Background:Recurrent implantation failure (RIF) presents a crucial obstacle to in vitro fertilization success. Previous research has shown that small extracellular vesicles (EVs) from endometrial RIF patients hinder embryo development, yet the underlying mechanism and potential solutions remain largely unexplored. In this study, we aimed to investigate the effectiveness of miR-218-5p as a molecular factor in RIF-EVs. Our findings revealed that miR-218-5p disrupted mouse embryo development, and this effect could be reversed by engineered extracellular vesicles (E-EVs) containing anti-miR-218-5p. Methods:The percentage of blastocyst development and hatching rates, embryo morphology, and the total cell number were measured. RNA-sequencing was used to analyze transcriptional changes in embryos post miR-218-5p agomir treatment. The abnormal segregation genes of trophectoderm (TE) and inner cell mass (ICM) were visualized via qRT-PCR and immunofluorescence staining. The E-EVs were using the EVs derived from Human Umbilical Cord Mesenchymal Stem Cells (HUMSCs). Characteristics of the EVs were measured using Western blotting, nanoparticle tracking analysis, and transmission electron microscopy. EVs internalization was visualized using BODIPY TR ceramide staining. Results:Mouse embryos were arrested at the morula stage and demonstrated reduced blastocyst and hatching rates following miR-218-5p agomir treatment (P < 0.001). Essential transcription factors for TE and ICM, such as Cdx2, Yap1, Sox2, Nanog, Tead4, were reduced at the mRNA level in the miR-218-5p treated morula. This was accompanied by decreased Cdx2 protein levels at the 8-16-cell stage (P < 0.001) and disruption of co-localization of Yap1 and Cdx2. The blastocyte rate was increased by anti-miR-218-5p-encapsulated E-EVs compared with miR-218-5p group (P < 0.001). Conclusion:This study offers valuable insights into the potential role of miR-218-5p in RIF and presents. The utilization of engineered vesicles containing anti-miR-218-5p may present a promising avenue for patients facing challenges with RIF.

Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The quality of oocytes in PCOS patients remains poor, leading to poor pregnancy outcomes. The molecular mechanisms underlying the poor quality of oocytes in PCOS are not fully understood. This study aimed to explore the potential functional microRNAs (miRNAs) in follicular fluid (FF)-derived extracellular vesicles (FF-EVs) and their role in oocyte developmental competence in PCOS. We analyzed DEmiRNAs in FF-EVs and DEGs in oocytes from PCOS patients and controls using GEO database. We identified 14 potential functional DEmiRNAs in FF-EVs and predicted the target genes of 14 DEmiRNAs using TargetScan. We performed conjoint analyses between the target genes of these miRNAs and DEGs in oocytes, identifying 12 DEmiRNAs whose target genes overlap with oocyte DEGs. Thus, 12 functional DEmiRNAs were the hub miRNAs. These miRNAs were predicted to target genes involved in oocyte development and signaling pathways such as PI3K/Akt, Ras, and MAPK pathways. KEGG enrichment analysis suggested that these miRNAs might impair oocyte developmental competence in PCOS by dysregulating PI3K/Akt signaling pathway. qRT-PCR validated the increase of miR-93-3p and miR-152-3p, and the decrease of miR-625-5p and miR-17-5p in FF-EVs of PCOS patients. This study highlighted the significance of FF-EVs in the pathology of PCOS and revealed the potential role of the increase of miR-93-3p and miR-152-3p, and the decrease of miR-625-5p and miR-17-5p in impairing oocyte developmental competence in PCOS. Further research is needed to elucidate the specific mechanisms by which these miRNAs affect oocyte development and to explore the potential therapeutic implications.

BACKGROUND:Cyclophosphamide (CTX)-induced ovarian dysfunction and infertility represent significant concerns for reproductive-age or younger female cancer patients. Although various fertility preservation techniques are currently accessible, there remains a pressing demand for an efficient, non-invasive strategy to protect ovarian function that can be employed concurrently with chemotherapy. Considering the significance of nicotinamide adenine dinucleotide (NAD+) in regulating DNA damage and apoptosis, we aimed to examine the protective effects of nicotinamide mononucleotide (NMN, an NAD+ precursor) on ovarian function against CTX-induced damage. RESULTS:Eight-week-old female C57 mice were underwent to a 14-day treatment protocol, receiving either saline, CTX, or CTX combined with NMN supplementation. The protective effects of NMN supplementation during CTX treatment on ovarian reserve, oocyte quality, and developmental competence were evaluated. NMN supplementation during CTX treatment increased NAD+ content in the ovary, improved ovarian reserve, enhanced endocrine function, reduced reactive oxygen species (ROS) levels, alleviated DNA damage, and reduced apoptosis. Furthermore, this supplementation improved the rates of two-cell embryo and blastocyst formation, increased total cell counts, while decreasing ROS levels, DNA damage, and apoptosis in blastocysts. Moreover, the protective mechanisms of NMN may involve key genes such as Banp and Rbm47 in the ovarian tissue, along with serum/glucocorticoid-regulated kinase 1 (Sgk1) in oocytes. CONCLUSIONS:Collectively, our results highlight the protective effects of NMN against CTX-induced damage to the reproductive function, thus addressing a critical gap in fertility preservation. We present a potential non-invasive strategy that does not interfere with cancer therapy timelines.

Clinical application of mesenchymal stem cells for endometrial repair has been hampered by variability in cell quality, large-scale production, and uncertainty regarding the optimal delivery route. In this study, we investigated the therapeutic potential of clinical-grade human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) for treating refractory moderate-to-severe intrauterine adhesion (IUA). In a rabbit IUA model, sub-endometrial injection of IMRCs significantly reduced fibrosis and enhanced endometrial angiogenesis, outperforming uterine perfusion. Transcriptomic analysis revealed distinct pro-angiogenic gene expression profiles between the two delivery routes. In vitro, IMRCs co-cultured with endometrial stromal cells (ESCs) markedly enhanced angiogenic potential compared to either cell type alone. Protein array analysis of the co-culture supernatant showed elevated levels of angiogenic factors, with functional assays confirming that inhibition of ANGPTL4, a non-canonical pro-angiogenic mediator, impaired angiogenesis. In a first-in-human, single-center, phase 1 dose-escalation trial involving 18 patients with refractory IUA, high-dose sub-endometrial IMRC injection promoted angiogenesis, reduced uterine scarring, and improved pregnancy outcomes, with no safety concerns observed over 3 years of follow-up. These findings highlight the translational promise of IMRCs as a novel therapeutic strategy for endometrial regeneration in severe IUA.

The endometrium, the inner lining of the uterus, assumes a crucial role in the female reproductive system. Disorders and injuries impacting the endometrium can lead to profound consequences, including infertility and compromised women's overall health. Recent advancements in stem cell research have opened new possibilities for the treatment and repair of endometrial issues. In the present study, we constructed a degradable hydrogel by loading adipose-derived stem cells (ADSCs) and melanin nanoparticles (MNP). In vitro cell experiments validated the biocompatibility of the prepared hydrogels and their adeptness in encapsulating ADSCs. Subsequently, we explored the impact of hydrogel@ADSC@MNP constructs in the healing process of uterine injury in mice. The results indicated that hydrogel@ADSC@MNP could augment endometrial thickness and ameliorate endometrial interstitial fibrosis. The injured tissue adjacent to hydrogel@ADSC@MNP constructs exhibited higher levels of bFGF, IGF-1, and VEGFA compared with the corresponding tissue in mice receiving hydrogel constructs alone or in the model group. Furthermore, the hydrogel@ADSC@MNP system enhanced the proliferative capabilities of uterine endometrial cells, facilitated microvasculature regeneration, and reinstated the endometrium's capacity to receive the embryos. Our findings strongly suggest that the hydrogel@ADSC@MNP system holds significant promise for repairing and regenerating damaged endometrium.

In this study, we aimed to investigate the molecular mechanisms of RNA N6-methyladenosine (m6A) modification and how its associated proteins affect granulosa cell aging. A granulosa cell senescence model was constructed to detect the differences in total RNA m6A modification levels and the expression of related enzymes. Changes in downstream molecular expression and the effects on the cellular senescence phenotype were explored by repeatedly knocking down and overexpressing the key genes fat mass and obesity-associated protein (FTO), YT521-B homology domain family member 2 (YTHDF2), and matrix metalloproteinase-2 (MMP2). There was an increased total RNA m6A modification and decreased expression of the demethylase FTO and target gene MMP2 in senescent granulosa cells. FTO and MMP2 knockdown promoted granulosa cell senescence, whereas FTO and MMP2 overexpression retarded it. YTHDF2 and FTO can bind to the messenger RNA of MMP2. The extracellular signal-regulated kinase (ERK) pathway, which is downstream of MMP2, retarded the process of granulosa cell senescence through ERK activators. In granulosa cells, FTO can regulate the expression of MMP2 in an m6A-YTHDF2-dependent manner, influencing the activation status of the ERK pathway and contributing to the aging process of granulosa cells.

BackgroundEndometriosis is a chronic inflammatory disease of women during their reproductive years. The relationship between the severity and location of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery remains unclear.MethodsWe explored the association between the various phenotypes of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery, using two-sample Mendelian randomization (MR) and summary data on endometriosis stages and locations from the FinnGen consortium and women’s menstruation, ovulation, reproductive function, and mode of delivery from OpenGWAS and ReproGen. Inverse-variance weighting was used for the primary MR analysis. In addition, a series of sensitivity analyses, confounding analyses, co-localization analyses, and multivariate MR analyses were performed.ResultsMR analysis showed a negative effect of moderate to severe endometriosis on age at last live birth (OR = 0.973, 95% CI: 0.960–0.986) and normal delivery (OR = 0.999, 95% CI: 0.998–1.000; values for endpoint were excluded), ovarian endometriosis on age at last live birth (OR = 0.976, 95% CI: 0.965–0.988) and normal delivery (OR = 0.999, 95% CI: 0.998–1.000; values for endpoint were excluded), and fallopian tubal endometriosis on excessive irregular menstruation (OR = 0.966, 95% CI: 0.942–0.990). Bidirectional MR analysis showed that age at menarche had a negative causal effect on intestinal endometriosis (OR = 0.417, 95% CI: 0.216–0.804). All MR analyses were confirmed by sensitivity analyses, and only the genetic effects of moderate to severe endometriosis on normal delivery and age at last live birth were supported by co-localization evidence.ConclusionOur findings deepen the understanding of the relationship between various types of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery and clarify the important role of moderate to severe endometriosis.

BackgroundReproduction-related congenital birth defects (RCBDs), including Klinefelter syndrome (KS), Turner syndrome (TS), and urogenital congenital anomalies (UCA), can lead to severe physical and psychosocial disorders. The global impact of RCBDs on children and adults is unknown, which limits high-quality development of populations and increases in life expectancy per capita.MethodsAnnual incidence rates, prevalence rates (PR), and disability-adjusted life year (DALY) rates were collected for KS, TS, and UCA for 204 countries and territories, including at birth, for children younger than 1 year, and age-standardized (AS) for all ages. Linear regression was used to calculate their estimated annual percentage changes (EAPCs). Finally, the relationships between EAPCs of each indicator and sociodemographic index (SDI) was investigated using Pearson correlation analysis.ResultsGlobally, the age-standardized prevalence rate (ASPR) trend is decreasing in KS and TS and increasing in UCA. The DALY rates for children younger than 1 year were on a downward trend in KS and UCA, while they were still rising for TS. The AS-DALY rates were all on a downward trend in KS, TS, and UCA. The DALY rates of KS, TS and UCA were found higher in high-income countries in North America. In addition, the burdens of TS and UCA went down with increasing SDI, whereas the burden of KS increased with increasing SDI.ConclusionThe global burdens of RCBDs have decreased since 1990. This finding can help policymakers implement cost-effective interventions to reduce the burdens of RCBDs.

Background:The sensitivity of breast cancer cells to radiation is a key cause of locoregional recurrence after postoperative radiotherapy.Several studies have reported that microRNAs （mi RNAs） are involved in the radiosensitivity of human breast cancer cells.One mi RNA microarray study showed that mi R-450b-5p was overexpressed 13.3-fold in patients with estrogen receptor–positive （ER + ） and human epidermal growth factor receptor 2–negative （HER2 - ） breast cancer and no local relapse compared with local relapse patients.However its underlying mechanism of action remains unknown.Methods:The predicted target m RNAs of miR-450b-5p were screened using the TargetScan,miRDB,and mi RWalk databases.Western blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays explored the association between cyclindependent kinase 6 （CDK6） and miR-450b-5p.The cell counting kit-8 assay and flow cytometry detected the proliferation of transfected MCF7 cel s.Colony formation and xenograft tumors detected the radiosensitivity of the transfected MCF7 cells.Results:Bioinformatics analysis,Western blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays demonstrated that CDK6 was the target gene of miR-450b-5p.Furthermore,in vitro and in vivo experiments showed that miR-450b-5p inhibited MCF7 cell proliferation and cel cycle progression,increased the sensitizer enhancement ratio,and decreased the volume of xenograft tumors after irradiation by regulating CDK6.Conclusions:This study demonstrates that miR-450b-5p enhances the radiosensitivity of hormone receptor–positive （HR + ） and HER2 - breast cancer cel s and elucidates its mechanism.miR-450b-5p may be considered a therapeutic target in HR + and HER2 - breast cancer treated with radiotherapy.

Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however, the underlying mechanisms linking obesity to breast cancer outcomes remain elusive. This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity. Methods:We conducted a reanalysis of gene expression profiles from normal-weight, overweight, and obese breast cancer patients to identify candidate genes. Subsequently, we validated the protein levels of these candidates using immunohistochemistry. Finally, we inves-tigated the association between candidate genes and breast cancer prognosis at Tongji Hospital, utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models. Results:The fold change of the circadian clock gene period 2 (PER2), which exhibited a declining trend with increasing body mass index, was 0.76 in obese patients compared with normal-weight patients. The expression rates of PER2 protein were 44.7％, 51.5％, and 61.3％in normal-weight, overweight, and obese patients, respectively. The 8-year recurrence-free survival rates were 75.9％, 69.6％, and 64.1％, whereas the 8-year overall survival rates were 86.8％, 83.0％, and 76.1％in normal-weight, overweight, and obese patients, respectively ( P< 0.05). Furthermore, the 8-year recurrence-free survival rates were 66.2％ and 76.4％, and the 8-year overall survival rates were 79.9％and 86.3％in the low and high PER2 expression groups, respectively ( P<0.05). The un-adjusted hazard ratio for PER2 was 1.550 (95％confidence interval, 1.029–2.335), and the adjusted hazard ratio was 3.003 (95％confidence interval, 1.838–4.907). Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.

BackgroundThere is a higher risk of preterm delivery (PTD) in singleton live births conceived after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) compared with spontaneously conceived pregnancies. The objective of our study was to build a predictive nomogram model to suggest the possibility of PTD in singleton pregnancies after IVF/ICSI treatment.Method11513 IVF/ICSI cycles with singleton live births were enrolled retrospectively. These cycles were randomly allocated into a training group (80%) and a validation group (20%). We used the multivariate logistics regression analysis to determine prognostic factors for PTD in the training group. A nomogram based on the above factors was further established for predicting PTD. Receiver operating characteristic curves (ROC), areas under the ROC curves (AUC), concordance index (C-index), and calibration plots were analyzed for assessing the performance of this nomogram in the training and validation group.ResultsThere were fourteen risk factors significantly related to PTD in IVF/ICSI singleton live births, including maternal body mass index (BMI) > 24 kg/m2, smoking, uterine factors, cervical factors, ovulatory factors, double embryo transferred (DET), blastocyst transfer, FET, vanishing twin syndrome (VTS), obstetric complications (placenta previa, placenta abruption, hypertensive of pregnancies, and premature rupture of membrane), and a male fetus. These factors were further incorporated to construct a nomogram prediction model. The AUC, C-index, and calibration curves indicated that this nomogram exhibited fair performance and good calibration.ConclusionsWe found that the occurrence of PTD increased when women with obesity, smoking, uterine factors, cervical factors, ovulatory factors, DET, VTS, and obstetric complications, and a male fetus. Furthermore, a nomogram was constructed based on the above factors and it might have great value for clinic use.

Ovarian tissue oocyte (OTO) in vitro maturation (IVM) is a strategy to improve fertility preservation efficiency. Here, the effects of capacitation IVM (CAPA-IVM) on OTO function were investigated. Immature cumulus-oocyte complexes (COCs) from unstimulated 28-day-old mouse ovaries (mimicking OTOs) underwent CAPA-IVM, standard IVM (S-IVM) or in vivo maturation following ovarian stimulation (OS; positive control), and oocyte meiotic maturation and cytoplasmic quality were assessed. CAPA-IVM resulted in improved oocyte meiotic maturation (P < 0.05) and cumulus expansion (P < 0.0001) compared to S-IVM, with expansion comparable to the OS group. MII OTO ROS was lower after CAPA-IVM than S-IVM (P < 0.0001) but not as low as in the OS group (P = 0.036). CAPA-IVM resulted in a better oocyte mitochondrial distribution than S-IVM (P < 0.05) and was similar to the OS group (P > 0.05). Mitochondrial membrane potential in MII OTOs was higher after CAPA-IVM than S-IVM and OS (P < 0.0001). Compared with S-IVM, CAPA-IVM resulted in lower rates of spindle/chromosome configuration and cortical granule distribution abnormalities (P < 0.05), which were similar to OS levels (P > 0.05). MII OTO intracellular Ca2+ levels were similar in the CAPA-IVM and OS groups (P > 0.05), while S-IVM decreased intracellular Ca2+ (P < 0.05). CAPA-IVM and S-IVM decreased mitochondrial Ca2+ levels (P < 0.05). CAPA-IVM increased expression of antioxidant genes (Sod2 and Sirt1) and Egfr (P < 0.05) but not apoptotic genes (Bcl2, Bax and Bcl2/Bax; P > 0.05). CAPA-IVM increased the OTO maturation rate and quality of oocytes from unstimulated mice to the extent that many features of oocyte cytoplasmic quality were comparable to superovulated in vivo matured oocytes.

Context Polycystic ovary syndrome (PCOS) is one of the most common diseases that contribute to subfertility. Recent evidence showed that oocytes of women with PCOS matured in vitro away from the follicular fluid presented better potentials, whereas the reason remained unclear. Objective This work aimed to investigate whether follicular extracellular vesicles (EVs) of PCOS patients interfere with the quality of oocytes. Methods Follicular EVs of women with PCOS (PCOS-EVs) and control women (CTRL-EVs) were isolated and determined using Western blotting, nanoparticle tracking analysis, and transmission electron microscopy. The 2 types of EVs were co-cultured with murine germinal vesicle oocytes, respectively. Fluorescence-labeled EVs were used to visualize internalization by oocytes. After co-culture, oocyte maturation rates were calculated. Mitochondria distribution and reactive oxygen species (ROS) level were detected in the different groups. Spindle morphology was evaluated using immunofluorescence. Moreover, the expression of catalase (CAT), glutathione synthetase (GSS), and superoxide dismutase (SOD) was determined in the oocytes. Results Both PCOS-EVs and CTRL-EVs are bilayered vesicles, approximately 100 to 150 nm in size, and enriched in EV-associating protein markers. EVs were internalized by oocytes within 1 hour. Oocyte maturation rate decreased significantly in the PCOS-EV group compared with the CTRL-EV group, whereas the abnormal mitochondria distribution rate and abnormal spindle rate were significantly increased in the PCOS-EV group. Moreover, PCOS-EVs increased the ROS level and the expression of CAT, GSS, and SOD in the oocytes. Conclusion PCOS-EVs interfered with oocyte mitochondria and spindles and inhibited oocyte maturation. Moreover, oxidative stress induced by PCOS-EVs might be a potential cause.

Uterine fibroids (UFs) are the most common benign gynecologic tumors in reproductive-aged women. The typical diagnostic strategies of UFs are transvaginal ultrasonography and pathological feature, while molecular biomarkers are considered conventional options in the assessment of the origin and development of UFs in recent years. Here, we extracted the differential expression genes (DEGs) and differential DNA methylation genes (DMGs) of UFs from the Gene Expression Omnibus (GEO) database, GSE64763, GSE120854, GSE45188, and GSE45187. 167 DEGs with aberrant DNA methylation were identified, and further Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed by the relevant R package. We next discerned 2 hub genes (FOS, and TNFSF10) with autophagy involvement by overlapping 167 DEGs and 232 autophagic regulators from Human Autophagy Database. FOS was identified as the most crucial gene through the Protein-Protein Interactions (PPI) network with the correlation of the immune scores. Moreover, the down-regulated expression of FOS in UFs tissue at both mRNA and protein levels was validated by RT-qPCR and immunohistochemistry respectively. The area under the ROC curve (AUC) of FOS was 0.856, with a sensitivity of 86.2% and a specificity of 73.9%. Overall, we explored the possible biomarker of UFs undergoing DNA-methylated autophagy and provided clinicians with a comprehensive assessment of UFs.

OBJECTIVE: To assess the efficacy of the Zishen Yutai Pill compared with placebo on live birth rates among women after fresh embryo transfer cycles. METHODS: We conducted a double-blind, multicenter, placebo-controlled, randomized trial to investigate whether administration of the Zishen Yutai Pill would improve pregnancy outcomes among women undergoing fresh embryo transfer after in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was live birth rate. Secondary outcomes were rates of implantation, biochemical pregnancy, clinical pregnancy, pregnancy loss, cycle cancellation, and maternal, fetal, and neonatal complications. A total sample size of 2,265 women (1:1 in two groups) was used to detect a live birth rate difference between the Zishen Yutai Pill and placebo. Participants were enrolled and randomized to receive 5 g of the Zishen Yutai Pill or placebo orally, three times per day during the study. RESULTS: Recruitment was completed between April 2014 and June 2017, with 2,580 patients screened. Two thousand two hundred sixty-five patients were randomized: 1,131 to the Zishen Yutai Pill and 1,134 to placebo. Characteristics were similar between groups. In intention-to-treat analysis, the rates of live birth in the Zishen Yutai Pill (ZYP) group and placebo group were 26.8% and 23.0% (rate ratio [RR], 1.16; 95% CI 1.01-1.34; P=.038), respectively. The implantation rates were 36.8% and 32.6% in the ZYP and placebo groups, respectively (RR 1.13; 95% CI 1.01-1.25; P=.027). The biochemical pregnancy rate for the ZYP group was 35.5% compared with 31.1% in the placebo group (RR 1.14; 95% CI 1.021.28; P=.026). The rates of clinical pregnancy in the ZYP and placebo groups were 31.2% compared with 27.3%, respectively (RR 1.14; 95% CI 1.00-1.30; P=.043). There were no significant between-group differences in the rates of pregnancy loss, maternal, or neonatal complications (all P>.05). CONCLUSION: The Zishen Yutai Pill increased the rate of live birth after fresh embryo transfer compared with placebo.

Background: Thin endometrium on ovulation triggering day is associated with impaired pregnancy outcomes in women after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), but the role of thick endometrium on pregnancy outcomes remains controversial. Moreover, there has been insufficient evidence currently to analyze the influence of endometrial thickness (EMT) on obstetric complications and perinatal outcomes. Thus, we performed this meta-analysis to evaluate the effect of EMT on pregnancy, maternal, and perinatal outcomes in an enlarged sample size.& nbsp;Methods: The databases Pubmed, Embase, Cochrane Libraries, and Web of Science were searched for English articles evaluating the correlation between EMT and pregnancy, maternal, or perinatal outcomes in women who underwent IVF/ICSI. We included studies that depicted a clear definition of outcomes and EMT grouping on ovulation triggering day. The EMT effect was analyzed in fresh cycle. Qualities of studies were assessed by the Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) and weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated for analyzing dichotomous and continuous outcomes respectively, under a fixed or random effect model.& nbsp;Results: A total of 22 pieces of literature were included for the final meta-analysis. A decreased trend towards pregnancy outcomes was observed, such as live birth rate (LBR), clinical pregnancy rate (CPR), and implantation rate (IR) in the thin endometrium groups (EMT < 7 mm). In contrast, thick endometrium (EMT > 14 mm) had no effect on pregnancy outcomes compared to medium EMT groups (EMT 7-14 mm). Moreover, thin endometrium (EMT < 7.5 mm) enhanced the incidence of hypertensive disorders of pregnancy (HDP) and small-for-gestational-age (SGA) infants, and decreased the birthweight (BW) of babies.& nbsp;Conclusions: Our studies indicated that thin endometrium not only had detrimental effect on pregnancy outcomes, but also increased the risk of HDP in women and SGA of babies, or decreased BW of babies. The thick endometrium does not have an adverse effect on IVF outcomes. Therefore, patients need to be informed on possible obstetric complications and perinatal outcomes caused by thin endometrium and are encouraged to actively cooperate with perinatal care.& nbsp;Systematic Review Registration(https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=242637), identifier CRD42021242637.

Women with hereditary breast cancer factors are more likely to be infertile and tend to receive fertility treatments. The safety of fertility treatments that contain hormone-related medications for ovarian stimulation has gained wide attention; however, evidence of the safety of fertility treatments is limited. This study aims to assess the association between fertility treatments and the incidence rate of breast cancer in women with a family history of breast cancer or BRCA mutations. A literature search was conducted in PubMed, Cochrane Library, and Embase. Studies concerning the effect of fertility treatments on breast cancer risk in genetically susceptible women were included. The fixed and random effects models were used to estimate the summary effects. Risk Of Bias In Non-randomized Studies - of Interventions instrument was used to assess the risk of bias in the included studies. A total of 5,282 studies were screened. Five cohort studies and three case-control studies were included. Breast cancer risk was not significantly increased by fertility treatments in general genetically susceptible women [pooled odds ratio (OR) 1.18, 95% confidence interval (CI) 0.96–1.45], women with a family history of breast cancer (pooled OR 1.35, 95% CI 0.97–1.89), or women with BRCA mutations (pooled OR 1.02, 95% CI 0.74–1.4). In subgroup analyses, there was no significant increase in breast cancer risk whether in BRCA1 mutation carriers (pooled OR 1.18, 95% CI 0.81–1.72), BRCA2 mutation carriers (pooled OR 0.54, 95% CI 0.09–3.34), or in the women treated with in vitro fertilization (pooled OR 0.75, 95% CI 0.51–1.1), clomiphene citrate (pooled OR 1.07, 95% CI 0.78–1.45) or gonadotropins (pooled OR 1.32, 95% CI 0.8–2.18). This is the first meta-analysis concerning the impact of fertility treatments on breast cancer risk in genetically susceptible women. Despite the finding that fertility treatment did not significantly increase breast cancer risk in genetically susceptible women, large prospective cohorts with more detailed information are required. Further investigations are needed to explore subtypes of breast cancer, genetic background of hormone-related breast cancer, and the association between BRCA mutations and the incidence of hormone receptor-positive breast cancer. Registration number PROSPERO(CRD42021281336).

Objective: We aim to identify the crucial genes or potential biomarkers associated with uterine fibroids (UFs), which may provide clinicians with evidence about the diagnostic biomarker of UFs and reveal the mechanism of its progression. Methods: The gene expression and genome-wide DNA methylation profiles were obtained from Gene Expression Omnibus database (GEO). GSE45189, GSE31699, and GSE593 datasets were included. GEO2R and Venn diagrams were used to analyze the differentially expressed genes (DEGs) and extract the hub genes. Gene Ontology (GO) analysis was performed by the online tool Database for Annotation, Visualization, and Integrated Discovery (DAVID). The mRNA and protein expression of hub genes were validated by RT-qPCR, western blot, and immunohistochemistry. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. Results: We detected 22 DEGs between UFs and normal myometrium, which were enriched in cell maturation, apoptotic process, hypoxia, protein binding, and cytoplasm for cell composition. By finding the intersection of the data between differentially expressed mRNA and DNA methylation profiles, 3 hub genes were identified, including transmembrane 4 L six family member 1 (TM4SF1), TNF superfamily member 10 (TNFSF10), and proteolipid protein 1 (PLP1). PLP1 was validated to be up-regulated significantly in UFs both at mRNA and protein levels. The area under the ROC curve (AUC) of PLP1 was 0.956, with a sensitivity of 79.2% and a specificity of 100%. Conclusion: Overall, our results indicate that PLP1 may be a potential diagnostic biomarker for uterine fibroids.

Precis: We reduced the tube length through a small limbal incision in eyes that underwent Ahmed glaucoma valve (AGV) implantation and found that the rate of corneal endothelial cell (CEC) density was markedly reduced from -12.2% per year to -3.5% per year after this simple procedure. Purpose: The aim was to evaluate the effect of postoperative tube tip trimming (TT) after AGV implantation on CEC loss. Methods: In this retrospective cohort study, a total of 75 eyes from 67 patients (41 eyes in the AGV implantation only group (AGVG: mean follow-up, 42.2 +/- 13.8 mo) and 34 eyes in the TT after AGV implantation group (TAGVG: mean follow-up, 64.9 +/- 18.5 mo) were analyzed. TT was performed through a small limbal incision at a mean of 41 months after AGV implantation. Both groups were followed up for at least 1 year and underwent at least 2 specular microscopic examinations after AGV implantation and/or TT. Results: In the AGVG, CEC density was reduced from 2247.0 +/- 527.3 to 1665.7 +/- 643.3 cells/mm(2) (P<0.001). In the TAGVG, it was reduced from 2383.1 +/- 619.4 to 1552.9 +/- 700.9 cells/mm(2) before TT (mean 41 mo of follow-up) and after TT, to 1394.6 +/- 654.7 cells/mm(2) (mean 26 mo of the follow-up). The reduction rate of CEC density before TT was -12.2 +/- 6.5% per year, and this rate was significantly reduced to -3.5 +/- 6.9% per year after TT in the TAGVG (P=0.002). The probability of corneal failure defined as a 15% reduction in CEC density was significantly reduced after TT in TAGVG (P=0.038). Conclusions: Tube TT after AGV implantation markedly reduced the rate of CEC loss without serious complications in eyes with AGV implantation.

Some concern has been expressed regarding the negative effects of low-level ionizing radiation exposure in the context of radiological evaluation prior to IVF/ICSI treatment, but the available evidence is limited and conflicting. The aim of this study is to evaluate pregnancy and neonatal outcomes of couples who did chest computed tomography (CT) prior to IVF/ICSI. This was a retrospective cohort study of 2680 IVF/ICSI fresh embryo transfer cycles conducted from January 2019 – August 2020. Fertility outcomes were compared between couples that had or had not undergone CT examination within 3 months prior to the date of oocyte retrieval and sperm collection. Miscarriage was the primary study outcome, while secondary outcomes included the number of oocytes collected, oocyte maturation, normal fertilization, number of good quality cleavage stage embryos, blastocyst formation, implantation, clinical pregnancy, ectopic pregnancy, live birth, multiple birth, Cesarean section rates, gestational weeks, maternal obstetric complications, birth weight, newborn sex ratio, and birth defect incidence. Propensity score matching was used to control for potential confounding variables. Of the 2680 cycles included in this study, couples underwent CT examination in 731 cycles. After 1:1 propensity score matching, 670 cycles were included in each group. When comparing demographic and fertility-related variables between groups that had and had not undergone CT examination after propensity score matching, we detected no significant differences in miscarriage rates (16.99