Melatonin application during cryopreservation improves the development and clinical outcomes of human vitrified-warmed oocytes.

In this clinical study, we investigated the potential of melatonin (MT) supplementation in the freeze-thaw medium used for cryopreserved human oocytes. In total, 152 patients who underwent in vitro fertilization between January 2020 and December 2022 were included and categorized into different groups as follows: the donor group, comprising 108 patients who donated their oocytes, with 34 patients using a vitrification and warming medium supplemented with MT (D-MT subgroup) and 74 patients using conventional medium without MT (D-0 subgroup); and the autologous group, comprising 38 patients who used their own oocytes, with 19 patients using medium supplemented with MT (A-MT subgroup) and 19 patients using medium without MT (A-0 subgroup). After thawing, the surviving oocytes in the D-MT and A-MT subgroups and D-0 and A-0 subgroups were cultured in a fertilization media with and without 10-9 MMT for 2.5 h, respectively, followed by intracytoplasmic sperm injection insemination, embryo culture, and transfer. The survival, cleavage, high-quality embryo, clinical pregnancy, ongoing pregnancy, and implantation rates were significantly higher in the D-MT subgroup than in the D-0 subgroup (all P < 0.05). Similarly, the survival, fertilization, high-quality embryo, and high-quality blastocyst rates were significantly higher in the A-MT subgroup than in the A-0 subgroup (all P < 0.05). These findings indicate that MT addition during cryopreservation can enhance the development of vitrified-warmed human oocytes and improve clinical outcomes.

Effect of melatonin on the clinical outcome of patients with repeated cycles after failed cycles of in vitro fertilization and intracytoplasmic sperm injection.

To explore whether embryo culture with melatonin (MT) can improve the embryonic development and clinical outcome of patients with repeated cycles after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) failure, immature oocytes from controlled ovarian superovulation cycles were collected for in vitro maturation (IVM) and ICSI. The obtained embryos were cultured in 0, 10-11, 10-9, 10-7 and 10-5 M MT medium respectively, and 10-9 M was screened out as the optimal concentration. Subsequently, 140 patients who underwent failed IVF/ICSI cycles received 140 cycles of embryo culture in vitro with a medium containing 10-9 M MT, these 140 MT culture cycles were designated as the experimental group (10-9 M group), and the control group was the previous failed cycles of patients (0 M group). The results showed that the fertilization, cleavage, high-quality embryo, blastocyst, and high-quality blastocyst rates of the 10-9 M group were significantly higher than those of the 0 M group (P < 0.01; P < 0.01; P < 0.0001; P < 0.0001; P < 0.0001). To date, in total, 50 vitrified-warmed cycle transfers have been performed in the 10-9 M group and the implantation rate, biochemical pregnancy rate and clinical pregnancy rate were significantly higher than those in the 0 M group (all P < 0.0001). Two healthy infants were delivered successfully and the other 18 women who achieved clinical pregnancy also had good examination indexes. Therefore the application of 10-9 M MT to embryo cultures in vitro improved embryonic development in patients with repeated cycles after failed IVF/ICSI cycles and had good clinical outcomes.Trial registration: ChiCTR2100045552.

Embryological Characteristics of Human Oocytes With Agar-Like Zona Pellucida and Its Clinical Treatment Strategy.

Zona pellucida (ZP) abnormalities are the cause of low fertility or infertility, agar-like ZP is more common in abnormal ZP. The purpose of this exploration is to systematically analyze the fertilization competence of agar-like ZP oocytes, the development characteristics of subsequent embryos as well as the results of embryo transfer, aiming to explore effective clinical treatment strategies. A total of 58 patients with agar-like ZP were set as the case group and the control group involved 3866 patients, in which the patients' oocytes presented normal ZP. BMI, basal hormone levels, and hormone levels were similar in both groups. The case patients suffered significantly longer infertility years than control (p<0.05), and most patients were diagnosed with pelvic inflammatory diseases. A distinct difference was observed in the structure of oocyte corona cumulus complexes between the two groups. The embryo development parameters, which include the rates of cleavage, high-quality embryo, blastocyst, and high-quality blastocyst in the case group were greatly lower than that in the control group (p<0.05). The rates of cumulative clinical pregnancy and live birth were comparable between the two groups. In the subsequent follow-up, thirty-four of the 58 patients receiving intracytoplasmic single sperm injection (ICSI) or early rescue ICSI (R-ICSI) treatment successfully gave birth to babies, and all of the newborns were with no neonatal defects. In addition, the fertilization rate of the R-ICSI group was significantly lower than that of the ICSI group (p<0.05). The occurrence of agar-like ZP impairs the development competence of human oocytes, however, the human oocytes with agar-like ZP can develop into healthy offspring, and an ICSI regimen is the optimal treatment strategy for them.

Prognostic impact of the pre-treatment controlling nutritional status score in patients with non-small cell lung cancer: A meta-analysis.

BACKGROUND: The influence of pre-treatment controlling nutritional status (CONUT) score on the prognosis of non-small cell lung cancer (NSCLC) patients is inconclusive. We performed this meta-analysis to evaluate the prognostic significance of CONUT score in NSCLC patients. METHODS: A systematic literature review was conducted using PubMed, Embase, and the Cochrane Library databases. The hazard ratio (HR) and 95% confidence interval (CI) were extracted to assess the correlation between the CONUT score and the overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), as well as the cancer-specific survival. RESULTS: A total of 11 studies with 3029 patients were included in the analysis. Pooled results indicated that a high CONUT score was positively correlated with poor OS (HR: 1.63, 95%CI: 1.40-1.88, P < .001) and shortened DFS/RFS (HR: 1.65, 95%CI: 1.35-2.01, P < .001), but no significant relationship with the cancer-specific survival (HR: 1.28, 95%CI: 0.60-2.73, P = .517) was identified. The negative effect of high CONUT score on the OS and DFS/RFS was detected in every subgroup with varying treatment methods, cancer stage, CONUT cut-off values, sample size, and analysis methods of HR. Additionally, preoperative high CONUT score was an independent predictor of postoperative complications (odds ratio: 1.58, 95%CI: 1.21-2.06, P = .001) in NSCLC. Last but not least, high CONUT score was not significantly correlated with the patients' sex, smoking status, cancer stage, lymphatic invasion, vascular invasion, pleural invasion, and pathological cancer type. CONCLUSION: These results demonstrate that high CONUT score is positively related to poor prognoses. The CONUT score may therefore be considered as an effective prognostic marker in NSCLC patients.

A ferroptosis-related lncRNA signature predicts prognosis in ovarian cancer patients.

BACKGROUND: Ovarian cancer (OC) is a common gynecological malignant tumor with poor prognosis. Ferroptosis is an iron-dependent modality of regulated cell death. The purpose of this study was to determine the prognostic ability of ferroptosis-related long non-coding RNAs (lncRNAs) in OC patients and construct a ferroptosis-related lncRNA prognostic model. METHODS: The Cancer Genome Atlas (TCGA) and FerrDb databases were used to collect RNA sequencing data of OC patients and ferroptosis-related genes, respectively. OC patients were randomly assigned to the training or testing set. Pearson correlation analysis was used to identify ferroptosis-related lncRNAs. Univariate Cox, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate regression analyses were performed in the training set to develop a predictive model. The model was validated in the testing set and entire set. Survival analysis, receiver operating characteristic curves, independent prognostic factor analysis, and correlation analysis with clinical features were performed to evaluate the predictive value of the model. A nomogram was established to predict the survivability of OC patients over 1, 3, and 5 years. The distribution of distinct groups was investigated using principal component analysis, and the underlying the biological functions were explored using gene set enrichment analysis. RESULTS: Eleven ferroptosis-related lncRNAs were determined to establish the prognostic model. Patients in the high-risk group had poor prognosis compared with the low-risk group in the training, testing and entire sets. The area under the receiver operating characteristic curve corresponding to 1-, 3-, and 5-year survival were 0.731, 0.796, and 0.805 in the training set; 0.704, 0.597, and 0.655 in the testing set; and 0.715, 0.691, and 0.736, in the entire set, respectively. The risk score correlated with age and grade. The risk score was also an independent prognostic factor in OC. A nomogram with high C-index (0.68) was constructed. An intuitive observation of the principal component analysis revealed a distinction between high- and low-risk groups, and gene set enrichment analysis indicated that cancer-related pathways were enriched in the high-risk group. CONCLUSIONS: The signature composed of 11 ferroptosis-related lncRNAs accurately predicted the prognosis of OC patients.