bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-243 Personalized pregnancy odds estimation can be obtained using AI embryo evaluation and individual patient characteristics
Authors: Seidman D , Maor R , Tauber Y , Amar Y , Gilboa D 
Published: June 2023

Abstract

Study question
Can EMATM (AIVF, Israel) artificial intelligence (AI) platform provide personalized success estimates based on the patient’s metadata and embryonic development?

Summary answer
Individual patients can be given an accurate estimation of their chances for a clinical pregnancy using AI-based embryo evaluation and patient metadata.
What is known already: AI models for embryo evaluation are trained on diverse datasets using data from multiple clinics and from patients with varying ages and clinical history. Precision medicine can be attained by AI models that provide individual patients with personalized success rates per embryo transfer based on their characteristics.

Study design, size, duration
A large dataset (9,812 embryos) from 3 geographically diverse IVF Clinics (Israel, Spain, USA) with known clinical pregnancy (fetal heartbeat) and patient characteristics obtained from Electronic Medical Records (EMR) were used to evaluate the importance of individual features contributing to pregnancy.

Participants/materials, setting, methods
Machine learning models were trained to predict clinical pregnancy on a large training and feature set which combines AI scores (EMATM, AIVF) with additional information obtained from EMR systems and intrinsic features that can be derived from the embryo cohort. The importance of each one of the features for the prediction ability of the models was evaluated.

Main results and the role of chance
AI embryo score, maternal age and cohort features were found to be the major contributing factors for the prediction models, thus improving the accuracy of the estimates for pregnancy probability. Significant contributing factors were: cohort size, number of viable embryos, patient age, number of past treatments, BMI and EMA score. The AUC of the AI embryo score model was 0.7, when factoring in the patient metadata and the cohort features, the AUC of the combined model was 0.75.

Limitations, reasons for caution
This study is limited by its retrospective design. A prospective study is needed to validate the results.

Wider implications of the findings
This study validates the use of AI-based scores for embryo evaluation, for relative grading of the embryos within the cohort, and also to estimate the true pregnancy odds of each embryo based on individual patient features. This can provide a superior decision support tool for doctors, embryologists, and patients.

Trial registration number
not applicable
O-249 Calcium directly influences pituitary function through the Calcium Sensing Receptor (CaSR)
Authors: Poulsen N N , Hjerresen J , Juel Mortensen L , Sørensen K , Juul A , Blomberg Jensen M 
Published: June 2023

Abstract

Study question
Does calcium have a direct effect on pituitary function through CaSR?

Summary answer
CaSR is important for Hypothalamus-pituitary-gonadal (HPG) axis signaling, and lack of CaSR in the anterior pituitary leads to smaller reproductive organs in female mice.

What is known already
In a randomized clinical trial, prepubertal children were given calcium supplementation or placebo and girls in the intervention group went into puberty 5 months earlier than the placebo group. This effect was not detected in the boys who participated. CaSR is the main receptor for systemic calcium homeostasis, and its presence has been established in the anterior pituitary.

Study design, size, duration
We performed a mouse study comparing knock-out mice with a deletion of the CaSR in the anterior pituitary to wildtype mice. 13/13 female and 6/13 male knock-out/controls mice were included in the study.

Participants/materials, setting, methods
Female and male knock-out and control mice were sacrificed at 8 weeks. We obtained blood samples and reproductive organs was dissected, weighted and stored at -80 °C or stored in formalin before being paraffin embedded.

Main results and the role of chance
Female reproductive organs showed significantly lower weight when comparing CaSR knock-out to control mice. This includes ovary weight (3.7 mg vs. 6.4 mg; p = 0.0004) and uterus weight (27.9 mg vs. 67.0 mg; p = 0.0008). The weight difference was still significant after correcting for total body weight (organ weight/total body weight%): (0.02176 vs. 0,03534; p = 0.0035 and 0.1788 vs. 0.3826; p = 0.0023 respectively).
We did not observe a significant difference in male reproductive organs, nor any difference in pituitary weight in either sex.

Limitations, reasons for caution
The difference in reproductive organ weights is interesting, but it is also an early finding. Further analysis of the collected organs and blood samples will be conducted to further investigate the phenotype of the mouse model. We are also looking into correcting weight differences for estrous cycle effects.

Wider implications of the findings
If CaSR proves to be important for the regulation of the HPG-axis, it has a clinical perspective since CaSR can be modulated by the drug Cinacalcet, an allosteric agonist of CaSR, already on the market where it is used to treat kidney patients.

Trial registration number
Not applicable
O-280 Reading between the lines: Evaluating the clinical benefit of laboratory interventions from published studies
Authors: Wilkinson J 
Published: June 2023

Abstract
Embryologists rely on both randomised and non-randomised studies evaluating the effectiveness and safety of interventions. However, many of these studies contain subtle but critical methodological limitations, which are not identified by peer reviewers. Embryologists must therefore be critical consumers of the published literature. In this talk, I will highlight some common, serious methodological flaws occurring in studies of embryological interventions, and will give intuitive explanations of both the problems and the impact they may have on study results. This includes methods of analysing randomised controlled trials which nullify the benefits conferred by randomisation, and flawed methods of identifying study groups in observational studies which prevent any meaningful evaluation of an intervention's benefit. I will discuss underappreciated methodological challenges in studies evaluating artificial intelligence algorithms for embryo selection, which limit their usefulness, and will outline superior approaches to evaluate these interventions.
P-003 Obstructive azoospermia; MESA should be employed as the method for sperm retrieval, not TESE
Authors: Hibi H , Sonohara M , Sugie M , Fukunaga N , Asada Y 
Published: June 2023

Abstract

Study question
TESE is widely used for obstructive azoospermia (OA) as a surgical method for sperm retrieval, but is it benefiting the patient?

Summary answer
Since MESA-ICSI has a very good fertilization rate, clinical pregnancy rate and delivery rate, MESA should be employed for the OA subjects, not TESE.

What is known already
TESE and micro-TESE are technically simple, and widely used as a sperm retrieval surgery because they do not require microsurgical skills. Some review articles have shown no significant differences in the rates of cleavage, good-quality embryos, implantation, clinical pregnancy between ICSI with epididymal sperm or testicular sperm. Clinical usefulness of MESA is still controversial according to previous reports.

Study design, size, duration
We studied 110 patients diagnosed with OA and treated with MESA at the Asada Ladies Clinic between April 2004 and December 2021.

Participants/materials, setting, methods
The MESA was performed using a micropipette with a micropuncture technique under operative microscope. When no sperm were present or motility was not observed, additional punctures to the epididymal tubule were performed. Aspirated samples were transferred into modified human tubal fluid and sent to the in vitro fertilization (IVF) laboratory for cryopreservation.

Main results and the role of chance
Motile sperm were recovered in all cases (110 cases). Of these, ICSI using frozen thawed sperm was performed in 101 cases. The rate of normal fertilization rate was 76%. Of the 399 embryo transfer (ET) cycles, 168 had a clinical pregnancy (41% per ET). Of the 101 patients who underwent ART, 94 (93% per case) had clinical pregnancies resulting in 90 (89.1%) deliveries. It should be emphasized that since MESA does not involve incision of the testes, there are fewer postoperative peritoneal irritation symptoms and no concerns about postoperative testicular atrophy or low testosterone levels. Some review articles showed no significant differences in the rates of cleavage, good-quality embryo, implantation, clinical pregnancy between ICSI with epididymal sperm or testicular sperm. Although clinical usefulness of MESA is still controversial, if the ART results of MESA-ICSI and TESE-ICSI are the same, MESA should be performed as it is less invasive on the patient and reduces the burden on the embryologist who have to process the TESE tissue.

Limitations, reasons for caution
Some authors have reported that since MESA specimens contain DNA fragmentated sperm when compared with specimen of TESE, subsequent ICSI results in poorer fertilization and pregnancy rates. We did not evaluate sperm DNA fragmentation.

Wider implications of the findings
A large quantity of uncontaminated sperm can be retrieved using MESA which is less invasive for the patient, and there is no need for special processing before cryopreservation. Additionally, it can reduce the laboratory workload.

Trial registration number
not applicable
P-012 Time, risk &amp; motion study of an integrated artificial intelligence robotic system for semen analysis
Authors: Hill K , Alvarez M , Mora F , Thomas D , Tozer A , Viñals Gonzalez X 
Published: June 2023

Abstract

Study question
Can integration of a robotic system for semen analysis reduce operational failure modes and eliminate risk in the IVF laboratory?

Summary answer
A robotic system for semen analysis reduces operational failure modes and eliminates severe risks including those associated with reduced patient experience and increased patient stress.

What is known already
Recently, the ever-evolving field of IVF has experienced a rise in innovations to boost laboratory performance. Considering the lack of robust evidence in some of them, decisions on implementation are often based on opinion and product cost. Currently, an approach to assess risk, time and effectiveness has not been fully described. IVF is not error-free (Sakkas et al., 2018), hence all new technology coming into the laboratory ought to reduce risk of errors happening.

Study design, size, duration
Failure mode effects analysis (FMEA) was carried out on the workflow integration into an IVF centre (&gt;500 cycles per annum) to evaluate the possible procedural risks of manual semen analysis compared to a digitalised pathway. Possible sources of error were identified, and the Risk Priority Number (RPN), a product of likelihood, severity and detection of incidence was associated with each risk, as previously described by Rienzi et al., 2015.

Participants/materials, setting, methods
Using a systematic decision-making approach to quantify the value of incorporating the use of a robotic system (Mojo AISA) for semen analysis.

Main results and the role of chance
Five process phases were identified for conventional specimen analysis. There were eight associated process steps and 29 failure modes, among which 13 risks were given a moderate (RPN 15-50, i.e. data entry errors, incorrect count and sperm classification) and three were severe RPNs (RPN&gt;50), resulting in reduction in efficacy of treatment. Protocol using the robotic system resulted in a reduction of process phases to four and failure modes to 16, with four moderate and none severe RPNs. Implementation of the robotic system improved workflow by optimising time in motion for the IVF specialist and further reducing active time by at least 30%.

Limitations, reasons for caution
FMEA is a proactive method to identify potential incidents and help to develop strategies to mitigate risks. Ultimately, this forms part of a scheme for responsible development. The likelihood of incidences and time analysis were estimated based on clinical experience. Risks inherent to sample handling remained present.

Wider implications of the findings
The robotic system has the potential to eliminate risks that exist when manually inputting data to electronic medical records, whilst offering support to IVF specialists.

Trial registration number
not applicable
P-017 Validation of origami microscope “Foldscope” as a preliminary screening tool for male infertility
Authors: Errazuriz J , Carlos C , Alvaro S M , Isabel F , Pablo S , Patricio G , Patricio D 
Published: June 2023

Abstract

Study question
Is there a concordance between the new optical microscope based on origami (Foldscope) with a traditional microscope for semen analysis as a screening method?

Summary answer
There is a 91% direct concordance between the foldscope and a traditional microscope as screening for initial approximation to male infertility.

What is known already
Semen analysis is a key element on men fertility evaluation. In order to obtain a semen sample, patients have to assist to a fertility clinic where the sample is analyzed. However, due to either time or distance problems, many patients cannot attend to fertility clinics. On the other hand, Foldscope is an origami-based microscope that can provide over 2000x magnification, and it can be attached to a smartphone and take photos and videos, which can be sent to fertility specialists for analysis. This technology might provide important information about semen status, especially in areas with limited fertility care access.

Study design, size, duration
A retrospective observational study was carried out, we included semen samples obtained by masturbation from volunteers were analyzed for count, concentration, and motility from patients who were undergoing a fertility study between November 2021 and November 2022 in Clínica Alemana, Santiago, Chile.

Participants/materials, setting, methods
A total of 188 human semen samples were evaluated by a single embryologist under a standard microscope and later used the same sample to make a cell phone video with Foldscope. This information was randomized and the videos were subsequently analyzed by the same embryologist blindly. Finally, the matching of the results was carried out.

Main results and the role of chance
Moderate and significant positive correlation for concentration calculated as &gt; or &lt; 15 million/ml between Conventional Microscopy and Foldscope (correlation coefficient= 0.67, p &lt; 0.005) Sperm motility for progressives A+B recorded with Foldscope demonstrated a significant correlation with the traditional microscope results (correlation coefficient = 0.69, p &lt; 0.005). Finally, the concordance for the sperm count between both methods was 91%, with a kappa index of 0.66 (p &lt; 0.0001).

Limitations, reasons for caution
One of the most important limitations of semen analysis by foldscope is that it must be interpreted by an embryologist, which means that the images must be sent to a specialized center.

Wider implications of the findings
In countries with few economic resources and not many options to for reproductive medicine centers, the use of the foldscope microscope as a screening as an initial approximation to male fertility allows a quick and economical immediate referral to men with reproductive problems.

Trial registration number
not applicable
P-024 Effect of microsurgical varicocelectomy on fertility potential in patients with low sperm vitality
Authors: Mahdi M , Majzoub A , Arafa M , Elbardisi H , Khalafalla K , Alsaid S , Al Malki A 
Published: June 2023

Abstract

Study question
Does microsurgical varicocelectomy improve semen parameters and fertility potential in patients with low sperm vitality?

Summary answer
Micro surgical varicocelectomy in patients with low sperm vitality is beneficial as it results in significant improvement in sperm count and progressive motility.

What is known already
Low sperm vitality (Necrozoospermia) indicates the presence of higher percentage of necrotic/ dead sperm in the ejaculate which can impair fertility potential. Varicocele induced testicular hyperthermia is among the most common causes of impaired semen quality, including necrozoosprmia. While many studies confirmed the beneficial effect of varicocelectomy on different semen parameters, very few have evaluated its role on sperm vitality in particular.

Study design, size, duration
A retrospective study of 1521 patients who underwent microsurgical sub inguinal varicocelectomy in our center from 2011–2021.
A total of 115 patients with clinical varicocele and low sperm vitality (&lt;58%) were included.

Participants/materials, setting, methods
The exclusion criteria were history of genitourinary tract infection, exposure to heat, drugs or toxic compounds, hormonal disturbances or prior infertility related treatments. Patients demographics, and clinical data were collected, in addition to the pre- and post-operative Semen analysis (WHO 5th edition), sperm DNA fragmentation (Halosperm) and hormonal profile (estradiol, FSH, LH, Prolactin, Testosterone). Spearman’s correlations and Wilcoxon Signed Ranked Test were used for data analysis.

Main results and the role of chance
Mean age was 34.9±7.6 years. Varicocelectomy was done on left side in 75 patients and bilateral in 40 patients.
Sperm vitality was significantly negatively correlated with sperm DNA fragmentation (-0.618, p = 0.000) and abnormal sperm morphology (-0.435, p = 0.000, while it was significantly positively correlated with total motility (0.674, p = 0.000) & progressive motility (0.272, p = 0.003).
The median (IQR) sperm vitality pre-operatively was 41% (30-50) and the level increased post-operatively to 54% (31-63). There was a significant improvement in post-operative sperm count, progressive motility as well as LH and FSH levels. Improvements were also noted in total motility, normal morphology and sperm DNA fragmentation however the result didn’t reach statistical significance.

Limitations, reasons for caution
The main limitation is the retrospective design of the study and it did not evaluate the pregnancy outcomes.

Wider implications of the findings
Improvement in semen parameters by microsurgical varicocelectomy in patients with low sperm vitality is important as it may change the management plan for patients and extend their fertility options to natural conception or intrauterine insemination instead of only intracytoplasmic sperm injection.

Trial registration number
not applicable
P-028 Loss of the m6A methyltransferase METTL5 impairs spermiogenesis and male fertility
Authors: Chen H , Zhang M , Lin S , Xu W 
Published: June 2023

Abstract

Study question
Whether and how METTL5 regulates germ cell development during spermatogenesis.

Summary answer
METTL5 is required for spermiogenesis. Loss of METTL5 resulted in teratozoospermia and male infertility via reduced translation of acrosome and flagellum formation proteins.

What is known already
The roles of m6A modifications on mRNA in spermatogenesis have been extensively studied. It was reported that METTL5 knockout mice showed the brain development defect and sterility of 16-week male mice. However, the detailed mechanism of METTL5 affecting male fertility remains elusive.

Study design, size, duration
Mettl5 KO mice were kindly gifted from Prof. Shuibin Lin of The First Affiliated Hospital of Sun Yat-sen University. Heterozygotes of Mettl5 mice were used to generate Mettl5 homozygous knockout mice. The phenotype of KO mice was assessed. Ribosomal sequencing, proteomics analysis and further validation of protein translation were performed to explore the mechanism.

Participants/materials, setting, methods
Fertility assessment, sperm parameter analyses, sperm nuclear morphology analysis, Transmission electron microscopy (TEM), tissue Collection and histological analysis, protein extraction and western blot analysis, immunofluorescence studies, cDNA synthesis and qRT-PCR, in vitro fertilization (IVF) were used in this study.

Main results and the role of chance
Here we reported that methyltransferase-like 5 (METTL5) is involved in spermiogenesis as a methyltransferase mediating m6A modification on rRNA. Mettl5 knockout mice were infertile with teratozoospermia. The acrosome in the sperm head was absent with reduced sperm motility. Furthermore, the fertilization ability of sperm in the IVF experiment failed. Mechanistically, the level of rRNA m6A modification was significantly decreased in the testes of Mettl5 KO mice. The translational efficiency and protein levels of acrosome and flagellum formation proteins such as FSIP2, ODF2, GK2, PGK2, and AKAP4 were significantly reduced when METTL5 was depleted.

Limitations, reasons for caution
The METTL5 mutation in the patient with teratozoospermia was not examined in the present study

Wider implications of the findings
The rRNA m6A modification is also involved in regulating spermatogenesis by METTL5. This study highlights the critical role of rRNA epigenetic modifications during spermatogenesis and provides novel theoretical explanations for the m6A modifications.

Trial registration number
Not applicable