bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-040 The characteristic of human seminal plasma extracellular vesicle (SPEVs) profiles with different sperm features in a large cohort of 309 Taiwanese men
Authors: Cheng Y , Lin Y  C , Chen H  Y , Hou H  C , Lin T  Y , Lin S  C 
Published: July 2024

Abstract

Study question
To investigate human seminal plasma extracellular vesicle profiles in different sperm characteristics and their potential clinical application.

Summary answer
Normozoospermic semen has significantly higher SPEV concentration than asthenozoospermic or oligozoospermic samples. Moreover, SPEV concentration was highly correlated with total motile sperm count.

What is known already
Seminal plasma extracellular vesicles (SPEVs) are cell-derived membrane structures that carry proteins, nucleic acid, and lipids, which can modify the constitution and biological function of sperm. However, the characteristics of SPEVs in different sperm features remained unclear.

Study design, size, duration
From January 2021 to September 2023, 309 men who visited the NCKUH andrology clinic agreed to collect semen samples for this study, which the Institutional Review Board has approved.

Participants/materials, setting, methods
Semen parameters were measured by the X1 CASA system (Bonraybio, Taiwan). SPEVs were isolated by size exclusion chromatography column and ExoQuick™. Next, the SPEVs’ concentration and size distribution were performed with nanoparticle tracking analysis. The Kruskal-Wallis test calculated comparison in multiple groups, and Dunn’s multiple comparison tests accessed group-group comparison. The Pearson correlation coefficient r of exosome concentration with individual sperm parameters was calculated. A p-value less than 0.05 was set as statistical significance.

Main results and the role of chance
Among them, 59 semen samples were presented with normozoospermia, 36 were oligozoospermia, 73 were asthenozoospermia, and 141 samples had no sperm in semen. Among these 141 azoospermic men, 89 men are characterized by non-obstructive azoospermia (NOA), while the other 52 men had a vasectomy. Our data showed that normozoospermic semen has significantly higher SPEV concentration than asthenozoospermic or oligozoospermic semen samples (26 x109 [IQR 17.25 x109-56.25 x109] versus 12 x109 [IQR 5.6 x109-19.5 x109] versus 15.5 x109 [IQR 8.575 x109-26.75 x109], p = 0.0001). Nevertheless, azoospermic semen has the lowest SPEV concentrations. The concentration of SPEVs from infertile men diagnosed with NOA is slightly lower than vasectomized men (3.9 x109 [IQR 1.875 x109-7.675 x109] versus 5.4 x109 [IQR 2.9 x109-8 x109], p = 0.0001). The Pearson r coefficient of SPEV concentration with sperm concentration, progressive motility, and total motile sperm count was 0.238, 0.303, and 0.451, respectively. (P &lt; 0.0001)

Limitations, reasons for caution
Because our data were collected from Taiwanese men, it is not yet known whether SPEV profiles differ among races.

Wider implications of the findings
Human SPEV concentration and its bio-content may be a potential non-invasive biomarker to predict the male reproductive outcome.

Trial registration number
not applicable
P-064 Adolescent varicocele: clinical profile and impact of treatment
Authors: Majzoub A , Fadol N , Elbardisi H , ElSaid S , AlMalki A , Khalafalla K , Ata Y , AlKubaisi K , Al Saeedi A , Arafa M 
Published: July 2024

Abstract

Study question
What is the clinical presentation of adolescent varicocele and the impact of its repair on semen quality?

Summary answer
Adolescent varicocele usually presents as testicular pain and does not influence semen quality. Varicocele ligation does not impact postoperative semen results in this patient population.

What is known already
Varicocele is a common condition characterized by the abnormal dilation of the pampiniform plexus of veins resulting in testicular dysfunction and impaired semen quality. While the effect of varicocelectomy on the fertility potential of adult men has been commonly explored, its impact on semen parameters of adolescents is less commonly investigated.

Study design, size, duration
The charts of 2171 patients who underwent microsurgical subinguinal varicocelectomy for clinically palpable disease between 2011-2023 were retrospectively reviewed. Patients &lt;19 years of age were included in the analysis.

Participants/materials, setting, methods
The patients’ medical charts were reviewed to include demographic and clinical characteristics; indication of surgery, body mass index, testis size, grade of clinical disease, vein diameter (assessed with scrotal ultrasound) and semen analysis results (WHO 2010). Data were analyzed using Wilcoxon Signed Ranked. Mean ± SD and median (IQR) were used to report normally and non-normally distributed data, respectively. A p value &lt;0.05 was considered significant.

Main results and the role of chance
A total of 94 adolescent patients were included in the study. Their mean BMI was 22.14±5 Kg/m2, mean left testis size was 12.26 ± 3.05 cm3 and right testis size 13.26±3.94 cm3. The maximum vein diameter 4.7±1.04 mm and right vein diameter 2.21±0.83 mm. 83 patients underwent unilateral Microsurgical Varicocelectomy while 5 patients underwent bilateral Microsurgical Varicocelectomy. Left varicocele was of grades 3, 2 and 1 in 65, 18 and 11 patients, respectively. Surgery was indicated for testis size discrepancy in 36.2% of cases and on elective basis (prior to army recruitment) in 63.8% of cases. Table 1 presents the pre- and post-operative semen parameter results. Patients had normal pre-operative medians of sperm count, total motility and normal morphology. No significant post-operative changes were observed in the semen quality of adolescents.

Limitations, reasons for caution
Results were obtained from a relatively small sample size. However, varicocele is less commonly performed on adolescents necessitating further studies on this patient population.

Wider implications of the findings
Results of this study shed the light on the characteristics of adolescents presenting with varicocele.

Trial registration number
NA
P-115 GATAD2B is required for pre-implantation embryo development by delaying zygotic genome activation
Authors: Cao G 
Published: July 2024

Abstract

Study question
Major zygotic genome activation (ZGA) involving the activation of thousands of genes occurs at the late-2cell stage, but the regulatory mechanisms governing ZGA remain unclear.

Summary answer
Our results demonstrate that GATAD2B is essential for early embryonic development, in part through facilitating zygotic genome activation (ZGA).

What is known already
Acetylation modifications of histone tails promote transcriptional activation, and the maternal deletion of H4K16ac leads to failure in ZGA. GATAD2B is one of the core subunits of the Nucleosome remodeling and histone deacetylation complex(NuRD).

Study design, size, duration
Using mouse embryos as the research model, the study was conducted over a period of approximately two years to ensure a relatively small-scale investigation.

Participants/materials, setting, methods
We examined the dynamic expression of NURD complex components, including GATAD2B, during pre-implantation embryonic stages. GATAD2B expression was specifically reduced via microinjection of GATAD2B-siRNA during the zygote stage, revealing its impact on early embryonic development in mice. Zygotic genome activation (ZGA), morula compaction, and blastocyst lineage differentiation were investigated using immunofluorescence, western blot, and other techniques. Additionally, we employed RNA-seq, protein immunoprecipitation, and mass spectrometry to uncover underlying molecular mechanisms.

Main results and the role of chance
Our research has shown that GATAD2B exhibits specific nucleus localization and high protein expression from the late-2-cell to 8-cell. This intriguing phenomenon prompted us to investigate the relationship between GATAD2B and the ZGA. We discovered a distinctive pattern of GATAD2B, starting from the late 2-cell stage with nuclear localization. GATAD2B depletion resulted in defective embryonic development, including increased DNA damage at morula, decreased blastocyst formation rate and abnormal differentiation of ICM/TE lineages. Consistent with the delay during the cleavage stage, the transcriptome analysis of the 2-cell revealed inhibition of the cell cycle G2/M phase transition pathway. Furthermore, the GATAD2B proteomics data provided clear evidence of a certain association between GATAD2B and molecules involved in the cell cycle pathway. As hypothesized, GATAD2B-deficient 2-cell embryos exhibited abnormalities in ZGA during the maternal-to-embryonic transition, with lower expression of the major ZGA mark MERVL.

Limitations, reasons for caution
Given the limitations of antibody effectiveness and specificity required for the experiments, the exploration of molecular mechanisms is still ongoing.

Wider implications of the findings
Our findings have elucidated the impact of GATAD2B on early embryonic development through the regulation of zygotic genome activation (ZGA), providing a novel genetic explanation for clinical defects in early embryonic development.

Trial registration number
not applicable
P-127 The RNA m6A landscape of mouse oocytes and preimplantation embryos
Authors: Li Y 
Published: July 2024

Abstract

Study question
Despite the significance of N6-methyladenosine (m6A) in gene regulation, the requirement for large amounts of RNA has hindered m6A profiling in mammalian early embryos.

Summary answer
We apply picoMeRIP-seq to map m6A in mouse oocytes and preimplantation embryos. We define the landscape of m6A during the maternal-to-zygotic transition.

What is known already
N6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic messenger RNA (mRNA), plays key regulatory roles in many biological processes (for example, RNA stability, splicing, transport and translation) and is involved in a variety of physiological processes (for example, cell differentiation and reprogramming, embryonic development and stress responses).

Study design, size, duration
We recently developed an m6A mapping assay for low RNA input, low-input methyl RNA immunoprecipitation and sequencing (picoMeRIP-seq), which enables mapping of the m6A methylome using a low number of cells. In this article, we applied picoMeRIP-seq to multiple developmental stages of mouse oocytes and early embryos to profile their m6A landscapes.

Participants/materials, setting, methods
We use mouse as study materials.Using picoMeRIP-seq, we generated transcriptome-wide m6A maps for six stages (GV, MII, zygote, two-cell, eight-cell and blastocyst), with two biological replicates per stage and 49–110 oocytes/embryos per replicate.

Main results and the role of chance
We define the landscape of m6A during the maternal-to-zygotic transition, including stage-specifically expressed transcription factors essential for cell fate determination. Both the maternally inherited transcripts to be degraded post fertilization and the zygotically activated genes during zygotic genome activation are widely marked by m6A. In contrast to m6A-marked zygotic ally-activated genes, m6A-marked maternally inherited transcripts have a higher tendency to be targeted by microRNAs. Moreover, RNAs derived from retrotransposons, such as MTA that is maternally expressed and MERVL that is transcriptionally activated at the two-cell stage, are largely marked by m6A. Our results provide a foundation for future studies exploring the regulatory roles of m6A in mammalian early embryonic development.

Limitations, reasons for caution
The effect of m6A on the turnover of retrotransposon-derived transcripts abundant in oocytes and early embryos needs to be further addressed in future studies.

Wider implications of the findings
Our results provide a foundation for future studies exploring the regulatory roles of m6A in mammalian early embryonic development.

Trial registration number
not applicable
P-137 A deep learning model using time-lapse imaging data to predict successful clinical pregnancy and embryo euploidy
Authors: Maekawa R , Tanaka A , Kuramoto T , Sugino N 
Published: July 2024

Abstract

Study question
Are the deep learning models helpful in selecting embryos with a high probability of clinical pregnancy and euploidy from time-lapse imaging during embryo growth?

Summary answer
Our deep learning models using time-lapse imaging data predicted the probabilities of successful clinical pregnancy and euploidy of embryos with high accuracy.

What is known already
Recent studies have attempted to select the most viable embryo using deep learning of time-lapse imaging during incubation. However, most studies included embryos that were not transferred due to low evaluation by the embryologist as embryos with unsuccessful pregnancies, or they mixed single and multiple embryo transfer cases in the analyses. Some studies’ algorithms rely on humans’ subjective interpretation of morphological and morphokinetic features, leading to embryologist-to-embryologist and within-embryologist variabilities. Some reports, including the study predicting embryo aneuploidy, used a snapshot image for prediction. These approaches have restricted the potential of deep learning in embryo selections.

Study design, size, duration
Retrospective analyses of time-lapse videos of 2,192 embryos with clinical pregnancy outcomes, defined as confirmed gestational sacs in utero, and 1,467 embryos with karyotype outcomes examined by preimplantation genetic testing for aneuploidy (PGT-A). The data were obtained from two different in-vitro fertilization clinics between November 2017 and December 2021. All transfers were performed as a single embryo transfer.

Participants/materials, setting, methods
The deep learning model was trained using time-lapse videos with known clinical pregnancy outcomes for predicting the probability of clinical pregnancy with given time-lapse video sequences and patient ages (CP model). Another deep learning model was trained using time-lapse videos with known karyotype outcomes by PGT-A for predicting the probability of euploidy (AP model). The models’ predictive powers were measured using the average area under the curve (AUC) of the receiver operating characteristic curve.

Main results and the role of chance
The CP model predicted clinical pregnancy with an AUC of 0.693. The AP model predicted embryo aneuploidy with an AUC of 0.702.

Limitations, reasons for caution
The CP model is based on the embryos that were transferred because the embryologist judged them as having a high probability of pregnancy. Clinical pregnancy may be associated with maternal factors besides embryo factors.

Wider implications of the findings
Our two deep learning models, the CP and AP models, will be helpful for selecting the embryos to be transferred. The CP model may increase pregnancy rates in patients undergoing assisted reproductive technology. The AP model may reduce the miscarriage caused by embryo aneuploidy.

Trial registration number
not applicable
P-280 Influences of CD8(+) tissue resident memory T cells on eutopic endometrial immune microenvironment and endometrial receptivity of minimal/mild endometriosis
Authors: Huang X , Wei H 
Published: July 2024

Abstract

Study question
Our study aimed to focused on the influence of CD8+ tissue resident memory T cells (CD8+ TRM) on endometrial immune microenvironment and endometrial receptivity.

Summary answer
CD8+TRM participated in inflammatory endometrial immune microenvironment, influenced expression of endometrial receptivity and decidualization markers of stromal cells of eutopic endometrium of minimal/mild endometriosis.

What is known already
CD8+ tissue resident memory T cells (CD8+ TRM) are abundant in endometrium,CD8+ TRM have important physiological functions and of pathological significance in endometrium.

Study design, size, duration
Endometrial samples were collected using Pipelle sampling from women with or without endometriosis (minimal/mild) during hysteroscopy-laparoscopy. Tissue for immunofluorescence was fixed in 4% paraformaldehyde, for cell analysis was isolated into single cell immediately.

Participants/materials, setting, methods
We analyzed number variation, tissue location, cytotoxicity, degranulation and cytokine secretion of CD8+TRM in endometriosis and control during menstrual cycle through flow cytometry and polychromatic tissue immunofluorescence. We cocultured CD8+TRM and endometrial stromal cell to know the influence of CD8+TRM to endometrial receptivity and decidualization. The concentration of TNF-α, IFN-γ, IGFBP-1 and PRL were analyzed via ELISA and q-PCR. Western blot and q-PCR were used to test the expression level of HOXA10 and FOXO1.

Main results and the role of chance
Flow cytometry founded that the number of CD8+TRM in proliferative phase were more than secretory phase in both endometriosis and control. CD8+TRM were not only scattered in stroma of endometria, and also gathered in lymphoid aggregates. During secretory phase, the cytotoxicity, degranulation, and inflammatory cytokine expression resourced from CD8+ TRM were higher in endometriosis than control. CD8+TRM inhibited the expression of endometrial receptivity markers (HOXA10 and FOXO1) and decidualization markers (IGFBP-1 and PRL) of endometrial stromal cells in coculture system. When blocking the IFN-γ in coculture system, the expression of endometrial receptivity markers and decidualization markers were improved.

Limitations, reasons for caution
The mechanism of CD8+TRM influence on endometrial receptivity and decidualization of endometriosis is needed to further investigation.

Wider implications of the findings
CD8+TRM participated in inflammatory endometrial immune microenvironment, influenced expression of endometrial receptivity and decidualization markers of stromal cells of eutopic endometrium of minimal/mild endometriosis. CD8+TRM and its secretion of IFN-γ could be immunotherapeutic target for defective endometrial receptivity of endometriosis.

Trial registration number
NA
P-503 Euploidy rate of day 4 fully developed blastocysts
Authors: Kato M , Tsuji H , Ooyama K , Takahashi M , Kudo C , Ikuta S , Fukunaga N , Asada Y 
Published: July 2024

Abstract

Study question
Do embryos that fully developed to blastocyst at day 4 have high aneuploidy rates as assessed by preimplantation genetic analysis?

Summary answer
Fully developed blastocysts at day 4 had a high euploidy rate.

What is known already
In ART, it is considered important to use good quality blastocysts to increase the pregnancy rate after embryo transfer. Some reports have demonstrated a high pregnancy rate for embryos that fully developed to blastocysts on day 4 after IVF (Ozgur et al., 2021). Furthermore, it has been reported that the speed of embryo development is related to the rate of chromosome aneuploidy (Taylor et al., 2014). There are though, limited reports on the euploidy rate of embryos developed to blastocysts at day 4.

Study design, size, duration
This retrospective study analyzed 763 embryos (from 184 PGT-A cases) that underwent TE biopsy on day 5 between January to December 2022 to determine their ploidy status.

Participants/materials, setting, methods
Embryos cultured in a time-lapse incubator were divided into two groups: those that developed to blastocyst (Gardner’s classification: ≥ expansion grade 3) at day 4 (96-100 h) (D4(+) group) and those that did not develop to full blastocyst at day 4 (D4(-) group) and the euploidy rates were compared. Statistical analysis was performed using Fisher’s exact test to determine significant differences (P &lt; 0.05).

Main results and the role of chance
The euploidy rate of the D4(+) group was 36.5% (80/219), which was significantly higher than the D4(-) group, 23.3% (127/544) (p &lt; 0.01). Moreover, when considering the age of the female, for age ≤39 years, the rates were significantly higher in the D4(+) group (52.1% (61/117) and 35.4% (97/274) p &lt; 0.01 respectively ). For age 40≥ years, it tended to be higher but was not significantly different in the D4(+) group vs D4(-) group (18.6% 19/102 and 11.1% 30/270 respectively). Even when limited to embryos that were graded as good quality blastocysts at day 5, the D4(+) group was significantly higher (p &lt; 0.01) than the D4(-) group (55.0% (60/109) vs 36.1% (90/249)).

Limitations, reasons for caution
This was a retrospective study limited to day 5 embryos with biopsies taken after vitrification-warming.

Wider implications of the findings
These results demonstrate that embryos that had already developed to blastocyst at day 4 had a higher rate of euploidy compared to day 5 blastocysts. Thus, when performing PGT-A, biopsy of embryos that have already developed to blastocyst at day 4 are expected to be prioritised for transfer.

Trial registration number
not applicable
P-514 Unequal pronucleus size is indicative of higher rates of diploidy in 3PN blastocysts
Authors: Stock-Myer S , Kelley R , Lee L  Y S , Agresta F , Gurner K , Williams C , Liew I , Demmers K , Lee E , Knight C , Cattrall F 
Published: July 2024

Abstract

Study question
What proportion of blastocysts developed from 3PN embryos are diploid, and is this associated with the relative size of the pronuclei?

Summary answer
Most 3PN blastocysts with even-sized pronuclei are triploid, while most 3PN blastocysts with uneven-sized pronuclei are diploid.

What is known already
Fertilised oocytes with three pronuclei (3PN, or tripronuclear) are generally considered unsuitable for use due to the high likelihood of triploidy, which is not compatible with an ongoing healthy pregnancy. Recent data on 3PNs with uneven-sized pronuclei (micro-3PN, or 2.1PN) indicates that many may actually be diploid if they form a good quality blastocyst.

Study design, size, duration
Prospective multi-centre study from October 2020 to December 2023. 81 3PN blastocysts from 69 patients were biopsied.

Participants/materials, setting, methods
ICSI-inseminated embryos were assessed on Day 1 and pronuclear size at 18 h post insemination was measured using EmbryoViewer software. Biopsy was performed at the blastocyst stage and genetic testing was performed using the Human Karyomap-12 SNP array to ascertain ploidy status. Pronuclei were classified as “Equal”, “Unequal” (smallest pronucleus is 61%-75% of the largest), or “Micro” (smallest pronucleus is &lt; 60% of the largest).

Main results and the role of chance
94% of the 3PN blastocysts with equal size pronuclei were triploid, and the remaining 6% were complex aneuploid or had genome wide uniparental disomy (n = 36). Of the 3PN blastocysts with unequal pronuclei (n = 19), 42% were triploid, whereas none of the embryos with a micro pronucleus were triploid (n = 26).

Limitations, reasons for caution
Only 3PN embryos that formed a good quality expanded blastocyst were biopsied. Only ICSI-inseminated embryos were included, not IVF. No 3PN embryos were transferred in the study, so any additional pregnancy and birth risks from diploid 3PN embryos are unknown.

Wider implications of the findings
Blastocysts that develop from 3PN oocytes with uneven pronuclei have a greater than 80% chance of diploidy and could be considered for clinical use with PGT. More data is needed to inform clinical guidelines.

Trial registration number
N/A