bluuebunny/crossref_metadata_2025 huggingface dataset:
#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.
#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.
#75 : Mechanisms and Active Ingredients of Chinese Herbal Medicine on Ameliorating Endometriosis-Associated Pain
Authors: Lin Yuezhen , Wang Chi Chiu
Published: January 2024

Background and Aims: Chinese herbal medicines (CHMs) have been effectively used to treat the endometriosis-associated pain (EAP), but its pharmacological and molecular mechanism remains unclear.

In this study, we aim to use a network pharmacology-based approach to identify the potential therapeutic targets and active ingredients of CHM for EAP, and to verify their pharmaceutical actions on an experimental mouse model.

Method: Pharmacological networks of 3 common CHM formulae for endometriosis (HXXYF, SFZYT and GXZYT) were built by targets collated from public databases, and the enrichment molecular pathway analysis was applied to select the potential pharmacological targets and CHM active ingredients. Pain assessments on the experimental mouse model were performed to evaluate efficacy of the CHM formulae and potential active ingredients. RT-PCR and immunostaining in endometriotic lesions were used to confirm the expression of the potential targets after treatment.

Results: ‘Inflammatory mediator regulation of TRP channels’ was a major molecular pathway with highest significance in pharmacological network and enrichment analysis. In mouse, 2 CHM formulae, HXXYF and SFZYT, significantly reduced pain responses, while pain-related inflammatory mediators, IL1[Formula: see text] and PGE2, were significantly decreased after treatment. Meanwhile, densities of nerve fibers in lesions were significantly lower as well, with significantly lower expressions of TRPA1 and TRPV1. 3 CHM ingredients (baicalein, paeoniflorin and quercetin) with highest degree in pharmacological network were then selected for in-depth investigation. However, only paeoniflorin significantly reduced stimuli-evoked and non-stimuli-evoked pain in mice, along with effective reduction in all above parameters.

Conclusion: Our study demonstrated multi-targets effects of CHM on EAP relief through inflammatory and neuropathic pathways, which supports CHM as alternative or complementary therapy for EAP. The active ingredients from CHM may provide a novel drug development and approach for EAP treatment.
#95 : Analysis of the Incidence of and Risk Factors for Chronic Endometritis Recurrence in Infertile Women
Authors: Shiobara Keisuke , Kuroda Keiji , Ishiyama Shunsuke , Nakao Kazuki , Moriyama Azusa , Horikawa Takashi , Takamizawa Satoru , Nakagawa Koji , Sugiyama Rikikazu
Published: January 2024

Background and Aims: Chronic endometritis (CE) is an inflammatory condition of the endometrium which is related to repeated implantation failure. Recovery from CE can increase opportunities for successful pregnancy; however, some of them remain incapable of conceiving or have a miscarriage and concern CE recurrence. The aim of this study is to identify the incidence rates of and risk factors for the recurrence of CE in infertile women.

Method: The study population consisted of 1,897 infertile women from a hospital specializing in reproductive medicine who recovered from CE between December 2018 and August 2021. Among the 152 women (13.0%) who did not conceive or experienced pregnancy loss, 105 consecutive women who underwent repeat endometrial biopsy for CD138 immunostaining and endometrial bacterial culturing within 18 months from CE recovery were recruited. Thereafter, patients with and without CE recurrence were compared.

Results: The total recurrence rate of CE was 29.5% (31 women). Multivariable logistic regression analysis to determine risk factors for CE recurrence revealed that hysteroscopic surgery (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.02–0.56) and pregnancy loss (OR, 4.13; 95% CI, 1.31–13.05) were significantly associated with decreased and increased CE recurrence rates, respectively. Also, re-examination with CD138 immunostaining after 16–18 months (OR, 9.75; 95% CI, 1.47–64.64) was significantly associated with increased CE recurrence rates. Among 40 patients without a history of hysteroscopic surgery and pregnancy loss, the cumulative CE recurrence rates after 6, 12, and 18 months were 12.5%, 23.3%, and 30.0%, respectively (Graph 1).

Conclusion: We recommend re-examination with endometrial CD138 immunostaining in patients with pregnancy loss or long-term infertility during fertility treatment. Hysteroscopic surgery without antibiotic therapy for CE associated with intrauterine abnormalities is also recommended.
#213 : Causal Associations Between Different Plasma Lipid and Apolipoprotein Parameters with the Risk of Endometriosis: A Two-Sample Mendelian Randomization Study
Authors: Yang Shuhan , Zhang Yaoyao , Hu Ying , Guo Weijie
Published: January 2024

Background and Aims: Endometriosis is a chronic gynecological disease with a high prevalence among reproductive-aged women. Several studies have investigated the causal effect of different plasma lipid and apolipoprotein parameters on the occurrence and progression of endometriosis. However, the results of these studies remained controversial. Herein, this study aims to analyze the causal associations of genetically predicted levels of different blood lipid and apolipoprotein traits with the risk of endometriosis using a two-sample Mendelian randomization (MR) approach.

Methods: The single-nucleotide polymorphisms (SNPs) of exposures which indicate the genetic variants were used as instrumental variables (IVs). We assessed the correlation between each blood lipid and apolipoprotein parameter and the occurrence of endometriosis from various cohorts of European ancestry, and the SNPs of them were obtained from the genome-wide association study (GWAS) from the IEU GWAS database. The causal effects were estimated through the inverse-variance weighted method (IVW). The sensitivity examinations of each result after the MR analysis were performed to detect if any heterogeneity and pleiotropy existed. Besides, sub-analyses were performed to provide more detailed information about the actual associations.

Results: Our results demonstrated that cholesterol in chylomicron (CM) and extremely large very low-density lipoprotein (VLDL) was causally linked to higher odds of endometriosis, while high-density lipoprotein (HDL) cholesterol showed the opposite correlation. No evidence was detected on the causal relations of low-density lipoprotein (LDL) cholesterol, VLDL cholesterol, triglyceride (TG), apolipoprotein A1 and apolipoprotein B with endometriosis. Neither pleiotropy nor heterogeneity was found in our study. In addition, subgroup analyses about subtypes of endometriosis suggested the causal association of several serum lipids with peritoneal endometriosis.

Conclusion: Our results suggested that dysregulated lipid metabolism is causally associated with the occurrence of endometriosis, especially peritoneal endometriosis. Our findings provided genetic insights on potential novel strategies in the primary prevention and treatment of endometriosis.
#219 : Comparative Efficacy and Safety of Interventions for Pain and Quality of Life in the Treatment of Endometriosis: A Network Meta-Analysis
Authors: Gibbons Tatjana , Leonardi Mathew , Stocking Katie , Vail Andy , Kuan Kevin , Lunky Isis , Liu Marina , Sekhon Jasleen , Schreurs Anneke , Shamsa Aiat , Ong Joz , Jung Albert , Cave Adele , Amour Mike , Hao Jessie , Yang Guoyan , Jacobson Tal , Hull Louise , Hodgson Ruth , Glanville Elizabeth , Mijatovic Velja , Becker Christian , Condous George , Johnson Neil
Published: January 2024

Background and Aims: Numerous endometriosis treatments exist, ranging from surgical to traditional medications to complementary and alternative medicines (CAMs). The ranking of treatments across management categories remains unknown. To address this research gap, this network meta-analysis (NMA) aims to rank endometriosis treatments in terms of efficacy and safety for endometriosis-related pain and quality of life.

Method: A systematic literature search and fixed effects NMA was conducted. Eight databases were searched from inception to August 2022. All randomised control trials (RCTs) in women with surgically confirmed endometriosis were considered.

Results: After screening 8,668 studies, 165 RCTs were included, consisting of 26,762 participants, investigating 48 medical, 13 CAMs and 16 surgical interventions. Preliminary analysis of the CAMs interventions (9 RCTs, n=522) suggested acupuncture (SMD -1.96; 95%CI: -2.63, -1.29), olive oil (SMD -1.68; 95%CI: -2.69, -0.67), fatty acid supplements (SMD -1.48; 95% CI: -2.15, -0.81), contraception + Chinese medicines (SMD -1.28; 95%CI: -2.39, -0.16), Chinese medicine (SMD -0.91, 95%CI: -1.78, -0.04) and vitamin C&E (SMD -0.38; 95%CI -0.89, 0.13) demonstrated a reduction in pain compared to placebo. There was insufficient evidence to detect a difference in pain using Vitamin D compared to placebo (SMD 0.09 95% CI: -0.55, 0.73). Complete results, including the individual and combined categories within a Bayesian framework and intervention ranking, will be available for ASPIRE 2023.

Conclusion: This is the first NMA to compare the evidence of all endometriosis treatments. The findings have the potential to guide treatment decisions and guideline development.
#222 : Exosomes Derived of Menstrual Blood Stem Cells Suppress IUA Endometrial Fibrosis Through P65-UBR4-YAP Pathway
Authors: Tan Jichun , Qi Jiarui , Zhang Xudong
Published: January 2024

Background and Aims: IUA is the second leading cause of secondary infertility in women, and it is urgent to find a new therapeutic method to achieve functional regeneration of endometrial. We previously found that menstrual blood stem cells (MenSCs) transplantation could improve endometrial fibrosis and restore fertility in IUA rats through exosomes (MenSCs-exos). We identified UBR4 as an E3 ubiquitin ligase that was abundantly enriched in MenSCs-exos by mass spectrometry sequencing, however, the role of UBR4 in MenSCs-exos treatment of IUA and the potential molecular mechanism remains unclear.

Method: IUA rats and endometrial stromal cells (EndoSCs) of IUA patients were treated with knock-down UBR4 exosomes (EXOUBR4−) and normal exosomes (EXO). HE staining and Masson staining were used to evaluate endometrial morphology and fibrosis area. The expression levels of fibrotic indicators COL I and CTGF were detected. The molecular mechanisms by which UBR4 in MenSCs-exos alleviate EndoSCs fibrosis were then explored using immunofluorescence, western blot, and co-immunoprecipitation. The molecular mechanism of transcription factor P65 regulating the expression of UBR4 were explored using ChIP and dual luciferase.

Results: MenSCs-exos could significantly restore the endometrial morphology of IUA rats, increase endometrial thickness and number of glands, and reduce the endometrial fibrosis area, however reducing the content of UBR4 in MenSCs-exos would alleviate its therapeutic effect on IUA rats. UBR4 in MenSCs-exos reduced the expression levels of COL I and CTGF through significantly decreasing the expression level of YAP by specifically ubiquitin-degrading YAP. In addition, P65 could bind to the UBR4 promoter region to transcriptionally promote the expression level of UBR4 in MenSCs.

Conclusion: This study clarified that UBR4, as the key molecule in repairing IUA fibrotic endometrium by MenSCs-exos, could inhibit endometrial fibrosis by ubiquitin-degrading YAP, while transcription factor P65 could promote the expression level of UBR4 in MenSCs by directly binding to the UBR4 promoter region.
#265 : Oocyte Outcome After Laparoscopy Cyst Drainage Procedure Before IVF Stimulation in Endometriosis Patients
Authors: Susanto Cynthia Agnes , Syahbana Luky Satria , Lie Vellyana , Wiweko Budi
Published: January 2024

Background: Endometriosis is the presence of endometrial-like tissue outside the uterine cavity. In late years, in order to control endometriosis, we often performed cystectomy either laparoscopy or laparotomy. However, cystectomy done in endometriosis patient undergoing IVF can decrease the AMH also the quality of the oocytes, thus cyst drainage procedures (with the insertion of hemostate agent) was considered as a replacement for cystectomy in endometriosis patients before they begin the IVF stimulations.

Aims: To see the effect of laparoscopic cyst drainage with the insertion of an absorbable hemostate towards the quality of the oocytes in endometriosis patient

Method: A retrospective cohort study took place at Center of Reproductive Medicine and Andrology Bocah Indonesia in Primaya Hospital, Tangerang between January 2021 and December 2022. Patients with endometriosis cysts before IVF stimulations were all included. Excluded were those declining to participate and with incomplete case notes. All of the subjects used ultra-long GnRH agonist protocols. A medical committee approved the study and all women provided written informed consent.

Results: 18 patients were included in the analysis (11 undergoing laparoscopy cyst drainage and insertion absorbable hemostatic agent’s vs 7 undergoing only cystectomy). There was a statistically significant difference in AMH values in patients with cystectomy vs drainage with an absorbable hemostatic agent in AMH values 1.002 ± 0.76 to 0.77 ± 0.76 vs 1 (0.30 – 3.31) to 1 (0.30 – 4.00) (p=0.003 vs p =0.678). Among those, there was no significant difference between cystectomy and drainage with the maturation of oocyte (p=0.231 vs p=0.381). On the other side, there was a significant difference between cyst drainage and cystectomy resulting in good embryos in cleavage (p=0.038). One of the patients has a naturally conceive pregnancy after a cyst drainage procedure.

Conclusion: Endometriosis with laparoscopic cyst drainage procedure can maintain AMH level, reduce inflammation, and proliferation of lesions so it can maintain better quality of oocytes.