The PRC2 complex epigenetically silences GATA4 to suppress cellular senescence and promote the progression of breast cancer.

BACKGROUND: The transcription factor GATA4 is pivotal in cancer development but is often silenced through mechanisms like DNA methylation and histone modifications. This silencing suppresses the transcriptional activity of GATA4, disrupting its normal functions and promoting cancer progression. However, the precise molecular mechanisms and implications of GATA4 silencing in tumorigenesis remain unclear. Here, we aim to elucidate the mechanisms underlying GATA4 silencing and explore its role in breast cancer progression and its potential as a therapeutic target. METHODS: The GATA4-breast cancer prognosis link was explored via bioinformatics analyses, with GATA4 expression measured in breast tissues. Functional gain/loss experiments were performed to gauge GATA4's impact on breast cancer cell malignancy. GATA4-PRC2 complex interaction was analyzed using silver staining and mass spectrometry. Chromatin immunoprecipitation, coupled with high-throughput sequencing, was used to identify GATA4-regulated downstream target genes. The in vitro findings were validated in an in situ breast cancer xenograft mouse model. RESULTS: GATA4 mutation and different breast cancer subtypes were correlated, suggesting its involvement in disease progression. GATA4 suppressed cell proliferation, invasion, and migration while inducing apoptosis and senescence in breast cancer cells. The GATA4-PRC2 complex interaction silenced GATA4 expression, which altered the regulation of FAS, a GATA4 downstream gene. In vivo experiments verified that GATA4 inhibits tumor growth, suggesting its regulatory function in tumorigenesis. CONCLUSIONS: This comprehensive study highlights the epigenetic regulation of GATA4 and its impact on breast cancer development, highlighting the PRC2-GATA4-FAS pathway as a potential target for therapeutic interventions in breast cancers.

Multimodal learning system integrating electronic medical records and hysteroscopic images for reproductive outcome prediction and risk stratification of endometrial injury: a multicenter diagnostic study.

OBJECTIVE: To develop a multimodal learning application system that integrates electronic medical records (EMR) and hysteroscopic images for reproductive outcome prediction and risk stratification of patients with intrauterine adhesions (IUAs) resulting from endometrial injuries. MATERIALS AND METHODS: EMR and 5014 revisited hysteroscopic images of 753 post hysteroscopic adhesiolysis patients from the multicenter IUA database we established were randomly allocated to training, validation, and test datasets. The respective datasets were used for model development, tuning, and testing of the multimodal learning application. MobilenetV3 was employed for image feature extraction, and XGBoost for EMR and image feature ensemble learning. The performance of the application was compared against the single-modal approaches (EMR or hysteroscopic images), DeepSurv and ElasticNet models, along with the clinical scoring systems. The primary outcome was the 1-year conception prediction accuracy, and the secondary outcome was the assisted reproductive technology (ART) benefit ratio after risk stratification. RESULTS: The multimodal learning system exhibited superior performance in predicting conception within 1-year, achieving areas under the curves of 0.967 (95% CI: 0.950-0.985), 0.936 (95% CI: 0.883-0.989), and 0.965 (95% CI: 0.935-0.994) in the training, validation, and test datasets, respectively, surpassing single-modal approaches, other models and clinical scoring systems (all P<0.05). The application of the model operated seamlessly on the hysteroscopic platform, with an average analysis time of 3.7±0.8 s per patient. By employing the application's conception probability-based risk stratification, mid-high-risk patients demonstrated a significant ART benefit (odds ratio=6, 95% CI: 1.27-27.8, P=0.02), while low-risk patients exhibited good natural conception potential, with no significant increase in conception rates from ART treatment (P=1). CONCLUSIONS: The multimodal learning system using hysteroscopic images and EMR demonstrates promise in accurately predicting the natural conception of patients with IUAs and providing effective postoperative stratification, potentially contributing to ART triage after IUA procedures.

The Scheduling Mode of Anesthesia Nurses Affects Postanesthesia Care Unit Efficiency: A Single-Center Retrospective Study From China.

PURPOSE: Anesthesia nurses play an important postsurgical role during the anesthesia recovery period, which is characterized by a high incidence of complications related to anesthesia and surgery. Strengthening staff allocation and skill management in the postanesthesia care unit (PACU) is therefore particularly important in managing length of stay. We aimed to investigate the effect of two schedule modes for anesthesia nurses on PACU efficiency. DESIGN: A retrospective observational cohort study. METHODS: We conducted a retrospective study in a large tertiary academic medical center. In 2018, the PACU operated with traditional scheduling and the nurse-to-patient ratio was 1.2:1. The PACU implemented intensive scheduling and this ratio was adjusted to 1:1 in 2019 by adjusting the anesthesia nurse allocation scheme. We compared the number of admitted patients, length of PACU stay, the incidence of anesthesia-related complications, and nurse satisfaction with the two modes. FINDINGS: The total number of admitted patients was 10,531 in 2018 and 10,914 in 2019. PACU admitted 401 more patients in 2019 than in 2018, even with two fewer nurses per day. Nevertheless, the median length of PACU stay in 2019 was statistically significantly shorter than in 2018 (29 [22-40] vs 28 [21-39], P < .001], while the incidence of anesthesia-related complications including postoperative pain, nausea and vomiting, hypertension, and shivering were comparable in the 2 years (P > .091). The intensive scheduling implemented in 2019 received more satisfaction from nurses than the traditional scheduling applied in 2018 (P < .01). CONCLUSIONS: The scheduling of anesthesia nurses affects PACU efficiency. The intensive scheduling mode implemented in 2019 resulted in a comparable number of admitted patients, a better quality of care, and higher nurse satisfaction than those under the traditional scheduling mode.

Pretreatment with long-acting gonadotropin-releasing hormone agonists improved pregnancy outcomes after hysteroscopic multiple polypectomies: A retrospective study of 660 frozen-thawed embryo transfer cycles.

OBJECTIVE: To compare the reproductive pregnancy outcomes of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) plus hormone replacement therapy (HRT) with HRT-only cycles, and investigate differences between single polypectomy and multiple polypectomies, and between one or two doses of GnRH-a. MATERIALS AND METHODS: This was a retrospective cohort study on patients undergoing polypectomy who underwent frozen-thawed embryo transfer (FET) from March 2018 to May 2019. They were divided into GnRH-a pretreatment and HRT-only groups. Each group was divided into single polypectomy or multiple polypectomies (in a single hysteroscopic session) subgroups. Clinical pregnancy rate and live birth rate (LBR) were the main outcomes. The effect of GnRH-a dosage was further analysed. RESULTS: There were 212 GnRH-a pretreatment cases (45 single and 167 multiple polyps) and 448 HRT-only cases (228 single and 220 multiple polyps). The LBR of the GnRH-a pretreatment group (53.3%) was significantly higher than the HRT group (43.3%; P = 0.016). Logistic regression analysis showed that GnRH-a pretreatment significantly affected the LBR (odds ratio, OR 1.470, 95% confidence interval, Cl 1.046-2.065; P = 0.026). In the multiple polypectomy subgroup, the LBR with GnRH-a pretreatment was higher than with HRT-only (54.5% vs 43.6%; P = 0.034). However, the LBR was not different between the respective single polypectomy subgroups (48.9% vs 43.0%; P = 0.466). For patients with multiple polyps, two GnRH-a pretreatments produced a higher LBR than a single GnRH-a pretreatment (62.7% vs 47.8%), but without significant difference (P = 0.055). CONCLUSION: GnRH-a pretreatment improved the LBR for FET cycles after hysteroscopic multiple polypectomies, independent of dose.

Granulocyte-macrophage colony-stimulating factor promotes endometrial repair after injury by regulating macrophages in mice.

Intrauterine adhesion (IUA) caused by endometrial injury is a common cause of female infertility and is challenging to treat. Macrophages play a critical role in tissue repair and cyclical endometrial regeneration. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has significant reparative and anti-fibrotic effects in various tissues. However, there is limited research on the role of GM-CSF in the repair of endometrial injury and the involvement of macrophages in GM-CSF-mediated endometrial repair. In this study, using a mouse model of endometrial scratching injury, we found that GM-CSF treatment accelerated the repair of endometrial injury and improved fertility. At the molecular level, we observed that GM-CSF can downregulate the transcript levels of tumor necrosis factor (TNF) in mouse bone marrow-derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS) and upregulate the expression of Arginase-1 (Arg-1) and mannose receptor C-type 1 (MRC1). Importantly, during the early and middle stages of injury, GM-CSF increased the proportion of M1-like, M2-like, and M1/M2 mixed macrophages, while in the late stage of injury, GM-CSF facilitated a decline in the number of M2-like macrophages. These findings suggest that GM-CSF may promote endometrial repair by recruiting macrophages and modulating the LPS-induced M1-like macrophages into a less inflammatory phenotype. These insights have the potential to contribute to the development of novel therapeutic approaches for the treatment of intrauterine adhesion and related infertility.

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.

circRNA_0001006 predicts prognosis and regulates cellular processes of triple-negative breast cancer via miR-424-5p.

BACKGROUND: circular RNAs (circRNAs) have been considered novel biomarker candidates for human cancers, such as triple-negative breast cancer (TNBC). circ_0001006 was identified as a differentially expressed circRNA in metastatic breast cancer, but its significance and function in TNBC were unclear. The significance of circ_0001006 in TNBC was assessed and exploring its potential molecular mechanism to provide a therapeutic target for TNBC. RESULTS: circ_0001006 showed significant upregulation in TNBC and close association with patients' histological grade, Ki67 level, and TNM stage. Upregulated circ_0001006 could predict a worse prognosis and high risk of TNBC patients. In TNBC cells, silencing circ_0001006 suppressed cell proliferation, migration, and invasion. In mechanism, circ_0001006 could negatively regulate miR-424-5p, which mediated the inhibition of cellular processes by circ_0001006 knockdown. CONCLUSIONS: Upregulated circ_0001006 in TNBC served as a poor prognosis predictor and tumor promoter via negatively regulating miR-424-5p.

CircRNA CircABCB1 Diminishes the Sensitivity of Breast Cancer Cells to Docetaxel by Sponging MiR-153-3p.

Resistance to docetaxel is a major problem to the success of docetaxel-based therapies for breast cancer. The present study was to identify the role of circABCB1 in altering the docetaxel resistance properties. Reverse transcription-quantitative PCR (qRT-PCR) was performed to quantify circABCB1 and miR-153-3p. The effects of circABCB1 on the viability, apoptosis and migration/invasion of docetaxel-resistant and -sensitive cells were investigated by cell function experiments, including Cell Counting Kit-8 and Transwell assays. Correlation between circABCB1 and the docetaxel-treated outcome was analyzed by multivariate Cox regression analysis, in addition to Kaplan-Meier analysis of time to treatment failure (TTF). The targeting relationship between circABCB1 and miR-153-3p was predicted and verified by dual-luciferase reporter assay and RNA immunoprecipitation. CircABCB1 was highly expressed in cancerous tissues, as well as the docetaxel-sensitive group and cells. The overexpression of circABCB1 contributed to cell viability, docetaxel-resistance and migration/invasion, but inhibited apoptosis. CircABCB1 can sponge miR-153-3p. CircABCB1 contributed to the docetaxel resistance of breast cancer, maybe via the miR-153-3p.

Hepatitis E Virus Seroprevalence Indicated a Significantly Increased Risk Selectively in Patients with Gastric Cancer among 17 Common Malignancies.

Background: The impact of hepatitis E virus (HEV) infection on cancer development has been poorly investigated. This study aimed to explore the relationship between HEV seroprevalence and cancer risks and to identify high cancer risk subgroups in HEV-exposed populations. Methods: HEV seroprevalence status was determined in cancer and non-cancer subjects. Logistic regression and sensitivity analyses were used to assess the relationship between HEV antibody seropositivity and cancer risk for 17 cancer types. Additionally, interaction analyses were applied to interpret the association of HEV seroprevalence and other cancer risk factors. Results: Of the enrolled 4948 cancer and 4948 non-cancer subjects, cancer subjects had a higher anti-HEV seropositivity than non-cancer subjects (46.36% vs. 32.50%, p < 0.01). However, this divergency varied in degrees across different cancer types. Additionally, HEV seroprevalence was associated with cancer risk in young males (OR: 1.64, 95% CI: 1.19−2.27, p < 0.01). Remarkably, a significant association between HEV seroprevalence and cancer risk was observed only in gastric cancer patients (OR: 1.82, 95% CI: 1.07−3.09, p = 0.03). Conclusions: HEV seroprevalence was associated with cancer risk selectively in gastric cancer patients and young males, suggesting that cancer screening, particularly gastric cancer, should be regularly performed in young males with a history of HEV exposure.

Immunosuppressive role of SPP1-CD44 in the tumor microenvironment of intrahepatic cholangiocarcinoma assessed by single-cell RNA sequencing.

PURPOSE: To demonstrate the biological function of Secreted Phosphoprotein 1(SPP1) and its immune suppressive role in the progression intrahepatic cholangiocarcinoma (ICC). METHODS: We collected 62,770 cells' published transcriptome data of nine patients whose paired adjacent liver and tumor tissues were both available. We applied differential gene expression analysis to screen potential ICC marker genes, survival analysis to verify the prognostic value of SPP1, and correlation analysis to decipher factors that are related to SPP1 expression. The CellChat was used to distinguish interactions between cancer and T cells. CytoSig was applied to query cytokines that modulate CD44. Further, we established a proliferation score and correlated the score with inhibitory signals to determine the proliferation-suppressive function of SPP1-CD44. RESULTS: SPP1 expression is significantly upregulated in tumoral epitheliums, and patients with higher SPP1 expression have worse survival (P < 0.05). Tumor cells communicate with T cells via SPP1-CD44 interactions. The average expression of SPP1 in malignant cells (SPP1m) and CD44 in T cells (CD44t) is moderately negatively correlated with T cell proliferation score. Immunosuppressive cytokine TGFß-3 identified as an inducer of CD44 and was significantly negatively correlated with proliferation score (R = - 0.88, P < 0.01), and the negative correlation was aggravated in samples with high CD44 expression. CONCLUSION: SPP1 is a prognostic marker of ICC and is associated with the genome heterogeneity. SPP1-CD44 hinders sustained proliferation of T cells, but immunosuppressive T cells in the tumor microenvironment may evade this inhibition by reducing CD44 expression.

A neglected cervicovesical fistula diagnosed and repaired by combined hysteroscopy and laparoscopy: A case report and review of literature.

Objective: To analyze a case of neglected cervicovesical fistula with intrauterine adhesions caused by cesarean section. Methods: A 36-year-old female patient with a history of two previous cesarean sections complained of the absence of menstruation for the last 18 months. The diagnosis of the cervicovesical fistula was made through hysteroscopy and cystoscopy. The reconstruction of the uterus and bladder was achieved by a laparoscopic repair technique. Results: The patient resumed normal menstruation postoperatively without complaining of any complications. Uterine continuity and cavity had been restored to normal at the second look of hysteroscopy. Conclusions: Cervicovesical fistula with intrauterine adhesions is very rare in our clinical work. Hysteroscopy might play an essential role in diagnosing cervicovesical fistula and IUA. In our literature review, a surgical approach was the mainstay and definitive management of the cervicovesical fistula following a cesarean section.

Improved FCOS for Detecting Breast Cancers.

PURPOSE: Breast cancer ranks first among cancers affecting women's health. Our goal is to develop a fast, high-precision, and fully automated breast cancer detection algorithm to improve the early detection rate of breast cancer. METHODS: We compare different object detection algorithms, including anchor-based and anchor-free object detection algorithms for detecting breast lesions. Finally, we find that the fully convolutional onestage object detection (FCOS) showed the best performance in the detection of breast lesions, which is an anchor-free algorithm. 1) Considering that the detection of breast lesions requires the context information of the ultrasound images, we introduce the non-local technique, which models long-range dependency between pixels to the FCOS algorithm, providing the global context information for the detection of the breast lesions. 2) The variety of shapes and sizes of breast lesions makes detection difficult. We propose a new deformable spatial attention (DSA) module and add it to the FCOS algorithm. RESULTS: The detection performance of the original FCOS is that the average precision (AP) for benign lesions is 0.818, and for malignant lesions is 0.888. The FCOS with a non-local module improves the performance of the breast detection; the AP of benign lesions was 0.819, and that of malignant lesions was 0.894. Combining the DSA module with the FCOS improves the performance of breast detection; the AP for benign lesions and malignant lesions is 0.840 and 0.899, respectively. CONCLUSION: We propose two methods to improve the FCOS algorithm from different perspectives to improve its performance in detecting breast lesions. We find that FCOS combined with DSA is beneficial in improving the localization and classification of breast tumors and can provide auxiliary diagnostic advice for ultrasound physicians, which has a certain clinical application value.

Intrauterine administration of G-CSF for promoting endometrial growth after hysteroscopic adhesiolysis: a randomized controlled trial.

STUDY QUESTION: Does intrauterine infusion of granulocyte colony-stimulating factor (G-CSF) prevent adhesion reformation and promote endometrial growth after hysteroscopic adhesiolysis? SUMMARY ANSWER: Intrauterine perfusion of G-CSF can increase endometrial thickness but does not prevent the recurrence of intrauterine adhesions (IUAs) in patients with Asherman syndrome (AS) after surgery. WHAT IS KNOWN ALREADY: Intrauterine infusion of G-CSF has been used in attempts to treat patients with recurrent miscarriage and an idiopathic thin endometrium for either fresh or frozen-thawed embryo transfer cycles but without uniform efficacy. There have been no reports on the effect of G-CSF on the recurrence of IUAs, endometrial regrowth or pregnancy results in specific populations with AS. STUDY DESIGN, SIZE, DURATION: This two-center prospective double-blind randomized controlled trial ran between April 2016 and August 2021. In it, 245 patients with moderate to severe AS were randomized to G-CSF and control groups at a 1:1 ratio; 229 women were included in the adhesion recurrence analysis; and 164 patients were analyzed for pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: All eligible patients received the first hysteroscopic adhesion separation and balloon placement procedure. Patients who met our inclusion and exclusion criteria were randomized after surgery. These patients returned for balloon removal and underwent intrauterine perfusion with 300 µg (1.8 ml) G-CSF or 1.8 ml normal saline according to randomization at 7 days after surgery. A second-look hysteroscopy was carried out 1-2 months later. The primary outcome was the rate of formation of new adhesions at the second hysteroscopy. The secondary outcomes included endometrial thickness in the periovulatory period after surgery, as well as the clinical pregnancy and live birth rates. MAIN RESULTS AND THE ROLE OF CHANCE: Age, menstrual cycle characteristics, pregnancy history and IUA score before surgery were similar between groups. There were no statistically significant differences in the adhesion reformation rate or median adhesion score reduction. However, G-CSF perfusion significantly improved endometrial thickness (7.91 ± 2.12 mm vs 7.22 ± 2.04 mm; P = 0.019, 95% CI for difference: -1.26 to -0.12), as well as cumulative pregnancy and live birth rate over time (P = 0.017 and P = 0.042). Furthermore, multivariate logistic regression analysis showed that postoperative endometrial thickness was an independent prognostic factor for pregnancy and live birth rates. LIMITATIONS, REASONS FOR CAUTION: These results cannot be extended to older patients or those without AS, as our subjects had moderate or severe AS and were aged <40 years. The low number of patients included in the fertility analysis could lead to biased results. WIDER IMPLICATIONS OF THE FINDINGS: Intrauterine perfusion of G-CSF could be an effective adjuvant therapy for patients with AS to increase endometrial thickness. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key Research and Development Program of China (2018YFC1004800), the National Natural Science Foundation of China (82001624 and 81871209), the Natural Science Foundation of Zhejiang Province (LQ20H040004) and the provincial and ministerial construction project of Zhejiang Province (2017 WKJ-ZJ-1721). The authors declare that they have no conflicts of interest regarding this work. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT02855632). TRIAL REGISTRATION DATE: 4 March 2016. DATE OF FIRST PATIENT'S ENROLMENT: 13 April 2016.

Analysis of risk factors for obstetric outcomes after hysteroscopic adhesiolysis for Asherman syndrome: A retrospective cohort study.

OBJECTIVE: To investigate the factors influencing placenta accreta in pregnant women who previously underwent hysteroscopic adhesiolysis (HA). METHODS: This retrospective study enrolled 265 women with intrauterine adhesions (IUAs) at the Sir Run Run Shaw Hospital from January 2014 to December 2018. We followed up their pregnancy outcomes and maternal complications. RESULTS: The menstrual pattern and gestational history before operation were significantly different between the live birth and pregnancy loss groups. The age, extent of cavity involved, type of adhesions, times of adhesiolysis performed, and time interval from surgery to pregnancy were not significantly different between these two groups. In the third trimester, 48 of 140 patients had 53 perinatal complications, including placenta accreta (27), gestational diabetes mellitus (10), pregnancy-induced hypertension (6), postpartum hemorrhage (4), intrahepatic cholestasis of pregnancy (2), placenta previa (1), oligohydramnios (1), and intrauterine growth restriction (1). Logistic regression analysis showed that extent of cavity involved and times of adhesiolysis performed were associated with placenta accreta. CONCLUSION: The extent of cavity involved and times of adhesive separation surgeries were risk factors for placenta accreta in patients. The menstrual model and gestational history may provide the main predictive factors for pregnancy loss.

Retraction Notice to: circRASSF2 Acts as ceRNA and Promotes Papillary Thyroid Carcinoma Progression through miR-1178/TLR4 Signaling Pathway.

[This retracts the article DOI: 10.1016/j.omtn.2019.11.037.].

Predictive Value of Preoperative Profiling of Serum Metabolites for Emergence Agitation After General Anesthesia in Adult Patients.

Background: Emergence agitation (EA) in adult patients under general anesthesia leads to increased postoperative complications and heavy medical burden. Unfortunately, its pathogenesis has not been clarified until now. The purpose of the present study was to explore the relationship between preoperative serum metabolites and EA. Methods: We used an untargeted metabolic analysis method to investigate the different metabolomes in the serum of EA patients and non-EA patients undergoing elective surgical procedures after the induction of general anesthesia. A Richmond Agitation-Sedation Scale score ≥ +2 was diagnosed as EA during postoperative emergence. Non-EA patients were matched with EA patients according to general characteristics. Preoperative serum samples of the two groups were collected to investigate the association between serum metabolites and EA development. Results: The serum samples of 16 EA patients with 34 matched non-EA patients were obtained for metabolic analysis. After screening and alignment with databases, 31 altered metabolites were detected between the two groups. These metabolites were mainly involved in the metabolism of lipids, purines, and amino acids. Analyses of receiver-operating characteristic curves showed that the preoperative alterations of choline, cytidine, glycerophosphocholine, L-phenylalanine, oleamide, and inosine may be associated with adult EA. Conclusion: Multiple metabolic abnormalities (including those for lipids, purines, and amino acids) and other pathological processes (e.g., neurotransmitter imbalance and oxidative stress) may contribute to EA. Several altered metabolites in serum before surgery may have predictive value for EA diagnosis. This study might afford new metabolic clues for the understanding of EA pathogenesis.

Pregnancy-related complications and perinatal outcomes following progesterone supplementation before 20 weeks of pregnancy in spontaneously achieved singleton pregnancies: a systematic review and meta-analysis.

BACKGROUND: Progesterone supplementation is widely performed in women with threatened miscarriage or a history of recurrent miscarriage; however, the effects of early progesterone supplementation on pregnancy-related complications and perinatal outcomes in later gestational weeks remain unknown. METHODS: Ovid MEDLINE, the Cochrane Library, Embase and ClinicalTrials.gov were searched until April 3rd, 2021. Randomized controlled trials regarding spontaneously achieved singleton pregnancies who were treated with progestogen before 20 weeks of pregnancy and were compared with those women in unexposed control groups were selected for inclusion. We performed pairwise meta-analyses with the random-effects model. The risk of bias was assessed according to the Cochrane Collaboration tool. The primary outcomes included preeclampsia (PE), and gestational diabetes mellitus (GDM), with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We identified nine eligible studies involving 6439 participants. The pooled OR of subsequent PE following early progestogen supplementation was 0.64 (95% CI 0.42-0.98, moderate quality of evidence). A lower OR for PE was observed in the progestogen group when the subgroup analysis was performed in the vaginal subgroup (OR 0.62, 95%CI 0.40-0.96). There was insufficient evidence of a difference in the rate of GDM between pregnant women with early progestogen supplementation and unexposed pregnant women (OR 1.02, 95% CI 0.79-1.32, low quality of evidence). The pooled OR of low birth weight (LBW) following oral dydrogesterone was 0.57 (95% CI 0.34-0.95, moderate quality of evidence). The results were affected by a single study and the total sample size of enrolled women did not reach the required information size. CONCLUSION: Use of vaginal micronized progesterone (Utrogestan) in spontaneously achieved singleton pregnancies with threatened miscarriage before 20 weeks of pregnancy may reduce the risk of PE in later gestational weeks. Among spontaneously achieved singleton pregnancies with threatened miscarriage or a history of recurrent miscarriage, use of oral dydrogesterone before 20 weeks of pregnancy may result in a lower risk of LBW in later gestational weeks. However, the available data were not sufficient to reach definitive conclusions, which highlighted the need for future studies.

Unresponsive thin endometrium caused by Asherman syndrome treated with umbilical cord mesenchymal stem cells on collagen scaffolds: a pilot study.

BACKGROUND: Unresponsive thin endometrium caused by Asherman syndrome (AS) is the major cause of uterine infertility. However, current therapies are ineffective. This study is to evaluate the effect of transplantation with collagen scaffold/umbilical cord mesenchymal stem cells (CS/UC-MSCs) on this refractory disease. METHODS: Eighteen infertile women with unresponsive thin endometrium, whose frozen-thawed embryo transfers (FETs) were cancelled due to reduced endometrial thickness (ET ≤ 5.5 mm), were enrolled in this before and after self-control prospective study. Hysteroscopic examination was performed to confirm no intrauterine adhesions, then twenty million UC-MSCs loaded onto a CS were transplanted into the uterine cavity in two consecutive menstrual cycles. Then uterine cavity was assessed through hysteroscopy after two transplants. FETs were performed in the following cycle. Pregnancy outcomes were followed up. Endometrial thickness, uterine receptivity and endometrial angiogenesis, proliferation and hormone response were compared before and after treatment. RESULTS: Sixteen patients completed the study. No treatment-related serious adverse events occurred. Three months after transplantation, the average ET increased from 4.08 ± 0.26 mm to 5.87 ± 0.77 mm (P < 0.001). Three of 15 patients after FET got pregnant, of whom 2 gave birth successfully and 1 had a miscarriage at 25 weeks' gestation. One of 2 patients without FET had a natural pregnancy and gave birth normally after transplantation. Immunohistochemical analysis showed increased micro-vessel density, upregulated expression of Ki67, estrogen receptor alpha, and progesterone receptor, indicating an improvement in endometrial angiogenesis, proliferation, and response to hormones. CONCLUSION: CS/UC-MSCs is a promising and potential approach for treating women with unresponsive thin endometrium caused by AS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03724617 . Registered on 26 October 2018-prospectively registered, https://register.clinicaltrials.gov/.