bluuebunny/crossref_metadata_2025_split huggingface dataset:
#273 : Comparative Analysis of Pregnancy Predictive Potential Using the Deep Learning Blastocyst Scoring Model Calculated from the Single Focus Blastocyst Image and Time-Lapse Image Sequences
Authors: Shioya Masashi , Kobayashi Tatsuya , Nakano Shun , Sugiura Tomoharu , Okabe-Kinoshita Miki , Fujita Maki , Takahashi Keiichi 
Published: January 2024

Background and Aims: Artificial Intelligence (AI) based embryo evaluation may objective and reduce inter-observer disagreement. Most commercially available AI models use blastocyst morphokinetics from time-lapse monitoring (TLM). Lifewhisperer (LW, FUJIFILM) is an AI-scoring model that uses a single-focus blastocyst image at a single-time point. LW may be more acceptable to many facilities than the TLM model as it does not require a time-lapse incubator. This study analyzed the predictive ability of LW for pregnant embryos and compared it to an AI model based on morphokinetics (iDAscore, Vitrolife) to assess their usefulness. Methods: This retrospective single-center study analyzed 666 vitrified-warmed blastocyst transfer cycles from January 2019 to December 2022. Inclusion criteria were blastocysts that developed within 5 days from insemination (maximum 120 h) using EmbryoScope+ (Vitrolife), intracytoplasmic sperm injection (ICSI) cycle, and a single-blastocyst transfer cycle. LW score (1.0–9.9) was calculated from single-focus blastocyst images taken before vitrification, while iDAScore (1.0–9.9) was calculated from time-lapse image sequences taken at 11 focal every 10 min after ICSI. We calculated the odds ratio for pregnancy and ROC analysis to compare these models. Results: The mean score was higher in pregnant blastocysts than in non-pregnant blastocysts in both models (LW: 7.47 vs. 6.72, p<0.01; iDAScore: 8.50 vs. 8.04, p<0.01, Willcoxon-test). The odds ratio (95% confidence interval) for pregnancy was 1.19 (1.10–1.28) for LW and 1.48 (1.27–1.74) for iDAScore, with the odds for clinical pregnancy increasing with higher scores (p<0.01). ROC curve analysis showed that the AUC values were 0.60 for LW and 0.62 for iDAScore. There was no significant difference in the predictive ability for pregnant blastocysts (p=0.51). Conclusions: LW allowed objective score calculation from a single focus at single time point blastocyst images without TLM. Moreover, in day 5 blastocyst, LW and iDAscore had comparable predictive pregnancy ability.
#60 : Is the Imbalance of Gender Ratio (GR) in IVF/ICSI Cycles Being Affected by the Current Blastocyst Selection Criteria?
Authors: Teng Zhi Xuan 
Published: January 2024

Background and Aims: Studies have reported a GR skewed towards male offspring in the assisted reproductive technology (ART) field due to the current blastocyst selection criteria. Male blastocysts have been observed to develop faster and with better grading than female blastocysts. Thus, more male blastocysts are chosen for being transferred. However, the underlying mechanism to cause the GR shift is still controversial. This study is aimed to investigate the preconception factors which may affect gender distribution. Method: In this single-centered retrospective cohort study from 2020 to 2022, a total of 1100 (Day 5: 439, Day 6: 661) blastocysts were biopsied. Blastocyst gender and chromosomal abnormalities were identified using next-generation sequencing-based pre-implantation genetic testing for aneuploidy. Blastocysts were categorized into: euploid, mosaic (25-80% mosaicism) and aneuploid. Pearson chi-square test was performed to analyze the GR and ploidy status between the genders. Results: Overall, the gender distribution skewed significantly towards female (54% vs 46%, p<0.05). However, male blastocysts possessed higher euploid rate than female blastocysts (39% vs 33%, p<0.05). No significant difference was shown in mosaic and aneuploidy rate between males and females (33% vs 36%, 28% vs 31%, p>0.05). Furthermore, the male-to-female ratio was not significant between day 5 and 6 blastocysts (1:1.23 vs 1:1.74, p>0.05), indicating a similar developmental speed between the genders. Conclusion: Among all the blastocysts analyzed, the GR is biased towards females, but higher euploid rate was observed in male than female blastocysts. Therefore, our results indicate that the imbalanced GR in favor of male offspring using ART may be correlated to the chromosomal issue, rather than blastocyst selection criteria. However, studies on intrapartum factors are necessary to further investigate the underlying mechanism to cause gender shift in ART.
#277 : Transcriptome Analysis Revealed a Delayed and Attenuated Estrogen Response in IUA Patients
Authors: Guo Qi 
Published: January 2024

Background and Aims: Intrauterine adhesion (IUA) is characterized by the formation of scar tissue in the endometrium following a variety of insults such as endometrial damage, miscarriage, and infection. Despite current management with intrauterine adhesion separation and adjuvant therapies such as estrogen supplementation, a high recurrence rate and inadequate therapeutic response persist in some patients. More importantly, compromised endometrial proliferation in these patients lead to subsequent infertility. However, effective therapies to improve the impaired response to estrogen have yet to be identified. This study seeks to elucidate the molecular basis for the adverse estrogen response in IUA patients and to identify novel therapeutic targets. Method: Whole-Transcriptome sequencing: proliferative endometrium of normal and IUA patients. Results: By performing differential and enrichment analysis of transcriptomic data, we observed a considerable downregulation of estrogen-relatedgenesets in IUA patients. The expression of enhancer RNAs (eRNAs) serves as a hallmark of transcriptional activation. By identifying eRNAs in transcriptomic data and co-analyzing with ERa ChIPseq and H3K27ac ChIPseq datasets, we identified a series of downregulated eRNAs, which is mediated by estrogen. We further confirmed the downregulation of eRNAs and target genes. Interestingly, the expression of ESR1 is similar in both groups, we performed immunofluorescence analysis and demonstrated a considerable reduction of ERa-positive cells with a loss of nuclear localization in IUA. This finding provides further evidence of the insensitivity of IUA patients to estrogen and suggests a loss of estrogen genomic effects. Furthermore, we found that prolonging estrogen exposure time and increasing estrogen concentration partially enhanced estrogen effects in IUA patients, yet remained compromised, indicating the need for alternative therapeutic strategies. Conclusion: The compromised response to estrogen in IUA patients is attributed to the attenuation of estrogen receptor alpha (ERa)-mediated genomic effect.
#376 : Septoplasty: Breaking the Divide. Management of Septate Uterus Presenting with Recurrent Pregnancy Loss
Authors: Cagalawan Ricca Mae 
Published: January 2024

Objective: To address Septate Uterus causing Recurrent Pregnancy Loss (RPL) with Septoplasty by creating an adequate adhesion-free uterine cavity. Methods: A 44-year old G4P0(0040) with recurrent pregnancy losses with 2 previous curettages after an abortion consulted. 3D ultrasound showed a uterus with a symmetrical septum extending up to the level of the isthmus with internal indentation of 2.04 cm. Hysteroscopic Septoplasty was done using a Bipolar Colin’s Electrode, resecting the septum in anterograde movement in the median plane of the septum. High dose estrogen was given for 8 weeks for faster re-epithelization. Second look hysteroscopy and 3D ultrasound after two menstrual cycles. Results: Post-operatively, the procedure and hormonal regimen were well-tolerated. The second look hysteroscopy revealed a small remnant of the septum and no adhesions present while the repeat 3D scan showed a 45% reduction of the internal indentation at 1.12 cm. Conclusion: In cases of Recurrent Pregnancy loss due to a septate uterus, it is reasonable to perform a Septoplasty with post-operative hormonal therapy to ensure sufficient intrauterine space and faster endometrial recovery to facilitate implantation and delivery at a viable age of gestation. A Second look Hysteroscopy is recommended to evaluate the procedure.
#83 : Human Sperm Cryo-Survival Rate
Authors: Saballa Cherrylyn , Spry Tyne , Jessop Linda , McArthur Steven 
Published: January 2024

Background and Aims: Sperm cryopreservation plays an important role in the suite of services available to fertility patients. The ability to preserve the motility and viability of human spermatozoa is a key component in delivering successful assisted reproductive technologies (ART) outcomes. Cryopreservation methods expose sperm to stress, resulting in cellular damage which consequently leads to a reduction in their survival rate. The aim of this study was to evaluate the average cryo-survival rate of semen samples frozen in a clinical setting, to help improve and manage patient expectations prior to accessing this service. Method: Pre and post sperm freeze data from patients who presented at the Genea Sydney clinic for sperm cryopreservation between 2017 and 2022 was analysed. The post-thaw survival rate for 1467 specimens was assessed by averaging the total post-thaw motility with total pre-freeze motility. Only ejaculated samples, frozen on-site, who had a raw motility calculated as well as a post-thaw motility analysis able to be performed were included in the study. Results: The range of post-thaw survival was 57% to 67% per annum over the six years of examined data, with an overall cryo-survival rate of 62%. Conclusions: The data shows a consistent recovery rate of post-thaw sperm motility over the time period analysed. Literature indicates average sperm cryo-survival rates range from 30% to 50%, and previous advice to patients has been to expect around 50% sperm survival. With this new data, Genea can revise its guidance to match the current average figure of around 60%. In addition, future internal freeze optimisation studies can use this figure as a benchmark to improve upon techniques and processes.
#202 : Adverse Effect on Pregnancy Outcome of Oocyte Preservation in Women with Advanced Maternal Age
Authors: Huang Yung-Ling , Hu Yu-Ming , Lin Ching-Mei , Chang Wei-Fang , Tan Shun-Jen , Lee Yi-Xuan , Wang Ruey-Sheng , Ho Yen-Ping , Lin Shyr-Yeu , Tzeng Chii-Ruey 
Published: January 2024

Background and Aims: For women facing inevitable fertility decline, oocyte freezing is an effective method for fertility preservation. However, few studies discussed the pregnancy potential from autologous freezing oocytes. Thus, this study characterizes the realistic outcomes of advanced maternal age patients who underwent oocyte thawing. Method: In this retrospective cohort study, the selected 694 patients underwent oocyte freezing cycles (n=1,163) and oocyte thawing cycles (n=218) from Mar 2020 to Mar 2022 at our fertility center. All oocytes thaw cycles from Mar 2020 to Mar 2022 at TFC clinic, including social egg freezing (SEF) and egg collection (EC). Parameters for IVF laboratory outcome and pregnancy outcome were recorded, and statistics were analyzed with Chi-square. Results: Those patients who underwent egg freezing at average age for 40.2 years old, and 49.7% were over 37 years old. Secondly, the survival rate of oocyte thawing was 94.9% in patients under 38 years old, 93.7% were 38-40 years old, and 91.4% for patients over 41 years old. For patients under 38 years old, 72.2% of were conceived for thawing cycle. For advanced maternal age groups, 46.7% for patients in 38-40 years old group, and only 23.3% of patients over 41 years old were conceived. The live birth rate declines as the age increases, which were 55.6%, 33.3%, and 7.1% in different age groups. Conclusion: In this study, we found the survival rate of oocytes and blastulation of embryo showed no significant difference between different age groups. Clinical pregnancy outcome demonstrated a dramatic decline in patients aged over 41 years old compared with other groups. Therefore, these data suggested that oocyte collection strategy is more suitable for patients who are under 41 years old.
#223 : Changes in Sperm Parameters in Semen Samples Collected on Procedural Day in Comparison to Semen Samples Collected for Routine Semen Analysis
Authors: Lee Su Xizn , Chee Fam May , Tee Sze Tian 
Published: January 2024

Background and Aims: Semen Analysis is the initial step in Assisted Reproduction Technology (ART) to help clinician decide the type of procedure such as Intra-Uterine Insemination (IUI), Intra-Cytoplasmic Sperm Injection (ICSI) or In-Vitro Fertilisation (IVF). The few main sperm parameters analysed were concentration, motility and the total sperm count. In this study, we aim to compare the sperm parameters during the routine sperm analysis with that of during the day of procedure. Method: This study involved 110 patients from TMC Fertility Ipoh from year 2017 to 2023. Routine semen analysis was performed for all patients during their initial consultation, prior to ART procedure. Sperm parameters during the routine semen analysis were recorded and compiled under Group A. The same group of patients came back for their ART treatment within 1-3 months after the first semen analysis. Sperm parameters recorded on the procedural day were then compiled under Group B. The parameters involved in this observation are sperm concentration, motility and total sperm count. The p-value of these parameters were calculated using T-test with two dependent means significant at p<0.05. Results: The result shows significant difference in the total sperm count parameter (120.67±94.80 × 106 vs 106.81±98.62 × 106, p=0.041) between Group A and Group B. However, motility (56.91±14.78% vs 55.62±13.66%, p=0.414) and concentration (47.83±33.03 × 106/mL vs 44.42±32.48 × 106/mL, p=0.140) showed no significant difference between the two groups. There was no significant difference in the duration of abstinence and sperm morphology. Conclusion: Based on the data, it was shown that the total sperm count was higher in Group A compared to Group B. This is hypothesised that there might be stress faced by the patient on the day of procedure. However, a larger study is required to verify the statement as there are many other factors contributing to fluctuating sperm parameters.
#373 : Demographic, Clinical Profiles and Semen Parameters of Men Seen for Baseline Semen Analysis at a Fertility Center in Davao City, Philippines — A Retrospective Study
Authors: Ibonia Kristine Andrea , Cabling Maria Lourdes 
Published: January 2024

Infertility is a worldwide problem that affects 13-15% of couples. Approximately 15% reproductive age couples experience infertility, with some attributed to male factors. Males are found to be solely responsible for 20-30% of infertility cases and contribute to 50% of cases overall. In male population, the most popular screening test is the semen analysis. This study was conducted to determine the association between demographic and clinical profile on semen parameters among males seen at a local fertility center in Davao City, Philippines. A 10-year retrospective descriptive study design with 399 randomly selected males who underwent baseline semen analysis were included in the study. Most of the respondents were married. 16% of the respondents had medical illnesses, with hypertension being the most common. Only 2 had urogenital surgery and 26 with long-term medication use. The majority had normal sperm concentration. Sperm motility among cases was desirable where majority had [Formula: see text]40%. The problem was seen on morphology where only 19% had normal result. Inferential analysis confirmed that most married men had higher percentage of mild oligozoospermia, abnormally low motility and normal sperm morphology. Males >30 years have higher percentage of normal sperm concentration and surprisingly, those [Formula: see text]30 years old had higher percentage of severe oligozoospermia. Moreover, most men [Formula: see text]30 years old had <40% sperm motility and those ages >30 years old presented a higher percentage of normal motility. History of smoking was significantly associated with sperm morphology where those who had history of smoking had [Formula: see text]4% sperm morphology. In the association of clinical profiles and semen parameters, data showed that medical illness was not associated with semen parameters. The history of urogenital surgery and long-term medication use were also not significantly related to semen parameters respectively. In conclusion, marital status, age and history of smoking are significantly correlated with semen parameters.
#187 : The Correlation Between Insulin Resistance with Serum Androgens Levels in Lean Women With and Without PCOS
Authors: Riayati Oki , Pratama Gita , Muharam R , Hestiantoro Andon , Wiweko Budi , Muna Naylah , Ampri Irfan Arieqal Hatta , Ezekia Kevin , Kenyia Niken Rivie , Iffanolida Pritta Ameilia , Mutia Kresna , Rahmala Ririn 
Published: January 2024

Background and Aims: Polycystic Ovarian Syndrome (PCOS) is a multifactorial disease resulting from the interaction of multiple predisposing genetic variations and environmental factors. Insulin resistance and hyperinsulinemia contribute to hyperandrogenism and impaired gonadotropin secretion by reducing sex hormone binding globulin (SHBG) levels and increasing testosterone bioavailability. However, this insulin resistance is not always present in PCOS patients, especially in lean PCOS patients. This study aims to determine whether insulin resistance correlates with serum androgens levels. Method: We collected 25 samples from lean women with PCOS, and 25 samples from lean women without PCOS. Peripheral whole blood samples will be taken from all samples. Data collected include Anthropometric data, Hormonal profile (using ELISA method), and HOMA-IR value. Results: The result showed that median(min-max) ages for patients was 25(17-34) years. In lean women with PCOS, there was a positive relationship between HOMA-IR with FAI (p=0.017, r=0.472) and negative relationship with SHBG (p=0.001, r=-0.610). Also, in lean women without PCOS, there were no correlation between HOMA-IR with FAI, and HOMA-IR with SHBG (p>0.05) Conclusion: This study shows that there was a correlation between insulin resistance and some serum androgens in lean women with PCOS, but there was no correlation between HOMA-IR with FAI, and HOMA-IR with SHBG in lean women without PCOS. Therefore, the results of this study are hoped to explain the correlation of insulin resistance with serum androgens in lean PCOS patients and can be the basis for further research to find the right solution for the treatment of PCOS patients.
Mechanistic Modeling of Intrathecal Chemotherapy Pharmacokinetics in the Human Central Nervous System
Authors: Li Jing , Wu Andrew , Kim Seongho 
Published: January 2024

Abstract

Purpose:
The pharmacokinetics of intrathecally administered antibody or small-molecule drugs in the human central nervous system (CNS) remains poorly understood. This study aimed to provide mechanistic and quantitative perspectives on the CNS pharmacokinetics of intrathecal chemotherapy, by using a physiologically based pharmacokinetic (PBPK) modeling approach.

Experimental Design:
A novel CNS PBPK model platform was developed and verified, which accounted for the human CNS general anatomy and physiologic processes governing drug distribution and disposition. The model was used to predict CNS pharmacokinetics of antibody (trastuzumab) and small-molecule drugs (methotrexate, abemaciclib, tucatinib) following intraventricular injection or intraventricular 24-hour infusion, and to assess the key determinants of drug penetration into the deep brain parenchyma.

Results:
Intraventricularly administered antibody and small-molecule drugs exhibited distinct temporal and spatial distribution and disposition in human CNS. Both antibody and small-molecule drugs achieved supratherapeutic or therapeutic concentrations in the cerebrospinal fluid (CSF) compartments and adjacent brain tissue. While intrathecal small-molecule drugs penetrated the deep brain parenchyma to a negligible extent, intrathecal antibodies may achieve therapeutic concentrations in the deep brain parenchyma. Intraventricular 24-hour infusion enabled prolonged CNS exposure to therapeutically relevant concentrations while avoiding excessively high and potentially neurotoxic drug concentrations.

Conclusions:
CNS PBPK modeling, in line with available clinical efficacy data, confirms the therapeutic value of intrathecal chemotherapy with antibody or small-molecule drugs for treating neoplastic meningitis and warrants further clinical investigation of intrathecal antibody drugs to treat brain parenchyma tumors. Compared with intraventricular injection, intraventricular 24-hour infusion may mitigate neurotoxicity while retaining potential efficacy.
AAV-Mediated Delivery of Plakophilin-2a Arrests Progression of Arrhythmogenic Right Ventricular Cardiomyopathy in Murine Hearts: Preclinical Evidence Supporting Gene Therapy in Humans
Authors: van Opbergen Chantal J.M. , Narayanan Bitha , Sacramento Chester B. , Stiles Katie M. , Mishra Vartika , Frenk Esther , Ricks David , Chen Grace , Zhang Mingliang , Yarabe Paul , Schwartz Jonathan , Delmar Mario , Herzog Chris D. , Cerrone Marina 
Published: January 2024

BACKGROUND:

Pathogenic variants in PKP2 (plakophilin-2) cause arrhythmogenic right ventricular cardiomyopathy, a disease characterized by life-threatening arrhythmias and progressive cardiomyopathy leading to heart failure. No effective medical therapy is available to prevent or arrest the disease. We tested the hypothesis that adeno-associated virus vector–mediated delivery of the human
PKP2
gene to an adult mammalian heart deficient in PKP2 can arrest disease progression and significantly prolong survival.

METHODS:
Experiments were performed using a PKP2-cKO (cardiac-specific, tamoxifen-activated PKP2 knockout murine model). The potential therapeutic, adeno-associated virus vector of serotype rh.74 (AAVrh.74)-PKP2a (PKP2 variant A; RP-A601) is a recombinant AAVrh.74 gene therapy viral vector encoding the human PKP2 variant A. AAVrh.74-PKP2a was delivered to adult mice by a single tail vein injection either before or after tamoxifen-activated PKP2-cKO. PKP2 expression was confirmed by molecular and histopathologic analyses. Cardiac function and disease progression were monitored by survival analyses, echocardiography, and electrocardiography.

RESULTS:
Consistent with prior findings, loss of PKP2 expression caused 100% mortality within 50 days after tamoxifen injection. In contrast, AAVrh.74-PKP2a–mediated PKP2a expression resulted in 100% survival for >5 months (at study termination). Echocardiographic analysis revealed that AAVrh.74-PKP2a prevented right ventricle dilation, arrested left ventricle functional decline, and mitigated arrhythmia burden. Molecular and histological analyses showed AAVrh.74-PKP2a–mediated transgene mRNA and protein expression and appropriate PKP2 localization at the cardiomyocyte intercalated disc. Importantly, the therapeutic benefit was shown in mice receiving AAVrh.74-PKP2a after disease onset.

CONCLUSIONS:
These preclinical data demonstrate the potential for AAVrh.74-PKP2a (RP-A601) as a therapeutic for PKP2-related arrhythmogenic right ventricular cardiomyopathy in both early and more advanced stages of the disease.