bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-059 ntermetabolites of cholesterol synthesis in granulosa cell and oocyte aging
Authors: Liu C , Lijun D , Haixiang S 
Published: June 2023

Abstract

With the development of society, there has been a significant delay in female fertility and an increasing desire for childbearing among females of advanced maternal age in recent decades. Nevertheless, women over 35 years old have more risk of infertility and miscarriage compared to young women, due to decreased oocyte quality. These changes are mainly caused by meiotic defects, especially aneuploidy. Therefore, exploring the mechanisms of aging-related meiotic defects and aneuploidy in oocytes is of great significant for improving the pregnancy outcomes of aged women.
Oocytes are enveloped by granulosa cells (GCs) to form follicles, which constitute the reproductive units in ovaries. GCs form a metabolic community with oocytes for oocyte growth and maturation. Numerous studies have reported that metabolic coupling between GCs and oocytes could affect the process of oocyte meiosis resumption, spindle assembly, and chromatin arrangement. Maternal aging is related to disruption of oocyte-GC interactions that leads to disorders of the oocyte meiotic process. Therefore, abnormal metabolic coupling between GCs and oocytes is an important reason for decreased quality in aged oocytes.
To further clarify the metabolic coupling changes between GCs and oocytes during ovarian aging, we systematically characterized the dynamic changes in the overall transcriptomic landscapes of oocytes and GCs from young and aged mice throughout oocyte meiosis (during the growing oocyte [GO], full-grown oocyte [FGO], metaphase I [MI] oocyte [MIO], and metaphase II [MII] oocyte [MIIO] phases). Data revealed that the mevalonate (MVA) pathway, an essential metabolic pathway that uses acetyl-CoA to produce cholesterol and isoprenoids, was specifically highly expressed in GCs with the resumption of oocyte meiosis, and the expression of MVA pathway in GCs decreased with age. Atorvastatin-mediated inhibition of MVA metabolism in GCs decreased the first polar body extrusion (PBE) rate, and increased oocyte meiotic defects and aneuploidy in young cumulus-oocyte complexes (COCs). Further studies showed that the effect of the MVA pathway on oocyte meiosis was mainly regulated by protein isoprenoylation mediated by the inter-metabolites of cholesterol synthesis. Importantly, upregulation of the MVA pathway in aged GCs could ameliorate the depletion of ovarian reserve, decrease oocyte meiotic defects, and improve oocyte quality.
In conclusion, metabolite in granulosa cell is an important factor determining the oocyte quality; MVA pathway in GCs is a critical regulator of meiotic maturation and euploidy in oocytes, and age-associated MVA pathway abnormalities contribute to oocyte meiotic defects and aneuploidy; Supplementation of inter-metabolites of cholesterol synthesis is a new therapeutic target for clinical intervention to improve oocyte quality.

Trial registration number
XXXX
P-368 Clinical impact of personalized embryo transfer (pET) guided by endometrial receptivity analysis (ERA) in patients with ≥ 1 failed transfers
Authors: Ruiz-Alonso M , Stankewicz T , Castellón J A , Gómez C , De La Fuente E , Gómez E , Simón C , Valbuena D 
Published: June 2023

Abstract

Study question
Does pET following ERA increase pregnancy (PR), ongoing pregnancy per transfer (OGPR) and live birth rates (LBR) in patients with ≥ 1 previous failed transfer?

Summary answer
In this group of patients, pET guided by ERA obtained a significantly higher PR, OGPR and LBR versus standard embryo transfer.

What is known already
pET consists of synchronizing embryo transfer with the optimal endometrial receptivity status of the patient by the transcriptomics identification of her personalized window of implantation (WOI). Controversial results have been published regarding the clinical usefulness of this precision medicine diagnosis in a range of clinical indications. Here we present data from patients with ≥ 1 previous failed transfer undergoing pET guided by ERA.

Study design, size, duration
Multicenter retrospective study involving 526 patients with at least one previous failed embryo transfer (ET) between 2017 and 2021. These patients were divided into two groups: cases (pET guided by ERA) (n = 385), or controls (standard blind ET) (n = 141). Clinical outcomes compared were PR, OGPR and LBR for each group.

Participants/materials, setting, methods
Age, body mass index (BMI), previous failed attempts, proportion of embryos with PGT-A and transferred embryo quality were compared between the two groups. ERA test was performed in HRT cycles and subsequent embryo transfer was carried out replicating the same conditions and following the recommendation given for pET. Standard ET was also performed in HRT cycles. Wilcoxon rank sum test was applied to quantitative comparations. Chi-square test was done for categorical variables.

Main results and the role of chance
In this retrospective analysis, age and number of previous failed ET was higher in the ERA group (p &lt; 0.05). Clinical results in terms of PR, OGPR and LBR were significantly higher when pET guided by ERA was performed when compared to the non-ERA group.

Limitations, reasons for caution
This is a retrospective study, having limitations of its nature.

Wider implications of the findings
These results show that pET guided by ERA in patients with ≥ 1 failed transfers increased significantly PR, OGPR and LBR versus standard blind ET.

Trial registration number
Hospital Clínico de Valencia Ethic Committee approval nº. 2021/018.
P-717 Segmental aneuploidies are not related to paternal age in young women
Authors: Bronet Campos F , Marta A , Mireia F , Amparo M , Eva M 
Published: June 2023

Abstract

Study question
Is there an impact of paternal age on embryo segmental aneuploidy rate?

Summary answer
Even when segmental aneuploidies are most linked to paternal origin, results do not show a relationship between paternal age and embryo segmental aneuploidies.

What is known already
Most studies consider maternal age as a risk factor for spontaneous abortion, infertility and genetic defects in the offspring. However, attention has only recently turned to the impact of paternal age on reproductive outcome. In Assisted Reproduction Technology male age has been related to a decrease in sperm quality and clinical outcomes and an increase in sperm DNA damage has been identified among elderly males. Studies assessing the type of chromosomal aneuploidy associated with paternal aging have reported mixed relative risk results for chromosomes 13, 18, 21, and X. Segmental aneuploidies are most linked to paternal origin.

Study design, size, duration
Observational, retrospective and multicentric study. The study was approved by the local institutional review board (IRB). All the patients underwent an IVF cycle with oocytes from egg donors, followed by Preimplantation Genetic Testing for Aneuploidy (PGT-A) at IVI-RMA Madrid, IVI-RMA Valencia and IVI-RMA Barcelona from January 2018 to August 2022. A total of 3412 biopsied embryos obtained from 660 cycles were included in the study.

Participants/materials, setting, methods
Exclusion criteria were the following: altered karyotype, single gene disorder and male factor (sperm concentration lower than 5 million/ ml). Embryo biopsies were performed at blastocyst stage (day 5/ 6). After the trophoectoderm biopsy, all embryos were vitrified. Main outcome was segmental aneuploidy rate among different male age groups (&lt;41 y.o./ ≥40 y.o.). Lineal regression analysis was used for continuous parameters and Chi square was used for categorical variables.

Main results and the role of chance
Descriptive parameters showed no differences, particularly in sperm concentration (43.2±15.6 vs. 40.1±14.3) and sperm motility (27.3±13.7 vs. 29.7±14.8). Lineal regression analysis showed no significant differences in segmental aneuploidy rate (p = 0.542). Statistical model showed no significant differences among male age groups (1.28% (0.76-2.01) vs 1.10% (0.69-1.66) p = 0.542).

Limitations, reasons for caution
The study has been conducted in three different clinics, there could be some unknown cofounding factors.

Wider implications of the findings
Male age don’t have an impact on the embryo segmental aneuploidy rate in young/donors’ oocyte

Trial registration number
Not applicable
P-732 High degree of concordance between the genetic results of Noninvasive Preimplantation Genetic Testing for Aneuploidies (NIPGT-A) and those obtained with analysis of the whole embryo
Authors: Franco J G , Petersen C G , Vagnini L , Massaro F C , Petersen B , Izidoro P M , Nicoletti A , Ricci J , Zamara C , Oliani A H , Dieamant F , Oliveira J B A 
Published: June 2023

Abstract

Study question
What is the degree of concordance between Noninvasive Preimplantation Genetic Testing for Aneuploidies (NIPGT-A) versus genetic analysis of the whole embryo?

Summary answer
Cell free DNA ploidy evaluated by NIPGT-A presents very good concordance that of the DNA from whole embryo cells (Cohen's Kappa concordance coefficient: 0.84).

What is known already
After many years of using PGT-A, there are still many concerns, such as risks of invasive action and difficulties in the correct interpretation of mosaicism, which may lead to errors in the interpretation of false-positive and false-negative results. Recently, a new technology (NIPGT-A) has arisen using cell-free DNA present in the spent culture media of human blastocysts. However, there are still few genetic analyses of concordance between NIPGT-A and the whole embryo (gold standard).

Study design, size, duration
This cohort study included a total of 56 blastocysts vitrified on Day-5 that were previously biopsied for PGT-A. All embryos had a diagnosis of aneuploidy and were donated under informed consent by patients following the Human Medical Authority regulations. Blastocysts were thawed and cultured in 15µl drops of culture medium under oil. After their expansion(4-8 hours), the blastocysts and their corresponding spent media were transferred to PCR tubes and stored at -80 °C until analysis.

Participants/materials, setting, methods
DNA in all samples(spent culture medium and whole embryo) was amplified by MALBAC® technology(Yikon Genomics). The DNA concentration of the amplified product was measured using a Qubit 3.0Fluorometer(Thermo Fisher Scientific). The samples were subjected to next-generation sequencing (NGS) using the Illumina MiSeq® system. The ploidy status results obtained from ChromGoTM software(Yikon Genomics) for spent culture medium and the whole embryo were compared to determine the accuracy of NIPGT-A for screening chromosomal abnormalities in each embryo.

Main results and the role of chance
DNA from all 56 spent medium samples and whole embryos were successfully amplified. Comparing the results of NIPGT-A and whole-embryo sequencing (Table 1), the positive predictive value (PPV) was 93.5%, and the false-positive rate (FPR) was 6.5%. Agreement analysis showed very good coefficient concordance (Cohen's Kappa coefficient: 0.84).
P-752 Cervical cerclage versus vaginal progesterone in the prevention of preterm birth in singleton pregnancies among women with a short cervical length: A retrospective cohort study
Authors: Liu Y , Cao T , Zeng S , Chen R , He L , Liu X 
Published: June 2023

Abstract

Study question
To compare the maternal and neonatal effects of cervical cerclage and vaginal progesterone in preventing singleton preterm births in women with a short cervical length.

Summary answer
Cervical cerclage showed no benefit in preventing preterm birth; however, it prolonged gestation by 39 days compared to vaginal progesterone treatment.

What is known already
Clinically, there may be a bias toward the choice of cervical cerclage if the cervix is short (&lt;10 mm) and, similarly, toward vaginal progesterone use if the cervix is long (&gt;30 mm). However, there are no clear treatment guidelines for the best options for singleton pregnant women with a CL between 10 and 30 mm. Furthermore, there is insufficient evidence to determine whether one treatment is superior to the other in preventing PTB and decreasing adverse neonatal outcomes in singleton pregnancies in such cases.

Study design, size, duration
Asymptomatic pregnant women having singleton pregnancies, with a CL between 10 and 30 mm, measured using transvaginal ultrasound at 12–26 weeks of gestation, who delivered at our hospital between January 2009 and August 2020, were included in our study. Based on the inclusion and exclusion criteria, 267 singleton pregnant women, of whom 116 were treated with cervical cerclage and 151 with vaginal progesterone, were finally included.

Participants/materials, setting, methods
Independent sample t-tests and differential analysis were used to analyze the data based on their distribution. The Cox semi-parametric regression model was used to analyze the gestation weeks at delivery and neonatal outcomes. The decision regarding cesarean delivery was based on a binary logistic regression model.

Main results and the role of chance
In the initial analysis, the number of preterm births was significantly higher in the cerclage group than in the vaginal progesterone group; however, after multivariate adjustment for confounding factors, the latency period from diagnosis to delivery was found to be significantly prolonged in the cerclage group.

Limitations, reasons for caution
There are currently no uniform criteria for determining whether study subjects are eligible for cervical cerclage or vaginal progesterone treatment, which may present some cases of noncompliance.

Wider implications of the findings
In our study, we found that cervical cerclage did not have significant advantages over vaginal progesterone treatment in preventing PTB. However, upon adjustment for confounding factors, it was shown to prolong the gestational age by 39 days compared to vaginal progesterone treatment.

Trial registration number
non-clinical trials
O-112 Jean Purdy - The silent partner
Authors: Kendrew H J 
Published: June 2023

Abstract
The development of a novel technique requires a diverse team whose individuals share the same goal but who each bring a different strength and aspect of their personality to the research/ project.
A “front man” with tenacity drive and vision needs the support of such team. To quote Aristotle “The whole is greater than the sum of it's parts”.
This expression could be aptly applied to the pioneers of IVF, Robert Edwards and Patrick Steptoe about whom much has been written. Their drive and determination in the face of societal opposition and competition from across the Atlantic, was supported by a silent group of lesser known individuals.
Jean Purdy (research nurse and laboratory assistant), Muriel Harris (operating theatre superintendent), Lillian Lincoln Howell (philanthropist) and Ruth Fowler (scientist and Robert Edwards wife). Not to mention the 280 unidentified women patients and their partners who played their part. All drawn together in the quest to try and help patients achieve the families they so desired.
In my presentation I am concentrating specifically on the life Jean Purdy and her contribution to the work which sees us all here today in Copenhagen.She had a short but pivotal life, often attributed to being the first embryologist, prematurely dying at the age of 39 from malignant melanoma.
As of March 2021 at least eight million babies worldwide have been born from IVF. I wonder how astounded these pioneers would be to see how far we have come and what they would make of the world wide impact they made in the face of significant criticism, moral outrage and scepticism from their professional peers, the church, media and society?
O-115 Fertility preservation or egg donation for hereditary cancer syndromes?
Authors: Filippi F 
Published: June 2023

Abstract
Individuals with hereditary cancer syndromes are at risk of developing multiple tumours and, therefore, undergo life-long surveillance procedures and risk-reducing and/or therapeutic surgeries. Knowledge and testing for hereditary cancer susceptibility genes is rapidly spreading, often performed at the first cancer diagnosis.
Different physical, psychosocial, ethical and economic considerations need to be taken into account when deciding on reproductive options in individuals with a hereditary cancer syndrome.
The psychosocial impact of genetic predisposition to cancer may be particularly problematic and still represents an ongoing challenge for the professional taking care of these patients. In fact, worries about passing on a genetic risk for cancer to offspring are concerns expressed by the 65% of female young adult cancer survivors when specifically interviewed.
At cancer diagnosis, fertility preservation procedures represent an effort to retain the opportunity to have genetically related children. Unfortunately, oocytes, embryo or ovarian cortex cryopreservation do not guarantee live birth. The success rates of these procedures are highly dependent on age, number of oocytes cryopreserved and may be influenced by other medical, lifestyle and (future) male factors. In addition, carriers of pathogenetic gene variants for cancer predisposition should also be thoroughly counselled about preimplantation genetic testing (PGT), a technique allowing the interruption of passing on the gene associated to cancer risk. However, this option inevitably lowers the efficacy of fertility preservation interventions in terms of future pregnancies.
Egg donation is a spreading procedure with higher success rates than fertility preservation techniques. This approach allows individuals to avoid undergoing oocytes retrieval or ovarian tissue cryopreservation surgery, thus avoiding procedural risks (infection, haemorrhage, ovarian hyperstimulation syndrome) and postponement of oncological treatments. On the other side, offspring will not have a genetic link with recipient and the beneficial psychological role of fertility preservation would be missing. In fact, several recent studies have underlined the message of hope that is indirectly perceived by oncological patients when counselled for fertility preservation. Moreover, counselling on the possibility of egg donation is challenging at the time of cancer diagnosis.
Making the right reproductive choice in carriers of hereditary cancer syndromes is a dilemma which can’t be solved generalizing. Even patients’ attitude could be different according to the time of counselling, whether is at cancer diagnosis or at the genetic predisposition diagnosis in healthy carriers. Egg donation should be considered in the available armamentarium. The complexity of the topic needs a personalized and multidisciplinary counselling.
P-781 Assisted reproductive technology-associated risk factors for retained placenta
Authors: Jwa S C , Tamaru S , Takamura M , Namba A , Kajihara T , Ishihara O , Kamei Y 
Published: June 2023

Abstract

Study question
What are the assisted reproductive technology-associated risk factors for retained products of conception (RPOC) following delivery?

Summary answer
Frozen embryo transfer (FET) with hormone replacement cycles (HRC) constitutes the largest risk factor for RPOC.

What is known already
RPOC is a key cause of secondary postpartum hemorrhage. Previous studies have shown that the use of ART increases the risk of RPOC and subsequent transfusion following delivery. However, the relationships between specific ART-treatment factors and the risk of RPOC have not been elucidated.

Study design, size, duration
We performed a registry-based retrospective cohort study using the Japanese national ART registry, in which all the ART cycles performed in Japan are recorded including the perinatal outcomes.

Participants/materials, setting, methods
Singleton live births between 2007 and 2017 were studied (n = 306,411). Odds ratios (ORs) and 95% confidence intervals (CIs) for the potential risk factors for RPOC associated with fresh and frozen cycles were obtained from multiple logistic regression analysis, incorporating adjustment for maternal age, infertility, and calendar year. Because information regarding assisted hatching (AH) and HRC for endometrial preparation only became available in 2012, these factors were analysed using the data collected between 2012 and 2017.

Main results and the role of chance
RPOC was diagnosed for 132 deliveries (0.04%), of which 122 (92.4%) followed FET cycles and only 10 (0.01%) followed fresh embryo transfer (ET). No significant risk factors for RPOC were identified using the fresh ET data. For FET cycles, the use of HRC as an endometrial preparation method represented the largest risk factor (adjusted OR, 4.9; 95% CI, 2.0 to 12.3), with RPOC occurring in 0.05% of deliveries following HRC (51/97, 958 deliveries) but in only 0.01% following natural cycles (5/47, 79 deliveries). AH was also associated with a significantly higher risk of RPOC (adjusted OR, 1.9; 95% CI, 1.2 to 3.1), although the risk was lower than that associated with HRC). Subgroup analysis showed that these significant associations of HRC and AH with RPOC were present for transvaginal deliveries, but not deliveries by caesarean section.

Limitations, reasons for caution
The registry lacks important information regarding risk factors for RPOC, such as parity, body mass index, and history of previous uterine surgery. Furthermore, the lower prevalence of RPOC in the present study (0.04%) than in other studies (approximately 1%) suggests the possibility of non-differential misclassification for the outcomes of RPOC.

Wider implications of the findings
Although the possibility of residual confounding factors remains, the present findings suggest that additional care should be taken in the management of patients undergoing vaginal deliveries following FET who have HRC or AH.

Trial registration number
Not applicable
O-156 Embryo-like models: Using 3D gastruloids to understand human development
Authors: Moris N 
Published: June 2023

Abstract
The mammalian embryo develops through coordinated cell fate decisions that enable emerging spatiotemporal and morphogenetic complexity. While much insight into this process has been gained through studying model organisms, including mouse embryos, equivalent experiments are technically and ethically challenging in the human embryonic context. Instead, we use gastruloids: 3-dimensional aggregates of pluripotent stem cells that undergo multilineage differentiation to all three germ layers, polarise their gene expression and exhibit axial organisation that recapitulates many of the features of gastrulation and early organogenesis. By closely examining the dynamics and coordination of cell fate decisions and spatial gene expression organisation, we hope to better understand the regulatory logic behind early developmental events, particularly those that are human-specific. Likewise, by carefully manipulating the environment in which these gastruloids are grown, we can bias the structures towards particular lineages and morphological structures of interest. Doing so allows us to explore many of the principles of early development, and provides an opportunity to probe the mechanisms of biomedically-relevant conditions, such as congenital abnormalities.