To compare endometrial tissue samples from cesarean scar (CS) sites and from the posterior uterine wall to better understand the pathophysiology of implantation into a CS.Endometrial samples were taken from both a CS site and the posterior wall in premenopausal women with CSs, and from the posterior wall in premenopausal women who had spontaneous vaginal deliveries (SVDs) only.In the secretory phase, there were significantly fewer leukocytes at CS sites than in the endometrium of women who had SVDs only (P<0.05). Significant differences in leukocytic infiltration and cell proliferation between the proliferative and secretory phases were only found in women who had SVDs only (P<0.05).Leukocyte recruitment to the endometrium during the secretory phase may be affected by the presence of a CS.

To determine the risk factors for development of caesarean scar defect (CSD), compare the efficacy of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) for CSD assessment, and investigate the association between CSD size and clinical symptoms.One hundred and eighty-nine women with CSD and 378 women without CSD with a history of caesarean section (CS) at the Obsterics and Gynaecology Hospital of Fudan University between January 2008 and February 2016 were enrolled. The potential risk factors for CSD were investigated using multivariate logistic regression analysis. TVS and MRI were performed for CSD measurements, including residual myometrial thickness, and depth, length and width of CSD. Associations between CSD size by TVS/MRI and symptoms were evaluated.CS time ≥85 min, peripartum fever or infection, and retroflexed uterus were risk factors for CSD, and age at last CS < 30 years, intraoperative blood loss <150 ml and double-layer closure were protective factors for CSD. Prolonged menstruation, dysmenorrhoea, chronic pelvic pain and infertility were the main clinical manifestations. Women with a larger CSD presented with more prolonged menstruation. Compared with TVS, measurements by MRI showed better prediction of the clinical symptoms of CSD.Various factors contribute to the development of CSD. Prevention of peripartum infection, reduction of CS time, reduction of blood loss and more careful uterine closure are needed to decrease the risk of developing CSD. MRI is a reliable method for the diagnosis and measurement of CSD, and can be utilized in clinical practice.Copyright © 2019 Elsevier B.V. All rights reserved.

There is a growing body of evidence that suggests that the surgical technique for uterine closure following Cesarean delivery influences the healing of the Cesarean scar, but there is still no consensus on the optimal technique. The aim of this systematic review and meta-analysis was to compare the effect of single- vs double-layer uterine closure on the risk of uterine scar defect.MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE and the Cochrane Central Register of Controlled Trials were searched from inception of each database until May 2016. All randomized controlled trials (RCTs) evaluating the effect of single- vs double-layer uterine closure following low transverse Cesarean section on the risk of uterine scar defect were included. The primary outcome was the incidence of uterine scar defects detected on ultrasound. Secondary outcomes were residual myometrial thickness evaluated by ultrasound and the incidence of uterine dehiscence and/or rupture in subsequent pregnancy. Summary measures were reported as relative risk (RR) or mean difference (MD), with 95% CIs. Quality of the evidence was assessed using the GRADE approach.Nine RCTs (3969 participants) were included in the meta-analysis. The overall risk of bias of the included trials was low. Statistical heterogeneity within the studies was low, with no inconsistency in the primary and secondary outcomes. Women who received single-layer uterine closure had a similar incidence of uterine scar defects as did women who received double-layer closure (25% vs 43%; RR, 0.77 (95% CI, 0.36-1.64); five trials; 350 participants; low quality of evidence). Compared with double-layer uterine closure, women who received single-layer closure had a significantly thinner residual myometrium on ultrasound (MD, -2.19 mm (95% CI, -2.80 to -1.57 mm); four trials; 374 participants; low quality of evidence). No difference was found in the incidence of uterine dehiscence (0.4% vs 0.2%; RR, 1.34 (95% CI, 0.24-4.82); three trials; 3421 participants; low quality of evidence) or uterine rupture (0.1% vs 0.1%; RR, 0.52 (95% CI, 0.05-5.53); one trial; 3234 participants; low quality of evidence) in a subsequent pregnancy.Single- and double-layer closure of the uterine incision following Cesarean delivery are associated with a similar incidence of Cesarean scar defects, as well as uterine dehiscence and rupture in a subsequent pregnancy. However, the quality level of summary estimates, as assessed by GRADE, was low, indicating that the true effect may be, or is even likely to be, substantially different from the estimate of the effect. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

A growing number of studies suggest that the incomplete healing of the CS scar in the uterus increase the risk of uterine dehiscence or rupture during subsequent pregnancies. Thus, the factors that affect wound healing should be evaluated. We aimed to determine whether the morphology of the CS scar in non-pregnant women after one elective CS was affected by the site of the uterine incision, uterine flexion, maternal age, and fetal birth weight.208 non-pregnant women were invited for participation in the study, but only 101 of them met inclusion criteria. Standardized scar parameters (residual myometrial thickness (RMT), depth (D) and width (W) of the hypoechoic niche) were measured using ultrasonography at least 6 weeks after the CS.Scar defect was detected in 26 of 101 subjects. Women without scar defect had significantly higher RMT values (1.87 vs. 0.87), lower newborn birth weight (3127 g vs. 3295 g), and higher scar location above the internal cervical os (62% vs. 16%), than those with scar defect. Maternal age was significantly correlated with D value (R = 0.40). Uterine retroflexion was significantly correlated with a larger D value (R = 0.63) and a larger D/RMT ratio (R = 0.24).In low-risk women who have undergone one elective CS, several risk factors are associated with development of the scar defect, but only scar location can be modified during surgery. Future research is needed to determine whether a relatively higher incision location in the uterus can ensure optimal healing of the CS scar.

Cesarean scar defect (CSD) is characterized by the presence of fibrotic tissue and decreased muscular density which is induced by cesarean section. Serious CSD may eventually result in infertility or obstetrical complications. Human amniotic epithelial cells (hAECs) have shown great promise in tissue regeneration. This study aims to investigate whether hAEC transplantation has the therapeutic effects on the rat uterine scar following full-thickness injury.A rat uterine scar model was established by excising the full-thickness uterine wall of about 1.0 cm in length and 1/2-2/3 of the total circumference in width. At day 30 post-surgery, hAECs were transplanted into the uterine scar. At day 30 and 60 post-transplantation, hematoxylin and eosin (H&E) staining, Masson staining, and IHC staining for vWF, VEGFA, α-SMA, and MMP-8 were performed to evaluate the regeneration of the scarred uterus and the underlying mechanism. Pregnancy outcomes were assessed at day 60 after hAEC transplantation. Finally, hAECs were incubated with hydrogen peroxide to verify the paracrine effect of hAECs.Collagen deposition, thin myometrium, and injured endometrium were observed in the rat uterine scar model. After hAEC transplantation, collagen deposition in the uterine scar decreased, and myometrial and endometrial recovery was facilitated. hAEC transplantation also increased the fetus number implanted within the scarred area. Moreover, we found hAECs promoted angiogenesis via upregulation of VEGFA and decreased collagen deposition by upregulating MMP-8 in the uterine scar. The in vitro studies further demonstrated an increase in the expression level of MMP-8 in hAECs cultured with hydrogen peroxide.These results suggested that hAEC transplantation may be efficacious in the functional repair and collagen degradation of uterine scars, which provides a new therapeutic strategy to CSD.

Around 20% of pregnant women undergo cesarean section (CS), and in most regions of the world CS rates continue to grow. There is still no clear definition of what is considered a normal physiologic aspect of a CS scar and what is abnormal. Cesarean scar defects (CSDs) should be suspected in women presenting with spotting, dysmenorrhea, pelvic pain, or infertility and a history of CS. CSDs can be visualized with the use of hysterosalpingography, transvaginal sonography, saline infusion sonohysterography, hysteroscopy, and magnetic resonance imaging. It is reasonable to consider hormone therapy for CSDs as a symptomatic treatment in women who no longer wish to conceive and have no contraindications. In case of failure of or contraindications to medical treatment, surgery should be contemplated according to the severity of symptoms, including infertility, the desire or otherwise to preserve the uterus, the size of the CSD, and residual myometrium thickness (RMT) measurement. Hysteroscopy is considered to be more of a resection than a repair, so women who desire pregnancy should be excluded from this technique if the RMT is <3 mm, in which case repair is essential and can be achieved by only laparoscopic or vaginal approach. Women with CSDs need to be given complete information, including available literature, before any treatment decision is made. Because prevention is better than cure, risk factors should be identified early to ensure appropriate management.Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

We aim to describe the sonographic uterine anatomy after a cesarean section (CS), test the reproducibility of predefined measurements from the BSUM study, and report the distribution of these measurements.This is a descriptive observational study where 200 women with a history of only one CS were recruited 12-24 months postoperatively. A 5-13 MHz micro-convex transvaginal transducer was used for the acquisition of volumetric datasets for evaluating the CS scars. We defined 15 distinct measurements including the residual myometrial thickness (RMT). RMT ratio was calculated as a percentage of RMT to the assumed pre-cesarean anterior uterine wall thickness. A P value below 0.05 is utilized for significant statistical analysis.Patients were included on average 18.5 months post-cesarean. The uterus was anteflexed in 82.5% and retroflexed in 17.5%. Myometrial defects at the site of CS manifest in two forms, either as a niche or as fibrosis. Patients are classified into four groups: those with isolated niches (45%), combined niches and fibrosis (38.5%), isolated fibrosis (11%), and lacking both (5%). The median RMT ratio for these groups was 63.09, 40.93, 59.84, and 100% with a standard deviation of 16.73, 12.95, 16.59, and 0, respectively. The interclass correlation coefficient (ICC) remained above 0.9 for all distinct measurements among these groups except for those of RMT, where ICC varied between 0.47 and 0.96. The RMT ratio shows a constant ICC at 0.94 regardless of the group.The post-cesarean uterus is often anteflexed, and a myometrial loss of about 50% is normally expected. The pattern of this loss is in the form of a predominantly sharp-edged and echogenic niche, fibrosis, or a combination of both. The proposed RMT ratio takes these changes into consideration and results in a reproducible quantification. We hypothesize that different adverse outcomes could be attributed to the different scar patterns.

目前剖宫产切口瘢痕缺损（cesarean scar defect, CSD）的手术效果不尽人意。郑州大学第一附属医院妇科基于CSD的病理变化，即：剖宫产切口局部肌层连续性中断及形成瘢痕缺损，瘢痕缺损部位内膜继发炎症反应、充血、异形血管、息肉形成等，采用宫腹腔镜联合手术，重建局部缺陷肌层，并处理继发病理变化，不切除任何本就缺陷的肌层，可显著改善异常子宫出血症状，创伤小、恢复快，且术后避孕时间短，推荐为治疗CSD的新的手术方式。

In women of reproductive age, severe injuries to the endometrium are often accompanied by endometrial scar formation or intrauterine adhesions (IUAs), which can result in infertility or miscarriage. Although many approaches have been used to treat severe IUAs, high recurrence rates and endometrial thinning have limited therapeutic efficiency. In this study, a collagen scaffold (CS) loaded with human umbilical cord-derived mesenchymal stem cells (UC-MSCs) was fabricated and applied for endometrial regeneration. The CS/UC-MSCs promoted human endometrial stromal cell proliferation and inhibited apoptosis in vitro through paracrine effects. In a model of endometrial damage, transplantation with the CS/UC-MSCs maintained normal luminal structure, promoted endometrial regeneration and collagen remodeling, induced intrinsic endometrial cell proliferation and epithelium recovery, and enhanced the expression of estrogen receptor α and progesterone receptor. An improved ability of the regenerated endometrium to receive embryos was confirmed. Together, our results indicate that the CS/UC-MSCs promoted endometrial structural reconstruction and functional recovery. Topical administration of the CS/UC-MSCs after trans-cervical resection of adhesions might prevent re-adhesion, promote endometrium regeneration and improve pregnancy outcomes for patients with severe IUAs. STATEMENT OF SIGNIFICANCE: Intrauterine adhesions due to severe endometrium injuries happen frequently in clinic and become one of the crucial reasons for women's infertility or miscarriage. Therefore, how to regenerate the damaged endometrium is a big challenge. In this study, a collagen scaffold (CS) loaded with human umbilical cord-derived mesenchymal stem cells (UC-MSCs) was fabricated and applied for endometrium regeneration. Herein, UC-MSCs, known for low immunogenicity and high proliferative potential, exhibit promising potential for endometrium regeneration; and collagen scaffolds provide suitable physical support. It was proved that transplantation with CS/UC-MSCs promoted endometrial regeneration and fertility restoration. It suggested that topical administration of CS/UC-MSCs in uterus could be a promising strategy for patients suffering severe intrauterine adhesion and infertility.Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

To compare the effect of a hysteroscopic niche resection with a Levonorgestrel-releasing intrauterine device (LNG-IUD, 52 mg) on postmenstrual spotting duration in patients with a symptomatic niche in the uterine cesarean scar.This prospective cohort study was conducted at the International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, China. Patients with postmenstrual spotting symptomatic niches were allocated to hysteroscopy group or LNG-IUD group based on the shared medical decision-making approach, and were followed up for 1 year after treatment.The primary outcome was reduced postmenstrual spotting days at 6th month after treatment. Secondary outcomes were effectiveness rate (proportion of patients with spotting days reduced by at least 50% from baseline), menstrual characteristics, menstruation satisfaction, direct medical costs, complications and side effects.78 out of the 82 eligible patients were included, 36 patients in both group finished 1-year follow-up. Reduced spotting days at the 6th month was 7 days in LNG-IUD group, significantly higher than 5 days in hysteroscopy group, P = 0.004; The effectiveness rate increased over time within 1 year after the insertion of LNG-IUD (63.89%, 83.33%, 88.89%, 88.89%, P for trend = 0.006), while no trend change was observed in hysteroscopy group (71.05%, 71.05%, 66.67%, 61.11%, P for trend = 0.77). The mean direct medical costs were 817[785,856] $ in the hysteroscopy group and 243[239,255] $ in the LNG-IUD group (p＜0.001). 2 patients removed IUD and 2 patients reported weight gain of more than 5 kg and breast distended pain in LNG-IUD group; 2 patients got pregnant in hysteroscopy group. No serious complications were observed in both groups.LNG-IUD is more effective in the treatment of postmenstrual spotting from the 6th month onwards than a hysteroscopic niche resection in patients with a symptomatic niche at lower direct costs.Copyright © 2021 Elsevier B.V. All rights reserved.

The disruption or defect of the myometrium in the uterine scar of a cesarean section (CS) has been known by various names, such as uterine niche, isthmocele, deficient uterine scar, scar pouch, or diverticulum. Symptomatology, risk factors for niche development, and available treatment modalities have been recently studied. However, the histologic features of this disease remain unknown.The histologic features of eight uterine niches are thoroughly described and a summary of the most important aspects of the uterine niche literature is provided. Five cases of CS scars without niche formation are comparatively examined.Most uterine niches harbor endocervical mucosa, often cystically dilated and/or an atrophic or disorganized endometrial mucosa of lower uterine segment origin. Regenerative epithelial atypia and fibroblastic stromal reaction are frequent features. No granulomatous reaction, important inflammation, or hemorrhage is seen. CS scars without niche formation do not harbor endocervical mucosa or inclusion cysts, fibroblastic stroma, or regenerative atypia.As more prospective studies of uterine niche development and treatment will be conducted, a detailed pathologic report with the criteria proposed herein can be designed.© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

To review systematically the medical literature reporting on the prevalence of a niche at the site of a Cesarean section (CS) scar using various diagnostic methods, on potential risk factors for the development of a niche and on niche-related gynecological symptoms in non-pregnant women.The PubMed and EMBASE databases were searched. All types of clinical study reporting on the prevalence, risk factors and/or symptoms of a niche in non-pregnant women with a history of CS were included, apart from case reports and case series.Twenty-one papers were selected for inclusion in the review. A wide range in the prevalence of a niche was found. Using contrast-enhanced sonohysterography in a random population of women with a history of CS, the prevalence was found to vary between 56% and 84%. Nine studies reported on risk factors and each study evaluated different factors, which made it difficult to compare studies. Risk factors could be classified into four categories: those related to closure technique, to development of the lower uterine segment or location of the incision or to wound healing, and miscellaneous factors. Probable risk factors are single-layer myometrium closure, multiple CSs and uterine retroflexion. Six out of eight studies that evaluated niche-related symptoms described an association between the presence of a niche and postmenstrual spotting.The reported prevalence of a niche in non-pregnant women varies depending on the method of detection, the criteria used to define a niche and the study population. Potential risk factors can be categorized into four main categories, which may be useful for future research and meta-analyses. The predominant symptom associated with a niche is postmenstrual spotting.Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Many papers and reviews have described the changes of the cervix during pregnancy, cervical cancer, sexually transmitted infections, and cervicovaginal microbiota. In this Views and Reviews, we focus on some specific topics in relation to the uterine cervix and infertility: early cervical cancer and fertility sparing surgery, cesarean scar defect, cervical incompetence, and cervical müllerian anomalies.Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Adenomyosis is a commonly diagnosed estrogen-dependent gynecological disorder that causes pelvic pain, abnormal uterine bleeding, and infertility. Despite its prevalence and severity of symptoms, its pathogenesis and etiology have not yet been elucidated. The aim of this manuscript is to review the different hypotheses on the origin of adenomyotic lesions and the mechanisms involved in the evolution and progression of the disease. Two main theories have been proposed to explain the origin of adenomyosis. The most common suggests involvement of tissue injury and the repair mechanism and claims that adenomyosis results from invagination of the endometrial basalis into the myometrium. An alternative theory maintains that adenomyotic lesions result from metaplasia of displaced embryonic pluripotent Müllerian remnants or differentiation of adult stem cells. Previous investigations performed in human adenomyotic lesions and corroborated by studies in mice supported the involvement of the epithelial-mesenchymal transition process in the early stages of progression and spread of adenomyosis. However, studies conducted in a recently developed baboon model indicate that collective cell migration may be implicated in the later events of invasion. This suggests that the invasiveness of this complex uterine disorder is not driven by a single mechanism of migration but by a time-dependent combination of two processes.Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.