Predictive model of IVF outcomes for polycystic ovarian morphology and polycystic ovary syndrome in GnRH antagonist protocol using AMH-MoM and ovarian sensitivity index.

AIM: To evaluate the relationship between AMH and ovarian response to controlled ovarian hyperstimulation in women with PCOM and PCOS. METHODS: A retrospective study was conducted on 559 patients who underwent the IVF-ET cycle between January 2018 and December 2022 at Gangnam Cha Hospital. Patients were divided into 3 groups matched for age and BMI: the PCOS group (n = 54), based on the new 2023 PCOS guideline; the PCOM group (n = 53); and the control group (n = 452) with normal ovaries. Serum AMH levels were converted to multiples of the median (MoM) for each corresponding age. The ovarian sensitivity index (OSI) was calculated as the number of retrieved oocytes divided by the total dose of recombinant FSH administered (per 1000 IU). RESULTS: There were significant differences in AMH-MoM value among women with PCOS [2.7 ± 1.3 (95% CI 2.3-3.0)], those with PCOM [2.0 ± 1.0 (95% CI 1.7-2.3)], and controls [0.8 ± 0.7 (95% CI 0.8-0.9)] (p < 0.001). The abortion rates in the normoovulatory, PCOM, and PCOS groups were 18.2%, 21.1%, and 25.0%, respectively. OSI and live birth rate were positively correlated with the AMH-MoM value in normoovulatory women (r = 0.389, p < 0.05, r = 0.122, p < 0.05), while no such correlation was observed in women with PCOM and PCOS. CONCLUSIONS: Ovarian response and live birth rate are possibly correlated with the AMH-MoM value in normoovulatory women, but not in women with PCOM and PCOS.

The Analysis of in vitro Fertilization Outcomes after Fertility-Preserving Therapy for Endometrial Hyperplasia or Carcinoma.

OBJECTIVES: This study aimed to evaluate the clinical efficacy of fertility-preserving therapy through in vitro fertilization (IVF) procedures in women who were pathologically diagnosed with endometrial hyperplasia or carcinoma. DESIGN: A retrospective cohort study on fertility-preserving therapy was conducted. Participants/Materials, Setting: A total of 82 women were enrolled who had simple endometrial hyperplasia (SH), complex hyperplasia (CH), complex atypical hyperplasia (CAH), and endometrioid endometrial carcinoma stage IA (EC IA) and underwent IVF at Gangnam CHA fertility center between January 2008 and December 2020. METHODS: The primary endpoints were oncologic outcomes and subsequent reproductive outcomes of patients who underwent fertility-preserving treatments analyzed by χ2 test or Fisher's exact test. RESULTS: Of the 82 patients, 33 had a cumulative clinical pregnancy (40.2%), and 25 had a cumulative live birth (30.5%) through IVF procedures following pathologic confirmation of complete remission or non-progressive status. The cumulative clinical pregnancy rates and live birth rates for SH were 50.0% and 30.0%, for CH were 37.8% and 28.9%, for CAH were 25.0% and 25.0%, and for EC were 38.5% and 38.5%, respectively. There were no significant differences in cumulative clinical pregnancy rates or live birth rates when comparing the four groups. There was a difference in endometrial thickness between medroxyprogesterone acetate (MPA) treatment group and intrauterine device (IUD) group (p = 0.036); however, there were no significant differences in clinical pregnancy rates among MPA, IUD, and MPA+IUD groups. LIMITATIONS: Because of the retrospective nature of the study, many factors relevant to the treatment decision were not strictly controlled. CONCLUSIONS: All endometrial hyperplasia and carcinoma groups had competent cumulative live birth rates by IVF procedures. There may be differences in endometrial thickness depending on the treatment methods, but this does not affect clinical pregnancy rates. Therefore, the fertility-preserving treatment for endometrial hyperplasia and carcinoma is a safe and feasible method that results in good IVF outcomes.

Gender Differences in the Association between Workplace Bullying and Depression among Korean Employees.

Workplace bullying is a prevalent issue with a significant impact on employees' mental health. This study aimed to explore the relationship between workplace bullying and the prevalence of depression, with a particular focus on the role of gender. A total of 12,344 Korean employees aged 19-65 years were included in the study. They completed the Center for Epidemiologic Studies Depression Scale (CES-D) and a score of 16 or higher in CES-D indicated depression. The association between workplace bullying and depression was analyzed using logistic regression analyses. The average CES-D scores were higher for both male and female employees who experienced bullying than for those who did not (p < 0.001). The association between the experience of workplace bullying and the prevalence of depression was statistically significant for both genders, with a stronger correlation observed among male employees (p for interaction < 0.001). Organizations are urged to address workplace bullying, particularly for male employees, through the implementation of anti-bullying strategies and policies, as well as the provision of mental health resources and support.

Compact SPICE Model of Memristor with Barrier Modulated Considering Short- and Long-Term Memory Characteristics by IGZO Oxygen Content.

This paper introduces a compact SPICE model of a two-terminal memory with a Pd/Ti/IGZO/p+-Si structure. In this paper, short- and long-term components are systematically separated and applied in each model. Such separations are conducted by the applied bias and oxygen flow rate (OFR) during indium gallium zinc oxide (IGZO) deposition. The short- and long-term components in the potentiation and depression curves are modeled by considering the process (OFR of IGZO) and bias conditions. The compact SPICE model with the physical mechanism of SiO2 modulation is introduced, which can be useful for optimizing the specification of memristor devices.

Effect of Post-Annealing on Barrier Modulations in Pd/IGZO/SiO2/p+-Si Memristors.

In this article, we study the post-annealing effect on the synaptic characteristics in Pd/IGZO/SiO2/p+-Si memristor devices. The O-H bond in IGZO films affects the switching characteristics that can be controlled by the annealing process. We propose a switching model based on using a native oxide as the Schottky barrier. The barrier height is extracted by the conduction mechanism of thermionic emission in samples with different annealing temperatures. Additionally, the change in conductance is explained by an energy band diagram including trap models. The activation energy is obtained by the depression curve of the samples with different annealing temperatures to better understand the switching mechanism. Moreover, our results reveal that the annealing temperature and retention can affect the linearity of potentiation and depression. Finally, we investigate the effect of the annealing temperature on the recognition rate of MNIST in the proposed neural network.

Efficacy and safety of newly developed ganirelix acetate in infertile women for assisted reproductive technology: a prospective, randomised, controlled study.

This study aimed to investigate the efficacy of Ganilever pre-filled syringe (PFS), a newly developed ganirelix acetate, for the inhibition of premature luteinising hormone (LH) surge in in vitro fertilisation (IVF). A prospective randomised controlled study was conducted (NCT03051087). A total of 236 women (Ganilever group: 114, Orgalutran group: 122) were finally analysed. The patients with LH of >10 mIU/mL on the day of human chorionic gonadotropin (hCG) injection were 0 (0.0%) and 3 (2.5%) in the Ganilever and Orgalutran groups, respectively (p= .25). The number of retrieved oocytes from two groups did not show any significant difference (12.0 ± 6.4 vs. 11.8 ± 6.3, p= .73). Furthermore, the two groups did not show significant differences in the number of good-quality oocytes and embryo, and the rate of fertilisation. Similar safety profiles were also observed. In conclusion, Ganilever PFS showed comparable IVF outcomes and safety profile in IVF, as compared to the Orgalutran. Impact StatementWhat is already known on this subject? Premature LH surge during controlled ovarian stimulation results in the induction of luteinisation of the immature follicles. Thus, gonadotrophin-releasing hormone (GnRH) antagonist protocol was suggested as an option for suppression of premature LH surge. Currently, one of GnRH antagonists being widely used is ganirelix acetate (Orgalutran®; Organon, Oss, The Netherlands). Ganilever pre-filled syringe (PFS) is a newly developed GnRH antagonist containing ganirelix acetate as an active ingredient.What do the results of this study add? Our study demonstrated that Ganilever PFS showed comparable IVF outcomes and patient safety profile in infertile women undergoing in IVF-ET, as compared to the Orgalutran.What are the implications of these findings for clinical practice and/or further research? The results of our study will provide another available GnRH antagonist to be used in patients with IVF.

The Ratio of Mitochondrial DNA to Genomic DNA Copy Number in Cumulus Cell May Serve as a Biomarker of Embryo Quality in IVF Cycles.

Previous studies have reported that the mitochondrial DNA (mtDNA) contents of cumulus cells (CCs) in ovarian follicular fluid are correlated with embryo quality. Quantification of mtDNA CCs has been suggested as a biomarker of embryo viability. The aim of this study was to determine the relationship between mitochondrial DNA (mtDNA)/genomic DNA (gDNA) ratio in CCs and IVF outcomes such as fertilization rates and embryo quality in infertile women. This is an observational study on 144 cumulus-oocyte complexes obtained from 144 patients undergoing IVF-intracytoplasmic sperm injection (ICSI) at a single fertility center. The CCs in ovarian follicular fluid from patients undergoing IVF-ICSI were collected by ovum pick-up. A relative copy number quantification was used to determine mtDNA/gDNA ratio. Quantitative real-time PCR for various markers (ß2M and mtMinArc gene) was used to determine average mtDNA/gDNA ratio of CCs. Investigation of the correlation between mtDNA/gDNA ratio in CCs and IVF outcomes showed no statistically significant correlation between the mtDNA/gDNA ratio in CCs and fertilization rates. However, mtDNA/gDNA ratio and embryo quality showed a statistically significant positive correlation. A significantly higher mtDNA/gDNA ratio was observed in the good quality embryo group compared with the poor quality embryo group (P < 0.05). In addition, the mtDNA/gDNA ratio showed negative correlation with the patient's age (correlation coefficient= -0.228, P < 0.05). Results of this study demonstrate a negative correlation of mtDNA/gDNA ratio in CCs with patient's age, and a low copy number of mtDNA in CCs may have adverse effects on embryo quality in IVF cycles. These results suggest that the ratio of mtDNA/gDNA in CCs may serve as a biomarker in predicting IVF outcomes.

Pre-conditioning modifies the TME to enhance solid tumor CAR T cell efficacy and endogenous protective immunity.

Chimeric antigen receptor (CAR) T cell therapy has led to impressive clinical responses in patients with hematological malignancies; however, its effectiveness in patients with solid tumors has been limited. While CAR T cells for the treatment of advanced prostate and pancreas cancer, including those targeting prostate stem cell antigen (PSCA), are being clinically evaluated and are anticipated to show bioactivity, their safety and the impact of the immunosuppressive tumor microenvironment (TME) have not been faithfully explored preclinically. Using a novel human PSCA knockin (hPSCA-KI) immunocompetent mouse model, we evaluated the safety and therapeutic efficacy of PSCA-CAR T cells. We demonstrated that cyclophosphamide (Cy) pre-conditioning significantly modified the immunosuppressive TME and was required to uncover the efficacy of PSCA-CAR T cells in metastatic prostate and pancreas cancer models, with no observed toxicities in normal tissues with endogenous expression of PSCA. This combination dampened the immunosuppressive TME, generated pro-inflammatory myeloid and T cell signatures in tumors, and enhanced the recruitment of antigen-presenting cells, as well as endogenous and adoptively transferred T cells, resulting in long-term anti-tumor immunity.

Does duration of cryostorage affect survival rate, pregnancy, and neonatal outcomes? Large-scale single-center study of slush nitrogen (SN2 ) vitrified-warmed blastocysts.

OBJECTIVE: To evaluate the effects of the duration of cryostorage on clinical outcomes after embryo transfer of vitrified blastocysts stored in an open-device slush-nitrogen (SN2 ) system. METHODS: A retrospective cohort study was carried out on 1632 autologous vitrified-warmed blastocyst transfer cycles between January 2013 and June 2014. Duration of cryostorage was divided into four groups: Group I: 0-6 months (n=937); Group II: 7-12 months (n=299); Group III: 13-24 months (n=165); and Group IV: ≥25 months (n=231). The effects of the duration of cryostorage on the survival rate (SR), clinical pregnancy rate (CPR), live birth rate (LBR), and neonatal outcomes of vitrified blastocysts stored in an open-device SN2 system were evaluated. RESULTS: There were no significant differences between groups in SR, CPR, LBR, and neonatal outcomes after autologous vitrified-warmed blastocyst transfer. Multivariate logistic regression analysis showed no effect on LBR from duration of cryostorage. CONCLUSION: Vitrification using SN2 and long-term cryostorage in an open-device system are safe and effective and do not significantly affect clinical outcomes after embryo transfer.

Erratum: Correction of Author ORCID in the Article: Efficacy of Random-start Controlled Ovarian Stimulation in Cancer Patients.

This corrects the article on p. 290 in vol. 30, PMID: 25729252.

Deformability in Unsaturated Polyester Resin-Based Concrete: Effects of the Concentration of Shrinkage-Reducing Agent and Type of Filler.

In this study, the effects of shrinkage reduction agent (SRA) content and filler type on the deformability characteristics of unsaturated polyester (UP) resin-based polymer concrete were experimentally investigated. Specifically, the setting shrinkage, thermal expansion, maximum compressive strain and the modulus of elasticity of UP polymer concrete were all analyzed. Setting shrinkage was found to be influenced by the UP resin, the SRA and filler. The thermal expansion, maximum compressive strain and modulus of elasticity were also affected by the aggregate. The effect of SRA content on deformability was found to be greater than that of the filler type. To put UP polymer concrete to efficient use, it is essential to secure proper deformability according to the intended purpose. At that time, it is desirable that the deformation characteristics resulting from the SRA content and filler type sufficiently reflect when the mix proportion is determined. The effects of filler type on the deformability of UP polymer concrete are such that: A uniform dispersion of filler particles impacts the setting shrinkage; the thermal expansion is influenced by the filler's various thermal expansion properties; the compressive strain is related to the nature of the small spherical particles that tend to fill porosity, producing better packing of the aggregate materials; and the modulus of elasticity is influenced by the density, which is related to the strength of the filler. However, additional in-depth studies are required on all of these elements.

Compressive and Flexural Strengths of EVA-Modified Mortars for 3D Additive Construction.

The compressive and flexural strengths of mortars modified with ethylene-vinyl acetate (EVA) were experimentally investigated for use in three-dimensional (3D) additive construction (3DAC). EVA powder, which is available in a premix type, was employed as an admixture. The test results for the cast specimens showed that, at a curing age of 28 days, the compressive strengths ranged from 32.92 MPa to 43.50 MPa, and the flexural strengths ranged from 12.73 MPa to 14.49 MPa. The compressive and flexural strengths of the printed specimens were relatively lower: 23% to 26% and 3% to 7%, respectively. The compressive strength also decreased and the flexural strength increased when the EVA/cement ratio was increased. The results of the experiment reveal that the EVA-modified mortar had a high rate of strength development early on, making the material advantageous for use in 3DAC. It was determined that the appropriate EVA/cement ratio ranged between 5% and 15%. However, the printed specimens exhibited lower compressive and flexural strengths than did the cast specimens, and the compressive strength decreased as the EVA content was increased. This study provides the compressive and flexural strengths of common EVA-modified mortars, important data for 3DAC applications.

Feasibility Study of SBR-Modified Cementitious Mixtures for Use as 3D Additive Construction Materials.

The primary purpose of this study was to investigate the feasibility of applying polymeric cementitious materials to three-dimensional additive construction (3DAC). Specifically, styrene-butadiene rubber (SBR) latex was employed as an admixture to produce SBR-modified cementitious mixtures, and their fresh properties were experimentally investigated to determine the feasibility of their use in the 3DAC process. The SBR/cement ratio was controlled based on four main materials (i.e., cement, sand, silica fume, and fly ash) in order to determine the optimal fresh properties. The test results revealed that the SBR-modified cementitious mixtures showed excellent flowability, extrudability, buildability, and open time, all of which are required for 3DAC materials. The optimal flow of the SBR-modified cementitious mixtures was 70% ± 1%, which is appropriate for 3DAC applications. According to the experiment results, the SBR-modified cementitious mixtures were sufficiently competitive to serve as a new class of materials for 3D additive construction.

Fresh Properties of EVA-Modified Cementitious Mixtures for Use in Additive Construction by Extrusion.

In this study, the fresh properties of ethylene-vinyl acetate (EVA)-modified cementitious mixtures were experimentally investigated to evaluate the feasibility of this type of material being used in additive construction by extrusion (ACE). The EVA/cement ratio was a main variable to determine the properties, including flowability, extrudability, buildability, and open time. According to the flow test results, the optimized flow of the EVA-modified cementitious mixtures was found to be 65% for buildability. This excellent flowability could be achieved because the flow increased as the EVA/cement ratio increased; conversely, the extrudability was slightly reduced when the EVA/cement ratio increased. However, if the flow of the EVA-modified cementitious mixtures was maintained at 65%, ACE could be achieved without significant issues. In addition, the height of the additive concrete walls created was not substantially reduced after printing of these mixtures, even though different EVA/cement ratios were applied. Plus, ACE can be operated longer with such mixtures because the open time becomes longer as the EVA/cement ratio increases. In summary, the results clearly demonstrated that EVA-modified cementitious mixtures were feasible for use as ACE materials.

Comparison of neonatal outcomes of very low birth weight infants by mode of conception: in vitro fertilization versus natural pregnancy.

OBJECTIVE: To compare the neonatal outcomes of very low birth weight (VLBW) infants born after IVF with those of VLBW infants born after natural pregnancy (NP). DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 6,871 VLBW infants born from January 2014 to December 2016. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Neonatal mortality and morbidities. RESULT(S): Of the 6,871 VLBW infants enrolled, 4,438 infants were born as singletons (IVF = 271; NP = 4,167), and 2,433 infants were born as multiplets (IVF = 1,301; NP = 1,132). After adjustment for maternal and neonatal baseline characteristics, infants born as singletons earlier than 28 weeks after IVF more frequently had high-stage retinopathy of prematurity than those born after NP, whereas infants born as multiplets between 28 and 31 weeks after IVF had fewer major congenital anomalies, high-grade intraventricular hemorrhage, and periventricular leukomalacia than those born after NP. Otherwise, no differences in mortality and neonatal outcomes were found. CONCLUSION(S): Very low birth weight infants born as singletons after IVF had comparable neonatal outcomes to those born after NP, except for an increased risk of high-stage retinopathy of prematurity. Very low birth weight infants born as multiplets after IVF had fewer neurologic morbidities than those born after NP.

Correlation between Morphologic Grading and Euploidy Rates of Blastocysts, and Clinical Outcomes in In Vitro Fertilization Preimplantation Genetic Screening.

BACKGROUND: The standard morphological evaluation has been widely used for embryo selection, but it has limitations. This study aimed to investigate the correlation between morphologic grading and euploidy rate of in vitro fertilization (IVF) preimplantation genetic screening (PGS) and compare the pregnancy rates in young and old ages. METHODS: This is a retrospective study using the medical records of patients who underwent IVF procedures with PGS between January 2016 and February 2017 in a single center. The embryo grades were categorized into 4 groups: excellent, good, fair, and poor. Basic characteristics, euploidy rates, clinical pregnancy (CP) rates and ongoing pregnancy rates were analyzed. RESULTS: The excellent group had significantly higher rate of euploid embryos than fair group (47.82% vs. 29.33%; P = 0.023) and poor group (47.82% vs. 29.60%; P = 0.005). When the four groups were recategorized into two groups (excellent and good vs. fair and poor), they also showed significant difference in euploidy rates (44.52% vs. 29.53%; P = 0.002). When the patients were divided into two groups by age 35, the CP rates for those under and over 35 years old were 44.74% and 47.83%, respectively, which showed no significant difference. CONCLUSION: The significant differences among the euploidy rates of different morphologic embryo grades demonstrated the positive correlations between the morphologic grading of the embryo and the euploidy rate of PGS. Additionally, there was no significant difference between the younger and older patients' CP rates. These findings emphasize the fact that old age patients might benefit from PGS whatever the indication of PGS is.

Effective Targeting of TAG72+ Peritoneal Ovarian Tumors via Regional Delivery of CAR-Engineered T Cells.

Impressive clinical efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy for hematological malignancies have prompted significant efforts in achieving similar responses in solid tumors. The lack of truly restricted and uniform expression of tumor-associated antigens, as well as limited T cell persistence and/or tumor trafficking pose major challenges for successful translation of CAR T cell therapy in solid tumors. Recent studies have demonstrated that aberrantly glycosylated cell surface proteins on tumor cells are amenable CAR targets. Tumor-associated glycoprotein 72 (TAG72) antigen is the sialyl-Tn found on multiple O-glycoproteins expressed at high levels on the surface of several cancer types, including ovarian cancer. Here, we developed a humanized TAG72-specific CAR containing a 4-1BB intracellular co-stimulatory signaling domain (TAG72-BBζ). TAG72-BBζ CAR T cells showed potent antigen-dependent cytotoxicity and cytokine production against multiple TAG72+ ovarian cancer cell lines and patient-derived ovarian cancer ascites. Using in vivo xenograft models of peritoneal ovarian tumors, regional intraperitoneal delivery of TAG72-BBζ CAR T cells significantly reduced tumor growth, extended overall survival of mice, and was further improved with repeat infusions of CAR T cells. However, reduced TAG72 expression was observed in early recurring tumors, which coincided with a lack of T cell persistence. Taken together, we demonstrate efficacy with TAG72-CAR T cells in ovarian cancer, warranting further investigations as a CAR T cell therapeutic strategy for this disease.

Effects and pregnancy outcomes of L-carnitine supplementation in culture media for human embryo development from in vitro fertilization.

AIM: Antioxidants have been studied to be effective in improving embryo qualities from in vitro fertilization. L-carnitine (LC) has been known to reduce reactive oxygen species and enhance adenosine triphosphate production, which contribute to the development of a high-quality embryo. This is the first study to include both mouse and human subjects and aimed to evaluate whether LC supplementation in culture media has any beneficial effect on the development of the embryos, as well as its clinical outcomes. METHODS: Mouse embryos were used as models in the animal studies for cell immunofluorescent staining evaluation. Inner cell mass and trophectoderm (TE) cells were counted and statistically analyzed between LC and control groups. For human studies, medical records of patients with infertility undergoing in vitro fertilization procedures from January to May 2017 were included and the embryos were divided into two groups at the two pronuclear stage. Statistical analysis was performed to compare the embryo status and clinical outcomes of the two groups. RESULTS: In the animal study, the LC group showed significantly higher numbers of cells in the inner cell mass and trophectoderm, indicating better development. In the human studies, there were significantly higher numbers of good-quality embryos on days 2, 3 and 5 in the LC group than in the control. The clinical outcomes, such as implantation, clinical pregnancy and ongoing pregnancy rates, were also higher in the LC group than in the control. CONCLUSION: LC supplementation in culture media improved human embryo quality and eventually achieved better pregnancy outcomes.

A Kaposi's Sarcoma-Associated Herpesvirus Infection Mechanism Is Independent of Integrins α3ß1, αVß3, and αVß5.

Host receptor usage by Kaposi's sarcoma-associated herpesvirus (KSHV) has been best studied using primary microvascular endothelial and fibroblast cells, although the virus infects a wide variety of cell types in culture and in natural infections. In these two infection models, KSHV adheres to the cell though heparan sulfate (HS) binding and then interacts with a complex of EphA2, xCT, and integrins α3ß1, αVß3, and αVß5 to catalyze viral entry. We dissected this receptor complex at the genetic level with CRISPR-Cas9 to precisely determine receptor usage in two epithelial cell lines. Surprisingly, we discovered an infection mechanism that requires HS and EphA2 but is independent of αV- and ß1-family integrin expression. Furthermore, infection appears to be independent of the EphA2 intracellular domain. We also demonstrated that while two other endogenous Eph receptors were dispensable for KSHV infection, transduced EphA4 and EphA5 significantly enhanced infection of cells lacking EphA2.IMPORTANCE Our data reveal an integrin-independent route of KSHV infection and suggest that multiple Eph receptors besides EphA2 can promote and regulate infection. Since integrins and Eph receptors are large protein families with diverse expression patterns across cells and tissues, we propose that KSHV may engage with several proteins from both families in different combinations to negotiate successful entry into diverse cell types.