bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-172 Effect of anti-centromere antibodies on multi pronuclear formation
Authors: Kumagawa Y , Ihara K , Tokoro M , Fukunaga N , Asada Y 
Published: June 2023

Abstract

Study question
Do the anti-centromere antibodies (ACA) affect the multi pronuclear formation (MPF) rate?

Summary answer
MPF rate was higher in patients with ACA. The MPF rate of ACA patients with antibody titers ≥160-fold was significantly higher than in titers 40-fold.

What is known already
ACA is an anti-nuclear antibody (ANA), and specifically recognizes the centromere. Recently, several studies have reported that the rate of oocyte maturation is lower in patients with ACA. Moreover, in MI oocytes collected from ACA patients, female chromosomes were frequently dispersed in the cytoplasm.

Study design, size, duration
A total of 4756 patients from our clinic were tested for ANA before oocyte retrieval from January 2014 to December 2021. After retrospective ANA testing, patients were classified according to 3 groups; 62 ACA patients (with only ACA), 1134 non-ACA patients (with ANA but not with included ACA) and 3560 non-ANA patients (without ACA and any ANA).We considered ACA-positive levels at titers ≥40. ACA patients were further classified into 6 groups by antibody titer.

Participants/materials, setting, methods
The MPF rate after ICSI was compared in the 3 groups (ACA patients, non-ACA patients, non-ANA patients) and at 6 ACA titers in each group (titer of ACA; 40-fold, 80-fold, 160-fold, 320-fold, 640-fold, ≥1280-fold).MPF rate was calculated by dividing the number of embryos that formed three or more pronuclei by the number of embryos inseminated by ICSI.Ryan's method was used for multiple comparisons of ratios.

Main results and the role of chance
MPF rate was 3.8% (1997/53240) in non-ANA patients, 4.3% (733/17003) in non-ACA patients, and 32.1% (351/1092) in ACA patients, being significantly higher in ACA vs other groups (P&lt;.01). In comparisons between ACA titers, MPN rate was 8.7% (4/46) at 40-fold , 13.0% (3/23) at 80-fold , 36.1% (56/155) at 160-fold , 32.4% (48/148) at 320-fold , 36.0% (111/308) at 640-fold , and 31.3% (129/412) at ≥ 1280-fold, respectively. MPN rate of patients with titers ≥160-fold was significantly higher than with 40-fold.

Limitations, reasons for caution
A potential limitation of the present study is the small sample size. This is because ACA patients account for only 1% of patients who underwent ART treatments.

Wider implications of the findings
MPF rate in ACA patients was significantly higher than in non-ANA and non-ACA patients and was also significantly higher in ACA patients with titers of ≥ 160-fold vs 40-fold. The dispersion of the female chromosome in the cytoplasm of MI oocytes may be a cause of MPN formation.

Trial registration number
None
O-155 Building bridges to harmonize different data collection systems worldwide - need and challenges
Authors: Kupka M S 
Published: June 2023

Abstract
In order to transfer data from individual IVF centers and a national register into a regional register and then merge this data into a world register, certain basic definitions must be established.
The treatment strategies of each country are influenced by the legislative and insurance framework.
The expectations of patient couples also vary greatly from region to region.
All of this can only work if there are definitions of what data is to be collected and in what way.
Above all, there are difficulties in creating statistics when the raw data first has to be adjusted and merged.
This article is intended to point out some difficulties, but also to show solution concepts.
O-199 Imprinting disorders in singletons conceived by assisted reproductive technology in Sweden
Authors: Ye M , Palomares A , Iwarsson E , Rodriguez-Wallberg K , Öberg S 
Published: June 2023

Abstract

Study question
Is singleton birth from assisted reproductive technology (ART) associated with imprinting disorders (IDs) independent of parental infertility and other background factors?

Summary answer
Singletons conceived using intracytoplasmic sperm injection (ICSI) and frozen embryos have higher risks of Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS) and Silver-Russell syndrome (SRS).

What is known already
Previous studies have suggested elevated risk of IDs in children conceived with ART compared with children conceived with spontaneous conception (SC). It is not clear to what extent the observed associations could be explained by parental infertility and related risk factors. Knowledge on specific ART procedures and their association with IDs is also limited.

Study design, size, duration
A nationwide register-based cohort study was carried out in which all liveborn singletons in 1997-2017 in Sweden were included with follow-up to 2018.

Participants/materials, setting, methods
Among 1 998 825 singletons, 60 210 were conceived using ART. The International Classification of Diseases (ICD) version 10 was used to identify three distinct ID groups: PWS/SRS, BWS, and central precocious puberty (CPP). Cox regression, combined with inverse probability treatment weights to account for birth year, parity, pregnancy loss history, parental age and country of origin, was used to compare ART singletons with all SC singletons and those born to couples with known infertility.

Main results and the role of chance
A total of 1012 children were diagnosed with the IDs of interest (654 PWS/SRS, 255 BWS, and 109 CPP), and 49 of them were conceived through ART. Compared with all SC singletons, higher risk of PWS/SRS and BWS was observed in ART singletons and the weighted hazard ratios (wHRs) were 1.57 [95% CI, 1.09-2.26] and 2.57 [95% CI, 1.60-4.12], respectively. The elevated risks remained when comparison was restricted to SC singletons of couples with known infertility, though the wHR for BWS was somewhat attenuated (1.87, 95% CI: 1.04-3.36). No difference in risk of CPP was observed between singletons conceived with and without ART irrespective of parental infertility. Further subgroup analysis revealed that ICSI in combination with frozen embryo transfer was responsible for the higher risks of PWS/SRS (wHR 6.32, 95% CI: 3.34-11.95) and BWS (wHR 9.04, 95% CI: 4.34-18.82).

Limitations, reasons for caution
The use of the Swedish ICD-10 did not allow distinction of PWS and SRS. The number of CPP cases in ART singletons was too small (N = 3) to make inference.

Wider implications of the findings
This study found that ART-conceived singletons, particularly those conceived using ICSI and frozen embryos, had a higher risk of IDs independent of parental infertility. However, the underlying mechanism is not clear, and the role of type and severity of infertility warrants further investigation.

Trial registration number
not applicable
O-215 Negative impact of the reduction in family income following the SARS CoV 2 Covid 19 pandemic on access to Assisted Procreation : observational study
Authors: Pacchiarotti A 
Published: June 2023

Abstract

Study question
What are the consequences of the health emergency and the consequent restrictive measures on the economic accessibility of medically assisted procreation techniques.

Summary answer
Reduction of family income rate and consequentely bias of PMA attempts rate

What is known already
- The birth rate in Italy over the past 10 years has been declining rapidly and continuously
- Fertility income correlation has an inversely proportional trend demonstrated in a study conducted by the Ministry of Economy and Finance and Istat
- Pandemic has further impoverished Italian families

Study design, size, duration
This is a transversal observational study conducted at the Assisted PReproduction Center of the San Filippo Neri hospital in Rome between Jenuary 2021 and December 2022
The results were obtained by administering an online questionnaire consisting of 20 multiple choice questions to which the participants answered anonymously.

Participants/materials, setting, methods
Two hundred and ninety-five patients were enrolled with an overall average age of 37.5 years (minimum age 25, maximum age 47).
Main outcomes measures. Bias of PMA attempts rate. Reduction of family income rate

Main results and the role of chance
Majority of people said they have not seen their desire for offspring reduced since the onset of health emergency. the willingness to use MAP techniques during the pandemic remained unchanged for 58.7% of respondents, increased for 12.5% and decreased for the remaining 28.8%. The individuals who have declared to have momentarily renounced to the procedures of PMA have been 31.7%, of these 24% has renounced because of economic factors. When asked about the cost of the necessary medical procedures, 62.5% of the participants considered the price in public facilities to be “adequate” and 79.8% defined the cost in private clinics as “excessive”.

Limitations, reasons for caution
A limitation of the study may be the comprehension of the questionnaire, since it could not be speieged verbally. The administration was done online, so there is no assurance that it was received by everyone. Therefore, the percentage of patients who did not respond may be overestimated

Wider implications of the findings
The study and analysis of these data provides a current overview of the condition of infertile couples in our country, so that all useful interventions can be put in place to restore the interest and economic conditions necessary for the initiation of medically assisted procreation.

Trial registration number
not applicable
O-226 Is there a place for polygenic risk scoring in PGT (PGT-P)?
Authors: Handyside A H 
Published: June 2023

Abstract
Preimplantation genetic testing (PGT), by embryo biopsy and genetic testing for inherited diseases and chromosome abnormalities following IVF, is now well established world-wide. PGT for monogenic conditions (PGT-M) is generally performed for childhood-onset, lethal disorders, but is increasingly accepted for certain adult-onset conditions, conditions with available treatment options or conditions with lower penetrance. Over recent years, machine learning methods applied to large genomic datasets, including genome-wide association studies (GWAS) using single nucleotide polymorphism (SNP) genotyping, has enabled polygenic risk scores (PRSs) to be calculated to identify individuals who are at elevated risk for a broad range of conditions including important common multifactorial diseases, such as coronary artery disease (CAD), diabetes, hypertension and various cancers. It is now possible to perform genome-wide SNP genotyping of embryo biopsy samples with the same accuracy as adult genomic DNA and the first live birth following PGT for polygenic risk scoring (PGT-P) was reported in 2019 (Treff et al (2019) Front Endocrinol 10, 845) . The clinical application of PGT-P is controversial and raises many practical, ethical and societal issues. To examine the question ‘is there a place for PRS in PGT’, the example of predisposition to breast cancer will be reviewed.
O-246 The molecular mechanism of miR-96-5p in the pathogenesis and treatment of polycystic ovary syndrome
Authors: Li X 
Published: June 2023

Abstract

Study question
Polycystic ovary syndrome, characterized by the androgen excess and arrest of antral follicles, is lacking novel specific diagnostic biomarkers and therapeutic targets.

Summary answer
Study of the molecular mechanisms of microRNAs in the etiology and its potential applications in PCOS provides the insight.

What is known already
Some of molecular mechanisms of microRNAs have been demonstrated involved in the etiology of PCOS

Study design, size, duration
Clinically, we collected the samples of serum, follicular fluid (FF) and primary human granulosa cells (hGCs) of PCOS patients (n = 70) vs. non-PCOS women (n = 60). Experimentally, we carried out studies with 3-types of induced PCOS-like mice.

Participants/materials, setting, methods
By analysing the expression levels of miR-96-5p in serum, follicular fluid (FF) and primary human granulosa cells (hGCs) of PCOS patients (n = 70) vs. non-PCOS women (n = 60). as well as in ovaries from 3-types of induced PCOS-like mice.

Main results and the role of chance
Clinically, we demonstrated that the elevated circulating miR-96-5p levels were significantly correlated with the PCOS disordered endocrine clinical features, and the area under the curve of receiver operating characteristic was 0.8344, with 75.71% specificity and 80% sensitivity. Mechanically, we identified miR-96-5p as an androgen-regulated miRNA that directly targets the forkhead transcription factor FOXO1. Inhibition of miR-96-5p decreased estrogen synthesis, while decreasing the cell proliferation index of KGN via regulating the expression of FOXO1 and its downstream genes. Inversely, inhibition of FOXO1 abrogated the effect of miR-96-5p on estrogen synthesis and proliferation index. Of note, ovarian intra-bursal injection of miR-96-5p agomir rescued the phenotypes of dehydroepiandrosterone-induced PCOS like mice.

Limitations, reasons for caution
This study needs a large-scale clinical investigation to confirm the specificity and sensitivity of miR-96-5p as a clinical biomaker.

Wider implications of the findings
In conclusion, our results clarified a vital role of miR-96-5p in the pathogenesis of PCOS and might serve as a novel diagnostic biomarker and therapeutic target for PCOS.

Trial registration number
no
O-306 Genome-wide association meta-analysis supports the association between MUC1 and ectopic pregnancy
Authors: Pujol Gualdo N , Mägi R , Laisk T 
Published: June 2023

Abstract

Study question
Can we identify genetic variants associated with ectopic pregnancy by undertaking the first genome-wide association study leveraging two large-scale biobank initiatives?

Summary answer
We identified two novel genome-wide significant associations with ectopic pregnancy, highlighting MUC1 as the most plausible affected gene.

What is known already
Ectopic pregnancy is an important cause of maternal morbidity and mortality worldwide. Despite being a common early pregnancy complication, the genetic predisposition to this condition remains understudied and no large scale genetic studies have been performed so far.

Study design, size, duration
A GWAS meta-analysis including 7,070 women with ectopic pregnancy and 248,810 controls from Estonian Biobank and the FinnGen study. Several post-GWAS analysis were conducted to characterise the genetic signals, as well as to analyse the genetic and phenotypic relationships with the condition.

Participants/materials, setting, methods
We identified ectopic pregnancy cases from national registers by ICD codes (ICD-10 O00), and all remaining women were considered controls.

Main results and the role of chance
We identified two genome-wide significant loci on chromosomes 1 (rs4971091, p = 5.32x10-9 ) and 10 (rs11598956, p = 2.41x10-8 ). Follow-up analyses propose MUC1, an epithelial glycoprotein with an important role in barrier function, as the most likely candidate for the association on chromosome 1. We also characterise the phenotypic and genetic correlations with other phenotypes, identifying a genetic correlation with smoking and diseases of the (genito)urinary and gastrointestinal system, and phenotypic correlations with various reproductive health diagnoses, reflecting the previously known epidemiological associations.

Limitations, reasons for caution
The main limitation is that the findings apply to European-based ancestry populations and we only captured maternal genomes.

Wider implications of the findings
This study encourages the use of large scale genetic datasets to unravel genetic factors linked to ectopic pregnancy, which is difficult to study in experimental settings. Increased sample size might bring additional genetic factors associating with ectopic pregnancy and inform its heritability.

Trial registration number
not applicable
P-040 The Role of ACE2 and DNA fragmentation index on covid-19 post infected, healthy and infertile men
Authors: Mohammed A 
Published: June 2023

Abstract

Study question
to investigate the relationship between ACE2 and DNA fragmentation index and their impact on men’s reproductive system in covid-19 post-infected patients.

Summary answer
the drastic effect of covid-19 on the male reproductive system might be due to elevated DFI and ACE2 levels.

What is known already
In the last two years, many studies had been devoted to uncovering the depraved impact of covid-19 by measuring ACE2 concentrations or sperm DNA fragmentation but no study was applied to measure both parameters, this study performed on both parameters to figure out the role of angiotensin-converting enzyme (ACE2) with seminal fluid parameters and DNA fragmentation index in covid-19 post infected men and infertile patient in comparison to healthy fertile men.

Study design, size, duration
This prospective cohort study was conducted from November 2021 to June 2022. one hundred and nine men who participated in this study.

Participants/materials, setting, methods
The participants were divided into four groups: post-infected men with Covid-19 who recovered from Covid-19 infection with a recovery interval of no more than three months from the time of symptoms onset and all were fertile married men, healthy fertile men who haven't been infected with Covid-19 in the last three months obtain normal seminal fluid parameters as control, The third group is composed of oligospermia, while the fourth group is constituted of azoospermia volunteers

Main results and the role of chance
In this study, the result showed that the seminal fluid parameters for post-infected men with covid-19; were demotion in sperm concentration, total count, motility, and morphology with a p-value &lt; 0.001 when compared with healthy men. DNA fragmentation in post-infected men was 4 times higher than in non-infected and it was found that post-infected men had 10 times more ACE2 concentrations in comparison with healthy men. The study showed that in oligospermia and azoospermia volunteers own a high ACE2 level compared to healthy volunteers and that the oligospermia subjects have a significantly high sperm DNA fragmentation index.
In conclusion, the drastic effect of covid-19 on the male reproductive system might be due to elevated DNA fragmentation and ACE2 levels, and there is a statistically significant positive correlation between the DNA fragmentation index and ACE2 levels.

Limitations, reasons for caution
number of post-infected men with covid-19

Wider implications of the findings
1- A positive relationship exists between DNA fragmentation index percentage (DFI) and angiotensin-converting enzyme level (ACE 2).
2- Covid-19 infection alters sperm parameters such as concentrations, total sperm count, motility, and morphology.
3- The percentage of DNA fragmentation rose significantly after covid-19 infection.

Trial registration number
self funding
P-162 Numeric Embryo Quality Scoring Index (NEQsi) is Predictive of IVF Cycle Outcome at any Endometrial Thickness
Authors: Pierson H , Invik J , Meriano J , Cadesky K , Laskin C , Pierson R 
Published: June 2023

Abstract

Study question
Is it possible to use NEQsi to determine the statistical contributions of embryo quality and endometrial thickness (ET) to IVF cycle outcome?

Summary answer
Yes. Analytics revealed that the likelihood of pregnancy is reliably predicted by the quality of the embryo at any endometrial thickness.

What is known already
ET is widely utilized to assess the quality of endometrial preparation in IVF cycles. The connection between endometrial thickness and cycle outcome is divided in the literature; studies report correlation between ET and cycle outcome while others find no link between the two. Regardless, the statistical interactions between ET and embryo quality remain understudied. NEQsi was recently developed as a method for converting Gardner embryo grades to interval variables for use in statistical modeling. The combination of NEQsi scores and endometrial thickness measurements provides an opportunity to assess the contributions of embryo quality and ET on IVF cycle outcomes.

Study design, size, duration
We conducted a retrospective analysis including IVF cycles conducted at a Canadian multi-clinician fertility care centre (n = 1623). Data were acquired from a chart review of deidentified patient files from 2014 – 2021.

Participants/materials, setting, methods
Participants were all patients who underwent single embryo transfer and had endometrial thickness measurements, Gardner embryo grading, and ultrasound based endometrial receptivity testing (usER) as part of their care program. No interventions were made. Gardner embryo grades on file were created using EmbryoScope (Vitrolife, Göteborg Sweden) and converted to NEQsi scores. We conducted multivariate statistical modelling analysis to determine the combined contribution of embryo grade and endometrial thickness on IVF cycle outcome.

Main results and the role of chance
NEQsi scores ranged from 3 – 11 (mean 8.32 ± 1.78 SD). Endometrial thicknesses ranged from 3.1 mm to 20.2 mm (mean 9.69 ± 2.23 SD). A positive linear relationship was observed between NEQsi score and probability of pregnancy. Multivariate logistical regression determined that embryo grade was a highly significant predictor of cycle outcome (p &lt; 0.0001). Endometrial thickness was not a statistically significant predictor of cycle outcome (p = 0.585).

Limitations, reasons for caution
We acknowledge that the single centre design is a limitation of this study. Future investigation with more cycles and multiple centres will strengthen the study and interpretation of the data.

Wider implications of the findings
The application of NEQsi was simple and this work confirms the utility of the NEQsi in conducting statistical analyses with embryo quality as a covariate. In addition, our findings imply that cancellation of embryo transfers based on ET measurements may not be warranted.

Trial registration number
Not applicable