Ovarian Hyperstimulation Syndrome Research Articles

P-605 Effectiveness of follitropin delta in patients with potential poor response: A post hoc analysis from the ESTHER-1 trial

Abstract Study question What is the effectiveness of individualised follitropin delta dosing compared to conventional follitropin alfa dosing in patients with potential poor response undergoing ovarian stimulation? Summary answer Individualised follitropin delta dosing provides a favourable efficacy and safety balance and is as good as follitropin alfa in patients with potential poor ovarian response. What is known already Poor ovarian response to controlled ovarian stimulation constitutes a challenge in in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment. The dosing algorithm of follitropin delta incorporates the prediction of ovarian response based on anti-Müllerian hormone (AMH), an accurate marker of ovarian reserve, and body weight, for an individualised dosing. In the general IVF/ICSI population and potential high responders, individualised follitropin delta reduces the risk of ovarian hyperstimulation syndrome (OHSS) and/or preventive interventions for OHSS, with sustained efficacy compared to conventional follitropin alfa. However, the performance of follitropin delta in the subpopulation of patients with potential poor response has not been evaluated. Study design, size, duration Post hoc analysis of 332 patients with potential poor response from the ESTHER-1 trial (determined by AMH level at screening <9 pmol/L). Patients received the maximum daily dose of 12 µg follitropin delta (fixed dosing throughout stimulation) as stipulated by the dosing algorithm for patients with AMH <15 pmol/l, or follitropin alfa at a starting dose of 150 IU, with potential dose adjustments from stimulation day 6 and onwards (maximum daily dose of 450 IU). Participants/materials, setting, methods Participants were women, 18–40 years, undergoing their first IVF/ICSI cycle in a GnRH antagonist protocol, including triggering with human chorionic gonadotrophin, IVF/ICSI insemination, and single or double blastocyst transfer on Day 5. Ultrasound was performed 10–11 weeks after transfer to confirm ongoing pregnancy. All pregnancies were followed until birth. Study outcomes include number of oocytes retrieved and number of good quality blastocysts, ongoing pregnancy and live birth rates, cycle cancellation and OHSS rates. Main results and the role of chance A total of 332 patients (25.0% of the overall ESTHER-1 population) had serum AMH at screening of < 9 pmol/l and were included in the analysis: 168 were treated with follitropin delta and 164 were treated with follitropin alfa. Baseline characteristics were similar between the treatment groups, with a mean age of 34.8 years, a median AMH of 5.7 pmol/l and a mean weight of 64.5 kg. With follitropin delta, the mean daily dose was 12.0 µg and with follitropin alfa 12.4 µg, resulting in mean total doses of 104.6 µg and 112.3 µg, respectively. The mean number of oocytes retrieved was 5.8 ± 3.5 with follitropin delta and 5.5 ± 3.6 with follitropin alfa and the mean number of good-quality blastocysts was 1.2 ± 1.4 with both treatments. The ongoing pregnancy rate was 29.8% with follitropin delta and 29.3% with follitropin alfa and the live birth rates were 29.2% and 28.7%, respectively. Thirteen patients (7.7%) treated with follitropin delta and 14 (8.5%) treated with follitropin alfa had their cycles cancelled due to poor response. One case of OHSS (0.6%) was observed in the follitropin delta group, and 3 cases (1.8%) were observed in the follitropin alfa group. Limitations, reasons for caution The main limitation of the study is its post hoc nature. Furthermore, the study is based on a relatively small number of patients. Wider implications of the findings This subgroup analysis, alongside the normoresponder and the potential hyperresponder subgroup of the ESTHER-1 trial, adds evidence for the effectiveness of follitropin delta across all ovarian reserve subgroups of the infertile population. Trial registration number NCT01956110

P-655 Live birth rate in the fresh cycle associated with number of oocytes in ovarian stimulation with individualised follitropin delta: an individual patient data meta-analysis

Abstract Study question What is the optimum number of oocytes retrieved to achieve a live birth for women undergoing ovarian stimulation with individualised follitropin delta? Summary answer The live birth rate (LBR) in the fresh cycle was highest in the range of 8-14 oocytes retrieved, peaking at 11 oocytes. What is known already The number of oocytes retrieved following ovarian stimulation for assisted reproductive technologies is regarded a prognostic marker of pregnancy outcome, where high numbers increase chances of live birth but also the risk of complications, especially ovarian hyperstimulation syndrome (OHSS). Thus, an optimum range of oocytes retrieved is essential. Still, there is no consensus regarding this range in fresh cycles. Optimum numbers between 6 and 15 oocytes have been suggested, taking the risk of OHSS into consideration. The individualised dosing algorithm for the recombinant follicle-stimulating hormone follitropin delta has a target range of 8–14 oocytes. Study design, size, duration Individual patient data meta-analysis of 1772 patients from 5 randomised controlled trials using individualised dosing of follitropin delta for ovarian stimulation, with fixed daily dosing based on serum anti-Müllerian hormone (AMH) and body weight. The analysis included patients with ≥1 oocyte retrieved. Outcomes of LBR and OHSS in the fresh stimulation cycle were evaluated in relation to number of oocytes retrieved. Subgroup analyses were performed based on age, AMH and number of oocytes retrieved. Participants/materials, setting, methods Participants were women, 18–42 years, undergoing first or second in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle in a GnRH antagonist/long agonist protocol with human chorionic gonadotrophin or GnRH agonist triggering and IVF/ICSI. Single or double embryo/blastocyst transfer was performed on Day 3/5. All pregnancies were followed until birth. Predicted live birth was obtained using a logistic regression analysis with fractional polynomials to assess the association between number of oocytes retrieved and live birth. Main results and the role of chance The studied population (n = 1772) had a mean age of 32.6 years and median AMH of 17.7 pmol/l. Mean number of oocytes retrieved was 10.4, the LBR was 32.1% and the OHSS rate (any grade and onset) was 6.6%. The LBR steadily increased with the number of oocytes retrieved up to a plateau starting at 8 oocytes, with a LBR above 34% in the range of 8-14 oocytes retrieved, peaking at 34.9% for 11 oocytes. Beyond 14 oocytes, LBR gradually declined. By number of oocytes (grouped), the LBR was 27.8%, 33.6% and 30.9% at 1-7, 8-14 and ≥15 oocytes. In patients with embryo transfer, corresponding rates were 32.8%, 37.2% and 38.7%. In the subgroup analyses, LBR decreased with increasing age (32.7%, 30.7% and 23.4% at < 35, 35-37 and 38-42 years) while it was similar for AMH <15 and ≥15 pmol/l (30.4% and 31.3%, respectively). LBR was highest at 8-14 oocytes in patients <35 years (28.0%, 36.2% and 32.4% at 1-7, 8-14 and ≥15 oocytes), while it was consistently low (<26%) in patients 38-42 years, irrespective of number of oocytes retrieved. The OHSS rate (any grade) increased from 2.1% with 1-7 oocytes, to 5.2% with 8-14 oocytes and 17.0% with ≥15 oocytes. Limitations, reasons for caution A limitation of this study is the small number of patients with >20 oocytes retrieved in the studied population. Wider implications of the findings The current individual patient data meta-analysis suggests an optimum range of 8-14 oocytes retrieved to achieve a live birth in fresh cycles with follitropin delta. Furthermore, the analysis demonstrates a marked increase in OHSS rate from 15 oocytes retrieved. The results support the appropriateness of individualised follitropin delta dosing regimen. Trial registration number NCT01956110, NCT03228680, NCT03296527, NCT03564509, NCT03809429

O-059 ART in PCOS

Abstract Polycystic Ovarian Syndrome affects an estimated 8 – 13% of women of reproductive age (WHO). It is the commonest cause of anovulation and infertility. The high AMH, LH, Insulin resistance and hyperandrogenism seen in PCOS women contributes to infertility along with poor oocyte quality and reduced endometrial receptivity. ART procedures are recommended as the third line of treatment after ovulation induction, IUI or ovarian drilling. Prior to IVF, metabolic assessment and lifestyle adjustments with weight management must be done. Adjuvant agents such as metformin melatonin, myoinositol and Vitamin-D have been tried to improve IVF outcomes. Mild stimulation is an option in patients as high risk for ovarian hyperstimulation syndrome (OHSS). Conventional stimulation with low dose FSH, GnRH antagonist down regulation, agonist trigger with freezing of all embryos, significantly reduces risk of OHSS without compromising cumulative live birth rates. Adjustments for stimulation protocols may need to be made for BMI, insulin resistance and AMH. In vitro maturation can be considered in patients with prior severe OHSS, though the results may be inferior. ART in PCOS patients is challenging and even after pregnancy is achieved, there may be a higher risk of adverse obstetric outcomes.

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-639 Are GnRH-agonists (GnRH-a) safer and more effective ovulation triggers than human chorionic gonadotrophin (hCG)? A retrospective analysis of frozen embryo replacement cycle (FERC) outcomes

Abstract Study question Are GnRH-agonists (GnRH-a) safer and more effective ovulation triggers than human chorionic gonadotrophin (hCG)? A retrospective analysis of frozen embryo replacement cycle (FERC) outcomes Summary answer GnRH-a trigger reduces the incidence and severity of ovarian hyperstimulation syndrome (OHSS) leading to significantly improved clinical outcomes when compared to hCG trigger for FERCs. What is known already Ovulation induction plays a crucial role in the success and safety of ART cycles. hCG is extensively used as an alternative to LH to trigger ovulation. However, high levels of sustained hCG exposure increases the risk of OHSS, a potentially life-threatening complication of ART. To eliminate the risk and incidence of OHSS, GnRH-a can be used to trigger ovulation. Although there are concerns regarding clinical outcomes with fresh transfers following GnRH-a trigger, it elicits a more physiological response compared to hCG. This may lead to improved embryo quality, utilisation, and better clinical outcomes following a freeze-all strategy, reducing patients’ time-to-pregnancy. Study design, size, duration This was a retrospective data analysis of FERC outcomes following fresh IVF or ICSI cycles, involving ovulation induction using either hCG or GnRH-a as a final trigger. The evaluation included results from cycles spanning an eight-year period, from January 2012 to December 2019 at Hammersmith Hospital London. A total of 160 cycles were included in the study, with 76 in the hCG trigger group and 84 in the GnRH-a trigger group. Participants/materials, setting, methods Strict inclusion criteria were employed to render the study groups as comparable as possible and to minimise the effect of independent variables, such as oocyte and sperm factors, on oocyte or embryo developmental competence. Inclusion criteria: women ≤37 years old at the start of treatment, GnRH antagonist stimulation, blastocyst vitrification-warming and transfers only. Statistical significance was calculated using independent t-test and Fisher’s Chi-square exact test. Main results and the role of chance The mean age (±SD) of patients at the time of oocyte retrieval was comparable across groups. The average number of oocytes collected were significantly higher in the GnRH-a group compared to hCG (28.31 vs. 18.07, respectively, P < 0.001). Embryological data (maturation, fertilisation, blastocyst formation, blastocyst utilisation and good quality blastocyst formation rates) were comparable across both groups. OHSS rate was significantly lower in the GnRH-a group (17% vs. 50%. P < 0.0001). The following clinical data were significantly higher (P < 0.05) in the GnRH-a group compared to hCG: implantation rate (56% vs. 36%), clinical pregnancy rate (56% vs. 36%) and live birth rate (42% vs. 27%). Limitations, reasons for caution The biggest limitation of this study is its retrospective nature and the application of various inclusion-exclusion criteria that have resulted in relatively small sample sizes. Additionally, numerous other confounders, e.g. patient body mass index, cause/duration of infertility and stimulation duration, have not been considered in this study. Wider implications of the findings The findings of this study are promising and demonstrate a great potential for benefit in the use of GnRH-a trigger with a freeze-all strategy to minimise the risk of OHSS, diminishing the associated patient morbidity and mortality, reducing healthcare costs, improving clinical outcomes, and reducing the overall time-to-pregnancy for patients. Trial registration number not applicable

O-086 Risk of serious adverse event after fertility preservation procedures: a comparison of cancer and non-cancer patients

Abstract Study question Do cancer patients have a higher risk of serious adverse event associated to fertility preservation procedures compared to non-cancer patients ? Summary answer No increased risk of adverse event after fertility preservation procedures was identified in cancer patients compared to non-cancer patients undergoing fertility preservation for other indications. What is known already Current recommendations encourage a prompt and exhaustive discussion on the different techniques of fertility preservation that can be performed in cancer patients of reproductive age prior to cancer treatments. Although cryopreservation of mature oocytes and/or embryos is the technique of reference in the absence of contraindication, ovarian stimulation and subsequent oocyte retrieval are associated to complications. Cancer patients might present an additional risk given tumoral hypervascularity and proinflammatory environment, as well as possible immune or coagulation disorders. However, whether cancer patients have an increased risk of serious adverse event associated to fertility preservation procedures compared to non-cancer patients remains unknown. Study design, size, duration A bicentric, retrospective study between January 1st, 2014 and December 31st, 2021. Participants/materials, setting, methods All women undergoing fertility preservation procedures by oocyte and/or embryo cryopreservation after controlled ovarian stimulation or in vitro maturation.The main endpoint was the occurrence of a serious adverse event (hospitalization for ovarian hyperstimulation syndrome, hemorrhage, infection, thromboembolic event, ovarian torsion, acute urine retention or death) in cancer patients compared to non-cancer patients undergoing fertility procedures. Main results and the role of chance A total of 4476 cycles (n = 3180 patients) were included, of which 3761 after controlled ovarian stimulation and 715 in vitro maturation cycles. Among the 4476 cycles, 1678 were performed in an oncological context (n = 1546 cancer patients) and 2798 were fertility preservation cycles for an indication other than cancer (n = 1634 patients). A total of 29 serious adverse events associated to fertility preservation procedures were registered, of which 17 intraperitoneal hemorrhages, 8 cases of ovarian hyperstimulation syndrome, 3 cases of infection and 1 case of acute urine retention. The risk of serious adverse event associated to fertility preservation procedures was not significantly different between cancer patients and non-cancer patients (0.36% vs. 0.82%, respectively, P = 0.06). Young age (P = 0.002), a higher number of oocytes retrieved (P = 0.006) and a higher number of oocytes vitrified (P = 0.002) were significantly associated to the risk of presenting a serious adverse event after fertility preservation. Limitations, reasons for caution Although rates of serious adverse events in our study are similar to that reported in previous literature and that the declaration and registration of any serious adverse event is mandatory according to French legislation, it is possible that not all serious adverse events were declared and registered. Wider implications of the findings Given the trend of delaying parenthood and the improved survival rates after cancer treatments, these findings are of particular importance, emphasizing the safety of performing fertility preservation procedures for cancer patients of reproductive age who might have a pregnancy desire after cancer treatment. Trial registration number not applicable

P-634 Medroxyprogesterone acetate as an alternative to gonadotropin-realeasing hormone antagonist in vitrified oocyte donation cycles: embryo assessment and clinical outcome

Abstract Study question Could Medroxyprogesterone Acetate (MPA) be a good alternative to gonadotropin-realeasing hormone (GnRH) antagonist in vitrified oocyte donation cycles? Summary answer MPA is a good alternative to GnRH antagonist in vitrified oocyte donation cycles, ensuring comparable embryo quality and clinical outcome. What is known already Progestin-primed ovarian stimulation (PPOS), such as oral administration MPA in the follicular phase appears to be an effective alternative to conventional protocols, as it prevents premature LH surge and ovarian hyperstimulation syndrome. The drawback of these treatments is that it requires vitrification of oocytes or embryos because the endometrium is out of phase when embryo transfer is performed. Our previous studies have shown similar oocyte retrieval rates in fertility preservation cycles and comparable clinical outcomes in fresh donation cycles. Our objective is to expand evidence on PPOS, extending its success to new populations like vitrified donation cycles. Study design, size, duration This retrospective cohort study performed at IVI Valencia compared the effect of the MPA (10 mg/day) versus ganirelix (0.25 mg/day) on egg donors undergoing ovarian stimulation whose eggs were vitrified after retrieval. Donor cycles were divided intro groups, with 495 cycles in the MPA group and 307 in the ganirelix group. After oocyte donations and warming, the artificial intelligence based embryo assessment and clinical outcome were compared and analyzed for the two study populations Participants/materials, setting, methods 497 recipients using oocytes from the MPA group and 307 from the ganirelix group were included in the study. Post-oocyte donation and warming, a follow-up of 10,108 oocytes was performed, analyzing survival, fertilization, and blastocyst development. The embryo score obtained with the deep learning based model iDAScore v2, and the ASEBIR evaluation performed by embryologists were compared between both study populations. Finally, comprehensive clinical outcome comparisons were conducted between the two study populations. Main results and the role of chance The mean number of thawed oocytes was significantly different* between the two groups (12.80±3.54 in the MPA group vs. 12.20±3.58 in the antagonist group). Survival, fertilization, and blastocyst development rates showed no significant differences (89.83%, 76.38% and 66.22% respectively in the MPA group and 88.67%, 76.75% and 64.29% in the antagonist group). However, ASEBIR embryo assessment showed a significantly higher percentage of embryos classified as A and B in MPA group* (10.5% and 58.0% respectively vs. 7.2% and 53.6%), and more C embryos* in the antagonist group (34.3% vs. 39.2%). Artificial intelligence-based embryo assessment revealed no significant differences between the two groups*, with mean evaluations being 4.97±2.60 in the MPA group and 5.07±2.68 in the antagonist group. Regarding clinical outcomes, the MPA group had significantly higher number of frozen embryos per cycle* (4.08±2.07 in the MPA group vs. 3.65±2.00 in the antagonist group) but no disparities in implantation, clinical pregnancy, ongoing pregnancy, live birth and cumulative live birth rates. A generalized estimation equation highlighted that the study group (MPA or antagonist) did not significantly impact the live birth rate, but was significantly influenced instead by the number of thawed oocytes, recipient BMI, and transferred embryo quality assessed with iDAScore*. (*p<.05) Limitations, reasons for caution This project is limited by its retrospective and single-center nature. Despite being the largest sample size ever reported for PPOS in vitrified donation cycles, the number of patients included could be considered low. Consequently, it would be advisable to conduct a multicenter RCT to confirm the conclusions of this study. Wider implications of the findings The administration of MPA as a gonadotropin adjuvant demonstrates clinical outcomes comparable to those achieved with ganirelix in vitrified oocyte donation cycles. Its user-friendly application encourages the wider adoption of this protocols. These promising results promote the widespread use of MPA-based protocols in vitrified oocyte donation cycles. Trial registration number not applicable

P-633 Impact of insulin resistance on reproductive medicine outcomes

Abstract Study question Does Homeostasis Model Assessment for insulin resistance (HOMA-IR) have an influence in reproductive medicine outcomes? Summary answer HOMA-IR is associated with fertility treatment parameters and has a significant influence on reproductive medicine outcomes. What is known already The HOMA model is used to yield an estimate of insulin sensitivity from basal (fasting) plasma insulin and glucose concentrations. Currently, the model has become a widely used clinical tool to evaluate glucose metabolism. Regarding fertility, the relation between polycystic ovary syndrome (PCOS) and insulin resistance (IR) has been studied. Insulin resistance may be potential contributor to impaired treatment outcomes in artificial reproductive technology (ART). Although a few studies have recently been published on the topic the association of HOMA-IR with fertility treatment parameters remains a black box in reproductive medicine research. Study design, size, duration The observational study was designed and conducted at the Kinderwunsch Institut Schenk GmbH (Dobl, Austria). The study included 175 patients (25 men and 150 women), aged 18-45. HOMA-IR was determined for each patient and then correlated with patient’s medical history, fertility treatment parameters and outcomes. Participants/materials, setting, methods HOMA-IR was determined by taking a blood sample during fasting state and measuring plasma values of glucose (mg/dl) and insulin (mU/ml). A HOMA-IR of ≥ 2 was considered as insulin resistance. HOMA-IR was correlated with medical history (polycystic ovarian syndrome (PCOS), endometriosis, Body-Mass-Index (BMI), nicotine abuse) and fertility treatment parameters (sperm quality, number of retrieved oocytes after controlled ovarian stimulation, number of mature and fertilized oocytes, embryo quality and pregnancy rate). Main results and the role of chance An increased HOMA-IR (³2) was observed in 90 patients (51.4%). They suffered from obesity (n = 36; 80%), PCOS (n = 22; 70.97%), ovarian hyperstimulation syndrome (n = 17; 77.27%) and experienced poor embryo quality (n = 249; 91.54%). A significant positive correlation was found between HOMA-IR and PCOS (p < 0.001), obesity (p < 0.001) and number of retrieved oocytes (p < 0.05). The pregnancy rate correlated negatively with the HOMA-IR (p < 0.001). Furthermore, trends of positive correlations of high HOMA-IR in endometriosis, BMI, pathological spermiogram, nicotine abuse and increased number of mature oocytes were determined. The relation between HOMA-IR and the number of retrieved and mature oocytes is consistent with its relation to PCOS. The data show that HOMA-IR is associated with fertility treatment parameters and has a significant influence on ART outcome. Limitations, reasons for caution The number of patients may be seen as a study limitation. Results should be confirmed with a bigger sample size. An interventional study should confirm the role of HOMA-IR in IVF outcomes. Wider implications of the findings These findings may help to better understand the importance of glucose and insulin metabolism in reproduction and suggest that evaluation of HOMA-IR may be a valuable parameter to be considered when collecting patients’ anamnesis prior to starting ART treatment. Trial registration number not applicable

P-162 Embryo transfer impact: a comprehensive national cohort analysis comparing maternal outcomes across varied embryo stages in fresh and frozen transfers

Abstract Study question What is the ideal choice between fresh and frozen embryos transfer, and should the transfer be done at the cleavage or blastocyst stage? Summary answer This study highlights the clinical pregnancy and live birth superiority of frozen embryo transfer in blastocysts but not in cleavage stage embryos. What is known already Frozen embryo transfer not only improves reproductive outcomes by increasing the chances of live birth and clinical pregnancy but also enhances safety by reducing the risks of OHSS and multiple pregnancies. Due to the consistent findings, there has been a growing discussion in recent years about whether it is advisable to adopt elective frozen embryo transfer as the standard practice. Study design, size, duration In this retrospective cohort study conducted in Taiwan, a comprehensive dataset from the national assisted reproductive technology (ART) database was utilized, covering the period from January 1st, 2013, to December 31st, 2017. The final cohort study encompassed eligible 51762 female participants who had undergone ART and embryo transfer. Pregnancy outcomes and maternal complications during the follow-up were assessed using the population registry dataset from January 1st, 2013, to December 31st, 2018. Participants/materials, setting, methods The study categorizes cases into groups based on whether they underwent fresh or frozen embryo transfers, with additional subgroups based on cleavage stage and blastocyst stage transfers. Exposure variables include clinical pregnancy rate, live birth rate, ovarian hyperstimulation syndrome (OHSS), pregnancy-induced hypertension, gestational diabetes mellitus (DM), placenta previa, placental abruption, and preterm premature rupture of membranes (PPROM). Main results and the role of chance For pregnancy outcomes, frozen blastocyst transfers exhibited higher rates of clinical pregnancy (OR 1.33, 95%CI 1.25-1.42) and live births (OR 1.27, 95%CI 1.19-1.36) when compared to fresh blastocyst transfers. However, frozen cleavage stage transfers had lower rates of clinical pregnancy (OR 0.73, 95%CI 0.69-0.77) and live births (OR 0.79, 95%CI 0.74-0.84) compared to fresh cleavage stage transfers. For maternal complications, frozen embryo transfers were associated with reduced risks of OHSS (OR 0.02, 95%CI 0.02-0.03 for blastocyst and OR 0.05, 95%CI 0.03-0.09 for cleavage stage) compared to fresh embryo transfers, but were linked to a higher risk of pregnancy-induced hypertension (OR 1.43, 95%CI 1.19-1.73 for blastocyst and OR 1.23, 95%CI 1.29-1.82 for cleavage stage). No significant differences were observed in the incidence of gestational DM and PPROM among the various transfer groups. Limitations, reasons for caution Our retrospective study design may not offer the same level of rigor as a randomized controlled trial. Furthermore, the reproductive database did not provide detailed information on specific endometrial preparation methods (such as hormone replacement therapy or natural cycle), which could potentially influence implantation outcomes. Wider implications of the findings The freeze-all strategy may not be suitable for universal application. When embryos can develop to the blastocyst stage, frozen embryo transfer is a favorable choice, but embryos can only develop to the cleavage stage, fresh embryo transfer becomes a more reasonable option. Trial registration number KMUHIRB-E(I)-20210222

P-685 An artificial intelligence based medication regimen recommendation model for optimizing the treatment outcomes of controlled ovarian stimulation

Abstract Study question Can a machine learning (ML) algorithm suggest an optimal controlled ovarian stimulation (COS) protocol for maximizing the number of retrieved and mature (MII) oocytes? Summary answer Based on historical electronic medical record patient data, using ML algorithm based medication regimen recommendation model may increase the number of retrieved oocytes. What is known already The application of artificial intelligence in the field of reproductive medicine is mainly focused on the image analysis of gamete and embryo, and prediction of treatment outcomes. The research on the optimization of COS process is limited. Previous studies mainly focused on one or several types of COS protocols such as GnRH-a protocol and GnRH-A protocol. And most of them aimed to assist single-node decision-making during COS process such as optimal gonadotropins starting dose and trigger day. Study design, size, duration The data used for developing this model consists of 38,355 COS cycles from women who underwent their first IVF/ICSI treatment in a large fertility center between January 2008 to December 2022, of which 33,853 were used as the model training set and 4,502 were used as the test set. This dataset contains a subset of 8,382 cycles with information about MII oocytes. Participants/materials, setting, methods The goal of model was to recommend the optimal COS protocol based on optimizing COS outcomes. The similarity of patient’s characteristic was used as model input. XGBoost algorithm was constructed to calculate the similarity of COS outcomes. The accuracy was compared with the patient similarity calculation method of KNN+Euclidean distance and KNN+cosine distance using mean absolute error (MAE). The performance of different models in improving the average number of retrieved and MII oocytes was compared. Main results and the role of chance The patient similarity calculation method based on XGBoost had lowest MAE when predicting the number of retrieved oocytes (XGBoost vs KNN+Euclidean distance+k=500 vs KNN+Euclidean distance+k=1000 vs KNN+cosine distance+k=500 vs KNN+cosine distance+k=1000: 3.729 vs 3.810 vs 3.815 vs 3.785 vs 3.788). Including AMH could improve the accuracy of all recommendation models in predicting protocols and the number of retrieved oocytes. When the optimal number of MII oocytes is used as the protocol recommended target, the patient similarity calculation method based on XGBoost had lowest MAE (XGBoost vs KNN+Euclidean distance+k=500 vs KNN+Euclidean distance+k=1000 vs KNN+cosine distance+k=500 vs KNN+cosine distance+k=1000: 2.868 vs 3.397 vs 3.452 vs 3.356 vs 3.395). The COS medication regimen recommended by the patient similarity calculation method based on COS treatment outcomes has resulted in higher numbers of retrieved oocytes in patients compared to those who did not adopt recommendation (P < 0.01). The medication regimen recommended model based on KNN+Euclidean distance algorithm (k = 500) has the best performance in improving the average number of retrieved oocytes（adopt recommendation vs not adopt recommendation: 13.01±6.61 vs 10.09±6.67, P < 0.01）There was no statistical difference in the number of MII oocytes between patients receiving the recommendation and those not adopt recommendation. Limitations, reasons for caution The medication regimen recommendation model is based solely on the predicted number of retrieved and MII oocytes, not including adverse treatment outcomes such as ovarian hyperstimulation syndrome. Moreover, the database used to train and validate the model is from a single fertility center. Wider implications of the findings The recommendation model is helpful to improve the number of retrieved oocytes. Based on the recommended COS protocol, further mining the medication content, medication time distribution and medication sequence transformation from the similar patient set can assist clinicians to develop individualized COS medication regimen for infertile patients. Trial registration number not applicable

P-618 Impact of ovarian stimulation on outcome of oocyte in-vitro maturation (IVM) in women with polycystic ovaries: corifollitropin alfa (CFA) versus follitropin beta (FSH-B)

Abstract Study question Do corifollitropin alfa and follitropin beta have different effects on oocyte yield and live birth rates after IVM in women with polycystic ovaries? Summary answer In patients who underwent IVM, one injection of CFA resulted in lower oocyte retrieval rates, but similar birth rates compared to three injections of FSH-B. What is known already IVM involves the maturation of cumulus oocyte complexes (COCs) from antral follicles and has been offered to women with polycystic ovaries as an alternative for conventional ovarian stimulation (OS). Exogenous FSH is typically administered for two to five days in IVM cycles to enhance meiotic and developmental competence of immature oocytes in vivo. Previous studies have shown that the number of COCs is associated with ongoing pregnancy after IVM. Because one injection of CFA yields more oocytes compared to daily FSH-B injections in conventional OS protocols, CFA has the potential to combine patient-friendliness and maximised COC yield in IVM cycles. Study design, size, duration We conducted a randomised controlled superiority trial from 12/2017 to 12/2023. The primary endpoint was the number of COCs at collection. We randomised 145 patients to either one CFA 100μg injection or three daily injections of FSH-B 150IU. Laboratory and safety parameters, and pregnancy outcomes after frozen embryo transfer (FET) were analysed on an intention-to-treat basis. All cycles were scheduled using oral contraceptive pretreatment. Participants/materials, setting, methods Eligible patients were <37 years, had ≥24 antral follicles, and BMI 18-30 kg/m2. We analysed serum estradiol, progesterone, LH, and FSH on stimulation day 1 and 3, at oocyte retrieval (OR), and at OR + 6d. Oocyte retrieval (OR) was performed five days after the start of OS. No ovulation trigger was given. Monophasic IVM for 30h, ICSI and elective freeze-all were done in a tertiary fertility clinic. Data were analysed using STATA 13.0. Main results and the role of chance After randomisation, 70 patients underwent OR after FSH-B and 72 had OR after CFA. Hormone levels at OR were significantly different between FSH-B-treated (FSH 6.8 ± 2.8IU/L, LH 3.3 ± 2.7IU/L, E2 106.7 ± 147.0ng/L, Prog 0.19 ± 0.16μg/L) and CFA-treated patients (FSH 24.3 ± 7.9IU/L, LH 1.8 ± 1.6IU/L, E2 575.6 ± 516.2ng/L, Prog 0.29 ± 0.21 μg/L, p ≤ 0.001). On average, 43.1 ± 21.7(FSH-B) vs. 50.8 ± 29.2(CFA) follicles, all <10mm, were punctured during OR (p = 0.06). More COCs per follicle were retrieved after FSH-B (68.3 ± 31.5% vs. 51.0 ± 24.7%, p = 0.001), resulting in a tendency towards more COCs after FSH-B (31.4 ± 23.3), compared to CFA (23.4 ± 11.7, p = 0.07). Maturation rates after IVM were similar (49 ± 19% vs. 50 ± 15%, p = 0.79). In spite of a tendency towards more mature oocytes after FSH-B (16.0 ± 14.6 vs. 11.7 ± 7.9, p = 0.09), the number of good-quality cryopreserved embryos was similar (3.9 ± 2.9(FSH-B) vs. 3.5 ± 2.7(CFA), p = 0.36). Live birth rate (LBR) after the first FET (25.7%(FSH-B) vs. 34.7%(CFA), p = 0.24) and cumulative LBR six months after OR (40.0%(FSH-B) vs. 45.8%(CFA), p = 0.48) were comparable. None of the patients developed ovarian hyperstimulation syndrome (OHSS). Limitations, reasons for caution Outcomes are only applicable for patients with high antral follicle count (AFC) who are treated using a monophasic IVM culture system. The sample size was too small to draw significant conclusions for live birth rate. Wider implications of the findings In subfertile patients with high AFC who have IVM treatment, follicle priming with one injection of CFA is safe, convenient, and as efficacious as priming with FSH-B. The observation of lower oocyte retrieval rates after CFA compared to FSH-B in the specific setting of an IVM cycle merits further scrutiny. Trial registration number EudraCT 2017-002571-25

P-197 Current status and hotspots of in vitro oocyte maturation: a bibliometric study of the past two decades

Abstract Study question What is the current research status and hotspot of in vitro maturation? And how could we improve the efficiency of IVM technique? Summary answer Five hotspots in IVM field were found, including culturing system, supplementation, cooperation in the ovarian follicle, gene expression, and cryopreservation of oocytes. What is known already In vitro maturation (IVM) of oocytes is a promising technique among assisted reproductive technologies. Because ovarian stimulation is minimal or absent in an IVM cycle, IVM technique reduces the risk of ovarian hyperstimulation syndrome (OHSS) and captures the reproductive potential of immature oocytes. However, the developmental competence of IVM oocytes is generally lower than the oocytes matured in vivo. A recent study showed the cumulative live birth rate in IVM is still inferior to standard IVF. The protocol for IVM still needs to be improved in some details. Study design, size, duration The articles and reviews related to IVM in the Web of Science Core Collection (WoSCC) were retrieved on January 16th, 2023. Three bibliometric tools including VOSviewer 1.6.18, CiteSpace 6.1.R6, and Bibliometrix R package 4.1.0 were used to generate network maps and explore frontier knowledge and trends. Participants/materials, setting, methods The data was retrieved and downloaded from WoSCC using the search formula: TS = (“in vitro maturation” OR “IVM”) AND TS = (follic* OR oocyte*) NOT TS=“ivermectin”. The timespan was set from 2003 to 2022. The language was limited to English, and publication types to article or review. VOSviewer detected indicators, including country, institution, journal, and author. CiteSpace analyzed reference co-citation and identified emerging keywords. Bibliometrix explored trending topics in IVM field. Main results and the role of chance A total of 5133 publications about IVM were retrieved from WoSCC, including 4706 articles and 427 reviews. The number of publications in IVM has increased steadily. China and University of Adelaide were the most prolific country and institution in IVM. Theriogenology was the most published and cited journal. Thompson, Jeremy G was the most productive author in the field of IVM, and Eppig, JJ’s papers were cited most. Furthermore, five hotspots were summarized and introduced, including culturing system, supplementation, cooperation in the ovarian follicle, gene expression, and cryopreservation of oocytes. This study comprehensively and visually analyzed the hotspots and frontiers of IVM in the past two decades. In our conclusion, further study could concentrate on: (1) the mechanism of oocytes matured in vivo and in vitro, especially in energy metabolism and intercellular communications; (2) establishment of IVM culture system, including standardized biphasic IVM culturing system and standardized supplementation; (3) the genetic differences between oocytes matured in vivo and in vitro; (4) the mechanism of cryopreservation-inflicted damage and the solution. Limitations, reasons for caution Due to the limitations of the software, the data we used for bibliometric analysis was only retrieved from WoSCC. Also, while bibliometric analysis can help us understand a field visually, it cannot completely replace system retrieval. Wider implications of the findings In this review, we explored and analyzed the field of IVM from 2003 to 2022 comprehensively and visually. Possible trends and hotspots in future were predicted, which may pave the way for future study directions and developments. Trial registration number not applicable

P-715 outcomes of in vitro fertilization and embryo transfer among ethnic Tibetan, Yi and Han Chinese women

Abstract Study question Does difference exist in the outcomes of in vitro fertilization and embryo transfer (IVF-ET) among ethnic Tibetan, Yi and Han Chinese women? Summary answer We report that the outcomes of IVF-ET were poorer among ethnic Yi women compared with ethnic Han and Tibetan women. What is known already It has been reported that the outcomes of IVF-ET are correlated with ethnicity/race in Europe and the United States as an independent factor. Sichuan is the only province in China where all 56 ethnic groups reside, with ethnic Han, Yi and Tibetan Chinese having the highest proportions. In Chengdu city (the capital of Sichuan province, basin), the majority ethnic group is Han, whilst in Liangshan and Aba Prefectures (plateau), the major ethnic groups are Yis and Tibetans. The living environment, diet, custom, medical condition and genetic backgrounds are different among different ethnic groups. Study design, size, duration In this multi-center retrospective cohort study, a total of 58374 Chines women aged 20 ∼ 45 had undergoing the first IVF or intracytoplasmic sperm injection (ICSI) ET treatment cycle with non-donor gametes from January 2014 to December 2022 were enrolled. Participants/materials, setting, methods The patients were enrolled from two University Affiliated Hospitals and one Reproductive Hospital in Chengdu. The controlled ovarian stimulation protocols were gonadotropin releasing hormone (GnRH) agonist protocol or GnRH antagonist protocol. The patients were divided into three groups based on their ethnic origins: Tibetans (n = 1069), Yis (n = 2273) and Hans (n = 55032). The outcomes of IVF-ET were compared, with the primary outcome being the live birth rate. Main results and the role of chance The proportion of GnRH agonist protocol and IVF fertilization, the rates of moderate and severe ovarian hyper-stimulation syndrome (OHSS), and cleavage embryo formation in ethnic Han women were significantly higher than in the ethnic Yis and Tibetans (P < 0.05). The rates of implantation, clinical pregnancy and live birth (35.5% vs. 42.4%) were significantly lower, whereas the late abortion rate was significantly higher in Yi women than that in Han women (P < 0.05). The live birth rate was significantly lower in Yi women (35.5%) than in Tibetan (43.3%) and Han women (42.2%) (P < 0.05). Adjustment was made for age, duration, type and etiology of infertility, history of spontaneous abortion, smoking, alcohol, tuberculosis infection, body mass index, antral follicle count, antimüllerian hormone, and so on, by multivariate logistic regression analysis. Yi women had significantly lower rates of moderate and severe OHSS (OR = 0.69, 95% CI = 0.49-0.94, P = 0.024) and clinical pregnancy (OR 0.8, 95% CI 0.70-0.93, P = 0.002) compared with ethnic Hans. Yi women had significantly lower live birth rate compared with ethnic Hans (OR = 0.79, 95% CI = 0.68-0.92, P = 0.002) and Tibetans (OR 0.73, 95% CI 0.58-0.92, P = 0.007). Limitations, reasons for caution The limitations are related with the retrospective study and lack of some demographic characteristics of the patients which may influence the outcomes of IVF-ET, including diet habits, educational level, and economic status. Wider implications of the findings The ethnic group is an independent factor for the outcomes of IVF-ET among ethnic Tibetan, Yi and Han women. Among the three ethnic groups, the Yis had lower live birth rate and moderate and severe OHSS, whilst ethnic Han women had more moderate and severe OHSS. Trial registration number ChiCTR2300070269

O-123 Trends and challenges in the practice of ART in China

Abstract China is a large country with a population of over 1.4 billion. In 1988, the first in-vitro fertilization-embryo transfer (IVF-ET) baby was born in Peking University Third Hospital. In the following 3 decades, assisted reproductive technology (ART) has developed rapidly in China, and the availability and accessibility of the ART service have improved markedly. In 2004 totally, only 37 institutions had passed the administrative licensing procedure to carry out ART. While in 2020, 536 institutions obtained the ART license. Since 2016, the total number of ART service cycles(Artificial insemination included)has exceeded 1 million, and the number of babies born has exceeded 300,000, accounting for about 2% of the total live births in China in 2016. At present, assisted reproductive technology has become one of the important medical interventions for the treatment of infertility in China, which has brought good news to infertile couples and their families, and has made great contributions to social harmony and family happiness. Cycles per million population (C/M) in 2009 was 120. In 2020, it has increased to 668, with more and more infertile couples having access to this technique in China. The success rate of assisted reproductive technology remained stable. In 2020, the clinical pregnancy rates (CPR)of conventional IVF and ICSI fresh embryo transfer cycles reached 52.4% and 49.4%, respectively, and the live birth rates were 43.0% and 40.6%, respectively. The clinical pregnancy rate and live birth rate of frozen-thawed embryo cycle were 51.3% and 40.5% per transfer. With the widespread application of embryo freezing technology, the cumulative live birth rate was estimated to reach 49.5% (CLBR estimate) in 2020. The safety monitoring indicators of assisted reproductive technology showed that since 2015, the multiple pregnancy rates of conventional IVF, ICSI and FET have decreased year by year, and have dropped to 22.4%, 21.4% and 17.6% in 2020, respectively. The incidence of moderate-severe ovarian hyper-stimulation syndrome (OHSS) and severe bleeding were also under control, within a reasonable range. Assisted reproductive technology, which involves many medical, social, ethical and legal issues, is a special clinical technology with limit application for medical indication. The Chinese government attaches great importance to the quality and safety management of assisted reproductive technology. A series of management documents such as the Administrative Measures for Human Assisted Reproductive Technology, the Regulations for Human Assisted Reproductive Technology and so forth, have been issued since 2001. Further improvement of key performance indicators (KPIs) correlated with ART quality and safety control is of the top priority and also challenging. In addition, the ART surveillance data in China is still aggregated data, which does not include important indicators such as age stratification, infertile factors or indications and delivery gestational age, maternal and infant outcomes, with some limitations for surveillance. Continuous improvement of data quality, and initiation of cycle-based data collection and security measures of case information are also challenging for the next step.

O-074 Dual trigger is not superior to GnRH Agonist alone for final oocyte maturation in elective fertility preservation. A Randomized Controlled Trial

Abstract Study question Is Dual trigger for final oocyte maturation associated with a higher number of mature (MII) oocytes compared to GnRH-a trigger alone in elective fertility preservation? Summary answer Adding hCG to GnRH-a for triggering final oocyte maturation does not increase the number of MII oocytes in elective fertility preservation cycles. What is known already Triggering final oocyte maturation represents a key step in ovarian stimulation. In good prognosis patients undergoing oocyte cryopreservation, the current standard approach involves the administration of a single bolus of GnRH-agonist 36 hours before the pick-up. Previous studies have shown a higher number of MII oocytes when Dual Trigger (hCG+ GnRH-a) is performed, compared to recombinant human chorionic gonadotropin (rhCG) alone. Nevertheless, a notable gap exists in the literature, as no studies have investigated the potential additional benefit in final oocyte maturation when dual trigger is compared to GnRH-a alone. Study design, size, duration This is a randomized controlled superiority trial including elective oocyte cryopreservation cycles performed in a University Hospital. A total of 109 women were enrolled in this study between October 2021 to April 2023 with a 1:1 allocation. Eligible patients were ≤40 years old, with an antral follicular count (AFC)<20 and anti-Mullerian hormone (AMH)≤3ng/ml. Patients were randomized to final oocyte maturation triggering with Triptorelin 0,2mg or a dual trigger (Triptorelin 0.2 mg + 250 ug rhCG). Participants/materials, setting, methods Controlled ovarian stimulation was performed using 225-300IU/day of rFSH alfa or beta, or equivalent rFSH delta (15-20μg), tailored to ovarian reserve and BMI. LH surge was suppressed through a progestin-primed ovarian stimulation (PPOS) protocol, with oral administration of micronized progesterone (200mg daily) from the beginning of ovarian stimulation until the trigger day. The primary outcome was the number of MII oocytes. Comparisons are presented as estimated mean difference (EMD) and corresponding 90% confidence interval (CI). Main results and the role of chance Overall, 104 patients were analyzed, 51 in the Dual trigger group and 53 in the control arm (GnRH-a). We found no statistically significant differences in the number of retrieved oocytes comparing Dual Trigger group (8.71 ± 4.90) and GnRH-a group (9.51 ± 5.19). Similarly, the number of MII oocytes demonstrated no significant differences, with 6.86 ± 4.40 in the Dual Trigger group compared to 7.87±4.40 in the GnRH-a group (EMD -1.01 [90%CI: -2.44;0.43]). Exploring the hormonal profile there were no notable variations in estradiol levels (2064.60 ± 890.50 pg/ml vs. 2494.41 ± 1341.05 pg/ml), progesterone levels (7.78 ± 3.88 ng/ml vs. 8.94 ± 5.10 ng/ml), LH (56.28 ± 26.83 IU/L vs. 63.41 ± 32.50 IU/L), and FSH (31.14 ± 7.86 IU/L vs. 31.53 ± 9.89 IU/L) on the day following the trigger. Notably, neither group exhibited any case of Ovarian Hyperstimulation Syndrome (OHSS). Limitations, reasons for caution The sample size was calculated to detect differences on the number of MII oocytes. Therefore, results for secondary outcomes (number of oocytes retrieved and hormonal profile) should be interpreted with caution. Wider implications of the findings Adding hCG to GnRH-a for triggering final oocyte maturation does not confer any additional benefits in elective fertility preservation in term of MII oocytes compared to the administration of GnRH-a alone. Trial registration number NCT04992468

P-650 Cumulative live birth rate after use of capacitation in vitro maturation in women with predicted excessive response to ovarian stimulation: an analysis of 1,563 cycles

Abstract Study question What is the cumulative live birth rate in biphasic (capacitation) in vitro maturation (CAPA-IVM) cycles in women with predicted excessive response? Summary answer The cumulative live birth rate achieved after CAPA-IVM in women with predicted excessive response was 37.8%. What is known already In vitro maturation (IVM) is an alternative infertility treatment for women at high risk of complications during conventional in vitro fertilisation with ovarian stimulation. There is debate about the merits of a newer biphasic approach (capacitation [CAPA]-IVM) versus standard IVM. At centres where it is used, CAPA-IVM has increased the maturation rate, and therefore the number of embryos available for transfer. However, there is a lack of data from large numbers of CAPA-IVM cycles, especially cumulative outcomes. Study design, size, duration This analysis included data from 1,563 individuals who underwent CAPA-IVM at a tertiary IVF center in Ho Chi Minh City, Vietnam from January 2016 to December 2023. Participants/materials, setting, methods All CAPA-IVM cycles in women with predicted excessive response (polycystic ovary syndrome or high antral follicle count) were included. Mean age was 29.6±3.5 years. Median duration of infertility was 3.3±2.5 years. CAPA-IVM was the first assisted reproductive technology in 90.5% of participants. Cumulative live birth rate was defined as the number of live births after using all embryos generated from a CAPA-IVM cycle. Main results and the role of chance Cumulative rates of clinical pregnancy, ongoing pregnancy and live birth were 54.9%, 44.4% and 37.8%, respectively. The median proportion of mature oocytes per cumulus-oocyte complex was 61.3% (IQR 50.0–73.3) and the median proportion of fertilized oocytes per cumulus-oocyte complex was 72.2% (IQR 55.6-85.7). The median total number of day-3 embryos per patient was 4.0 [IQR 3.0–7.0] and the total number of good day-3 embryos per patient was 3.0 [IQR 2.0–5.0]. The proportion of patients with no embryo was 5.2%. The number of frozen embryo transfer cycles was 1 (53.6% of patients), 2 (24.9%), 3 (7.0%), 4 (0.8%) or 5 (0.3%); 7.9% of patients had not undergone transfer of day-3 embryos at the time of analysis. Median [IQR] number of embryos and good embryos transferred was 2.0 [2.0–4.0] and 2.0 [1.0–2.0], respectively. No case of ovarian hyperstimulation syndrome recorded. Limitations, reasons for caution The characteristics of the study population (relatively young, lean women from Vietnam with predicted excessive response to ovarian stimulation) limit the external generalisability of the findings. Wider implications of the findings The cumulative live birth rate from all CAPA-IVM cycles performed in women with predicted excessive response at our centre was comparable to that of IVF. CAPA-IVM could be an alternative for this selected group of patients to avoid ovarian hyperstimulation. Trial registration number not applicable

P-631 Extended letrozole regimen versus routine letrozole regimen in women with polycystic ovary syndrome undergoing their first ovulation induction cycle

Abstract Study question Whether an extended letrozole regimen could result in a higher ovulatory rate than a routine regimen in PCOS women undergoing their first ovulation induction cycle. Summary answer PCOS women using the extended letrozole regimen failed to obtain a statistically higher rate of ovulation in comparison with the routine letrozole regimen. What is known already Letrozole has become the first-line agent for ovulation induction, however, nonresponsive cycles occurred in 10-58.8% of PCOS women during their ovulation induction therapy with letrozole alone. The extended letrozole regimen has been demonstrated to be a feasible method for inducing ovulation in those nonresponders. However, whether it could be applied to all the PCOS women as a first choice in the induction of ovulation remains to be explored. Study design, size, duration This is a prospective randomized controlled trial including 148 women with PCOS undergoing their first ovulation induction cycle with letrozole from January 2021 to October 2022. Participants/materials, setting, methods Participants were randomly assigned to receive an extended letrozole regimen (5 mg letrozole daily for 7 days) or a routine regimen(5 mg letrozole daily for 5 days) for one treatment cycle. Ovulation rate was the primary outcome. Secondary outcomes included the clinical pregnancy rate, the number of preovulatory follicles, the rate of multiple pregnancies. Main results and the role of chance The ovulation rate among women receiving a 7-day regimen was slightly higher than the rate with a 5-day regimen, but it did not reach a statistical significance in both the intention-to-treat analysis (90.54%[67/74]vs. 82.43%[59/74], P = 0.065) and per-protocol analysis (90.54%[67/74]vs. 84.29%[59/70], P = 0.257). The number of preovulatory follicles was nearly identical in the two groups (1.39±0.62 vs.1.37±0.59, P = 0.956), and no cases of ovarian hyperstimulation syndrome were observed. In the per-protocol analysis, the rates of clinical pregnancy (20.27%[15/74]vs.16.95%[10/70], P = 0.343) and live birth (13.51%[10/74]vs.11.43%[8/70], P = 0.976) did not differ significantly between treatment groups. Moreover, all the conceptions were singletons without neonatal defects. Limitations, reasons for caution The major concern of the current research is its single-centre and open label nature. Additionally, the limited number of lean PCOS women with a mean body mass index of 23-25 kg/m2 enrolled in our trial also restrict the generalizability of our findings. Wider implications of the findings Letrozole 5-day regimen remains to be the first choice for PCOS women undergoing ovulation induction therapy. Additional prospective trials with a larger sample size and different subgroups of PCOS are needed to assess the ovulatory effects of different letrozole treatment duration. Trial registration number ChiCTR2100042082

P-678 Cabergoline has inhibitory effects on FSH-induced cell differentiation and estrogen secretion in a primary culture system of rat ovarian granulosa cells

Abstract Study question How does cabergoline have effects on cell differentiation and hormone secretion induced by FSH stimulation in ovarian granulosa cells? Summary answer Cabergoline suppresses LH receptor expression and Estradiol (E2) secretion in primary cultures of rat ovarian granulosa cells by inhibiting cAMP production induced by FSH stimulation. What is known already Cabergoline is a dopamine receptor 2 agonist that has been used to treat hyperprolactinemia and, more recently, to prevent ovarian hyperstimulation syndrome. Although it has been previously reported that cabergoline suppresses E2 and Progesterone secretion induced by FSH stimulation in a primary culture system of rat ovarian granulosa cells, but the effect on LH receptor expression has not been investigated. It has also been reported that the activation of dopamine receptor 2 suppresses VEGF secretion and reduces the incidence of early-onset OHSS by inhibiting the VEGF/VEGFR2 pathway in research using human luteinized granulosa cells. Study design, size, duration We used a primary culture system of ovarian granulosa cells obtained from immature female rats treated with diethylstilbestrol to examine the effect of cabergoline addition on the changes in ovarian granulosa cells induced by FSH stimulation. Participants/materials, setting, methods FSH and cabergoline were added alone or co-added to a primary culture system of rat ovarian granulosa cells, and the changes induced by them were measured and compared. (1) mRNA expression of Lhcgr, Cyp19a1, and Fshr by RT-qPCR (2) E2 concentration in the culture medium (3) Measurement of hCG binding on the cell surface (4) cAMP concentration Main results and the role of chance Co-addition of cabergoline suppressed each of the changes induced by FSH stimulation as follows. (1) The mRNA expression levels of Lhcgr, Cyp19a1, and Fshr decreased in a concentration-dependent manner (0.01-10 µM) of co-added cabergoline compared to FSH alone. In the 10 µM of co-added cabergoline group, they decreased to 14%, 9%, and 49% of FSH alone, respectively. (2) E2 concentration in the culture media also decreased in a concentration-dependent manner (1-10 µM) of co-added cabergoline compared to FSH alone. In the 10 µM of co-added cabergoline group, it decreased to 49% of FSH alone. (3) The amount of hCG binding on the cell surface also decreased in a concentration-dependent manner (0.1-10 µM) of co-added cabergoline compared to FSH alone. In the 10 µM of co-added cabergoline group, it decreased to 7% of FSH alone. (4) FSH-stimulated cAMP production decreased in a concentration-dependent manner (0.01-1µM) of co-added cabergoline compared to FSH alone. In the 1µM of co-added cabergoline group, it decreased to 50% of FSH alone. These results suggest that cabergoline suppresses LH receptor and aromatase expression and E2 production by inhibiting cAMP production induced by FSH stimulation. Limitations, reasons for caution Since this is an in vitro experiment using a rat primary culture system, the results of this research cannot be considered directly applicable to humans. Wider implications of the findings Our findings imply that cabergoline administration during the follicular phase may inhibit ovarian granulosa cell differentiation and estrogen secretion. In women taking relatively high doses of cabergoline, attention may need to be paid regarding the effects of cabergoline on follicular development and estrogen secretion. Trial registration number not applicable

O-320 Does applying an ‘elective freeze-all’ policy work in practice? A matched cohort study of over 9,000 embryo transfers

Abstract Study question Does application of a Freeze All Embryo (FAE) policy achieve superior live birth rates in practice compared to fresh IVF transfer cycles? Summary answer FAE FETs achieved significantly higher LBRs than fresh for both the first ET per cycle and cumulatively per cycle. What is known already The efficacy of vitrification methods has led to segmentation between the ovarian stimulation and embryo transfer cycle becoming increasingly applied. Randomised controlled trials have shown that for high responders, especially those at risk of ovarian hyperstimulation syndrome, the FAE approach is likely to be favourable. However, whether a routine freeze all approach applied in routine clinical practice improves outcomes in a broader group of patients remains unclear. Study design, size, duration This is a retrospective analysis of 7,647 autologous fresh oocyte retrievals and 9,609 subsequent ETs, performed between 2016-2022. The primary study aim was to compare (cumulative) live birth rates between fresh and frozen thawed embryo transfers after FAE IVF cycles. The groups consisted of 3,707 fresh IVF transfers plus 1,533 subsequent FETs derived from those cycles, versus 3940 FAE cycles with 3969 subsequent FETs. Participants/materials, setting, methods 5,808 patients underwent fresh oocyte retrievals (2016-2022) at a single UK-based centre. In total, 4,997 of these patients underwent 9,609 ETs; either fresh or frozen. For analysis, FAE cycles and fresh IVF cycles underwent 1:1 full propensity score matching for age and number of eggs collected, using probit regression of treatments on covariates. Logistic regression analyses were fit including full matching weights in the estimation to compare LBR superiority between groups. Main results and the role of chance Patients undergoing fresh transfers were significantly older and yielded significantly fewer oocytes per retrieval (37 and 36, P < 0.001; 7 ± SE 0.07 and 12 ± SE 0.1, P < 0.001, respectively). After full 1:1 matching for age and oocytes collected, the means for both groups were 36 and 15, respectively. Standardised mean differences after matching was <0.2. The first FET from FAE cycles achieved significantly superior LBRs and was a significant predictor of LB compared to fresh ETs when adjusted for covariates (37% and 26%, respectively, aOR 1.3; 95% CI 1.2-1.5, P < 0.001). Cumulative LBs achieved per cycle were also significantly higher for FAE cycles (56% and 37%, respectively). When stratifying by age, first ET LBRs between groups were comparable for <35s (FAE 42%, fresh 40%). However, with increasing age, FAE first FETs achieved higher live births than fresh transfers (35-37, 36% and 33%; 38-39, 34% and 23%; 40-42, 27% and 14%; 43-45, 15% and 5%, respectively). Limitations, reasons for caution This is a retrospective analysis and, although cohorts underwent full 1:1 matching, inherent bias may be present within the data and must be considered when drawing conclusions. Wider implications of the findings These findings suggest that in clinical practice, FETs after a FAE cycle may achieve superior LBRs compared to fresh ETs, particularly in older patients and for higher responders. Overall, FAE cycles were observed to result in higher cumulative LBRs per cycle than cycles that begin with a fresh transfer. Trial registration number Not applicable

P-129 Transferring blastocysts derived from frozen-thawed cleavage embryos versus frozen-thawed blastocysts: A comparative analysis of pregnancy outcomes

Abstract Study question Is there an enhancement in pregnancy outcomes when cleavage-stage embryos are thawed, cultured for transfer as blastocysts, as opposed to transferring thawed blastocysts? Summary answer The strategy of culturing frozen-thawed cleavage embryos for 2 days and transferring them as blastocysts is not inferior to the transfer of frozen-thawed blastocysts. What is known already Embryo cryopreservation in IVF has many advantages, allowing couples to postpone pregnancy for personal reasons and reducing the risk of ovarian hyperstimulation syndrome. In the past, the common practice involved freezing and transferring cleavage embryos. However, a current trend favors single-embryo transfers at the blastocyst stage, promoting potential self-selection during extended culture. Several studies have raised concerns about potential damage during blastocyst vitrification, prompting investigation into whether cryopreserving cleavage-stage embryos for subsequent culturing to blastocysts yields superior outcomes compared to direct transfer of thawed blastocysts. Study design, size, duration This observational study was conducted at Hung Vuong Hospital from January 2022 to December 2023. We included 509 patients who underwent IVF followed by FET cycles. The D3-5 group (n = 167) comprised embryos that were frozen and thawed at the cleavage stage, subsequently extended two more days of culturing to the blastocyst stage for transfer. The D5 group (n = 342) involved frozen and thawed blastocysts. We excluded donor cycles, surrogacy, and cycles with preimplantation genetics testing. Participants/materials, setting, methods We used vitrification method for embryo cryopreservation. The freezing and thawing process were performed using either Kitazato or Cryotec medium kit, following manufacture’s instruction. Regarding the D3-5 group, thawed cleavage embryos were cultured for two more days until blastulation and transfer. Regarding the D5 group, blastocysts transfer was performed at least 2 hours after warming. The embryo transfer procedure was performed under abdominal ultrasonographical guidance. Pregnancy results were recorded and compared between two groups. Main results and the role of chance Regarding the D3-5 group, a noteworthy proportion of 65.3% cycles were unfortunately cancelled. The primary reason for cycle cancellations was the absence of developed blastocysts for transfer (85.3%). The remaining 14.7% of cancellations were attributed to other reasons. Fertilization rates were comparable between the two groups, with 80.8% in the D3-5 group and 81.5% in the D5 group (p = 0.464). However, the blastulation rate in the D3-5 group (40.1%) was lower than in the D5 group (46.4%), (p = 0.016). Patients in the D5 group demonstrated slightly better pregnancy outcomes compared to the D3-5 group: implantation rate (59.9% versus 51.7%, p = 0.302), clinical pregnancy rate (52.3% versus 44.8%, p = 0.36), ongoing pregnancy rate (37.7% versus 34.5%, p = 0746), live birth rate (33.9% versus 31%, p = 0.78), and miscarriage rate (26.3% versus 20.7%, p = 0.46). However, these differences were not statistical significance. Limitations, reasons for caution This is an observational study, we observed that thawing the cleavage-stage embryos then subsequently culture to the blastocyst stage may lead to the lower blastulation rate or even absence of developed blastocysts for transfer. This approach also increases the workload for embryologists. Wider implications of the findings Culturing frozen-thawed cleavage embryos for 2 days and transferring them as blastocysts increases workload for embryologists and poses a risk of cycle cancellation. We propose that the use of frozen-thawed blastocysts may be a more efficient and patient-friendly option. Trial registration number not applicable