Search Results (21)

Background/Objective: Cesarean scar pregnancy (CSP) represents a challenging and potentially life-threatening form of ectopic pregnancy. This study aims to assess the feasibility, safety, and clinical efficacy of employing the hysteroscopic mechanical tissue removal system as a primary treatment modality for CSP. Methods: This retrospective cohort study included 53 patients diagnosed with CSP who underwent primary hysteroscopic resection at a tertiary care center. The surgical procedure was performed by prioritizing the “no-touch” vaginoscopic approach, which avoids instrumentation. Success rates, operation time, time to negative serum β-hCG, complications, and differences between the anatomical types of CSP (Type 1 vs. Type 2) were analyzed. Results: Primary hysteroscopic treatment was successful in 51 of 53 patients (96.2%). For the entire cohort, the median operative time was 7 min (range: 2–30), and the median interval to β-hCG negativization was 11 days (range: 6–45). The overall major complication rate was 3.8% (n = 2). One case was deemed unsuccessful due to conversion to laparotomy following uterine perforation during cervical dilation. Another patient, diagnosed with persistent trophoblastic disease requiring methotrexate (MTX) therapy, was also considered a treatment failure. Operative time was significantly longer in patients with Type II CSP compared with Type I (median 9 min vs. 5 min; p = 0.0004). Conclusions: Hysteroscopic mechanical tissue removal as a primary treatment for cesarean scar pregnancy represents an effective and safe “one-step” approach, characterized by a high success rate, rapid β-hCG resolution, and a low incidence of complications. This fertility-preserving, minimally invasive technique may be considered a primary treatment option for hemodynamically stable patients with CSP, provided that appropriate patient selection is undertaken and sufficient surgical expertise is available. Full article

The human endometrium, previously considered a sterile environment, is now recognized as a low-biomass but biologically active microbial niche critical to reproductive health. Advances in sequencing technologies, particularly shotgun metagenomics, have provided unprecedented insights into the taxonomic and functional complexity of the endometrial microbiome. While 16S rRNA sequencing has delineated the distinction between Lactobacillus-dominant and non-dominant microbial communities, shotgun metagenomics has revealed additional diversity at the species and strain level, uncovering microbial signatures that remain undetected by amplicon-based approaches. Current evidence supports the association of Lactobacillus dominance with endometrial homeostasis and favorable reproductive outcomes. Dysbiosis, characterized by increased microbial diversity and enrichment of anaerobic taxa such as Gardnerella, Atopobium, Prevotella, and Streptococcus, is linked to chronic endometritis, implantation failure, and adverse IVF results. Beyond compositional differences, the endometrial microbiome interacts with the host through immunological, metabolic, and epigenetic mechanisms. These interactions modulate cytokine signaling, epithelial barrier integrity, and receptivity-associated gene expression, ultimately influencing embryo implantation. However, discrepancies between published studies reflect the lack of standardized protocols for sampling, DNA extraction, and bioinformatic analysis, as well as the inherent challenges of studying low-biomass environments. Factors such as geography, ethnicity, hormonal status, and antibiotic exposure further contribute to interindividual variability. Culturomics approaches complement sequencing by enabling the isolation of viable bacterial strains, offering perspectives for microbiome-based biotherapeutics. Emerging 3D endometrial models provide additional tools to dissect microbiome–host interactions under controlled conditions. Taken together, the growing body of data highlights the potential of endometrial microbiome profiling as a biomarker for reproductive success and as a target for personalized interventions. Future research should focus on integrating multi-omics approaches and functional analyses to establish causal relationships and translate findings into clinical practice. This review gives a new insight into current knowledge on the uterine microbiome and its impact on implantation success, analyzed through the lenses of microbiology, immunology, and oxidative stress. Full article

Background and Objectives: A cesarean scar defect (CSD), also referred to as a niche or isthmocele, is often detected incidentally during transvaginal sonography (TVS) and is typically asymptomatic. However, the exact prevalence of symptomatic niches remains unclear. This study aimed to evaluate the incidence of cesarean scar niches and identify potential risk factors in a prospectively gathered cohort of Egyptian women. Materials and Methods: The primary endpoint was to determine the incidence of isthmoceles after six months following a cesarean section (CS) and to investigate any associated symptoms and risk factors. The study included 420 women, divided into three groups: Group A included 140 women who had undergone their first CS, Group B included 140 women with a history of two CSs, and Group C consisted of 140 women with more than two prior CSs. Results: Niches were identified in 23.8% of the participants via TVS. The highest incidence was observed in women with more than two previous CSs (31.2%, 39/125), followed by those with two prior CSs (24.4%, 30/123), and the lowest was among women with one previous CS (16.3%, 22/135). Of the 91 women diagnosed with a CS niche, only 23 (25.27%) reported symptoms—most commonly postmenstrual spotting (7.7%) and dyspareunia (8.8%). Conclusions: The findings indicate that multiple cesarean deliveries, the uterine positioning (as assessed via TVS), a postpartum fever, breastfeeding, low post-cesarean platelet counts, and maternal anemia are contributing factors to the development of cesarean scar niches. Full article

Background/Objectives: To assess the effectiveness of the levonorgestrel-releasing intrauterine device (LNG-IUD) compared to hysteroscopic resection for managing women with symptomatic cesarean scar defects (CSDs). Methods: This systematic review and meta-analysis followed PRISMA guidelines. A comprehensive search of four electronic databases was conducted to identify studies comparing LNG-IUD with hysteroscopic management for symptomatic CSDs. Studies reporting outcomes of bleeding and spotting days and effectiveness rates were included. Quality assessment was performed using the ROBINS-I and RoB-2 tools. Results: Three studies involving 344 patients met the inclusion criteria. At 6 months, LNG-IUD use significantly reduced total bleeding days (MD −4.13; 95% CI: −5.17 to −3.09; p < 0.00001) and spotting days (MD 1.90; 95% CI: 0.43 to 3.37; p = 0.01) compared to hysteroscopic treatment. By 12 months, LNG-IUD demonstrated superior effectiveness (OR 3.46; 95% CI: 1.53 to 7.80; p = 0.003), with fewer total bleeding days (MD −5.69; 95% CI: −6.55 to −4.83; p < 0.00001) and spotting days (MD 3.09; 95% CI: 1.49 to 4.69; p = 0.0002). Approximately 50% of LNG-IUD users experienced amenorrhea within 1 year. Conclusions: LNG-IUD offers a minimally invasive and effective alternative to hysteroscopic resection for women with symptomatic CSD and no desire for future pregnancies. Its role should be considered in clinical practice, but further research is needed to validate these findings and define its long-term benefits and limitations. Full article

(1) Background: SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) is a rare and aggressive cancer that urgently requires novel therapeutic strategies. Despite the proven efficacy of immunotherapy in various cancer types, its application in SDUS remains largely unexplored. This study aims to investigate the immune microenvironment of SDUS to evaluate the feasibility of utilizing immunotherapy. (2) Methods: Multiplex immunofluorescence (mIF) was employed to examine the immune microenvironment in two cases of SDUS in comparison to other subtypes of endometrial stromal sarcomas (ESSs). This research involved a comprehensive evaluation of immune cell infiltration, cellular interactions, and spatial organization within the tumor immune microenvironment (TiME). Statistical analysis was performed to assess differences in immune cell densities and interactions between SDUS and other ESSs. (3) Results: SDUS exhibited a significantly higher density of cytotoxic T lymphocytes (CTLs), T helper (Th) cells, B cells, and macrophages compared to other ESSs. Notable cellular interactions included Th–CTL and Th–B cell interactions, which were more prominent in SDUS. The spatial analysis revealed distinct immune niches characterized by lymphocyte aggregation and a vascular-rich environment, suggesting an active and engaged immune microenvironment in SDUS. (4) Conclusions: The results suggest that SDUS exhibits a highly immunogenic TiME, characterized by substantial lymphocyte infiltration and dynamic cellular interactions. These findings highlight the potential of immunotherapy as an effective treatment approach for SDUS. However, given the small number of samples evaluated, these conclusions should be drawn with caution. This study underscores the importance of additional investigation into immune-targeted therapies for this challenging cancer subtype, with a larger sample size to validate and expand upon these preliminary findings. Full article

Background and Objectives: This study aims to report the location of the placenta in the first trimester of pregnancy in groups of women according to the number of previous caesarean deliveries and the visibility of the caesarean scar niche. Materials and Methods: The prospective observational research included adult women aged 18 to 41 years during pregnancy after one or more previous caesarean sections (CSs). Transvaginal (TVS) and transabdominal sonography (TAS) was used to examine the uterine scar and placental location during 11–14 weeks. The CS scar niche (“defect”) was bordered in the sagittal plane as a notch at the previous CS scar’s site with a depth of 2.0 mm or more. A comparative analysis of the placental location (high or low and anterior or posterior) was performed between groups of women according to the CS number and the CS scar niche. Results: A total of 122 participants were enrolled during the first-trimester screening. The CS scar defect (“niche”) was visible in 40.2% of cases. In cases after one previous CS, the placenta was low in the uterine cavity (anterior or posterior) at 77.4%, and after two or more CSs, it was at 67.9%. Comparing the two groups according to the CS scar niche, the placenta was low in 75.5% of cases in the participant group with a CS scar niche and in 75% of cases without a CS scar niche (p = 0.949). Conclusions: The number of previous caesarean deliveries has no effect on the incidence rate of low-lying placentas in the first trimester. Moreover, the presence of the CS scar niche is not associated with anterior low-lying placentas. Full article

The tumor microenvironment significantly affects the transcriptomic states of tumor cells. Single-cell RNA sequencing (scRNA-seq) helps elucidate the transcriptomes of individual cancer cells and their neighboring cells. However, cell dissociation results in the loss of information on neighboring cells. To address this challenge and comprehensively assess the gene activity in tissue samples, it is imperative to integrate scRNA-seq with spatial transcriptomics. In our previous study on physically interacting cell sequencing (PIC-seq), we demonstrated that gene expression in single cells is affected by neighboring cell information. In the present study, we proposed a strategy to identify niche-specific gene signatures by harmonizing scRNA-seq and spatial transcriptomic data. This approach was applied to the paired or matched scRNA-seq and Visium platform data of five cancer types: breast cancer, gastrointestinal stromal tumor, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, and ovarian cancer. We observed distinct gene signatures specific to cellular niches and their neighboring counterparts. Intriguingly, these niche-specific genes display considerable dissimilarity to cell type markers and exhibit unique functional attributes independent of the cancer types. Collectively, these results demonstrate the potential of this integrative approach for identifying novel marker genes and their spatial relationships. Full article

Cesarean scar defect, also known as niche, isthmocele, uteroperitoneal fistula and uterine diverticulum, is a known complication after cesarean delivery. Due to the rising cesarean delivery rates, niche has become more common and can present as irregular bleeding, pelvic pain, infertility, cesarean scar pregnancy and uterine rupture. Treatments for symptomatic cesarean scar defect vary and include hormonal therapy, hysteroscopic resection, vaginal or laparoscopic repair, and hysterectomy. We report on the safety and efficacy of our method of repairing cesarean scar defects in 27 patients without adverse outcomes: two-layer repair where the suture does not enter the uterine cavity. Our method of laparoscopic niche repair improves symptoms in nearly 77% of patients, restores fertility in 73% of patients, and decreases the time to conception. Full article

Chronic pelvic pain (CPP) is one of the main isthmocele symptoms, together with abnormal uterine bleeding and secondary infertility. When patients undergo a laparoscopic niche repair surgery, it is important to determine if they present associated pathologies, such as adenomyosis and/or endometriosis, which are also a cause of CPP. A retrospective study was performed on 31 patients with CPP undergoing a laparoscopic niche repair. The pre-operative ultrasound was analyzed to determine the presence of adenomyosis. Endometriosis was histologically diagnosed. CPP outcome was evaluated at early (3–6 months) and late (12 months) post-operative follow ups. In our population of 31 women presenting CPP, only six of them (19.4%) did not have any associated pathology. In the group of 25 patients with associated pathology, 10 (40%) had no benefit from the reconstructive surgery in terms of CPP at early follow-up (3–6 months) and 8 (32%) in the post-operative period at 12 months. Patients with CPP who undergo niche repair should be carefully selected as CPP does not seem to be a good indication for uterine scar repair in patients with concomitant adenomyosis and endometriosis. Full article

Tissue-resident macrophages (Mø) play tissue/organ-specific roles, and the physiological/pathological implications of uterine Mø in fertility and infertility are not yet fully understood. Herein, we report a simple propagation method for tissue-resident Mø by mixed culture with the respective tissue/organ-residing cells as the niche. We successfully propagated mouse uterine Mø by mixed culture with fibroblastic cells that exhibited properties of endometrial stromal cells. Propagated mouse uterine Mø were CD206- and arginase-1-positive; iNOS- and MHC-II-negative, indicating M2 polarization; and highly phagocytic, similar to endometrial Mø. Furthermore, uterine Mø were observed to express steroidogenic molecules including SRD5A1 and exhibited gap junction formation, likely with endometrial stromal cells. Accordingly, uterine Mø propagated by mixed culture may provide a new tool for studying immune–endocrine interactions related to fertility and infertility, particularly androgen’s intracrine actions in preparing the uterine tissue environment to support implantation and pregnancy as well as in the etiology of endometriosis. Full article

Caesarean Scar Pregnancy (CSP) is an ectopic pregnancy with implantation into the niche of the uterine scar. We aimed to describe the local management of consecutive cases of CSP to develop a standard operating procedure (SOP). Between December 2019 and June 2022, there were 19,100 maternities. Of these, 23 were CSPs in 19 patients. Median BMI was 29 (range 20.5–52), median number of Caesarean deliveries (CS) was 2 (range 1–4) and 7/23 (30%) were cigarette smokers. At diagnosis, 9/23 were live pregnancies, 3/23 were retained products of conception (RPOC), 9/23 were pregnancies of uncertain viability (PUV), and 2/23 were non-viable. In six, the initial management was expectant, surgical suction evacuation with transrectal ultrasound guidance in 16, and one had a hysterectomy. The median blood loss was 100 mL (range 50–2000 mL). Two patients (9%) required a blood transfusion. Median hospital stay was 1 day (range 0–4). At follow-up after 10 weeks, no patients had an ongoing haematoma, and one had significant RPOC electing hysterectomy. Eight women were known to have 9 subsequent pregnancies (recurrent CSP n = 4, livebirth n = 2, miscarriage n = 2, tubal ectopic n = 1). Outcomes as rated by low blood loss, short hospital stay, and rare need for further intervention were favorable. Factors associated included prompt ultrasonographic diagnosis, availability of transrectal ultrasound guided surgery, and specialist follow-up, which form the basis of the SOP. Full article

(1) Background: Uterine niche is a frequent condition in patients with a history of cesarean section. Although the relation to uterotomy seems to be clear, the exact pathogenesis is not fully understood. Uterine niche can easily be diagnosed by transvaginal ultrasound. It can be related to symptoms like dysmenorrhea, bleeding disorders, dysuria and dyspareunia. Uterine niche can be the cause of scar pregnancy, a rare form of ectopic pregnancy which can be related to severe complications; (2) Methods: We present a series of nine cases with different uterine niche related findings and discuss the diagnostic and therapeutic options reviewing the current literature and introduce a novel intrauterine ICG use for laparoscopic niche detection in one case; (3) Results: Most of uterine niche related symptoms and complications can be treated by a minimally invasive approach. Laparoscopic fluorescence guided niche detection is feasible; (4) Conclusions: Hysteroscopic and laparoscopic techniques allow the treatment of uterine niche related symptoms and complications. Intrauterine ICG application during fluorescence guided laparoscopy may allow easy niche detection. Full article

Background and Objectives: The aim of this study is to evaluate changes in uterine scar thickness after previous cesarean delivery longitudinally during pregnancy, and to correlate cesarean section (CS) scar myometrial thickness in the first trimester in two participants groups (CS scar with a niche and CS scar without a niche) with the low uterine segment (LUS) myometrial thickness changes between the second and third trimesters. Materials and Methods: In this prospective longitudinal study, pregnant women aged 18–41 years after at least one previous CS were included. Transvaginal sonography (TVS) was used to examine uterine scars after CS at 11–14 weeks. The CS scar niche (“defect”) was defined as an indentation at the site of the CS scar with a depth of at least 2 mm in the sagittal plane. Scar myometrial thickness was measured, and scars were classified subjectively as a scar with a niche (niche group) or without a niche (non-niche group). In the CS scar niche group, RMT (distance from the serosal surface of the uterus to the apex of the niche) was measured and presented as CS scar myometrial thickness in the first trimester. The myometrial thickness at the internal cervical os was measured in the non-niche group. The full LUS and myometrial LUS thickness at 18–20 and 32–35 weeks of gestation were measured in the thinnest part of the scar area using TVS. Friedman’s ANOVA test was used to analyse scar thickness during pregnancy and Mann–Whitney test to compare scar changes between CS scar niche and non-niche women groups. For a pairwise comparison in CS scar thickness measurements in the second and third trimesters, we used Wilcoxon Signed Ranks test. Results: A total of 122 eligible participants were recruited to the study during the first trimester of pregnancy. The scar niche was visible in 40.2% of cases. Uterine scar myometrial thickness decreases during pregnancy from 9.9 (IQR, 5.0–12.9) at the first trimester to 2.1 (IQR, 1.7–2.7) at the third trimester of pregnancy in the study population (p = 0.001). The myometrial CS scar thickness in the first trimester (over the niche) was thinner in the women’s group with CS scar niche compared with the non-niche group (at internal cervical os) (p < 0.001). The median difference between measurements in the CS scar niche group and non-niche group between the second and third trimester was 2.4 (IQR, 0.8–3.4) and 1.1 (IQR, 0.2–2.6) (p = 0.019), respectively. Myometrial LUS thickness as percentage decreases significantly between the second and third trimester in the CS scar niche group compared to the non-niche group (U = 1225; z = −2.438; p = 0.015). Conclusions: CS scar myometrial thickness changes throughout pregnancy and the appearance of the CS scar niche was associated with a more significant decrease in LUS myometrial thickness between the second and third trimesters. Full article

Objective: The aim of this study is to propose a standardized management of care for patients diagnosed with cesarean scar pregnancy (CSP). There are two types of CSP: Type 1 (on the scar) vs. type 2 (in the niche). To date there is no international standard to predict the extent of invasion or the optimal management of CSP. Materials and methods: We used intramuscular methotrexate injection followed by uterine artery embolization combined with suction evacuation as a conservative approach for the treatment of seven patients diagnosed with CSP. Our inclusion criteria, to be satisfied simultaneously, were established as follows: (1) patients with CSP; (2) early gestational age ≤ 9 weeks, and (3) written consent of the proposed treatment of the patient. Results: This course of treatment produced a positive outcome in all cases. We did not have any complications (e.g., emergency hysterectomy, perforation of the uterine cavity, severe hemorrhage, or endometritis) during the procedures or in the follow-up. The most important predictors of successful management are early diagnosis of CSP and orientation of the invasive trophoblast opposite to the scar. Conclusions: The main finding from this series of cases is that associating systemic methotrexate and uterine artery embolization provides efficient and low-risk management of CSP. This treatment regime is adequate for both types of CSPs. We consider that early localization diagnosis of pregnancy following a cesarean delivery is mandatory for CSP morbidity prevention. Full article

Objective: To evaluate the effect of laparoscopic isthmocele repair on isthmocele-related symptoms and/or fertility-related problems. The residual myometrial thickness before and after subsequent cesarean section was also evaluated. Design: Retrospective, case series. Setting: Public university hospital. Population: Women with isthmocele (residual myometrium < 5 mm) complaining of abnormal uterine bleeding, chronic pelvic pain or secondary infertility not otherwise specified. Methods: Women’s complaints and the residual myometrium were assessed pre-operatively and at three to six months post-operatively. In patients who conceived after surgery, the latter was measured at least six months after delivery by cesarean section. Main Outcome Measures: Resolution of the main symptom three to six months after surgery and persistence of laparoscopic repair benefits after subsequent cesarean section were considered as primary outcome measures. Results: Overall, 31 women underwent laparoscopic isthmocele repair. The success rates of the surgery as improvement of abnormal uterine bleeding, chronic pelvic pain and secondary infertility were 71.4% (10 of 14), 83.3% (10 of 12) and 83.3% (10 of 12), respectively. Mean residual myometrial thickness increased significantly from 1.77 mm pre-operatively to 6.67 mm, three to six months post-operatively. Mean myometrial thickness in patients who underwent subsequent cesarean section (N = 7) was 4.49 mm. In this sub-group, there was no significant difference between the mean myometrial thickness measured after the laparoscopic isthmocele repair and that measured after the subsequent cesarean section. None of these patients reported recurrence of their symptoms after delivery. Conclusion: Our findings suggest that the laparoscopic isthmocele excision and repair is an appropriate approach for the treatment of isthmocele-related symptoms when done by skilled laparoscopic surgeons. The benefit of this new surgical approach seems to persist even after a subsequent cesarean section. Further investigations and prospective studies are required to confirm this finding. Full article