Preterm birth (PTB), complications of which account for approximately 35

Background Evidence from the Istanbul consensus workshop suggests correlations between morphological parameters and embryo developments. 8-cell embryos are the best blastomere stage on day 3. No good quality evidence exists to support high-quality embryonic selection following blastulation and clinical outcomes. This study aimed to investigate the factors that affect blastocyst formation, blastocyst quality, and clinical outcomes of high-quality cleavage-stage embryos in fresh cycles. Methods This study was a retrospective analysis of 9608 high-quality cleavage-stage embryos from 2987 couples between January 2017 to June 2021, namely 1520 embryos categorized as “812” (8-cell, grade 2, mild fragmentation), 2961 as “821” (8-cell, grade 2, mild asymmetry), 896 as “711” (7-cell, grade 1), and 517 as “911” (9-cell, grade 1) compared with 3714 embryos categorized as “811” (8-cell, grade 1). The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Blastulation rate (BR), available late blastocyst rate (ABR) and high-quality late blastocyst rate (HBR) were secondary outcome measures. Results BR, ABR, and HBR had significant differences among the five groups ( P < 0.001), while CPR and LBR were also significantly different in cleavage-stage fresh transfer ( P < 0.01). The multivariable multilevel logistic regression analysis revealed a significant association between cell number, cell size, blastocyst development and clinical outcomes. For 7 to 9-cell highest-quality embryo, mild fragmentation and more blastomeres were more conducive to blastocyst formation and clinical outcomes. While cleavage-stage embryos developed into blastocysts, the negative impact of their initial morphology on clinical outcomes would be erased. Conclusions Our study firstly evaluated blastocyst development and clinical outcomes of high-quality cleavage-stage embryos in fresh cycles, with rankings of 811, 812, 911, 821, and 711. We found the initial morphological characteristics of the high-quality cleavage-stage embryos did not adversely impact clinical outcomes, even as they progressed to the blastocyst stage.

Background:Overweight and obese individuals are steadily increasing in recent years. Male overweight or obesity has adverse impact on reproductive functions. The study aimed to evaluate the potential impact of paternal overweight or obesity on sperm quality and clinical pregnancy outcome in patients undergoing intrauterine insemination (IUI) treatment. Methods:This retrospective study included 1,036 couples from our reproductive center between July 2019 and August 2022. All males were categorized into normal weight, overweight, or obese groups according to their body mass index (BMI). Baseline characteristics and reproductive hormones were analyzed. Semen parameters, clinical pregnancy and live birth outcomes were compared among the different BMI groups. Results:There were no significant differences in sperm concentration, total sperm motility, progressive sperm motility, normal sperm morphology and sperm DNA fragmentation index (DFI) among the three groups. However, the obese group exhibited a significantly decreased semen volume compared to the other two groups (P<0.01). No differences were found in clinical pregnancy rate (CPR), abortion rate (AR) and live birth rate (LBR) among the groups (P>0.05). Slight higher ARs were observed in overweight and obese groups compared to normal group (13.64%, 21.05% vs. 11.11%, P=0.49). Conclusions:These data suggest that male obesity leads to a significant decrease in semen volume. It is thus recommended that male BMI should be regarded as one of the predictors for IUI treatment to avoid a decrease in semen volume.

The treatment for recurrent pregnancy loss (RPL) has been addressed in international guidelines. However, limited studies have investigated the risk factors associated with pregnancy and live birth outcomes in patients with RPL after treatment. The objective of this study was to offer a comprehensive assessment of the risk factors for pregnancy loss in patients with a history of RPL following therapeutic interventions. This retrospective cohort study involved 431 women in early pregnancy with a history of RPL who experienced treatment at the Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, between June 2018 and June 2020. The main outcome measures were the ongoing pregnancy ≥ 12 weeks and the live birth outcomes. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for pregnancy loss < 12 weeks and live birth outcomes. Patient’s age and the prevalence of uterine malformations were significantly different between the patients with and without ongoing pregnancy ≥ 12 weeks (32.64 ± 5.08 vs. 31.54 ± 4.34, P = 0.026; 34.70

Early spontaneous abortion (ESA) is a common adverse pregnancy outcome mainly attributed to embryo chromosomal abnormalities. However, as a quantitative marker, whether the anti-Müllerian hormone (AMH) can reflect oocyte quality is still controversial. By integrating biological evidence and adjusting many cofounders, this study aimed to clarify the controversies about the association between AMH and ESA caused by embryo aneuploidy during assisted reproductive technology (ART) treatment. We strictly preselected 988 patients receiving first ART treatment for analyzing clinical data, while 55 of them acquired chorionic villi karyotype results. In addition, 373 biopsied embryos from 126 patients receiving preimplantation genetic diagnosis (PGT) were tracked to compare embryo karyotypes. Univariate and multiple factor regressions were applied to analyze the risk factors leading to ESA. As covariates unadjusted, AMH (odds ratio 0.87, 95

Hepatocellular carcinoma (HCC) is significantly associated with adverse prognostic outcomes. The development and progression of different types of human tumors are significantly influenced by APOB. Nevertheless, the significance and pathomechanisms of APOB in HCC have not been conclusively determined. We assessed APOB expression levels in HCC using three publicly available databases of TIMER2.0, UALCAN and Human Protein Atlas. To identify the biological function of APOB, we conducted enrichment analysis via LinkedOmics. Moreover, UALCAN was employed to assess the relationship between APOB expression and clinicopathological features among HCC patients. Additionally, the Kaplan–Meier plotter was utilized to investigate the prognostic relevance of APOB in HCC. To explore potential regulatory ncRNAs that could bind to APOB, we utilized StarBase and GEPIA. Furthermore, the correlation between APOB expression and immune cell infiltration, as well as immune checkpoint genes, was investigated using Spearman's correlation analysis in TISIDB, GEPIA, and TIMER2.0. The findings of our investigation showed a notable decrease in the expression levels of APOB among individuals diagnosed with HCC. Moreover, a noteworthy correlation was observed between the expression of APOB and immune checkpoint genes, alongside the occurrence of immune cell infiltration. The levels of APOB expression in HCC tissues also showed correlations with various clinicopathological features. According to Cox regression analysis, decreased APOB expression emerged as a potential autonomous predictor for OS, RFS, DSS, and PFS among HCC patients. Furthermore, we identified six potential pathways associated with non-coding RNA (ncRNA) as the most promising pathway for APOB in HCC. Our results illuminate the possible involvement of APOB in HCC and offer understanding into its governing mechanisms and medical importance.

BackgroundThis study focuses on the risk of early miscarriage in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). These patients commonly experience heightened stress levels and may discontinue treatment due to emotional burdens associated with repeated failures. Despite the identification of numerous potential factors contributing to early miscarriage, there exists a research gap in integrating these factors into predictive models specifically for IVF/ICSI patients. The objective of this study is to develop a user-friendly nomogram that incorporates relevant risk factors to predict early miscarriage in IVF/ICSI patients. Through internal and external validation, the nomogram facilitates early identification of high-risk patients, supporting clinicians in making informed decisions.MethodsA retrospective analysis was conducted on 20,322 first cycles out of 31,307 for IVF/ICSI treatment at Sun Yat-sen Memorial Hospital between January 2011 and December 2020. After excluding ineligible cycles, 6,724 first fresh cycles were included and randomly divided into a training dataset (n = 4,516) and an internal validation dataset (n = 2,208). An external dataset (n = 1,179) from another hospital was used for validation. Logistic and LASSO regression models identified risk factors, and a multivariable logistic regression constructed the nomogram. Model performance was evaluated using AUC, calibration curves, and decision curve analysis (DCA).ResultsSignificant risk factors for early miscarriage were identified, including female age, BMI, number of spontaneous abortions, number of induced abortions and medical abortions, basal FSH levels, endometrial thickness on hCG day, and number of good quality embryos. The predictive nomogram demonstrated good fit and discriminatory power, with AUC values of 0.660, 0.640, and 0.615 for the training, internal validation, and external validation datasets, respectively. Calibration curves showed good consistency with actual outcomes, and DCA confirmed the clinical usefulness. Subgroup analysis revealed variations; for the elder subgroup (age ≥35 years), female age, basal FSH levels, and number of available embryos were significant risk factors, while for the younger subgroup (age <35 years), female age, BMI, number of spontaneous abortions, and number of good quality embryos were significant.ConclusionsOur study provides valuable insights into the impact factors of early miscarriage in both the general study population and specific age subgroups, offering practical recommendations for clinical practitioners. We have taken into account the significance of population differences and regional variations, ensuring the adaptability and relevance of our model across diverse populations. The user-friendly visualization of results and subgroup analysis further enhance the applicability and value of our research. These findings have significant implications for informed decision-making, allowing for individualized treatment strategies and the optimization of outcomes in IVF/ICSI patients.

This study aimed to investigate the potential benefits of frozen testicular sperm and to retrospectively analyze the clinical pregnancy and live birth outcomes following intracytoplasmic injection of fresh or frozen testicular sperm. A total of 468 infertile couples undergoing intracytoplasmic sperm injection cycles utilizing either fresh or frozen testicular sperm extracted between January 2017 and December 2021 were included in this analysis. Participants were categorized into two groups: those utilizing fresh testicular sperm (n = 324) and those utilizing frozen testicular sperm (n = 144). Outcome measures encompassed fertilization rate, embryo development, clinical outcomes, and birth status of infants. Statistical analysis revealed no significant differences in 2PN fertilization rate, Day 3 (D3) available embryo rate, high-quality embryo rate, blastocyst formation rate, clinical pregnancy rate, live birth rate, and preterm birth rate between the two groups. Although the preterm birth rate in the frozen testicular sperm group was lower compared to the fresh testicular sperm group, the difference was not statistically significant (5.6% vs. 15.1%). Notably, there were no discernible distinctions in clinical pregnancy and birth outcomes, as well as infant birth parameters, between the fresh and frozen testicular sperm groups. These findings suggest that frozen testicular sperm holds practical value and warrants consideration for clinical application.

Obesity has been confirmed to be associated with infertility. However, the association between metabolically healthy obesity (MHO), a subset of obesity with no metabolic abnormalities, and female infertility has not yet been investigated. This study aimed to examine the association between MHO and the risk of female infertility among United States. This study utilized a cross-sectional design and included 3542 women aged 20–45 years who were selected from the National Health and Nutrition Examination Survey (NHANES) 2013–2020 database. The association between MHO and the risk of infertility was evaluated using risk factor–adjusted logistic regression models. Higher BMI and WC were associated with increased infertility risk after adjusting for potential confounding factors (OR (95

Objective: To investigate the incidence of subchorionic hematoma (SCH), pregnancy outcomes and health status of offspring in patients with recurrent spontaneous miscarriage (RSA) treated with intravenous immunoglobulin (IVIg). Methods: The records of 775 patients with RSA were retrospectively reviewed. RSA with SCH were all treated with IVIg. Pregnancy outcomes examined were the rates of miscarriage, stillbirth, pre-term birth, and live birth. The pregnancy complications and comorbidities examined included oligohydramnios, hypertensive disorders, gestational diabetes, premature membrane rupture, placental adhesions, placenta previa, postpartum hemorrhage, placental abruption, and low birth weight. The health status of offspring of RSA patients with SCH was followed up by telephone, record physical and neurodevelopmental performance, and diseases under 5 years old, then compare with common children. Based on the ratio of SCH volume to that of the gestational sac, SCH was divided into small (ratio < 20%), moderate (ratio = 20%–50%), and large (ratio > 50%). Statistical analysis was performed with IBM SPSS Statistics 23.0. Comparison of continuous variables was analyzed using t-test. Categorical variables were compared by using χ2 test or Fisher’s exact test. Multivariable logistic regression was used for adjusting certain confounders. Results: Of the 775 patients with RSA, 110 RSA had a SCH (incidence = 14.2%). SCH was firstly found at 8.29 (5.00–11.58) weeks pregnant. There was no statistical difference in age, number of pregnancies, parity and miscarriages between patients with and without an SCH. The incidence of SCH in in-vitro fertilization embryo transfer (IVF-ET) patients was higher than in natural pregnancy patients (27.9% vs. 13.1%, P < 0.05). RSA with SCH patients with pregnancy outcome data called Group A (n = 94), RSA without SCH patients with pregnancy outcome data called Group B (n = 556), the rates of miscarriage (17.0% vs.12.4%), stillbirth (0 vs. 0.4%), pre-term delivery (9.6% vs. 10.8%), live birth (84.7% vs. 80.9%), and pregnancy complications were not different between Group A and B. The rate of vaginal bleeding in the Group A was higher than in the Group B (P < 0.05). There was no significant difference in the birth weight, the rate of low birth weight infants, neonatal asphyxia, or neonatal pneumonia between the groups. 43 puerpera in the experimental group were willing to receive telephone follow-up, who gave birth from December 2015 to November 2016. A total of 43 live births were delivered. By March 2022, the children were 5 years and 4 months old to 6 years and 3 months old. There is no difference in the physical development compared with common children. A child was diagnosed with neuropsychological delay. The incidence rate of community acquired pneumonia (CAP) was 27.9 per 1000 person-years for children under 5 years. In patients with a SCH and vaginal bleeding, the rate of preterm birth was 16.7%. The rate of preterm birth was highest (36.4%) in RSA patients with a large SCH, and only 5.7% in patients with a small SCH (P < 0.05). Patients treated with IVIg had mild adverse reactions such as hypothermia, dizziness, and rash with rates of 1.8%, 1.8%, and 0.9%, respectively. Conclusion: The incidence of SCH was 14.2% in RSA. Pregnancy outcomes were similar between the RSA patients with a SCH treated with IVIg treatment and RSA patients without a SCH. There is no difference in the physical development between offspring of RSA with SCH and common children, and effect of SCH on neurodevelopment of offspring needs to be further verified by expanding the sample size. RSA patient with a SCH are prone to have vaginal bleeding and abdominal pain. For RSA patients with a SCH and vaginal bleeding, or SCH volume ratio > 50%, even after IVIg, still leads to a significantly higher preterm birth rate.

Zygotes without a pronuclear (0PN) or with one pronuclear (1PN) were defined as abnormal fertilization in conventional in vitro fertilization (IVF). The removal of 0PN and 1PN zygotes from conventional IVF cycles has always been controversial. This study aimed to investigate the chromosomal aneuploidy rates of 0PN- and 1PN-derived blastocysts in conventional IVF cycles and to assess the concordance rate between TE-biopsy PGT-A and miPGT-A. TE biopsies and culture media with blastocoel fluid (CM-BF) samples were whole-genome amplified by multiple annealing and looping-based amplification cycle-based single-cell ChromInst method. Next generation sequencing was performed for comprehensive chromosomal screening on a NextSeq550 sequencer using the NextSeq 500/550 High Output kit v2. The aneuploidy rates of 0PN-derived blastocysts were 19.7% for TE-biopsy PGT-A, and 36.1% for miPGT-A; the concordance rate for ploidy was 77.0%; and the sensitivity and specificity were 83.3% and 75.5%, respectively. The aneuploidy rates of 1PN-derived blastocysts were 37.5% and 37.5% by TE-biopsy PGT-A and miPGT-A, respectively; the concordance rate between TE biopsies and CM-BF samples was 83.3%; and the sensitivity and specificity were 77.8% and 86.7%, respectively. Regarding TE-biopsy PGT-A, there were no significant differences in aneuploidy rates among 0PN-, 1PN- and 2PN-derived blastocysts (PGT-M cycles) (19.7% vs. 37.5% vs. 24.3%, P = 0.226), but the aneuploidy rate of 1PN-derived blastocysts was slightly higher than the other two groups. An increase in aneuploidy rates was observed for 0PN/1PN-derived day 6 blastocysts compared to 0PN/1PN-derived day 5 blastocysts (TE-biopsy PGT-A: 35.7% vs. 19.3%, P = 0.099; miPGT-A: 39.3% vs. 35.1%, P = 0.705). The present study is the first that contributes to understanding the chromosomal aneuploidies in 0PN- and 1PN-derived blastocysts in conventional IVF cycles using TE-biopsy PGT-A and miPGT-A. The clinical application value of 0PN- and 1PN-derived blastocysts in conventional IVF should be assessed using TE-biopsy PGT-A or miPGT-A due to the existence of chromosomal aneuploidies.. In terms of consistency, the miPGT-A using blastocoel fluid enriched culture medium is promising as an alternative to TE-biopsy PGT-A for aneuploidy testing of 0PN- or 1PN-derived blastocysts in conventional IVF.

Despite advancements made in the therapeutic strategies on hepatocellular carcinoma (HCC), the survival rate of HCC patient is not satisfactory enough. Therefore, there is an urgent need for the valuable prognostic biomarkers in HCC therapy. In this study, we aimed to screen hub genes correlated with prognosis of HCC via multiple databases. 117 HCC-related genes were obtained from the intersection of the four databases. We subsequently identify 10 hub genes (JUN, IL10, CD34, MTOR, PTGS2, PTPRC, SELE, CSF1, APOB, MUC1) from PPI network by Cytoscape software analysis. Significant differential expression of hub genes between HCC tissues and adjacent tissues were observed in UALCAN, HCCDB and HPA databases. These hub genes were significantly associated with immune cell infiltrations and immune checkpoints. The hub genes were correlated with clinical parameters and survival probability of HCC patients. 147 potential targeted therapeutic drugs for HCC were identified through the DGIdb database. These hub genes could be used as novel prognostic biomarkers for HCC therapy.

BackgroundUnexplained recurrent spontaneous abortion is a serious reproductive problem of unknown etiology. Thyroid peroxidase antibodies (TPO-Ab) may be associated with pregnancy outcomes in unexplained recurrent spontaneous abortion with normal thyroid function.ObjectiveThis study aimed to investigate the relationship between TPO-Ab and the first trimester miscarriage rate/live birth rate in women of unexplained recurrent spontaneous abortion with normal thyroid function.MethodsWe retrospectively analyzed the clinical data of 297 women who met our strict inclusion criteria, comparing the first trimester miscarriage rate/live birth rate between the TPO-Ab positive and TPO-Ab negative groups. For the same purpose, we also performed subgroup analysis.ResultsOf the included women, 76 (25.6%) were TPO-Ab positive, and 221 (74.4%) were negative. First trimester miscarriage rate differed between the two groups (36.8% vs 24.0%, RR = 1.54, 95% CI: 1.05–2.24, P = 0.030). In the younger subgroup (<35 years) and the primary RSA subgroup, First trimester miscarriage rate was also higher in the TPO-Ab positive group (33.3% vs 19.0%, RR = 1.75, 95% CI: 1.07–2.87, P = 0.030; 36.5% vs 21.7%, RR = 1.69, 95% CI: 1.10–2.58, P = 0.020). While the live birth rate was lower in women with TPO-Ab positive, the difference did not reach statistical significance, even in the subgroup analysis.ConclusionOur results suggest that TPO-Ab is associated with first trimester miscarriage rate in euthyroid women with unexplained recurrent spontaneous abortion.

Abstract Purpose To determine the utility of short gamete coincubation in in vitro fertilization (IVF‐S) combined with early rescue intracytoplasmic sperm injection (R‐ICSI) and split IVF‐ICSI in preventing low fertilization based on a retrospective cohort study. Methods Couples with a high risk of low IVF fertilization during the first ART cycle underwent IVF‐S with R‐ICSI or split IVF‐ICSI. Fertilization rate, embryo quality, and clinical outcomes were measured. Results After propensity score matching, we included 188 couples in the IVF‐S with R‐ICSI group as Group 1 and 720 in the split IVF‐ICSI group as Group 2. Normal fertilization rates were similar; however, Group 1 had a higher multiple pronuclei rate (10.42% vs. 4.50%, p < 0.001) but a higher embryo utilization rate (59.84% vs. 53.60%, p < 0.001). The groups were similar in the rates of high‐quality embryos, embryo implantation, clinical pregnancy, and live birth. Low IVF fertilization rate was 4.79% and 9.03% in Group 1 and Group 2, respectively, with similar fertilization rate and embryo development. Conclusion IVF‐S with early R‐ICSI and split IVF‐ICSI were effective strategies in preventing low fertilization rate. IVF‐S with early R‐ICSI could become the preferred approach because of its advantages—higher embryo utilization rate, fewer ICSI procedures, similar clinical pregnancy rate, and live birth rate.

Background: Emerging research suggests that long non-coding RNAs (lncRNAs) play an important role in a variety of developmental or physiological processes of hepatocellular carcinoma (HCC). Various differentially expressed lncRNAs have been identified in HCC. Thus, a deeper analysis of recent research concerning lncRNA and HCC development could provide scientists with a valuable reference for future studies. Methods: Related publications were retrieved from the Web of Science Core Collection database. CiteSpace version 5.6.R4 was employed to conduct bibliometric analysis. Several network maps were constructed to evaluate the collaborations between different countries, institutions, authors, journals, and keywords. Results: A total of 2,667 records were initially found from the year of 2010–2020. The annual related publications output had increased dramatically during these years. Although China was the most prolific country in terms of research publication, the United States played a leading role in collaborative network. The Nanjing Medical University was the most productive institute in the field of lncRNAs in HCC development. Gang Chen was the most prolific researcher, while Yang F was the most frequently co-cited author. Oncotarget, Cell, and Oncogene were the most highly co-cited journals. The most recent burst keywords were interaction, database, and pathway. Conclusion: This study provides a comprehensive overview for the field of lncRNAs in HCC development based on bibliometric and visualized methods. The results would provide a reference for scholars focusing on this field.