IVF Practice Research Articles

Comparative study of machine learning approaches integrated with genetic algorithm for IVF success prediction.

IVF is a widely-used assisted reproductive technology with a consistent success rate of around 30%, and improving this rate is crucial due to emotional, financial, and health-related implications for infertile couples. This study aimed to develop a model for predicting IVF outcome by comparing five machine-learning techniques. The research approached five prominent machine learning algorithms, including Random Forest, Artificial Neural Network (ANN), Support Vector Machine (SVM), Recursive Partitioning and Regression Trees (RPART), and AdaBoost, in the context of IVF success prediction. The study also incorporated GA as a feature selection method to enhance the predictive models' robustness. Findings demonstrate that AdaBoost, particularly when combined with GA feature selection, achieved the highest accuracy rate of 89.8%. Using GA, Random Forest also demonstrated strong performance, achieving an accuracy rate of 87.4%. Genetic Algorithm significantly improved the performance of all classifiers, emphasizing the importance of feature selection. Ten crucial features, including female age, AMH, endometrial thickness, sperm count, and various indicators of oocyte and embryo quality, were identified as key determinants of IVF success. These findings underscore the potential of machine learning and feature selection techniques to assist IVF clinicians in providing more accurate predictions, enabling tailored treatment plans for each patient. Future research and validation can further enhance the practicality and reliability of these predictive models in clinical IVF practice.

A View of Civil Law and Islamic Law on the Practice of Surrogate Mother

IVF is one of the modern methods that can help legal couples obtain children. Both Indonesian Civil Law and Islamic Law allow this practice. Still, it must be carried out based on the provisions, namely by involving couples who are legal in the eyes of the law. IVF carried out through surrogate motherhood is prohibited by both positive law and Islamic law because its existence can disrupt lineage. Children born from this practice are not considered legitimate due to confusion and ambiguity during the process. This research is a normative juridical literature study that is processed based on primary and secondary legal sources consisting of primary, secondary, tertiary legal materials, and non-legal materials with the aim of: 1) Understand how Indonesian civil law and Islamic law view the issue of surrogate mothers; and 2) Knowing how the guardianship status of IVF children born through surrogacy practices. It was found that both Positive Law and Islamic Law prohibit the practice of IVF with surrogate mothers because it results in legal confusion for the child. This research is expected to contribute to further research, especially research that raises the theme of IVF.

The relationship between socioeconomic status and perinatal outcomes in in vitro fertilization conceptions

ObjectiveTo evaluate whether socioeconomic status has an impact on perinatal outcomes in in-vitro-fertilization pregnancies. We hypothesize that with greater coverage there may be an alleviation of the financial burden of IVF which can facilitates application of evidence-based practices. BackgroundIn-vitro fertilization (IVF) is the most used assisted reproductive technology in the United States, with growing efficiency and demand for in-vitro fertilization. Certain states have mandated coverage that enable low-income individuals to undergo in-vitro fertilization treatment. Study DesignA retrospective population-based observational study was conducted in accordance with the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database over the six-year period from 2008 to 2014 examining 10,000 in-vitro-fertilization deliveries. Maternal outcomes of interest included preterm pre-labor rupture of membranes (PPROM), preterm birth (i.e., before 37 weeks of gestation), placental abruption, Caesarean Section (C/S), operative vaginal delivery, spontaneous vaginal delivery (SVD), maternal infection, chorioamnionitis, hysterectomy, and postpartum hemorrhage. Neonatal outcomes included small for gestational age (SGA) defined as birth weight less than tenth percentile, intrauterine fetal death (IUFD), and congenital anomalies. ResultsOur study found that socioeconomic status did not have a statistically relevant effect on perinatal outcomes in women who underwent in-vitro-fertilization to conceive after adjusting for the potential confounding effects of maternal demographic, pre-existing clinical characteristics, and comorbidities. ConclusionThe literature suggests that in states with mandated in-vitro-fertilization coverage, there are better perinatal outcomes due in part to greater utilization of best IVF practices, such as single-embryo transfers. Moreover, the quality of medical care in states with coverage is in the highest quartile in the country. Therefore, our findings of equivalent perinatal outcomes in IVF care irrelevant of socio-economic status suggests that a possibly of lack of access to quality medical care may be a factor in the health disparities usually seen in lower socioeconomic status individuals.

Predictive factors of aneuploidy in infertile patients undergoing IVF: a retrospective analysis in a private IVF practice

BackgroundPGT-A has become an important part of IVF treatments. Despite its increased use, there are contradicting results on its role in improving reproductive outcomes of ART cycles. Given that aneuploidy is a main limiting factor for IVF success, we aimed to study the predictive factors of aneuploidy in infertile patients undergoing IVF and hence highlight the patients who would benefit the most from genetic testing.ResultsA retrospective analysis of 1242 blastocysts biopsied in the setting of PGT-A cycles was performed. The euploid group included 703 embryos, while the aneuploid group had 539 embryos. The factors included in the analyses were the couple’s history as well as the embryo characteristics. The primary outcome was the rate of aneuploid embryos per patient’s history as well as per embryo characteristics. The aneuploidy rate (AR) in our cohort was 43.4%. The woman’s age was found to be a significant predictor (OR 1.045, 95% CI 1.008–1.084, p = 0.016). Biopsy on day 5 as well as degree of expansion 3 was also found to affect significantly (OR 0.724, 95% CI .541–.970, p = 0.03 and OR 2.645, 95% CI 1.252–5.585, p = 0.011). Lack of consanguinity decreased the AR by an OR 0.274 with 95% CI .137–.547, p < 0.001. The number of blastocysts available, trophectoderm quality, embryo grade, gonadotropins as well as trigger used were not found to be significant predictors (p = 0.495, 0.649, 0.264, 0.717 and 0.659 respectively).ConclusionAdvanced female age, consanguinity, the day of embryo biopsy, and the degree of blastocyst expansion were all found to affect the incidence of AR. The age of the male partner, cause of infertility, and grade of embryo at biopsy were not found to correlate with aneuploidy.

#282 : Maximizing IVF Success Rates: Optimized Simulation Using a Novel Decision-Support Tool

Background and Aims: A mathematical procedure and a decision support tool, Opt-IVF, were developed to overcome the shortcomings of the current IVF practice of dosage profile determination by trial and error, which can provide a personalized model and optimized drug treatment. This paper describes the decision support tool for improving outcomes of IVF treatment for both antagonist and agonist protocols used in real practice. We present the results of two clinical trials. Method: Our earlier work developed models for agonist and antagonist protocols based on an analogy between superovulation and batch crystallization. This model was customized for each patient using two days of follicular data, and the optimal control method was applied to optimize the dosage profile. Validation of the model was conducted with retrospective data from 150 patients from India and 50 from the United States. Opt-IVF reduced total hormone dosage by 20 to 60%, reduced US testing by 50 to 75%, and provided a higher number of oocytes and high-quality embryos. Results: The primary outcome measures studied for two clinical trials with Opt-IVF include total hormonal dosage, % follicles retrieved, MII oocytes, Embryos, and Grade A Embryos. Results showed that Opt-IVF reduces drug dosage and testing and increases the number of embryos, Grade A embryos, and high-quality blastocysts significantly. Subgroup analysis showed improvements in outcomes were more significant for both Poor-responder and PCOS patients than for normal responders. Pregnancy rates were significantly higher with Opt-IVF patients than with standard protocol control patients. Conclusions: A mathematics-based approach to dosage profile determination results in optimal mature follicles, better embryos, and higher pregnancy with reduced dosage and the need for testing.

Facilitation of Ovarian Response by Mechanical Force-Latest Insight on Fertility Improvement in Women with Poor Ovarian Response or Primary Ovarian Insufficiency.

The decline in fertility in aging women, especially those with poor ovarian response (POR) or primary ovarian insufficiency (POI), is a major concern for modern IVF centers. Fertility treatments have traditionally relied on gonadotropin- and steroid-hormone-based IVF practices, but these methods have limitations, especially for women with aging ovaries. Researchers have been motivated to explore alternative approaches. Ovarian aging is a complicated process, and the deterioration of oocytes, follicular cells, the extracellular matrix (ECM), and the stromal compartment can all contribute to declining fertility. Adjunct interventions that involve the use of hormones, steroids, and cofactors and gamete engineering are two major research areas aimed to improve fertility in aging women. Additionally, mechanical procedures including the In Vitro Activation (IVA) procedure, which combines pharmacological activators and fragmentation of ovarian strips, and the Whole Ovary Laparoscopic Incision (WOLI) procedure that solely relies on mechanical manipulation in vivo have shown promising results in improving follicle growth and fertility in women with POR and POI. Advances in the use of mechanical procedures have brought exciting opportunities to improve fertility outcomes in aging women with POR or POI. While the lack of a comprehensive understanding of the molecular mechanisms that lead to fertility decline in aging women remains a major challenge for further improvement of mechanical-manipulation-based approaches, recent progress has provided a better view of how these procedures promote folliculogenesis in the fibrotic and avascular aging ovaries. In this review, we first provide a brief overview of the potential mechanisms that contribute to ovarian aging in POI and POR patients, followed by a discussion of measures that aim to improve ovarian folliculogenesis in aging women. At last, we discuss the likely mechanisms that contribute to the outcomes of IVA and WOLI procedures and potential future directions.

Changing clinical significance of oocyte maturity grades with advancing female age advances precision medicine in IVF

In current IVF practice, metaphase-2 (M2) oocytes are considered most efficient in producing good quality embryos. Maximizing their number at all ages is standard clinical practice, while immature germinal vesicle (GV) oocytes are mostly automatically discarded. We present preliminary evidence that oocyte maturity grades with advancing age significantly change in their abilities to produce good quality embryos, with M2 oocytes significantly declining, GV oocytes improving, and M1 oocytes staying the same. These data contradict the over-40-year-old dogma that oocyte grades functionally do not change with advancing age, supporting potential changes to current IVF practice: (1) Stimulation protocols and timing of oocyte retrieval can be adjusted to a patient's age and ovarian function. (2) In older and younger women with prematurely aging ovaries, GV oocytes may no longer be automatically discarded. (3) In some infertile women, rescue invitro maturation of immature oocytes may delay the need for third-party egg donation.

Does a public online IVF prediction tool help set patient expectations? A mixed methods evaluation study.

Does a public online IVF success prediction calculator based on real-world data help set patient expectations? The YourIVFSuccess Estimator aided consumer expectations of IVF success: one quarter (24%) of participants were unsure of their estimated IVF success before using the tool; one half changed their prediction of success after using the tool and one quarter (26%) had their expectations of IVF success confirmed. Several web-based IVF prediction tools exist worldwide but have not been evaluated for their impact on patient expectations, nor for patient perceptions of usefulness and trustworthiness. This is a pre-post evaluation of a convenience sample of 780 online users of the Australian YourIVFSuccess Estimatorhttps://yourivfsuccess.com.au/ between 1 July and 31 November 2021. Participants were eligible if they were over 18 years of age, Australian residents, and considering IVF for themselves or their partner. Participants filled in online surveys before and after using the YourIVFSuccess Estimator. The response rate of participants who completed both surveys and the YourIVFSuccess Estimator was 56% (n = 439). The YourIVFSuccess Estimator aided consumer expectations of IVF success: one quarter (24%) of participants were unsure of their estimated IVF success before using the tool; one half changed their prediction of success after using the tool (20% increased, 30% decreased), bringing their predictions in line with the YourIVFSuccess Estimator, and one quarter (26%) had their IVF success expectations confirmed. One in five participants claimed they would change the timing of IVF treatment. The majority of participants found the tool to be at least moderately trustworthy (91%), applicable (82%), and helpful (80%), and would recommend it to others (60%). The main reasons given for the positive responses were that the tool is independent (government funded, academic) and based on real-world data. Those who did not find it applicable or helpful were more likely to have had a worse-than-expected prediction, or to have experienced non-medical infertility (e.g. single women, LGBTQIA+), noting that at the time of evaluation the Estimator did not accommodate these patient groups. Those who dropped out between the pre- and post-surveys tended to have a lower education status or have been born outside of Australia or New Zealand, therefore there may be issues with generalizability. With consumers demanding increasing levels of transparency and participation in decisions around their medical care, public-facing IVF predictor tools based on real-world data are useful for aligning expectations about IVF success rates. Given differences in patient characteristics and IVF practices internationally, national data sources should be used to inform country-specific IVF prediction tools. The YourIVFSuccess website and evaluation of the YourIVFSuccess Estimator are supported by the Medical Research Future Fund (MRFF) Emerging Priorities and Consumer Driven Research initiative: EPCD000007. BKB, ND, and OF have no conflicts to declare. DM holds a clinical role at Virtus Health. His role did not influence the analysis plan or interpretation of results in this study. GMC is an employee of the UNSW Sydney, and Director of the UNSW NPESU. UNSW receives research funding on behalf of Prof Chambers from the MRFF to develop and manage the Your IVF Success website. Grant ID: MRFF Emerging Priorities and Consumer Driven Research initiative: EPCD000007. N/A.

O-110 Mild stimulation is the future in ART

Abstract The World Health Organisation has called for a simple, safe, and effective IVF treatment which could be both affordable and widely accessible. Unfortunately, IVF practice in developed countries seems to be trending in the opposite direction, making ovarian stimulation more intense, complex, expensive, and globally inaccessible, under the pretext of maximising the cumulative live birth rate (LBR) or by offering a ‘package’ of a ‘complete family’ from a single attempt of IVF. In reality, data from randomised controlled trials (RCTs) has found no difference in fresh cycle as well as cumulative LBRs whether a mild or high stimulation dose is administered. This is because, higher oocyte yield with high ovarian stimulation does not translate into better-quality embryos and this has been demonstrated in systematic reviews and meta-analyses. There appears to be confusion between stimulation ‘dose’ and ‘response’. Young women with good ovarian reserve are more likely to have a high response to stimulation despite being treated with a dose that falls within the definition of ‘mild stimulation’, whereas aggressive stimulation fails to improve the response in poor responders. A rising cumulative LBR with increasing number of oocytes is attributable to these good responders, but this is disconnected with the intensity of ovarian stimulation. The euploid embryo yield similarly is related to the number of oocytes and cumulative LBR which are influenced by the woman’s age and ovarian reserve but not the stimulation dose. Both the numbers of aneuploid and euploid embryos rise with increasing oocyte yield, keeping the proportion unchanged. Advocates of ‘one and done’ approach have shown that only 1 in 5 women can produce the requisite number of oocytes to have more than 1 child. This means, the remaining 80% patients would be subjected to intense stimulation, incurring risks of overstimulation, treatment burden and cost without achieving the goal of ‘completing’ their family. Psychological analysis from a RCT reported a higher incidence of post-treatment depression after Conventional compared to Mild IVF. Even in the era of agonist trigger and ‘freeze all embryos’, OHSS has not been totally eliminated- the World Registry reported around 40 cases of severe OHSS in 10 000 cycles. Clinical complications such as haemorrhage and infection associated with overstimulation could be magnified in low-resource settings with lack of facilities and expertise. Livebirth rates albeit of key importance cannot be the only index of success. Our commitment should be to make IVF accessible globally by adopting effective stimulation protocols that reduce treatment burden and cost for the patient and improve health outcomes for mother and baby. Only mild stimulation IVF can fulfil this global vision and need as an increasing body of evidence has confirmed that mild stimulation is as successful as conventional stimulation, while being safer and less expensive. Individualised mild stimulation protocols are the smartest way forward in a global setting for all patient groups. It is time to reflect on what is best for our patients and society in the long-term.

P-744 Reporting chromosomal mosaicism reduces the overall accuracy of preimplantation genetic testing for aneuploidies: results from the extended in vitro culture of 230 human embryos

Abstract Study question What is the accuracy of reporting chromosomal mosaicism in the context of next generation sequencing (NGS)-based preimplantation genetic testing for aneuploidies (PGT-A)? Summary answer Extended in vitro culture of human embryos demonstrated that reporting mosaicism increased the risk of false positives, reducing the overall accuracy of PGT-A to 70%. What is known already PGT-A has been introduced into IVF practice to improve clinical outcomes. However, diagnostic accuracy remains controversial, particularly regarding chromosomal mosaicism. While NGS allows the detection and reporting of mosaicism from a trophectoderm (TE) biopsy, the inability to discern biological variability from technical artefacts continues to limit the interpretation of PGT-A results. As reports of mosaicism often have a major impact on patient management, achieving an appropriate level of standardization will be vital to avoid overestimation. Extended in vitro culture of human embryos up to 12 days post fertilization (D12) delivers an important, clinically relevant platform for the validation of PGT-A. Study design, size, duration A total of 230 clinically unsuitable blastocysts were included in the study. Embryos were selected based on their original diagnosis following PGT-A as: uniformly abnormal (n = 158), aneuploid and mosaic (n = 21), mosaic only (n = 36) and euploid (n = 15) but carrying a monogenic disease mutation in homozygosis. Blastocysts were originally classified as mosaic if they contained 30-70% abnormal cells, with &amp;lt;50% mosaicism defined as low level and &amp;gt;50% considered high level mosaicism. Participants/materials, setting, methods Vitrified blastocysts were warmed and cultured to D12 using established protocols to generate embryo outgrowths. A total of 90 outgrowths were selected for NGS. Outgrowths were collected whole (n = 64) or separated into 2-4 portions (n = 26), which were then analyzed individually. We correlated the original PGT-A diagnoses to developmental outcomes and the chromosomal status of the embryo outgrowths. Fisher’s Exact test (two-sided) was used for evaluating associations. All p-values &amp;lt;0.05 were considered significant. Main results and the role of chance Following extended culture, 49.1% (113/230) of embryos remained viable and attached, while 50.9% (117/230) degenerated and detached. As previously observed in our model, euploid blastocysts and embryos diagnosed with trisomies, duplications or chromosomal mosaicism were significantly more likely to attach throughout the extended culture, while monosomies, deletions and complex chromosomal constitutions impaired in vitro development (total attached, 78.3% vs. 24.8%, p &amp;lt; 0.0001). When compared to the original biopsy, we established 100% concordance when reporting euploidy and uniform whole chromosome aneuploidies, demonstrating an overall high sensitivity of PGT-A. Of the blastocysts diagnosed as mosaic only, 80.6% (29/36) remained viable throughout the extended culture. These were sequenced either whole (n = 11) or in parts (n = 18). At D12, 69.0% (20/29) of these embryos were uniformly euploid, while 27.6% (8/29) were uniformly aneuploid across all outgrowth samples. Notably, the latter were all originally diagnosed as high level mosaics. One embryo (3.4%) revealed a true mosaic configuration, with evidence of a reciprocal event across the different outgrowth samples. Ultimately, the proportion of embryos accurately diagnosed as euploid was 25.0% (8/35), with an overall false positive error rate of 77.1%. False positives were largely attributed to the diagnosis of mosaicism, 85.2% (23/27) or segmental aberrations, 14.8% (4/27). Limitations, reasons for caution This study was performed using a single PGT-A assay and cannot be extrapolated to other platforms. To evaluate the predictive value of chromosomal mosaicism, we selected embryos based on their chromosomal profiles. This may underestimate the accuracy of PGT-A, as sampling of embryos was not performed randomly. Wider implications of the findings We confirm the high sensitivity of PGT-A, as euploidy and uniform whole chromosome abnormalities were detected with high accuracy. However, predictive value is considerably reduced when diagnosing mosaicism. Given the high false positive rate, reporting mosaicism remains difficult to justify, as potentially viable embryos continue to be excluded for transfer. Trial registration number NA

O-263 Effect of clindamycin and a live biotherapeutic containing lactobacilli on the reproductive outcomes of IVF patients with abnormal vaginal microbiota: a double-blind, placebo-controlled multicentre trial

Abstract Study question Does treatment of abnormal vaginal microbiota improve the reproductive outcomes of IVF patients? Summary answer Data is being analysed and will be presented at ESHRE 2023. What is known already An increasing number of studies reported an association between abnormal genital tract microbiota and adverse reproductive outcomes in IVF patients. One hypothesis could be that vaginal microbiota ascend to the endometrium where the microbiota hampers implantation. To the best of our knowledge, this is the first study powered to investigate causality between abnormal genital tract microbiota - in this study defined by a bacterial vaginosis like vaginal microbiota - and clinical pregnancy rate in IVF patients. Study design, size, duration Double-blind, placebo-controlled multicentre trial in IVF patients diagnosed with abnormal vaginal microbiota and subsequently randomised into three parallel groups 1:1:1. The first group received clindamycin 300 mg ×2 daily for 7 days followed by vaginal Lactobacillus crispatus until the clinical pregnancy scan. The second group received clindamycin and placebo, whereas the third group received placebo/placebo. A total of 1518 patients were screened, and 338 patients were randomised. The study duration was from 2017 to 2023. Participants/materials, setting, methods IVF patients with any cause of infertility embarking on their first, second or third IVF stimulation cycle or embryo transfer were approached for inclusion. At a minimum 12 days prior to embryo transfer, patients were screened for abnormal vaginal microbiota defined by a qPCR assay, targeting high quantitative loads of Fannyhessea vaginae and Gardnerella spp. Patients were excluded if they had intrauterine malformations like polyps, septum, and fibroma. Main results and the role of chance Data and safety monitoring board has decided not to open the randomization code yet. The final dataset is being completed. Data is being analysed and will be presented at ESHRE 2023. Limitations, reasons for caution Data is being analysed and will be presented at ESHRE 2023. Wider implications of the findings The present drug intervention study used clindamycin and a live biotherapeutic containing Lactobacillus crispatus. The results of the study could have a worldwide important clinical impact on daily IVF practice as currently there is no evidence that screening and treating IVF patients with abnormal vaginal microbiota improves the reproductive outcome. Trial registration number EudraCT 2016-002385-31

O-295 Dual trigger does not improve reproductive outcomes in advanced maternal age women

Abstract Study question Could dual trigger increase oocyte yield and maturation rate in women of advanced maternal age (≥ 40) undergoing IVF? Summary answer Dual trigger does not result in higher oocyte yield or maturation rates compared to hCG monotrigger What is known already Advanced maternal age is related to poor ovarian response (POR) and remains a major therapeutic challenge in routine IVF practice, because of the association with low live birth rates and high cancellation rates. hCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome (by improving oocyte quantity and quality) in normal responders, while evidence in poor responders remains controversial. Study design, size, duration This is a retrospective cohort study including patients attending a private IVF clinic from 1st January 2018 until 1st June 2022. Participants/materials, setting, methods All women who underwent IVF/ICSI in antagonist protocol in our center were included. Patients may have undergone triggering of the final oocyte maturation either with 250mcg of rhCG or 0.2 mg of GnRH agonist. Mature oocytes were inseminated using ICSI. Main results and the role of chance In total, 2242 patients were included, 454 (20.2%) in the rhCG group and 1788 (79.8%) in the dual trigger group. There was no significant difference in female age [41.3 (1.12) vs 41.3 (1.19), p value 0.94]. Total stimulation units and duration were also comparable between groups. The number of oocytes and MII oocytes did not differ significantly between rhCG and dual trigger group [5.8 (4.1) vs 6.3 (4.7) and 4.7 (3.3) vs 4.9 (3.4), p = 0.15 and 0.49, respectively]. Maturation rates were similar 81.7% (22.4) and 79.8% (23.5), p = 0.15, as well as fertilization rates (defined as the number of oocytes fertilized divided by the total number of cumulus-oocyte complexes recruited) [57% (29.7) vs 58.8% (29.4), p value=0.2]. Embryo utilization rates (defined as the total number of embryos transferred and cryopreserved divided by the number of oocytes fertilized) were comparable between the two arms: 69.7% (34.2) vs 70% (33.9), p value =0.22. Multivariate Poisson regression analysis adjusting for relevant confounders (AMH, total stimulation units) showed that the type of triggering strategy (dual trigger vs rhCG) was not associated with either the number of MII oocytes (coefficient 0.2, p value=0.24) or maturation rates (coefficient -1.8, p value 0.12). Limitations, reasons for caution The main limitation is the retrospective design of our study, with an inherent risk of bias. Wider implications of the findings To the best of our knowledge, this is the largest study evaluating dual trigger strategy in advanced maternal age women. Our data demonstrate that dual trigger cannot improve the outcome of low prognosis women and should not be used as a panacea for all IVF patients. Trial registration number NA

Assuring quality in assisted reproduction laboratories: assessing the performance of ART Compass - a digital art staff management platform.

Staff management is the most cited ART/IVF laboratory inspection deficiency. Small ART/IVF clinics may be challenged to perform these activities by low staff volume; similarly, large ART/IVF networks may be challenged by high staff volume and large datasets. Here, we sought to investigate the performance of an automated, digital platform solution to manage this necessary task. The ART Compass (ARTC) digital staff management platform was used to assess the clinical decision-making of ART laboratory staff. The survey modules presented standardized instructions to technologists and measured inter- and intra-technologist variability for subjective "clinical decision-making" type questions. Internal and external comparisons were achieved by providing technologists two answers: (1) a comparison to their own lab director and (2) to the most popular response collectively provided by all lab director level accounts. The platform is hosted on HIPAA compliant Amazon web servers, accessible via web browser and mobile applications for iOS (Apple) and Android mobile devices. Here, we investigated the performance of a digital staff management platform for single embryologist IVF practices and for three IVF lab networks (sites A, B, C) from 2020 to 2022. Embryology dish preparation survey results show variance among respondents in the following: PPE use, media volume, timing of oil overlay, and timing of moving prepared dishes to incubators. Surveying the perceived Gardner score and terms in use for early blastocysts reveals a lack of standardization of terminology and fair to poor agreement. We observed moderate inter-technologist agreement for ICM and TE grade (0.47 and 0.52, respectively). Lastly, the clinical decision of choice to freeze or discard an embryo revealed that agreement to freeze was highest for the top-quality embryos, and that some embryos can be highly contested, evenly split between choice to freeze or discard. We conclude that a digital platform is a novel and effective tool to automate, routinely monitor, and assure quality for staff-related parameters in ART and IVF laboratories. Use of a digital platform can increase regulatory compliance and provide actionable insight for quality assurance in both single embryologist practices and for large networks. Furthermore, clinical decision-making can be augmented with artificial intelligence integration.

‘All planned babies must be born’: Women’s experience of infertility and assisted reproductive technologies in Hungary

In recent years, the issue of reproduction has been increasingly thematized in Hungarian political discourse. This has not only occurred at the discursive level, but the government has also introduced new policies regarding reproduction and family life, thus new regulations have been introduced concerning the medical practice of IVF and other ART which have affected practices associated with infertility. The article aims to discuss the ways that policies and discourses shape the views of women struggling with infertility. The medical and political discourse seems to emphasize the responsibility of women in relation to fertility-related issues, despite the fact that the problem also affects men. Furthermore, with the increased surveillance of women undergoing assisted reproductive treatment, the importance of the latter’s self-reflexivity, discipline, and responsibility is emphasized. To discuss these issues, the article uses a multi-method approach. The primary data source is in-depth narrative interviews with IVF participants, supplemented by the analysis of political discourses about childbearing and infertility which help in the examination of how different policies and discourses shape individual experiences and desires. I argue that recent policies on IVF and related medical discourses and practices can potentially emphasize the responsibility of women. Women who cannot or do not want to reproduce may be presented as selfish or treated with pity, and these notions are intensified due to the government's explicit pronatalist agenda, which only supports those who conform to conservative heteronormative reproductive standards.

A NOVEL BLASTOMERE MORPHOLOGY MARKER IN CLEAVAGE STAGE EMBRYOS STRONGLY PREDICTS BLASTOCYST DEVELOPMENT AND PREGNANCY OUTCOME

In our IVF practice we have observed that a novel morphological feature of cleavage stage embryos seems to correlate well with blastocyst formation and clinical pregnancy. We performed this retrospective cohort study to examine whether our observed blastomere marker in cleaving embryos has any impact on blastocyst development and clinical pregnancy rates following single blastocyst transfers.

THE ROLE OF ADVANCED PRACTICE PROVIDERS IN THE MODERN IVF PRACTICE, CAN THEY HELP FILL THE DEARTH OF NEW REPRODUCTIVE ENDOCRINOLOGISTS?

IVF procedures nationwide have increased over the last decade while the graduation of fellowship trained reproductive endocrinologists (RE) has decreased; thus, creating an imbalance in doctor to patient ratios. This imbalance results in larger wait times and general patient unsatisfaction. One way to meet the growing need of infertile patients is the introduction of advanced practice providers (APP’s) to the modern IVF practice. It is the goal of study to determine and compare the conversion rates and embryo transfer (ET) rates of APPs to those of RE’s.

Predicting cumulative live birth for couples beginning their second complete cycle of in vitro fertilization treatment.

STUDY QUESTIONCan we develop an IVF prediction model to estimate individualized chances of a live birth over multiple complete cycles of IVF in couples embarking on their second complete cycle of treatment?SUMMARY ANSWERYes, our prediction model can estimate individualized chances of cumulative live birth over three additional complete cycles of IVF.WHAT IS KNOWN ALREADYAfter the completion of a first complete cycle of IVF, couples who are unsuccessful may choose to undergo further treatment to have their first child, while those who have had a live birth may decide to have more children. Existing prediction models can estimate the overall chances of success in couples before commencing IVF but are unable to revise these chances on the basis of the couple’s response to a first treatment cycle in terms of the number of eggs retrieved and pregnancy outcome. This makes it difficult for couples to plan and prepare emotionally and financially for the next step in their treatment.STUDY DESIGN, SIZE, DURATIONFor model development, a population-based cohort was used of 49 314 women who started their second cycle of IVF including ICSI in the UK from 1999 to 2008 using their own oocytes and their partners’ sperm. External validation was performed on data from 39 442 women who underwent their second cycle from 2010 to 2016.PARTICIPANTS/MATERIALS, SETTING, METHODSData about all UK IVF treatments were obtained from the Human Fertilisation and Embryology Authority (HFEA) database. Using a discrete time logistic regression model, we predicted the cumulative probability of live birth from the second up to and including the fourth complete cycles of IVF. Inverse probability weighting was used to account for treatment discontinuation. Discrimination was assessed using c-statistic and calibration was assessed using calibration-in-the-large and calibration slope.MAIN RESULTS AND THE ROLE OF CHANCEFollowing exclusions, 49 314 women with 73 053 complete cycles were included. 12 408 (25.2%) had a live birth resulting from their second complete cycle. Cumulatively, 17 394 (35.3%) had a live birth over complete cycles two to four. The model showed moderate discriminative ability (c-statistic: 0.65, 95% CI: 0.64 to 0.65) and evidence of overprediction (calibration-in-the-large = −0.08) and overfitting (calibration slope 0.85, 95% CI: 0.81 to 0.88) in the validation cohort. However, after recalibration the fit was much improved. The recalibrated model identified the following key predictors of live birth: female age (38 versus 32 years—adjusted odds ratio: 0.59, 95% CI: 0.57 to 0.62), number of eggs retrieved in the first complete cycle (12 versus 4 eggs; 1.34, 1.30 to 1.37) and outcome of the first complete cycle (live birth versus no pregnancy; 1.78, 1.66 to 1.91; live birth versus pregnancy loss; 1.29, 1.23 to 1.36). As an example, a 32-year-old with 2 years of non-tubal infertility who had 12 eggs retrieved from her first stimulation and had a live birth during her first complete cycle has a 46% chance of having a further live birth from the second complete cycle of IVF and an 81% chance over a further three cycles.LIMITATIONS, REASONS FOR CAUTIONThe developed model was updated using validation data that was 6 to 12 years old. IVF practice continues to evolve over time, which may affect the accuracy of predictions from the model. We were unable to adjust for some potentially important predictors, e.g. BMI, smoking and alcohol intake in women, as well as measures of ovarian reserve such as antral follicle count. These were not available in the linked HFEA dataset.WIDER IMPLICATIONS OF THE FINDINGSBy appropriately adjusting for couples who discontinue treatment, our novel prediction model will provide more realistic chances of live birth in couples starting a second complete cycle of IVF. Clinicians can use these predictions to inform discussion with couples who wish to plan ahead. This prediction tool will enable couples to prepare emotionally, financially and logistically for IVF treatment.STUDY FUNDING/COMPETING INTEREST(S)This study was supported by an Elphinstone scholarship scheme at the University of Aberdeen and Aberdeen Fertility Centre, University of Aberdeen. The authors have no conflict of interest.TRIAL REGISTRATION NUMBERN/A.

P-379 Ongoing pregnancy rate (OPR) of day (D) 7 euploid blastocysts is inferior to D5/D6 euploid blastocysts in frozen embryo transfer (FET) cycles

Abstract Study question Do delayed-grown D7 euploid blastocysts have similar OPRs as D5 or D6 euploid blastocysts in FET cycles? Summary answer Although OPR is significantly higher with D5/D6 euploid blastocysts than D7, patients aged &amp;gt;38 years might benefit when slow-developing blastocysts are routinely cultured till D7. What is known already Current IVF practice suggests that embryos of optimal development reach blastocyst stage 116±2 hours after insemination. Recently, high reproductive potential has been reported with D6 as well as with D7 blastocysts. Although D7 blastocysts have a delayed embryo development, euploidy rates range between 25% and 49% if biopsy is performed. Usable D7 blastocysts represent nearly 5% of embryos in IVF with acceptable pregnancy and live birth rates, however, data are still limited. Therefore, further evidence of FET outcomes with D5, D6 and D7 euploid blastocysts are needed to investigate whether prolonged in-vitro embryo culture till D7 should be performed routinely. Study design, size, duration A single centre observational study was performed between June 2017 and November 2021, including 1396 single euploid FET cycles with blastocysts biopsied on D5 (N = 795), D6 (N = 572) or D7 (N = 29). Patients underwent endometrial preparation for a FET in a natural cycle (NC) or hormone replacement treatment (HRT). Only blastocysts graded ≥ BL3CC (Gardner scoring) before trophectoderm (TE) biopsy on D5, D6 or D7, which re-expanded within 1-hour post-warming, were considered in the analysis. Participants/materials, setting, methods All warmed blastocysts were transferred after 120 hours of progesterone (P4) exposure. In NC, P4 was administered after ovulation until pregnancy test (PT). For HRT cycles, estradiol was prescribed until endometrial thickness reached ≥6 mm or a trilaminar pattern was seen on which P4 was supplemented until PT. OPR was recorded at 12 weeks by the presence of a gestational sac/s and fetal heartbeat. A multivariate logistic regression model with generalized estimating equation was performed. Main results and the role of chance Women’s mean age differed significantly for FET cycles performed with D5, D6 and D7 euploid blastocysts (33.2±5.6, 34.5±5.3 and 36.1±4.5 years old; P &amp;lt; 0.001) as well as AMH values (ng/mL) (3.6±3.6, 2.9±2.8 and 2.3±1.8; P &amp;lt; 0.001; respectively). OPR with D5 euploid blastocysts was significantly higher than D6 and D7 (55.6%, 44.9% and 10.3%; P &amp;lt; 0.001), however, miscarriage rates did not differ (9.3%, 6.6% and 6.9%; P = 0.201; respectively). Following an adjusted multivariate logistic regression model, the factors associated with a reduced OPR were: D7 FETs (OR: 0.19 [0.06-0.63]; P = 0.006), ICM grade C (OR: 0.29 [0.17-0.48]; P &amp;lt; 0.001) and TE grade C (OR: 0.58 [0.38-0.89]; P = 0.012). Contrary, OPR outcomes were increased in NC compared to HRT cycles (OR: 1.35 [1.06-1.71]; P = 0.013). A sub-analysis showed that advanced maternal age was a risk factor of having a D7 FET cycle (OR: 1.09 [1.01-1.17]; P = 0.025). In patients &amp;gt;38 years, OPR was improved if D7 FET cycles were performed however, this finding was nonsignificant (OR: 2.33 [0.19-29.4], P = 0.510). In patients &amp;lt;38 years, D7 FET cycles were significantly negatively associated with OPR outcomes (OR: 0.07 [0.01-0.54], P = 0.011). Regardless of patient’s age, OPR outcomes with D5/D6 were higher than D7 FETs. Limitations, reasons for caution The current results are based on an observational study including a limited sample size of D7 euploid blastocysts FET cycles. Additionally, live birth rates should be considered in a further analysis to validate the performance of D5 and D6, compared to D7 euploid blastocysts, in both, NC and HRT cycles. Wider implications of the findings Considering age as a risk factor of having delayed grown blastocysts in-vitro, culturing embryos till D7 can be a strategy to increase OPR in patients &amp;gt;38 years old. With an increase in age, patients are more likely to have blastocysts biopsied on D6/D7. OPR outcomes are increased in NC FETs. Trial registration number non-clinical trials

P-540 Is there a necessity to process preimplantation genetic aneuploidy testing (PGT-A) of embryos in all patients undergoing Assisted Reproductive Technology (ART) programs?

Abstract Study question Should each embryo undergo preimplantation genetic testing for aneuploidy (PGT-A), or a personalized approach following indications such as age should be applied? Summary answer PGT-A does not increase clinical pregnancy and live birth rates in women under 35, however results are significantly improved for female patients over 35 years. What is known already PGT is a powerful tool in standard IVF practice however, despite all the benefits of the technology, it remains one of the most controversial topics that continue to generate interest, discussion, and debate in the field of reproductive medicine. Proponents believe that the potential of PGT-A allows effectively selecting a euploid embryo based on its genetic status and achieving a result in a short time regardless of the patient's age. Opponents consider that PGT-A cannot reflect the chromosomal status of the entire embryo with 100% accuracy, and embryo manipulation is inherently invasive and traumatic, which may reduce the life-birth potential. Study design, size, duration The retrospective single-center study included 2164 ART cycles performed from 2017 to 2020 at the Institute of Reproductive Medicine, Almaty, Kazakhstan. Clinical pregnancy rates (CPR), live birth rates (LBR), and pregnancy losses were analyzed. Results of frozen embryo transfer (FET) cycles with PGT-A as Group A (n = 637), FET without PGT-A as Group B (n = 705) and fresh cycle transfer as Group C (n = 822) have been compared. Moreover, selection were categorized by female age: ≤35 and &amp;gt;35. Participants/materials, setting, methods In the “fresh” IVF cycle (Group C), day 5 blastocysts of excellent/good quality according to the Gardner classification were selected for transfer. Trophectoderm (TE) biopsy of about 5-10 cells was performed on day 5/6 followed by vitrification (Kitazato). PGT-A was processed by comparative genomic hybridization (aCGH) on the Agilent platform. The transfer of thawed embryos of Group A (with PGT-A) and Group B (without PGT-A) was conducted into the uterine cavity under ultrasound control. Main results and the role of chance A total of 2318 blastocysts have been analyzed for the study. The proportion of euploid/aneuploid embryos in females under 35 years was 60.5/39.5%, respectively. In the category of over 35, this ratio was inverse - 41.9/58.1%. The results of the study haven't revealed statistical differences in age category under 35 years in CPR between Groups A, B, and C and amounted to 58.9% (227/385), 58.7% (637/1084), and 58.9% (482/936), respectively. However, in the category of women over 35 CPR was significantly higher (p &amp;lt; 0.001) in Group A - 53.2% (134/252) compared with Groups B - 40.9% (167/408) and C - 39.0% (185/474). Early pregnancy losses in patients under 35 in Group B were remarkably higher compared to Group A and composed to 12.2% (16/227) vs 7.1% (78/637), respectively (p &amp;lt; 0.05). A similar trend was traced in these groups in females over 35 -14.4% (24/167) vs 8.9% (12/134). The percentage of LBR in women over 35 years was significantly higher (p &amp;lt; 0.001) in Group A - 48.4%, compared to Groups B and C (35 and 34.2%). We did not find a notable difference between the two groups in women aged under 35. Relationships between variables were assessed by Student’s T-test. Limitations, reasons for caution The current study is limited due to the results of mosaic embryo transfers were excluded. Wider implications of the findings Although using PGT-A is growing each year, a significant increase in the rate of CPR and LBR was noted only in women over 35 years of age. However, concerning safety, in patients undergoing PGT-A, the risk of having a child with chromosomal diseases is significantly reduced. Trial registration number NA

#ESHREjc report: seeing is believing! How time lapse imaging can improve IVF practice and take it to the future clinic.

#ESHREjc report: seeing is believing! How time lapse imaging can improve IVF practice and take it to the future clinic.