Cancellation Rate Research Articles

Comparisons of cumulative live birth rates after embryo transfers at day 2/3 versus day 5/6: a French national study

Research questionAre there significant differences between cumulative live birth rates (CLBR) after short or extended embryo culture when comparisons are performed per cycle? DesignThis French national study included all IVF cycles performed from January 2016 to December 2019 with at least one cleaved embryo at day 2. The day 2/3 and day 5/6 groups were identified using the National Biomedicine Agency register. Only attempts involving the vitrification method were included. CLBR was assessed with 1 and 2 years of follow-up using a logistic regression model. The evolution of CLBR per cycle was compared over 1 year of follow-up. ResultsIn total, 133,250 cycles met the inclusion criteria (70,528 and 62,722 in the day 2/3 and day 5/6 groups). In multivariate analysis including several patient and cycle characteristics, the CLBR per cycle was significantly lower in the day 5/6 compared with the day 2/3 group. A significantly higher rate of fresh embryo transfer cancellation was observed in the day 5/6 compared with the day 2/3 group. The evolution of the CLBR was significantly different in favour of the day 2/3 group in cases with three or fewer day 2 embryos, whatever the patient's age, in their two first attempts as well as in their third or further attempts. ConclusionsOverall, the nationwide results per cycle suggest that extended embryo culture until the blastocyst stage, even when used in combination with vitrification, could not improve live birth rates. Moreover, where three or fewer day 2 embryos are obtained, it might be preferable to use the short embryo culture strategy.

Three years of COVID-19-related school restrictions and mental health of children and adolescents in Japan

During the 3 years of the COVID-19 pandemic, Japanese children had to live with strict mitigation measures at school, such as eating school lunches silently and wearing masks during physical exercise classes, even after those mitigation measures have been relaxed worldwide. Excursions and other school events were frequently cancelled, especially in 2020 and 2021. This study conducts a retrospective survey on school experiences to understand how the strict mitigation measures were related to children's mental health and well-being. Results revealed school excursion cancellation to be associated with a higher risk of developing depressive symptoms {odds ratio [OR] 1.543 [95% confidence interval (CI) 1.109–2.148]}, and high cancellation rate of other school events to be associated with dissatisfaction in school experience [OR 1.650 (95% CI 1.222–2.228)]. In the subsample analysis, we found that girls and children with no extracurricular activities tended to exhibit depressive symptoms due to the cancellation of school excursions. Overall, the study demonstrated that persistent strict mitigation measures at schools might be a key factor in understanding children’s mental health and psychological well-being during a long-lasting pandemic.

Bilayer Intelligent Omni-Surface-Assisted Full-Duplex Systems: Simultaneous Self-Interference Cancellation and Sum Rate Maximization.

Recently, reconfigurable intelligent surfaces (RISs) have attracted increasing attentions in the design of full-duplex (FD) systems due to their novel capability of propagation environment reconfiguration. However, in conventional RIS-assisted FD systems, the beamforming for self-interference cancellation (SIC) and sum rate maximization (SRM) are highly coupled during RIS optimization, which significantly degrades the system performance. To tackle this issue, we exploit a novel bilayer intelligent omni-surface (BIOS) structure in FD systems. Compared with the conventional RIS designs, the BIOS provides independent beams on both sides, thus enabling more flexible achievement of SRM and SIC. For the BIOS-assisted FD system, we first formulate an optimization problem to achieve SRM and efficient SIC simultaneously. Then, we exploit the relationship between the SRM and mean square error (MSE), and propose a weighted MSE minimization with SIC algorithm to solve the problem. Specifically, we jointly design the beamforming at the base station and the BIOS with manifold optimization while guaranteeing an SIC constraint. Furthermore, we theoretically derive a lower band for the BIOS size required for efficient SIC in FD systems. Simulation results indicate that the BIOS outperforms the conventional RIS designs in FD systems, and verify the accuracy of the derived lower bound for the BIOS size.

P-435 Superiority of modified natural cycle vs hormonal replacement therapy in non-menopausal egg recipients of advanced maternal age: clinical outcomes from 1273 single blastocyst transfer cycles

Abstract Study question Is the modified natural cycle (mNC) better than hormonal replacement therapy (HRT) for endometrial preparation in non-menopausal egg recipients of advanced maternal age? Summary answer In women above 40 years, mNC shows better reproductive and obstetrical outcomes compared to hormonal replacement therapy, especially in the subgroup 45-50 years old. What is known already There is extensive evidence showing the superiority of mNC over HRT in terms of live birth rates, miscarriages, and even obstetric complications. Apparently, the presence of the corpus luteum plays a major role in endometrial receptivity and embryo implantation, probably allowing for better placentation. Nevertheless, there is a general belief that the ovulatory cycle of older women is not the best choice for endometrial preparation, although paradoxically they are the group of patients who could benefit most from the reduction of obstetric complications. An increase in cancellation rates for mNC is claimed, without consistent data available. Study design, size, duration Retrospective single-centre comparative clinical study, including 1273 endometrial preparation cycles for frozen single-blastocyst transfer between January 2020 and December 2022: 892 (70,2%) on HRT protocol and 381 (29,8%) on mNC protocol. The two groups were homogeneous for donor’s age (25,7 years HRT vs 25,3 years mNC), recipient’s age (42,2 years HRT vs 42,1 years mNC), severe male factor (6% HRT vs 5% mNC), and the need for a sperm donor (28% HRT vs 26% mNC). Participants/materials, setting, methods Among 1273 started non-menopausal recipient’s cycles, we compared cancellation rates between HRT and mNC due to either medical reasons (inadequate endometrium, bleeding, premature ovulation) or other issues (no embryo survival, COVID-19, etc). We studied the outcomes of the 1096 elective frozen single-blastocyst transfers performed, comparing HRT and mNC cycles for: pregnancy, clinical pregnancy, miscarriage, live birth and <35weeks preterm birth rates. We stratified the results by age and used Chi-square test to compare groups (p < 0,05). Main results and the role of chance The overall cancellation rate was 13.9%. No significant differences in cancellation for medical reasons were found between HRT (7%) and mNC (6.8%), p = 0.93. When we analyse results stratified by age, patients aged 39 or less (270 cycles: HRT 75.9%, mNC 24.1%) showed no statistically significant differences in pregnancy (58% vs 64.6%, p = 0.35), clinical pregnancy (50.7% vs 56.9%, p = 0.34), miscarriage (18.3% vs 18.9%, p = 0.93), and live birth rates (41.5% vs 46.2%, p = 0.5). In the 40-44 age group (494 cycles: HRT 64.2%, mNC 35.8%), no statistically significant differences were found between HRT and mNC in pregnancy (58.2% vs 61.5%, p = 0.47), clinical pregnancy (50.8% vs 51.1%, p = 0.96), and live birth rates (40.4% vs 45.8%, p = 0.25). The HRT group had a significantly higher miscarriage rate (21%) compared to mNC (10%), p = 0.03. For patients aged 45-50 years (332 cycles: HRT 72%, mNC 28%), no statistically significant differences were observed in pregnancy (56.5% vs 62.4%, p = 0.33) and miscarriage rates (24.3% vs 15.1%, p = 0.18). Clinical pregnancy (44.8% Vs 57%, p = 0.04) and live birth rates (33.9% vs 48.4%, p = 0.01) were significantly higher in the mNC group compared to HRT. No significant differences were found between HRT and mNC in preterm birth rates <35 weeks (3.6% vs 4.6%, p = 0.75). Limitations, reasons for caution This study is a single-centre retrospective comparative trial. Our homogeneity study included several confounding variables, however other bias such as severe uterine factor, embryo quality or repeated implantation failure cases were not taken into account. Wider implications of the findings Modified natural cycle should be encouraged as the first option for endometrial preparation in non-menopausal egg recipients of advanced maternal age, having shown superiority over hormonal replacement therapy in patients aged 45-50 years. Moreover, modified natural cycles are more patient friendly and cost-effective, with no increase in the cancellation rates. Trial registration number not applicable

P-147 Number of autologous mature oocytes as a predictor of live birth rate in women aged over 40 who do not accept egg donation

Abstract Study question Is the number of mature oocytes (M2) retrieved a reliable predictor of success for women aged over 40 with autologous oocytes? Summary answer 79.5% of live births were achieved in patients with ≥3M2 retrieved, 14.3% in women with 2M2, and 6.5% in women with 1M2. What is known already The delayed desire for parenthood has become a social phenomenon, particularly among women over 35. Reproductive outcomes in women over 40, using their own oocytes, are usually poor due to a decrease in follicle and oocyte quantity and quality, along with an increased prevalence of oocyte chromosomal abnormalities. While using donated oocytes is often recommended, it remains an unacceptable option for many couples. Furthermore, in Argentina the legislation on Assisted Reproduction Technologies endorses assisted reproductive treatments employing womeńs own oocytes up to the age of forty-four. Study design, size, duration This retrospective observational study, was performed between January 2004 and December 2022 in 5757 patients aged 40 and above undergoing autologous oocyte retrieval and fresh embryo transfer because they do not accept PGTa. Statistical analysis was performed using the InStat GraphPad statistical package. One-way ANOVA and two-tailed Student’s t-test were performed as required. Participants/materials, setting, methods Group1(G1): 40 years (N = 1600); Group 2(G2): 41years (N = 1300); Group 3(G3): 42 years (N = 1087); Group 4(G4): 43 years (N = 735); Group 5(G5): 44 years (N = 496); Group 6(G6): 45 years (N = 302); Group 7(G7): 46 years (N = 140); Group 8(G8): 47 years (N = 61); Group 9(G9): 48 years (N = 23); Group 10(G10): 49 years (N = 13). Primary outcome was relationship between number of M2 and live birth rate. Secondary outcomes were live birth rate, cancellation rate, miscarriage rate, clinical pregnancy rate. Main results and the role of chance Number of M2 retrieved: G1=3.9±3.4 [1-16]; G2=3.6±2.7 [1-14]; G3= 3.5±2.3 [1-12]; G4= 3.4±2.8 [1-14], G5=2.5±1.5 [1-7]; G6=2.3±2.2 [1-12]; G7=1.8±1.5 [1-8]; G8=1.5±0.9 [1-3]; G9=1.3±0.6 [1-3]; G10=1.0±0 [1-1]. Cancelation rate (%): G1=18.2 (292/1600); G2=20.9(272/1300), G3=22.3(243/1087); Gr4= 29.9(220/735); G5=28.0(139/496); G6=38.1 (115/302); G7= 42.8(60/140); G8= 44.3 (27/61); G9=47.8 (11/23); G10= 61.5 (8/13). Clinical pregnancy/transfer rate(%): G1=24.2 (316/1308); G2=21.7 (223/1028); G3=18.0(152/844); G4=18.0 (93/515); G5=9.2 (33/357); G6=11.2 (21/187); G7=3.7 (3/80); G8=0 (0/34); G9=8.3 (1/12); G10=0 (0/5). Live birth rate (%): G1= 11.8 (147/1250); G2= 10.0 (99/993); G3= 6.8 (57/831); G4= 6.6 (34/515); G5= 3.2 (11/348); G6= 2.1 (4/187); G7= 1.2 (1/80); G8= 0 (0/34); G9=0 (0/12); G10=0 (0/5). Miscarriage rate (%) 40 to 46 years: G1= 43.0 (111/258); G2= 47.3 (89/188); G3= 59.0 (82/139); G4= 63.4 (59/93); G5= 66.7 (22/33); G6= 80.9 (17/21); G7=66.7 (2/3) and 100 (1/1) for 48 years (G9). Cancellation rates increased with age. The number of M2 retrieved was significantly associated with clinical pregnancy, live birth and miscarriage rates. The average number of mature oocytes retrieved in cases resulting in live births was consistently higher across all age groups: G1=5.8±2.7 [1-16]***; G2= 4.8±3.5 [1-14]***; G3= 4.0±2.1 [1-9]***; G4= 5.7±2.7 [3-13]***; G5= 4.2±1.4 [2-7]***; G7= 6.0±1.4 [5-8]***; G8= 7.0±0 [7,7]*** (***= p < 0.0001). Limitations, reasons for caution This extensive retrospective study’s conclusions should be cautiously applied, limited to a specific group of elderly women unwilling to consider egg donation. 106 clinical pregnancies were not included because we did not have information on live births. Wider implications of the findings Identifying parameters associated with higher live birth rates in this population may aid in providing realistic expectations for achieving pregnancy with autologous oocytes. This information could guide medical advice and potentially suggest alternative options, such as egg donation or adoption. Trial registration number NOT APPLICABLE

P-026 Retrospective descriptive analysis of 1300 ICSI-AOA cycles: evaluating clinical outcomes and child health in the context of artificial oocyte activation (AOA)

Abstract Study question How does the outcomes of ICSI-AOA and child health differ from those reported in the literature? Summary answer ICSI-AOA clinical outcomes, including fertilization, embryo quality, pregnancy, live birth rates, and anomaly rates in children, align with those reported for ICSI alone. What is known already The use of AOA to artificially induce calcium rises by employing calcium ionophores has been shown as an effective approach in overcoming fertilization failure following ICSI, especially in couples facing severe male factor infertility. However, a significant gap exists in reporting live birth outcomes. On the other hand, uncertainties surrounding the health implications for children born through this method necessitate further investigation due to the limited sample sizes in previous reports. This descriptive analysis fills that gap by assessing 1300 cases, providing crucial insights into the clinical outcomes and health status of babies resulting from ICSI-AOA treatment. Study design, size, duration This retrospective study analyzes 1300 cases of ICSI-AOA between 2018 and 2020. Clinical outcomes in this study includes: fertilization, embryo quality, pregnancy, and live birth rates. Questionaries regarding the children health were included from birth to two years. Participants/materials, setting, methods The study included 1300 cases that referred to Isfahan Fertility and Infertility Center (Isfahan, Iran) and underwent ICSI-AOA due to: 1) cases with testicular biopsy (N = 458), 2) cases with 99-100% sperm head abnormal morphology and/or 3) previous low fertilization or total fertilization failure after ICSI (N = 842). In all cases, to induce AOA, oocytes were subjected to a 10-minute exposure of 10 micromolar ionomycin following ICSI. Main results and the role of chance From 1300 couples, 11,756 mature, 2,012 immatures, 193 degenerate, and 76 uninjectable oocytes were obtained. Fertilization were 59.69%, and 52.18% for mature and immature oocytes, resulting in cleavage rates of 96.93% and 93.80%, respectively. On day 3, 25.14% grade A, 31.49% grade B, and 43.36% grade C were observed. In 321 couples, 571 fresh embryos were transferred on day 3, resulting in clinical pregnancy and live birth rates of 20.82%, and 19.55%, respectively. For 32 couples with 44 fresh ET on day 5, rates were 9.38%, and 9.38% respectively. Out of 3270 vitrified embryos on day 3, 1743 were thawed (337 couples) and 1147 were transferred in 643 ET cycles. Clinical pregnancy and live birth rates were 21.61%, and 20.37%, respectively. 1527 embryos remain frozen. Out of 2,974 day 5-embryos, 2,571 did not reach blastocyst, leaving 403 vitrified embryos in 699 cases. Among them, 197 embryos remain frozen (80 cases) while 206 were transferred, with clinical pregnancy and live birth rates of 22.11%, and 21.80%, respectively. Cancellation rate, encompassing failed fertilization, cancellations on multiple days, and after freeze-thawing, was 20.16%. Among 266 live births, seven children showed anomalies, including achondroplasia, combined immunodeficiency, left eye deviation, intrauterine growth restriction, hydrocephaly, epilepsy, and umbilical hernia. Limitations, reasons for caution The main limitations of this study were the lack of comprehensive information on previous cycles, the absence of an ICSI control group, and the limited long-term follow-up on the physical and mental health of children born through the ICSI-AOA method beyond age two. Wider implications of the findings ICSI-AOA yields helpful clinical outcomes in high fertilization, pregnancy, and live birth rates in infertile couples, especially those with severe male factor infertility similar to ICSI in literature. Furthermore, presently, there seem to be no real concerns about health of babies born through this method, aligning with ICSI studies. Trial registration number IR.ACECR.ROYAN.REC.1401.038

P-286 Comparative study of frozen-thawed embryo transfer with modified natural cycle versus HRT cycle in previously cancelled true natural cycle patients

Abstract Study question Is there any difference in outcome of frozen embryo transfer(FET) between hormone replacement therapy(HRT) and modified natural cycle(MNC) in previously cancelled true natural cycle patients Summary answer In patients with previous history of cancelled true natural cycle, MNC results in higher clinical pregnancy rates after FET, when compared to HRT cycle What is known already Preparation of endometrium lays down the foundation for conception and subsequent successful pregnancy.There has been a plethora of endometrial preparation protocols described in the literature. The established protocols are true natural cycle,MNC with or without luteal phase support(LPS) and HRT cycle with or without gonadotrophin releasing hormone agonist(GnRha) suppression. Nevertheless,there is no consensus on protocol which may provide the best outcome in patients who have had cancelled true natural cycle.In such situations,HRT cycle may be considered as an easy option as the cancellation rate is low.However,HRT treatment is known for higher early pregnancy and obstetric complications,compared to MNC Study design, size, duration Prospective observational study,where 155 patients undergoing FET who had minimum one true natural cycle cancellation were recruited.They were divided into group A undergoing HRT cycle(n = 77) and group B for MNC cycle(n = 78).The study was conducted in a fertility unit over six months from June-November 2023.Primary outcome measures were serum betaHCG estimation and ultrasonographic documentation of intrauterine pregnancy.Results were analysed using statistical software SPSS version25 and p value of less than 0.05 was considered statistically significant Participants/materials, setting, methods HRT patients received injectable GnRha 3.75 mg on day21 of previous cycle.Oral estradiol valerate 6mg daily started on day2 of menses. When ET was minimum 7mm, luteal phase support(LPS) was started with daily oral and vaginal progesterone(30mg and 600mcg respectively),followed by FET. MNC patients received Letrozole 5mg daily from day 2-6 of menstruation.rhCG 250mcg was given subcutaneously,when ET was at least 7mm,dominant follicle 16-18mm and progesterone(P4) less than 1ng/ml.LPS(vaginal progesterone600mcg) was started 36hours after rHCG,followed by FET Main results and the role of chance Mean ET in MNC group was 8.92mm ± SD1.38, which was higher than HRT group (8.31 mm ± SD0.89). This difference was statistically significant with a p value of 0.014.Serum beta HCG estimation was done 2weeks after FET. In HRT group beta HCG was positive in 41 out of 77(53.25%) and in MNC group positivity was higher being 48 out of 78(61.54%). However, this difference was not statistically significant. Transvaginal ultrasonography(TVS) was done to confirm intrauterine pregnancy 2weeks after beta HCG assay. Clinical pregnancy rate(CPR) was higher in MNC group with 32 out of 78(41.03%),compared to 18 out of 77(23.38%) in HRT group. This difference is statistically significant with p value of 0.019 Limitations, reasons for caution Relatively small population in this study may be the reason for caution to interpret the statistical data. Study with higher numbers may bring about more robust conclusions Wider implications of the findings Patients with failed true natural cycles may be considered for modified natural cycle(MNC) stimulation for FET, without attempt of another true natural cycle stimulation Trial registration number NOT APPLICABLE

P-670 The impact of fixed day-one versus day-six progestin initiation on ovarian response following progestin primed ovarian stimulation

Abstract Study question Does ovarian response differ between a fixed stimulation day (SD) 1 and SD 6 progestin start in a progestin primed ovarian stimulation (PPOS) protocol? Summary answer Fixed SD 1 and SD 6 PPOS protocols showed no significant differences in terms of ovarian response to stimulation. What is known already Ovulation prior to oocyte retrieval is a potential concern during ovarian stimulation (OS). Progestins, when compared to GnRH analogues, also effectively prevent premature ovulation with the added convenience in terms of its oral administration and lower costs. For this purpose, progestins may be started immediately with OS (SD 1) or later in the cycle, usually around SD 6, when the risk for ovulation increases. While the latter approach may be associated with a lower follicle growth suppression, evidence regarding the impact of the two protocols on ovarian response is still lacking. Study design, size, duration We conducted a single center retrospective cohort study in a private fertility clinic, including 923 patients (584 in the SD1 group and 339 in the SD6 group) who underwent 1064 OS cycles (652 in the SD1 group and 412 in the SD6 group) using a PPOS protocol between January 2016 and May 2023. Among these, 394 (37.03%) were oocyte donation cycles, 341 (32.05%) were autologous IVF/ICSI cycles and 329 (30.92%) were autologous vitrification cycles. Participants/materials, setting, methods We included women under the age of 44 who performed an OS cycle following a PPOS protocol. LH peak suppression was performed with daily desogestrel 75µg started either on SD 1 or on SD 6. The number of oocytes retrieved, number of mature (MII) oocytes, follicle-to-oocyte index (FOI) and follicular output rate (FORT) were compared between the groups. Comparisons are presented as adjusted regression coefficients (β) and 95% confidence intervals (95%CI) following multivariable linear regression. Main results and the role of chance The majority of patients in the SD1 group were donors (59.66%), while in the SD6 group most patients were doing assisted reproductive techniques (ART) with autologous oocytes (98,78%). In the SD1 group, patients were older (38.93±3.81 vs. 37.93±4.00, p < 0.001), had a higher antral follicle count (AFC) (20.79±8.66 vs. 14.12±9.96, p < 0.001), underwent OS with a lower gonadotropin dose (2036.25±766.20IU vs. 2715.20±976.40IU, p < 0.001) and triggered mostly with GnRHa (86.44% vs. 57.50%, p < 0.001). Both groups presented a similar body mass index (BMI) (22.80±2.96 vs. 21.71±3.25kg/m2, p = 0.175). Bivariate analysis revealed a higher number of oocytes retrieved (19.40±12.02 vs. 10.10±8.19, p < 0.001), number of MII oocytes (12.05±5.97 vs. 7.42±5.91, p < 0.001), FORT (81.53±20.59% vs. 73.72±23.80%, p < 0.001) and FOI (95.49±48.78% vs. 76.31±47.60%, p < 0.001) in the SD1 group. No difference was found in the cancellation rates among the two groups (1.99% for SD1 vs. 3.16% for SD6, p = 0.322). Following adjustment for age, BMI, AFC, ART treatment, type of trigger and total gonadotropin dose, no difference was found regarding the number of oocytes retrieved (β=-0.62; 95%CI -2.53 to 1.30), number of MII oocytes (β=-1.66; 95%CI -3.43 to 0.10), oocyte maturation rate (β = 2.30; 95%CI -4.60 to 9.20), FOI (β=-3.29; 95%CI -13.15 to 6.57) or FORT (β=-1.78; 95%CI -5.66 to 2.10). Limitations, reasons for caution Despite attempting to mitigate confounding effects through multivariable linear regression analysis, the retrospective nature of the study and limited sample size may still be insufficient to eliminate bias. Moreover, reproductive and perinatal outcomes were not reported. Wider implications of the findings Our study suggests that both the SD1 and SD6 PPOS protocols can be employed based on patients’ and clinicians’ preference, regardless of the type of ART treatment or patient’s ovarian reserve, without impact on ovarian response to stimulation. Trial registration number not applicable

O-206 Natural, modified natural or artificial endometrial preparation strategies for frozen embryo transfer in ovulatory women (MONART): a randomized controlled trial

Abstract Study question Are live birth rates after natural (NC), modified natural (mNC) endometrial preparation superior to artificial cycle (AC) strategies for ovulatory women undergoing frozen embryo transfer? Summary answer Live birth rates were comparable between NC, mNC, and AC. However, NC and mNC resulted in a significantly higher cycle cancellation rate. What is known already The number of frozen embryo transfer (FET) cycles has increased dramatically. In ovulatory women undergoing FET, three common strategies can be used for endometrial preparation: NC, mNC (NC + human chorionic gonadotropin trigger), and AC protocols. Previous studies comparing the effectiveness of these strategies had several drawbacks, including small sample size, lack of consistency between studies in the assessment and reporting of outcomes, and the retrospective origin, which introduced potential biases. Therefore, there is a lack of consensus on the optimal endometrial preparation protocol for FET. Study design, size, duration This single-center, open-label, randomized controlled trial was conducted at IVFMD, My Duc Hospital in Ho Chi Minh City, Vietnam. From March 2021 to March 2022, a total number of 1,428 participants were randomized (476 per group). The primary outcome of the study was live birth after one FET. Secondary outcomes were fertility outcomes, early pregnancy complications, obstetrical outcomes, perinatal and neonatal complications, and endometrial preparation cycle cancellation rates. Participants/materials, setting, methods Eligible participants were ovulatory women aged 18–45 with FET treatment, underwent no more than three IVF/intracytoplasmic sperm injection-FET cycles, had no more than two day-3 or one blastocyst transferred. Women with menopause/anovulation, contraindications for hormonal administration, uterine abnormalities who underwent in-vitro maturation, pre-implantation genetic testing, oocyte donation cycles were excluded. The FET strategies included FET after the first endometrial preparation cycles with AC, mNC, or NC, as per randomization, and the second with AC. Main results and the role of chance A total of 4,779 participants were screened, of whom 1,428 eligible individuals (476 per group) were randomized after written informed consent. The live birth rate after one FET was 36.6% (174/476) in the natural cycle strategy group, 33.4% (159/476) in the modified natural cycle strategy group, and 34.0% (162/476) in the artificial cycle strategy group (relative risk [95% confidence interval] for natural versus artificial cycle strategy: 1.07 [0.87–1.33] and for modified natural versus artificial cycle strategy: 0.98 [0.79–1.22]). Maternal and neonatal outcomes were comparable between groups, in particular,hypertensive disorders in pregnancy. For both natural and modified cycle groups, 20.08% (99/476) of the first FET cycles were canceled before subsequent successful ET versus none in the artificial cycle group. Limitations, reasons for caution Due to the nature of the intervention, blinding was not possible. The study was conducted in ovulatory women in a single center in Vietnam, which may limit the generalisability of the findings. Wider implications of the findings Live birth rates and obstetric/neonatal outcomes after the natural cycle, modified natural cycle, or artificial cycle strategies for ovulatory women undergoing FET are comparable, with higher cancellation rates in both the natural cycle and the modified natural cycle groups. Trial registration number NCT04804020

P-410 A modified artificial cycle-frozen embryo transfer(mAC-FET) protocol with evidence of corpus luteum(CL) formation as determined by serum relaxin-2 in early pregnancy :a prospective proof-of-concept study

Abstract Study question Can a mAC-FET protocol for endometrial preparation in ovulatory patients lead to formation of a CL as evidenced by serum relaxin-2 in the pregnant patients? Summary answer CL forms in the mAC-FET protocol as serum relaxin-2 in early pregnancy was comparable to that in spontaneous conception.Late luteal rise of relaxin-2 wasn’t demonstrated. What is known already Clinical evidence points to increased incidence of preeclampsia in pregnancies by AC-FET cycles compared to ovulatory FET cycles-natural cycle(NC) and mNC. The absence of CL and it’s secretory products like relaxin-2 is a contributing factor. FET protocols for endometrial preparation in ovulatory patients need to be optimised. NC/mNC-FET protocols need frequent monitoring. Also there is a temporal variability between LH/hCG and progesterone levels. We studied a mAC-FET protocol in ovulatory patients with a delayed start(day3-5 of the cycle),low dose transdermal 17β estradiol gel to see the formation of CL as elucidated by the presence of serum relaxin-2 in early pregnancy. Study design, size, duration A proof-of- concept prospective study was conducted at a tertiary centre (July2023-Dec2023). Serum relaxin-2(R&D/Quantikine/ELISA) was determined in 4 groups of patients- Group-A. mAC-FET(n = 34) 1.On the day of start of progesterone 2.Post-ET day5-9 (along with serum progesterone) 3.In pregnancy(6-9 weeks of gestation) Group-B. AC-FET(n = 8) 1.On the day of start of progesterone 2.In pregnancy(6-9 weeks) Group-C. Spontaneous conception (n = 9) 1.In pregnancy(6-9 weeks) Group-D. Infertility patients ( n = 24) 1.Preovulatory. All patients were ≤40 years with a BMI ≤30kg/m2. Participants/materials, setting, methods In the AC-FET cohort-oral estradiol 6mg/day was started from day1/2 of the cycle. When endometrial thickness was>7mm,progesterone<1ng/ ml then intramuscular progesterone was started- 50mg/day-3 days,100mg on day4-the day of ET(Day-3 embryos) and continued every alternate day.Progesterone gel was added post-ET. In the mAC-FET cohort-17β transdermal estradiol gel(0.06%) 3mg/day was started from day3-5,rest of the protocol was similar. Statistical analysis was performed using appropriate non-parametric tests.Pearson coefficient(r) was used to assess linear-relationship.Two-tailed P<.05 indicated statistical significance. Main results and the role of chance Mean age and BMI of the patients with mAC-FET was 33.3±4.7 years and 24.4±3.7 kg/ m2 which was comparable across all groups (P=.14,P=.52 respectively). Clinical pregnancy rate in the mAC-FET group was 52.94%(18/34). 3 patients had an early abortion. Baseline relaxin-2 levels, median[Interquartile range(IQR)] were comparable- AC-FET cohort-9.1pg/mL(8.6-16.8), mAC-FET cohort-11.5pg/mL(9.6-13.7) and the infertility cohort-10.9pg/mL(8.4-14.5) (P=0.74) The primary outcome was the comparable levels of serum relaxin-2, in early pregnancy in the mAC-FET group and spontaneous conception group - median (IQR) 449.8pg/mL(73.1-492.3) and 487.9pg/mL(419.1-497.8) respectively (P=.12) The relaxin-2 levels, in early pregnancy in the mAC-FET group were significantly higher than the AC-FET group median(IQR) 449.8pg/mL(73.1-492.3) and 7.9pg/mL(7.8-9.5) respectively (P=.0005). As secondary outcomes, we studied the late luteal rise of relaxin-2 in the mAC-FET group and the relationship of late luteal progesterone with relaxin-2 in early pregnancies in the mAC-FET cohort. A late luteal rise of relaxin-2 was not demonstrated in the mAC-FET cohort. The serum relaxin-2, on the day of start of progesterone and on day5-9 post ET- median(IQR) 11.5pg/mL(9.6-13.7) and 11.4pg/mL(9.0-18.5), respectively was comparable (P=.18). The relationship between serum relaxin-2 in early pregnancy and the progesterone levels on day5-9 post ET in the mAC-FET cohort was not significant r = -.059 (P=.07) Limitations, reasons for caution This was a small proof- of-concept single centre study. Due to the limited numbers and short duration of the study, we could not compare efficacy, cancellation rates and pregnancy outcomes of the mAC-FET protocol with other FET protocols. Wider implications of the findings The mAC-FET protocol studied for endometrial preparation was similar to the AC -FET protocol regarding monitoring,flexibility and consistent progesterone exposure with the added advantage of the presence of the CL.This may decrease the risk of maternal/neonatal complications. Larger studies are needed to confirm it’s efficacy and impact on pregnancy outcomes. Trial registration number Not Applicable

P-366 Short- and long-term safety outcomes in patients undergoing fertility preservation (FP) with controlled ovarian stimulation prior to chemotherapy

Abstract Study question The Impact of pre-chemotherapy fertility preservation (FP) with controlled ovarian stimulation (COS) on mortality and complications in cancer patients Summary answer The 5-year survival was higher in women who proceeded with FP than those who did not. What is known already FP in the form of egg/embryo freezing is a well-established option to preserve fertility in patients requiring gonadotoxic treatment. This method introduces a slight delay in chemotherapy initiation, raising theoretical concerns about its impact on long-term patient outcomes. Additionally, safety concerns exist for estrogen-sensitive pathologies. However, data on safety outcomes, especially mortality and cancer recurrence in women undergoing fertility preservation, remain limited. Study design, size, duration This study utilized a prospectively collected database of 603 patients referred from the UK South and South East cancer network for fertility preservation to a tertiary Assisted Conception Unit between 2003 and 2019. Participants/materials, setting, methods All female patients attended the Fertility Preservation Service post-cancer diagnosis to discuss options. Patient demographics, stimulation details, and treatment outcomes were recorded. Living status was confirmed up to January 2024 through Health Record Registry. Data analysis included basic demographics, hazard ratios, and 5-year survival analysis, with a log-rank test comparing patients who received or did not receive fertility preservation treatment. Main results and the role of chance As many as 603 patients were counselled re: FP over the studied period. The biggest majority of patients n = 320 (53%) had a diagnosis of breast cancer, followed by 67 patients (11.1%) presenting with lymphomas. The majority of counselled patients (n = 340 (56.4%)) went ahead with fertility preservation. Mean age of participants was 32.7 with an average BMI of 24.6, average AMH of 19.2 pmol/L, and median AFC of 15. Short term complication was estimated at 2% of the sample. Successful stimulation was noted in almost all cases (cancellation rate 1.5%) requiring on average 14 days to complete the treatment. A short protocol was mainly used (98% of cases) with a median daily FSH injection at 300 IU/L and an average oocyte yield of 14. Mortality in patients who received fertility preservation was estimated and the respective hazard ratio was 0.74 (95% CI 0.47 to 1.15, p = 0.18). With regards to survival, the log-rank test yielded a chi-square value of 3.9 with 1 degree of freedom. The resulting p-value was 0.05, indicating a statistically significant difference in survival probabilities between patients who underwent fertility preservation compared to those who did not (p = 0.05). Limitations, reasons for caution Information on the cause of death was unavailable, limiting the ability to minimize bias and estimate disease recurrence. However, the young age of the patient population reduces the likelihood of death due to unrelated medical conditions. Wider implications of the findings The data suggests that fertility preservation with controlled ovarian stimulation is a safe option for cancer patients. This finding provides reassurance to patients considering this well-established fertility treatment, offering realistic chances of survival. Trial registration number not applicable

P-278 The impact of previous pituitary suppression protocols on IVF outcomes in patients with endometriosis undergoing freeze-all approach

Abstract Study question Do embryological parameters and live birth rates differ in patients with endometriosis undergoing freeze-all approach when GnRH-antagonist protocol or progestin primed pituitary suppression(PPOS) was preferred? Summary answer When comparing the GnRH antagonist protocol, the PPOS protocol was associated with more usable cleavage stage embryos but with a similar live birth rate. What is known already Optimal COH protocol for patients with endometriosis is still controversial. Initially, the GnRH agonist protocol was hypothesized to be superior because it was assumed to increase pregnancy rates by improving the inflammatory process of endometriosis. However, available data represented similar pregnancy rates in GnRH antagonist and GnRH agonist protocols. Recently, progestins have been used for suppression of endogenous LH surge instead of GnRH analogs in COH for various indications. Since, recent data indicates that utilization of progestins for more than eight days can reduce the inflammatory process of endometriosis, PPOS protocol might be employed in this patient group. Study design, size, duration This retrospective cohort study conducted at Bahçeci Health Group between January 2021-January 2023. Inclusion criteria were female age between 20-44 years, patients with endometrioma diagnosed by transvaginal ultrasonography and freeze-all cycles. Exclusion criteria were pre-implantation genetic testing (PGT) cycles, patients with uterine myoma distorting the endometrial cavity, congenital uterine anomaly and presence of hydrosalpinx.Each patient was included only once. A total of 607 patients;407 in GnRH antagonist group and 200 in PPOS group were recruited. Participants/materials, setting, methods The study analyzed the embryological parameters and live birth rates undergoing freeze-all cycles. COH was performed with recombinant FSH or HMG at a starting dose 150-300 IU depending on ovarian reserve and body mass index (BMI). LH surge was controlled by a flexible GnRH antagonist or fixed PPOS protocol. Primary outcome for embryological parameters were usable cleavage embryo after OS and live birth after the first frozen embryo transfer (FET) cycles. Main results and the role of chance Female age in PPOS group was older than GnRH antagonist group (33.3±4.9 vs.32.4±4.8,p=0,02).Other demograhic characteristics were similar among two groups.Total gonadotrophin dose and duration of stimulation in PPOS group were lower than antagonist group (2602.3±1083.5 vs.2866.9±1147.9 IU, p = 0,002 and 10.86±1.77 vs. 11.59±1.82 days, p < 0.001). No significant difference regarding endocrinological parameters of OS and number of oocytes retrieved, mature oocyte, maturation and fertilization rates was found in two groups. However, the number of day 3 usable embryos were higher in the PPOS group than GnRH antagonist group (4.66±4.38 vs. 3.84±3.72 p = 0.04). There was no difference in the cancellation rates. A total of 478 FET cycles of 607 were evaluated; 323 in GnRH antagonist and 255 in PPOS group. No significant difference in FET cycle and embryological characteristics was found in two groups. The clinical pregnancy rate, miscarriage rate, live birth rate and multiple pregnancy rates per transfer were comparable between the two groups [59.1% (191/323) vs. 59.4% ( 92/155) p = 0,963;17.3%(33/191) vs 0.9%(10/92) p = 0,16; 48.6%(157/323) vs. 52.9% (82/155) p = 0,379; 7.3%(14/191) vs.10.9% (10/92) p = 0317, respectively].Multivariate binary regression analysis revealed that female age, embryo day embryo quality.number of embryos transferred were significant independent factors for live birth but not the PPOS vs GnRH antagonist. Limitations, reasons for caution Although we used regression models to adjust all possible confounders, it was a retrospective study with its intrinsic limitations. Further prospective RCTs are warranted. Wider implications of the findings Although cleavage stage usable embryo was significantly higher in PPOS group,the pregnancy outcomes were comparable between groups.Those results suggest that theoretical advantages of progestin in preceding OS does not seem to present a significant difference on live birth,but should be confirmed with prospective trials within cohort of women with endometriosis. Trial registration number not applicable ( retrospective study)

P-613 Natural cycles monitoring for frozen embryo transfers: is it beneficial to start immediately after ovarian stimulation?

Abstract Study question Are there more advantages in performing frozen embryo transfer (FET) immediately after ovarian stimulation or in delaying it by at least one menstruation? Summary answer In natural cycles, timing of frozen embryo transfer does not affect clinical pregnancy rates, but immediate transfer is associated with higher rates of cycle cancellation. What is known already In order to achieve a reduced time to pregnancy and avoid additional stress for the couple, some Centers initiate FETs immediately, i.e. on the first menstrual cycle after ovarian stimulation. However, the detrimental effect of hormonal stimulation on ovarian function and endometrial receptivity may persist in the following cycle and immediate FETs may increase the possibility of cycle cancellation and reduce pregnancy rate. Available evidence on this subject, mainly focused on endometrial preparation with hormonal replacement therapy (HRT), showed contrasting results. Moreover, studies on FETs performed on natural cycles are lacking. Study design, size, duration This is a retrospective study conducted at the Infertility Unit of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, Italy. A large amount of single FETs, performed between 2014 and 2021, was considered and was then divided in two groups according to their timing (immediate or delayed). The primary outcome was to assess the clinical pregnancy rate (CPR); secondary outcomes were live birth rate (LBR) and the cycle cancellation rate. Participants/materials, setting, methods True natural cycles (T-NC) and modified cycles with the use of triggered ovulation (M-NC) protocols for endometrial preparation were pursued in women with regular menses; otherwise, HRT was used. Immediate FET was defined when performed on the first menstruation following ovarian stimulation (i.e. withdrawal bleeding occurring after ovarian stimulation or after a failed fresh embryo transfer). Delayed FETs included those performed after at least two menstruations. Only the first transfer after ovarian stimulation was considered. Main results and the role of chance A total of 5,765 FET cycles were included in the study. FET cycles were achieved through T-NC in 4,477 cases (78% of all FETs), of which 364 were immediate and 4,113 were delayed. M-NC cycles accounted for 1% of the total amount of FETs and HRT protocols were pursued in 11% of cases. The analysis showed no impact of FET timing on CPR both in the whole cohort and in the subgroups based on different endometrial preparation protocols. Focusing on T-NC cycles, the CPR in the immediate group was comparable to that of the postponed group (29 vs. 32% respectively, OR 0.90 [95% CI 0.71 - 1.14]). On the other hand, LBR in T-NC cycles was significantly lower in the immediate group than in the delayed group (20% vs. 25% respectively, OR 0.74 [95% CI 0.56 - 0.96]). Consequently, immediate FETs resulted to be associated with a significantly higher rate of pregnancy loss (31% vs. 21% respectively, p = 0.03). Furthermore, cycle cancellation occurred more frequently in the immediate T-NC group, compared with the delayed group (18% vs. 12% respectively, p = 0.003). Similar results were observed in HRT cycles (15% in immediate FETs vs. 7% in delayed FETs, p = 0.08). Limitations, reasons for caution The retrospective nature of this study involves a risk of selection bias. Moreover, the reason for cycle cancellation was not always available; thus, these data were not included in the analysis. Lastly, these outcomes are only applicable to a similar cohort, that is Centers following a non-elective freeze-all policy. Wider implications of the findings This is the largest investigation on T-NC FETs and is among the very few studies providing separate results on different endometrial preparation protocols. Evidence from this study is in line with some previous retrospective analyses and in contrast with others. Thus, randomized controlled trials are needed to confirm these results. Trial registration number not applicable

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-614 The use of home ovulation prediction kits (OPKs) in true natural cycle frozen embryo transfer (NC FET)

Abstract Study question Do urinary OPKs have inferior ability to detect the LH surge compared to daily serum monitoring among patients undergoing true NC FET? Summary answer OPKs are highly accurate and may serve as reliable tests to detect the LH surge among patients undergoing NC FET. What is known already Frozen embryo transfers continue to increase worldwide and recent evidence suggests natural cycle protocols may be superior to hormone replacement protocols because of lower risk of miscarriage and lower risk of pregnancy complications. Patients undergoing NC FET attend multiple clinic appointments which has been associated with increased patient stress levels during fertility treatment. OPKs have been found to be accurate at detecting the LH surge in the trying to conceive population and have high user acceptability. Study design, size, duration A prospective single cohort study including 139 fertility seeking participants was completed at an academic-affiliated fertility center for a duration of 12 months. Participants/materials, setting, methods Patients scheduled for NC FET (regular cycles 27-35 days, mid luteal progesterone >30 nmol/L, no luteal phase concern) with the ability to provide informed consent and access to SMS texting devices were eligible for participation. On the same day they started daily morning bloodwork as per the standard protocol (2-3 days prior to anticipated LH surge), participants began twice daily OPK testing. Upon exiting the study, patients completed a questionnaire on satisfaction with OPK use. Main results and the role of chance LH surge detection rate was 85.6% (n = 119/139) with serum monitoring and 93.5% (130/139) with OPK use (Kappa agreement 90.7%, K = 0.51, p < 0.001). Among patients with a serum-detected LH surge, OPK was positive within +/- 12 hours of the serum LH surge detection in 84.8% of patients. In 23.7% of cycles, OPK was positive the same morning as serum blood work. In 27.1% of cycles, OPK was positive 12h prior and in 33.9% of cycles, OPK was positive 12h after serum LH surge detection. Actual NC FET cycle cancellation rate was 16.6% (n = 23/139) compared to an anticipated cycle cancellation rate of 20.9% (29/139) if OPKs had been used to initiate serum monitoring. The average reduction in the number of serum monitoring visits and distance travelled in kilometers with OPK use was 3.9 visits (SD 2.1) and 155km (SD 174), respectively. The majority of participants reported satisfaction with OPK use. Of 135 patients, 110 (81.5%) strongly agreed the OPK was easy to use, 100 (74.1%) strongly agreed they would be open to using OPKs in future fertility treatments and 120 (88.9%) reported a reduction or no impact on stress levels associated with fertility treatments. Limitations, reasons for caution This study only used Clearblue Digital Ovulation Tests and the reported reliability in our study cannot be extrapolated to all OPKs. Additionally, the accuracy of the reported serum LH surge detection rate may be limited by physician specific definitions of serum LH surge. Wider implications of the findings OPKs are highly accurate and may serve as a reliable trigger for serum monitoring in NC FET. While their use would reduce the number of clinic appointments and distance travelled for patients undergoing NC FET cycles, patients should be advised OPK use may be associated with higher cycle cancellation rates. 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-683 Progestins vs flexible GnRH antagonist for LH suppression during controlled ovarian stimulation in POSEIDON groups 3 and 4 patients: Analysis of effectiveness and cycle outcomes

Abstract Study question How do cycle outcomes differ between controlled ovarian stimulations using progestins vs flexible GnRH antagonists for LH suppression in women with diminished ovarian reserve (DOR)? Summary answer While progestin use is associated with significantly higher blastocyst rate than GnRH antagonists in POSEIDON group 4, the latter gives better results in group 3. What is known already Controlled ovarian stimulation (COS) in patients with DOR carries the additional risk of premature luteinizing hormone (LH) surge and ovulation.GnRH antagonists are popular for LH suppression in COS because of their convenient, quicker onset of action, flexibility to use GnRH agonist as a trigger and continue as double stimulation, allowing rapid pooling of embryos. Ease of oral administration, combined with cost-effectiveness and retention of all the benefits of GnRH antagonists makes progestins an attractive alternative to GnRH antagonists for COS in patients with DOR who often need multiple stimulation cycles to enable the pooling of embryos. Study design, size, duration An open-label, multicentric, randomized controlled study was conducted over 1 year from January 2023 to December 2023. 140 women aged 21- 42 years and with AMH <1.2 ng/dl were randomized into 2 groups in a 1:1 ratio, using either oral progestins or GnRH antagonists for LH suppression. The two groups were further comparative analyzed under POSEIDON 3 and 4 subgroups. Those with BMI >40kg/m2 and with partners having severely compromised semen parameters were excluded. Participants/materials, setting, methods In Group A (PPOS): Medroxyprogesterone acetate 10 mg orally was given daily with gonadotropins (hMG 300- 375 IU) from cycle day 2 until trigger. In Group B (Antagonist), patients had daily GnRH antagonist, cetrotide 0.25 mg, subcutaneous administration started when the dominant follicles reached 12-14 mm size during controlled ovarian stimulation. This was continued until the trigger. Following oocyte retrieval and ICSI, embryos were cultured until D5 and vitrified fortransfer in subsequent HRT cycles. Main results and the role of chance Patients in Group A, using PPOS, were noted to have significantly better fertilization rates than those in Group B, using flexible GnRH antagonists (0.82 + 0.2 vs 0.66 + 0.4, p-value <0.01). Though the number of top-quality embryos (TQE) frozen was not significantly different between groups A and B (p-value = 0.44), a significant difference in the outcome was noted when comparatively analyzed under the subgroups of POSEIDON groups 3 and 4. While patients in POSEIDON group 4 got significantly more top-quality embryos (TQE) when progestins were used for LH suppression (1 + 0.11 vs 0.77 + 0.41, p-value <0.01), those in POSEIDON group 3 got significantly more top-quality embryos when GnRH antagonist was used (0.94 vs 2, p-value <0.01). Patients in Group A and B were found to have no significant difference in the following outcomes: incidence of premature LH surge (4.3% vs 7.1%, p value= 0.71), number of days of stimulation (10.26 + 2.18 vs 10.26 +2.94, p value= 0.99), total gonadotropin dosage used (3448.64+ 1007.98 vs 3087.41 + 1260.56, p value=0.06), total number of oocytes retrieved (5.84 + 3.3 vs 4.9 + 3.4, p value=0.09) and total cycle cancellation rate (30.1% vs 35.7%, p value= 0.11). Limitations, reasons for caution The small sample size of the cases limits the current statistical power of the study. The results being encouraging need to be confirmed in a larger patient population and followed for a longer duration to enable calculation of implantation and clinical pregnancy rates for all patients. Wider implications of the findings Oral progestins are an effective and cheaper, patient-friendly alternative to injectable GnRH antagonists during COS in women with DOR. Considering the significantly higher TQEs formed, PPOS can be preferred in older, POSEIDON group 4 patients, whereas flexible GnRH antagonist protocol can be our choice in the younger, POSEIDON group 3. Trial registration number Not applicable

O-010 Luteal estradiol versus follicular GnRH antagonist for ovarian follicular synchronization in POSEIDON poor responders: a multicentric randomized controlled trial

Abstract Study question In order to improve follicular synchronization, is pre-treatment with Luteal Estradiol (LE) more efficacious than Follicular GnRH Antagonist (FA) among poor responders? Summary answer Luteal Estradiol is better than Follicular GnRH Antagonist to improve maturation rates in Poor Ovarian Responders (POR) What is known already In poor responders, follicular asynchrony is a major obstacle in optimizing the pregnancy rates and leads to more cycle cancellations and increases the requirement of additional pool up cycles. It imposes significant financial burden on patients. ESHRE recommendations on FA and LE are conditional and require better quality studies. Several studies have evaluated the individual role of pre-treatment with LE or FA in synchronising the number of mature oocytes retrieved. There have been no studies comparing the efficacy of luteal estradiol versus follicular antagonist Study design, size, duration A randomised controlled trial was conducted at multiple centres of a private fertility clinic over 1year. Block randomization was performed using a Web-based randomization system.Allocation concealment was done using envelopes. 196 POR patients were randomized and 145 successfully completed the study. 80 patients(55.17%) received LE while 65 patients (44.83%) received FA. A per-protocol analysis was conducted. A subgroup analyses was done after excluding endometriosis and male-factor infertility as they could have been significant confounding factors. Participants/materials, setting, methods We randomised POR patients(POSEIDON criteria) into 2 arms, in their previous menstrual cycle. LE arm received oral Estradiol valerate 4 mg/day from 7days before expected menses to Day1 of menses. FA arm received Inj.Cetrorelix 0.25mg S.C from Day1 to Day5 of menses. The primary outcomes analysed were oocytes retrieved ,Follicular Output Rate(FORT), Follicle-to-Oocyte Index(FOI), Ovarian Sensitivity Index(OSI), maturation rate and MII /AFC. Secondary outcomes were cycle cancellation rates, fertilization rate, cleavage rate and blastulation rate. Main results and the role of chance There was a significant improvement in maturation rates with luteal phase pre-treatment using estradiol (LE) compared to follicular GnRH antagonist (FA) (0.72 ± 0.03 vs. 0.63 ± 0.03, p-value = 0.045). However, there were no statistically significant differences observed in the oocytes retrieved, Follicle-to-Oocyte Index (FOI), Follicular Output Rate (FORT), or Ovarian Sensitivity Index (OSI) between the two pre-treatment groups. These non-significant differences remained consistent among both expected (poseidon category 3 and 4) and unexpected (posiedon group 1 and 2) poor responders. Secondary outcomes, including cycle cancellation rates, fertilization rate, cleavage rate, and blastulation rate, did not show significant variations between the luteal estradiol (LE) and follicular GnRH antagonist (FA) pre-treatment groups. Subgroup analyses without endometriosis (N = 136) and severe male factor infertility (N = 122), revealed no significant differences between the two study groups in these specific subpopulations. Limitations, reasons for caution Limited generalizability due to small sample size, potential bias from lack of blinding, restricted insight into long-term outcomes, and patient heterogeneity are notable limitations in this study. Wider implications of the findings Among poor responders, luteal estradiol demonstrated a significant improvement in maturation rates, probably due to better follicle synchronicity at trigger, compared to follicular antagonist. It’s also more cost-effective and patient-friendly. However, further research with larger sample size and long-term clinical endpoints are needed to validate these findings and optimise clinical strategies. Trial registration number CTRI registration no. CTRI/2023/06/053760

P-680 Comparison of ovarian hyperstimulation syndrome (OHSS) rates resulting from conventional dosing versus personalized dosing of follitropin delta in ovarian stimulation, analysis of RITA, ESTHER-1 trials

Abstract Study question To compare OHSS rates with conventional dosage of follitropin delta in the RITA-1 and RITA-2 trials (hereafter ‘RITA’) to personalized dosing in the ESTHER-1 trial. Summary answer RITA and ESTHER-1 had similar efficacy and OHSS rates despite differences in dosing regimens, possibly due to differences in fresh transfer cancellation rates. What is known already Follitropin delta is a human cell-line derived follicle stimulating hormone whose fixed dosage in ovarian stimulation, personalized based upon body weight and serum anti-Müllerian hormone (AMH) and body weight, has been shown to be safe and effective in Gonadotrophin Releasing Hormone (GnRH) antagonist ovarian stimulation protocols. In the present trial, conventional dosing of follitropin delta allowing for dose revisions has been evaluated in GnRH antagonist ovarian stimulation protocols to demonstrate the broad utility of this gonadotrophin therapeutic and to address United States (US) regulatory considerations. Study design, size, duration RITA were randomized, double-blind, controlled, US multicentre trials of follitropin delta. The primary endpoint was cumulative ongoing pregnancy rate after fresh/frozen transfers within 12 months of cycle start. 1058 women 18-42 years randomized 10:1 to follitropin delta or placebo. ESTHER-1 was a randomized, European multicentre, assessor-blind, noninferiority trial of follitropin delta. The primary endpoints were fresh transfer ongoing pregnancy and implantation rates. 1329 women 18-40 years randomized 1:1 to follitropin delta or follitropin alfa. Participants/materials, setting, methods In RITA, 12 µg/day, 15 µg/day dosages were used for 4 days: 18-34 or 35-42 years, respectively, with 3 µg dose adjustments thereafter depending on response. Human chorionic gonadotropin (hCG) was used if < 20 follicles of ≥ 12 mm and estradiol level <3,000 pg/mL. Else, agonist trigger and fresh transfer cancellation; ≥20 oocytes retrieved also cancelled fresh transfer. In ESTHER-1, hCG was used if < 25 follicles of ≥ 12 mm. Else, agonist trigger, and fresh transfer cancellation. Main results and the role of chance The ongoing pregnancy rate per fresh transfer with follitropin delta was 41.9% in RITA and 36.3% in ESTHER-1. The primary efficacy endpoint was met for all 3 trials. Rates and severity defined by Golan criteria of OHSS observed in RITA and ESTHER-1 were similar, respectively for: all OHSS, any grade (3.1% versus 3.5%), Grade 1 (0.3% versus 0.5%), Grade 2 (0.8% versus 0.9%), Grade 3 (1.8% versus 1.1%), Grade 4 (0.2% versus 0.6%), and Grade 5 (0.1% versus 0.5%). The rate of early OHSS, defined as onset ≤9 days after trigger of final follicular maturation, was also similar, respectively for any grade (2.2% versus 2.6%), Grade 1 (0.3% versus 0.3%), Grade 2 (0.6% versus 0.9%), Grade 3 (1.1% versus 0.8%), Grade 4 (0.1% versus 0.3%) and Grade 5 (0.1 % versus 0.3%). However, the fresh transfer cancellation rate was >3x higher in RITA (35.2%) than in ESTHER-1 (11.1%). Limitations, reasons for caution Other reasons for transfer cancellation in all trials included adverse events or no blastocyst available for transfer; however, no significant differences were observed. A placebo comparator was selected for RITA to meet regulatory requirements for double-blinding; women with ≤3 oocytes retrieved were offered support for treatment outside of the trials. Wider implications of the findings Stimulation with follitropin delta is effective and associated with low rates of OHSS when used with either conventional or personalized dosing. However, stricter criteria for the use of hCG as trigger and allowance of fresh transfer may be required with conventional dosing to maintain this safety profile. Trial registration number NCT01956110, NCT03740737, NCT03738618

O-187 Real-word data on effectiveness of ICSI over conventional IVF according to infertility factors based on human fertilisation and embryology authority dataset

Abstract Study question Can the analysis of Human Fertilisation and Embryology Authority (HFEA) dataset provide real-word data on effectiveness of ICSI over conventional IVF according to infertility factors? Summary answer A statistically significant reduction in live birth rate was shown to be associated with ICSI use in cycles with female infertility factors. What is known already The adoption of ICSI has seen a considerable increase over the years, even in cases without an evident male-factor infertility. Available studies including large retrospective studies and meta-analyses evaluating the effectiveness of the two strategies tend to support the idea that in the absence of a male factor, ICSI does not offer a significant advantage over conventional IVF(cIVF). However, some uncertainties still exist regarding live birth rates and in relation to various infertility factors. Study design, size, duration Retrospective study of 275.825 first cycles treated with cIVF or ICSI between 2005-2018, included in the HFEA database. Infertility indications were simplified into three groups: 1) female only (endometriosis, tubal, ovulatory and cervical factors); 2) male (male only or with male and female factors together); 3) unexplained infertility. The primary outcome was live birth rate in the first fresh cycle. Secondary outcomes included fertilization, implantation, miscarriage rates, cycle cancellation rate and neonatal outcomes. Participants/materials, setting, methods Outcomes were evaluated through binomial logistic regression including the following predictors: female age, inseminated oocytes, number/stage of transferred embryos (condensed with principal component analysis), subtype of female infertility, year of treatment. A paired-analysis was also performed matching couples in a 1:1 ratio between ICSI and conventional IVF based on female age, indication, inseminated oocytes, year of treatment. Results were reported according to infertility cause using crude and adjusted Odds Ratios (OR) with 95%CI. Main results and the role of chance The study revealed a consistent balance in treatment distribution between conventional IVF and ICSI, with a slight increase in ICSI cycles in recent years. Based on logistic regression analysis, a significant reduction in live birth rate was demonstrated using ICSI compared to conventional IVF in cycles with female factors (adjusted OR = 0.95, 95%CI: 0.91-0.99). No significant differences emerged in unexplained factor cycles. With the use of conventional IVF, the overall odds of having a total fertilization failure increased by a factor of 1.84 (95%CI: 1.75-1.94). No significant differences in implantation rates between conventional VF and ICSI were seen after adjustment. The OR for male sex in newborns compared to female sex from single pregnancies was significantly influenced by ICSI use across the three groups of infertility causes and ranged between 0.84 and 0.87. The matched dataset confirmed a reduced occurrence of live birth per cycle in case of female factors (aOR=0.91, 95%CI: 0.86-0.96) and an overall significant lower proportion of cycles ending in cancellation for absence of viable embryos using ICSI compared to conventional IVF. Limitations, reasons for caution Some biases are intrinsic in the availability and quality of retrospective data obtained from registries and unmeasured confounders may influence the generalizability of the results. The study does not provide information on cumulative live birth rates. Wider implications of the findings ICSI introduces an additional, invasive step in assisted reproduction with a potential reduction in live birth rates for specific patients’ groups. These findings emphasize the importance of tailoring treatments to specific patient profile.The routine use of ICSI for all cases should not be considered an appropriate clinical practice. Trial registration number not applicable