 11 to continue 2 weeks of intravenous antibiotics. Nine months after myomectomy, the patient was diagnosed as having Asherman's syndrome. She subsequently had an early pregnancy loss with retained products of conception, requiring hysteroscopic lysis of adhesions and dilation and curettage. Ultimately, careful patient selection is critical for the optimal application of the Sonata procedure. Limiting the extent of fibroid necrosis after treatment is a reasonable goal to minimize the risk of secondary bacterial infection and adhesiogenesis as procedural sequelae.

Homogenous subpopulation of human mesenchymal stem cells and their extracellular vesicles restore function of endometrium in an experimental rat model of Asherman syndrome.

BACKGROUND: Asherman syndrome (AS), or intrauterine adhesions, is a main cause of infertility in reproductive age women after endometrial injury. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) are promising candidates for therapies that repair damaged endometria. However, concerns about their efficacy are attributed to heterogeneity of the cell populations and EVs. A homogenous population of MSCs and effective EV subpopulation are needed to develop potentially promising therapeutic options in regenerative medicine. METHODS: AS model was induced by mechanical injury in adult rat uteri. Then, the animals were treated immediately with homogeneous population of human bone marrow-derived clonal MSCs (cMSCs), heterogenous parental MSCs (hMSCs), or cMSCs-derived EV subpopulations (EV20K and EV110K). The animals were sacrificed two weeks post-treatment and uterine horns were collected. The sections were taken, and hematoxylin-eosin was used to examine the repair of endometrial structure. Fibrosis was measured by Masson's trichrome staining and α-SMA and cell proliferation by Ki67 immunostaining. The function of the uteri was explored by the result of mating trial test. Expression changes of TNFα, IL-10, VEGF, and LIF were assayed by ELISA. RESULTS: Histological analysis indicated fewer glands, thinner endometria, increased fibrotic areas, and decreased proliferation of epithelial and stroma of the uteri in the treated compared with intact and sham-operated animals. However, these parameters improved after transplantation of both types of cMSCs and hMSCs and/or both cryopreserved EVs subpopulations. The cMSCs demonstrated more successful implantation of the embryos in comparison with hMSCs. The tracing of the transplanted cMSCs and EVs showed that they migrated and localized in the uteri. Protein expression analysis results demonstrated downregulation of proinflammatory factor TNFα and upregulation of anti-inflammatory cytokine IL-10, and endometrial receptivity cytokines VEGF and LIF in cMSC- and EV20K-treated animals. CONCLUSION: Transplantation of MSCs and EVs contributed to endometrial repair and restoration of reproductive function, likely by inhibition of excessive fibrosis and inflammation, enhancement of endometrial cell proliferation, and regulation of molecular markers related to endometrial receptivity. Compared to classical hMSCs, cMSCs were more efficient than hMSCs in restoration of reproductive function. Moreover, EV20K is more cost-effective and feasible for prevention of AS in comparison with conventional EVs (EV110K).

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

OBJECTIVE: To describe an effective in-office hysteroscopic strategy to restore fertility of patients with severe Asherman's syndrome. DESIGN: 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. SETTING: Tertiary care University Hospital. INTERVENTIONS: 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. CONCLUSION: 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.

Asherman Syndrome after Uterine Artery Embolization: A Cohort Study about Surgery Management and Fertility Outcomes.

STUDY OBJECTIVE: To study the severity of intrauterine adhesions (IUA) after uterine arterial embolization and to evaluate fertility, pregnancy, and obstetrical outcomes after hysteroscopic treatment. DESIGN: Retrospective cohort. SETTING: French University Hospital. PATIENTS: Thirty-three patients under the age of 40 years who were treated by uterine artery embolization with nonabsorbable microparticles between 2010 and 2020 for symptomatic fibroids or adenomyosis, or postpartum hemorrhage. INTERVENTIONS: All patients had a diagnosis of IUA after embolization. All patients desired future fertility. IUA was treated with operative hysteroscopy. MEASUREMENTS AND MAIN RESULTS: Severity of IUA, number of operative hysteroscopies performed to obtain a normal cavity shape, pregnancy rate, and obstetrical outcomes. Of our 33 patients, 81.8% had severe IUA (state IV et V according to the European Society of Gynecological Endoscopy or state III according to the American fertility society classification). To restore fertility potential, an average of 3.4 operative hysteroscopies had to be performed [CI 95% (2.56-4.16)]. We reported a very low rate of pregnancy (8/33, 24%). Obstetrical outcomes reported are 50% of premature birth and 62.5% of delivery hemorrhage partly due to 37.5% of placenta accreta. We also reported 2 neonatal deaths. CONCLUSION: IUA after uterine embolization is severe, and more difficult to treat than other synechiae, probably related to endometrial necrosis. Pregnancy and obstetrical outcomes have shown a low pregnancy rate, an increased risk of preterm delivery, a high risk of placental disorders, and very severe postpartum hemorrhage. Those results have to alert gynecologists and radiologists to the use of uterine arterial embolization in women who desire future fertility.

Autologous bone marrow-derived nucleated cell (aBMNC) transplantation improves endometrial function in patients with refractory Asherman's syndrome or with thin and dysfunctional endometrium.

PURPOSE: The purpose was to evaluate the effect of intrauterine injection of aBMNC on the endometrial function in patients with refractory Asherman's syndrome (AS) and/or thin and dysfunctional endometrium (TE). STUDY DESIGN: This is a prospective, experimental, non-controlled study MATERIAL AND METHODS: The study was carried out between December 2018 and December 2020 on 20 patients, who were of age < 45 years and had oligo/amenorrhea and primary infertility due to refractory AS and/or TE. One hundred ml BM was extracted. aBMNC cells were separated according to generic volume reduction protocol by using the Cell Separation System SEPAX S-100 table top centrifuge system. We have evaluated CD34+, mononuclear cell (MNC), and total nucleated cell (TNC) counts. The transplantation aBMNC was performed by two intrauterine injections at an interval of one week, transvaginally into the endometrial-myometrial junction by an ovum aspiration needle. Midcyclic endometrial thickness (ET) and gestations after transplantation were evaluated. RESULTS: The mean TNC, MNC, and CD34+ cells were 11.55 ± 4.7 × 108, 3.85 ± 2.01 × 108, and 7.00 ± 2.88 × 106 at first injection, respectively, and 6.85 ± 2.67 × 108, 2.04 ± 1.11 × 108, and 3.44 ± 1.31 × 106 at second injection, respectively. The maximum posttransplantation ET was significantly higher than the maximum pretransplantation ET: 2.97 ± 0.48 vs. 5.76 ± 1.19 (mean ± standard deviation, p < 0.01). Twelve patients had frozen-thaw embryo transfers after the study. In 42% (n = 5 of 12) of the patients, pregnancy was achieved. One of the five patients delivered a healthy baby at term. CONCLUSIONS: Autologous BMNC transplantation may contribute to endometrial function in patients with AS and/or TE.