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ObjectiveThis study aims to evaluate the utility of polygenic risk scores (PRS) in women with early menopause (EM) and to investigate the clinical characteristics and risk factors associated with EM based on genetic risk.Study designGenotyping data and clinical data from women with EM and women with normal age of menopause retrieved from UK Biobank were used for early menopause risk prediction model establishment. Subsequently, 99 women diagnosed with EM and 1027 control women underwent PGT-M were recruited for model validation from across eight hospitals in China. According to PRS percentiles, these participants were further classified into high risk and intermediate risk groups. Characteristics among women at different risk levels were compared, and risk factors with early menopause were also statistical analyzed.Main outcome measuresThe proportion of women at high risk in EM and control groups; Characteristics with significant difference among women at different risk levels; risk factors associated with EM.ResultsThe proportion of high-risk women in the EM group was significantly higher than that in control women underwent PGT-M (Group PGT-M) (OR = 3.78), and that in women with normal age menopause from UK Biobank (Group UKB) (OR = 5.11). Notably, the women with high risk of EM exhibited distinct characteristics compared to women with the intermediate-risk of EM, and identified several risk factors associated with EM.ConclusionsWe established a PRS model to serves as a valuable instrument for EM risk prediction. The exploratory analysis revealed that women with high risk of EM exhibited a higher height, suggesting EM related genetic loci may also influence growth and development level. Several risk factors were found to be potentially associated with EM, such as excessive familial contentment, COVID-19 vaccination, staying up late, and the husband’s engagement in smoking and alcohol abuse.

Introduction Embryo implantation provides an efficient way for patients with repeated implantation failure (RIF) to achieve pregnancy. The aim of this study is to compare the implantation outcomes of RIF patients in artificial cycle to those in natural cycle, both were treated with RNA sequencing endometrial receptivity test (rsERT) based personalized embryo implantation.Methods The endometrial receptivity (ER) analysis was performed using rsERT followed by personalized embryo transfer at optimal window of implantation (WOI). The implantation rate (IR), clinical pregnancy rate (CPR) and live birth rate (LBR) were calculated. The expression levels of biomarkers involved in pregnancy process in the patients detected as in receptivity status were also analyzed.Results The rsERT shown that 44.8% (natural cycle) and 47.8% (artificial cycle) patients were in non-receptive status, which indicated a WOI displacement. After personalized embryo transfer, the IR of patients in artificial cycle was higher than those in natural cycle (52.2% vs 27.6%). The expressions of FKBP52, MUC1 and LPAR3 were significantly lower in artificial cycle than in natural cycle.Conclusion Using artificial cycle for personalized embryo transfer based on rsERT may yield better pregnancy outcomes for RIF patients. A gene expression analysis of FKBP52, MUC1 and LPAR3 provided a potential way to increase implantation outcomes for RIF patients.

BackgroundResearch on the relationship between ambient temperature and preterm birth has received increasing attention, but the conclusions of the previous literature are inconsistent.ObjectiveTo explore the impact of environmental temperature exposure in Ningbo on premature delivery of pregnant women.MethodsThe birth information, preterm birth data, and age of pregnant women from January 2016 to September 2020 were collected by the electronic medical record system of Ningbo Women’s and Children’s Hospital. Meteorological data for the same period were obtained through Ningbo Meteorological Bureau, including daily average temperature, daily average relative humidity, and daily average air pressure. Daily concentrations of SO2, NO2, and PM10 were derived through the air quality real-time release system on the website of Ningbo Environmental Protection Bureau. A distributed lag nonlinear model was used to analyze the impact of environmental temperature on preterm birth by stratifying pregnant women’s age and birth delivery mode.ResultsThe incidence rate of preterm birth in Ningbo from 2016 to 2020 was 5.91%. The exposure-response curve between environmental temperature and preterm birth presented a “U” shape. Taking 22.5 ℃ as a reference, the cumulative effect of 31 ℃ (the 95th percentile) and 32 ℃ (the 99th percentile) over a 21-day lag on preterm delivery was statistically significant, and the related RR (95%CI) values were 1.67 (1.05-2.65) and 1.85 (1.09-3.14) respectively. The results of stratified analysis showed that among pregnant women ≥30 years old, the 21-day cumulative effects of 31 ℃ and 32 ℃ on preterm delivery were statistically significant, and the related RR (95%CI) values were 2.09 (1.08-4.05) and 2.36 (1.11-5.03) respectively; among pregnant women with natural delivery, the 21-day cumulative effect of 32 ℃ on preterm delivery was statistically significant, and the RR (95%CI) was 1.95 (1.02-3.74).ConclusionExposure of pregnant women to high temperature during pregnancy could increase the risk of preterm birth, and there is a delayed cumulative effect.

Abstract Mitochondrial diseases are a group of heterogeneous genetic metabolic diseases caused by mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) gene mutations. Mining the gene-disease association of mitochondrial diseases is helpful for understanding the pathogenesis of mitochondrial diseases, for carrying out early clinical diagnosis for related diseases, and for formulating better treatment strategies for mitochondrial diseases. This project researched the relationship between genes and mitochondrial diseases, combined the Malacards, Genecards, and MITOMAP disease databases to mine the knowledge on mitochondrial diseases and genes, used database integration and the sequencing method of the phenolyzer tool to integrate disease-related genes from different databases, and sorted the disease-related candidate genes. Finally, we screened 531 mitochondrial related diseases, extracted 26,723 genes directly or indirectly related to mitochondria, collected 24,602 variant sites on 1474 genes, and established a mitochondrial disease knowledge base (MitDisease) with a core of genes, diseases, and variants. This knowledge base is helpful for clinicians who want to combine the results of gene testing for diagnosis, to understand the occurrence and development of mitochondrial diseases, and to develop corresponding treatment methods.

ObjectiveTo study patients’ new treatment methods and mechanisms of repeated implantation failure.DesignA retrospective study.SettingIn vitro fertilization (IVF) unit in a Three-A hospital.Patient(s)Ninety-three patients with repeated implantation failure in IVF and embryo transfer.Intervention(s)the luteal phase support.Main outcome measure(s)According to whether human chorionic gonadotropin(HCG) was added, the two groups were divided into an observation group and a control group, and the clinical outcomes of the two groups were compared. Furthermore, 20 patients were selected for whole exome sequencing to investigate the mechanism.ResultsThe observation group’s clinical pregnancy rate and live birth rate were significantly higher than those in the control group (P=0.004). Functional enrichment analysis showed that these genes were significantly enriched in embryo implantation or endometrial receptivity processes, such as microtubule-based movement, NABA CORE MATRISOME, superoxide anion generation, protein localization to vacuole, extracellular matrix organization, fertilization, microtubule-based transport, cell junction organization, microtubule cytoskeleton organization. Furthermore, variants detected in these pathway genes were missense mutations that affect the protein’s biological activity but do not effectuate its inactivation.ConclusionsAdding HCG in the luteal phase might improve the clinical pregnancy and live birth rates in RIF patients. The potential pathogenesis of RIF genetic level may be caused by microtubule-based movement, extracellular matrix organization, and the Superoxide Anion generation pathway.

ObjectiveA 2-dose varicella vaccine immunization strategy has been implemented in many cities in China, but there is few evidence on a long-term evaluation of the efficacy of the 2-dose varicella vaccine from China. This study aims to assess the long-term vaccine efficacy of the two doses varicella vaccine and analysis of its influencing factors.MethodsA retrospective study was carried out in 837,144 children born between 2011 and 2017 in Ningbo, Easten China. The logistic regression was performed to estimate varicella vaccine effectiveness (VE).ResultsThe overall VE of 2 doses of varicella vaccine compared without the vaccine was 90.31% (89.24–91.26%), and the overall incremental VE of 2 doses of varicella vaccine compared to the 1-dose was 64.71% (59.92–68.93%). Moreover, the varicella vaccination age of the second dose and the interval between 2 doses were both associated with VE. The VE compared to that without the vaccine in children vaccinated at

Background: The aim of this study was to investigate the effects of intravenous immunoglobulins (IVIg) in the immunotherapy of in vitro fertilization and embryo transfer (IVF-ET) patients and to provide insights into the treatment strategy for implantation failure. Methods: A retrospective observational study of 245 patients with unexplained repeated implantation failure in our hospital from 2016 to 2021 was conducted. Among these patients, 124 were administered IVIg according to their preferences during the preparation of implantation, while the others were not given IVIg as a control group. The basic characteristics of the patients in the two groups did not show any significant differences. Biochemical pregnancy rate, clinical pregnancy rate, and live birth rate were compared in the two groups, and also in the IVIg group and the control group, by age (

Mitochondrial DNA (mtDNA) mutations are often associated with incurable diseases and lead to detectable pathogenic variants in 1 out of 200 babies. Uncoupling of the inheritance of mtDNA and the nuclear genome by spindle transfer (ST) can potentially prevent the transmission of mtDNA mutations from mother to offspring. However, no well-established studies have critically assessed the safety of this technique. Here, using single-cell triple omics sequencing method, we systematically analyzed the genome (copy number variation), DNA methylome, and transcriptome of ST and control blastocysts. The results showed that, compared to that in control embryos, the percentage of aneuploid cells in ST embryos did not significantly change. The epiblast, primitive endoderm, and trophectoderm (TE) of ST blastocysts presented RNA expression profiles that were comparable to those of control blastocysts. However, the DNA demethylation process in TE cells of ST blastocysts was slightly slower than that in the control blastocysts. Collectively, our results suggest that ST seems generally safe for embryonic development, with a relatively minor delay in the DNA demethylation process at the blastocyst stage.

Oocytes reconstructed by spindle transfer (ST) are prone to chromosome abnormality, which is speculated to be caused by mechanical interference or premature activation, the mechanism is controversial. In this study, C57BL/6N oocytes were used as the model, and electrofusion ST was performed under normal conditions, Ca2+ free, and at room temperature, respectively. The effect of enucleation and electrofusion stimulation on MPF activity, spindle morphology, γ-tubulin localization and chromosome arrangement was compared. We found that electrofusion stimulation could induce premature chromosome separation and abnormal spindle morphology and assembly by decreasing the MPF activity, leading to premature activation, and thus resulting in chromosome abnormality in oocytes reconstructed via ST. Electrofusion stimulation was an independent factor of chromosome abnormality in oocytes reconstructed via ST, and was not related to enucleation, fusion status, temperature, or Ca2+. The electrofusion stimulation number should be minimized, with no more than 2 times being appropriate. As the electrofusion stimulation number increased, several typical abnormalities in chromosome arrangement and spindle assembly occurred. Although blastocyst culture could eliminate embryos with chromosomal abnormalities, it would significantly decrease the number of normal embryos and reduce the availability of embryos. The optimum operating condition for electrofusion ST was the 37°C group without Ca2+.