bluuebunny/crossref_metadata_2025_split huggingface dataset:
#285 : Amphiregulin Increases Pentraxin 3 Production via the EGFR-Mediated Erk1/2 Signaling in Human Granulosa Cells
Authors: Chang Hsun-Ming 
Published: January 2024

Background and Aims: Pentraxin 3 (PTX3) plays a key role in the assembly of the extracellular matrix, which is critical for cumulus expansion, ovulation, and in vivo fertilization. As a member of the epidermal growth factor family, amphiregulin (AREG) mediates luteinizing hormone (LH)-induced oocyte maturation and cumulus expansion in mammalian follicles. The aim of this study was to investigate whether AREG regulates the expression and production of PTX3 in human granulosa cells and to examine its underlying molecular determinants. Method: Immortalized human granulosa cells (SVOG cells) and primary human granulosa-lutein (hGL) cells obtained from women undergoing in vitro fertilization in an academic research center were used as the study models. The expression and accumulated levels of PTX3 were examined following cell incubation with AREG at different time points using the RT-qPCR and ELISA, respectively. Two kinase inhibitors (AG1478, and U0126) and small interfering RNAs targeting EGF receptor (EGFR) were used to verify the specificity of the effects and to investigate the molecular mechanisms. The results were analyzed by one-way analysis of variance. Results: The results showed that AREG upregulated the expression and production of PTX3 in primary and immortalized hGL cells. Additionally, using a dual inhibition approach (kinase inhibitors and siRNA-based expression knockdown), we demonstrated that this effect was mainly mediated by the EGFR receptor. Furthermore, we revealed that the Erk1/2 signaling is the downstream signaling pathway that mediates the increase in PTX expression and production in response to AREG treatment in hGL cells. Conclusion: AREG upregulated the expression of PTX3, leading to increased production of PTX3 in hGL cells. The AREG-induced cellular activities were most likely driven by the EGFR-mediated Erk1/2-dependent signaling pathway. Our findings shed light on the detailed molecular mechanisms by which AREG regulates the process of cumulus expansion and subsequent ovulation in humans.
#43 : Expression of miRNA-21-3p in Polycystic Ovary Syndrome and its Related Functions
Authors: Zhang Guoqing , Mukhri B. Hamdan , Zheng Lianwen 
Published: January 2024

Background and Aims: PCOS is an endocrine-related disease related to abnormal folliculogenesis and is a leading cause of infertility worldwide. Inhibition of GCs proliferation and increased GCs apoptosis have been identified as the major factors in aberrant follicle maturation. Recently, the roles of miRNAs were identified in polycystic ovary syndrome (PCOS). For instance, miR-21-3p was identified as an important miRNA regulating autophagy of BGCs. Besides, studies showed that AMSC-EXOs can rescue the polycystic phenotype and metabolic dysfunction in PCOS ovaries by transferring miR-21-5p to the livers of rats with PCOS, finally improve reproduction. However, there is no research clarified the association between miRNA-21-3p and GCs function to date. Method: In the present study, letrozole was used to establish the PCOS rat model. Separate the ovary and then miRNA-21-3p expression will be analyzed by RT-PCR. Primary rat ovarian GCs were isolated and incubated and transfected with mimic or inhibitor of miRNA-21-3p, CCK8 kit was used to detect cell viability, PR-PCR was used to detect cell proliferation and apoptosis related gene expression. Finally, flowcytometry was used to test apoptosis rate of Gcs. Results: The expression of miR-21-3p in the ovaries of PCOS rats was significantly increased compared with that in control rats. Primary rat ovarian GCs were isolated and incubated successfully, and then CCK-8 experiment showed that GCs viability was significantly decreased when miR-21-3p was overexpressed. Additionally, the miR-21-3p mimic significantly decreased the expression of PCNA, Bcl-2, cell cycle-related genes (CDK2, CCNE1) and increased the expression of Bax and caspase3 in primary rat ovarian GCs. By contrast, transfected primary rat ovarian GCs using the miR-21-3p inhibitor significantly upregulated the expression of PCNA, Bcl-2, cell cycle-regulated genes (CDK2, CCNE1) and reduced the expression of Bax and caspase3. Finally, flow cytometry analysis demonstrated that overexpression of miR-21-3p significantly increased the apoptosis rate of GCs. By contrast, the suppression of miR-21-3p resulted in a significant decrease in the apoptosis rate of GCs. Conclusion: In PCOS rat model, miRNA-21-3p was proved significantly increased compared with that in control rats. Which is participant in the development of PCOS by regulating the function of granular cells.
#109 : Differential Effects of Age and Lifestyle on Anti-Mullerian Hormone Levels and Ovarian Reserve in Asian Women with and Without Polycystic Ovarian Syndrome (PCOS)
Authors: Huang Zhongwei , Yang Qian , Lee Jovin , Benny Paula 
Published: January 2024

Background and Aims: Polycystic ovarian syndrome (PCOS) afflicts 4-20% of all women at reproductive age and is a common cause of infertility. Elevated anti-Mullerian hormone levels (AMH), a clinical marker for ovarian reserve, are routinely associated with PCOS, however, an exact cut-off value has remained elusive. Interestingly, observational studies reported that women with PCOS have purported higher ovarian reserves, implied from higher AMH levels, and later age of menopause delayed by 2 years when compared to women without PCOS. Our study focuses on the Asian population, a demographic frequently under-represented in cohort studies. We posit that our results will bridge the gap in the collective understanding of PCOS and how age and lifestyle effects on ovarian reserves in Asian women. Method: A large retrospective study was conducted at a tertiary-care hospital in Singapore from 2016-2020. AMH and clinical demographics from 3,739 Asian women aged 21-53 years were collected. Wilcoxon Rank Sum was used to analyze the data and significance was established if p<0.05. Logistic regression and ROC were generated in R. Results: AMH (aOR=1.07), age (aOR=0.89) and BMI (aOR=1.12) were significantly associated with PCOS(p<0.001) in Asian women. AMH declined with age but the decline in the PCOS group was less severe, with 80% AMH retained in women in their 40s, as compared to controls which retained only 40% AMH(Fig. 1). BMI>25 and smoking status affected AMH levels with higher BMI and smoking associated with lower AMH. An ethnic stratification revealed that average AMH levels of Malay women with PCOS were lower than Chinese and Indian women in each age group (Fig. 2). The constructed model incorporating all variables had an ROC AUC=0.89. Conclusion: This study highlights the importance of improving the resolution of PCOS diagnosis through AMH profiling, especially in Asian populations. The results from this study suggest potential beneficial effects of lifestyle modifications such as maintaining a healthy BMI and stopping smoking, especially in Asian women with PCOS.
#140 : Combined Use of Letrozole, Cabergoline and GnRH Antagonist to Prevent Ovarian Hyperstimulation Syndrome Completely in Polycystic Ovarian Syndrome Treatment
Authors: Yanagihara Yasuho , Ohno Motoharu , Kuwazuru Tomoichiro , Nakajima Daisuke , Nagayoshi Motoi , Tanaka Izumi , Tanaka Atsushi , Itakura Atsuo 
Published: January 2024

Background and Aims: The main difficulty to treat polycystic ovarian syndrome (PCOS) is the possibility of ovarian hyperstimulation syndrome (OHSS). There are several clinical approaches to avoid dangerous complications of OHSS: laparoscopic ovarian drilling (LOD), in vitro maturation (IVM), and GnRH antagonist-GnRH agonist based controlled ovarian stimulation (COS) with low dose of gonadotrophin. However, clinical outcomes after using these methods are less satisfactory than COS in normal ovarian function. We started a new approach combining the use of three kinds of medicine, Letrozole, Cabergoline and GnRH antagonist from just after the oocyte pick up and continue for five consecutive days to prevent the occurrence of OHSS in the PCOS treatment. Method: We compared the severity of OHSS after using a new treatment (the novel COS) in 53 women (55 cycles) with the severity of OHSS in a group of 37 women (37 cycles) who received the most widely used conventional GnRH antagonist-GnRH agonist- based COS for PCOS in retrospective cohort study. Results: This table shows the comparison of clinical outcomes between two groups. Conclusion: PCOS patients have been treated with hypostimulation methods and IVM to prevent OHSS. However, our method is considered to be more effective, safer and more versatile than any other treatment method. It seems to be an important alternative treatment method for PCOS patients. We believe this new treatment is highly recommended for the complete prevention of OHSS.
#226 : Comparison of Letrozole vs Letrozole Plus Metformin as First Line Ovulation Induction Drug for Infertile PCOS Women
Authors: Kar Sujata , Maharana Lipika 
Published: January 2024

Background: Letrozole is currently considered as first line ovulation induction drug in anovulatory PCOS women. Insulin sensitizers like Metformin have a proven role as an adjuvant to improve ovulatory function in resistant PCOS women. Letrozole and Metformin combined as first line ovulation induction option has not been studied much, neither has been compared to other options. Objective: The aim of this study was to compare Letrozole plus Metformin vs Letrozole alone as first line ovulation induction drug in treatment naive infertile PCOS women. Materials & Methods: 125 PCOS patients with anovulatory infertility were randomized by a computer generated randomization list to receive either Letrozole 5 mg from day 3-7 of menses plus Metformin daily (65 patients,150 cycles, Group I) or Letrozole 5mg/day from day 3-7 (60 patients, 121 cycles, Group II). The primary outcome studied was live birth rates and the secondary outcomes reported were ovulation rate, mono / multifollicular development, endometrial thickness, pregnancy rates, abortion and twinning rates. Results: Live birth rate was 33.8% in group I and 45.8% in group II (p=0.17) which was not statistically significantly different. The ovaluation rate was 85.9% and 86.7% (P=0.85) respectively. Multi follicular ovulation was slightly more in Group 2 (38.6% vs 48.1%). Conclusion: There was no significant benefit of adding Metformin to Letrozole as first line ovulation induction drug in terms of live birth rate or ovulation rates.
#234 : Impact of Visceral Adiposity Index on the Pregnancy Outcomes of Women with Polycystic Ovary Syndrome
Authors: Nguyen Thanh Nam , Ho N A Vu , Nguyen L Duy , Nguyen H N Minh , Pham D Toan , Ly D Luong , Tran T N Mai , Ho M Tuong , Vuong N Lan 
Published: January 2024

Background and Aims: Despite the widely used of body mass index (BMI) to indicate body fatness, it does not take into account muscle mass, bone density, overall body composition, and racial and sex differences. Visceral adiposity index (VAI) is an empirical-mathematical model gender-specific to indicate fat distribution and function. VAI was calculated based on simple anthropometry and metabolic parameters. There may be a correlation between VAI and reproductive outcomes. This study investigates the correlation between VAI and pregnancy outcomes in PCOS women. Method: This prospective cohort study was conducted at IVFMD, My Duc Hospital, from June 2020 to August 2022. This study included infertile PCOS women aged between 18 and 40 years. At the initial workup, PCOS women were evaluated for their VAI. We then classified them into four groups based on their VAI: <1.5, 1.5-<3.0, 3.0-<4.5, and ≥4.5. We continued to follow their reproductive outcomes for up to 12 months since the initial evaluation. The primary outcome was the pregnancy rate 12 months after the first workup. Secondary outcomes were insulin resistance, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), pre-diabetes, and type 2 diabetes mellitus (T2DM). Results: A total of 1,200 PCOS women were included in this study; of which, only 794 patients had complete data after 12-month follow-up. The mean age of patients was 29.2 ± 3.7 years. Mean BMI was 23.0 ± 4.0 kg/m2. Median VAI was 2.1 [1.3; 3.8]. Ongoing pregnancy rate was significantly lower in groups of women with higher VAI (47.9% in group with VAI of <1.5, 40.2% in 1.5-<3.0, 38.5% in 3.0-<4.5, and 33.9% in ≥4.5, respectively, P = 0.04). In addition, insulin resistance, IFG, IGT, and T2DM were found to be higher with increased VAI except for pre-diabetes. Conclusion: VAI has a negative impact on ongoing pregnancy and is associated with an increased risk of glucose metabolic abnormalities in infertile women with PCOS. Clinicians may use VAI as a predictor of pregnancy outcomes and GDM to advise these patients on their pregnancy care.
#313 : The Correlation Between Ultrasound Morphological Parameters and Phenotypes of Polycystic Ovary Syndrome in Indonesian Women
Authors: Lubis Hilma Putri , Halim Binarwan , Almon Willy Kurnia , Tala Muhammad Rhiza Z , Sukatendel Khairani , Alhair Tanzil 
Published: January 2024

Background and Aims: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age. Ultrasound morphological parameters of ovarian morphology, ovarian volume, follicle number, endometrial plate thickness, and doppler analysis are necessary for the diagnosis of PCOS. The aim of this study is to evaluate the correlation between ultrasound morphological parameters and classic and nonclassic phenotypes of PCOS in Indonesian Women. Method: A single-center, observational analytic study from May 2022 until October 2022 was performed upon 50 women with PCOS at Halim Fertility Center (HFC), Indonesia. Fifty PCOS women were classified into two groups: 20 PCOS women with classic phenotype and 30 PCOS women with non-classic phenotype. Data on patient’s age, body mass index (BMI), LH level, FSH level, LH: FSH ratio, Testosterone, Free testosterone index, SHBG, HOMA-IR, Ultrasound parameters (antral follicle count, follicle size, ovarian volume, stromal volume, Stromal/total area (S/A) ratio, Pulsatility index (PI), Peak systolic velocity (PS) and follicle distribution) were assessed and compared between the two groups. Results: The antral follicle count was higher in classic phenotype of PCOS than in nonclassic phenotype and there was a significant difference between the groups (p<0.05). The stromal volume and PI were higher in non-classic phenotype PCOS than in classic phenotype and there was significantly difference between the groups (p<0.05). Most of the follicle distribution in the classic phenotype of PCOS was central and the follicle distribution in the non-classic phenotype was peripheral and there was significantly difference between the groups (p<0.05). The number of antral follicles, stromal volume, PI, and follicle distribution were positively correlated with the PCOS phenotypes (r=0.734; r=0.594; r=0.577; r=0.196), respectively. Conclusion: Classic phenotype of PCOS in Indonesian women has high antral follicle count and central follicle distribution and nonclassic phenotype has high stromal volume, PI and peripheral follicle distribution.
#324 : Gasdermin D-Mediated Pyroptosis Underlies Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome
Authors: Huang Jiana , Zeng Haitao , Liang Xiaoyan , Zhou Chuanchuan 
Published: January 2024

Background and Aims: Intestinal microflora disturbance is one of the important etiologies of polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the mechanism of macrophage pyroptosis induced by intestinal microbiota disturbance in PCOS. Method: The PCOS mouse model was established using dehydroepiandrosterone, and was studied by 16S rDNA sequencing, western blot, ELISA, GSDMD gene knockout/oral pyroptotic inhibitors, single cell transcriptomics and translatomics analysis. Results: PCOS mice showed abnormal estrous cycle, elevated serum testosterone and polycystic ovaries. Fecal 16S rDNA sequencing showed that Muribaculacea (26.76%), and Lactobacillus (40.98%) were the most abundant microbe in the intestinal tracts of control mice and PCOS mice, respectively. Difference analysis showed a significant decrease in the abundance of intestinal probiotics Akkermansia and a significant increase in Gram-negative bacteria (Desulfovibrio and Burkholderia) in PCOS mice. Intestinal microbial disturbance in PCOS mice was associated with increased serum lipopolysaccharide (LPS). LPS intraperitoneal injection can induce pyroptosis of ovarian macrophages, which also exists in the ovaries of PCOS mice. The cleavage of GSDMD protein is the final key step in pyroptosis of macrophages. GSDMD knockout ameliorated PCOS in mice. Oral administration of pyroptotic inhibitors disulfiram and metformin can increase the abundance of intestinal Akkermansia, inhibit pyroptosis of ovarian macrophages and ameliorated PCOS in PCOS group mice. Mechanically, transcriptome and translatome sequencing of primary granulosa cells showed that pyroptosis of macrophages disrupted estrogen production and promoted granulosa cell apoptosis. Conclusion: This study revealed that macrophage pyroptosis induced by intestinal flora disorder can lead to the occurrence of PCOS through granulosa cell apoptosis and estrogen synthesis dysfunction. Macrophage pyroptotic inhibitors may be a potential therapeutic strategy for PCOS.
#325 : A Comparison of Three Different IVF FSH Dosing Strategies for PCOS Patients; A Retrospective Analysis of 855 IVF Cycles
Authors: Lahoud Robert , Venetis Christos , Whitton Kath , Agresta Franca 
Published: January 2024

Background and Aims: IVF responses to gonadotrophins may be difficult to predict in patients with PCOS. Nowadays there are various options including using the strategy of GnRH agonist trigger and freeze all embryos. The follitropin delta dosing algorithm has been used to predict an ovarian response that reduces the effects of ovarian hyperstimulation syndrome. The aim of this study was to compare the outcomes of three different FSH dosing strategies in PCOS patients. Methods: This retrospective multi-centre trial enrolled 626 PCOS women. They underwent 855 stimulated IVF cycles using a GnRH antagonist protocol and 634 frozen embryo transfers with embryos from the original stimulated cycles. Patients were classified into 3 groups: Group 1 (underdosing), Group 2 (algorithm dosing) and group 3 (overdosing). The algorithmic dose was based on the follitropin delta algorithm using AMH and body weight. The main outcome measure was the live birth rate per cycle started. Results: The live birth rate per cycle was 40.8% for group 1, 42.1% for group 2 and 45.5% for group 3. Group 3 had the greatest average number of embryos frozen (1.55 embryos in group 1, 2.45 group 2 and 2.96 group 3). The average number of eggs collected was greatest in group 3 (8.7 eggs in group 1, 11.9 group 2 and 14.2 group 3). The most frozen of all cycles occurred in group 3 (45.6%). Conclusions: Higher FSH dosing resulted in more eggs and more live births per cycle started. It also resulted in less fresh embryo transfers. These results could be used when choosing an FSH dosing strategy for PCOS patients.
#46 : Outcomes of Transfer Abnormally Chromosomal Embryos
Authors: Nguyen Truong Thai Ha , Huynh Bao G , Nguyen Duy L , Dao Thuy TH , Ho Tuong M 
Published: January 2024

Background and Aims: In some couples, there was no normal chromosomal embryos after preimplantation genetic testing (PGT) for aneuploidy (PGT-A), for structural chromosomal rearrangements (PGT-SR) or for monogenic (PGT-M). The couples decided to use the abnormal embryos for transfer after thorough genetic counselling. This study reports the outcomes of transfer abnormally chromosomal embryos. Method: This retrospective study was conducted from January 2020 to December 2022 at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. The abnormally chromosomal embryos that were considered for transfer included aneuploidy related to [Formula: see text]3 chromosomes (except trisomy 13, 18, 21 and monosomy X); or mosaicism has [Formula: see text]50% of aneuploidy after PGT-A, PGT-SR or PGT-M (except mosaic trisomy 13, 18, 21 and monosomy X). Results: 94 patients transferred 94 single abnormally chromosomal embryos. Out of 94 embryos, 62 were mosaic and 32 were aneuploid. Among the group of mosaic embryos, 25 (40.3%) had segmental, 32 (51.6%) had 1 or 2 chromosomal abnormalities and 5 (8.1%) had 3 or more. Among the group of aneuploid embryos, 4 (12.5%) had segmental, 13 (40.6%) had 1 chomosomal abnormalities, 5 (15.6%) had 2 chomosomal abnormalities and 10 (31.3%) complexes (both mosaic and aneuploid chromosome). Among 20 live births, 2 cases have normal fetal karyotype, and 11 cases have normal CNVs blood results. Conclusion: Mosaic embryos can be considered for transfer in cases having no normal embryos after PGT. More than 50% of babies born from chromosomally abnormal embryo transfer have normal chromosomal results.
#161 : Validation and Concordance of Non-Invasive Preimplantation Genetic Testing for Aneuploidy (niPGT-A) Using Cell Free DNA from Spent Culture Media (SCM) with Gold Standard Trophectoderm Biopsy
Authors: Singh Neeta , Sethi Ankita , Rani Lata , Gupta Ritu , Saini Monika 
Published: January 2024

Background and Aims: Recent studies suggests that cell free(cf)-DNA is secreted in the spent culture medium (SCM) during embryo development, this can be used as non-invasive approach for PGTA. We aimed to validate Non-invasive Preimplantation Genetic Testing for aneuploidies (niPGT-A) using cf-DNA from SCM Methods: Prospective cohort study, tertiary centre from January-August 2021-2022. A total of 23 aneuploid/high mosaic embryos were donated by couples who had Trophectoderm (TE) biopsy for aneuploidy testing. All aneuploid blastocyst (WB) that were donated for research were thawed and transferred to RNAase and DNAase free PCR tubes. DNA extraction and amplification are carried out using Sureplex DNA amplification system. Libraries prepared using VeriSeqTM PGS Library Prep kit. A total of 24 libraries were pooled, denatured subjected to Next Gen Sequencing (NGS) using MiSeq system. Copy Number Variation (CNV) visualization and analysis for each sample was carried out using BlueFuse Multi Software. Results: NGS results from SCM and TE were respectively used against same positive control to find out accuracy with corresponding WB. NGS profiles generated from aneuploid WB, were manually analysed for CNV. Quality control(qc) was performed using Illumina qc requirements, only samples satisfying were used for analysis. Out of 23 embryos, 14 were aneuploid and 9 were high mosaic based on TE biopsy. Out of 14 aneuploid blastocysts on TE biopsy, 9 (64%) showed corresponding aneuploidy (full chromosomal concordance) on WB NGS profile. The rest 5 showed aneuploidy or mosaicism of a different chromosome on WB NGS profile. Only 5 out of 23 (21.7%) had full chromosome concordance between SCM and WB. The ploidy concordance between WB vs TE and WB vs SCM was 100% and 69.5% (16/23), which was statistically significant (p[Formula: see text]0.05). The decreased ploidy concordance with SCM could be due to suspected maternal contamination. Conclusions: Aneuploidy testing using Cf DNA in SCM is a promising technique but needs more research.