Epigenetic alternations and targeted therapy in intrauterine adhesion: A comparative study.

Although intrauterine adhesion (IUA) has been well recognized as a critical factor in infertility, little information is available regarding the molecular mechanisms. We performed a high-throughput RNA sequencing in the endometrium of three IUA patients and three normal controls. And another two gene expression profiles (PMID34968168 and GSE160365) were analyzed together. A total of 252 DEGs were identified. Cell cycle, E2F target, G2M checkpoint, integrin3 pathway and H1F1 signaling were aberrantly regulated in the IUA endometrium. 10 hub genes (CCL2, TFRC, THY1, IGF1, CTGF, SELL, SERPINE1, HBB, HBA1, LYZ) were exhibited in PPI analysis. FOXM1, IKBKB and MYC were three common transcription factors of DEGs. Five chemicals (MK-1775, PAC-1, TW-37, BIX-01294, 3-matida) were identified as putative therapeutic agents for IUA. Collectively, a series of DEGs associated with IUA were disclosed. Five chemicals and ten hub genes may be further explored as potential drugs and targets for IUA treatment.

Comparison of miRNA landscapes between the human oocytes with or without arrested development.

PURPOSE: By exploring the role of miRNAs in human oocyte development, the study was conducted to investigate the epigenetic mechanism contributing to the arrest of oocyte development. METHODS: In total, 140 oocytes from 22 patients were collected in the developmentally arrested oocyte (DAO) group, whereas 420 oocytes from 164 patients were harvested in the control group. The pooled RNA was extracted from all 20 oocytes to establish a RNA library. The total RNA of every ten oocytes was extracted for qPCR validation of miRNA candidates. Bioinformatic software was applied to explore the miRNA candidates and their target genes. RESULTS: Generally, the expression levels of miRNAs altered slightly during normal oocyte development but changed dramatically in the DAOs. Among the top 10 differential miRNAs, let-7a-5p and let-7g-5p, which were abundantly expressed throughout the oocyte development stages, had the broadest biological impact on oogenesis. Validated by qRT-PCR, both miRNAs were profoundly suppressed in the DAOs. During normal oocyte development, the expression levels of let-7a-5p and let-7g-5p at the GV stage were significantly higher than at MI and MII stages. Bioinformatic analysis demonstrated that let-7a-5p and let-7g-5p might regulate oocyte development by targeting PI3K-Akt, P53, cell cycle, and FoxO signaling pathways. CONCLUSIONS: There are dramatic differences in miRNA landscapes between the human oocytes with or without development arrest. In addition, the suppression of let-7a-5p and let-7g-5p might be associated with the occurrence of development arrest. The findings could provide therapeutic targets to correct the arrest of oocyte development in the future.

Low-frequency electrical stimulation promotes the recovery of gastrointestinal motility following gynecological laparoscopy (Review).

The rapid recovery of gastrointestinal transit is critical for clinical recovery following laparoscopic procedures, including gynecological laparoscopies (GLs). Rehabilitation interventions post-surgery may provide significant prevention against early post-operative gastrointestinal motility disorders and maid aid in the acceleration of post-operative recovery in patients undergoing GLs. Among others, low-frequency electrical stimulation (LFES) has been demonstrated to pronouncedly mitigate the symptoms caused by gastrointestinal motility disorders; thus, this has attracted increasing attention over the past decade. The present study aimed to present an overview of the efficacy and application of LFES in gastrointestinal motility recovery following GL procedures.

Nomogram to predict overall survival based on the log odds of positive lymph nodes for patients with endometrial carcinosarcoma after surgery.

PURPOSE: Aims to compare the prognostic performance of the number of positive lymph nodes (PLNN), lymph node ratio (LNR) and log odds of metastatic lymph nodes (LODDS) and establish a prognostic nomogram to predict overall survival (OS) rate for patients with endometrial carcinosarcoma (ECS). METHODS: Patients were retrospectively obtained from Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2015. The prognostic value of PLNN, LNR and LODDS were assessed. A prediction model for OS was established based on univariate and multivariate analysis of clinical and demographic characteristics of ECS patients. The clinical practical usefulness of the prediction model was valued by decision curve analysis (DCA) through quantifying its net benefits. RESULTS: The OS prediction accuracy of LODDS for ECS is better than that of PLNN and LNR. Five factors, age, tumor size, 2009 FIGO, LODDS and peritoneal cytology, were independent prognostic factors of OS. The C-index of the nomogram was 0.743 in the training cohort. The AUCs were 0.740, 0.682 and 0.660 for predicting 1-, 3- and 5-year OS, respectively. The calibration plots and DCA showed good clinical applicability of the nomogram, which is better than 2009 FIGO staging system. These results were verified in the validation cohort. A risk classification system was built that could classify ECS patients into three risk groups. The Kaplan-Meier curves showed that OS in the different groups was accurately differentiated by the risk classification system and performed much better than FIGO 2009. CONCLUSION: Our results indicated that LODDS was an independent prognostic indicator for ECS patients, with better predictive efficiency than PLNN and LNR. A novel prognostic nomogram for predicting the OS rate of ECS patients was established based on the population in the SEER database. Our nomogram based on LODDS has a more accurate and convenient value for predicting the OS of ECS patients than the FIGO staging system alone.

Development and validation of a model for individualized prediction of cervical insufficiency risks in patients undergoing IVF/ICSI treatment.

BACKGROUND: Women who conceived with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) are more likely to experience adverse pregnancy outcomes than women who conceived naturally. Cervical insufficiency (CI) is one of the important causes of miscarriage and premature birth, however there is no published data available focusing on the potential risk factors predicting CI occurrence in women who received IVF/ICSI treatment. This study aimed to identify the risk factors that could be integrated into a predictive model for CI, which could provide further personalized and clinically specific information related to the incidence of CI after IVF/ICSI treatment. PATIENTS AND METHODS: This retrospective study included 4710 patients who conceived after IVF/ICSI treatment from Jan 2011 to Dec 2018 at a public university hospital. The patients were randomly divided into development (n = 3108) and validation (n = 1602) samples for the building and testing of the nomogram, respectively. Multivariate logistic regression was developed on the basis of pre-pregnancy clinical covariates assessed for their association with CI occurrence. RESULTS: A total of 109 patients (2.31%) experienced CI among all the enrolled patients. Body mass index (BMI), basal serum testosterone (T), gravidity and uterine length were associated with CI occurrence. The statistical nomogram was built based on BMI, serum T, gravidity and uterine length, with an area under the curve (AUC) of 0.84 (95% confidence interval: 0.76-0.90) for the developing cohort. The AUC for the validation cohort was 0.71 (95% confidence interval: 0.69-0.83), showing a satisfactory goodness-of-fit and discrimination ability in this nomogram. CONCLUSION: The user-friendly nomogram which graphically represents the risk factors and a pre-pregnancy predicted tool for the incidence of CI in patients undergoing IVF/ICSI treatment, provides a useful guide for medical staff on individualized decisions making, where preventive measures could be carried out during the IVF/ICSI procedure and subsequent pregnancy.

Impact on using cryopreservation of testicular or epididymal sperm upon intracytoplasmic sperm injection outcome in men with obstructive azoospermia: a systematic review and meta-analysis.

PURPOSE: To determine whether there was a significant impact on using cryopreservation of testicular or epididymal sperm upon the outcomes of intracytoplasmic sperm injection (ICSI) in patients with obstructive azoospermia (OA). METHOD: Systematic review and meta-analysis of 20 retrospective studies in databases from January 1, 1995, to June 1, 2020. RESULT: Twenty articles were included in this study. A total of 3602 (64.1%) of 5616 oocytes injected with fresh epididymal sperm were fertilized, compared with 2366 (61.2%) of 3862 oocytes injected with cryopreserved sperm (relative risk ratio (RR) 0.96, 95% confidence interval (CI) (0.90, 1.02), P > 0.05). A total of 303 (44.1%) of 687 ICSI cycles using fresh epididymal sperm resulted in a clinical pregnancy, compared with 150 (36.6%) of 410 ICSI cycles using cryopreserved epididymal sperm (RR 0.84, 95% CI (0.72, 0.97), P < 0.05). In the testis, a total of 2147 (68.7%) of 3125 oocytes injected with fresh sperm were fertilized, compared with 1623 (63.5%) of 2557 oocytes injected with cryopreserved sperm (RR 0.97, 95% CI (0.90, 1.06), P > 0.05). A total of 151 (47.8%) of 316 ICSI cycles using fresh testicular sperm resulted in a clinical pregnancy, compared with 113 (38.2%) of 296 ICSI cycles using cryopreserved sperm (RR 0.87, 95% CI (0.72, 1.05), P > 0.05). CONCLUSIONS: In men with OA, there was a statistical lower clinical pregnancy rate (CPR) by using frozen epididymal sperm compared with fresh epididymal sperm, but showing no difference on fertilization rate (FR). Additionally, FR and CPR were not affected by whether the retrieved testicular sperm was frozen or fresh.

The Effect of Growth Hormone on the Clinical Outcomes of Poor Ovarian Reserve Patients Undergoing in vitro Fertilization/Intracytoplasmic Sperm Injection Treatment: A Retrospective Study Based on POSEIDON Criteria.

The aim of this retrospective analysis is to explore whether growth hormone (GH) pretreatment is beneficial for patients with poor ovarian reserve undertaking in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Poor ovarian reserve patients with anti-Mullerian hormone (AMH) <1.2 ng/mL were recruited and divided into the GH adjuvant group (GH+ group) and the counterpart without GH pretreatment (GH- group). One-to-one case-control matching was performed to adjust essential confounding factors between the GH+ group and GH- group. A total of 676 cycles were included in the present study with 338 cycles in each group. Conventional ovarian stimulation protocols were applied for ART treatment. Patients were further divided into POSEIDON group 3 (PG3, age <35 years) and POSEIDON group 4 (PG4, age ≥35 years), based on POSEIDON criteria. The demographic data, cycle characteristics, and clinical outcomes between the GH+ group and GH- group, as well as in the further stratified analysis of PG3 and PG4 were compared. GH adjuvant showed a beneficial effect on the ovarian response and live birth rate in poor ovarian reserve patients. Further stratification revealed that in PG4, there was a significantly increased number of good-quality embryos in the GH+ group compared to the GH- group (1.58 ± 1.71 vs. 1.25 ± 1.55, P = 0.032), accompanied by a reduced miscarriage rate and a greatly improved live birth rate (29.89 vs. 17.65%, P = 0.028). GH adjuvant failed to promote the live birth rate in PG3. In conclusion, GH pretreatment is advantageous by elevating ovarian response and correlated with an improved live birth rate and reduced miscarriage rate in POSEIDON poor ovarian reserve patients older than 35.