Oocyte Donation Research Articles

P-690 Medroxyprogesterone acetate versus cetrotide in oocyte donation: Non-randomized clinical trial

Abstract Study question Is oral medroxiprogesterone acetate non-inferior compared to cetrotide with respect to the number of mature oocytes retrieved at ovum pick-up in oocyte donation (OD) cycles? Summary answer MPA is comparable to cetrotide in terms of number of mature oocytes (MII) retrieved at ovum pick-up (OPU) in oocyte donation cycles. What is known already Progesterone primed ovarian stimulation (PPOS) uses progestin as an alternative to a GnRH analog for suppressing a premature LH surge during the follicular phase. Published reports indicate that both the number of MII retrieved and pregnancy rates from these oocytes are comparable to protocols using GnRH analogues. Among new stimulation approaches to OD, the use of MPA taken orally has been used successfully, avoiding the need for injecting a GnRH analogue, allowing for more comfortable and cost-effective ovarian stimulation. Another advantage is that vitrification is avoided because the woman undergoing stimulation is not the recipient of the transfer. Study design, size, duration A prospective, non-randomized clinical trial including 23 oocyte donors was performed between February 2020 and February 2021 to evaluate the non-inferiority of MPA (10 mg/day) versus cetrotide (0.25 mg/day) from day 6, in ovarian stimulation cycles triggered with triptorelin acetate. Trigger criterion was ≥6 follicles with a diameter >18 mm Participants/materials, setting, methods All oocyte donors who came for the first time were included. Two OS were performed, the first with a fixed antagonist protocol (hMG and cetrotide), the second PPOS (hMG and MPA). Transvaginal ultrasound was performed, and serum estradiol levels were recorded during monitoring. The main outcome was the number of MII retrieved at OPU. Secondary outcomes were embryological laboratory outcomes and reproductive outcomes in recipients. Main results and the role of chance Basic characteristics, such as age and BMI were comparable, less than 12 months between one donation and another. Duration of stimulation was similar in both OS (10 days), as well as the total gonadotropin dose up to trigger (2544 IU in MPA and 2630 IU in cetrotide). The number of MII retrieved was no different: 11.9 (SD 2.9) with MPA and 10.9 (SD 3.8) in cetrotide (p = 0.5). Recipients and embryo transfer (ET) characteristics were also similar between groups. The mean number of MII assigned to each recipient was 9.2 (SD 2.8) in MPA and 8.2 (SD 3.09) in cetrotide (P = 0.58). MII were fertilized with partner sperm in 93% cycles overall and fertilization rate was 70% in MPA versus 69% in cetrotide (P = 0.61). The number of D5 blastocysts was 4 (SD 2.9) in MPA and 3.56 (SD 2.6) in cetrotide. Overall, there was 99% of double ET and 1% of single ET, with 93.2% of ETs were performed in D5. No significant difference was found in the clinical pregnancy rate 55.3% versus 54.5% (P = 0.785); ongoing pregnancy rate 55.3% versus 50.9% (P = 0.419) and live birth rate 51.1%versus 45.5%, (P = 0.255). Limitations, reasons for caution The patients and physician were not blinded to the study. Further, a large proportion of patients were still pregnant at the end of the clinical trial, therefore live birth rates were not observed in the follow-up period. Wider implications of the findings Ovarian stimulation using MPA for LH surge prevention produces a comparable number of MII oocytes, fertilization rates and live birth rate compared to cetrotide in oocyte donation cycles with the advantage of being a more comfortable and cost-effective ovarian stimulation. Trial registration number Not applicable

P-087 Obstetrical and perinatal outcomes from intracytoplasmic sperm injection couples with oocyte donation are not affected by advanced paternal age measured as a continuous variable

Abstract Study question Does paternal age (PA), considered a continuous variable, have any effect on obstetrical and perinatal outcomes in intracytoplasmic sperm injection (ICSI) with donated oocytes? Summary answer PA does not affect clinically relevant obstetrical and perinatal outcomes, but it significantly increases the pregnancy’s duration in ICSI with autologous sperm and donated oocytes. What is known already Currently there has been an evident delay in childbearing, therefore studies relating advanced PA with reproductive risks are increasing and results are controversial. These studies frequently study PA by dividing it in groups arbitrarily constructed, but probably a more precise evaluation is obtained using PA as a continuous variable. Furthermore, oocyte donation standardizes female factor, to some extent, allowing a more realistic male factor evaluation. In this regard, we aimed to evaluate the effect of PA at conception (continuous variable) on obstetrical and perinatal outcomes in ICSI couples with autologous sperm and donated oocytes in a large population of patients. Study design, size, duration This retrospective observational multicentric cohort study evaluated data from couples that performed an ICSI between January 2008 and March 2020 using autologous sperm and donated oocytes. We included only singleton deliveries and the first delivery of each couple. PA was analysed as a continuous variable, considered more informative in comparison to its analysis as categorical. Data available and included consisted of 15,696 patients who had a delivery with or without a live birth. Participants/materials, setting, methods PA ranged from 21-54 years. Clinical database was constructed with reproductive outcomes from electronic medical records. Erroneous or incomplete data were removed. Statistical analysis included a descriptive analysis, followed by univariate and multivariate models using binary logistic regression or linear regression. We adjusted for maternal age and body mass index, PA, fresh sperm concentration and progressive motility, cycle type, gestational age, transfer on day 5 and delivery type (when appropriate). P < 0.05 was considered statistically significant. Main results and the role of chance Mean PA was 41.45 (41.38-41.51). We included a total of 15,696 deliveries and 15,673 live births. Results from multivariate models are presented as adjusted odd ratio or regression coefficient with 95% confidence intervals and adjusted p. In terms of obstetrical outcomes, PA results were 1.086 (0.959-1.229) p = 0.194 for gestational diabetes, 0.963 (0.849-1.093) p = 0.561 for anemia, 0.947 (0.837-1.072) p = 0.388 for hypertension, 0.959 (0.878-1.048) p = 0.356 for preterm birth and 0.986 (0.929-1.046) p = 0.641 for caesarean delivery. Regarding perinatal outcomes, PA results were 0.442 (0.005-0.879) p = 0.047 for gestational age, -0.216 (-15.559-15.126) p = 0.978 for infant weight, 1.101 (0.941-1.288) p = 0.231 for low birth weight (<2,500 g), 0.710 (0.463-1.088) p = 0.116 for very low birth weight (<1,500g), 0.988 (0.933-1.047) p = 0.684 for female sex, 0.002 (-0.076-0.08) p = 0.96 for length, -0.012 (-0.088-0.064) p = 0.763 for cranial perimeter, 0.991 (0.876-1.12) p = 0.88 for NICU admission, and 0.027 (-0.028-0.083) p = 0.337, 0.025 (-0.012-0.061) p = 0.18 and -0.045 (-0.096-0.007) p = 0.089 for Apgar 1, 5 and 10 minutes, respectively. According to our results, PA does not affect clinically relevant outcomes for the health during pregnancy and of the infant. However, PA significantly increases the duration of the pregnancy in ICSI with autologous sperm and donated oocytes. Limitations, reasons for caution The study’s major strengths are the consideration of PA as a continuous variable, the use of oocyte donation (controlling female factors) and the inclusion of a huge sample size. However, due to its retrospective nature there are some biases derived from the clinical practice and the presence of missing data. Wider implications of the findings Current evident delay in childbearing merits further research on the effect of PA on reproductive outcomes, addressed in this study. Our study suggests that PA is not associated with obstetrical and perinatal outcomes, except for gestational age, which sends a hopeful message to fathers of advanced paternal age. Trial registration number not applicable

P-510 The impact of the severe male factor in the egg donation cycles using preimplantation genetic test for aneuploidy

Abstract Study question Does severe male factor affect the euploidy rate and IVF outcomes in donor egg ICSI cycles using PGT-A? Summary answer Severe male factor affects the euploidy rate in egg donation cycles, however, no statistical differences were reported in live birth and cumulative live birth rate. What is known already Around 50% of couples seeking fertility treatment have male-factor infertility. Intracytoplasmic sperm injection (ICSI) relies on evaluating sperm morphology, but the direct relationship between semen quality and embryonic potential remains unclear. Evidence indicates that poor semen characteristics correlate with an increase in aneuploidy rate of spermatozoa. Therefore, pregenetic testing for aneuploidies (PGT-A) is recommended in cases of male factor infertility. The relationship between aneuploidy rates and abnormal sperm remains a debated topic. The use of the egg donation model offers a valuable chance to isolate the male-related factor and evaluate its influence on the occurrence of embryonic aneuploidies. Study design, size, duration This is a retrospective, observational, cohort study including all European IVI clinics. The study included egg donation cycles using pre-implantation genetic testing for aneuploidies (PGT-A) generated in IVI clinics from January 2017 until December 2023. 690 egg donation cycles were included in the study, N = 202 in the group with sperm < 5mil/ml, N = 102 in the sperm group with 5-15 mil/ml and N = 386 in the group with sperm >15 mil/ml. Participants/materials, setting, methods The study included women between 30-49 years undergoing egg-donor cycles, using fresh/frozen sperm Sperm samples were derived after 2-5 days of abstinence. The cycles of egg donation were divided into three groups according to sperm concentration, severe oligozoospermia (SO, < 5mil/ml), moderate oligozoospermia (MO, between 5-15 mil/ml), and control group(>15 mil/ml). Trophectoderm biopsy was performed on day 5 or 6 and subsequent analysis used the next sequencing generation (NGS). Single euploid blastocyst transfers were included. Main results and the role of chance The fertilization rate was decreased in SO (73.33 ± 16.19) than in the MO group (79.07 ±12.45) and control group (77.80 ±14.72) p = 0.0047. The number of blastocysts was higher in the control (5.80 ± 2.72) and MO (5.97± 2.78) than in the SO group (4.99 ± 2.40), p = <0.001. The number of euploid blastocysts was decreased in SO (3.21 ± 2.07) than in the control (4.09 ± 2.41) and MO group (4.05 ± 2.15), p = <0.001. The euploidy rate of SO decreased (63.32 ±26.39) compared to the control (69.67 ± 25.08) and MO group (68.55 ± 20.37), p = 0.012. The logistic regression model included possible confounders (male age, age donor, male BMI, sperm motility, sperm morphology and sperm concentration) that showed no effect on the euploidy rate. The pregnancy rate was similar across the groups 69.77% vs 66.05% vs 66.23%, p = 0.54. No statistical differences were reported for the clinical pregnancy rate 62.79% vs 61.73% vs 58.40%, p = 0.44, and the live birth rate 62.79% vs 61.73% vs 58.40%, p = 0.44. 48.05 vs 46.38% vs 42.64%, p = 0.37. No differences were reported in the miscarriage rate (p = 0.37) and CLBR (p = 0.26). Limitations, reasons for caution The retrospective nature of the study and the sample size represent the principal limitations of the study. The clinical reason for severe male factors was not considered in the study. Wider implications of the findings SO affects the quality affect the early embryonic potential through an increase in aneuploidy, despite no clinical effects.The use of PGT-A in case of severe male factor remains not justified in the egg donation.Future prospective multi-center studies are needed to highlight the effect of sperm quality on early embryonic potential. 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

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-607 Reproductive outcomes of oocyte donors using subdermal etonogestrel implants and levonorgestrel intrauterine devices

Abstract Study question Does the use of progesterone contraceptive devices during controlled ovarian stimulation (COS) affect ovarian response in oocyte donation cycles? Summary answer Progesterone contraceptive devices during COS did not impact ovarian response, measured by oocyte retrieval and maturity rates, in oocyte donation cycles. What is known already Subdermal etonogestrel implants and levonorgestrel intrauterine devices (L-DIU) are widely used contraceptives amongst oocyte donors. While the safe and effective use of L-DIU during COS has been documented, the impact of subdermal etonogestrel implants on ovarian response is less understood. Given their distinct mechanisms of action and varying local and systemic pharmacodynamics, a comprehensive understanding of the impact of these contraceptives on ovarian response during COS will be crucial for guiding informed clinical practice. Study design, size, duration In this retrospective cohort study, we analyzed 3,452 heterologous ICSI cycles from 1,975 oocyte donors (18-35 years), performed between March 2021 and September 2023, across two centers. We identified 40 COS in donors using contraceptive devices, either a subdermal etonogestrel implant (n = 18) or L-DIU, (n = 22). These were matched with 80 COS without a device. We primarily compared ovarian response amongst the two groups. Secondary outcomes included biochemical pregnancy, clinical pregnancy and live birth rates. Participants/materials, setting, methods We applied a propensity matching score model (PsmPy package, Python), trained on 3,388 oocyte donation cycles, for matching donors with and without contraceptive devices. Matching was based on age, BMI, anti-müllerian hormone (AMH) and antral follicle count (AFC), maintaining a 1:2 ratio. Ovarian response outcomes (oocyte retrieval and maturation rates) were analyzed using Student’s t-tests, while and clinical outcomes were evaluated using Fisher’s exact test. P-values <0.05 were considered significant. Main results and the role of chance Mean age was 26.22, BMI 24.7, AMH 2.63 ng/ml and AFC 18.77. We evaluated a total of 120 COS, leading to 176 heterologous ICSI cycles. The oocyte retrieval rate (total number of cumulus-oocyte-complexes (COCs) per total number of follicles > 14mm at final follicular scan), averaged 109.64%. We observed no differences in the number of COCs retrieved from donors with and without contraceptive devices (17.5 ±7.6 and 18.5 ± 9.6, respectively). Similarly, oocyte maturation rates (total number of MII oocytes per total number of COCs), were comparable amongst the two groups (78.6% overall, 77.6% with contraception device and 79.1% without contraception device, p > 0.05). The presence of the device did not affect biochemical pregnancy (69.7% with contraceptive device, 61.1% without contraceptive device, p > 0.05), clinical pregnancy (54.6% with contraceptive device, 52.9% with contraceptive device, p > 0.05) and ongoing pregnancy (36.4% with contraceptive device, 35.3% without contraceptive device). These results were consistent regardless of the type of device used. Limitations, reasons for caution The main limitation is the retrospective nature of the study, potentially influencing causal inferences, and that both devices were analyzed as one same group. The small subset of COS with contraceptive devices may impact statistical power. Perinatal outcomes were not analyzed. Wider implications of the findings This research provides clinicians with reassurance that the use of progesterone contraceptive devices during COS does not adversely affect clinical outcomes. These findings offer valuable insights for patient counseling, affirming the safety of contraceptive methods and encouraging further research for a more comprehensive understanding in diverse populations and clinical settings. Trial registration number not applicable

O-302 Feasibility and efficacy of a flexible and simplified ovarian stimulation protocol for oocyte donors, combining random-start corifollitropin alpha and progestin primed ovarian stimulation protocol (PPOS)

Abstract Study question Is the total number of retrieved oocytes in donors equivalent, according to the onset phase of stimulation with corifollitropin alpha in a random-start PPOS protocol? Summary answer The total number of retrieved and mature oocytes were not different after starting stimulation in the early, mid or late follicular or luteal phases. What is known already Recent studies have shown the ability to obtain oocytes of equivalent quality after follicular or luteal phase ovarian stimulation and have also demonstrated the efficacy and safety of the PPOS protocol in oocytes donors. In order to provide a more friendly, simplified and flexible ovarian stimulation protocol reducing the burden for donors, we studied the impact on oocyte yield of combining a random start corifollitropin alpha stimulation with the concomitant prevention of premature LH surge by progestin administration. Study design, size, duration This multicenter open-labelled RCT was performed in 4 oocytes donation centers from July 2020 to September 2023 to assess the equivalence in terms of number of retrieved oocytes of a delayed onset of corifollitropin alpha stimulation with concomitant administration of desogestrel in Mid Follicular Phase (MFP/D4-D7 of the natural cycle), Late Follicular Phase (LFP/D8-D11), Ovulatory Phase (OP/D12-D15) or Luteal Phase (LP/D16-D30) compared to the standard start in Early Follicular Phase (EFP/D1-D3). Participants/materials, setting, methods From 110 randomized oocyte donors,102 reached triggering of ovulation with triptoreline acetate and OPU : EFP n = 22, MFP n = 20, LFP n = 19, OP n = 18 and LP n = 23. The sample size was calculated to show an equivalence between groups in total number of retrieved oocytes. Secondary endpoints were the number of mature oocytes, premature LH surge and Ovarian Hyperstimulation Syndrome rates. Differences were tested using a ANOVA test or a Pearson’s Chi2 test, as appropriate. Main results and the role of chance Donors were 33 [29.2-35.0] years old [95% Confidence interval] with a mean BMI of 23.4 [21.1-26.3] kg/m2. The mean number (SD) of retrieved oocytes was 14.2 (9.1). In intention to treat analysis, there was no significant difference between the 5 groups, regarding the total number of retrieved oocytes. The mean numbers of retrieved oocytes from the 5 groups were 12.5 (7.7), 13.2 (8.0), 15.7(9.8), 17.8 (11.4), and 12.8(8.3), respectively in the EPF group, the MPF group, the LPF group, the OP group and the FP group, with no significant differences between the groups (p = 0.30). The mean (SD) number of mature oocytes was 11.8 (7.6) with no significant differences between the 5 groups. Only one premature LH surge was reported in the MFP group (0.98%). Four minor to moderate OHSS were reported (3.9%). Limitations, reasons for caution The main limitation of our study is the small sample size responsible for a lack of power. But to our knowledge, this is the first RCT to compare the number of oocytes retrieved, according to the onset phase of ovarian stimulation in a random-start PPOS protocol, for oocyte donors. Wider implications of the findings The proportion of ovarian stimulation cycles with freeze-all is constantly increasing worldwide. Therefore simplified, ultra-flexible ovarian stimulation protocols could be proposed to maintain the spread of the workload along the working days without programming, with fewer injections and reduced burden for patients, with the same efficacy. Trial registration number NCT03895099

P-167 The sperm parameters in doubling oocytes by the 1st polar body transfer technique: does it matter?

Abstract Study question Does sperm parameters affect the effectiveness of the 1st polar body (PB) transfer in oocytes and embryo doubling? Summary answer Certain sperm conditions affect the transfer technique efficiency. What is known already Previous studies have shown the effectiveness of the 1st polar body (PB) transfer. The technique allows for the modification of donor oocytes to increase the number of cells suitable for fertilization and at the same time preserve the genetic relatedness to the patient. We established that the effectiveness depends on the morphology of the 1stPB. We also showed that the yield of high-quality blastocysts does not depend on whether fresh or thawed donor oocytes are used. But it is also important to understand whether sperm parameters have a significant effect on the performance of the technique. Study design, size, duration The study was performed in the Medical Center IGR from December 2017 to December 2023 and involved 93 patients (mean age 39.7±5.4 years) who underwent the 1st PB transfer and had indicated sperm parameters used for fertilization, including: normozoospermia (NS, n = 43), asthenozoospermia (AS, n = 24), asthenoteratozoospermia (ATS, n = 20), oligozoospermia (OS, n = 5), cryptozoospermia (CS, n = 1). We evaluated the pronuclear scoring, number of embryos on the 3rd and the 5th post-fertilization day, euploidy according to sperm conditions. Participants/materials, setting, methods We used donor oocytes, patients’ oocytes and their 1stPBs obtained from 93 women and their partners sperm with defined parameters in accordance with WHO norms for 2021. The procedure of donor oocyte enucleation and the 1stPBs transfers was carried out using Nikon Ti Eclipse(Japan) inverted microscope, Saturn 3 laser console(UK). Preimplantation genetic testing for aneuploidy was performed using trophectoderm biopsy. Samples were diagnosed using Ion S5(USA). Statistical analysis was carried out using Chi-square test. Main results and the role of chance The total number of donor oocytes modified by the 1stPB of patient’ oocytes was 364, which were distributed as follows by sperm status: NS - 159 oocytes, AS - 103 oocytes, ATS - 77 oocytes, OS - 19 oocytes, and CS - 6 oocytes. The mean age of the female patients according to the groups was similar (39.6±4.9, 39.8±6.2, 40.0±3.8, 37.8±6.1,40, respectively). The number of 2PN pattern during pronuclear scoring was distributed among groups (NS:AS:ATS:OS:CS) with the following percentages 69.2:65.1:62.3:73.7:66.7, respectively. Among the developing embryos on the 3rdday the distribution was 46.6:46.5:36.4:57.9, respectively. No viable embryos were formed in the CS group, so the group was not included in further calculations. Statistically significant difference (SSD) was not found between the groups on the above-mentioned stages of development (p0.05). On the 5thday the number of developing embryos (percents) was distributed as follows: 23.3:28.2:11.7:31.6 for NS:AS:ATS:OS, respectively. It is worth noting that SSD was found between NS and ATS, OS and ATS groups (p < 0.05) and AS and ATS groups (p < 0.001). Percentage of euploid embryos relative to the number of examined blastocysts from groups NS:AS:ATS was 30.8:23.1:22.2, respectively, SSD wasn’t found between the groups(p > 0.05). Limitations, reasons for caution To increase performance of the 1st PB transfer technique it is also worth considering such parameters as sperm DNA fragmentation and level of sperm oxidative stress, which reflect the chromatin state of the male gamete. Wider implications of the findings The study showed that among patients with asthenoteratozoospermia, the yield of viable embryos was significantly lower compared to the other sperm conditions studied. This fact must be taken into account when predicting the result of using the 1st PB transfer technique. Trial registration number N/A

P-728 Age limits in medically assisted reproduction: Assessing clinical and pregnancy outcomes in women over 50 years of age undergoing donor oocyte in vitro fertilization

Abstract Study question Is pregnancy in women over 50 years of age undergoing donor oocyte IVF associated with adverse clinical and pregnancy outcomes? Summary answer In vitro fertilization treatment in women over 50 years of age using donor oocytes is not associated with adverse clinical and pregnancy outcomes. What is known already In vitro fertilization with donor oocytes (d-IVF) has become a common strategy for managing cases of very advanced maternal age. However, there is ongoing scientific debate entailing legal and societal implications regarding the age limit beyond which d-IVF should no longer be considered safe. Different age limits and guidelines have been proposed, with no globally accepted consensus. The most commonly reported age limit is 50 years, representing the median age of menopause. However, there is a lack of robust data to support that d-IVF beyond the age of 50 is associated with adverse clinical and pregnancy outcomes. Study design, size, duration A retrospective single-centre study was conducted to evaluate medical records of d-IVF cycles between July 2021-January 2023. A total of 575 medical records of women undergoing d-IVF were analyzed. The study population was divided into two groups based on maternal age: women aged 45-49 years (group A, n = 318) and women aged 50-54 years (group B, n = 257). The outcome measures were positive-hCG, clinical pregnancy, viable pregnancy at 12 weeks of gestation, pregnancy loss and live birth. Participants/materials, setting, methods For oocyte recipients advanced maternal age was the sole infertility etiology and endometrial preparation was performed employing conventional protocols. Oocyte donors were up to 35 years of age and oocyte donation cycles were performed according to national guidelines. Single or double embryo transfers (ETs) were performed at the cleavage or blastocyst stage. Embryo quality assessment was performed according to Veeck and Gardner grading systems. Statistical analysis was performed employing R Programming Language for Statistical Purposes. Main results and the role of chance The mean age of group A was 47.02 ± 1.35 while the mean age of group B was 51.84 ± 1.59. No statistically significant difference was observed regarding the age of oocyte donors (25.17 ± 4.18 vs 26.09 ± 4.13; p-value=0.26). Considering embryo transfer, 90 cleavage stage and 228 blastocyst stage transfers were performed in group A, and 75 cleavage stage and 182 blastocyst stage transfers were performed in group B (p-value=0.23). No statistically significant difference was observed between the two groups with regards to the number of transferred embryos (1.89 ± 0.35 vs 1.90 ± 0.36; p-value=0.69) and embryo quality (Group A: Good 157, Fair 143, Poor: 18; Group B: Good 121, Fair 117; Poor 19; p-value=0.66). Considering clinical and pregnancy outcomes no statistically significant difference was observed between the two groups regarding positive hCG rate (147/318 vs 109/257, respectively; RR: 0.91; 95%CI: 0.76-1.10; p-value=0.36), clinical pregnancy rate (129/318 vs 98/257, respectively; RR: 0.94; 95%CI: 0.77-1.15; p-value=0.55), viable pregnancy rate at 12 weeks of gestation (96/318 vs 70/257, respectively; RR: 0.90; 95%CI: 0.70-1.17; p-value=0.44), pregnancy loss rate (39/129 vs 33/98, respectively; RR: 1.13; 95%CI: 0.76-1.63; p-value=0.58) and live-birth rate (90/318 vs 65/257, respectively; RR: 0.91; 95%CI: 0.68-1.17; p-value=0.42). Limitations, reasons for caution The retrospective and the single-centre nature of the study are important reasons for caution. In addition, the relatively small sample size may serve as another limitation. The lack of neonatal outcomes may also be considered an additional limitation when interpreting data on the safety of d-IVF in the over-50s. Wider implications of the findings Women over 50 who undergo d-IVF are not at increased risk of complications. This highlights the need to reconsider age limits and provide robust evidence ascertaining both safety and reproductive autonomy. Studies are needed to assess neonatal outcomes and maternal age impact on long-term infant health from an epigenetic standpoint. Trial registration number Not applicable

P-478 Investigating the attitudes, beliefs and motivations of egg donors, recipients and egg sharers

Abstract Study question What are the attitudes, motivations and experiences of egg donors, sharers and recipients in the United Kingdom? Summary answer Participants’ experiences were generally very positive, but also diverse and nuanced. What is known already Most studies on egg-sharers are based on quantitative surveys rather than explorative interviews, precluding a more nuanced understanding of insights. A study found that 54% of egg-sharers would have donated their oocytes regardless of their ability to afford their own treatment. Another study demonstrated that around half of egg-sharers believed that the child’s parents should decide whether to disclose the nature of the conception to their children, while the other half believed in the offspring’s right to knowledge. These studies demonstrate the divided nature of certain topics and the need for a deeper exploration. Study design, size, duration Participants who consented to research were recruited via email to participate in exploratory, semi-structured interviews. The interviews were transcribed and analysed via thematic analysis. Braun and Clarke highlighted various analytical approaches to consider when writing a thematic analysis. For this paper, an ‘inductive’ analytical framework was chosen, in which themes were grounded strongly in data. This minimised the influence of researchers’ epistemological preconceptions on the analysis. Participants/materials, setting, methods Participants were recruited from Lister Fertility Clinic London, one of the largest private IVF clinics in UK. These patients had begun their treatment with Lister Fertility Clinic after 2019, thus minimising recall bias. After holding the initial set of interviews, the team then decided whether theoretical saturation was reached. Interviews were conducted with a total of 22 patients, half of whom were egg-donors/-sharers and half of whom were egg-recipients. Main results and the role of chance The first theme explored two negative emotions amongst egg-recipients — grief and tension. Most women, while feeling overwhelming love for their children, all shared strategies they adopted to establish strong maternal ownership of their child. The loss associated with infertility dealt a severe emotional blow to many women, especially when they foresaw having biological children as a virtually guaranteed part of their future. Nonetheless, as participants grappled with the grieving process, feelings of acceptance gradually emerged. All egg-recipients believed that it was their child’s right to contact their biological parents. However, a few participants admitted feeling reluctant about a potential connection between their child and their biological mother, due to fears that the new mother-figure may threaten the exclusivity of the child-to-mother bond. The next theme explored participants’ motivations and their in-clinic experiences. All interviewees cited altruism as an important motivating factor. The final theme focused on reciprocal donor-/sharer-recipient thoughts. Amongst the egg-donors and -sharers, none of the participants minded who their eggs were received by, regardless of demographics. A few stressed the importance of good parenting behaviour over any superficial characteristics in determining a potential parent’s merit. Limitations, reasons for caution Future investigation into assisted donor-conception experiences in diverse family systems (eg. gay males and surrogate families) and the use of a prospective study design to minimise selection bias would enrich this study’s promising findings. Wider implications of the findings The Human Fertilisation and Embryology Authority decided not to ban egg-donation or -sharing. Some ethicists responded with concern that subsidies still form a financial incentive, compromising the validity of consent. This study provides support to HFEA by demonstrating that reciprocity, rather than exploitation, is the more likely principal driver. Trial registration number Not applicable

P-281 Surgery and IVF for diagnosed ovarian endometriosis and deep infiltrative endometriosis

Abstract Study question To evaluate the effectiveness of surgical treatment of endometrioid cysts and deep infiltrative endometriosis before an IVF program Summary answer Laparoscopic excision of deep infiltrative endometriosis has a positive effect on the reproductive function of women What is known already One of the most severe and aggressive manifestations of endometriosis is deep infiltrative endometriosis. Endometriosis is a socially significant disease that reduces a woman’s quality of life and affects reproductive health. Women with endometriosis often experience severe menstrual and non-menstrual pain affecting the lower abdomen, pelvis or lumbosacral region, profound dyspareunia, dyschezia and dysuria (Uimari et al., 2021) and infertility in 30–50% of cases (Prescott et al.., 2016). Patients with endometriosis suffer from chronic fatigue (Ramin-Wright et al., 2018) and have a higher risk of mental health problems (56.4%) than patients without endometriosis (43.6%) (Pope et al., 2015) Study design, size, duration The our institute is conducting a controlled, non-randomized, retro- and prospective study on genital endometriosis. The study period is from 2012 to the present. Participants/materials, setting, methods The study included 450 women with deep infiltrating endometriosis in combination with infertility All patients were divided into 4 groups Group 1 – 128 patients with deep infiltrative endometriosis, sent for IVF without surgery Group 2 – 297 patients with deep infiltrative endometriosis, initially referred for surgery Group 2a – 156 patients with ovarian cysts, sent for preliminary collection of eggs before surgery Group 2c – 141 patients with ovarian cysts, referred for surgery without prior egg retrieval Main results and the role of chance In group 1, the number of pregnancies occurred was 65.6% (84 women), in group 2a - 71.7% (112 women), in group 2 - 53.9% (76 women). Pregnancy occurred spontaneously in 18 (4.2%) women from group 2 after surgery. In group 2, four women, after three unsuccessful attempts at in vitro fertilization, became pregnant after using donor eggs - the results were excluded from the final pregnancy calculations. In terms of pregnancy, IVF with preliminary surgery (Me: 2.10; Q1-Q-3:0) had a statistically significant advantage compared to IVF without surgery (Me: 5.00; Q1-Q-3:0), and IVF with surgery without egg retrieval (Me:3.0; Q1-Q-3:0). The lowest statistically significant pregnancy rate was recorded during laparoscopic surgery without prior egg retrieval (Me: 6.95; Q1-Q-3:1). When performing a post-hoc analysis, a statistically significant shorter pregnancy time was also found when performing IVF with preliminary laparoscopy and egg freezing: group 1 (M: 126.25; SD111.1), group 2a (M: 79.97; SD: 19.785 ), group 2c (M: 130.50; SD: 82.149) (p = 0.000). During the period of observation of women for twelve years after surgery, 93% of patients noted an improvement in the quality of life and 63.7% of women on average achieved reproductive function after the IVF program for endometriosis. Limitations, reasons for caution no restrictions Wider implications of the findings The results of the IVF program for deep infiltrative endometriosis are statistically higher after surgery, but with preliminary cryopreservation of oocytes. The question of radical resection of the rectum in comparison with shaving when planning an IVF program remains open, which forms the planning of further research in this area. Trial registration number not applicable

P-246 Use of image recognition to quantify oocyte quality improved the accuracy of prediction of blastulation by 26-48%

Abstract Study question Can an AI oocyte quality model improve blastulation prediction accuracy? Summary answer An AI oocyte quality model presented an overall accuracy of 61-74%. Exhibiting an improvement of 26-48% for prediction of blastulation over random. What is known already Nowadays, the assessment of whether sufficient oocytes have been cryopreserved is purely based on patient age and number of oocytes collected. No morphological abnormalities provide quantitative guidance about the reproductive potential of the oocyte. Additionally, interobserver agreement and prediction of blastulation by experienced embryologists has been reported to be worse than chance (Behr et al., 2018). Therefore, there is a need to implement oocyte quality assessment tools to predict blastulation in oocyte donation, cryopreservation programs and IVF treatments. Study design, size, duration A retrospective study using an AI oocyte quality score (CHLOE-OQ, Fairtility Ltd) was performed in three private clinics evaluating 1749 oocytes that were inseminated with ICSI and cultured between October 2019 and December 2021. Overall and per clinic analysis were conducted (Clinic 1 n = 1131; Clinic 2 n = 576; Clinic 3: n = 42). Participants/materials, setting, methods An AI model provided an oocyte quality (OQ) score to assess prediction of blastulation, measured by binary logistic regression (AUC) per clinic and overall. The correlation between the OQ score and blastulation was measured using t-test. OQ score was classified into groups, Group A: 0.9-1.0, Group B: 0.7-0.9, Group C: 0.4-0.7 and Group D: 0-0.4. Blastulation rate was assessed in each OQ score subgroup using chi-square. Main results and the role of chance OQ score prediction of blastulation presented an overall accuracy of 63% (1107/1749). Accuracy per clinic ranged from 61-74%, Clinic 1: 61% (690/1131), Clinic 2: 67% (386/576) and Clinic 3: 74% (31/42). Exhibiting an improvement of 24-48% for prediction of blastulation over random. Oocyte quality score was predictive of blastulation per clinic and overall Clinic 1: AUC 0.62, n = 1130; Clinic 2: AUC 0.62, n = 575; Clinic 3: AUC 0.78, n = 41; Overall: AUC=0.62, p < 0.001, n = 1749). Overall blastocyst development rate was 53% (929/1749). OQ score was higher in oocytes that blastulated than those that did not blastulate (0.85 ± 0.14 vs 0.74 ± 0.2, p < 0.001). There was a significant direct association between OQ score subgroups and blastulation rate. Group A with the highest score subgroup had the highest blastulation rate [61% (554/903), p < 0.05]. The blastulation rates for Group B [53% (283/539) p < 0.001], Group C [38%, (71/188), p < 0.001] and Group D [18% (21/119), p < 0.001] were decreasingly lower. Limitations, reasons for caution This study was done in 3 centers in the same country. Therefore, further studies should focus on diversifying in terms of geographical location to address generalization of this AI assessment. Further studies should focus on comparing the efficacy of blastulation prediction by humans. Wider implications of the findings Using AI to do an objective oocyte assessment aids clinicians in determining the optimal time to transition to oocyte donor programs. It assists the decision-making for oocyte banking, minimizing unnecessary cycles and guiding timely additional oocyte collections. This approach at the point of cryopreservation, mitigates risks associated with delayed decisions. Trial registration number N/A

P-725 Automated follicular tracking with three-dimensional ultrasound and SonoAVC saves costs: debunking myths

Abstract Study question What is the incremental cost per patient and the budgetary impact of the SonoAVCTMfollicle technique compared to two-dimensional ultrasound in a private assisted reproduction center? Summary answer Our results support the implementation of follicular tracking with 3D ultrasound and SonoAVCTM from an economic point of view. What is known already Advantages of follicular tracking with 3D US and SonoAVC include increased precision and reproducibility, increased patient comfort, decreased ultrasonographer’s time and improved workflow. The main benefit of SonoAVC is that it allows quick measurements of follicular volume, which has been shown to be more precise than 2D diameters for estimation of follicular size. Until now, it has been assumed that 3D ultrasound represents an increase in costs, this being the main justification of professionals who refuse to implement it. Study design, size, duration Cost study and economic analysis. The costs associated with the adoption of the SonoAVC™follicle software and the 2D ultrasound were estimated as well as the cost of medical dedication time. Since the cost of the equipment represents an initial investment, we proceeded to annualize it. For the economic analysis we calculated a) cost for each patient included in the study and b) total annual cost for a private center to incorporate the SonoAVC™follicle program. Participants/materials, setting, methods Population: patients treated in our center in 2019 (N = 295). Budget impact analysis was performed from the perspective of a private assisted reproduction center with a 5-year time horizon. The analysis was adapted to three scenarios according to the size of the center: a private center with: a) 600 cycles/year including IVF/ICSI and oocyte donation b) 300 cycles/year and c) 100 cycles/year. Main results and the role of chance Equivalent annual cost of the ultrasound device and transvaginal probe after annualization was 3985.93 € for 2D and 4572.10 € for 3D. The corresponding cost per patient/cycle was 13,51€ for 2D and 15,50 € 3D. Medical dedication time cost was 5,6 € for 2D follicular monitoring and 3,3 € for 3D follicular monitoring. Total cost per patient/cycle for follicular monitoring, including hardware and medical dedication was 69,5€ for 2D and 48,5€ for 3D ultrasound. For the budget impact analysis, three different sizes of centers were considered: 600, 300 and 100 cycles/year. In all of them there was a saving with 3D ultrasound of 2101 €, 6303 € and 12606 € respectively. The net budgetary impact over 5 years, i.e., the difference between the current scenario (2D ultrasound) and the new scenario (3D ultrasound with SonoAVC™follicle) for a center with approximately 300 cycles/year, would be 31.515€. Therefore, the implementation of the new technique with SonoAVC™follicle would save costs. Limitations, reasons for caution In centers 600 cycles/year an extra ultrasound device may be included in the analysis. Wider implications of the findings Follicular monitoring with 3D ultrasound is cheaper than 2D ultrasound even in small centers and this saving is greater the larger the center is. Therefore, our results demonstrate that cost savings are another added advantage of follicular monitoring with 3D ultrasound and sonoAVC. Trial registration number not applicable

P-803 Intra-ovarian injection of plasma rich in stem cell-secreted and platelet-enclosed factors to promote follicle rescue and reproductive outcomes in women with very low ovarian reserve

Abstract Study question Could intraovarian injection of plasma rich in stem-cell and platelet growth factors optimize ovarian reserve and IVF outcomes in women with very low ovarian reserve? Summary answer Intraovarian injection of G-CSF mobilized plasma rich in grown factors improved follicle count since first follow-up and led to better fecundation, implantation and pregnancy’ rates. What is known already Autologous stem cell ovarian transplantation (ASCOT) of bone marrow derived stem cells optimized ovarian reserve and reproductive outcomes in poor responders (POR) and this effect seems to be due to the growth factors secreted by the stem cells, acting through paracrine pathways. Similarly, platelet-rich Plasma (PRP) has been also offered to promote ovarian reactivation in patients with impaired ovarian reserve by providing positive growth factors contained in platelets. Indeed, a technique that combines both the non-cellular components of ASCOT and PRP (ASCOT-1) has been proposed to optimize follicle rescue and IVF outcomes in women with very low reproductive prognosis. Study design, size, duration Retrospective observational study with 159 women (≤ 45 years) diagnosed with POR and primary ovarian insufficiency (POI) according to ESHRE criteria, who underwent the ASCOT-1 technique after refusing oocyte donation, between June 2021-October 2023 at IVIRMA Alicante, Spain (IRB approval 2310-FIVI-188-SH). The ASCOT-1 consisted in the intraovarian injection of plasma rich in both stem cell-secreted and platelet-enclosed factors obtained after granulocyte colony stimulating factor (G-CSF) mobilization and PRP obtention (Endoret Kit BTI, Biotechnology institute). Participants/materials, setting, methods Medical records of patients who underwent the ASCOT-1 as an ovarian reactivation treatment were examined. Follow up of AFC and AMH was carried out for a maximum of 4 menstrual cycles to evaluate follicular activation. Moreover, when follicle growth was detected, patients underwent a controlled ovarian stimulation (COS). IVF and reproductive outcomes were compared with previous COS cycles started in our clinics, when available. T-test was used where appropriate. Main results and the role of chance Overall 159 POR/POI women (age 38.7±4.2years, AMH0 0.22±0.41ng/ml; AFC0 1.4±1.9) underwent the ASCOT-1 technique. Mean volume of plasma injected was 6.8±0.8ml, distributed equally in both ovaries. First follow-up was done in 131 women showing statistically significant improvements in the AFC during the entire follow-up compared to the basal levels measured before the treatment (AFC1 3.3±3.4, p < 0.001; AFC2 3.3±3.6, p < 0.001; AFC3 2.9±2.6, p < 0.001; AFC4 2.4±2.6, p = 0.07). After ASCOT-1, 98 COS were initiated in 48 women in our clinics, which were compared to their previous 66 cycles. Although age was significantly higher in their posterior cycles (38.0±2.9 vs40.0±3.6; p < 0.001), after ASCOT-1 oocyte retrieval was reached in a greater amount of cases (75.5% vs87.5%, p=NS). ASCOT-1 showed a positive, but non statistically significant effect in the number of MII-oocytes (2.8±4.1 vs3.2±3.9, p=NS) and blastocysts obtained (1.8±2.8 vs2.4±3.1, p=NS), but relevant improvements were observed in quality related parameters such as oocyte maturation (61.5%, 95%IC 45.8-77.3, vs86.1%, 95I%IC 69.9-85.5; p 0.03), fertilization (62.6%, 95%CI 53.0-71.3, vs76.5%, 95%CI 70.0-82.0; p < 0.001), implantation (25.0%, 95%CI 8.3-52.5 vs41.1%, 95%CI 19.4-66.5; p < 0.001) and clinical pregnancy rate (25.0%, 95%CI 8.3-52.5 vs46.6%, 95%CI 22.2-72.5; p < 0.001). Ultimately, 14 clinical pregnancies (7 after ET and 7 by natural conception) were obtained after ASCOT-1. Limitations, reasons for caution This retrospective study involves short periods of follow up and limited amount of IVF attempts. Thus, further prospective studies with increased sample size are required to validate our results, to establish the duration of the effects, and to identify which subgroups of patients could benefit the most from this treatment. Wider implications of the findings Growth factors contained in the G-CSF mobilized PRP could play a role in follicular development, providing a new tool to increase the reproductive potential of women with very low ovarian reserve where oocyte donation is the only practical option, allowing them to access to homologous IVF treatment. Trial registration number 2310-FIVI-188-SH

O-071 Stringent statistical analysis of 108,684 oocyte donation cycles identifies 2.6% of donors with specific oocyte/embryo developmental arrest phenotypes for genome association studies

Abstract Study question Can statistical modelling accurately identify an outlier group of presumed fertile donors with specific reduced embryological outcomes suggestive of an underlying infertility-related genomic condition? Summary answer Statistical modelling identified a highly specific group of donors as embryologically under-performing outliers across multiple treatment cycles for the optimisation of downstream genomic association studies. What is known already Female infertility has a wide range of clinical presentations. While some causes of infertility are well defined, the aetiology of most infertility remains unexplained. Since IVF allows for in vitro monitoring of oocyte and embryo, it is now possible to identify subtle infertility endophenotypes, characterized by specific developmental failure that would otherwise go undetected in natural conception. Currently, the lack of large and well-categorized datasets of infertility endophenotypes has limited research in the area. Therefore, a clear and methodological definition of infertility endophenotypes in IVF is the first crucial step towards a better understanding of their mechanism and biological/genetic aetiology. Study design, size, duration A retrospective analysis was performed on clinical and embryological data from 40497 egg donors, undergoing 108.684 stimulations, with 4.235.036 oocytes retrieved. The data also included information on the 85482 recipients and their 190996 oocyte reception cycles, spanning from 1999 to 2023. Infertility endophenotypes were able to be well categorized as oocyte donors are presumed fertile based on their young age and on normal ranges displayed for the parameters assessed during typical oocyte donation work-up. Participants/materials, setting, methods Donor performance was calculated according to: (I) oocyte maturation rate (MR); (ii) survival rate of cryopreserved oocytes (SR); (iii) oocyte fertilization rate (FR;2PN/Injected MII); and (iii) blastulation rate (BR;blastocyst/2PN). Donors with significantly impaired rates, considering ≥2 stimulations and/or recipients, were identified as outliers using probabilistic modelling (Binomial test, Bonferroni corrected P < 0.05). Outliers were computed for each rate on data subsets after applying this stringent filtering criteria and excluding inconsistent or missing data. Main results and the role of chance 2.6% of donors were identified as underperforming outliers when summing the rate observed for each embryological outcome using the stringent statistical modelling. The average MR was 79.8% (95%CI: 79.6-80). Taking into account the correlation of follicle size during ultrasound tracking and the number of mature oocytes collected, a total of 168/29768 (0.56%) donors with statistically lower MR (mean MR = 43% 95%CI:40.1-45.7) across ≥2 egg collection cycles were identified as outliers. The average SR was 88% (95%CI:87.9-88.2). A total of 176/18544 (0.95%) donors with ≥2 stimulations and ≥2 recipient cycles were deemed outliers, showing a statistically reduced SR (mean SR = 51% 95%CI:48.9-53.1). The average FR was 74% (95%CI: 73.8-74.2). 164/31657 (0.52%) donors were found to have statistically low FR (mean FR = 37% 95%CI:34.6-38.7) and deemed outliers when assessed over ≥2 stimulation cycles with ≥2 recipient cycles. The average BR was 53.4% (95%CI: 53.1-53.7). After considering only donors with ≥2 recipients and ≥2 stimulations, a total of 142/24716 (0.57%) donors with statistically low BR (mean BR = 14% 95%CI:12.4-15.3) were considered outliers. Limitations, reasons for caution The stringent criteria applied to our statistical modelling has likely resulted in underestimating the true level of outlier donors. This is also likely compounded by the selection bias associated with donor recruitment and the retention policies after the first stimulation cycle preventing the evaluation of recurrent patterns in some cases. Wider implications of the findings The analytical tools developed on this unprecedentedly large dataset are fundamental to define a methodological workflow for accurately identifying unexpectedly infertile individuals. This is crucial for investigating the genetic and biological mechanisms underlying infertility endophenotypes, leading to improvements in treatment and developing screening tool to predict infertility and related pathologies. Trial registration number not applicable

O-290 Reduced uterine artery pulsatility index (UtAPI) in artificial frozen embryo transfer pregnancies leads to underestimation of 1st-trimester preeclampsia risk. An analysis of over 30,000 pregnancies

Abstract Study question Does the mode of conception (spontaneous, ovulation induction, fresh or frozen embryo transfer) impact Uterine Artery Pulsatility Index (UtAPI) values in 1st-trimester preeclampsia screening? Summary answer A significant reduction in UtAPI during 1st-trimester screening is observed in artificial frozen embryo transfer (AC-FET) pregnancies, resulting in underestimated preeclampsia risk. What is known already Accumulating evidence indicates that AC-FET cycles are associated with an increased risk of preeclampsia. Uterine artery (UtA) Doppler is a crucial biomarker for first-trimester preeclampsia screening, along with maternal factors and serum biomarkers, identifying “high-risk” patients. Guidelines strongly recommend the administration of aspirin(150mg/day) in these women, owing to robust evidence demonstrating a 40% reduction in the incidence of preeclampsia. Despite small studies suggesting a lower UtAPI after frozen ET, no previous studies explored the impact of the type of endometrial preparation in UtAPI Doppler or its influence on estimating preeclampsia risk Study design, size, duration This is a retrospective single-center study including 33880 singleton pregnancies (spontaneous or after ART) who underwent the 1st-trimester ultrasound screening at our University Hospital between January 2010 - May 2023. Overall, 33880 pregnancies were included: 29709 spontaneous, 429 ovulation induction, 1015 fresh ET and 2727 after frozen ET pregnancies (326/2727 in NC-FET and 2401 in AC-FET). Participants/materials, setting, methods The study included only singleton pregnancy for which a first trimester ultrasound (11+0- 13+6 wks) with UtA Doppler was performed. The primary aim of the study was to assess whether there was an association between the mode of conception and the UtA Doppler and whether UtAPI differed according to the type the endometrial preparation for FET. Continuous variables were expressed as mean ± SD. ANOVA test and multivariate regression analysis were performed. Main results and the role of chance Overall, the 1st-trimester UtAPI in pregnancies conceived after AC-FET was 1,036±0,160 [CI95%:0,723;1,349], after NC-FET 1,354±0,162 [CI95%:1,037;1,671], Fresh-ET 1,418 ±0,161 [CI95%:1,104;1,733], OI 1,413±0,162 [CI95%:1,096;1,730] and spontaneous pregnancies 1,373 ± 0,160 [CI95%:1,060;1,686]. A multivariable regression analysis, adjusting for confounding factors (age, weight, smoking, and oocyte donation), demonstrated that the value of uterine artery UtAPI is significantly lower when artificial cycle for frozen embryo transfer is performed compared with spontaneous pregnancies (-0,337 ± 0,014 [CI95%:-0,378;-0,297]), ovulation induction (-0,377 ± 0,028 [CI95%:-0,455; -0,298]) Fresh-ET (-0,383 ±0,021 [CI95%:-0,442; -0,323]), and NC-FET (-0,318 ± 0,029[CI95%:-0,401; -0,23]). On the contrary none of the other modes of conception are different in terms of UtAPI as compared with spontaneous pregnancies. Among screened patients, the number of patients classified at high risk for preeclampsia was significantly lower in pregnancies following AC-FET 7.8%(156/2002) as compared to NC-FET 15.9%(46/289), fresh-ET 11.0%(58/527), ovulation induction 10.5%(26/248) and spontaneous pregnancies (1452/15624) p < 0.001. Nonetheless, despite the lower number of high-risk patients in the AC-FET group, the actual incidence of PE was more than three times higher in AC-FET group 5.2%(125/2401) as compared with spontaneous 1.5%(431/29709), ovulation induction 1.4%(6/429) or NC-FET pregnancies 1.5%(5/326) and more than two times higher when compared to fresh-ET pregnancies 2.3%(23/1015) p < 0.001. Limitations, reasons for caution Despite employing a robust methodology with a substantial sample size and multivariate statistical analysis to address confounding factors, it’s essential to acknowledge the possibility of residual bias. However, its impact on the presented outcomes is anticipated to be minimal. Wider implications of the findings Existing 1st-trimester preeclampsia screening calculators overlook the notably lower UtAPI in AC-FET pregnancies, as discovered in our study. This poses a threat of underestimating high-risk patients and neglecting prophylactic aspirin. Algorithms should be adjusted to accurately assess risk for those undergoing AC-FET Trial registration number Not applicable

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

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

P-318 Reproductive ageing: the seed, the soil, or both?

Abstract Study question Is it all about the embryo? Can a single euploid blastocyst transfer sustain reproductive outcomes in women with advanced reproductive age? Summary answer Despite euploid embryo transfer, endometrial senescence appears to play a crucial role in determining reproductive success, particularly in older patients undergoing in vitro fertilization (IVF). What is known already Advanced reproductive age significantly impairs oocyte and embryo quality. Effective crosstalk and synchronization between embryo and endometrium are pivotal for successful pregnancies, both in vivo and in vitro. Implantation failure remains a persistent challenge in IVF, exacerbated by delayed family planning trends. The transfer of euploid blastocysts through preimplantation genetic testing for aneuploidy (PGT-A) is a potential strategy to address implantation issues, decrease miscarriages, and shorten time-to-pregnancy. However, a significant proportion of IVF treatments remain unsuccessful, suggesting critical factors beyond the embryo. Study design, size, duration This retrospective study analyzed 457 single euploid blastocyst transfers performed by two doctors at a private IVF center from January to November 2023. Inclusion criteria encompassed cases with PGT-A indications (advanced maternal age, repeated implantation failure, recurrent pregnancy loss, etc.) or cases where embryo biopsy was patient-requested. The primary outcome was ongoing pregnancy rate (OPR), with secondary outcomes including pregnancy rate (PR) and clinical pregnancy rate (CPR). Participants/materials, setting, methods Participants were categorized into four groups: Group 1 (< 35 years old; N = 100), Group 2 (35-37 years old; N = 102), Group 3 (38-40 years old; N = 118), and Group 4 (> 41 years old; N = 87). A control group (oocyte donation; N = 50) with single euploid embryo transfers showed a mean recipient age of 43 years. Donors were always less than 32 years old. Endometrial preparation protocols were consistent across all groups. Chi-square test was used to compare groups. Main results and the role of chance Among the 457 transfers analyzed, with a mean female age of 37 years, the overall PR was 71.3%, CPR was 64.8%, and OPR was 60.2%. Groups showed no differences in demographic variables and cycle parameters. Group 1 demonstrated higher PR (83.3%), CPR (78.4%), and OPR (73.5%) compared to Group 2 (PR 70.9%, p = 0.034; CPR 66%, p = 0.047; OPR 62.1%, p = 0.081), Group 3 (PR 68.2%, p = 0.009; CPR 61.2%, p = 0.005; OPR 56.6%, p = 0.008), and Group 4 (PR 65%, p = 0.002; CPR 56.1%, p < 0.001; OPR 51.2%, p = 0.001). Furthermore, the control group (oocyte recipients) showed significantly lower PR (68%, p = 0.031), CPR (54%, p = 0.002), and OPR (46%, p < 0.001) compared to Group 1, but not with the other groups. These findings demonstrate that even with euploid embryos originating from young donors, older women exhibited lower pregnancy rates than young women transferring single euploid blastocysts from their own oocytes and similar rates compared to those with advanced reproductive age transferring their own euploid blastocysts, implying that endometrial ageing may disproportionately influence IVF treatment outcomes. Limitations, reasons for caution The retrospective design introduces inherent bias, notably selection bias and unmeasured confounders. This preliminary data did not account for male infertility factors and their impact on embryo quality. Wider implications of the findings Reproductive aging appears to be influenced by factors beyond the embryo itself, especially in women above 35 years. Further research is warranted to elucidate the causes and impact of reproductive aging on implantation potential, aiming to refine clinical practices and enhance the success of IVF treatments. Trial registration number not applicable

P-774 Conventional-IVF versus NC-IVF: unravelling the origins of fetal cardiac programming in ART

Abstract Study question Do fetuses from natural cycle IVF (NC-IVF) present signs of cardiac remodeling and suboptimal function similar to those observed in fetuses from conventional IVF (cIVF)? Summary answer Fetuses from both NC-IVF and cIVF present signs of fetal cardiac remodeling and suboptimal function as compared to spontaneously conceived fetuses (SC) from fertile couples. What is known already Previous publications have demonstrated that fetuses conceived by IVF present cardiac remodeling and suboptimal function. These fetuses show dilated atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation. However, the pregnancies included in these studies were obtained following cIVF. In IVF cycles, ovarian stimulation has an impact on the oocyte quality and the endometrial milieu that may potentially affect perinatal results and fetal cardiovascular programming. Our aim was to compare cardiac morphometry and myocardial function in fetuses conceived by cIVF with those obtained after NC-IVF, without ovarian stimulation. Study design, size, duration This is a nested case-control study of 120 singleton pregnancies within a prospective cohort recruited from 2017 to 2021, including 40 SC from fertile couples, 40 following NC-IVF and 40 after cIVF with fresh embryo transfer, matched by maternal age, ethnicity, and gestational age at scan. IVF pregnancies were recruited from a single assisted reproduction center, ensuring homogeneity in ovarian stimulation protocols, laboratory procedures, and embryo culture conditions. Participants/materials, setting, methods The study protocol included prospective collection of parental demographics, reproductive and ART data, a fetal ultrasound scan at 28-34 weeks assessing biometry, feto-placental Doppler and morphological and functional echocardiography, and perinatal outcomes. Comparisons between groups were adjusted by gestational age and fetal weight at scan, and birthweight centile. Oocyte donation and PGT cycles were exclusion criteria. All the laboratory procedures including gamete manipulation, fertilization methods and embryo culture conditions were identical for NC-IVF and cIVF. Main results and the role of chance There were no significant differences in demographic data, perinatal outcomes, biometry and feto-placental Doppler parameters between the study groups. Reproductive data and IVF indications were also similar among the IVF groups. As compared to the SC, both IVF groups showed significant signs of fetal cardiac remodeling (higher cardio-thoracic ratio: cIVF mean 0.31 [SD 0.04]* versus NC-IVF 0.31 [0.03]* versus SC 0.28 [0.04], adjusted P-value <0.001; larger right atria-to-heart ratio: cIVF 19.1% [3.0]*† versus NC-IVF 18.8% [3.3]* versus SC 17.4% [2.9], adjusted P-value <0.001; increased relative wall thickness: c IVF 0.80 [0.2]* versus NC-IVF 0.85 [0.3]* versus SC 0.72 [0.3], adjusted P-value <0.001) and suboptimal function (tricuspid ring displacement (mm): cIVF 7.1 [0.8]* versus NC-IVF 7.3 [0.9]* versus SC 7.5 [1.4], adjusted P-value 0.003; left myocardial performance index: cIVF 0.50 [0.06]* versus NC-IVF 0.49 [0.06]* versus SC 0.48 [0.08], adjusted P-value <0.001). * Adjusted P value <0.05 as compared with SC. † Adjusted P value <0.05 as compared to NC- IVF. Limitations, reasons for caution The sample size was limited by the difficulty in recruiting viable pregnancies obtained by NC-IVF from a single center. The reported cardiac changes are subclinical and, although they are recognized as potential cardiovascular risk factors, their association with the long-term cardiovascular disease in these subjects remains to be proven. Wider implications of the findings Our findings contribute to assess the safety of different ART procedures in terms of cardiac performance in fetal life, before the influence of postnatal factors, in order to unravel the origins of fetal cardiac remodeling in ART. Studies evaluating the long-term health in this population are needed. Trial registration number Not applicable

P-413 Retrospective observational study: evaluating progesterone levels on the day prior to euploid embryo transfer and its impact on pregnancy rate

Abstract Study question What significance does progesterone levels hold on the day prior to the transfer of euploid embryos, and how is this correlated with pregnancy rates? Summary answer Progesterone levels prior to embryo transfer play a crucial role in endometrial receptivity What is known already In the realm of assisted reproductive technology, creating optimal conditions for embryo transfer is crucial for successful pregnancies. Progesterone, a key hormone for endometrial receptivity, plays a pivotal role in this process. This retrospective observational study aims to evaluate the importance of progesterone levels the day before euploid embryo transfer and their correlation with pregnancy rates. For this reason, we study patients with low progesterone levels prior to transfer and the effectiveness of “rescue protocols”. Study design, size, duration This was a Retrospective Observational Study, that covers 121 women who underwent embryo transfer (euploid embryos and oocyte donation) who had their progesterone measured the day before the transfer, from January 1st 2023– December 31st 2023. The primary endpoint was pregnancy rate. Participants/materials, setting, methods During the study period, endometrial preparation was carried out by administration of progesterone, both orally or vaginally. The patients were divided into three groups based on the level of progesterone the day before the embryo transfer. • >10ng/mL • 8-10 ng/mL • <8ng/mL. These participants were treated with the daily administration of 1 or 2 doses of injectable Prolutex until confirmation of pregnancy by ultrasound. Eligible patients were aged ≤50 years with adequate endometrium thickness after receiving estrogen. Main results and the role of chance Preliminary findings underscore a significant correlation between progesterone levels exceeding 10 ng/ml the day before embryo transfer and elevated pregnancy rates. Conversely, in cases with lower progesterone levels, a personalized supplementation approach involving Prolutex demonstrates positive impacts on pregnancy outcomes. This highlights the pivotal role of tailored progesterone supplementation, utilizing Prolutex, in enhancing endometrial receptivity and, consequently, elevating the likelihood of successful pregnancies. The study emphasizes the need for personalized strategies, shedding light on the nuanced interplay between progesterone levels, supplementation methods, and the potential influence on reproductive success. As we explore these results, it becomes evident that chance alone does not govern outcomes; rather, strategic interventions hold the key to optimizing the path to successful pregnancies. Limitations, reasons for caution The main limitation of the study is the lack of randomized control studies. Furthermore, in this study, we are not including as the main group those who with low progesterone do not undergo rescue intervention with Prolutex. Wider implications of the findings Preliminary findings reveal a substantial link between progesterone levels exceeding 10 ng/ml before embryo transfer and heightened pregnancy rates. Conversely, in cases of lower progesterone, personalized Prolutex supplementation positively influences outcomes, emphasizing the pivotal role of tailored progesterone strategies in optimizing endometrial receptivity for successful pregnancies. Trial registration number not applicable