Ovarian Response Research Articles

P-564 Decoding ovarian response: the predictive power of FSH receptor gene expression in controlled ovarian stimulation

Abstract Study question Can profiling of variation in follicle-stimulating hormone receptor (FSHR) gene expression forecast response to Controlled Ovarian Stimulation (COS) in Assisted Reproductive Techniques? Summary answer Full-length FSHR transcript was the most common mRNA species. Nine distinct transcripts were characterised, but only one (deletion Exon 6) was associated with altered response. What is known already AMH levels and age are considered useful predictors of ovarian response to COS (high AMH and young age typically associated with high yields of oocytes; older ages and low AMH associated with fewer oocytes). However, it is not uncommon to see patients who do not fit this pattern, highlighting the limitations of these parameters in predicting response. Age-independent biomarkers capable of revealing patients at elevated risk of hyperstimulation, or those who might produce fewer than the optimal number of oocytes, are desirable. Alternative transcripts of the FSHR gene have been proposed as an explanation for variation in response to COS. Study design, size, duration FSHR splice variants in mRNA in granulosa cells from 126 patients were examined utilising long-read nanopore sequencing. This strategy permitted the sequencing of mRNA variants without fragmentation, allowing the detection of all splicing events in each mRNA strand. In addition to being categorised based on age and AMH levels, patients were also classified by the expression of FSHR transcript variants and their response to stimulation (high, low, or normal response). Participants/materials, setting, methods Patterns of FSHR mRNA splice variants were analysed in each of 126 patients. This involved extraction of RNA from the granulosa cells, followed by long-read nanopore sequencing, permitting analysis of whole transcripts in a single, contiguous sequence ‘read’. Patients were classified based upon their level of response to COS (low, normal, high), taking into account their age, AMH level and the number of oocytes retrieved. Patterns of FSHR transcript variation were compared to COS response. Main results and the role of chance Full-length FSHR transcript was detected in 97.6% of patients and skipping of Exon 6 was observed in 68%. Five novel transcripts were discovered, including partial insertion of ∼100bp segments of introns 1 or 2, seen in 6.55% of samples. In total, nine distinct FSHR mRNA variants were detected. As expected, increasing age was associated with higher FSH requirement per oocyte collected (p = 0.018), and AMH levels declined with age (2.8± 1.42 in women <38 versus 1.58 ±1.29 in women ≥38; p = 0.011). Consistent with previous analyses, AMH levels and amount of FSH per oocyte retrieved were negatively correlated (p < 0.001). One-third of the patients (33%) in this cohort displayed responses to COS that were not considered to be consistent with expectations based upon age and AMH levels. Expression of the novel FSHR transcript variants was not associated with FSH needed per oocyte retrieved (p = 0.78), nor the proportion of mature oocytes (p = 0.95).The only transcript potentially linked to an altered response to COS was the previously reported mRNA species, lacking exon 6, associated with significantly greater numbers of oocytes produced (p = 0.0087). Interestingly, women ≥38 expressed novel variants more frequently than their younger counterparts (p = 0.018), potentially indicative of an age-related decline in transcriptional fidelity. Limitations, reasons for caution It is possible that the use of controlled ovarian stimulation might alter the dynamics of transcription in cumulus cells. Therefore, it is possible that the spectrum of transcripts seen in this study might differ from those present in unstimulated cycles. Wider implications of the findings Expected associations between age, AMH levels and response to COS were observed. Skipping exon 6 may be associated with a superior response to COS, suggesting FSHR mRNA profiling might have a role in tailoring controlled ovarian stimulation protocols. Novel transcript variants were detected and seen most often in older women. Trial registration number not applicable

O-303 What is the ideal dose of daily FSH after corifollitropin-alfa? A multicentre-randomized control trial

Abstract Study question Does the mean serum trigger-progesterone levels show significant variation based on the administered rFSH dose from day 8 onwards during ovarian stimulation using corifollitropin-alfa? Summary answer Lower rFSH doses from day 8 of ovarian stimulation onwards are linked to reduced serum progesterone (P4) levels without impact on cumulus-oocyte complexes. What is known already Progesterone elevation during ovulation trigger prompts a non-elective freeze-all strategy, given the lower live birth rates in fresh embryo transfers. Ongoing research explores methods to mitigate late follicular phase P4 rise to allow a fresh embryo transfer. Granulosa cells’ progesterone production is an FSH-driven and dose-dependent process, and FSH dose is furthermore pivotal for a good ovarian response. Balancing FSH dose is crucial for both optimal ovarian response and preventing undesirable P4 elevation while maintaining an adequate number of retrieved oocytes and allowing a fresh embryo transfer. Study design, size, duration This study is an interim-analysis of a randomized-controlled multi-center clinical-trial comparing three ovarian-stimulation-protocols: (A) corifollitropin alfa (CFA) followed by rFSH 50 IU/day; (B) CFA followed by rFSH 150 IU/day; (C) CFA followed by rFSH 250 IU/day.The primary outcome is the serum-progesterone-level on the day of hCG among the study groups, secondary outcomes included number of oocytes, clinical pregnancy rates and freeze-all cycles. 167 women (of 261) were randomized between July 2019-November 2023, with a 1:1allocation. Participants/materials, setting, methods Young (<40 years old), normo-ovulatory cycle (25-35 days), with AFC>7 and <20, and a BMI<29 Kg/m2 patients were recruited in the fertility clinic of three different tertiary university hospitals. On day 8 of ovarian stimulation (OS) following CFA administration, patients who needed additional rFSH were randomized into 3 groups (A-B-C). The OS was performed in a GnRH-antagonist protocol and the ovulation triggered with hCG. A fresh embryo-transfer was performed on day 5 following oocyte retrieval. Main results and the role of chance Overall, 167 patients were randomized, 60 in group A, 55 in group B and 52 in group C. The mean age and BMI were comparable between the groups. Mean AMH was respectively 2.2, 2.1 and 2.2 ng/mL, for group A, B and C (p = 0.95). Group A resulted in a significantly lower P4 level at trigger as compared with group B and C (respectively, 0.4ng/mL, 0.9 ng/mL and 1.4 ng/mL; p < 0.001). The mean number of retrieved oocytes was 10.7, 11 and 12.1 for group A, B and C, respectively (p = 0.47), while the mean number of mature oocytes was 7.3, 6.9 and 7.8 for group A, B and C, respectively (p = 0.7). A freeze-all approach was decided for 27%, 29% and 46% for group A, B and C respectively (p = 0.057). No significant differences were found for fresh-embryo-transfer outcomes (chemical pregnancy rates: 33%, 31% and 29%, respectively for A, B and C (p = 0.12).Of interest, comparisons between serum FSH at trigger showed a mean of 12.5, 17 and 20.5 IU/L for group A, B and C, respectively (p < 0.001) while the serum estradiol levels on day of trigger were comparable among the groups (1659, 2092 and 2098 ng/L for group A, B and C, respectively (p = 0.091). Limitations, reasons for caution This is an interim analysis planned to detect the mean difference in COC between groups. Therefore, the mean differences of the primary outcome should be interpreted as exploratory findings which warrant future investigation. Wider implications of the findings Administering a lower rFSH dose from day 8 onward during ovarian stimulation results in comparable numbers of COC but also leads to significantly lower serum P4 levels. Consequently, this finding has the potential to reduce the overall consumption of rFSH, thereby possibly increasing the likelihood of a fresh embryo transfer. Trial registration number NCT03686852

P-669 Not the oocyte yield but the number of embryos predicts live birth at high response: analysis of 39,136 fresh IVF/ ICSI cycles from National Database

Abstract Study question Oocyte or embryo yield- which is a better predictor of live birth (LB) in fresh cycle IVF/ ICSI? Summary answer The embryo yield is better than oocyte in predicting fresh-cycle LB and positively correlates with LB at high ovarian response when the oocytes yield doesn’t. What is known already As the LB rates plateau after a certain oocyte yield, the number of oocytes collected no longer can predict the live birth in IVF/ ICSI cycles with fresh embryo transfer.Since pregnancy outcomes also depend on the number of mature oocytes obtained, fertilisation rate and subsequent embryo development, it can be postulated that the number of total or transferrable embryos could be a better predictor of LB. Study design, size, duration Retrospective analysis of 39,136 fresh IVF/ ICSI cycles that met the inclusion criteria from the national database published by Human Fertilisation and Embryology Authority (HFEA) in the United Kingdom. We analysed 2 years of published data between January 2015 and December 2016. Participants/materials, setting, methods Only the first cycles of IVF/ ISCI that had oocyte retrieval procedure with intended fresh embryo transfer were included. Couples with any cause of infertility and female partners aged up to 44 years were included. Very few cycles with >25 oocytes had fresh transfer, therefore excluded. The ovarian response has been graded by 0-5, 6-10, 11-15, 16-20, 21-25 collected oocytes. Significant confounders found in univariate analysis were adjusted for in the multiple regression model. Main results and the role of chance Women’s age, method of insemination (IVF or ICSI) and number of transferred embryos and stage of transfer significantly associated with LB in univariate analysis (p < 0.0001 each). The oocyte yield predicted fresh-cycle LB only in low response group (0-5 oocytes), but not in higher response groups. Total number of embryos, the number of transferable embryos and embryo utilisation rate remained positively correlated with LB in all response groups. The number of transferable embryos found to be the best predictor of LB with the highest adjusted OR 1.51 (CI:1.4-1.65, p < 0.0001) in the lowest response (0-5 oocyte) group, that gradually declined to 1.06 (CI:1.03-1.10, p = 0.0003) in 21-25 oocytes group. Followed next by the total number of embryos with the highest adjusted OR of 1.20 (CI:1.13-1.27, p < 0.0001) in the lowest response (0-5 oocytes) group, down to 1.04 (CI:1.02-1.06, p = 0.0003) in the 21-25 oocytes group. The number of oocytes was the weakest in predicting LB (adjusted OR 1.07 (CI 1.02-1.12; p = 0.003) in the 0-5 oocytes group only. The inference remained the same when ICSI cycles with supposedly sperm factor was excluded. Limitations, reasons for caution Information on patient’s BMI or stimulation dose is not available in the HFEA database. However, it might have little impact in our findings, given large sample size. Ages are given in groups, so the groups taken as ordinal (dummy) variables in multiple regression analysis. Cumulative LB data were not available. Wider implications of the findings Having been influenced by both oocyte and sperm competency, the number of transferable embryos may have a stronger relation with the pregnancy outcomes than merely the oocyte number. On theory, this may be applicable for cumulative LB too, but awaiting confirmation by data evidence. Trial registration number Not applicable

P-684 Anti-müllerian hormone predictive value for cumulative pregnancy rate in non-infertile women following four intrauterine insemination with donor sperm

Abstract Study question Are anti-Müllerian hormone (AMH) levels predictive of cumulative pregnancy rate in non-infertile women undergoing intrauterine insemination with donor sperm (ds-IUI)? Summary answer AMH has limited predictive value for clinical pregnancy after 4 cycles of ds-IUI in non-infertile women. Decreased AMH concentration does not necessarily reduce pregnancy rates. What is known already Physiologically, pregnancy rates decline due to oocyte quality deterioration upon advancing maternal age. AMH is a widely-used marker of ovarian reserve and follicular response but not an infertility test, despite being sometimes referred to as such. This misconception can lead to unnecessary complex ART treatments only based on low AMH. Indeed, the predictive value of AMH for natural conception and IUI remains uncertain and highly controversial in the literature. Study design, size, duration This multicenter prospective observational study evaluated the correlation between AMH levels and pregnancy rates in 182 non-infertile women undergoing ds-IUI. Participants were recruited from June 2020 to December 2022 from three centers: Hospital del Mar in Barcelona (Spain), Fertty Clinic in Barcelona (Spain) and Clinica de la Mujer in Viña del Mar (Chile). Participants/materials, setting, methods The study included women aged 25-39 years, normal BMI, regular periods, and without ovarian pathology or endometriosis, who were undergoing ds-IUI for severe oligoasthenoteratozoospermia, female partner, or single status. Baseline AMH and antral follicle count (AFC) by TVUS was registered. Reproductive outcomes were compared between women with AMH >1.1 and AMH ≤1.1 ng/mL. The main outcome was the cumulative clinical pregnancy rate after up to 4 ds-IUIs in a 3-year frame. Main results and the role of chance Kaplan Meier’s analysis did not show cumulative pregnancy rate superiority in women with AMH >1.1 ng/mL vs < 1.1 ng/mL (log rank Mentel Cox 1,502; p-value 0.46; ROC curve analysis predictor for clinical pregnancy, AUC=0.586). AMH and AFC were found to be significantly correlated (Pearson’s coefficient r = 0.632, p-value <0.001). Additionally, women who achieved pregnancy were found to be significantly younger (p-value <0.05) versus women who did not. However, no differences in AMH levels were found between them (p-value 0.33). Limitations, reasons for caution Limitations of the study include interpretation of results in extreme concentrations of AMH, potential impact of polycystic ovary syndrome (PCOS) in women with high AMH values, lower representation of patients with low AMH levels, and variability in ovulation induction regimens prior to ds-IUI (exposure to different rFSH dosages). Wider implications of the findings AMH is not a reliable predictor for pregnancy in ds-IUI. Even women with extremely low AMH levels can achieve successful outcomes, which are associated with age. The results of this multicenter study support that low AMH should not be used as an exclusion criterion for non-infertile women seeking ds-IUI. Trial registration number IRB Protocol ID 2020/9445

P-592 Comparison of the cumulative live birth rate of different doses of rFSH in poor ovarian reserve women undergoing GnRH antagonist ART treatment: a Randomized Controlled Trail

Abstract Study question Does an increased FSH dosage result in higher cumulative live birth rates in advanced age women with poor ovarian reserve treated with IVF or ICSI? Summary answer In poor ovarian reserve women, FSH dose of 300 IU/day does not improve cumulative live birth rates as compared to 150 IU/day. What is known already Natural fecundity and pregnancy rate following ART decrease dramatically in women aged 35 years and above. An open-label multicenter RCT described no difference in the cumulative live birth rate between the increased FSH dose (225/450 IU/day) and standard dose (150 IU/day) in women with a predicted poor ovarian response. Nevertheless, it is still unclear whether advanced age women with poor ovarian reserve who are undergoing IVF/ICSI benefit from a higher gonadotrophin dose. Therefore, we aimed to assess whether rFSH 300 IU/day compared to 150 IU/day in advanced age women with poor ovarian reserve resulted in higher cumulative live birth rates. Study design, size, duration A single center prospective randomized controlled trail that included first in vitro fertilization cycle with a GnRH-ant protocol and subsequent fresh and frozen-thawed cycles from April 2019 to December 2022. The study group included 104 women that received rFSH 150 IU/day and 99 women received rFSH 300 IU/day in antagonist protocol. Participants/materials, setting, methods Women for their first stimulation cycle, aged 35 to 42 years with antral follicle count（AFC）≤ 5 or anti-mullerian hormone （AMH） ≤ 1.2 ng/ml were randomized. Study group and control group respectively received 300 IU and 150 IU rFSH from menstrual cycle day 2 or 3 till the day of trigger. The primary outcome was cumulative live birth rate per woman per stimulation over a 2-year period to account for the first live birth. Main results and the role of chance This study included 203 women with the GnRH antagonist protocol. Of them, 99 patients were in 300 IU/day rFSH group, and 104 patients were in 150 IU/day rFSH group, respectively. The two groups were comparable for all baseline characteristics. The cumulative live birth rate for increased rFSH dosing (300 IU) versus standard dosing (150 IU) was 13.13% (13/99) versus 25% (26/104) per stimulation cycle. (P = 0.049). There were no differences in cumulative pregnancy rates 27.27% (27/99) vs 35.58% (37/104) per stimulation cycle. (P = 0.262). The cumulative live birth rate and cumulative pregnancy rates per transfer cycle in 300 IU/day rFSH group vs 150 IU/day rFSH group presented no statistical difference. No significant difference was found in secondary outcomes including time to live birth, number of MII oocytes, number of transferable embryos, implantation rate, multiple pregnancy rate, ectopic pregnancy rate and miscarriage rate between the two groups. Limitations, reasons for caution As this study is open-label, potential selective cancelling of cycles in women could have influenced the cumulative results. Also, this study practiced in a single-center and specific patient population, the results may not be generalizable to a broader population. Wider implications of the findings In women 35 years or older with poor ovarian reserve, improving rFSH dosage to 300IU in GnRH-ant protocol did not improve cumulative live birth rate. rFSH 150IU/day may be recommended at the start of COS to achieve live birth outcomes while decrease costs. Trial registration number ’not applicable

P-630 Assessing Bologna and POSEIDON criteria as predictors of PGT-A in Poor Ovarian Response: A comparative analysis

Abstract Study question Do Bologna or POSEIDON criteria more accurately predict PGT-A outcomes in poor ovarian response, considering aneuploidy rates and clinical outcomes? Summary answer Comparing Bologna and POSEIDON criteria highlights higher aneuploidy rates in Bologna patients, with no significant differences in mosaicism rate or clinical outcomes in either group. What is known already Ovarian reserve stands out as the primary factor influencing reproductive senescence. Approximately 9-24% of individuals undergoing ovarian stimulation are categorized as ‘low-responders’. Key indicators of Poor Ovarian Response (POR) include age, antral follicle count (AFC), Anti-Müllerian Hormone (AMH), and response to controlled ovarian stimulation. While some studies link ovarian reserve to embryo quality, others dispute any correlation with embryo abnormalities. The Bologna criteria classify patients meeting at least two of the following: advanced maternal age, low AFC, and AMH. The more precise POSEIDON criteria combine these factors, forming four distinct groups for classification. Study design, size, duration We conducted a retrospective case-control study, examining PGT-A results of 2740 embryos derived from 797 IVF cycles conducted in our clinic between 2021 and 2022. Trophoectoderm biopsies, taken at D + 5/6, underwent Next-Generation Sequencing. Embryos were vitrified and transferred after analysis. Regarding the interpretation of the results, embryos with ≤25% cells aneuploids were considered euploid, between 25% and 50% were classified as mosaic and those with >50% cells were considered aneuploid. Participants/materials, setting, methods All patients used their own oocytes. Bologna and POSEIDON criteria were used for the classification of POR and non-POR patients. Univariate analysis was performed using Pearson’s chi-square statistical test for categorical variables and binary logistic regression to compare the rates of aneuploidy and embryonic mosaicism, pregnancy rate miscarriage, ongoing pregnancy rate and implantation rate with the above variables taking into account possible confounding factors. Main results and the role of chance Patient ages ranged from 22 to 47 years, with a mean of 38.9 years. In Bologna groups, mean ages were 41.15 years for Bologna and 38.43 years for the control. For POSEIDON: 32.47 group I, 39.85y group II, 32.11y group III, 40.41y group IV and 38.24y control group of the classified by POSEIDON criteria. The mean AFC was 10.95 and the AMH value was 13.15pmol/L. Among 797 cycles, 59.16% (449/797) met POR criteria by POSEIDON, distributed across groups: 1.19% (9/797) in group I, 1.32% (10/797) in group II, 22.66% (172/797) in group III and 33.99% (258/797) in group IV. Using Bologna criteria, 17.74% (486/797) were classified as POR. Our findings reveal that individuals identified with POR by Bologna criteria exhibit a significantly elevated incidence of embryo aneuploidy (78.8% POR patients vs. 59.9% control patients; p = 0.004). However, no such distinction was observed when employing the POSEIDON criteria for classification. In terms of embryo mosaicism, no notable differences were detected between POR and non-POR patients under both Bologna and POSEIDON criteria. Furthermore, no significant variations in clinical data were observed between the two groups, even after correcting for maternal age. Limitations, reasons for caution The study is constrained by the inherent limitations of a retrospective design and a restricted sample size. Moreover, the complexity and heterogeneity involved in classifying patients with POR contribute to additional challenges in the interpretation of results. Wider implications of the findings The study indicates that diminished ovarian reserve does not significantly augment the probability of embryo aneuploidies. Particularly noteworthy is the observation that young women with low ovarian reserve do not exhibit an increased susceptibility to aneuploidies. This finding holds implications for understanding reproductive outcomes among ovarian reserve variations. Trial registration number No aplicable

P-702 New era in donor programs. Is it time to leave behind the antagonist for a progestin-primed ovarian stimulation protocol? Retrospective cohort analysis of 711 cycles

Abstract Study question Are GnRH-antagonist and progestin-primed ovarian (PPOS) stimulation protocols comparable in terms of effectiveness and efficiency in an egg donor program? Summary answer The PPOS protocol would have similar efficacy to the antagonist protocol, despite a slightly lower rate of useful blastocyst, without impact on recipient’s clinical results. What is known already There are numerous studies based on the comparison of oral progestin (P) vs. subcutaneous GnRH-antagonist (A) as pituitary suppressors during ovarian stimulation with gonadotropins, showing similar results in terms of ovarian response and reproductive outcomes in IVF cycles. Limited data are available on the comparison of both protocols in egg donor programs to evaluate their effectiveness and efficiency. Study design, size, duration Retrospective and observational cohort study with 711 oocyte donor cycles included over 18 months (July 2022-Dec 2023). As pituitary suppressors during ovarian stimulation, Ganirelix was used in 394 cycles and Medroxyprogesterone in 317. We obtained 626 reception cycles (369 from A group and 257 from P group). 499 egg-recipients underwent an embryo transfer (309 form A group and 190 from P group). Live birth rates were calculated only over the 192 informative embryo transfer cycles. Participants/materials, setting, methods Variables such as duration of the ovarian stimulation, number of mature oocytes (MII), maturation rate, fertilization rate, useful blastocysts (uBL) rate and their quality (>3BB/≤3BB), clinical pregnancy and live birth rate, have been evaluated. An economic analysis has been conducted for both protocols. Statistical analysis was performed using T-Student and Chi-Square tests. Main results and the role of chance There were no significant differences between groups A and P in terms of: average stimulation days (11.44±1.45 vs. 11.39±1.38, p = 0.62), average number of MII (15.69±7.46 vs. 15.12±7.12, p = 0.30), maturation rate (78.97% vs. 80.01%, p = 0.13), and fertilization rate (68.6% vs. 70.1%, p = 0.15). However, a statistically significant difference was observed in the rate of viable blastocyst formation (uBL/2PN) between groups A and P (70.4% vs. 66.8%, p < 0.05), although there were no differences in embryo qualities obtained (>3BB: 89.4% vs. 90.6%, ≤3BB: 10.6% vs. 9.1%, p = 0.083). Regarding obstetric outcomes, no differences have been found in live birth rates between the two groups (52,4% vs 64,5%, p = 0,11). The cost of the antagonist protocol was significantly higher being 8.48% more expensive than the oral progestin protocol (p < 0.05). Limitations, reasons for caution A regulated randomization has not been used to assign donors to both treatments. The population size, although enough to provide significant differences, could be wider. The number of cycles performed with P are smaller compared to A. Most clinical pregnancy are still ongoing so these data are lacking Wider implications of the findings Besides being more donor-friendly, the progestin-primed ovarian stimulation offers a significant economic advantage. Both protocols have proven similar efficacy. Clinical data are necessary to evaluate the impact of the lower BLu rate on the reproductive outcomes. Trial registration number Not applicable

O-300 Dydrogesterone versus GnRH-antagonists to supress the LH surge in IVF/ICSI cycles

Abstract Study question Does Dydrogesterone block premature Luteinaizing hormone surge and ovulation during the controlled ovarian stimulation without compromising of IVF/ICSI outcomes? Summary answer Dydrogesterone and GnRH-antagonist have equal effectivness for prevention of premature luteinizing hormone surge and ovulation without any adverse effect on laboratory and clinical results. What is known already Premature LH surge and premature ovulation during the controlled ovarian stimulation is one of the main causes of cycle cancellation.Traditionally, during in-vitro fertilization for controlled ovarian stimulation to prevention of premature LH surge clinicians use GnRH antagonists. Recent data indicates that premature LH surge may be prevented also by progestins, since they have a role in suppression of preovulatory LH surge. In past, progesterone was not used during ovarian stimulation due to the negative effect on endometrial receptivity, while nowadays advanced techniques give possibility to use it as an alternative to a GnRH antagonists using the freeze-all strategy. Study design, size, duration In this prospective, randomized study were participated sixty -seven egg donors. Sudy was conducted on the basis of Clinic Leadermed (Georgia, Tbilisi) from October of 2021 to November 2023. The Ethics Committee of clinic Leadermed approved this study and appropriate informed consent was obtained from all participants. Participants/materials, setting, methods Recombinant gonadotropin was administered for control ovulation stimulation in oocyte donors. According to the ovarian response HMG was added. Intervention group (group I, n = 34) received 20 mg of Dydrogesterone from the first day of stimulation till trigger day and the control group (group II, n = 33) received GnRH-antagonist when the leading follicle reached 14 mm in diameter till trigger day. Triptorelin acetate 0.3 mg was administered when at least 3 follicles reached ≥18 mm in diameter. Main results and the role of chance There were no statistically significant differences in the oocyte donors age, BMI and AMH levels between two groups. None of the participants experienced a premature LH surge and ovulation. There was no statistically significant difference in the number of MII oocytes (23,7 vs 25.9 p = 0.3). The duration of stimulation and total dose of gonadotropins was similar in both groups (9.6 vs 9.9 days, p = 0.41), (2269.2 IU vs 2423.4 IU, p = 0.08) respectively. There was no difference in fertilization rates (85.62% vs 83.94%, p = 0.41), as well as blastulation rates and top-quality blastocysts (65.78% vs 69.72%, p = 0.17; 54.50% vs 51.75%, p = 0.21). Regarding clinical pregnancy rate, the results were similar, with no significant differences between two groups (66.28% vs 68.10%, p = 0.8). Limitations, reasons for caution The limitation of the study is that embryotransfer was performed as in patients (age till 49years), as well as in surrogate mothetrs (age till 41 years). Wider implications of the findings Dydrogesterone and GnRH-antagonist has equal effectiveness for prevention of premature LH surge without affecting of IVF outcomes. It is a financially profitable and easy to use which can be used as in oocyte donors as well as in patients where embryo transfer is not planned in the current cycle. Trial registration number non-clinical trial

P-608 Cumulative live birth rates after 3 consecutive embryo transfers in freeze-all cycles following gonadotropin-releasing hormone antagonist protocol versus progesterone-primed ovarian stimulation

Abstract Study question Do cumulative live birth rates in freeze-all cycles differ between gonadotropin-releasing hormone (GnRH) antagonist protocol and progesterone-primed ovarian stimulation (PPOS)? Summary answer GnRH antagonist and PPOS protocols have similar cumulative live birth rates in freeze-all cycles. What is known already GnRH antagonists and progesterone have been used for pituitary suppression in ovarian stimulation cycles. While PPOS protocol has the advantage of oral usage and lower cost, data regarding the laboratory and clinical outcome is limited and confounding. Freeze-all cycles might provide a better model to assess the impact of PPOS protocol and GnRH antagonist protocol on laboratory, clinical outcomes and cumulative live birth rates. Study design, size, duration A retrospective cohort study on IVF cycles performed (n = 568) between January 2020 and May 2022.The entire cohort of embryos were cryopreserved at the blastocyst stage.Inclusion criteria were 18-42 years of age,ICSI for severe male factor infertility.Exclusion criteria were PGD and severe endometriosis.Indications for cryopreservation in the antagonist group were high ovarian response (n:102),endometrial polyps (n:34),high follicular phase P4(n:48) and elective purposes(n:260).PPOS was used due to a transient shortage of GnRH antagonist in the market (n:124). Participants/materials, setting, methods 568 women (GnRH antagonist:444; PPOS:124) were included in the analysis.The primary outcome was the cumulative live birth rate (CLBR) after 3 consecutive embryo transfer cycle, and the secondary outcome parameters were the number of M-II oocytes, fertilization rate and blastocyst utilization rate. Student’s t-test was used for normally distributed continuous data and Fisher’s exact tests for categorical data were used. A generalized estimating equation model and logistic regression analysis were performed to adjust for confounding factors. Main results and the role of chance The mean age of the GnRH antagonist group was 34.1 ± 5.3 and 34.5 ± 5.7 years in PPOS group (p = 0.38). The baseline characteristics including BMI, serum AMH levels, duration of infertility, duration of stimulation and gonadotropin ampules used were similar in both groups. Estradiol and progesterone levels at the time of ovulation trigger were higher in GnRH antagonist cycles (2383.5 ± 1375.4 vs 2034.5 ± 1218.3, p = 0.02 and 0.7 ± 0.6 vs 0.5 ± 0.4, p = 0.01, respectively) The mean number of cumulus-oophorus complexes (12.9 ± 7.4 vs 11.5± 10.0, p = 0.61), M-II oocytes (10.0± 6.1 vs 9.1± 6.1, p = 0.14), frozen blastocysts (4.8± 3.5 vs 4.7± 3.6, p = 0.71) were similar between GnRH antagonist and PPOS groups, respectively. Fertilization rates (84.4% vs 87.2%, p = 0.12) and blastocyst utilization rates (63.4% vs 65.9%, p = 0.34) were also similar between GnRH antagonist and PPOS groups, respectively. The number of transferred embryos and the number of unused blastocysts were similar between groups. The CLBRs after one IVF cycle and 3 consecutive frozen-thawed blastocyst transfers were comparable in GnRH antagonist and PPOS cycles (56.8% and 53.2%, p = 0.37, respectively). Limitations, reasons for caution This was a retrospective study with relatively small sample size performed at a single fertility center, which may limit the generalizability of our findings. Wider implications of the findings If the fresh embryo transfer is not intended, PPOS protocol can be used in all patient types with cost-effective and patient-friendly manner. Trial registration number 2024.013.IRB2.012

P-750 Is maximalization of the ovum pick-up (OPU) procedure beneficial for the outcome of assisted reproductive technology (ART) cycles?

Abstract Study question Is aspiration of more oocytes than the antral follicle count (AFC) beneficial for the current (pregnancy/live birth rates) and future products of an ART cycle? Summary answer Aspirating more oocytes than the AFC does not influence the outcome of the fresh cycle but is beneficial for fertility preservation and cumulative pregnancy rates. What is known already AFC is a reliable and immediate indicator for ovarian reserve assessment and is in correlation with the ovarian response to gonadotropin stimulation. Additionally, correlation between AFC and embryo quality, clinical pregnancy and live birth rates was reported. There is no data concerning the impact of the ratio between the AFC and actual number of oocytes retrieved on cycle outcome. Study design, size, duration Data of the first oocyte aspiration for ICSI performed between 2018-2022 in attempt to conceive (ICSI, n = 399) or for planned oocyte vitrification (fertility preservation FP, n = 283) was retrieved. Each group was divided into two subgroups according to their ‘oocyte/AFC index’ (OAFCI): <1 and ≥1. The stimulation parameters, number of aspirated oocytes, their maturity rate, number of cryopreserved oocytes/embryos, clinical pregnancy (CPR) and live birth rates (LBR) were compared between the subgroups. Participants/materials, setting, methods The AFC was determined by professional sonographers using a 9 MHz transvaginal ultrasound probe. The most adjacent measurement to the stimulation initiation was used. Stimulation protocol and FSH dose were determined according to the AFC and individual clinical consideration. Patients not in their first cycle, natural cycle aspirations, and cases in which no oocytes were retrieved, were excluded. Main results and the role of chance OAFC≥1 was associated with higher pre-trigger estradiol (6159 pmol/L vs. 4304, p < 0.001 for ICSI, 4949 vs. 3488, p < 0.001 for FP), and longer duration of simulation (9.8 days vs. 9, p < 0.001 for both FP and ICSI). More oocytes were aspirated in OAFC≥1 groups in both FP (16.9±11.2 vs. 7.9±5.9, p < 0.001) and ICSI (17.4±9.8 vs. 10.7±6.7, p < 0.001). Oocyte maturity was unaffected by the OAFCI in the ICSI group, but was lower in FP group at OAFC≥1 (0.79 vs.0.84 p = 0.005). OAFCI≥1 was associated with a higher number of cryopreserved embryos (3.9 vs. 2.3, p < 0.001 for ICSI) and a higher number of vitrified oocytes (13.4 vs. 6.4 p < 0.001 for FP). The OAFCI had no impact on CPR (39% vs. 60%, p = 0.27) and LBR (19.9% vs. 24.8%, p = 0.33). On multivariate analysis controlling for age, gonadotropin dosage and duration of stimulation, OAFC≥1 was associated with a higher number of cryopreserved embryos (ICSI group aOR 1.2, 95% CI 1.1-1.3, p < 0.001), and vitrified oocytes (aOR 1.2, 95% CI 1.1-1.2, p < 0.001) and lower maturity index (aOR 0.1, 95% CI 0.03-0.51, p < 0.001) in the FP group. Limitations, reasons for caution Retrospective study analyzing results of treatment cycles without an intention to aspirate differently. Wider implications of the findings Aspiration of a more oocytes than the current AFC was not associated with higher CPR or LBR in the fresh cycle, but harbors the possibility to cryopreserve more oocytes and embryos. This might translate into higher cumulative pregnancy rates later on. Trial registration number Not applicable

P-687 High anti-müllerian hormone is associated with lower live birth rate in IVF/ICSI cycle with fresh transfer but not cumulative live birth rate in PCOS women

Abstract Study question Can serum AMH levels affect pregnancy outcomes particularly live birth rate (LBR) and cumulative live birth rate (CLBR) in PCOS women receiving IVF/ICSI treatment? Summary answer Higher serum AMH indicated a decreased LBR and increased miscarriage rate in PCOS women undergoing IVF/ICSI cycle. However, AMH has no association with CLBR. What is known already AMH could reduce follicle sensitivity to FSH and acts as an inhibitor of primordial follicle recruitment, which is essential for follicle growth. Therefore, AMH has widely been suggested to reflect ovarian reserve and predict ovarian response to assisted reproductive technology (ART). Women with PCOS presented AMH level around 2 to 4-fold higher than normal female. The pathological mechanisms of PCOS are complex. Ovarian follicular arrest is regarded as an important pathophysiology of PCOS, which is a consequence of insufficient FSH secretion or inhibition FSH action. Consequently, increased AMH arise might be associated with severity and poor pregnancy outcomes of PCOS. Study design, size, duration This was a retrospective cohort study included 4719 PCOS patients undergoing IVF/ICSI treatment at the Reproductive Center of Peking University Third Hospital from February 2017 to January 2022. Participants/materials, setting, methods Participants were divided into three groups according to the cutoffs defined by the 25th and 75th percentiles of serum baseline AMH level, low-AMH group, n = 1198 (AMH ≤ 4.98 ng/mL); average-AMH group, n = 2346 (4.98 < AMH < 10.65 ng/mL); high-AMH group, n = 1175 (AMH ≥ 10.65 ng/mL). Baseline parameters and pregnancy outcomes including clinical pregnancy rate (CPR), miscarriage rate, LBR and CLBR were compared among three groups. Main results and the role of chance In our cohort, we observed a significant progressively increase in the number of oocytes retrieved and the number of good-quality embryos per cycle from low- to average- to high-AMH group. No statistical significance was observed in fertilization rate (62% vs 60% vs 60%, P = 0.453). In addition, there was no significant difference in CPR among three groups (44.8% vs 42.8% vs 36.8%, P = 0.069). The miscarriage rate was progressively increased from low, average, and high AMH group (11.2% vs 18.5% vs 20.0%, P = 0.023). Importantly, LBR in fresh transfer was progressively decreased from low, average, and high-AMH group (39.6% vs 33.9% vs 29.0%, P = 0.004). However, no statistical difference but an increasing trend was observed in the CLBR among three groups (55.2% vs 56.9% vs 58.1%, P = 0.753). After adjusting by logistic regression analysis, the results indicated that elevated AMH was still strongly associated with decreased LBR in fresh transfer. In addition, BMI, endometrial thickness, and fertilization rate also have correlations with LBR. Nevertheless, the positive relationship between AMH and miscarriage rate remained only in low and average AMH group. Finally, no significant association was shown between AMH and CLBR in logistic regression analysis. Limitations, reasons for caution Firstly, this was a single-center study and might result in bias. Another limitation was due to its retrospective and non-randomized design. Besides, our study indicated an increasing trend in CLBR without statistical significance. Therefore, further large-scale, high-quality prospective cohort studies are still needed to confirm these findings. Wider implications of the findings These findings bring into consideration the potential role of AMH as the guidance in clinical regime. Since high AMH level might act as a biomarker in predicting worse pregnancy outcomes of PCOS women with IVF/ICSI fresh cycle. Trial registration number not applicable

P-573 Reframing reproductive odds: live birth rate in women with undetectable or negligible anti-mullerian hormone (AMH) levels

Abstract Study question what is the Live birth rate in women with undetectable or negligible AMH levels ? Summary answer Based on our findings, we suggest considering IVF for twith undetectable or negligible AMH levels. What is known already The reproductive outcomes of women with undetectable or negligible AMH levels have not been well studied. Nevertheless, it is widely believed that females with extremely low AMH levels may have difficulty conceiving and may experience early menopause. An undetectable AMH value is indicative of an ovarian reserve similar to that of a 44-year-old woman. It is important to note that fertility is not solely determined by AMH levels and that other variables, such as age, can also have an impact. Study design, size, duration This study was a retrospective cohort design. Data were collected from October 2009 to April 2022, and included 81 consecutive female participants aged 24 to 43 years with undetectable or negligible levels of AMH who had previously experienced a failed in vitro fertilization (IVF) cycle due to poor ovarian response. The participants were given DHEA after at least one failed IVF cycle, The primary outcome measure was live birth rate (LBR). Participants/materials, setting, methods The study participants were divided into two groups based on AMH levels. Group A had undetectable AMH equivalent to < 0.14 ng/ml (For SI units <1 pmol/L), and group B had negligible AMH levels between 0.14 ng/ml and 0.5 ng/ml (For SI units; 1 pmol/L to 3.6 pmol/L) as defined by Tocci et al. (2009). Both groups underwent IVF, and if the cycle failed, women received DHEA before next IVF cycle. The Primary outcome was LBR. Main results and the role of chance The study, which was conducted from October 2009 to April 2022, analysed a total of 81 cycles, with 41 in Group A and 40 in Group B. There were no significant differences in patient characteristics between the two groups. The overall spontaneous pregnancy rate was 17% (7/41) for women in Group A and 7.5% (3/40) for women in Group B, who received DHEA while waiting to start their next IVF cycle. All pregnancies resulted in live births. Additionally, one case in Group A converted from IVF to IUI and also resulted in a live birth. The overall LBR per woman and per embryo transfer (ET) were 53% (43/81) and 62.3% (43/69) respectively. The LBR per started cycle for Group A and Group B was 51.2% (21/41) and 55% (22/40) (p = 0.12), respectively. The LBR per ET for Groups A and B were 60% (21/35) and 64.7% (22/34) (p = 0.16), respectively. The rate of first trimester miscarriages was similar in both groups. The sub-analysis of patient age showed that the overall LBR for women under 37 years old was 44.4% (36/81) and 55.5% (45/81) for women aged 37 years old and above. The cycle cancellation rate was 14.81% (12/81). Limitations, reasons for caution The small sample size and the study’s retrospective design may introduce bias. Additionally, during the 12 years of the study period, AMH measurement techniques have changed. These limitations should be taken into account when interpreting the results. Further research is needed to establish the cost-effectiveness of these findings. Wider implications of the findings The presence of undetectable or negligible AMH levels should not automatically exclude the use of assisted reproductive technology. Supplementation with DHEA and a tailored ovarian stimulation protocol may improve reproductive outcomes in these cases and should be considered before resorting to oocyte donation. Trial registration number Not Applicable

P-358 Fertility preservation outcome in patients with onco-hematological malignancies versus solid tumor neoplasms

Abstract Study question Do women diagnosed with onco-hematological malignancies exhibit poorer response to ovarian stimulation in comparison to those with localized neoplasms? Summary answer There are no significant differences between women undergoing fertility preservation for onco-hematological malignancies compared to those with solid tumor malignancies. What is known already Oocyte cryopreservation is now considered the first choice for fertility preservation in post-pubertal women scheduled for gonadotoxic anticancer treatments. Patients with onco-hematological diseases, such as leukemia or lymphoma, encounter unique challenges due to their aggressiveness and multi-organ nature, potentially impacting ovarian function. Conversely, patients with solid malignancies may experience more favorable outcomes, as the impact on their reproductive function is likely less severe. However, comparative data on oocyte cryopreservation outcomes in both groups remain limited, hence further research is essential to guide personalized fertility preservation counselling. Study design, size, duration This is a single center case-control retrospective study that included data collected from 142 patients who underwent oocyte cryopreservation in our center between 2013 to 2023. Laboratory exams, ovarian stimulation and oocyte retrieval were all performed in our center. Participants/materials, setting, methods The main group of patients (or group 1) comprised 71 women with onco-hematological malignancies such as leukemia and lymphoma. Patients from group 1 were matched for age and study period in a 1:1 ratio with solid malignancies (group 2), such as breast cancer. Gynecological tumors were excluded. Significance was considered with a p < 0.05. Data are reported as median [interquartile range - IQR] or number (percentage). Main results and the role of chance In both groups, the mean age at oocyte cryopreservation was 30 years [25-34]. Only a minority of patients were undergoing estroprogestin therapy (10% in group 1 vs. 19% in group 2) (p=ns). Menstrual cycles were found to be regular in 88% and 90% of patients respectively (p=ns). Stimulation protocols were also comparable: 48% and 55% underwent GnRH antagonist, and the remaining underwent progestin-primed ovarian stimulation (p=ns). Duration of stimulation and total dose of gonadotropins did not differ between the two groups. Ovarian stimulation was interrupted due to inadequate response in two patients in the onco-hematological group and one in the control group (p=ns). At oocyte retrieval, the number of oocytes retrieved was 12 [7 - 18] and 15 [7-20] respectively (p=ns), and the number of cryopreserved oocytes was 10 [6-15] and 13 [7-15], respectively (p=ns). This result aligns with the antral follicle counts (AFC) detected before ovarian stimulation: 18 [12 - 24] vs. 20 [12 - 26], respectively (p=ns). However, a notable difference was found in anti-Mullerian hormone (AMH) levels, being 1.96 ng/mL [1.14 - 3.10] in onco-hematological patients and 3.11 ng/ml [1.52 - 4.52] in control patients (p = 0.01). Limitations, reasons for caution This is a retrospective, monocentric study with patients selected from a 10-year period. Wider implications of the findings When planning fertility preservation in women with systemic diseases like cancer, relying solely on AMH levels to estimate ovarian response to stimulation may be limited. In this scenario, AFC proves more reliable. Further evidence is needed to understand the clinical meaning of the lower AMH in onco-hematological cancer patients. Trial registration number NA

P-622 Prospectively randomized study of intraovarian injections of autologous platelet-rich plasma (PRP) into one alternating ovary in Primary Ovarian Insufficiency (POI)

Abstract Study question Does intraovarian injection of autologous PRP affect ovarian function in women with POI? Summary answer Ovaries that were injected with PRP demonstrated a significant increase in follicles >4mm in size compared to the untreated contralateral ovaries. What is known already The injection of PRP into ovaries has been reported to improve subsequent ovarian response to ovulation induction in women with POI and is now widely used in fertility centers in women with POI as well as in women with premature ovarian aging (POA). Prospectively randomized studies are, however, lacking. Study design, size, duration This is a Randomized Controlled Trial with recruitment from July 2018 - November 2023. 40 patients were screened; 34 qualified. POI was defined by amenorrhea among women < 40 years old, with FSH > 30 mIU/mL, undetectable AMH, and no follicles >4mm. For each participant one ovary was randomly selected for treatment ( with the Sealed Envelope Ltd 2022 tool). The study was powered to detect a 20% response in the treated versus untreated ovary. Participants/materials, setting, methods For each patient (n = 34), 10mL of blood was drawn into ReganLab vacutainer and centrifuged. Platelets were re-suspended in 1.5mL of plasma. PRP was injected into the stroma of one randomly selected ovary under iv sedation and ultrasound control. Patients were followed with ultrasounds, estradiol, and FSH q3-4 days for two weeks. Our primary outcome was the development of new follicles >4mm in the treated vs. untreated ovary, using Chi-Square. Main results and the role of chance Study population description: age 33.9±5.5 years (range 21-40.4 years); BMI 23.4±4.2; FSH 96.7±27.6 mIU/mL; AMH 0.019±0.03 ng/mL; length of amenorrhea 2.2 years (3 months-14 years). 10 patients developed no follicles > 4 mm, 21/34 (62%) did develop follicles > 4 mm in treated ovaries; 9/34 (26%) developed a follicle > 4 mm in untreated ovaries (Chi-square = 8.59; P = 0.003). Most follicles developed without significant estradiol production; nine showed sufficient follicle development to initiate ovulation induction with initiation of gonadotropins, four produced eggs and one produced an embryo; one patient had four oocytes banked and resumed menses following PRP treatment for several months. Limitations, reasons for caution N/A Wider implications of the findings This demonstrates the first objective evidence that intraovarian PRP injections into POI ovaries initiate some follicle activation. Though the observed degree of activation was small, findings suggest that remaining follicles in women with POI can be activated through injections into ovaries, suggesting that better agents than PRP may be discovered. Trial registration number N/A

P-619 AMH/AFC ratio as a predictive factor for ovarian responsiveness to gonadotropins during ovarian stimulation

Abstract Study question Does AMH/AFC ratio correlate to the number of follicles on the day of trigger and to the number of oocytes retrieved after ovarian stimulation? Summary answer The AMH/AFC ratio correlates significantly to the number of pre-ovulatory follicles and the number of oocytes collected after ovarian stimulation (OS). What is known already Although AFC is a robust marker of oocyte yield after OS, its combination with Anti-Mullerian hormone (AMH) seems to improve the predictability. Besides, Follicular Output Rate [FORT: (number of pre-ovulatory follicles on day of trigger/AFC at baseline) x 100] and Follicle-to-Oocyte Index [FOI: (number of retrieved oocytes/AFC) × 100] evaluate the ovarian responsiveness to gonadotropins during OS, representing its sensitivity to exogenous FSH. Both parameters take antral follicle count (AFC) only into consideration. AMH and AFC as a ratio might optimize the accuracy of FORT and FOI metrics, helping to predict which patients are at higher risk of suboptimal results. Study design, size, duration This retrospective study analyzed 2,163 ovarian stimulation cycles for IVF/ICSI, performed between May 2015 and October 2023 in a tertiary referral IVF centre. For all the cycles, measurement of AMH using Elecsys (Roche®) no longer than 6 months before starting OS, AFC at baseline, number of pre-ovulatory follicles on the day of trigger, and the treatment outcomes were available. Participants/materials, setting, methods Couples with primary/secondary infertility who underwent OS with antagonist protocol, starting on day 2/3 for IVF/ICSI were included, independent of their age or ovarian reserve parameters. Exclusion criteria were patients with body mass index (BMI) >40 kg/m2, non-vaginal ultrasound measurement for AFC and/or follicles during OS, cycles with previous estradiol priming or oral contraceptives. Ethical approval was obtained from the Research Ethics Committee. Main results and the role of chance 2,163 ovarian stimulation cycles were included in the analysis. The mean age, BMI, AMH, AFC, FOI and FORT of the included women were: 35.6±6.1 years, 27.5±4.7 kg/m2, 2.4±2.1 ng/mL, 12±7 follicles, 1.02±0.66 and 1.38±0.79. The correlation of AMH/AFC ratio (coefficient: 0.62, 95% CI: 0.59 to 0.65, p<0.001) to FOI was stronger than the correlation of AMH (coefficient: 0.31, 95% CI: 0.27 to 0.34, p<0.001) or AFC alone (coefficient: -0.09, 95% CI: -0.14 to -0.05, p<0.001). The correlation of AMH/AFC ratio (coefficient: 0.62, 95% CI: 0.59 to 0.64, p<0.001) to FORT was also stronger than the correlation of AMH (coefficient: 0.21, 95% CI: 0.16 to 0.25, p<0.001) or AFC alone (coefficient: -0.23, 95% CI: -0.27 to -0.19, p<0.001). AMH/AFC ratio was better at predicting stimulation efficiency parameters, FOI and FORT, compared to joint use of AMH and AFC (p>0.001 for both). However, regression analysis showed stand-alone use of the AMH/AFC ratio did not provide a better prediction for collected oocyte count compared to joint use of AMH and AFC. In fact, prediction errors were significantly larger for the AMH/AFC ratio (median: -0.4, range: -11 to 11) compared to the model using AMH and AFC separately (median: -0.2, range: -6 to 7). Limitations, reasons for caution Although clinical assessment was performed in the same centre following the same methodology, inter-observer variability for AFC is a limitation. Additionally, AMH levels used in the study were not obtained in the same cycles, which may adversely affect the performance of the ratio. Wider implications of the findings While AMH/AFC ratio was better at predicting stimulation efficiency compared to FOI and FORT parameters, it was not significantly better at predicting absolute oocyte yield. This may imply AMH/AFC ratio can represent the ovarian sensitivity to exogenous FSH. Trial registration number Not applicable

P-656 Comparative clinical outcome following individualized follitropin delta dosing in Japanese women undergoing progestin-primed ovarian stimulation for in vitro fertilization /intracytoplasmic sperm injection

Abstract Study question Is ovarian stimulation with follitropin delta (FD) in its individualized regimen as efficacious as follitropin alfa and human menopausal gonadotropin (FAHMG)? Summary answer Ovarian stimulation with individualized FD dosing resulted in a significantly higher fertilization rate and number of blastocysts with good quality compared to conventional FAHMG dosing. What is known already Previous randomized controlled trials conducted in Japan, China, Europe, and both North and South America have demonstrated that ovarian stimulation using the individualized FD dosing regimen, which is based on serum anti-Müllerian hormone (AMH) levels and body weight, effectively modulated the ovarian response without compromising pregnancy and live birth rates. Study design, size, duration A retrospective study was conducted by reviewing the medical records of 1,720 IVF/ICSI cycles in 1,272 Japanese patients. The primary endpoint of the study was the ongoing pregnancy rate, assessed at 8 weeks of gestation, in the frozen-thawed embryo transfer. Participants/materials, setting, methods The FD treatment consisted of a fixed daily dose individualized according to each patient’s initial AMH level and body weight (AMH <2.04 ng/ml: 12 μg; AMH ≥2.04 ng/ml: 0.19 to 0.10 μg/kg; min-max 6–12 μg). The FAHMG dose was determined by the antral follicle count (AFC), with the following protocol: for AFC <25, 300 IU/day; for 40> AFC ≥25, 225 IU/day; and for AFC ≥40: 150 IU/day). A progestin-primed ovarian stimulation (PPOS) protocol was applied. Main results and the role of chance Multiple regression analyses (MRA) showed that the use of FD was negatively correlated with the number of oocytes retrieved (NOR) (P = 0.001), and positively correlated with the fertilization rate (FR) (P = 0.02). NOR was comparable between FD and FAHMG (10.9 ± 6.4 versus 11.8 ± 7.8) when the Mann-Whitney test (MW) was applied (P = 0.111), but significantly higher in FAHMG when the patient is younger than 40 years old with AMH ≥2 ng/ml (P < 0.01). The total gonadotropin use was significantly (P < 0.001) reduced from an average of 167.1 ± 46.9 μg (2789.9 ± 782.9 IU) FAHMG to 102.6 ± 31.6 μg FD. FR was significantly higher in FD compared with FAHMG (78.7% versus 74.1%, P < 0.05) on MW. Additionally, MW indicated a significantly higher number of good-quality blastocysts in FD (2.9±2.6) versus with FAHMG (2.4±2.5) (P < 0.05). The blastocysts obtained from FD also showed a significantly higher implantation rate (50.1% versus 39.7%, P < 0.01) and a comparable ongoing pregnancy rate (28.7% versus 25.7%, P = 0.292) compared to those from FAHMG as determined by chi-square test. The higher implantation rate in FD may be attributed to the greater number of good-quality blastocysts obtained compared with FAHMG. Limitations, reasons for caution This study only covered the clinical outcome of women undergoing PPOS protocol with frozen-thawed blastocyst transfers. Wider implications of the findings The present study shows that FD in its individualized fixed-dose regimen has the potential to improve the success rate in frozen-thawed embryo transfer across all ages and with a lower gonadotropin consumption compared to conventional FAHMG dosing. Trial registration number not applicable

P-710 Comparison of cumulative delivery rates per aspiration cycle in patients fulfilling Bologna and POSEIDON criteria

Abstract Study question Do cumulative delivery rates (CDRs) per aspiration cycle differ in low-prognosis patients according to the Bologna and POSEIDON (Patient-Oriented-Strategies-Encompassing IndividualizeD-Oocyte-Number) classification criteria? Summary answer The CDR was 8.7% in Bologna and 22.7% in POSEIDON. The odds of achieving live-birth were ∼3-fold higher in POSEIDON than in the Bologna group. What is known already Bologna criteria were generated to address the heterogeneity in the definition of the Poor Ovarian Response (POR). However, patients meeting these criteria may not be homogeneous in terms of the number of oocytes retrieved and live birth rate. Subsequently, as a more inclusive classification, the POSEIDON criteria were proposed to stratify low-prognosis patients according to female age and suboptimal response to ovarian stimulation. To our knowledge, there is a paucity of data comparing CDRs between the POSEIDON and Bologna groups. Study design, size, duration Retrospective cohort study including 1250 patients undergoing their first ovarian egg retrieval cycle at Hacettepe University IVF Center in Ankara between 2017 and 2023. Exclusion criteria were female age >45 years old, body mass index >35 kg/m2, azoospermia, pre-implantation genetic testing (PGT) for structural rearrangement or monogenic disorders, fertility preservation cycles, dual-stimulation cycles, premature ovarian insufficiency, and hypogonadotropic hypogonadism. The primary outcome measured was CDR defined by ICMART (International Committee for Monitoring Assisted Reproductive Technologies). Participants/materials, setting, methods The Bologna patients have at least two of the following three features; female-age ≥40 or prior ovarian surgery, AMH<1.1ng/ml or antral-follicle-count (AFC)<5-7, and obtaining ≤3 oocytes in prior conventional stimulation. POSEIDON patients were categorized into four groups; younger(<35) and older(≥35) women with AMH≥1.2/AFC≥5 experiencing an unexpected poor(<4 oocytes-retrieved) or suboptimal(4–9 oocytes-retrieved) response, along with respective younger and older counterparts with AMH<1.1/AFC<5. Non-POSEIDON patients were those with AMH≥1.2/AFC≥5 and >9 oocytes-retrieved. General-Estimated-Equation(GEE) analysis was employed. Main results and the role of chance Out of 1250 patients, 79.6% were classified as POSEIDON, with sub-groups as follows: 5.28% Group 1a, 23.4% Group 1b, 3.6% Group 2a, 10.1% Group 2b, 14.64% Group 3, and 22.48% Group 4. The number of patients meeting Bologna criteria was 17.4% (218). For POSEIDON patients, median[IQR] values were: age 34 [30-38], AMH 1.33 [0.65-2.69], oocytes retrieved 4 [2-6], and embryo transfers 1 [1-2]. For non-POSEIDON patients: age 30 [27-33], AMH 4.63 [2.93-7.07], oocytes retrieved 13 [11-15], and embryo transfers 2 [1-3]. In Bologna patients: age 40 [36-42], AMH 0.46 [0.20-0.76], oocytes retrieved 2 [1-3], and embryo transfers 1 [0-1]. For non-Bologna patients: age 31 [28-36], AMH 2.30 [1.17-4.29], oocytes retrieved 6 [3-9], and embryo transfers 1 [1-2]. CDR for non-POSEIDON: 49.8%; Group 1a, 24.2%; Group 1b, 34.1%; Group 2a, 15.6%; Group 2b, 27.6%; Group 3, 20.8%; Group 4, 10.7%. In clustered-GEE analysis, using non-POSEIDON as reference, odds ratios (ORs) for live birth were: Group 1a OR 0.32 [0.18 - 0.60]; Group 1b OR 0.52 [0.37-0.74]; Group 2a OR 0.19 [0.08-0.43]; Group 2b OR 0.38 [0.24-0.61]; Group 3 OR 0.26 [0.17-0.41]; Group 4 OR 0.12 [0.08-0.19]. CDR for the Bologna group: 8.7% (OR: 0.10, 0.06-0.16); non-Bologna patients: 32.4% [OR: 0.48, 0.39-0.60]. Limitations, reasons for caution The limitations of the study encompass its retrospective cohort design and the variability introduced by different individuals conducting antral follicle counts using 2D ultrasonography. Wider implications of the findings Significant CDR differences exist between Bologna and Poseidon groups. POSEIDON patients show ∼2-fold lower CDR than normal responders, and Bologna patients exhibit ∼4-fold lower CDR than non-Bologna patients. Poseidon criteria cover a broader range of low-prognosis patients, while meeting Bologna criteria indicates a narrower, more specific group with poorer outcomes. Trial registration number N/A

P-594 Retrospective comparative study of follitropin delta vs follitropin alfa in progestin-primed ovarian stimulation (PPOS) protocol in IVF

Abstract Study question Could the individualized fixed-dose algorithm with follitropin delta show a similar pregnancy rate to conventional dosing with follitropin alfa in PPOS protocol? Summary answer Individualized fixed-dose algorithm with follitropin delta showed a similar pregnancy rate to follitropin alfa In PPOS protocol. What is known already Follitropin delta (REKOVELLE, Ferring Pharmaceuticals, Switzerland) is the first human cell line driven recombinant follicle-stimulating hormone (FSH) with an individualized fixed-dose algorithm based on serum AMH level and body weight. Follitropin alfa is a Chinese hamster ovarian cell driven recombinant FSH and its dosing is adjusted according to follicular response during the stimulation period. There was no significant difference between follitropin delta and follitropin alfa in terms of pregnancy rate under GnRH antagonist protocol. Study design, size, duration A retrospective analysis of 355 patients aged under 40 years who underwent ovarian stimulation in PPOS protocol using follitropin delta or follitropin alfa and on whom frozen-thawed single blastocyst transfer was conducted between August 2021 and November 2023 was performed. Participants/materials, setting, methods 193 cycles of women who used follitropin delta were compared to 162 cycles of women who used follitropin alfa. The following clinical outcomes on each treatment group were analyzed: chemical pregnancy rate (serum β hCG), clinical pregnancy rate (gestational sac), ongoing pregnancy rate(gestational sac and fetal heartbeat), serum E2 level at trigger day, cycle proportion of ≥ 10 oocytes retrieval, blastocyst formation rate, cycle proportion of ≥ 5 blastocysts and cycle proportion of ≥ 2 good quality blastocysts. Main results and the role of chance Baseline demographics in the follitropin delta group and the follitropin alfa group were not significantly different: age, 33.9 ± 3.5 years vs 34.5 ± 3.2 years; body weight, 53.5 ± 8.3 kg vs 53.8 ± 5.9 kg; number of previous IVF cycles, 0.2 ± 0.6 vs 0.3 ± 0.7; serum AMH level, 5.5 ± 2.9 ng/mL vs 5.3 ± 3.8 ng/mL, respectively. The chemical pregnancy rate (69.9% vs. 64.8%, P = 0.308), clinical pregnancy rate (58.0% vs. 56.2%, P = 0.748) and ongoing pregnancy rate (51.8% vs. 46.3%, P = 0.338) were comparable between the follitropin delta group and the follitropin alfa group. The individualized follitropin delta treatment resulted in a smaller cycle proportion of ≥ 10 oocytes retrieval (77.7% vs. 90.8%, P < 0.001) with lower serum E2 level at trigger day (3273 ± 1577 pg/mL vs. 3927 ± 1732 pg/mL, p < 0.001). However, the blastocyst formation rate was significantly higher in the follitropin delta group (75.5% vs. 68.7%, p < 0.001). Moreover, the cycle proportion of ≥ 5 blastocysts (71.0% vs. 76.4%, P = 0.286) and the cycle proportion of ≥ 2 good quality blastocysts (51.8% vs. 60.3%, P = 0.115) were comparable between the groups. Limitations, reasons for caution This is a non-controlled, retrospective study. Wider implications of the findings Follitropin delta in its individualized fixed-dose regimen could have the potential to decrease the risk of OHSS by minimizing excessive ovarian response, whereas a similar pregnancy rate to conventional dosing regimen could be expected due to the number of good quality blastocysts secured. Trial registration number not applicable

P-601 Monitoring reproductive hormones during ovarian stimulation: performance and usability of a self-operated at-home urine test

Abstract Study question How effective and user-friendly is a non-invasive, patient-operated urine test (Kinder) in tracking reproductive hormone levels during ovarian stimulation (OS) treatment in an IVF cycle? Summary answer Urinary E1-3G correlates well with blood E2 levels and ovarian follicle development. Patients found it easy and stress-free to perform the urine test at home. What is known already Monitoring blood reproductive hormone levels during OS is a widely accepted practice to ensure the optimal ovarian response to gonadotropin treatment, timing of oocyte maturation triggering and mitigating hyperstimulation risk. However, conventional blood testing is invasive, necessitating patients to travel to clinics for blood sampling, adding to their overall burden. Previous studies have revealed a robust correlation between blood E2 levels, and its corresponding urinary metabolites E1-3G. Kinder is a portable device designed for quantifying urinary E1-3G, allowing patients to conduct tests in the privacy of their homes, and for many obviating the need to travel substantial distances for monitoring. Study design, size, duration This is a prospective, single-cohort, study of Caucasian patients (28-34 years), conducted at Fertility Specialists of Western Australia in Perth, Australia, where patients may travel vast distances for treatment. Twenty-five patients were enrolled from Aug 2022-Aug 2023, and performed home urine tests utilizing the Kinder device in parallel with clinic scheduled blood (ELISA) and ultrasound tests. The primary end point of the study was the correlation between urinary and blood reproductive hormone concentrations (E1-3G). Participants/materials, setting, methods Spearman and Pearson correlation coefficients (CC) and 95% confidence intervals were calculated for E1-3G and E2, and E1-3G/E2 and follicle development (total volume of ovarian follicles by ultrasound). To assess patient acceptability patient-reported outcomes (PRO) were assessed using the State Trait Anxiety Inventory (STAI) questionnaire. Further, patient-reported experiences (PRE) were evaluated through the System Usability Scale (SUS) questionnaire, along with assessing their likelihood to recommend Kinder to their friends or family undergoing IVF treatment. Main results and the role of chance Upon analysing 100 concurrent urine and blood samples from 25 patients, a robust correlation was found between E1-3G and E2 levels (Spearman CC: 0.818, 95% CI: 0.680-0.904; Pearson CC: 0.847, 95% CI: 0.712-0.939). Additionally, we observed a moderate correlation between E1-3G levels and ovarian volume (Spearman CC: 0.701, 95% CI: 0.556-0.805; Pearson CC: 0.670, 95% CI: 0.519-0.781, n = 72), resembled the correlation between E2 levels and ovarian volume (Spearman CC: 0.874, 95% CI: 0.804-0.920; Pearson CC: 0.849, 95% CI: 0.770-0.902, n = 75). PRE: 22 out of 23 patients who completed the survey confirmed that they would definitely, or probably, recommend Kinder. The mean SUS score (91.4) signified an excellent user experience. PRO: Anxiety levels were not affected by use of Kinder (STAI score below threshold of 42.38) in 18/20 patients who completed three STAI surveys (first one before and second one after the initial Kinder test; third one after the third/fourth Kinder test). Although 2/20 patients reported a STAI score of 49 in the final survey, suggesting increased anxiety, both affirmed in the PRE survey that they “will definitely recommend Kinder”, suggesting that the elevated STAI score can be attributed to the overall IVF treatment rather than the use of Kinder itself. Limitations, reasons for caution The sample size is relatively small, necessitating further multi-centre studies with a larger sample size to validate the findings. Wider implications of the findings The results suggest an acceptable interchangeability between at-home urine E1-3G and at-clinic blood E2 monitoring hormone levels during OS treatment. A digital health approach, combining tele-counselling, remote at-home hormone monitoring, and follicle tracking, could reduce patient burden and save many patients the inconvenience of travelling large distances for cycle monitoring. Trial registration number ACTRN12622000488707

P-577 A randomized trial to compare the live birth rate following the progestin-primed ovarian stimulation versus the antagonist protocol in women with anticipated high ovarian responses

Abstract Study question Is there difference in the live birth rate following the progestin-primed ovarian stimulation (PPOS) versus the antagonist protocol in women with anticipated high ovarian responses? Summary answer The live birth rates of the first frozen embryo transfer following PPOS and the antagonist protocol were comparable in women with anticipated high ovarian responses. What is known already Progestin when given orally inhibits the pituitary LH surge during ovarian stimulation when taken orally i.e. progestin-primed ovarian stimulation. Two randomized trials showed similar number of oocytes for PPOS and the antagonist protocol in oocyte donation cycles. However, there is still no randomized trial to compare the live birth rate between PPOS and the antagonist protocol. Study design, size, duration This is a randomized controlled trial of 784 infertile women conducted from June 2020 and October 2021. Participants/materials, setting, methods Infertile women aged <43 years undergoing the first IVF cycle in a tertiary fertility center and having antral follicle count >15 randomly assigned in a 1:1 ratio into two groups: PPOS group and the antagonist group. Medroxyprogesterone 10 mg daily was given from the start of ovarian stimulation until the day of ovulation trigger in the PPOS group. The primary outcome was the live birth rate of the first frozen embryo transfer. Main results and the role of chance 784 women were randomly assigned into two groups: PPOS group (n = 392) and antagonist group (n = 392). Embryo transfer was either cancelled or postponed in 62 (62/392, 15.8%) women in the PPOS group and 65 (65/392, 16.6%) in the antagonist group because of no transferable embryos or no frozen embryo transfer within 6 months following randomization. The two groups were similar in demographic characteristics and number of oocytes obtained/fertilized, the number of cleaving embryos, number of good quality embryos at day 3, number of blastocysts developed and number of embryo/blastocyst frozen. There was no statistically significant difference in the live birth rate of the first frozen embryo transfer cycle between the progestin-primed ovarian stimulation and antagonist groups based on both intention to treat [37.5.0% (147/392) versus 32.7% (128/392), RR 1.148 (95% CI = 0.949–1.390), P = 0.16] and per protocol analysis [44.5% (147/330) versus 39.1.% (128/327), RR 1.138 (95%CI = 0.950–1.364), P = 0.16]. Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and cumulative live birth rates. Limitations, reasons for caution Women with anticipated high ovarian responses were recruited and the results may not be extrapolated to the general population seeking IVF. This is not a blind study although the live birth rate as the primary outcome is objection. The duration of the study is 6 months since randomization. Wider implications of the findings In situations in which fresh embryo transfer is not required such as oocyte/embryo freezing for fertility preservation, oocyte donation or preimplantation genetic testing, the PPOS protocol may be preferred over the antagonist protocol. Trial registration number NCT04414761