In Vitro Fertilization Success Research Articles

Artificial intelligence system for outcome evaluations of human in vitro fertilization-derived embryos.

In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on days or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for aneuploidy prediction and consequent live-birth outcomes. These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709-0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Our study underscores the AI model's ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

Harnessing Artificial Intelligence to Predict Ovarian Stimulation Outcomes in In Vitro Fertilization: Scoping Review.

In the realm of in vitro fertilization (IVF), artificial intelligence (AI) models serve as invaluable tools for clinicians, offering predictive insights into ovarian stimulation outcomes. Predicting and understanding a patient's response to ovarian stimulation can help in personalizing doses of drugs, preventing adverse outcomes (eg, hyperstimulation), and improving the likelihood of successful fertilization and pregnancy. Given the pivotal role of accurate predictions in IVF procedures, it becomes important to investigate the landscape of AI models that are being used to predict the outcomes of ovarian stimulation. The objective of this review is to comprehensively examine the literature to explore the characteristics of AI models used for predicting ovarian stimulation outcomes in the context of IVF. A total of 6 electronic databases were searched for peer-reviewed literature published before August 2023, using the concepts of IVF and AI, along with their related terms. Records were independently screened by 2 reviewers against the eligibility criteria. The extracted data were then consolidated and presented through narrative synthesis. Upon reviewing 1348 articles, 30 met the predetermined inclusion criteria. The literature primarily focused on the number of oocytes retrieved as the main predicted outcome. Microscopy images stood out as the primary ground truth reference. The reviewed studies also highlighted that the most frequently adopted stimulation protocol was the gonadotropin-releasing hormone (GnRH) antagonist. In terms of using trigger medication, human chorionic gonadotropin (hCG) was the most commonly selected option. Among the machine learning techniques, the favored choice was the support vector machine. As for the validation of AI algorithms, the hold-out cross-validation method was the most prevalent. The area under the curve was highlighted as the primary evaluation metric. The literature exhibited a wide variation in the number of features used for AI algorithm development, ranging from 2 to 28,054 features. Data were mostly sourced from patient demographics, followed by laboratory data, specifically hormonal levels. Notably, the vast majority of studies were restricted to a single infertility clinic and exclusively relied on nonpublic data sets. These insights highlight an urgent need to diversify data sources and explore varied AI techniques for improved prediction accuracy and generalizability of AI models for the prediction of ovarian stimulation outcomes. Future research should prioritize multiclinic collaborations and consider leveraging public data sets, aiming for more precise AI-driven predictions that ultimately boost patient care and IVF success rates.

O-257 Comparing the accuracy of the novel clustering model versus phenotype classification in predicting live birth in polycystic ovary syndrome women undergoing In-Vitro fertilization

Abstract Study question Is the clustering model more accurate than phenotype classification in predicting live birth in polycystic ovary syndrome (PCOS) women undergoing in vitro fertilization (IVF)? Summary answer Novel PCOS clusters, identified by patients’ endocrine and metabolic profiles, more accurately predict live birth rates in women undergoing IVF than the traditional phenotype classification What is known already PCOS is a heterogeneous condition that affects fertility and IVF success. It is classified based on three factors: hyperandrogenism (HA), ovulatory dysfunction (OD), and polycystic ovaries (PCOM). The ESHRE/ASRM classification system identifies four phenotypes: A (including all three factors), B (HA and OD), C (HA and PCOM), and D (OD and PCOM). Although this classification is widely used, its focus solely on clinical signs and symptoms, while neglecting underlying endocrine and metabolic factors, may limit its effectiveness in predicting fertility outcomes in PCOS patients. Therefore, classifying PCOS patients may require a more comprehensive and inclusive assessment approach. Study design, size, duration This prospective cohort study was conducted from June 2020 to August 2022 at a tertiary IVF center in Ho Chi Minh City, Vietnam. Clustering models were built based on the endocrine and metabolic profiles of 731 PCOS patients. Patients were grouped into novel clusters based on their endocrine and metabolic profiles and compared with traditional phenotypes classification. The primary outcome measured was the live birth rate. Participants/materials, setting, methods Patients aged 18–45, diagnosed with PCOS according to the Rotterdam 2003 criteria, and undergoing IVF treatment were included in the study. Patients with hypothyroidism, Cushing’s syndrome, congenital adrenal hyperplasia, or contraindications to hormonal treatment were excluded. We employed Gaussian Mixture Models for clustering, using endocrine and metabolic data as the key features. We then compared the accuracy of the clustering model with phenotype classification in predicting IVF outcomes using a logistic regression model. Main results and the role of chance We identified three distinct clusters among polycystic ovary syndrome (PCOS) patients. Cluster 0 (n = 298) was characterized by significant insulin resistance and dyslipidemia. Cluster 1 (n = 219) displayed the lean PCOS phenotype, and Cluster 2 (n = 214) had moderate insulin resistance with severe hyperandrogenism. Our findings indicated that Clusters 1 and 2 had a higher cumulative live birth rate (CLBR) (39.7% and 37.9% versus 28.5% in Cluster 0, p = 0.015) and lower gestational diabetes rates (8.68% and 6.07%, respectively) compared to Cluster 0 (12.4%, p = 0.048). Additionally, the prevalence of hypertensive disorders during pregnancy showed differences across clusters (3.69% in Cluster 1, 0.46% in Cluster 2, and 2.8% in Cluster 0, p = 0.059). In contrast, the traditional phenotype classification did not demonstrate significant differences in CLBR, gestational diabetes, and hypertensive disorders. The cluster-based method provided a more accurate prediction of CLBR using logistic regression, with an AUC of 0.67 (95% CI: 0.57-0.76) compared to 0.49 (95% CI: 0.41-0.59) for traditional classifications (p = 0.001) Limitations, reasons for caution This is a single-center study conducted on Vietnamese patients. Therefore, the generalizability may be limited. The novel clustering’s predictive value for IVF outcomes in PCOS patients requires further validation in prospective studies. Wider implications of the findings This study suggests a potential shift towards personalized IVF treatment strategies for PCOS, using machine learning-based PCOS clustering identified by patients’ endocrine and metabolic profiles. Trial registration number NCT04364087

O-043 Con

Abstract Dual and/or double trigger improve IVF success - CON The improvement of in vitro fertilization (IVF) outcomes remains a pivotal area of reproductive medicine research, with the dual trigger approach emerging as a significant innovation. This con abstract explores the scientific basis, methodology, and outcomes associated with the dual trigger strategy, juxtaposed with conventional triggering methods in IVF protocols. The dual trigger, incorporating both Gonadotropin-Releasing Hormone Agonist (GnRHa) and Human Chorionic Gonadotropin (hCG), has been posited to improve oocyte maturation, retrieval-, and live birth rates. By scrutinizing recent studies, clinical trials, and meta-analyses, this debate aims to delineate the efficacy, safety, and application scope of this approach. Initial investigations into the dual trigger method have highlighted its potential to ameliorate oocyte quality and maturity, which are crucial determinants of IVF success. The mechanism underlying this improvement involves the simultaneous activation of LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone) receptors, enhancing follicular response and oocyte developmental competence. Studies have demonstrated an increase in the number of mature oocytes retrieved, attributed to the more synchronized and comprehensive follicular stimulation afforded by the dual trigger. This augmentation in oocyte quality and quantity directly correlates with enhanced embryo development profiles, and higher implantation and clinical pregnancy rates. Furthermore, the dual trigger method has shown promise in reducing the incidence of Ovarian Hyperstimulation Syndrome (OHSS), a severe complication of IVF treatments. By leveraging the luteolytic effects of GnRHa, this strategy minimizes the risk associated with exogenous hCG administration, thus offering a safer alternative for patients predisposed to OHSS. The application of the dual trigger in specific patient cohorts, such as those with PCOS or poor ovarian responders, has been underlined, indicating its potential for personalized reproductive medicine. However, the implementation of the dual trigger strategy is not without challenges. Variability in patient response necessitates a highly individualized approach, with precise dosing and timing adjustments to optimize outcomes. The existing literature presents a heterogeneity in study designs, populations, and outcome measures, which complicates the direct comparison of dual trigger efficacy against traditional methods. Furthermore, the long-term safety and potential impacts on offspring warrant further investigation, given the recent adoption of this approach. In conclusion, the dual trigger strategy may offer significant benefits in enhancing IVF outcomes. Its potential to improve oocyte maturity and quality could increase the number of retrievable oocytes and reduce the incidence of OHSS. However, it is important to acknowledge that, while the GnRH agonist trigger combined with a freeze-all strategy eliminates the risk of OHSS in women with PCOS, the dual trigger approach followed by fresh embryo transfer does not. Further research is imperative to refine its application, understand its mechanisms fully, and establish comprehensive guidelines for its use. The promise of the dual trigger approach underscores the importance of continuous innovation and evidence-based practices in enhancing the efficacy and safety of IVF treatments.

P-664 Insulin-like peptide 3 as a potential biomarker in predicting IVF success and ovarian reserve in women with unexplained infertility and diminishing ovarian reserve

Abstract Study question Could insulin-like peptide 3 (INSL3) predict ovarian reserve and in vitro fertilization (IVF) success in women with unexplained infertility (UI) and diminishing ovarian reserve (DOR)? Summary answer In women with DOR, reduced intrafollicular and serum INSL3 levels correspond with low AMH and high FSH levels, similar to established ovarian reserve markers. What is known already INSL3, belonging to the insulin-like peptide family, is produced by theca interna cells within antral follicles and the corpora lutea. It is hypothesized that INSL3 is integral to the initial development and function of antral follicles, specifically through its regulatory effect on androgen biosynthesis in the thecal cells of these follicles. Moreover, INSL3 is implicated in the modulation of the ovarian microenvironment, which is essential for facilitating the maturation of oocytes. Study design, size, duration This research was carried out at the IVF centers of two tertiary university hospitals, assessing 49 infertile women with either UI (n = 24) or DOR (n = 25) during IVF treatment. A control group (n = 26) comprised women with normal ovarian reserve undergoing IVF due to male or tubal factors. Outcome parameters are ovarian reserve markers (serum FSH, estradiol, AMH, INSL3 concentration and antral follicle count [AFC]), positive pregnancy rate and live birth rate (LBR) (gestational age ≥28 weeks). Participants/materials, setting, methods Women aged between 20-40 with a body mass index (BMI)<30 kg/m² were included. Serum FSH, estradiol, AMH, INSL3 levels and AFC were evaluated on menstrual cycle days 2 or 3, and INSL3 in follicular fluid from dominant follicles (>14 mm) were evaluated during oocyte retrieval. Exclusions included endocrine abnormalities (e.g., polycystic ovary syndrome, hyperprolactinemia, hypo and hyperthyroidism) cycle cancellation due to lack of a viable embryo, uncorrected Mullerian anomalies, recurrent miscarriage history and hydrosalpinx presence. Main results and the role of chance The mean age in the study groups was 28.41±3.5 (UI), 32.40±4.21 (DOR), and 29.65±3.91 (control). In the DOR group, female age (p = 0.001), BMI (p = 0.049), duration of infertility (p = 0.006), previous IVF attempts (p < 0.001), basal FSH (p < 0.001), and basal estradiol (p < 0.001) were higher, while AMH (p < 0.001), AFC (p < 0.001), and follicular fluid INSL3 (p < 0.001) were lower. Serum INSL3 in DOR was lower but not statistically significant. No correlation was found between serum INLS, follicular fluid INSL3, ovarian reserve markers, positive pregnancy rates, miscarriage, and LBR. DOR group had longer stimulation durations (p = 0.017), but lower max estradiol (p < 0.001), fewer oocytes (p < 0.001), mature follicles (p < 0.001), and PN (p < 0.001). Pregnancy rates were 54.1% (UI), 24% (DOR), and 53.84% (control); LBRs were 54.1% (UI), 20% (DOR), and 42.3% (control), with significant differences in pregnancy tests (p = 0.04) and LBR (p = 0.03), both lower in DOR. Univariate analysis identified duration of infertility (p = 0.019) and basal FSH (p = 0.009) as significant LBR predictors. Multivariable analysis confirmed basal FSH (p = 0.033) as significant, with increased duration of infertility and basal FSH level reducing LBR probability. Limitations, reasons for caution The limited sample size of our study potentially undermines the robustness of circulating INSL3 as a predictive biomarker for DOR, evidenced by the non-significant decrease in serum INSL3 levels in the DOR group. Moreover, the lack of INSL3 level assessment during oocyte retrieval further constrains our findings. Wider implications of the findings Our research explored INSL3 as a viable biomarker for predicting ovarian reserve and IVF success in UI and DOR cases. Reduced INSL3 levels in circulation and follicular fluid in DOR patients could be beneficial in clinical practice. Trial registration number not applicable

P-524 Ethnicity and aneuploidy rates in a global perspective: a comparative genomic study of 16,543 embryos from the United Kingdom, India and Japan

Abstract Study question Is embryonic aneuploidy, as determined by Next Generation Sequencing (NGS) based Pre-Implantation Genetic Testing for Aneuploidy (PGT-A) related to female ethnicity? Summary answer In this study, when determining aneuploidy through NGS-based PGT-A, female ethnicity did not have an impact on embryonic aneuploidy. What is known already Inequalities in pregnancy outcomes following in-vitro fertilization (IVF) have often been attributed to potential disparities in genetic susceptibility, with past studies showing higher pregnancy rates in older Caucasian patients compared to younger South-Asian patients. With aneuploidy as one of the best-characterized barriers to IVF success, critics argue that potential ethnic variations in aneuploidy rates may contribute to inequalities in IVF success, raising concerns about the appropriateness of standardized protocols. Proponents stress the importance of personalized medicine accounting for individual genetic backgrounds. Acknowledging genetic diversity and ensuring equitable access to successful fertility treatments remains a complex challenge. Study design, size, duration In this retrospective cohort review, data reflecting 4,354 women undergoing an IVF±ICSI cycle with concomitant NGS-based PGT-A from 65 centres in the United Kingdom, India and Japan was requested. Trophectoderm biopsy results from 16,513 embryos tested through a single genetic laboratory over a five-year period (2019-2023) were analysed. Patients were categorised by ethnicity (Caucasian, African, East Asian, or South Asian) and further stratified by age (<35, 35-37, 38-39, 40-42, >42). Participants/materials, setting, methods Women aged between 25–45 years undergoing an IVF±ICSI cycle with concomitant NGS-based PGT-A were included. Patients undergoing PGT for inherited genetic disorders (PGT-M) or gamete donation cycles were excluded, and only autologous oocyte cases were included. Trophectoderm biopsy was performed on day 5, 6 or 7 and NGS was performed from amplified deoxyribonucleic acid (DNA). Primary outcome of interest was aneuploidy rate (>30% abnormality). Statistical analysis included ANOVA, Kruskal Wallis, and linear regression tests analysis. Main results and the role of chance In our analysis, the mean number of embryos tested overall was 3.46 (SD 2.07) and the mode was 4. The mean number was 3.84 for South Asian, 3.47 for Caucasian, 2.4 for African and 2.87 for East Asian. This was not statistically different between groups (P = 0.48). Subgroup analysis did not identify any statistically significant differences in the number of oocytes retrieved, MII oocytes retrieved and fertilization rates. When categorising by female age alone, there was a statistically significant difference in aneuploidy and female age overall (<35: 32.1±29.7%; 35-37: 42.1±31.3%; 37-39: 50.4±29.3%;40-42: 64.7±33.5% and > 42:73.9±38.7%, p-value: <0.001). When subcategorised by ethnicity, linear regression analysis did not identify a significant association with aneuploidy rate and ethnicity. The was no statistically significant difference in mean aneuploidy rate by ethnicity: East Asian 67.2±32.2%, African 58.3±42.2%, European 55.6±35.6%, and South Asian 53±32.4% (p-value 0.57). With Caucasian as the reference population, coefficients for South Asian (3.20, p-value:0.61), East Asian (8.50 p-value: 0.31), and African (7.20, p-value: 0.60) were not statistically significant. No statistically significant differences in aneuploidy rates were observed across female age categories (<35, 35-37, 38-39, 40-42, >42) and ethnicities, with a p-value of 0.17. Limitations, reasons for caution The study type was retrospective in nature. Ethnic groups are not homogenous, and there can be significant genetic, cultural, and environmental diversity within a group. Failure to account for this heterogeneity may result in oversimplification and misinterpretation of findings. There was under representation of patients from African origin (2%). Wider implications of the findings These data do not support differences in embryonic aneuploidy among various ethnicities in patients undergoing IVF±ICSI /NGS-PGT-A. We limited our analysis to a single genetic laboratory to reduce reporting variation and technical confounders. It does not appear that specific recommendations for aneuploidy screening should be made based upon ethnic heritage. Trial registration number Not applicable

ОСОБЕННОСТИ ПЕРЕЖИВАНИЯ СИТУАЦИИ ПСИХОГЕННОГО БЕСПЛОДИЯ У ЖЕНЩИН, ИМЕЮЩИХ ОПЫТ ЭКСТРАКОРПОРАЛЬНОГО ОПЛОДОТВОРЕНИЯ

This article presents the results of a psychodiagnostic study of the experiences of women suffering infertility of unknown origin (psychogenic infertility) and having experience of in vitro fertilization (IVF). Our study involved 59 women who had no physiological problems with reproductive health. The control group included 39women with the first pregnancy, who had no negative pregnancy experience. The experimental group consisted of 20 women with no history of pregnancy who underwent in vitro fertilization (IVF) without success. The main assumption is that the characteristics of the experience are associated with the success of IVF. Experience was studied in terms of four components: semantic, emotional, temporal and cognitive. The aim of the work was to study the characteristics of experiences in women with psychogenic infertility who underwent IVF. The study was carried out using psychodiagnostic methods: test of life-purpose orientations by D. A. Leontyev, Luscher Color Test, Life Line test adapted by T. D. Vasilenko, questionnaire of socio-psychological personality attitudes by O. F. Potemkina. Statistically significant differences were found in the temporal and cognitive components of the experience. A conclusion was made about the relationship between the above components of the experience and unsuccessful IVF procedure.

Motives for parenthood, psychosocial factors and health in women undergoing IVF: A systematic review

IntroductionInfertility affects 8-12% of reproductive-age couples globally, leading to significant psychosocial challenges. This review explores the psychological aspects of in vitro fertilization (IVF) treatment and its impact on mental well-being.MethodsA systematic review of 13 studies was conducted using Google Scholar, Tandfonline, Medrxiv, and PubMed. Inclusion criteria included studies on women aged 18-50 undergoing IVF, focusing on psychosocial and health factors, published in English or Greek.ResultsWomen undergoing IVF reported increased anxiety during the second and third trimesters. Psychological interventions, such as hope-oriented group counseling, improved mental health and quality of life. Patient satisfaction with IVF was generally high, influenced by demographic variables and psychological factors. Higher stress levels were linked to lower IVF success rates. The COVID-19 pandemic exacerbated psychological distress and treatment delays.ConclusionsAddressing psychological well-being in IVF is crucial. Integrating psychological support, counseling, and stress management interventions can enhance patient experience, improve treatment outcomes, and promote overall mental health. Further research is needed to develop tailored interventions that address the unique needs of individuals undergoing IVF.

Screening embryos for polygenic disease risk: a review of epidemiological, clinical, and ethical considerations.

The genetic composition of embryos generated by in vitro fertilization (IVF) can be examined with preimplantation genetic testing (PGT). Until recently, PGT was limited to detecting single-gene, high-risk pathogenic variants, large structural variants, and aneuploidy. Recent advances have made genome-wide genotyping of IVF embryos feasible and affordable, raising the possibility of screening embryos for their risk of polygenic diseases such as breast cancer, hypertension, diabetes, or schizophrenia. Despite a heated debate around this new technology, called polygenic embryo screening (PES; also PGT-P), it is already available to IVF patients in some countries. Several articles have studied epidemiological, clinical, and ethical perspectives on PES; however, a comprehensive, principled review of this emerging field is missing. This review has four main goals. First, given the interdisciplinary nature of PES studies, we aim to provide a self-contained educational background about PES to reproductive specialists interested in the subject. Second, we provide a comprehensive and critical review of arguments for and against the introduction of PES, crystallizing and prioritizing the key issues. We also cover the attitudes of IVF patients, clinicians, and the public towards PES. Third, we distinguish between possible future groups of PES patients, highlighting the benefits and harms pertaining to each group. Finally, our review, which is supported by ESHRE, is intended to aid healthcare professionals and policymakers in decision-making regarding whether to introduce PES in the clinic, and if so, how, and to whom. We searched for PubMed-indexed articles published between 1/1/2003 and 1/3/2024 using the terms 'polygenic embryo screening', 'polygenic preimplantation', and 'PGT-P'. We limited the review to primary research papers in English whose main focus was PES for medical conditions. We also included papers that did not appear in the search but were deemed relevant. The main theoretical benefit of PES is a reduction in lifetime polygenic disease risk for children born after screening. The magnitude of the risk reduction has been predicted based on statistical modelling, simulations, and sibling pair analyses. Results based on all methods suggest that under the best-case scenario, large relative risk reductions are possible for one or more diseases. However, as these models abstract several practical limitations, the realized benefits may be smaller, particularly due to a limited number of embryos and unclear future accuracy of the risk estimates. PES may negatively impact patients and their future children, as well as society. The main personal harms are an unindicated IVF treatment, a possible reduction in IVF success rates, and patient confusion, incomplete counselling, and choice overload. The main possible societal harms include discarded embryos, an increasing demand for 'designer babies', overemphasis of the genetic determinants of disease, unequal access, and lower utility in people of non-European ancestries. Benefits and harms will vary across the main potential patient groups, comprising patients already requiring IVF, fertile people with a history of a severe polygenic disease, and fertile healthy people. In the United States, the attitudes of IVF patients and the public towards PES seem positive, while healthcare professionals are cautious, sceptical about clinical utility, and concerned about patient counselling. The theoretical potential of PES to reduce risk across multiple polygenic diseases requires further research into its benefits and harms. Given the large number of practical limitations and possible harms, particularly unnecessary IVF treatments and discarded viable embryos, PES should be offered only within a research context before further clarity is achieved regarding its balance of benefits and harms. The gap in attitudes between healthcare professionals and the public needs to be narrowed by expanding public and patient education and providing resources for informative and unbiased genetic counselling.

IVF and obstetrics outcomes among women of very advanced maternal age (45+) using donor egg

Research QuestionDoes very advanced maternal age (VAMA, aged 45+) influence obstetric outcomes among women using donor oocytes in in vitro fertilization (IVF)? DesignThis retrospective cohort study analysed data from a nationwide IVF registry in Taiwan, focusing on IVF cycles involving women aged 45 or older using donated oocytes between 2007 and 2016. The study assessed cumulative live birth rates (CLBR) and secondary outcomes such as clinical pregnancy, miscarriage, live birth, and twin pregnancy rates, alongside perinatal outcomes like caesarean section rates, preeclampsia, gestational diabetes, and birth weight. ResultsThe study included 1,718 embryo transfer cycles from 745 women, with a stable live birth rate of about 40% across the study period. The CLBR was slightly lower in women over 50 (54.2%) compared to those aged 45-46 (58.0%), but these differences were not statistically significant (p=0.647). Secondary outcomes and perinatal outcomes did not significantly differ across age groups. Regression analysis suggested a non-significant decrease in live birth rates and birth weight with increasing maternal age. The study also found that single embryo transfer (SET) minimized the risk of twin pregnancies without significantly affecting live birth rates. ConclusionsIVF with donor oocytes remains a viable option for women of VAMA, with consistent live birth rates across age groups. However, the study underscores the importance of elective SET to reduce the risk of twin pregnancies and associated adverse outcomes. Further research is needed to explore the impact of other factors such as paternal age and embryo development stage on IVF success in this population.

The Influence of IGF-1, Progesterone, Androstenedione, Aromatase, and Estrogen in Successful and Unsuccessful IVF Treatments

Follicular steroidogenesis, involving proteins including insulin-like growth factor 1 (IGF-1), progesterone (P4), androstenedione, aromatase, and estrogen (E2), may influence the success of in vitro fertilization (IVF) treatments. This research aimed to 1) compare levels of these proteins in follicular fluid (FF) between subjects with successful (n=10) and unsuccessful (n=20) outcomes; 2) compare these proteins between FF and serum within each group; and 3) investigate correlations of these proteins with reproductive hormones. Classification into successful and unsuccessful groups was based on the detection of fetal heartbeat. Blood samples were collected to measure anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) at baseline as well as IGF-1, FSH, P4, androstenedione, aromatase, and E2 in FF and serum on the day of ovum pick-up (OPU). In unsuccessful pregnancies, FF and serum IGF-1 levels and FF aromatase levels were significantly higher, whereas FF and serum androstenedione levels were significantly lower when compared to successful pregnancies ( P<0.05 all). There were no significant differences in FF E2 and P4 levels between groups; however, there was a non-significant trend towards decreased FF E2 levels in unsuccessful pregnancies. Levels of IGF-1, P4, androstenedione, and E2 were significantly higher in FF than in serum in both successful and unsuccessful groups ( P<0.01 all). The FF/serum ratios for successful and unsuccessful subjects were 2.28 and 2.06 for IGF-1, 7,920.61 and 1,919.26 for P4, 5.49 and 4.00 for androstenedione, and 193.45 and 225.60 for E2, respectively. For correlation analyses, basal AMH showed significant positive correlations with serum androstenedione in all subjects and a significant negative correlation with FF E2 in unsuccessful subjects ( P<0.05 all). Basal FSH levels were significantly negatively correlated with serum androstenedione levels in all subjects ( P<0.05). On OPU day, FF androstenedione levels showed significant positive correlations with FF and serum E2 levels in unsuccessful subjects ( P<0.05 all). Serum androstenedione levels were significantly positively correlated with FF E2 levels in successful subjects and with serum E2 levels in all and unsuccessful subjects ( P<0.01 all). FF aromatase levels had significant positive correlations with serum FSH levels in all and unsuccessful subjects ( P<0.01 all). FF E2 levels were significantly positively correlated with FF androstenedione levels in unsuccessful subjects and with serum androstenedione levels in successful subjects ( P<0.01 all). In unsuccessful pregnancies, elevated aromatase levels, despite similar or insignificantly lower FF E2 levels, could likely result from high FSH levels, potentially indicating defective FF E2 production processes that may be due to inadequate substrate availability or decreased aromatase activity. Lower androstenedione levels in unsuccessful pregnancies suggest that there may be a defect in substrate production; however, we could not determine whether there is a defect in aromatase function in these subjects. Lower FF and serum androstenedione levels in unsuccessful pregnancies might be due to poor ovarian response, as indicated by lower basal AMH and higher FSH levels observed in these subjects in our previous study, findings further supported by a positive correlation between androstenedione and basal AMH, and a negative correlation with basal FSH. The elevated IGF-1 levels in the unsuccessful group might be attributable to high FSH levels. Higher levels of IGF-1, P4, androstenedione, and E2 in FF than in serum indicate that these hormones might be primarily secreted into FF before being released into circulation. In conclusion, unsuccessful pregnancies exhibited lower FF and serum androstenedione levels, but higher FF aromatase and IGF-1 levels in both FF and serum, indicating a decreased substrate availability for E2 production in subjects with poor ovarian response. IGF-1, P4, androstenedione, and E2 were likely synthesized primarily in FF rather than serum. This research was funded by the Faculty of Medicine Siriraj Hospital Research Fund ((IO) R016433005 and Grant to support Strategic Driving Project for pushing the World University Rankings by Subject, Fiscal Year 2021 ((IO) R016421007). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Advancements and Applications of Preimplantation Genetic Testing in In Vitro Fertilization: A Comprehensive Review.

Preimplantation genetic testing (PGT) has become an integral component of assisted reproductive technology (ART), offering couples the opportunity to screen embryos for genetic abnormalities before implantation during in vitro fertilization (IVF). This comprehensive review explores the advancements and applications of PGT in IVF, covering its various types, technological developments, clinical applications, efficacy, challenges, regulatory aspects, and future directions. The evolution of PGT techniques, including next-generation sequencing (NGS) and comparative genomic hybridization (CGH), has significantly enhanced the accuracy and reliability of genetic testing in embryos. PGT holds profound implications for the future of ART by improving IVF success rates, reducing the incidence of genetic disorders, and mitigating the emotional and financial burdens associated with failed pregnancies and genetic diseases. Recommendations for clinicians, researchers, and policymakers include staying updated on the latest PGT techniques and guidelines, exploring innovative technologies, establishing clear regulatory frameworks, and fostering collaboration to maximize the potential benefits of PGT in assisted reproduction. Overall, this review provides valuable insights into the current state of PGT and its implications for the field of reproductive medicine.

Predictive Role of Progesterone Levels for IVF Outcome in Different Phases of Controlled Ovarian Stimulation for Patients With and Without Endometriosis: Expert View.

The study aimed to review the role of basal, trigger, and aspiration day progesterone levels (PLs) as predictors of in vitro fertilization (IVF) success for patients with and without endometriosis. A non-systematic review was conducted by searching papers published in English during the period of 1990-2023 in MEDLINE and PubMed, Embase, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), and Web of Science. The most widely used IVF predictor success was the trigger day progesterone serum level. Many studies utilize the threshold level of 1.5-2.0ng/ml. However, the predictive power of only progesterone level failed to show high sensitivity and specificity. Contrary, progesterone level on the trigger day combined with the number of mature retrieved oocytes had the highest predictive power. High baseline progesterone level was associated with poor IVF outcomes. Research on progesterone and IVF success in patients with endometriosis is limited but indicates that endometriosis patients seem to benefit from higher progesterone concentrations (≥ 37.1ng/ml) in IVF cycles. Currently, there is limited data for a definitive insight into the mportance of progesterone in the estimation of IVF success. Nonetheless, this summarized evidence could serve as up-to-date guidance for the role of progesterone in the prediction of IVF outcomes, both in patients with and without endometriosis.

Investigation of the relationship between vitamin D serum level with pregnancy success rate in a cycle of in vitro fertilization

Aims: The importance of vitamin D in women's health is clear, and many studies have been conducted on the role of this vitamin in reproductive physiology. The main purpose of this examination was to define the association between serum vitamin D level and pregnancy success rate in an in vitro fertilization (IVF) cycle on infertile women between the ages of 20-45. Methods: This retrospective cohort study was done between March 2020 and August 2023, including 134 infertile women with insufficient and 152 infertile women with sufficient vitamin D level. This study investigated the effect of sufficient vitamin D serum level on the IVF method's success. The threshold for determining insufficient vitamin D level was 30 ng/mL, measured by ELISA method seven days before embryo transfer. Results: Our results found that gestational sac and fetal heart rate were statistically significant higher than women with sufficient vitamin D level (p<0.05). Also, there was a statistically significant association between case and control groups regarding live births (p<0.05; 13.4% vs. 75.7%). Based on multiple logistic regression and adjusting for confounding variables, there was a significant difference between the groups in terms of pregnancy success rate (p<0.05). Conclusion: It is concluded that sufficient vitamin D levels increase the chance of success in IVF in Turkish infertile women.

Advances in microfluidic technology for sperm screening and in vitro fertilization.

About 18% of reproductive-age adults worldwide are affected by infertility. In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are widely used assisted reproductive technologies (ARTs) aimed at improving clinical outcomes. Efficient and noninvasive selection and isolation of highly motile sperm with intact DNA are essential for the success of IVF and ICSI and can potentially impact the therapeutic efficacy and the health of the offspring. Compared to traditional methods, microfluidic technology offers significant advantages such as low sample consumption, high efficiency, minimal damage, high integration, similar microenvironment, and high automation, providing a new platform for ARTs. Here, we review the current situation of microfluidic technology in the field of sperm motility screening and evaluation and IVF research. First, we focus on the working principle, structural design, and screening results of sperm selection microfluidic platforms. We then highlight how the multiple steps of the IVF process can be facilitated and integrated into a microfluidic chip, including oocyte capture, sperm collection and isolation, sperm sorting, fertilization, and embryo culture. Ultimately, we summarize how microfluidics can complement and optimize current sperm sorting and IVF protocols, and challenges and possible solutions are discussed.

Sperm DNA Fragmentation: Causes, Effects and Relevance in IVF Outcomes

Sperm DNA fragmentation, characterized by damaged or broken DNA strands within sperm cells, has been recognized as an important factor in male infertility and poor ART outcome. This lecture aims to provide an overview of the causes, effects, and relevance of sperm DNA fragmentation in in vitro fertilization (IVF) outcomes and look into the latest evidences from the literatures. Causes: Sperm DNA fragmentation can result from various factors, including oxidative stress, advanced paternal age, lifestyle factors such as smoking and excessive alcohol consumption, environmental exposures, genotoxic agents, and underlying genetic abnormalities. These factors can induce DNA damage during sperm development, during the transit of sperm through the male reproductive tract or during the storage of the sperm in epididymis. Relevance in IVF Outcomes: The assessment of sperm DNA fragmentation has emerged as a valuable tool in evaluating male infertility and predicting IVF success. Several methods, including the sperm chromatin structure assay (SCSA), terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL), comet assay, and other commercial detection kits, are available to measure sperm DNA fragmentation. Previous small cohort studies have demonstrated that higher levels of sperm DNA fragmentation are associated with lower pregnancy rates, decreased embryo quality, and an increased risk of pregnancy loss in IVF cycles. Therefore, incorporating sperm DNA fragmentation analysis into the routine assessment of male infertility can aid in optimizing treatment strategies and improving IVF outcomes. Recent evidences: Latest large clinical studies showed a limited association to IVF outcome. The DFI remains controversial as a predictive tool. Nonetheless, sperm DNA fragmentation is still believed to be a significant factor affecting male fertility and IVF outcomes. Further research is warranted to explore the mechanisms underlying DNA fragmentation, develop standardized assessment methods, and explore potential interventions to mitigate the adverse effects of sperm DNA damage on IVF success.

#53 : Pregnancy Outcome After Hydrosalpinx Aspiration in In-Vitro Fertilization Cycle

Background and Aims: Hydrosalpinx is a severe manifestation of tubal disease-causing infertility in women. It has an adverse effect on the outcome of in vitro fertilization (IVF), reducing live birth rate (LBR) by 50% compared to other tubal factors. Laparoscopic salpingectomy can effectively improve IVF outcome but is contraindicated in some women. It can also be expensive and is not without complications. Ultrasound-guided hydrosalpinx aspiration is a cheaper, less invasive procedure alternative to salpingectomy. It has been shown to improve clinical and ongoing pregnancy rates compared to patients with no aspiration. However, the published literature on the effectiveness of hydrosalpinx aspiration is equivocal. Method: This retrospective study aimed to evaluate the outcome of minimal stimulation (mild) IVF cycles wherein the women underwent hydrosalpinx aspiration prior to embryo transfer at a private fertility clinic in the Philippines. Results: A total of 98 IVF cycles satisfied the inclusion criteria. The average patient age was 35.22 ± 4.57 and average duration of infertility was 5.87 ± 3.70 years. The biochemical pregnancy rate was 48% and the clinical pregnancy rate was 39.8%. Live birth rate was 35.7%, which is comparable to that of mild IVF patients without hydrosalpinx. There was a negative correlation between patient age and biochemical pregnancy rate, clinical pregnancy rate, and LBR, however, the correlations were statistically insignificant (Pearson correlation, P = 0.081, 0.197, and 0.344, respectively). Binary logistic regression analyses showed that age, infertility type, infertility factor, basal hormone levels, and number of eggs retrieved were not predictive of the success of IVF among the women in the study. Conclusion: Our results show that hydrosalpinx aspiration is a safe and effective option in improving pregnancy and live birth rates in women undergoing mild IVF.

#164 : In-Vitro Vitamin D Treatment on Human Sperm Improves Capacitation, Acrosome Reaction, and Protein Expression of Sperm-Oocyte Activation Factors (SOAF)

Background and Aims: Although many studies have been done to investigate the relationship between serum vitamin D and male infertility, the effect of in-vitro vitamin D treatment on sperm remains unclear, particularly the effect on sperm capacitation, hyperpolarisation, sperm-oocyte fusion and oocyte activation. This study aims to examine whether in-vitro vitamin D treatment on sperm can improve the condition of sperm parameters and further increase fertilisation and pregnancy rate. Method: Fifty men (N=50, fertile n=26; infertile men n=24, were recruited during their visit to fertility clinics for semen analysis. Each washed semen sample was aliquoted and divided into control and in-vitro vitamin D treatment groups. For in-vitro vitamin D treatment, semen samples were treated with 1nM in-vitro for 1 hour at 37°C. Intracellular calcium released, capacitation status and mitochondria membrane potential were measured after incubation in both the control and in-vitro vitamin D treatment groups. Furthermore, immunofluorescence of sperm-origin SOAF, Phospholipase C Zeta (PLC[Formula: see text]), was done to investigate fluorescence intensity. Results: Compared to the control, higher intracellular calcium release was noted following in-vitro vitamin D treatment, represented by higher Fluo-4AM staining (MD=25043, P=0.02). In the treatment group, sperm capacitation rate and CTCF were higher when Chlortetracyclin (CTC) (MD=4.7%, P=0.01) and immunofluorescence of phosphotyrosine (MD=0.03, P=0.01) were examined. More hyperpolarised mitochondria membranes in the treatment group showed by JC-1 staining (P=0.01) compared to the control group. The red-to-green, fluorescent ratio is 1.62 in the control group and 2.24 in the treatment group. Moreover, immunofluorescence of PLC[Formula: see text] shows that the treatment improves this protein’s expression (MD=8.013×10[Formula: see text], P=0.02). Thus, in-vitro vitamin D enhances the functionality of sperm by increasing intracellular calcium ions, sperm capacitation, hyperpolarisation and protein expression. Conclusion: Adding vitamin D in in-vitro fertilisation (IVF) in media culture is beneficial as capacitation, sperm membrane polarisation and SOAF protein expression were increased and therefore contributed to successful IVF.

Using feature optimization and LightGBM algorithm to predict the clinical pregnancy outcomes after in vitro fertilization.

According to a recent report by the WHO, approximately 17.5\% (about one-sixth) of the global adult population is affected by infertility. Consequently, researchers worldwide have proposed various machine learning models to improve the prediction of clinical pregnancy outcomes during IVF cycles. The objective of this study is to develop a machine learning(ML) model that predicts the outcomes of pregnancies following in vitro fertilization (IVF) and assists in clinical treatment. This study conducted a retrospective analysis on provincial reproductive centers in China from March 2020 to March 2021, utilizing 13 selected features. The algorithms used included XGBoost, LightGBM, KNN, Naïve Bayes, Random Forest, and Decision Tree. The results were evaluated using performance metrics such as precision, recall, F1-score, accuracy and AUC, employing five-fold cross-validation repeated five times. Among the models, LightGBM achieved the best performance, with an accuracy of 92.31%, recall of 87.80%, F1-score of 90.00\%, and an AUC of 90.41%. The model identified the estrogen concentration at the HCG injection(etwo), endometrium thickness (mm) on HCG day(EM TNK), years of infertility(Years), and body mass index(BMI) as the most important features. This study successfully demonstrates the LightGBM model has the best predictive effect on pregnancy outcomes during IVF cycles. Additionally, etwo was found to be the most significant predictor for successful IVF compared to other variables. This machine learning approach has the potential to assist fertility specialists in providing counseling and adjusting treatment strategies for patients.

What do women undergoing in vitro fertilization (IVF) understand about their chance of IVF success?

How well informed are Australian women who undergo IVF about their chances of having a baby? Only one in four women estimated their individual chance of success with IVF accurately, with most women overestimating their chance. Limited knowledge about infertility and infertility treatment in the general population is well-documented. The few studies that have investigated patients' knowledge about the chance of IVF success suggest that while IVF patients are aware of average success rates, they tend to be unrealistic about their own chance of success. We conducted an anonymous online survey of 217 women who had started IVF since 2018 in Australia. The survey was advertised on social media, enabling women from across Australia to participate. Responses were collected in June 2021. The survey included questions on demographic characteristics and IVF history. It asked what participants thought their chance of having a baby from one IVF treatment cycle was, how they rated their knowledge about chance of success, and about their experience of receiving IVF-related information. Participants' estimations of their chance of success were compared with their chance as calculated by the Society for Assisted Reproductive Technology's (SART) online calculator. Responses to a free-text question about what information women wished they had been given when they started treatment were analysed thematically. Only about a quarter (58/217, 27%) of participants accurately estimated their chance of having a baby within 20% relative to their SART calculated chance, with more than half (118/217, 54%) overestimating their chance. Ninety percent of women indicated that their preferred source of treatment information was a consultation with their doctor, despite less than half (44%) reporting that doctors explained the probability of having a baby with IVF well (mean 5.9/10). In free-text responses, many women also reported that they wished they had been given more realistic information about IVF and their chance of success. The dissemination method precludes calculation of response rate, and it is not possible to know if participants are representative of all women undergoing IVF. Additionally, we only surveyed women undergoing IVF, while those who decided not to have IVF were not included. Therefore, women who overestimated their chance may have been overrepresented. There is also inherent imprecision in the way understanding of chance of success was estimated. The potential impact of recall bias could neither be quantified nor excluded. It is difficult to determine to what extent women's lack of understanding of what is possible with IVF is due to poor information-provision by clinicians and the clinic, and how much can be explained by optimism bias. The finding of poor understanding of personal chance of success amongst women undergoing IVF in Australia requires further investigation to determine potential reasons for this. The findings can be used by clinics to develop strategies for improvement in the information-provision process to ensure that women can make informed decisions about their fertility treatment. This study received no external funding. S.L. is supported by a NHMRC Investigator Grant (APP1195189). R.W. is supported by a NHMRC Investigator Grant (APP2009767). B.W.M. is supported by a NHMRC Investigator Grant (GNT1176437). B.W.M. reports consultancy for Merck and ObsEva and has received research funding and travel funding from Merck. The other authors have no conflicts of interest. N/A.