bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-005 Mullerian anomalies overview
Authors: Prasad S 
Published: August 2021

Abstract text
Mullerian Duct Anomalies- An Overview
Prof. Sudha Prasad
President Indian Fertility Society, Director, Matritava Advanced IVF & Training Centre, New Delhi, India
Congenital anomalies of the mullerian duct system is one of the complex disorder encountered in gynecological practice. Mullerian ducts are paired embryological structures which undergo fusion and resorption in utero to form the uterus, fallopian tubes, cervix and upper two-thirds of the vagina. Disruption in the mullerian duct development throughout embryogenesis could result a large spectrum of inherent abnormalities identified as mullerian duct anomalies (MDAs).
There is a wide variation in the prevalence of MDAs across various studies, ranging from 1–10% in the general population to 2–8% among infertile women and 5–30% among women with a history of miscarriage. These discrepancies in the reported prevalence are mainly attributed to lack of a universal classification system.
Different varieties of malformations can occur when this system is not well developed. It ranges from absence of uterus, cervix or vagina, septum/duplication of vagina to of the uterus and vagina to minor uterine cavity abnormalities. Mullerian malformations are frequently associated with abnormalities of the renal and axial skeletal systems. Therefore, on initial examination of MDAs patients, these points should be kept in mind.
Most mullerian duct anomalies (MDAs) are associated with functioning ovaries and age-appropriate external genitalia. These abnormalities are often recognized after the onset of puberty. After the onset of puberty, young women often present to the gynecologist with menstrual disorders. Late presentations include infertility and obstetric complications.
A meta-analysis of nine studies comprising 3805 women with congenital uterine anomalies reviewed the obstetric outcome. The study reported that canalization defects such as septate and partial septate uteri had reduce fertility and increase rates of miscarriage and preterm delivery. None of the unification defects (bicornuate, unicornuate and didelphic uteri) reduce fertility but some are related to miscarriage and prematurity. Arcuate uteri are specifically associated with second-trimester miscarriage. All uterine abnormalities increase the risk of fetal malformation during delivery1.
A retrospective longitudinal study concluded that reproductive performance of the unicornuate and didelphys uteri was poor (20–30% chance of carrying a pregnancy to term), while that of the septate and bicornuate uteri (live birth rate of 62%) was better than expected. The arcuate uterus had no impact on reproductive performance of women2.
Agenesis of uterus and vagina requires surgical techniques, such as the Vecchietti and McIndoe procedures, have enabled many women to have normal sexual relations. Uterine transplant has changed the perspective of all other surgical advances and assisted reproductive technologies to improve fertility and obstetric outcomes3, 4,5.
O-008 Improving outcomes in women with Mullerian anomalies
Authors: Malhotra J , Malhotra N , Malhotra N 
Published: August 2021

Abstract text
Mullerian Anomalies are present in approximately 5% to 7% of the general population and the incidence is a little more in infertile and recurrent miscarriage women. Most of the recent studies have reported that the obstetric outcome is compromised in this group with greater risk of infertility, recurrent pregnancy loss, intrauterine growth retardation, preterm birth and many other obstetric complications, which may be individually related to the different types of Mullerian Anomalies. In this presentation, We are going to discuss on how the outcomes are different in the various Mullerian Anomalies depending upon the degree of the defects related to different complications with more profound defects. We will also discuss on how to optimize the pregnancy outcomes with various interventions and what the literature review supports.
Trial registration number
Study funding
Funding source
P-523 Whole-chromosome aneuploidies revealed by transcriptome of trophectoderm biopsied from human pre-implantation blastocyst
Authors: Song L , Yanwen X , Bing C , Yan X , Xiu Y , Canquan Z 
Published: August 2021

Abstract

Study question
Whether mRNA transcriptome of biopsied trophectoderm (TE) in human pre-implantation blastocyst can predict embryo karyotype?

Summary answer
mRNA transcriptome of biopsied TE can precisely predict whole-chromosome aneuploidies but not mosaicism or segmental aneuploidies.

What is known already
Karyotype of human pre-implantation blastocyst is well recognized by PGT-A. However, genome can’t demonstrate gene expression level which might infer the development potential of euploidy. Transcriptome of blastocyst by singe-cell RNA-seq has revealed the lineage segregation of human pre-implantation blastocyst. It is not known whether transcriptome of biopsied TE used in PGT-A can infer the karyotype of human pre-implantation blastocyst.

Study design, size, duration
A total of 74 TE samples were biopsied from 26 blastocysts which were donated from patients who underwent PGT at our Reproductive Medicine Center. All of these embryos have been previously diagnosed as aneuploidies (n = 19) or euploidies (n = 7) with monogenic disorder.

Participants/materials, setting, methods
The DNA and mRNA of all biopsied TEs were separated independently using a modified oligo-dT bead capture, followed by PGT-A of DNA and smart2-sequencing of mRNA (G&T-seq). Karyotype of biopsied TEs were confirmed with PGT-A performed in MiSeq system (Illumina) in our PGT laboratory with the use of next-generation sequencing. Data of transcriptome was analyzed using Rstudio and R package InferCNV to predict aneuploidies by referring to euploidies which were inferred with corresponding PGT-A results.

Main results and the role of chance
In human pre-implantation blastocyst, all whole-chromosome aneuploidies could be inferred by transcriptome of biopsied TE, which were consistent with PGT-A result. But chromosomal mosaicism or segmental aneuploidies were hard to be predicted precisely by transcriptome of TE.

Limitations, reasons for caution
The main limitation of this study lies in the inability to retrieve the exact copy number variations from mRNA transcription. Gene expression is in a great imbalance in such an early development of human pre-implantation blastocyst.

Wider implications of the findings
Our data suggest that mRNA transcriptome is enough for prediction of whole-chromosome aneuploidies. The method and value for predicting mosaicism and segmental aneuploidies by transcriptome should be further investigated.

Trial registration number
not applicable
O-034 Infertility treatment law making in Europe: the clash of knowledge, ethics and business
Authors: Wilinska-Zelek A 
Published: August 2021

Abstract text
Infertility treatment law making in Europe: the clash of knowledge, ethics and business
Today, there is no common European set of rules for Assisted Reproduction Technology (ART). ART is now controlled by legislation in almost all European countries, substantial variations exist within the detail of that legislation.
Main legal differences between countries relate to: embryo selection, particularly by genetic screening, embryo freezing and embryo transfer, preimplantation genetic diagnosis (PGD), oocyte donation, anonymity of gamete donors, surrogacy, patient eligibility criteria (eg, sexual orientation, age), reimbursement and state funding.
The most complete survey ever of the ART legal and funding framework of 43 European countries was published in the ESHRE medical journal Human Reproduction Open: Calhaz-Jorge C, De Geyter C, Kupka MS, et al. Survey on ART and IUI: Legislation, regulation, funding and registries in European countries. Hum Reprod Open 2020; doi:10.1093/hropen/hoz044.
Unfortunately, changes of legislation are so dynamic that much of the information in this article is no longer up-to-date.
Lawyers observe that one of the most important rule of law “When the Law ceases to reflect the realities of Life, it is the Law that will Change” does not work in ART. In regard to this matter dominant rule is: “The Law will change only when it ceases to reflect the government’s point of view and lobbyists’ needs”. Modern medical knowledge and the society’s needs are often not the main concern during the law making discussion.
The speech discusses the issues related to infertility treatment law making in Europe with a focus of the problem that modern medical knowledge in this process is not taken into account at all. The author diagnoses numerous problem related to determining the border between medical knowledge, ethics and business in law making process.
The observed problems will be discussed on selected examples (from Poland, Greece and the United Kingdom) during presentation at the ESHRE on-line 37th Annual Meeting.
O-035 Searching for the perfect country - mapping out differences in fertility treatments and access to treatments across Europe
Authors: Bye K 
Published: August 2021

Abstract text
Fertility Europe has established a working group that is examining secondary data on legislation, regulation and funding of fertility treatment across Europe. The data has been mapped in order to easily visualize the “perfect country” in terms of fertility treatments[Vi1] . The map will be updated every two years in order to show progress towards more countries reaching the status of “perfect country”. As the map provides a clear picture on the differences in access to treatments[Vi2] across Europe, it is expected to be a useful advocacy tool for patient[Vi3] associations working to influence the current treatment situation in their country. This talk focuses on the work that has been done by the Fertility Europe working group to date, to create the map of the “perfect country”, and the possibilities that such a map represents from a patient advocacy perspective.
treatmentS [Vi1] [Vi1]
treatmentS [Vi2] [Vi2]
patient associations’ [Vi3] [Vi3]
O-039 Mitochondrial ATP generation in mammalian eggs and Ca2+ signaling
Authors: Swann K 
Published: August 2021

Abstract text
In metaphase II arrested mammalian oocytes (eggs) and cleavage stage embryos the mitochondria are responsible for nearly all ATP production because glycolysis is inactivated. Luciferase assays show that ATP levels in eggs are strictly dependent upon pyruvate and fatty acid oxidation. The level of ATP in eggs appears to be maximal in conventional medium because the addition of extra mitochondrial substrates to eggs does not increase cytosolic ATP. The only clear elevation of ATP is seen at fertilization and is associated with sperm induced Ca2+ oscillations. Our recent findings suggest that the level of ATP modulates events at fertilization.
At fertilization, the egg is activated by sperm derived PLCzeta which triggers a series of Ca2+ oscillations, with each Ca2+ release event causes by inositol trisphosphate (InsP3). Previous studies have shown that mouse eggs are more sensitive to PLCzeta, and generate higher frequency Ca2+ oscillations, than human eggs. Mouse eggs also generate Ca2+ oscillations and activate in response to Sr2+ that directly stimulates InsP3 receptors. In contrast, human eggs that contain the same type of InsP3 receptors do not generate Ca2+ oscillations in response to Sr2+.
The difference in sensitivity of Ca2+ release between species can be explained by the fact that mouse eggs are about ten times more sensitive to InsP3 than human eggs. The reason for this difference appears to be due to ATP. The ATP level in unfertilized mouse eggs is about twice that in human eggs. Furthermore, the ability of mouse eggs to Sr2+ medium can be abolished by removing the mitochondrial substrate pyruvate, which reduces the ATP level. Adding back pyruvate to such eggs restores ATP levels promotes Sr2+ induced Ca2+ levels in mouse eggs. These data suggest that the level of ATP, possibly as ATP4-, modulates the sensitivity of the InsP3 receptor and the ability of eggs to generate Ca2+ oscillations. The level of cytosolic ATP may represent a significant ‘egg factor’ in determining the success of fertilization in humans. Enhancing mitochondrial ATP production could be useful in improving activation and embryo development after fertilization, or after artificial egg activation.
References:
Dumollard et al. (2009) Seminar in Cell and Developmental Biology 20, 346-353
Campbell and Swann (2006) Developmental Biology 298, 225-233
Storey et al. (2021) Molecular Human Reproduction 27, gaaa086
O-044 Chinese Society of Reproductive Medicine 2018 annual report on ART
Authors: Deng C 
Published: August 2021

Abstract text

Objective
To analysis the Chinese ART data in 2018 to provide evidence for utilization of various ART.

Methods
The data of ART of 263 Reproductive Centers in the mainland of China in 2018 were collected by CSRM ART Data Reporting System. A cross-sectional survey of the use of ART technology was performed.

Results
In 2018, the CSRM data reporting system reported 105 610 AID/AIH cycles, 323 938 oocyte retrieval cycles, 147 129 fresh embryo transfer cycles, 254 012 frozen-thawed embryo transfer (FET) cycles, and 204 688 newborn . The patient's age was mainly concentrated in the group &lt;35 years old, accounting for 63.75%. The pregnancy rate and live birth rate of retrieval cycles were 52.49% and 42.23% respectively. The pregnancy rate and live birth rate of FET cycles were 48.71% and 37.68% respectively. Among ART complications, the incidence of moderate to severe OHSS was 1.42%, 0.03% postoperative bleeding, 0.01% postoperative pelvic infection, and 0.04% the other complications. The incidence of birth defects of IVF was 0.87%.

Conclusions
This study uses "CSRM data reporting system" data to describe and analyze the current status of ART, basically consistent with the comparison in 2016 and 2017 that most cycles with good outcomes. However, no clear conclusions have been drawn on the changes of PGD/PGS cycle, all-freeze cycle and comprehensive analysis should be conducted by combining with laboratory data.
Trial registration number:
Study funding:
Funding source:
O-045 Synthetic human embryo-like structures: a new paradigm for human embryology
Authors: Fu J 
Published: August 2021

Abstract text
Early human development remains mysterious and very difficult to study. Recent advances in mammalian embryology, stem cell biology, organoid technology, and bioengineering have contributed to a significant interest in bottom-up, synthetic stem cell-derived models of human development (or embryoids). The controllability and reproducibility of human embryoids coupled with the ease of genetically modifying stem cell lines, the ability to manipulate culture conditions and the simplicity of live imaging make them robust and attractive systems to disentangle cellular behaviors and signaling interactions that drive human embryogenesis. In this talk, I will describe our effort in using human pluripotent stem cells (hPSCs) to develop tractable experimental models of the peri-implantation embryonic development and neurulation. The peri-implantation human embryoids developed by us recapitulate key early post-implantation developmental landmarks successively, including pro-amniotic cavity formation, amniotic ectoderm-epiblast patterning, primordial germ cell specification, and development of the primitive streak with controlled anteroposterior polarity. I will further discuss an hPSC-based neuroectoderm patterning model to recapitulate the formation of the neural plate and another patterned neural tube model with fully defined anterior-posterior and dorsal-ventral axes.
O-053 Early life factors that may influence adult male reproductive
Authors: Hart R 
Published: August 2021

Abstract text
This presentation will provide a brief overview of testicular development and will describe a critical period of development at approximately 8-14 weeks of gestation, when the testicle may be vulnerable to external influences, potentially having a negative effect on subsequent development. The talk with then describe the testicular dysgenesis syndrome hypothesis, proposed by Niels Skakkebæk, and using the presenters work within the Western Australian (Raine) Cohort will go onto demonstrate how early life exposures may influence mature testicular function. Worryingly, the presentation will describe how adolescent features of early metabolic disturbance within the Raine Cohort are already having a determinantal effect on the reproductive function of these men in late adolescence, many years before the majority are seeking paternity.
O-055 Why we should be testing embryos for polygenic traits
Authors: Savulescu J 
Published: August 2021

Abstract
Abstract text
The past few years have brought significant breakthroughs in understanding human genetics. This knowledge has been used to develop ‘polygenic scores’ (or ‘polygenic risk scores’) which provide probabilistic information about the development of polygenic conditions such as diabetes or schizophrenia. They are already being used in reproduction to select for embryos at lower risk of developing disease. The world’s first baby, Aurea, has been born after being selected on the basis of a Genomic Health Index score provided by Genomic Prediction (https://www.youtube.com/watch?v=HE5ADe7BgdM&ab_channel= GenomicPrediction).
I argue for the use of this technology not only for the selection of embryos at lower risk of disease but for the selection of advantageous non-disease traits.
Currently, the use of polygenic scores for embryo selection is subject to existing regulations concerning embryo testing and selection. Existing regulatory approaches include ‘disease-based’ models which limit embryo selection to avoiding disease characteristics (employed in various formats in Australia, the UK, Italy, Switzerland and France, among others), and ‘laissez-faire’ or ‘libertarian’ models, under which embryo testing and selection remain unregulated (as in the USA). With Sarah Munday, I have introduced a novel ‘Welfarist Model’ which limits embryo selection according to the impact of the predicted trait on well-being. We compare the strengths and weaknesses of each model as a way of regulating polygenic scores. Polygenic scores create the potential for existing embryo selection technologies to be used to select for a wider range of predicted genetically influenced characteristics including continuous traits. Indeed, polygenic scores exist to predict future intelligence, and there have been suggestions that they will be used to make predictions within the normal range in the USA in embryo selection. We examine how these three models would apply to the prediction of non-disease traits such as intelligence. The genetics of intelligence remains controversial both scientifically and ethically. This paper does not attempt to resolve these issues. However, as with many biomedical advances, an effective regulatory regime must be in place as soon as the technology is available. If there is no regulation in place, then the market effectively decides ethical issues.
O-141 Mapping of SARS-CoV-2-associated receptors and proteases mRNA in human endometrium during natural and stimulated cycles
Authors: Haouzi D , Entezami F , Brouillet S , Barry F , Gala A , Ferrieres-Hoa A , Tal A , Hamamah S 
Published: August 2021

Abstract

Study question
Covid-19 pandemic has significantly affected the assisted reproductive technology (ART) practice. Understanding whether SARS-CoV-2 could infect endometrial tissues during ART is crucial for risk mitigation

Summary answer
Analyses of gene expression profiles of SARS-CoV-2 host entry candidates from microarray data suggest that endometrium should be considered as potential target for SARS-CoV-2 infection.

What is known already
Very few studies analyzed the gene expression profiles of SARS-CoV-2-associated receptors and proteases, mainly focusing on ACE2 and TMPRSS2 expression, resulting incomplete knowledge in different specimens from female genital tract. However, no studies have analyzed the potential impact of controlled ovarian stimulation (COS) protocols during ART procedure on the endometrial gene expression profiles of SARS-CoV-2-associated receptors and proteases

Study design, size, duration
To address this question, we retrospectively examined the gene expression profile of SARS-CoV-2-associated receptors and proteases in endometrial biopsies of a cohort of ART candidates using Affymetrix microarray data

Participants/materials, setting, methods
Human endometrial tissue under natural (n = 62) and COS cycles (n = 42) were analyzed. A focus was particularly made on the renin-angiotensin system relates genes with a prominent role in the virus infection, and gene expression levels of receptors and proteases closely related to SARS-CoV-2 infectionwas also studied.

Main results and the role of chance
Using our large cohort of endometrial samples, we reported a high prevalence of genes related to the ACE2 pathway, including AGT, AGTR1, ANPEP, CTSA, ENPEP, LNPEP, MME, NLN, THOP1, BSG and CTSL during both phases(early- and mid-secretory phase), and mainly during the mid-secretory phase for ACE2. The highest signal intensities were found for CTSA, LNPEP, MME, NLN, BSG and CTSL. The most representative of dual coexpression of SARS-CoV-2-associated receptor and protease in endometrium was BSG-CSTL and BSG-CTSA. It s also important to note high variation of SARS-CoV-2 receptors inter-patients under natural cycle.Globally, the impact of COS on endometrial gene expression profile of SARS-CoV-2-associated receptors and proteases of non Covid-19 patients is low, suggesting no additional potential risks of SARS-CoV-2 infection during stimulated ART procedure compared with natural cycles.

Limitations, reasons for caution
Analyses of Affymetrix microarray gene expression data were performed in non-COVID-19 patients. Whether the SARS-CoV-2 infection changes the endometrial gene expression profile of SARS-CoV-2-associated receptors and proteases is under investigation

Wider implications of the findings
Specimens from female genital tract may be considered as potential targets for SARS-CoV-2.

Trial registration number
not applicable