IVF Success Rates Research Articles

O-199 IVF success rates: challenging the concept of recurrent implantation failure

Abstract Study question What is the likelihood of pregnancy in successive IVF attempts, and how does it relate to the concept of recurrent implantation failure? Summary answer The first two IVF transfer attempts have the highest pregnancy chances, while subsequent attempts show stability, challenging the notion of recurrent implantation failure. What is known already According to the theory of recurrent implantation failure (RIF), around 10% of patients undergoing several embryo transfers fail to implant due to certain risk factors. This should eventually enrich this subset as more transfers are performed. According to conventional thinking, this group’s IVF success rates should therefore soon start to significantly fall. Recent studies on euploid embryo transfers, however, have started to challenge this idea. They suggest that the IVF success rate drop may be less than previously believed, and that RIF may be less prevalent than previously expected. Study design, size, duration This registry study of the Danish IVF registry used historical data from 1994 to 2019, comprising a large cohort of 85,453 unique women who underwent 171,159 transfers. Participants/materials, setting, methods A participant could receive up to ten transfers in a row. The live birth rate (LBR) for every transfer cycle, as well as the cumulative LBR was calculated. After achieving a pregnancy, the woman was censored. The mean age of the patients included in the study was 33.8 (33.7-33.8) years at the time of the first ovarian stimulation with a mean BMI of 24.2 kg/m2. Main results and the role of chance The median number of stimulations was 2 and a total median number of 8 oocytes were obtained per patient. The first two transfer-attempts had the highest LBR, with 38.48% and 33.99%, respectively. Subsequent attempts showed a gradual decline but maintained relative stable: the LBR was 30.61% in the third attempt, followed by 28.00% for the fourth and 27.14% for the fifth attempt.Beyond the fifth attempt, the success rates were around 25%. Moreover,we conducted an analysis of 25,433 transfers performed from 2017-2019 transfers, predominantly involving blastocyst-transfers. Herein, the LBRs were higher: 42.31% in the first attempt and 37.81% in the second attempt. Like in the whole cohort, subsequent cycles demonstrated a gradual decline in LBR, however with the 8th attempt still yielding 28.87%. Notably, cumulative live birth rates (CLBR) revealed a steady increase for those having enough blastocysts to transfer: By the fifth attempt, the CLBR had reached 89.86%, and this trend continued to rise, culminating in 98.40% CLBR after the tenth attempt. These findings challenge the conventional notion of RIF,as they suggest that, while a slight decline in LBR is evident with additional IVF attempts, the cumulative chances of achieving a livebirth remain substantial for patients able to pursuing multiple cycles. Limitations, reasons for caution As a retrospective register study, we relied on historical data from 1994 to 2019. It does not take potential changes in clinical practices over time or patient-specific factors that may influence fertility, such as age, underlying conditions, or specific treatment protocols into account. Wider implications of the findings Our findings challenge the conventional understanding of RIF in IVF. The consistency of pregnancy rates over several transfers may have significant effects on patient counseling and clinical practice. Understanding that IVF success is possible even after multiple attempts may reduce anxiety, making informed decisions for couples pursuing reproductive treatments easier. Trial registration number not applicable

P-717 Add-ons availability and quality of online information provided by Brazilian IVF clinics

Abstract Study question How do Brazilian fertility clinic websites advertise four IVF add-ons: assistedhatching (AH), preimplantation genetic testing for aneuploidies (PGT-A), ERA and sperm DNA fragmentation test. Summary answer Available information, about ivf add-ons in Brazil, on researched websites is heterogeneous and is not evidence-based according to the last published recommendations. What is known already Over 1 billion people worldwide use online resources to obtain health-related information. People struggling with infertility are increasingly turning to online resources for infertility-related content and social support. “Add-on” procedures are actively promoted on some fertility clinic websites as means to improve IVF success rates. However, the actual contribution of these interventions to IVF success rates remains debatable. ESHRE has recently issued 42 recommendations were formulated on the use of add-ons in IVF. At present, no study has evaluated the type and quality of the information provided on the Brazilian IVF clinics’ websites regarding the merits of “add-ons. Study design, size, duration Prospective evaluation of the availability and quality of information on four common add-ons provided by IVF clinics in the southeast of Brazil between October-November 2023. Clinics were identified using the national registry (SisEmbrio) as well as through manual online search. As only public online available information was used no ethical approval was necessary. Statistical analyses were restricted to descriptive of the frequency of each add-on and frequency of claims made in relation to their use. Participants/materials, setting, methods One reviewer took screenshots of the included clinic pages and claims and a second reviewer double-checked everything. The folowing information was colletced: availability of of the four add-ons; information on the effectiveness on: implanation rate(IR), pregnancy rate (PR) or live-birth rate (LBR); information on the scientifc uncertainty of the use of add-on and possible negative impact; for PGT-A if the clinic informed that the data obtained should be confirmed by prenatal diagnostic testing. Main results and the role of chance The websites of 122 IVF clinics were included. Nine clinics had no website or were offline. PGT-A was the most frequent available add-on (n = 77; 68%) but only two of them (2,5%) informed on PR. There was no information on IR nor LBR. Thirteen clinics (16,8%) acknowledged it could have adeverse effects but only one mentioned the scientifc uncertainty related to its use. Forty (35%) websites displayed AH with 7 reporting on possible negative effects but none disclosed success rates (PR, IR or LBR). Eight clinics admitted AH had uncertain benefits and seven noted possible negative impact. The sperm DNA fragmentation test was presented in 37 (33%) websites but none reported on potential adverse effects nor success rates in terms of PR, IR nor LBR. No website provided information on the uncertainty of the benefit of the test. The ERA-test was advertised in 28 (25%) websites with no information on its benefits on sucess rates. Three clinics advised it could have a negative impact and six agreed its effectiveness was unclear. The cost was never pesented for any of the add-ons researched in accordance to national regulations. Of note, 36 websites advertised other add-ond such as MSOME, ZYMOT and endometrial scrathcing. Limitations, reasons for caution The study was restricted to 122 clinics websites in the southeast of Brazil. Evalaution was restricted to four commons add-ons and the quality of the information provided could not be assessed as the clinics follow no specific regulation on how to advertise scientifc information to their patiens and general public. Wider implications of the findings The information provided by Brazilian IVF clinics could be misleading. The use of add-ons is surrounded by scientific uncertainly related to their benefits and cost-effectiveness therfeore it is of utmost importance that clinics reviewt heir websites and offer sound scientific data to patients and the general public as well. Trial registration number Not applicable

O-029 Atosiban in women with previous single implantation failure undergoing frozen-thawed blastocyst transfer: a placebo-controlled randomized trial

Abstract Study question Does the administration of Atosiban before frozen-thawed blastocyst transfer improve the live birth rate in women with a history of a single implantation failure? Summary answer In women with a single implantation failure undergoing frozen-thawed blastocyst transfer, Atosiban did not improve the ongoing pregnancy rate. What is known already Uterine peristalsis preceding embryo transfer is believed to adversely impact the success rates of IVF. Atosiban can reduce uterine peristalsis and act as a role of oxytocin antagonist. The effectiveness of Atosiban in the general population of IVF patients has not been conclusively shown by randomised clinical trials or meta-analyses. It has been suggested that women with previous implantation failure may potentially benefit from the use of Atosiban, particularly in the presence of uterine peristalsis. We aim to evaluate if Atosiban before embryo transfer increases live birth rate in women undergoing frozen-thawed blastocyst transfer? Study design, size, duration We conducted a single-centre, double-blind placebo randomised controlled trial (RCT) in women with previous single implantation failure undergoing frozen-thawed blastocyst transfer. Between July 2019 and June 2023, we randomised 1,100 participants to either Atosiban or placebo. The primary outcome was live birth (≥20 weeks of gestation) in the first FET after randomization. In this abstract, we present results on ongoing pregnancy. Data on live birth will be available at the conference. Participants/materials, setting, methods We randomised women with a history of one failed fresh or frozen blastocyst, with at least one cryopreserved blastocyst into two groups on the day of transfer. In the Atosiban group, women were administered 37.5mg of Atosiban intravenously 30-min prior to FET. In the placebo group, women received a saline infusion for the same duration. Uterine peristalsis was measured using transvaginal ultrasound prior to administration of study drugs. The analysis was done based on intention-to-treat. Main results and the role of chance The ongoing pregnancy rates were 50.46% (277/549) and 46.82% (258/551) in the Atosiban and control groups, respectively (RR 1.08, 95% CI 0.95 to 1.22, P = .23). Uterine peristalsis was measured in 720 (65%) of all participants. Within this cohort, of the 163 (22%) women with abnormal contractions, the ongoing pregnancy rates were 51.9% and 41.7%, respectively (RR 1.25, 95% CI 0.90 to 1.73, P = .19). Among 208 women (29%) with peristalsis but without abnormal contraction waves, ongoing pregnancy rates were 50.9% and 48.0% (RR 1.06, 95% CI 0.81 to 1.40, P = .67). In 349 women (48%) without peristalsis, the ongoing pregnancy rates were 48.6% in the Atosiban group versus 50.6% in the control group (RR 0.96, 95% CI 0.78 to 1.19, P = .71). Limitations, reasons for caution Our study only included women with previous blastocyst implantation failure. Uterine peristalsis was not initially assessed, resulting in only 65% (720/1,100) of the participants having peristalsis measured. In this abstract, we only report on the ongoing pregnancy rate. We will present data on live birth at the congress. Wider implications of the findings In unselected women undergoing frozen-thawed blastocyst transfer with previous single implantation failure, Atosiban does not enhance the ongoing pregnancy rate. Future research regarding Atosiban in IVF should assess uterine peristalsis and focus on women with abnormal contractions. Trial registration number ChiCTR1900022333

P-444 The battle between a machine learning model, a gynecologist and an embryologist to predict pregnancy outcomes after single day-5 embryo transfer

Abstract Study question Are algorithms more effective than clinicians/embryologists at predicting pregnancy outcomes in the context of Assisted Reproductive Technology (ART) following the transfer of a single blastocyst? Summary answer Evaluation of a pregnancy prediction algorithm, trained on local data and assessed by two ART professionals, yielded an accuracy comparable to a coin toss. What is known already Artificial Intelligence’s ability to synthesize multifaceted embryological and clinical data and process extensive datasets holds promise for elevating IVF success rates through data-driven, individualized treatments. Refining embryo selection through deep learning and computer vision, individualizing treatment protocols, predicting oocyte retrieval after Controlled Ovarian Hyperstimulation (COH) and ultimately predicting Live Birth (LB) following embryo transfer are one of the early promises of this technology. Study design, size, duration A retrospective analysis was conducted on 475 stimulation cycles that resulted in a single day-5 blastocyst transfer (fresh or frozen, classical IVF or ICSI) from January 2015 to January 2022 at the Poissy/Saint-Germain-En-Laye hospital, France. The study encompassed 32 clinical and biological parameters, ranging from general characteristics of patients to controlled ovarian hyperstimulation (COH) details and embryo grading. Exclusively, embryos fertilized with autologous oocytes and sperm were considered, excluding any donor-fertilized embryos. Participants/materials, setting, methods Preliminary testing with Machine Learning algorithms (XGboost, LightGBM, Random Forest (RF), Support Vector Machine (SVM), Multi-layer Perceptron (MLP)) were conducted before selecting XGboost model for this study. Data was split into a training (n = 331) and testing (n = 144) set. Pregnancy outcome predictions (binary) were compared between the model, a clinician, and an embryologist. Feature extraction was conducted, and both professionals were asked to give the top 5 most relevant parameters used to make the pregnancy predictions. Main results and the role of chance The study analyzed 475 stimulation cycles, including 362 frozen and 114 fresh transfers. Participants’ mean age was 33, with a Body Mass Index (BMI) of 24.9. The average Antral Follicle Count (AFC) was 16.8, and the mean starting gonadotropin dose was 225 UI, yielding 8.3 MII oocytes on average. 36 patients were active smokers. Preliminary AUC results showed XGboost leading (AUC = 0.57) compared to LightGBM (AUC = 0.56), Random Forest (AUC = 0.56), SVM (AUC = 0.49), and MLP (AUC = 0.47) in predicting pregnancy outcomes. After hyperparameter optimization via GridSearch, the XGboost model enhanced its AUC to 0.61, outperforming the embryologist (AUC = 0.58) and the gynecologist (AUC = 0.44). Top predictive features identified after feature extraction included endometrial thickness at or before ovulation trigger, AMH levels at patient admission, AFC, BMI, and age. The gynecologist primarily prioritized age, BMI, embryo grading (TE and ICM), and the number of mature oocytes retrieved. The embryologist, valued embryo grading (TE and ICM) foremost, followed by age, smoking status, BMI, and COH duration. Limitations, reasons for caution The study’s limited dataset due to dynamic practices and difficulty maintaining curated data over the years, necessitates caution. The selected 32 parameters from 762 available reflect typical incomplete datasets in such settings, highlighting the importance of careful interpretation and potential need for broader data integration to enhance representativeness and reliability. Wider implications of the findings The findings advocate for developing ART-specific AI, integrating multimodal data and novel parameters, to enhance live birth predictions. This approach underscores the complex synergy between algorithmic precision and clinical expertise in ART, highlighting the stochastic nature of pregnancy prediction and the potential of tailored, data-driven strategies to improve outcomes. Trial registration number not applicable

O-056 Can we tailor ART to endometriosis patients?

Abstract ART remains an effective treatment for endometriosis-associated infertility, although there is evidence that pregnancy rates are diminished in women with endometriosis compared with other etiologies of infertility. In this lecture, the literature relating to endometriosis-associated infertility will be evaluated and recommendations will be made on the management of patients both pre-ART and during ART in order to improve ART outcomes in women with endometriosis. Surgery as an adjuvant to ART appears to have a favorable effect in patients with minimal to mild endometriosis prior to IVF. However, this evidence is based on only one study and more research is needed. As deep endometriosis (DE) is usually accompanied by advanced intra-abdominal disease resulting in distortion of the pelvic anatomy and tubal dysfunction, it is not surprising that IVF is considered as first line treatment. Observational data are available on the outcomes of DE surgery regarding conception rates in infertile patients with endometriosis suggesting that surgery may increase natural pregnancy rates as well as improve IVF outcomes. However, randomized trials comparing IVF to DE surgery are non-existent, as DE surgery is still mainly performed for pain and reduced quality of life rather than for treating infertility. In order to improve IVF success rates in endometriosis, various pre-ART treatments have been suggested. The oldest one relates to the use of gonadotropin releasing hormone (GnRH) agonist prior to IVF. Currently there is uncertainty as to whether long-term GnRH agonist therapy is beneficial when compared to standard IVF/ICSI in endometriosis. In addition, there is no evidence to support the use of oral GnRH antagonists and oral contraceptives as pre-treatment prior to ART, but results of ongoing studies will determine further. More recent studies support defects in endometrial receptivity as a cause of IVF failure. In recent years a new marker for endometrial receptivity in endometriosis emerged: BCL6, a biomarker for endometrial inflammation as it stimulates endometrial cytokine expression. Prospective cohort data provide a proof of concept that high BCL6 expression is associated with adverse IVF outcomes in women with endometriosis and that patients with high BCL6 expression may benefit from medical and surgical treatment prior to IVF. In order to improve IVF success rates in endometriosis, various pre-ART treatments have been suggested. The oldest one relates to the use of gonadotropin releasing hormone (GnRH) agonist prior to IVF. Contrary to previous findings, there is currently uncertainty as to whether long-term GnRH agonist therapy is beneficial when compared to standard IVF in endometriosis. In addition, there is also no evidence to support the use of oral GnRH antagonists and oral contraceptives as pre-treatment prior to ART in endometriosis, but results of ongoing studies will determine further. It has been hypothesized that applying local endometrial injury might induce a beneficial effect on endometrial receptivity prior to ART. However, scratching the endometrium as well as infusing fluids (Lipiodol and ExEm gel) into the uterine cavity (uterine bathing) in endometriosis patients prior to ART did not improve IVF success. During ART, a specific protocol for ART in women with endometriosis cannot be recommended. Both GnRH agonist and antagonist protocols can be used. For ovarian stimulation, a higher dose of gonadotropins may be required in stage III-IV endometriosis due to a poorer ovarian response. There is insufficient evidence for the routine use of prophylactic antibiotics at the time of oocyte retrieval in patients with endometriosis, but their use is recommended in patients with endometrioma. Considering fertilization, there appears no added benefit in using ICSI over IVF in endometriosis unless male-factor infertility is present. Finally, there is insufficient evidence to recommend any particular luteal support in women with endometriosis undergoing ART.

O-072 The canonical Hippo signalling pathway controls the first lineage segregation in the human preimplantation embryo

Abstract Study question What is the role of the canonical Hippo signalling pathway during the first lineage segregation in the human preimplantation embryo? Summary answer Canonical Hippo signalling regulates the first lineage segregation by controlling the expression of trophectoderm (TE) and inner cell mass (ICM) associated genes. What is known already The Hippo signalling pathway is a conserved regulatory network that plays a critical role in the first lineage segregation in mouse, rat, bovine and human preimplantation embryos. This pathway consists of two distinct branches (canonical, non-canonical). Despite their shared role in lineage segregation, the respective functions of canonical and non-canonical Hippo signalling branches remain largely unexplored. Since these branches are regulated by distinct upstream mechanisms, they may have different roles in embryonic growth, function, and survival. Unravelling the distinct roles of these branches is essential for understanding the intricate mechanisms that govern early human embryonic development. Study design, size, duration This experimental study involved the functional characterization of the canonical Hippo signalling pathway by pharmacologically inhibiting the core kinase MST1/2. Eight-cell stage human embryos donated for research were warmed and incubated with or without the inhibitor, till completion of the first lineage segregation days post fertilization (dpf) 5. The control (n = 20) and treated embryos (n = 17) were evaluated based on embryonic development (kinetics, morphology), and expression of lineage-specific markers. Participants/materials, setting, methods The optimal concentration (1μΜ) of the highly selective XMU-MP-1 inhibitor targeting the MST1/2 core kinase of the canonical Hippo signalling pathway was established in titration experiments. Time-lapse imaging (Miri TL, Esco Medical) captured effects on embryonic development (kinetics, morphology). Changes in the main effectors of the Hippo signalling pathway (YAP1, p-YAP1 and WWTR1) and the expression of lineage-specific markers (ICM: NANOG, SOX2; TE: GATA3) were assessed through immunofluorescence imaging and confocal microscopy (LSM800, Zeiss). Main results and the role of chance For the first time, we provide a complete spatiotemporal analysis of the main effectors of the Hippo signalling pathway YAP1 and WWTR1. They are co-localised in the nuclei of outer cells in compacting (dpf3) and compacted (dpf4) embryos. In the dpf5 blastocyst, YAP1 and WWTR1 are detected in the nuclei of the TE cells. Phosphorylated effector p-YAP1, indicative of active Hippo signalling, was first detected in the inner cells of the compacted embryo (dpf4) and remained in the ICM of the dpf5 blastocyst, supporting the role of the Hippo signalling pathway in the first lineage segregation. Treatment of human embryos with XMU-MP-1 reduced p-YAP1 levels, confirming its specificity for MST1/2. Inhibition of the MST1/2 kinase had a significant effect on the developmental kinetics as treated embryos had lower blastocyst formation rates. Embryo morphology was significantly compromised as treated embryos formed ICMs with less cells compared to control embryos. Immunofluorescence analysis revealed that the XMU-MP-1 treatment led to the upregulation of YAP1 and upregulation of TE marker GATA3, while the ICM markers SOX2 and NANOG were downregulated. Overall, our data suggest that active Hippo signaling promotes ICM formation, while TE formation requires inactive Hippo signaling. Limitations, reasons for caution Caution is warranted due to potential non-specific effects of the XMU-MP-1 inhibitor, although this compound has been shown in other models to be very specific. Further studies should explore off-target impacts to ensure result reliability. Wider implications of the findings Understanding the signalling pathways that regulate human preimplantation embryo development is fundamental for understanding embryonic growth, function, and survival, and can also help improve IVF success rates by addressing deficiencies that lead to embryo developmental arrest. Trial registration number Not applicable

Does Gonadotropin-Releasing Hormone Agonist Administration Before Assisted Reproduction Techniques Improve Pregnancy Rates in Women With Endometriosis?

Axial downregulation with a 3- to 6-month administration of gonadotropin-releasing hormone agonists (GnRH-a) prior to assisted reproduction techniques has been proposed in order to improve clinical pregnancy rates in women with endometriosis. Although reduced inflammation, improved oocyte quality, and restored endometrial receptivity have been postulated, further investigation of their actual benefit and mechanism of action is considered essential. In that direction, well-designed clinical trials regarding the role of GnRH-a in IVF are necessary. The purpose of this review is to clarify whether GnRH-a administration prior to IVF-FET procedures improves pregnancy rates in women with endometriosis. A literature review was conducted in MEDLINE (PubMed), Cochrane, and Google Scholar and concluded on September 10, 2022. Two Cochrane meta-analyses and 16 selected studies present various interesting data of assisted reproduction technique procedures on patients with endometriosis-related infertility with or without depot GnRH-a pretreatment. The regimen may have a positive clinical effect on cases of severe endometriosis (American Society for Reproductive Medicine stages III-IV), but their use is not routinely recommended in order to improve pregnancy rates. Endometriosis and infertility are closely related through various pathogenetic mechanisms. Endometriosis has been traditionally considered to negatively affect fundamental aspects of the in vitro fertilization-frozen embryo transfer procedure. Numerous interventions, both medical and surgical, have been proposed in order to improve IVF success rates, and the optimal management of these cases poses an ever pressing challenge.

Regulation of Assisted Reproduction in Hungary

Following the implementation of state oversight of human reproductive procedures in 2020, several regulations have been introduced to mitigate potential issues. To enhance patient care and alleviate the workload of IVF centers, a network of specialized infertility outpatient clinics will be established alongside existing centers of assisted reproduction. These changes aim to address the challenges faced by infertility centers and improve the chances of patients having children. The policy currently allows for up to five insurance-funded treatment cycles, while cryopreserved embryo transfers are not subject to a specific limit. Furthermore, the previous threemonth waiting period between treatment cycles has been eliminated, and restrictions on the number of embryos that can be implanted have been implemented. Limiting the number of embryos transferred during IVF procedures is a common practice aimed at reducing the risks associated with multiple pregnancies. By allowing only one embryo for the first transfer up to the age of 36, especially when transferred on day five of embryonic development, this initiative prioritizes the health and safety of both the mother and potential offspring. It helps to minimize the chances of complications such as preterm birth and low birth weight, which are more common with multiple pregnancies. Additionally, it can improve the overall success rates of IVF by focusing on the quality of the transferred embryo rather than the quantity. The Hungarian government anticipates that these measures will enhance the success rates of IVF treatments, consequently leading to a rise in future childbirths and a decrease in the number of frozen embryos. This study aims to delineate the effectiveness of the introduced changes in 2023 and provide recommendations accordingly.

BlastAssist: a deep learning pipeline to measure interpretable features of human embryos.

BlastAssist: a deep learning pipeline to measure interpretable features of human embryos.

Asszisztált reprodukció újragondolva

Following the implementation of state oversight of human reproductive procedures in 2020, several regulations have been introduced to mitigate potential issues. To enhance patient care and alleviate the workload of IVF centres, a network of specialized infertility outpatient clinics will be established alongside existing centres of assisted reproduction. These changes aim to address the challenges faced by infertility centres and improve the chances of patients having children. The policy currently allows for up to five insurance-funded treatment cycles, while cryopreserved embryo transfers are not subject to a specific limit. Furthermore, the previous three-month waiting period between treatment cycles has been eliminated, and restrictions on the number of embryos that can be implanted have been implemented. Limiting the number of embryos transferred during IVF procedures is a common practice aimed at reducing the risks associated with multiple pregnancies. By allowing only one embryo for the first transfer up to the age of 36, especially when transferred on day five of embryonic development, this initiative prioritizes the health and safety of both the mother and potential offspring. It helps to minimize the chances of complications such as preterm birth and low birth weight, which are more common with multiple pregnancies. Additionally, it can improve the overall success rates of IVF by focusing on the quality of the transferred embryo rather than the quantity. The Hungarian government anticipates that these measures will enhance the success rates of IVF treatments, consequently leading to a rise in future childbirths and a decrease in the number of frozen embryos. This study aims to delineate the effectiveness of the introduced changes in 2023 and provide recommendations accordingly.

Effect of Intrauterine Laser Therapy at the IVF Success Rate on Infertile Patients with a History of IVF Failure: A Pilot Non-Blinded Study

Effect of Intrauterine Laser Therapy at the IVF Success Rate on Infertile Patients with a History of IVF Failure: A Pilot Non-Blinded Study

The role of epigenetics in women's reproductive health: the impact of environmental factors.

This paper explores the significant role of epigenetics in women's reproductive health, focusing on the impact of environmental factors. It highlights the crucial link between epigenetic modifications-such as DNA methylation and histones post-translational modifications-and reproductive health issues, including infertility and pregnancy complications. The paper reviews the influence of pollutants like PM2.5, heavy metals, and endocrine disruptors on gene expression through epigenetic mechanisms, emphasizing the need for understanding how dietary, lifestyle choices, and exposure to chemicals affect gene expression and reproductive health. Future research directions include deeper investigation into epigenetics in female reproductive health and leveraging gene editing to mitigate epigenetic changes for improving IVF success rates and managing reproductive disorders.

Assessment of Differential Expression of Progesterone Receptors A & B in Endometriosis Undergoing IVF Treatment: A Personalized Approach for Better IVF Success

Objective: Estrogen and Progesterone hormones play a pivotal role in the pathogenesis of Endometriosis. In the present study, relative quantification of PR-A and PR-B expression in eutopic endometrial tissue and endometriotic implants was done. By examining their expression profiles, we aim to gain deeper insights into the molecular mechanisms that can influence IVF success or failure in endometriotic patients. Our study also observed certain ART outcomes in both endometriosis and control groups, to evaluate the IVF success rate. Methods: This study was conducted at MHRT, a tertiary care center, and referral centers from other hospitals. The research encompassed an examination of 125 cases of infertility spanning from January 2019 to January 2023. Finally, biopsy samples were collected from 60 patients with endometriosis during laparoscopic procedures, while control biopsy samples were gathered from 18 patients who exhibited no signs of endometriosis lesions during the same laparoscopic procedures. The biopsy samples were then sent for Progesterone assay and later evaluated for ART outcomes. Results: It was observed from the results of our study that there was a significant downregulation of PR-A in stage III, and IV compared to Stage I and II. However, there was no significant change in PR-B expression in grades I and II, III and IV. Our study also observed certain ART outcomes in both endometriosis and control groups, revealing that women with endometriosis have lower chances of achieving pregnancy than women with other causes of infertility (95% CI, 22/60 vs. 12/18, p-value = 0.024). Conclusion: Our study results shed light on the complex role of progesterone isoforms in endometriosis. Progesterone receptor-A significant downregulation in severe cases challenges existing paradigms and opens new avenues for research.

Does Mitochondrial Transfer An Alternative to Egg Donation?

Objective
 To evaluate the utility of pronuclear transfer using healthy oocytes from donors in poor prognosis patients.
 Design
 Retrospective study.
 Subjects
 A total of 29 patients with no blastocyst development or total fertilization failure were included.
 Main Outcome Measures
 Our primary outcome was the blastocyst rate. Secondary outcomes measures included euplody rate, clinical pregnacy rate and live birth rate.
 Results
 On day 5/6 of blastocyst development, an average blastocyst rate of 49.2% was obtained. The average rate of euploid blastocysts obtained after PGT-A was 69.5%. All patients underwent frozen embryo transfer. Single blastocyst transfer was performed in all patients, and the clinical pregnancy rate was 48.3%. Of these patients, 14 had a live birth, and the live birth rate was 48.3%. No genetic or morphologic abnormalities have been detected in the babies born. The 29 patients were grouped based on their age, as <35 (n=2), 35-27 (n=6), 38-40 (n=9), 41-42 (n=6) and >42 (n=6). Based on these age groups, blastocyst formation rates were 47.8%, 50.0%, 45.0%, 50.0% and 66.7%, respectively; euploidy rates were 63.6%, 61.1%, 66.7%, 100.0% and 83.3%, respectively; clinical pregnancy and live birth rates were 100.0%, 50.0%, 44.4%, 50.0% and 33.3%, respectively.
 Conclusions
 The results of this study show that pronuclear transfer can result in a high blastocyst formation rate, euploidy rate and live birth rate. This was shown among patients across all age groups, particularly in older patients who often show diminished IVF success rates.

The Clinical Embryologist: Past, Present and Future Challenges

Embryologist is an essential part of infertility care defined as a highly skilled and well-trained person who can work in teamwork to execute continuous tasks with near-zero error and pay attention to detail with excellent clinical judgment. At the very beginning, embryologist’s routine daily tasks were quite simple including processing the sperm and eggs for natural insemination. Following that, advanced infertility treatment emerged quickly including intracytoplasmic sperm injection (ICSI), vitrification-warming, embryo shipping, intracytoplasmic morphologically sperm injection (IMSI), as well as trophectoderm biopsy as a source of chromosomal copy number testing or monogenic disorders analysis. Collectively, the implementation of such improved treatments renders complexity in the IVF laboratory that could be simplified in the future. Apparently, the implementation of advanced technology in the field of IVF nowadays has two main purposes. The first is to improve the IVF success rate including finding precise markers for embryo selection such as genomics, proteomics, and metabolomics fingerprint and images-based artificial intelligence algorithm for embryo selection. The second is to standardize or simplify routine daily tasks in the embryology laboratory by implementing automated software such as for laboratory quality control maintenance, a microfluidic system that allows standardization of handling gametes, micro-robotic for immobilizing sperm for ICSI, fully automated semen analysis, electronic tagging of laboratory devices to improve traceability. All such automated systems will serve as advanced clinical decision tools to boost IVF success rate and infertility care quality. An elevated automated system in the future in an embryology laboratory would impact the clinical embryologist in terms of reduced quantity and conversely, increased qualities of highly scientific embryologists with proper education. Embryologist roles may change from conventional routine daily tasks to well-trained and experienced embryologists who are able to scientifically evaluate the effectiveness of certain approaches or potential clinical use of such implementation in their clinical laboratory setting.

When Should We Recommend Egg Freezing and When Is It Too Late?

Social oocyte freezing (SOF), a fast-growing field in ART is the elective cryopreservation of one’s own oocytes at a younger age when oocytes are of higher quality with the goal of prolonging a woman’s childbearing opportunity without any urgent medical reasons. The optimum age for SOF is said to be below the age of 35 years ( ASRM , 2013 ; ESHRE , 2012 ). SOF in women above 35 years of age is associated with lower post-thaw survival rates, a lower live birth rate per thawed oocyte, and an increased overall cost per livebirth as more cycles of oocyte freezing and thawing may be required. Beyond 42 years of age, SOF is unlikely to result in a livebirth due to suboptimal response to stimulation and a higher cycle cancellation rate ( ASRM , 2013 ; Doyle, et al. , 2016 ; Wennberg, et al. , 2019 ). The number of oocytes needed to freeze varies widely between studies but should be individualized according to the woman’s ovarian reserve as well as the IVF center’s own success rate data ( Teo, et al. , 2021 ). The utilization rate of frozen oocyte is low, ranging from 6 to 15%. The main reasons cited are a) women not wanting to start a family without a partner; b) preference for natural conception and, c) refusal to use a sperm donor ( Hammarberg, et al. , 2017 ). With the use of relatively safe IVF techniques and success rates similar to that of fresh oocytes, SOF has become an acceptable reproductive option for women today to extend their reproductive ability to achieve parenthood using their own eggs. It is, however, expensive and more than one cycle of oocyte freezing may be required to improve its efficacy. Thorough counselling must be done to advise women regarding the lack of robust evidence on its efficacy, long-term risks, and costs.

#212 : Does Hyaluronic Acid-Containing Transfer Media Improve the Live Birth Rate in Frozen Embryo Transfer Cycles?

Background and Aims: The glue is typically composed of hyaluronan, a natural substance found in the female reproductive tract, and other nutrients that help to support the embryo. The glue is believed to improve the chances of successful implantation by helping the embryo adhere to the uterine lining and promoting communication between the embryo and the uterine environment. The effectiveness of embryo glue is still being studied, and limited evidence on its benefits is available. The objective of our study is to find the effect of hyaluronidase containing transfer media (Embryo Glue) on ART outcomes. Method: This retrospective study is based on central hospital recorded data between January 2015 and January 2022. The females aged 20-40 years and Body mass index (BMI) of 18.0 to 35 kg/m2 were included. Results: Univariate logistic regression showed that the duration of progesterone administration on (6-Days vs 7-days (OR 1.693; (1.045-2.740); P = 0.032), endometrial thickness on the day of P start (OR 1.167; (1.056-1.290); P = 0.002), Embryo Glue (ref. Standard treatment) (OR 1.700; 95% (1.364-2.118); P<0.001) were independent factors for predicting live birth. Multivariate logistic regression analysis showed that female age (OR 0.927; (0.893-0.963) P < 0.001), Number of blastocysts transferred (DET), (ref. SET) (OR 1.618; (1.086-2.410); P = 0.018), Endometrial thickness at the day of P start (OR 1.147; (1.014-1.298); P = 0.029) and Embryo Glue (ref. Standard treatment) (OR 1.593; (1.170-2.168); P = 0.003) were independent factors for predicting live birth. Conclusion: Embryo glue has shown significant outcomes in the present study and effectively improves IVF success and implantation rates. However, the decision to use embryo glue should be made on a case-by-case basis in consultation with a fertility specialist, and it may not be necessary or beneficial for all IVF procedures.

#316 : Improved Time to Pregnancy When Combining an Artificial Intelligence Score and Morphology Grading for Embryo Selection During IVF

Background and Aims: Embryo selection is critical in determining IVF success yet continues to be challenging due to the subjectivity of morphology grading methods, especially when grading fair/average quality embryos. Improving embryo selection could optimise implantation rates and minimise financial/emotional burden on patients. Artificial Intelligence (AI) algorithms represent promising, non-invasive methods of standardising embryo grading and potentially increasing IVF success rates. This study assessed whether an AI algorithm (Life Whisperer Viability) for evaluating the likelihood of clinical pregnancy improves time to pregnancy (TTP) when compared to or combined with standard morphology grading. Method: 305 de-identified 2D images of day 5 blastocysts (121 fresh/184 frozen) with matched clinical pregnancy outcomes (fetal heartbeat at first scan) from women who underwent IVF treatment from 2020-2023 were retrospectively assessed. All images were taken prior to transfer/freezing. TTP was assessed using a simulated cohort ranking method, with TTP being defined as the average number of transfers needed to obtain a clinical pregnancy. Results: A positive linear correlation of LWV scores with pregnancy outcomes was observed (p<0.001). ROC-AUC results indicate that LWV is selecting embryos leading to pregnancy at least as well, if not better, than Gardner morphology grading (0.641 vs 0.624), with further improvement observed when LWV and Gardner grading were combined. The TTP analysis showed a 7.3% reduction in TTP when using LWV over Gardner grading. Combined use of LWV+Gardner grading reduced TTP by up to 10.8%, with the largest improvement (5.3%) seen in the frozen group, where there was a higher distribution of average quality embryos. Conclusion: LWV showed improved embryo rankingand reduction in the estimated average number oftransfers needed to achieveclinical pregnancy. Furthermore, evaluation of TTP supports the combined use of LWV+Gardner grading, showing that they work synergistically to further improve ranking performance when selecting average quality embryos.

PSIV-11 The Effects of Vanillic Acid Supplementation During in Vitro Oocyte Maturation in Pigs

Abstract In vitro fertilization (IVF) typically has low success rates in pigs partially due to the negative effects of oxidative stress on both the sperm and egg. Antioxidants, such as vanillic acid, are known to have protective effects on the oocyte in terms of maturation. The purpose of this study was to determine the effects of vanillic acid supplementation during porcine oocyte maturation on reactive oxygen species (ROS) generation, IVF, early embryonic development success rates, membrane lipid peroxidation, and catalase activity. Oocytes were matured for 40 to 44 h supplemented with vanillic acid (0, 3, 6, 12 mg/mL; Sigma-Aldrich Co.). After maturation, oocytes were denuded and either evaluated for ROS production (n = 183, r = 3) by measuring the fluorescent intensity from the oxidation of 2’,7’-dichlorodihydrofluorescein diacetate, membrane lipid peroxidation (n = 360), catalase activity (n = 724), or fertilized using frozen-thawed boar semen (1.0 x 105 sperm cells/mL) and co-incubated for 6 to 8 h followed by embryo culture for 144 h. After IVF, presumptive zygotes were fixed, permeabilized, and stained with bisBenzimide H 33342 trihydrochloride and evaluated for penetration, polyspermy, and pronucleus formation rates (n = 390) and embryos were evaluated for cleavage and blastocyst formation (n = 529) at 48 h and 144 h post-IVF, respectively. Fluorescent intensities indicating ROS of individual oocytes, lipid peroxidation, catalase activity, and were analyzed using GLM, and means were compared using LSD. The IVF and embryo development data were reported as the percent observed/drop, and mean percentages, and means were analyzed using a GLM with differences being compared using Tukey’s test. Supplementation of 6 g/mL vanillic acid or 12 mg/mL vanillic acid reduced (P < 0.05) the amount of ROS (0.68 ± 0.06, 0.63 ± 0.06; respectively) compared with no vanillic acid supplementation (1 ± 0.06). Vanillic acid supplementation did not have any effect on oocyte penetration rates; however both 6 mg/mL and 12 mg/mL vanillic acid decreased (P < 0.05) polyspermic penetration rates (23.79 ± 0.02, 24.03 ± 0.02; respectively), and increased (P < 0.05) pronuclear formation (83.76 ± 0.02, 84.80 ± 0.02; respectively). Supplementation of vanillic acid had no effect on cleavage rates (78.69 ± 0.02) by 48 h post-IVF or blastocyst formation (31.18 ± 0.03) by 144 h post-IVF. Supplementation of 6 mg/mL vanillic acid decreased (P < 0.05) membrane lipid peroxidation (0.46 ± 0.06) and catalase activity (0.01 ± 0.01) compared with no vanillic acid supplementation (0.79 ± 0.06, 0.03 ± 0.01; respectively). Based on these results, supplementation of 6 mg/mL vanillic acid or 12 mg/mL vanillic acid during oocyte maturation reduces the amount of ROS formed in vitro and improves IVF success rates. Supplementation of 6 mg/mL decreases catalase activity and membrane lipid oxidation following oocyte maturation.

Egg Freezing: Risk, Benefits, Steps and Results: Review

Thanks to the development of quick freezing of human oocytes, numerous programmes have achieved IVF success rates comparable to those attained with fresh eggs and thawed frozen embryos. Egg freezing (EF) technology advancements over the previous ten years have offered women more control over their chances of getting pregnant. The option for healthy women to cryopreserve their oocytes to avoid future infertility has grown in favour recently. But women often cryopreserve their oocytes in their late thirties, which is undesirable from a therapeutic perspective because the quantity and quality of the oocytes have already greatly decreased and there are therefore less odds of successfully conceiving a child. Egg freezing is now gaining regulatory and professional acceptance as a safe and efficient method for women who want to avoid throwing away extra embryos, who are undergoing treatments that could endanger their fertility, or who want to store their eggs for use when they are later ready to start a family. The applications and logic of egg freezing are the main topics of this article.