bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-058 Metabolism, histone modification and early embryo development
Authors: Li J 
Published: June 2023

Abstract
Cellular metabolism provides fundamental components for chromatin dynamics and epigenetics. However, metabolic features, and their impact on epigenetic remodeling during mammalian pre-implantation development, remain poorly understood. In this study, we established the metabolic landscape of mouse pre-implantation embryos from zygote to blastocyst, and quantified their absolute carbohydrate metabolites. We found that amino acid/carbohydrate/lipid metabolism increased during pre-implantation development, whereas nucleotide metabolism increased at the 4- and 8-cell stages. We further demonstrated that oxidized nicotinamide adenine dinucleotide (NAD+) is indispensable for mouse pre-implantation development. Mechanistically, NAD+ avoids excessive minor zygotic gene activation (ZGA) by cooperating with deacylase SIRT1 to remove zygotic H3K27ac. In human, NAD+ supplement can promote the removal of zygotic H3K27ac and benefit preimplantation development. Our findings demonstrate that precise and timely regulation of minor ZGA is controlled by metabolic dynamics, and enhance our understanding of the metabolism of mammalian early embryos.
O-073 Delta-9-THC acts on the calcium channel CatSper and alters human sperm function
Authors: Wehrli L , Zufferey F , Rossier M , Nef S , Rahban R 
Published: June 2023

Abstract

Study question
Do the main psychoactive phytocannabinoid delta-9-tetrahydrocannabinol (THC) and its non-psychoactive analog cannabidiol (CBD) affect human sperm function?

Summary answer
THC reduces the ligand-dependent activation of sperm-specific Ca2+ channel CatSper and affects human sperm functions in vitro.

What is known already
Marijuana (Cannabis sativa) is one of the most commonly used recreational drugs worldwide. Although the impact of phytocannabinoids on reproductive health has been investigated, there is no evidence of a direct effect of THC on CatSper function.

Study design, size, duration
We studied the effects of the main psychoactive phytocannabinoid, THC, its non-psychoactive analog, CBD, as well as their major metabolites on Ca2+ influx via CatSper in human spermatozoa. THC and CBD were selected to further evaluate their action on progesterone-, prostaglandin-, and pH-induced activation of human CatSper. The effects of THC and CBD on hyperactivation, progressive motility in viscous media, and acrosomal exocytosis were also assessed.

Participants/materials, setting, methods
The impact of phytocannabinoids on CatSper activity was investigated on sperm samples from healthy volunteers using kinetic Ca2+ fluorimetry. Motility assessment was performed using Computer-Assisted Sperm Analysis (CASA). Sperm penetration into viscous media was assessed using a modified Kremer test. Acrosomal exocytosis was evaluated by flow cytometry using Pisum sativum agglutinin-stained spermatozoa.

Main results and the role of chance
Both THC and CBD suppress natural ligand-induced calcium influx via CatSper. In particular, THC inhibits progesterone-induced Ca2+ influx via CatSper at pharmacologically relevant concentrations in a non-competitive manner and reduces the pH-induced activation of CatSper. In addition, THC impaired sperm hyperactivation and penetration into viscous media and induced spontaneous acrosomal exocytosis in vitro.

Limitations, reasons for caution
This is an in vitro study. Future studies are needed to test the physiological relevance in vivo and whether THC can disrupt human sperm function.

Wider implications of the findings
The action of THC on CatSper in human sperm might impair the fertilization process. Healthcare providers, especially fertility clinicians, should be aware of the potentially negative effects of cannabis consumption on sperm physiology

Trial registration number
not applicable
P-685 Extracellular vesicles of human follicular fluid as biomarkers of ovarian disease
Authors: Chiechio R , Moulin G , Neyroud A S , Ducarre S , Ouzaid Y , Dupont A , Even-Hernandez P , Le Cornu Q , Marchi V , Ravel C 
Published: June 2023

Abstract

Study question
Our aim is to analyze the morphology of follicular fluid extracellular vesicles (EVs) according to ovarian pathology by labeling the vesicles with luminescent gold nanoclusters.

Summary answer
Cryo-TEM analysis reveals that EVs from the follicular fluid of patients presenting with polycystic ovary syndrome have a particularly complex morphology compared to normo-ovulatory women.

What is known already
EVs are particles enclosed by a lipid membrane and secreted by cells. Previously considered as cellular debris, they are in fact involved in a multitude of biological functions and are potential biomarkers. Development of an optical biosensor based on luminescent nanoparticles would make it possible to analyze them in biological fluids.

Study design, size, duration
Samples were provided by GERMETHEQUE, Biobank dedicated to human fertility. Samples from 32 patients presenting with ovarian pathology (ovarian failure, polycystic ovary syndrome) and 32 normo-ovulatory patients were analyzed.

Participants/materials, setting, methods
Luminescent gold nanoclusters (1 to 2 nm in diameter) have been synthesized and functionalized in order to interact with extracellular vesicles. Analysis of the morphology of EVs was carried out by cryoTEM. Qualitative results were analyzed by Chi2 or Fisher tests. The quantitative results were analyzed by the Kruskal Wallis test.

Main results and the role of chance
The interactions between luminescent gold nanoclusters and lipid membranes show that it is possible to induce electrostatically and in a controlled manner either significant structural changes in the membranes or membrane labeling. Patients presenting with ovarian pathology have more oval vesicles (p = 0.0014). Differences are especially significant in polycystic ovary syndrome showing that simple vesicles are less abundant than controls (p &lt; 0.0001) and large tubules more frequent (p = 0.0023).

Limitations, reasons for caution
The first results concerning the interactions between luminescent nanoclusters and vesicles demonstrate their potential for labeling these membrane structures

Wider implications of the findings
The characterization of these anomalies could allow a better understanding of ovarian pathology and open up new therapeutic fields. An efficient method of encapsulation in liposomes of gold nanoclusters has been developed.

Trial registration number
GERM 20220705
P-686 Long photoperiod exposure results in glycometabolism disorder in the cumulus-oocyte complex in SD rats
Authors: Ying Y , Yao S , Chen X , Zhang D 
Published: June 2023

Abstract

Study question
Does long photoperiod exposure cause glycometabolism changes in the cumulus-oocyte complex?

Summary answer
The levels of key enzymes and substrates involved in glycometabolism have changed in the cumulus-oocyte complex in SD rats due to circadian rhythm changes.

What is known already
Circadian rhythm is essential for maintaining the required reproductive activities in mammalians. In our previous research, long photoperiod exposure results in the reduction of ovulation number and the increase of ROS level in oocytes. In the process of oocyte maturation, the tricarboxylic acid cycle and energy metabolism gradually increase, while the ability of the oocyte to absorb glucose is low. It is mainly metabolized by cumulus granulosa cells into pyruvate and then transported to oocytes for subsequent metabolism. Metabolomics is a comprehensive analysis of small molecules, which provides key information about cellular metabolic states.

Study design, size, duration
Female SD rats, 6-8 weeks old, were randomized into two groups. The rats (n = 20) were exposed to the control photoperiod (12 hours light/12 hours dark) or long photoperiod (16 hours light/8 hours dark) for 12 weeks.

Participants/materials, setting, methods
Cumulus-oocyte complexes were collected after ovarian stimulation and numbers were counted. The parameters compared include MII rate, fertilization rate, and ovarian follicle number. We used mass spectrometry-based metabolomics to directly measure metabolite abundance. The glycometabolism pathway and its regulatory signaling molecules were analyzed by qPCR and/or Western blots.

Main results and the role of chance
Long photoperiod exposure significantly reduced the ovulation rate, MII rate and fertilization rate. Interestingly, we find secondary follicle and antral follicle were decreased (p &lt; 0.01), while primordial follicle and primary follicle were increased (p &lt; 0.01). We identified a total of 318 metabolites in COC. Among them, 59 metabolite levels have significant differences between the two groups (FDR &lt; 0.05). The metabolical function analysis suggested that the phosphatidylinositol phosphate metabolism, pyruvate metabolism, phosphatidylcholine biosynthesis, and glycolysis pathways were influenced by circadian interference. In addition, hexokinase, glucose-6-phosphate isomerase, phosphofructokinase glyceraldehyde 3-phosphate expression level were down regulated.

Limitations, reasons for caution
More studies are required to address how clock gene regulating glycometabolism process. And Translating results in rat model to the human setting is a limitation of this study.

Wider implications of the findings
Our study findings are first to demonstrate that glycolmetabolism is regulated by long photoperiod exposure in follicle development. This knowledge could help to develop strategies to modulate specific recovery strategies based on metabolic regulator to improve human IVF.

Trial registration number
Not applicable
P-688 The relationship between higher levels of serum AMH and in vitro fertilization outcomes
Authors: Albu A , Iancu E M , Albu D 
Published: June 2023

Abstract

Study question
What is the relationship between increased serum anti-mullerian hormone (AMH) levels and in vitro fertilization (IVF) outcomes in women with infertility?

Summary answer
High levels of AMH are associated with higher oocytes and embryo number, but a lower proportion of GQE from the transferred and the total number.

What is known already
Although serum AMH level is considered a predictor of ovarian response to controlled ovarian stimulation, the predictive value of higher AMH levels is not clearly established due to contradictory reports, with both positive and negative associations with IVF outcomes.

Study design, size, duration
We performed a retrospective study in the Department of Reproductive Medicine of a private hospital. The medical records of all consecutive patients who underwent IVF between January 2014 and December 2021 with all causes of infertility were reviewed. The study group included 1401 patients with a median age [interquartile range] of 35 [6] years and median AMH of 1.99 [2.79] ng/mL.

Participants/materials, setting, methods
Patients with various causes of infertility undergoing IVF-ICSI and normal ovarian reserve (defined as a serum level of AMH above 1.1 ng/mL) were included in the study. Only patients with serum levels of AMH and age available for analysis were included in the study. The outcomes included were oocytes and obtained embryos number, the proportion of good-quality embryos from the total number of embryos obtained (GQE/T) and from the transferred number of embryos (GQE/Tr).

Main results and the role of chance
Patients were divided according to their serum AMH level into 3 groups: group 1 with AMH between 1.1 ng/ml and 5 ng/mL, group 2 with AMH between 5 and 8 ng/mL and group 3 with AMH more than 8 ng/mL. After adjustment for age, patients in groups 2 and 3 had a higher number of oocytes (beta 0.231, p &lt; 0.0001 and beta 0.206, p &lt; 0.0001) and embryos (beta 0.143, p &lt; 0.0001 and beta 0.158, p &lt; 0.0001). After adjustment for age, patients in group 2 had a lower proportion of GQE/T in comparison with patients in group 1 (beta -0.077, p 0.037) and patients in both groups 2 (beta -0.119, p 0.001) and 3 (beta -0.103, p 0.004) had a lower proportion of GQE/Tr in comparison with group 1. Being in groups with higher AMH (2 and 3) was not associated with the number of GQE.

Limitations, reasons for caution
Patients included in this study are infertile patients with an indication for IVF treatment. Therefore, the results of this study should be used with caution in other populations

Wider implications of the findings
Our study suggests that having higher levels of serum AMH (above 5 ng/mL) is not associated with better IVF outcomes in terms of the number of good-quality embryos. Moreover, obtaining a higher number of embryos is not associated with a proportional increase in good-quality embryo availability.

Trial registration number
NA
P-690 RESEarch on ovarian reseRVE among Neurologic patients: the RESERVEN study
Authors: Di Girolamo R , Carbone L , Conforti A , Iorio G G , Cariati F , Alviggi C 
Published: June 2023

Abstract

Study question
Could Multiple Sclerosis (MS) reduce the levels of main ovarian reserve markers, measured through automated systems?

Summary answer
There is no statistically significant difference in ovarian reserve markers between women affected by Multiple Sclerosis and healthy controls.

What is known already
Few studies evaluated the issue of ovarian reserve in women affected by MS, so far. The majority of them observed no differences in ovarian reserve markers between women affected by MS and healthy controls. However, interestingly, women with MS in case of a more active disease were observed to have lower levels of ovarian reserve markers. In fact, evidence suggests that an inflammatory status may reduce the ovarian reserve, where autoimmune-related diseases are considered a possible cause of Premature Ovarian Insufficiency (POI).

Study design, size, duration
This is a single-center multidisciplinary prospective case-control (44 cases and 72 controls) study performed from September 2019 to September 2022.

Participants/materials, setting, methods
Cases were reproductive-age women affected by MS recruited at our MS unit, controls were age- and body mass index (BMI) - matched healthy women recruited at our assisted reproductive technology (ART) unit. During the early follicular phase, a transvaginal ultrasound was performed with sonoAVC software (GE medical systems) for 3D antral follicle count and a blood sample taken for hormonal assays (Anti-Müllerian hormone levels was measured using the Roche Elecsys AMH Plus).

Main results and the role of chance
There are no differences in age (p = 0.11), BMI (p = 0.96) as per protocol. Moreover, differences in FSH (p = 0.14), LH (p = 0.13), estradiol (p = 0.92), and AMH (p = 0.99) levels were not statistically significant. The 3D antral follicle count showed a statistically significant difference (p = 0.03), but following a re-evaluation of pictures in post-processing, removing the small antral follicles (2-4 mm) the difference was not statistically significant (p = 0.14).

Limitations, reasons for caution
We could not assess women before they started on medication for MS. Therefore, we could not exclude that medication have an impact in these results, also because the sample is small and patients were not treated with the same drug. Moreover, all patients were in disease remission at enrollment.

Wider implications of the findings
This is the first study to evaluate ovarian reserve markers with automated systems. Our results confirmed the ones previously published. However, the interesting data on 3D antral follicle count increased in MS women should be confirmed and studied in order to evaluate if follicular dynamics are altered in Multiple Sclerosis.

Trial registration number
Not applicable
P-705 Homozygous missense variant in MEIOSIN causes premature ovarian insufficiency
Authors: Guo T , Zhang Q , Zhang W , Zhao S , Qin Y 
Published: June 2023

Abstract

Study question
Are the gene variants involved in meiosis initiation responsible for premature ovarian insufficiency (POI)?

Summary answer
MEIOSIN variant participates in the pathogenesis of human POI by impairing meiosis due to insufficient transcriptional activation of essential meiotic genes.

What is known already
Meiosis is the key event for the establishment of the ovarian reserve, and several gene defects impairing meiotic homologous recombination have been found to contribute to the pathogenesis of POI. However, the genes involved in meiosis initiation have not been associated with POI.

Study design, size, duration
Retrospective genetic study. An in-house whole exome sequencing (WES) database of 1,030 idiopathic POI patients was screened for variations of meiosis initiation genes.

Participants/materials, setting, methods
Gene variations involved in meiosis initiation were screened in the in-house WES database of 1,030 POI cases. The pathogenicity of the variation was verified by in vitro experiments, including protein structure prediction and dual-luciferase reporter assay. The effect of the variant on ovarian function and meiosis was demonstrated through histological analyses in a point mutation mouse model.

Main results and the role of chance
A homozygous variant of MEIOSIN that initiates meiosis via the retinoic acid dependent pathway was identified in a patient with idiopathic POI. The dual-luciferase reporter assay revealed that the variant adversely affected the transcriptional function of MEIOSIN in upregulating meiotic genes. Further knock-in mice with the homologous mutation confirmed that the variation impacted the meiotic prophase I program and accelerated oocyte depletion.

Limitations, reasons for caution
Further studies are needed to explore the role of other meiosis initiation genes in the pathogenesis of POI.

Wider implications of the findings
The present study firstly identified pathogenic MEIOSIN variants in patients with POI. Although the causative variation in meiotic initiation genes is rare in POI, our study expanded the spectrum of causative genes and elucidated the different mechanisms in human infertility.

Trial registration number
Not available
P-735 Are there any differences in preimplantation blastocyst chromosomal abnormalities between polycystic ovary syndrome patients and controls? A multi-center retrospective cohort study
Authors: Luo L , Wenjun W , Yan X , Limei Z , Fei G , Qiong W 
Published: June 2023

Abstract

Study question
Are there possible differences in the preimplantation blastocyst chromosome aberrations between polycystic ovary syndrome (PCOS) patients and controls?

Summary answer
PCOS lowers aneuploidy risk but increases mosaicism risk in preimplantation embryos, and PCOS-related insulin resistance should be investigated as a potential cause.

What is known already
PCOS is thought to alter granulosa cell functions and effects on oocyte development, potentially leading to chromosomal abnormalities and increasing the risk of pregnancy loss. However, few studies have compared the chromosomal status of preimplantation embryos from PCOS patients to those from healthy controls.

Study design, size, duration
This was a multi-center retrospective cohort study conducted at 3 IVF centers. A total of 707 blastocysts from 147 PCOS patients and 3006 blastocysts from 821 control women receiving preimplantation genetic testing (PGT) between 2015 and 2021.

Participants/materials, setting, methods
PGT was performed using next-generation sequencing (NGS). Differences in the chromosome aberrations were compared. Multivariate and subgroup analyses were conducted to control for confounders. Influences of insulin resistance and PCOS phenotype on the risks of specific chromosomal abnormalities were also examined.

Main results and the role of chance
Compared to controls, blastocysts from PCOS patients demonstrated lower aneuploidy rate (14.7% vs. 25.4%, P &lt; 0.001) but greater mosaicism rate (16.5% vs. 8.7%, P &lt; 0.001). Multivariable analysis adjusting for age, IVF center, body mass index (BMI), total gonadotropin (Gn) dose, and peak serum estradiol (E2) on trigger day, identified PCOS as an independent protective factor against embryonic aneuploidy (adjusted OR = 0.56, 95% CI, 0.42–0.76, P&lt;0.001) but a risk factor for embryonic mosaicism (adjusted OR = 2.05, 95% CI 1.48–2.85, P&lt;0.001). These differences in chromosomal spectrum were also observed in subgroups stratified by age, IVF center and BMI. Further multivariate analysis suggested that insulin resistance could be responsible for the increased risk of embryonic mosaicism among PCOS patients (OR = 1.89, 95% CI, 1.06–3.34, P=0.03).

Limitations, reasons for caution
The main limitation is the retrospective design. Besides, methodological uncertainties still exist in detecting mosaicism in current reproductive medicine. A longer-term, multiple-center prospective study with greater methodological standardization is warranted to confirm the present results.

Wider implications of the findings
These results suggest that PCOS pathology may increase the risk of mitosis errors but not the risk of meiosis errors during oocyte development, and PCOS-related insulin resistance should be investigated as a potential cause.

Trial registration number
2020[325]
P-749 Increased accuracy in infertility workup by the additional use of new modern diagnostic methods (“diagnostic TRIO”): results from a large retrospective analysis
Authors: Török P , Boldogh B Z , Lipták M G , Herman T , Lampé R , Di Donna M C , Laganà A S 
Published: June 2023

Abstract

Study question
Is there any positive effect of adding new modalities to the traditional infertility work-up, like 3D sonography, office hysteroscopy and endometrial biopsy?

Summary answer
During infertility workup conventional diagnostic tests should be combined with new approaches (3D-TVS, OHSC and endometrial biopsy) to achieve more accurate and less invasive diagnostics.

What is known already
Female infertility can be explained by functional or organic abnormalities affecting the reproductive system. The most common organic causes include abnormalities within the uterine cavity (e.g. endometrial polyp, submucosal fibroid, intrauterine adhesion), morphological disorders (e.g. dysmorphic uterus, uterine septum) and abnormalities of the endometrium (e.g. chronic endometritis).

Study design, size, duration
In our retrospective study, we examined patients with primary and secondary infertility. All the patients were assessed by 3D-TVS and OHSC to detect morphological and intrauterine disorders, and in special cases (repeated implantation failure – RIF), endometrial biopsies were carried out to detect endometrial disorders.

Participants/materials, setting, methods
Data of 606 patients examined between 2018 and 2022 were analyzed retrospectively.

Main results and the role of chance
In 606 cases 3D-TVS and OHSC were performed in patients (65.51 % primary, 34.49 % secondary infertility), who had unknown reason to infertility. By the combination of 3D-TVS and OHSC we could verify uterine disorders in 39.93 % of cases. Together these two diagnostic methods found the probable infertility causing lesion almost 40 % of our patients. In the subgroup of 40 repeated implantation failure (RIF) patients, the “diagnostic TRIO” confirmed a disorder in 57.50 % of the cases.

Limitations, reasons for caution
Number of patients should be more to conclude more accurate data.

Wider implications of the findings
The proper condition of the uterine milieu, through correction of uterine cavity if necessary, endometrial receptivity are of paramount importance for the success of the treatment; as a result, intrauterine surgery as a new subspecialty has been developing.

Trial registration number
DE RKEB/IKEB: H.0250-2020