bluuebunny/crossref_metadata_2025_split huggingface dataset:
#165 : Application of a Highly Reliable Protocol of Non-Invasive Preimplantation Genetic Testing for IVF Cycles and Its Clinical Outcome
Authors: Tang Yen-An , Huang I-Ning , Lee Shiow-Jan , Sun H. Sunny , Pan Hsien-An 
Published: January 2024

Background and Aims: The non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) using cell-free DNA (cfDNA) from the spent culture medium (SCM) has been reported. Nevertheless, the recommendation of niPGT-A in routine IVF clinics has been controversial due to diverse study conditions. To establish a reliable clinical protocol, the critical factors affecting accuracy of niPGT-A assay and clinical outcomes were investigated. Methods: Three hundred and sixty-two blastocysts from 94 patients undergoing IVF between January 2021 and August 2022 were analyzed. In a frozen embryo arm (n=100), the accuracy of niPGT-A and PGT-A using SCM and corresponding trophectoderm (TE) biopsy, respectively, was examined when compared with whole blastocysts as gold standard. In a fresh embryo arm (n=262), the concordance between niPGT-A and PGT-A were analyzed. Results: Comparing different commercial kits, the PicoPLEX Gold showed the highest sequencing quality and accuracy. Through applying an optimized threshold for mosaicism, the overall PPV, NPV, specificity, sensitivity, and accuracy of niPGT-A reached to 92.1%, 88.2%, 75.0%, 96.7%, and 91.3%, respectively. Regarding the fresh embryos, niPGT-A and PGT-A had reached a ploidy concordant rate of 76.5% and sex concordant rate of 90.7%. Applying assisted-hatching effectively elevated the amplification rate ( [Formula: see text] [Formula: see text]0.001), and the accuracy of niPGT-A (91.3%) was significantly better than PGT-A (79.2%, [Formula: see text] =0.033). The longer culture duration improved the ploidy concordance (1-day: 63.6%, 2-day: 73.5%, 3-day: 83.6%). Finally, 21 frozen-thawed embryo transfer cycles were performed and guided by euploid results of the TE biopsy. Live-birth rate was higher in euploid-TE/euploid-SCM (54.4%) than in euploid-TE/aneuploid-SCM (30.0%), and no miscarriages were observed in euploid-TE/euploid-SCM. Conclusions: Our current niPGT-A workflow adopts from the most common clinical setting of embryo culture and shows superior accuracy. Given the nature of niPGT-A that reflects the ploid state of the whole blastocyst, larger scale studies are warranted to support niPGT-A in routine clinical practice.
#275 : A Comparative Study of Hatching Methods for Biopsy Time and Ploidy Status Assessment
Authors: Truong Son Dang , Phuong Huy Tran , Tuan Anh Do , Thi Phuong Dao , Duc Thuan Nguyen 
Published: January 2024

Background and Aims: Preimplantation genetic testing plays a crucial role in assisted reproductive technologies by aiding in the selection of embryos with optimal developmental potential. This study aims to compare the time required for biopsy and evaluate the ploidy status between Day3 and Day4 hatching-based methods and cases without assisted hatching (AH). Method: We retrospectively analyzed data from 257 embryos from 56 patients between November 2022 and March 2023. Embryos were categorized into three groups: Day3 hatching-based method (n=43), and Day4 hatching-based method (n=134), and cases without AH (n=80). We used Kruskal-Wallis tests and chi-square tests to compare the groups with R software (version 4.1.0) at a significance level of 0.05. Results: There was a significant difference in the median biopsy time per embryo between the hatching-based methods (H = 6.01, p = 0.049). The Day4 hatching-based method had a significantly shorter biopsy time per embryo than cases without AH (W = 95, p = 0.037). There were no significant differences in the percentages of euploid, aneuploid, or mosaic embryos between the hatching-based methods. The Chi-square test showed no significant differences between the observed and expected percentages of euploid ([Formula: see text] = 0.22, p = 0.893), aneuploid ([Formula: see text] = 2.35, p = 0.308), or mosaic ([Formula: see text]= 0.58, p = 0.748) embryos across all hatching-based methods. The Chi-square test of independence showed no significant differences in the percentages of euploid ([Formula: see text] = 0.56, p = 0.755), aneuploid ([Formula: see text] = 1.41, p = 0.495), or mosaic ([Formula: see text] = 0.22, p = 0.896) embryos between the hatching-based methods. Conclusion: We suggest that the Day4 hatching-based method may provide a significant advantage in terms of shorter biopsy time per embryo compared to cases without AH, but there were no significant differences in the percentages of euploid, aneuploid, or mosaic embryos between the hatching-based methods.
#291 : Association of Maternal Age with Embryonic Aneuploidy and Morphological Score Among Good-Prognosis Infertile Women: A Secondary Analysis of Multicenter, Randomized Controlled Trial
Authors: Huang Yumei , Zhou Wei , Zhang Qian , Ni Tianxiang , Yan Junhao 
Published: January 2024

Background and Aims: Maternal age has been reported to impact on embryo genetic status. However, current data on the association between maternal age and early embryo development are limited and inconclusive, especially among good-prognosis women. This study aims to determine the association between female age and embryonic aneuploidy based on next generation sequencing (NGS), as well as morphological score among women aged 20-37 years with a good prognosis. Method: This is a secondary analysis of a multi-center, randomized controlled trial conducted from July 2017 through June 2018, which investigated the efficacy of preimplantation genetic testing for aneuploidy (PGT-A) in good-prognosis infertile population. The women with PGT-A treatment were divided into three groups (20-24 yrs, 25-30 yrs, 31-37 yrs) according to maternal age. The diversity of embryo testing results based on NGS and morphological score were compared between three groups. Results: A total of 1809 embryos were analyzed in this study. The rates of embryonic overall aneuploidy (14.5%) and monosomy (3.0%) among females in the 25-30 age group were lower than those (aneuploidy 21.3%, monosomy 6.9%) in the 31-37 age group (adjusted P= 0.009, 0.004, respectively). However, the rates of embryonic aneuploidy (18.9%) and monosomy (3.9%) of females in the 20-24 age group did not differ from other two age groups. Although there was no significant difference in subsegmental aneuploidy rate among the three groups (P=0.215), the variation trend with age was consistent with that of embryonic aneuploidy. There was no significant difference in embryo morphological scores between the three groups. Conclusion: For young infertile women with a good prognosis, embryonic aneuploidy and monosomy are more likely to occur in advanced age more than 30 years. And embryonic development scores do not change significantly with increasing age.
#322 : A Rare Case Report of Successfull Live Twin Birth in a Couple Who are Carriers of Mucopolysaccharidoses VII-Sly Syndrome
Authors: Jagannathan Vasundara , Ranganathan Srinidhi 
Published: January 2024

Introduction: Mucopolysaccharidoses VII or sly syndrome is an autosomal recessive condition discovered in 1972 by William Sly, occurs due to mutation in the beta glucoronidase encoding gene, it is an ultra-rare neurometabolic disorder caused by inherited deficiency of the lysosomal enzyme [Formula: see text]eta-glucuronidase. Precise data regarding its epidemiology is scarce, but birth prevalence is estimated to vary from 0.02 to 0.24/100,000 live births with 54 types of recorded mutations. The clinical course and disease progression are widely heterogeneous. So far 9 pregnancies have been recorded in patients with sly syndrome of which the majority showed some deformity. Here we present a case of a couple with two different variants of GUSB gene who delivered live twin birth with normal development. Background: A couple aged 29 & 31 who were anxious to conceive came to the clinic with a previous history of two abortions for pre conceptual counselling. Both pregnancies had features suggestive of non-anemic type nonimmune hydrops with increased nuchal fold thickness in USG. Both her pregnancies were terminated mid trimester with the autopsy results conclusive of the findings. Method & Results: Whole exome sequencing showed that both were carriers of GUSB gene of two different variants encoding for Sly syndrome. Based on the WES and karyotyping reports genetic counselling was given, and PGT-M was suggested. The patient underwent antagonist protocol and 12MII were retrieved. ICSI was done and the embryos were cultured to day 5 and subjected to PGT-A, PGT-M. The resultant 2 carrier blastocysts were transferred. Post transfer Beta Hcg was positive. The patient had an uneventful obstetric course and delivered normal twin girl babies on 27/01/23. The twins showed no physical abnormality and their genetic profiling showed they were carriers of GUSB gene. Conclusion: This case demonstrates that with appropriate pre-conceptual evaluation, genetic counselling, constant maternal and fetal surveillance, carriers of sly syndrome can be given multidisciplinary care leading to successful outcome.
#340 : Autologous Platelet-Rich Plasma (PRP) Treatment for Thin Endometrium in Yasmin IVF Clinic RSCM
Authors: Muna Naylah 
Published: January 2024

Background and Aims: PRP is a biological product defined as a portion of the plasma fraction of autologous blood with a platelet concentration above the baseline. PRP is one of the trends in regenerative medicine and also being used in reproductive medicine area, one of which is to treat thin endometrial problems by infused intrauterine. The goal of this treatment is to reach suitable endometrial thickness by enhancing proliferation of endometrial cells. A good and receptive endometrium is necessary to achieve successful embryo implantation, both in natural pregnancy and assisted reproductive technology. This study aimed to analyze the outcome of PRP treatment during 2022 in Yasmin IVF Clinic RSCM. Method: This is a retrospective study which collected PRP service data during 2022 in Yasmin IVF Clinic RSCM. 76 subjects underwent PRP intrauterine infusion with thin endometrium indication ([Formula: see text]6 mm). Subjects were then categorized into two groups, first only underwent PRP procedure once and another group underwent intrauterine PRP procedure two times. Subjects underwent intrauterine PRP procedure more than two times were excluded from this study. All data were then statistically analyzed. Results: 76 subjects underwent intrauterine PRP infusion in Yasmin IVF Clinic RSCM during 2022. All subjects were diagnosed with thin endometrium ([Formula: see text]6 mm). Only 23 subjects underwent one intrauterine PRP procedure based on endometrial thickness assessment. The rest of the subjects, 53 patients underwent intrauterine PRP infusion two times. After PRP infusion, the endometrium thickness in PRP group was 8.37 ±0.22 mm, which was significantly thicker than that in control group (6.05 ±0.23 mm) (P [Formula: see text]0.05). However, implantation rate and clinical pregnancy rate in PRP group were not significantly higher than those in control group (28% vs 9%; 37% vs 20%; P [Formula: see text]0.05; respectively). Conclusion: Intrauterine PRP infusion seemed to be a good option in facing thin endometrium diagnosis. It is able to enhance endometrial thickness. However, the result of clinical pregnancy still needs to be improved.
#160 : Detection of Alpha Thalassemia Silent Carriers Having Point Mutation Among Infertile Patients by Gene Sequencing
Authors: Vuong Vu Viet Ha , Tran Thi Huyen Trang , Le Thi Phuong , Dang Thi Minh Nguyet , Nguyen Thi Nha , Tran Van Khanh 
Published: January 2024

Background and Aims: Thalassemia is a highly prevalent genetic disease in Vietnam. Importantly, silent carriers pose a risk of having children with two mutated alleles hence serious health conditions requiring hematological treatments for the lifetime. Early detection of silent carriers would assist doctors in counseling and offering preimplantation genetic testing for monogenic defects (PGT-M), in this case for thalassemia, which would help carrier couples eventually have healthy babies. Approximately 5% of [Formula: see text]-thalassemia diseases are caused by point mutations while 95% are caused by deletions. Although rare, [Formula: see text]-thalassemia point mutations can be missed when conventional screening methods fail to detect them. DNA sequencing is considered a gold standard method for identifying novel, unreported point mutations. This study aims to apply sequencing to detect point mutations in infertile [Formula: see text]-thalassemia silent carriers. Method: Couples seeking fertility treatments were invited and consented to take part in the study. The control group had five healthy people possessing normal complete blood count results as well as a healthy family history. The study group consisted of nine people, who had hypochromic microcytic anemia (MCH [Formula: see text] 27 pg; MCV [Formula: see text] 80 fL) without any detected deletion mutations. DNA was extracted from whole blood samples. PCR products were then sequenced using SeqStudio Genetic Analyzer 3500 and analyzed by CLC Sequencing Analysis Software v6 together with Mutation Taster ( http://www.mutationtaster.org/ ) and CAAD ( https://cadd.gs.washington.edu/ ). Results: The study identified four variants of the HBA2 gene in nine heterozygous carriers. Among them, 5/9 carried the -[Formula: see text] [Formula: see text]variant, 2/9 had the -[Formula: see text] [Formula: see text], one carried the c.2delT variant, and one bore a new variant, c.-2C[Formula: see text]T, which has not been reported elsewhere. Conclusion: DNA sequencing is effective in detecting point mutations of the [Formula: see text]-thalassemia gene in carriers. The results can significantly contribute to the fertility treatment plan in order to have healthy babies.
#235 : The Impact of Endometrial Scratch Performed in Mid-Luteal Phase on the Endometrium Whole Genome Transcriptomic Profiles in Following Menstrual Cycle
Authors: Huang Jin , Tian Yichao , Wang Chiu , Lin Huizhen , Huang Xiaona , Zhao Yue , Liu Liu , Zhang Songying 
Published: January 2024

Background and Aims: To verify whether endometrial scratch in mid-luteal phase affect the genomic characteristics of peri-implantation endometrium in the following cycle. Method: A Retrospectively self-control cohort study was conducted in a university assisted reproductive unit. A total of eight women with recurrent implantation failure were included. Each participant had endometrial biopsy twice, one biopsy was done on day LH+7 in a natural cycle, and the second biopsy was performed on day LH+7 of the following cycle. R package was used for identifying differentially expressed genes between the first biopsy group and the second biopsy group, and for gene set enrichment analysis. Results: The paired sample showed no significant difference in gene expression profiles of endometrium before and after endometrial scratch. Conclusion: It suggests that endometrial scratch performed during previous mid-luteal phase did not affect the genomic profiles of endometrium on day LH+7 in women with recurrent implantation failure.
#248 : Maternal Hypercholesterolemia Would Increase the Incidence of Embryo Aneuploidy in Couples with Recurrent Implantation Failure
Authors: Liu Yang , Ni Tianxiang , Yan Junhao 
Published: January 2024

Background and Aims: The association of dyslipidemia with reproductive outcomes is largely unknown, especially in recurrent implantation failure (RIF) patients. This study aimed to explore the impact of abnormal blood lipid levels on embryo genetic status and pregnancy outcomes in unexplained RIF (uRIF) patients after preimplantation genetic testing for aneuploidy (PGT-A). Method: In this retrospective study, they were divided into 4 groups according to the levels of cholesterol and triglyceride: non-hyperlipidemia group (NonH group), simple hypercholesterolemia group (SHC group), simple hypertriglyceridemia group (SHC group) and mixed hyperlipidemia group (MixH group). Additionally, patients were divided into 2 groups according to their HDL-C level. Embryos’ genetic status and pregnancy outcomes after transfer of euploid embryos were analyzed. Binary logistic regression and/or generalized estimating equation model were conducted to investigate the association of different types of dyslipidemia with aneuploid embryo rate and cumulative live-birth rate. Results: A total of 474 women were divided into four groups: NonH group (N=349), SHC group (N=55), SHT group (N=52) and MixH group (N=18). Compared with the NonH group, SHC group had a significantly increased aneuploid embryo rate [48.3% vs. 36.7%, P=0.006; adjusted OR (95% CI) = 1.52(1.04-2.22)], as well as a reduced number of good-quality blastocysts [3.00±2.29 vs. 3.74±2.77, P=0.033]. The SHC group showed a lower cumulative live-birth rate (47.0% vs. 40.0%), good birth outcome (37.2% vs. 34.5%) and a higher risk of clinical pregnancy loss (11.1% vs. 17.9%) but did not reach statistical significance. The incidences of obstetric or neonatal complications and other adverse events were similar in the four groups. Conclusion: We found that uRIF women with hypercholesterolemia had an increased proportion of aneuploid embryos and a reduced number of high-quality embryos, while different types of hyperlipidemias had no correlation with cumulative live birth rate as well as pregnancy and neonatal outcomes.
#286 : Circus Recurrent Pregnancy Loss by Modulating SETD1B/H3K4me2/me3 LoopK40 Regulates Cell Survival and Participates in
Authors: Tang Rong , Zhou Tingting , Lyv Chunzi , Yan Junhao 
Published: January 2024

Background and Aims: The epigenetic mechanisms involved in the etiology of unexplained recurrent pregnancy loss (uRPL) is largely unknown. This study aims to investigate the molecular mechanisms of circRNAs modulating decidua function by regulating methylation modification of histones and whereby participating in uRPL. Method: RNA sequencings on decidua of uRPL couples and endometrial stromal cells (ESCs) after overexpressed with circSTK40 were performed to confirm the regulatory relationship between circSTK40 and SETD1B. Functional experiments including TUNEL, autophagy double-label system, the tests of glucose intake, lactic acid production were performed to determine the effects of circSTK40 and SETD1B on ESCs. Mechanism studies were conducted using RNA pulldown, RNA binding protein immunoprecipitation, chromatin immunoprecipitation et al. Results: The expression levels of circSTK40 and SETD1B were significantly downregulated in the decidua of uRPL patients, and a positive regulatory relationship was observed between them. Both circSTK40 and SETD1B promoted cell survival and participated in the maintenance of pregnancy by regulating apoptosis, autophagy and glycolysis of decidualized ESCs. After the knockdown of SETD1B, the protective effect of circSTK40 could be eliminated, resulting in elevated apoptosis, reduced autophagy level and increased cellular glycolysis, leading to pregnancy loss. Regarding mechanism studies, circSTK40 is directly bound to SETD1B and histone H3 to promote their interaction and increase the methylation level of H3K4. H3K4me2 and H3K4me3 reversely bound to the promoter region of SETD1B and enhanced its transcription, resulting in upregulation of SETD1B, and consequently formed a SETD1B/H3K4me2/3 regulatory loop. Conclusion: CircSTK40 influences cell survival by modulating the SETD1B/H3K4me2/me3 regulatory loop. Downregulation of circSTK40 and SETD1B in decidua may contribute to uRPL via promoting cell apoptosis. Our findings indicate a novel epigenetic mechanism for uRPL pathogenesis involving circSTK40 activity and histone methylation modification.
#326 : Multi-Omics Analysis Reveals Translational Landscapes and Regulations in Mouse and Human Oocyte Aging
Authors: Huang Jiana , Zeng Haitao , Liang Xiaoyan , Zhou Chuanchuan 
Published: January 2024

Background and Aims: Abnormal resumption of meiosis and decreased oocyte quality are hallmarks of maternal aging and ultimately lead to infertility. Transcriptional silencing makes translational control an urgent task during meiosis resumption in maternal aging. However, insights into aging-related translational characteristics and underlying mechanisms are limited. Method: Here, using multi-omics analysis of oocytes, including single-cell proteomics, ultrasensitive translatomics and transcriptomics, we profiled the multi-omics landscapes of mouse and human oocyte aging. The role and mechanisms underlying oocyte aging were explored and verified using immunofluorescence staining, electroporation, RNA immunoprecipitation (RIP) sequencing, quantitative PCR (qPCR), methylated RIP, and dual-luciferase reporter assay etc. Results: We found that translatomics during aging was related to changes in the proteome and revealed decreased translational efficiency with aging phenotypes in mouse oocytes. Notably, the translational efficiency decrease was associated with the N6-methyladenosine (m6A) modification of transcripts. We clarified that the expression of the m6A reader YTH N6-methyladenosine RNA-binding protein 3 (YTHDF3) was significantly decreased in aged oocytes and inhibited oocyte meiotic maturation. YTHDF3 intervention perturbed the translatome of oocytes and suppressed the translational efficiency. We further identified Hells as an aging-associated maternal factor whose translation was suppressed during oocyte aging in a YTHDF3-dependent manner. Moreover, we profiled the translational landscape in human oocyte aging, and observed the same translational changes of DNA methylation regulatory enzymes and different regulation of histone modifications between human and mice oocytes aging. Translation efficiency was not changed in human oocytes aging. Due to translational silence of YTHDF3 in human oocytes, translation activity was not associated with m6A modification, but was related to alternative splicing factors, such as SRSF6. Conclusion: Together, our findings profiled the specific translational landscapes during oocyte aging in mice and human and uncovered non-conservative regulators on translation control in meiosis resumption and maternal aging.