Egg Donation Program Research Articles

Informed consent and coercion in recruitment advertisements for oocyte donors

BackgroundAs the use of donor eggs for in vitro treatment has increased, both medically affiliated and private donor egg agencies have turned to online advertisements to recruit donors. The American Society for Reproductive Medicine provides recommendations encouraging ethical recruitment of donors, however there is no formal regulation for the informed consent process for egg donor recruitment and compensation. Underrepresentation of risks and targeted financial incentives may pose a risk to the informed consent process.MethodsData from online advertisements for egg donors active between January 1 - August 31, 2020, were collected to analyze content related to risks, Covid-19 precautions, donor payment, and desired donor characteristics. Advertisements for egg donors on Google, Craigslist, and social media were analyzed. Primary outcomes included the mention of the risks of egg donation, including the risk of Covid-19 exposure, in donor egg advertisements. Secondary outcomes included language targeting specific donor characteristics and financial compensation.Results103 advertisements were included. 35.9% (37/103) of advertisements mentioned some risk of the egg donation process, and 18.5% (19/103) mentioned risks or precautions related to Covid-19 exposure. Of advertisements for private donor egg agencies, 40.7% (24/59) mentioned any risk, compared to 29.6% (13/44) of medically affiliated egg donation programs; the difference was not statistically significant (p-value = 0.24). Agencies targeting students and donors of a specific race were more likely to offer payments over $10,000 for an egg donation cycle. Among advertisements offering over $20,000 for donor compensation, 72.7% (8/11) recruited women under the age of 21.ConclusionEgg donor recruitment advertisements, for both medically affiliated programs and private agencies, were unlikely to mention risks including the risk of exposure to Covid-19. Non-medically affiliated private donor egg agencies were more likely to violate multiple American Society for Reproductive Medicine ethics guidelines, including offering higher than average compensation, and recruiting donors from young and vulnerable populations.

Enhancing predictive models for egg donation: time to blastocyst hatching and machine learning insights

BackgroundData sciences and artificial intelligence are becoming encouraging tools in assisted reproduction, favored by time-lapse technology incubators. Our objective is to analyze, compare and identify the most predictive machine learning algorithm developed using a known implantation database of embryos transferred in our egg donation program, including morphokinetic and morphological variables, and recognize the most predictive embryo parameters in order to enhance IVF treatments clinical outcomes.MethodsMulticenter retrospective cohort study carried out in 378 egg donor recipients who performed a fresh single embryo transfer during 2021. All treatments were performed by Intracytoplasmic Sperm Injection, using fresh or frozen oocytes. The embryos were cultured in Geri® time-lapse incubators until transfer on day 5. The embryonic morphokinetic events of 378 blastocysts with known implantation and live birth were analyzed. Classical statistical analysis (binary logistic regression) and 10 machine learning algorithms were applied including Multi-Layer Perceptron, Support Vector Machines, k-Nearest Neighbor, Cart and C0.5 Classification Trees, Random Forest (RF), AdaBoost Classification Trees, Stochastic Gradient boost, Bagged CART and eXtrem Gradient Boosting. These algorithms were developed and optimized by maximizing the area under the curve.ResultsThe Random Forest emerged as the most predictive algorithm for implantation (area under the curve, AUC = 0.725, IC 95% [0.6232–0826]). Overall, implantation and miscarriage rates stood at 56.08% and 18.39%, respectively. Overall live birth rate was 41.26%. Significant disparities were observed regarding time to hatching out of the zona pellucida (p = 0.039). The Random Forest algorithm demonstrated good predictive capabilities for live birth (AUC = 0.689, IC 95% [0.5821–0.7921]), but the AdaBoost classification trees proved to be the most predictive model for live birth (AUC = 0.749, IC 95% [0.6522–0.8452]). Other important variables with substantial predictive weight for implantation and live birth were duration of visible pronuclei (DESAPPN-APPN), synchronization of cleavage patterns (T8-T5), duration of compaction (TM-TiCOM), duration of compaction until first sign of cavitation (TiCAV-TM) and time to early compaction (TiCOM).ConclusionsThis study highlights Random Forest and AdaBoost as the most effective machine learning models in our Known Implantation and Live Birth Database from our egg donation program. Notably, time to blastocyst hatching out of the zona pellucida emerged as a highly reliable parameter significantly influencing our implantation machine learning predictive models. Processes involving syngamy, genomic imprinting during embryo cleavage, and embryo compaction are also influential and could be crucial for implantation and live birth outcomes.

P-227 Blastocyst rate prediction by artificial intelligence: evaluation of static oocyte images in patients and donors

Abstract Study question Can a deep learning tool accurately predict blastocyst development from single static oocyte images across diverse patient populations? Summary answer The automatic oocyte score was directly correlated with the blastocyst formation rate in conventional treatments using patient oocytes and in the egg donation program. What is known already The implementation of artificial intelligence (AI)-based algorithms has revolutionized gamete and embryo evaluation in assisted reproduction, providing a standardized basis for clinical decisions. Despite these advances, the implementation of AI algorithms in oocyte evaluation has faced unique challenges. This study explores the predictive ability of an AI algorithm on the actual blastocyst arrival rate from static oocyte images, focusing on finding differences or similarities in these predictions between patients and donors. Study design, size, duration This retrospective cohort study analyzed 1092 static images of oocytes before ICSI. The sample included 791 donor and 301 patient oocyte images. A deep learning algorithm was employed to assess oocyte scores, categorizing them into quartiles. The study explored the correlation between oocyte scores and the actual rate of blastocyst arrival for all oocytes. The rates were also compared between patients and donors, assessing an effective cut-off point to improve the accuracy of the predictions. Participants/materials, setting, methods The oocyte images analyzed were captured with cameras connected to microinjection microscopes immediately before the ICSI procedure. Oocyte images and oocyte age were used as input data for the blind analysis performed by the deep learning-based algorithm. The algorithm predicted blastocyst arrival probability for each oocyte, and these predictions were compared with actual outcomes. This evaluation assessed the algorithm’s performance across patient and donor populations, providing valuable insights into its predictive accuracy for blastocyst arrival. Main results and the role of chance Significant differences in blastocyst formation rates were observed between quartiles of scores assigned by the artificial intelligence (AI) algorithm. Oocytes classified in Quartile 1 showed a significantly lower blastocyst arrival rate (54.63±49.99, n = 216) compared to Quartiles 3 (71.88±45.06, n = 224) and 4 (66.82±47.19, n = 220)*. In general, each increased unit in the algorithm was significantly associated with an increased probability of blastocyst formation (OR = 1.10 [95% CI: 1.02-1.16])*. The algorithm successfully predicted the blastocyst arrival rate, with an area under the curve (AUC) of 0.60 (95% CI: 0.56-0.65). When assessing differences between patients and donors, both groups exhibited similar rates in the first quartile (59.68% and 52.60%, respectively) and the three last quartiles combined (67.55% and 66.02%, respectively). However, an effective cutoff point was identified at 2.8 (between first and second quartile), where both populations experienced a notable increase in blastocyst formation rates. (*p<.05) Limitations, reasons for caution This project is limited by its retrospective, single-center nature and small sample size. Consequently, it would be advisable to conduct a large-scale multicenter study to confirm the conclusions of this study. Wider implications of the findings This study highlights the efficiency of the artificial intelligence algorithm in predicting blastocyst arrival from oocyte images. Establishing a cutoff point in oocyte scoring could enhance the management of the egg donation program and provide individualized guidance to patients based on the quality of their gametes. Trial registration number not applicable

P-204 Automated embryo assessment: a simple web application correlates scores with embryo morphology, developmental velocity, ploidy, and clinical outcomes

Abstract Study question How does the novel automated scoring system in our laboratory correlate with treatment success in different subpopulations? Summary answer The web app automates embryo assessment, linking scores to morphology, development speed, ploidy, and clinical outcomes in treatments with both patient and donor oocytes. What is known already In the realm of assisted reproductive technologies, numerous platforms employing artificial intelligence (AI) have emerged for embryo assessment. Substantial research has been dedicated to evaluating the efficacy of AI in predicting pregnancy outcomes, particularly following blastocyst transfer. However, not all available options have undergone external validation, a crucial step deemed necessary before investing in such tools. This project endeavors to validate the utility of EMBRYOAID v1.0, a straightforward web application capable of assessing embryos through photos and/or videos. Study design, size, duration This is a retrospective cohort study including 485 patients who underwent IVF treatments with embryos (n = 5,710) cultured in EmbryoScope® time-lapse systems. Senior embryologists routinely assessed blastocysts using ASEBIR morphological criteria (A-D). Then, time-lapse videos were scored by the EMBRYOAID algorithm (0-10). We investigated the relationship between automated scoring and: (I) conventional morphology, (II) morphokinetic parameters, (III) euploidy rate, and (IV) implantation in cycles with own oocytes, egg donation, and preimplantation genetic testing for aneuploidies (PGT-A). Participants/materials, setting, methods The association with morphology and morphokinetics was investigated in 5,710 embryos. Ploidy correlation involved 258 blastocysts undergoing trophectoderm biopsy and next-generation sequencing analysis. Implantation association was studied in 381 single blastocyst transfers. Finally, a multivariable analysis considered oocyte age, body mass index, type of transfer (fresh-frozen) and day of transfer (5-6) to quantify the relevance of automated scoring in different treatment subpopulations. Model performance was assessed through ROC curves and area under the curve calculations. Main results and the role of chance The results that involved grouping were quartiled based on sample size, calculated by the statistical software. This deep-learning score was related to conventional morphology (7.9±1 for A, n = 295; 6.9±1.3 for B n = 1168; 5.9±1.3 for C, n = 830; and 3.1±1.8 for D, n = 3,417)*. Embryos with faster development in early stages received higher scores, considering division times at 2, 3, 4, and 5 cells*. Euploidy rate increased as the embryo score was higher: 39.1% for ≤5.6 (n = 54), 45.5% for 5.6-6.2 (n = 61), 48.5% for 6.2-6.9 (n = 65) and 58.2% for >6.9 (n = 78). Similarly, the implantation rate was also higher in accordance with the score: 42.7% for ≤6.2 (n = 73), 50.6% for 6.2-7.4 (n = 87), 60.2% for 7.4-8.2 (n = 103) and 69.4% for >8.2 (n = 118). The stepwise multivariate analysis showed that embryo score was related to the odds of implantation in conventional treatments with patient oocytes (OR = 1.4; 95% CI [1.1-1.8]*) and in the oocyte donation program (OR = 1.2; 95% CI [1–1.4]*). The AUCs demonstrated the following performance: 0.643 (0.559-0.727) for patient oocytes and 0.677 (0,624-0,731) for the oocyte donation program. There was no significant association of embryo score with implantation in PGT-A treatments. Limitations, reasons for caution The retrospective nature of the study, despite serving as a thorough external validation, introduces inherent limitations. Notably, in PGT-A treatments, embryos underwent assisted hatching on day 3, potentially influencing the model’s performance. Wider implications of the findings The implications of our findings validate a user-friendly tool for automated embryo scoring in the laboratory. The achieved performance is comparable or superior to other tested models, particularly in egg donation programs, potentially encouraging clinics to adopt this tool routinely. Trial registration number Not applicable

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

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

P-423 Fertility outcomes of an egg donation program for hematologic cancer survivors: an 11-year retrospective cohort study

Abstract Study question What is the effectiveness of IVF/intracytoplasmic sperm injection with egg donation (IVF/ICSI-ED) in hematological cancer survivors (HCS) with reproductive desire and iatrogenic ovarian failure (IOF)? Summary answer The probability of clinical pregnancy and having a live birth does not significantly differ between women treated for hematological cancer and non-oncological patients using IVF/ICSI-ED. What is known already The most common hematological malignancies in women before or during reproductive age are lymphoma and leukemia. Oncological therapies cause premature ovarian failure, uterine fibrosis and infertility. Fertility preservation measures are not always possible or advisable. Egg vitrification in post-pubertal women has temporary implications as it requires ovarian stimulation; cryopreservation of ovarian tissue carries the risk of introducing back malignant cells. Fertility preservation is performed in 4-20% of cases: only 5% of patients have the chance to consult a reproductive specialist before cancer treatment. There are no published comparative studies on the effectiveness of ED in hematologic cancer survivors. Study design, size, duration We conducted a retrospective cohort study of 47 HCS with IOF, all of them nulliparous and without infertility diagnosis nor fertility preservation prior to oncological treatment and compared them with a control group (CG) of 19 infertile non-oncologic patients who underwent IVF/ICSI-ED with eggs from the same donors obtained during the same period of time (2012-2022). After evaluation by the center’s Oncofertility Committee, 45 HCS were eligible for IVF/ICSI-ED, and 23 agreed to undergo treatment. Participants/materials, setting, methods On the 47 patients HCS group we studied all the oncologic information: mean age at cancer diagnosis, mean age at IVF/ICS-ED treatment, type of tumor and oncologic treatment received. We compared the 23 patients HCS group with the 19 patients CG for: mean age of the egg recipient, mean age of the egg donor, single embryo transfers performed per patient, pregnancy and life bith rate per IVF/ICSI-ED treatment. We used chi-square statistic for the comparison. Main results and the role of chance The 47 women HCS group was aged between 25 to 50 years. The mean age at cancer diagnosis was 25.9 ± 7.6 years. The most frequent neoplasms were Hodgkin lymphoma (46.8%), non-Hodgkin lymphoma (21.2%), acute myeloid leukemia (12.7%), chronic myeloid leukemia (10.6%), other leukemias (8.5%). Lymphomas (68%) predominated over leukemias (32%). In this group 95.8% of the HCS were treated with chemotherapy: 21.2% as monotherapy, 14.8% combined with radiotherapy, 6.3% with surgery, and 6.3% with tyrosine kinase inhibitors (TKIs). Bone marrow transplantation was required in 46.8% of cases. At least 5 years elapsed from diagnosis to evaluation by the Oncology Committee. The mean egg recipient age was 36.5 ± 4.9 years for the HCS group and 41.3 ± 2.6 years for the CG (p < 0.05); there were no significant differences in the egg donor’s mean age (26.5±4.5 Vs 26.1±4.9, p=ns). We found no significant differences between the HCS and the CG in the mean single embryo transfers performed per patient (1.7 Vs 1.9, p=ns), in the pregnancy rate per ED cycle (88.4% vs 89.4%, p=ns), nor in the live birth rate per ED cycle (73% vs 64%, p=ns). Limitations, reasons for caution The retrospective nature of the study, the small number of cases and the under-recording of data in the medical history are the main limitations of this study. Wider implications of the findings It is important to have a comprehensive understanding of cancer therapies on fertility so that both doctors and patients can make informed decisions. Fertility preservation methods must be proposed before initiating oncological treatment, so multidisciplinary teamwork and timely referral to reproductive medicine centers specialized in fertility preservation are recommended. Trial registration number Not applicable

P-603 Combined oral contraceptive pill (COCP) before controlled ovarian hyperstimulation (COH) in donors could negatively affect egg donation outcomes in recipients: a multicentre retrospective study

Abstract Study question Could COCP use before COH with a progestin primed ovarian stimulation protocol (PPOS) in donors also negatively influence the egg donation outcomes in recipients? Summary answer Synchronization with a combined oral contraceptive pill (COCP) before controlled ovarian hyperstimulation (COH) involving progestin for pituitary suppression shows worst outcomes in egg donation treatments. What is known already It is well known that COCP leads to a long-lasting pituitary suppression, a reversible reduction in AMH and antral follicle count with higher risk of inappropriate response to COH and GnRH-agonist trigger, potentially reducing number and quality of retrieved oocytes. This is supported by the latest international guidelines on COH that strongly discourage COCP use before GnRH antagonist protocols because of a reduced efficacy of such cycles, also, in terms of ongoing pregnancy rate (OPR). They also underlie that interactions between COCP pretreatment and PPOS protocols remain inadequately explored and more research are needed to clarify discrepancies persisting in literature. Study design, size, duration Multicentre retrospective cohort study evaluating egg donation outcomes, depending on the use or not of COCP pre-treatment in donors, in terms of OPR, Live Birth Rate (LBR), and secondly of fertilization rate (FR), blastulation rate (BR), implantation rate (IR) and miscarriage rate (MR). The treatments were realized in a Private Fertility Clinic (where donors also underwent COH with PPOS protocol) and a public hospital (transnational egg donation program) between January 2022 and September 2023. Participants/materials, setting, methods 216 egg donation cycles were studied. Excluding cases of fertilization and/or embryo development failure and cases for which embryo transfer outcomes were not available at the time of data collection, the study analysed the outcomes of 90 embryo transfers (ETs). After the first analysis on total cycles, a stratification was made to evaluate whether COCP could have a different influence depending on the oocytes type used: fresh or vitrified. Main results and the role of chance COCP-No and COCP-Yes groups show similar FR and BR, after donation of same oocytes number (6,4 ± 1,1 vs 6,5± 1). Interestingly, vitrified oocytes from COCP-Yes donors produced a statistically lower yield of viable blastocysts (22,2% versus 37,9%; p = 0,007). IR was higher in the COCP-No group, (46,4% vs. 28,6%), data confirmed also in the two subgroups (fresh: 42,9% vs. 14,3%; vitrified: 48,8% vs. 35,7%). Higher MR was observed in the COCP-Yes group, achieving statistical significance both for total oocytes (66,7% vs. 9,4%; p = 0,006) and vitrified ones (60% vs. 5%; p = 0,016). Pregnancy rate was higher in the COCP-No group (46,4% vs. 28,6%), the same trend was found regardless of the type of oocytes used (fresh: 42,9% vs. 14,3%; vitrified: 48,8% vs. 35,7%). The greatest discrepancies were observed in OPR and LBR subcategories. In fact, a statistically higher OPR was obtained in the COCP-No group (42% vs. 9,5%, p = 0,008), which leads to a statistically higher LBR (30,4% vs. 0%; p = 0,004). Notably, the LBR after using both fresh and vitrified oocytes was markedly higher in the COCP-No group (fresh: 28,6% vs. 0%, p = 0,385; vitrified: 31,7% vs. 0%, p = 0,041), presenting a significant difference when vitrified oocytes were used with potential clinical relevance. Limitations, reasons for caution The main limitation lies in the retrospective nature of the study and the small sample size, but the multicentre design gives greater reliability. Further research is needed to confirm these findings and better understand the specific circumstances in which COCP may or may not be beneficial. Wider implications of the findings COCP pretreatment in egg donors undergoing PPOS protocol may negatively impact embryo development and pregnancy outcomes in recipients, with increased MR, and reduced OPR, and LBR. Particularly, the worst outcomes involve vitrified oocytes, providing valuable insights to reconsider COCP use in transnational egg donation programs, but also fertility preservation ones. Trial registration number Not Applicable

O-060 Ovarian rejuvenation - fact or fiction?

Abstract Ovarian aging is a reality and a physiological process which occurs with age resulting in to premature depletion of eggs . POI occurs in approximately 1% of the women who have not reached 40 years of age. The frequency is roughly 4–8% in women experiencing secondary amenorrhea and 10–28% in cases of primary amenorrhea .The prevalence of POI was higher in countries with medium and low human development indexes . . We analysed 1000 infertile patients of less than 40 years . 110 patients had AFC less then 2 and opted for egg donor program . cycle cancellation was due to nonavailability of eggs on OPU was seen in 4% cases in our analysis . Presence of oogonial stem cells (OSCs) in the ovarian cortex , hinting at a possibility of therapeutic stimulation of post-natal folliculogenesis in subfertile women it is postulated that ovarian aging or insufficiency could be reversed if OSCs are provided a healthy environment. Ovarian rejuvenation therapy is a new and innovative approach to enhancing fertility in this group of patients . It is often carried out using platelet-rich plasma (PRP) or stem cell therapy. Ovarian Rejuvenation with Stem cells is also called Autologous Stem Cell Transplant in the Ovary (ASCOT). PRP is having lots of advantages like therapeutic effect, cost effectiveness, ease of isolation and autologous nature. However some drawbacks are also there like inconclusive efficacy and lack of understanding of mechanism of action, lack of RCT /fundamental research . regenerative processes organized by platelet cytokines in somatic cells are poorly understood . PRP infusion may only be an appropriate treatment for select ovarian disorders. perimenopausal women and women deemed to be POR benefitted the most from the treatment, more so than POI and menopausal patients . platelet cytokines are ligands that attach to cell membrane receptors—not the nucleus . no case of tumorogenic activity observed in any clinical context so far . Further reassurance comes from work in other human tissue treated with PRP, where accelerated growth of healthy cells was noted without triggering malignant transformation . 13 registered clinical trials investigating the effect of PRP on ovarian rejuvenation .few of these trials describe the inclusion of appropriate PRP controls. It is only from well-controlled trials, built on detailed mechanistic understanding that we can clarify the platelet-mediated effects of PRP therapy in ovarian rejuvenation and folliculogenesis. The PRP injections into the ovaries are safe, productive, and a natural treatment that may help women with premature ovarian insufficiency to give birth to their own child . Stem cell therapy is attracting attention in the field of regenerative medicine and is advancing rapidly. Many recent studies have applied stem cell therapy to treat reproductive system diseases; however, data are not yet available as to whether this therapy shows enhanced therapeutic effects. It is evident that stem cell therapies have potential in treating POI. Stem cells and their exosomes, including content such as miRNAs, show positive effects in enhancing and restoring various aspects of ovarian function, such as folliculogenesis, the GC apoptosis rate, vascular formation, and genetic stability. Among the 10 clinical trials in the NIH database, only 4 have been completed; the rest are ongoing, recruiting and/or active. Research subjects have been selected by strict standards. Although there are several active ongoing clinical trials for POI using stem cell-based therapeutics, there are restrictions in each country regarding ethical and clinical concerns from the health-care community .Potential of stem cell therapies in treating POI still needs further research and clinical results.

P-711 Are there any differences among blastocyst euploid and mosaicism rate (high or low) using fresh or frozen ejaculate sperm in donated oocytes?

Abstract Study question To compare euploid and mosaicism rate (high or low) among blastocysts derived from fresh and frozen ejaculate sperm in donated oocytes. Summary answer No statistically significant differences were found on blastocyst euploid and mosaicism rate between blastocysts derived from fresh versus frozen. What is known already Even though 5%-10% autosomal aneuploidies and 5%-100% sex chromosomes aneuploidies are paternally derived, the clinical relevance of paternal contribution to chromosome aneuploidy is frequently overlooked. Besides, male infertility could contribute to the generation of chromosomal abnormalities in the resulting embryos. Sperm cryopreservation is a widely used technique in assisted reproduction for different reasons. However, little is known regarding the potential effect of sperm freezing on embryo aneuploidies. Study design, size, duration Retrospective, observational and multicenter study of patients undergoing Preimplantation Genetic Testing for Aneuploidies (PGT-A) from January 2017 to December 2022 in IVIRMA Madrid, Valencia and Barcelona. To elucidate the effect of advance maternal age, 1,780 biopsied blastocysts coming from the egg donation program were analyzed. Autologous sperm samples with less than 2 million spermatozoa per milliliter and male partners with altered karyotype, abnormal spermatozoa fish or any genetic disease were excluded from the study. Participants/materials, setting, methods Embryos were cultured in regular incubators, with an atmospheric concentration of 5% O2, 6.5% CO2 and a temperature of 37ºC. Blastocyst biopsy was performed either on day 5 or day 6 of embryo development and analyzed through Next Generation Sequencing (NGS). Sperm freezing was done following manufacturer’s instructions (Sperm freeze, Origio). Continuous variables were compared with a student´s t-test and categorical variables with a Chi-square using SPSS statistical program. Main results and the role of chance Mean paternal age (44.3±5.20 years old vs 43.2±5.20 years old), sperm concentration (46.67±33.05 mill/ml vs 35.1±32.92 mill/ml) were not significantly different among fresh versus frozen sperm group (p > 0.05). A total 1780 blastocysts tested for PGT-A were included: 1267 blastocysts coming from fresh ejaculate sperm (n = 194 patients) and 513 blastocysts from frozen sperm (n = 81 patients). No statistically significant differences were found in blastocyst euploid rate between fresh versus frozen ejaculate sperm (64.5% versus 67.2%, p = 0.278 ;) respectively. Blastocyst mosaicism rate: High mosaicism (>50% of aneuploidy trophectoderm cells) and low mosaicism (30-50% of aneuploidy trophectoderm cells) was comparable between fresh versus frozen sperm (2.7% versus 4.5%; p = 0.90) and (3.9% versus 3.7%), respectively. Limitations, reasons for caution This study is based on a retrospective data. Wider implications of the findings According to our findings, there are no statistically significant differences in the blastocyst euploid and mosaicism rate between fresh and frozen ejaculate sperm. Trial registration number Not Applicable

O-022 Shall we go “natural” for endometrial preparation in egg donation programs? Live birth rates and obstetrical outcome from 797 frozen single-blastocyst transfers cycles

Abstract Study question Frozen single blastocyst transfer in modified natural cycle (mNC) increases success rates reducing obstetric risks in egg recipients, compared to Hormone Replacement Therapy (HRT) protocols? Summary answer In egg recipients, single-blastocyst transfer in mNC showed higher pregnancy rates, lower miscarriage rates, higher new-born rates compared to HRT, being preterm birth rate comparable. What is known already When choosing endometrial preparation protocols for egg recipients, we must consider medication safety and costs, cycle’s cancellation rate, clinical outcomes as maternal and fetal risks. The superiority of mNC over HRT for frozen embryo transfers (FET) has been reported in terms of delivery and miscarriage rates as well as obstetrical complications, but few data are available on egg recipients, being HRT protocols the routine treatment in most cases. In donor programs, when a blastocyst freeze-all strategy or egg banking is applied, there is no longer need for donor-recipient synchronization and many FET could be performed in mNC cycles. Study design, size, duration Retrospective single-centre comparative clinical study, including 797 frozen single-blastocyst transfer (FSBT) initiated cycles between January 2020 and December 2021: 590 (74%) in HRT protocol and 207 (26%) in mNC protocol. The two groups were homogeneous for donor’s age (25,4 yo HRT Vs 25,8 yo mNC), recipient’s age (42,1 yo HRT Vs 42,4 yo mNC), severe male factor (6% HRT Vs 4% mNC), and the need for a sperm donor (28% HRT Vs 22% mNC). Participants/materials, setting, methods Among 797 started cycles, we compared cancellation rates between HRT and mNC groups due to either medical reasons (inadequate endometrium, bleeding, ovulatory leak) or other issues (no embryo survival, flight cancellations, COVID-19 restrictions). We studied the clinical outcomes of the 683 FSBT performed, comparing HRT and mNC cycles for pregnancy rate, clinical pregnancy rate, miscarriage rate, live birth rate, and preterm birth rate <35 weeks. We used Chi-square test to compare groups (p < 0,05). Main results and the role of chance CANCELLATION RATES: Out of the 797 endometrial preparation cycles started, the overall cancellation rate was 14% from which 72,8% due to medical reasons (inadequate endometrium, bleeding, ovulatory leak) and 27,2% due to other issues (no embryo survival, SARS-Cov-2 related issues, flight cancellations, etc.); when evaluating cancellation for medical reasons, we didn’t find significant differences between HRT protocol cycles (9%) and mNC protocol cycles (7%), p = 0,33. CLINICAL OUTCOMES: Out of the 683 frozen single blastocyst transfers performed, no twin pregnancies occurred as expected. There were no statistically significant differences between HRT Vs mNC endometrial preparation protocol when comparing pregnancy rates (59% Vs 63%, p = 0,35), clinical pregnancy rates (49% Vs 57%, p = 0,10) and miscarriage rates (19% Vs 16%, p = 0,48). Live birth rate was significantly higher in the mNC (47%) compared to HRT (38%), p = 0,046. Overall preterm birth rate <35 weeks was 3,9%, including <32 weeks 1,1% and <28 weeks 0,3%. There were no significant differences between HRT and mNC endometrial preparation protocol for preterm birth rate <35 weeks (3,6% Vs 4,6%, p = 0,75). Limitations, reasons for caution Single-centre retrospective comparative trial. Homogeneity studies included several confounding variables, but other bias could have been studied such as uterine factor, PGT-A rate or previous fertility treatments. Wider implications of the findings In donor programs, the use of modified natural cycle should be encouraged as first option irrespectively from recipient’s age for FET in normo-ovulatory patients, considering the increased live birth rates when compared to HRT-FET cycles. Moreover, mNC cycles are more patient’s friendly and cost-effective. Trial registration number not applicable

P-617 Combined oral contraceptive pill (COCP) pre-treatment and progestin-primed ovarian stimulation (PPOS) protocol: a detrimental combination for the oocyte yield in egg donation programs

Abstract Study question Could the use of combined oral contraceptive pill (COCP) pre-treatment before controlled ovarian hyperstimulation (COH) have a negative effect on oocyte yield in normo-responders patients? Summary answer When COH with progestin-primed ovarian stimulation (PPOS) protocol in normo-responders patients is performed, the COCP pre-treatment could have a detrimental effect on oocyte yield. What is known already COCP pre-treatment is widely used to schedule the start of COH and to organize the working week, but its usefulness and efficiency are still not clear. Most of studies on IVF outcomes have shown no effect of COCP on oocyte yield. For oocyte donation only few studies were carried out showing controversial effects on oocyte yield, but all considered short antagonist or long agonist protocols and no one PPOS protocol. COCP leads to long lasting pituitary suppression and lower LH level in follicular phase that could reduce the ability to effectively respond to GnRH-agonist trigger leading to poor oocyte yield. Study design, size, duration The egg donation cycles carried out from January to September 2022 in Next Fertility Valencia were retrospectively analyzed. Two analyses were conducted. Analysis A, comparative retrospective cohort study of 397 COH cycles: 290 with COCP and 107 without COCP. Analysis B, comparative retrospective paired study of 90 COH cycles: 45 with COCP and 45 without COCP, in which, to attempt to eliminate possible bias due to interpersonal differences, every patient was her own control. Participants/materials, setting, methods All donors underwent to COH with FSH monotherapy, PPOS protocol for pituitary suppression and a GnRH-agonist triggering. The oocyte yield was analyzed focusing on: the number of oocytes retrieved, mature (MII) oocytes and useful oocytes (good mature oocytes used for ICSI), the appropriate response to the GnRH-agonist trigger, the stimulation days, the total gonadotropins dose used and the cancellation rate (for low response or low LH level in follicular phase the first day of COH). Main results and the role of chance In both analyses, the data showed no differences in terms of stimulation days, total FSH dose, number of follicles ≥ 15 mm on the trigger day regardless of use of COCP. After conducting the analysis based on the administration or not of COCP, in the Analysis A a higher number of total oocytes retrieved, mature oocytes and useful oocytes were found in the group that did not used COCP. A significant difference in a nominal variable (Pearson's chi-square test) was observed, consisting of a higher proportion of cancellations due to low LH level (< 2,5 mUI/ml) in the group that used COCP (COCP no: 0.7% vs. COCP yes: 3.7% ). While, in the Analysis B (analysis of variance of one factor, Anova test), the variables total oocytes retrieved, total MII oocytes and total useful oocytes showed significant differences consisting of a higher number of oocytes in the group that did not received COCP. These results have statistical significance both before removing the cases in which the values were 0 due to a cancellation (p < 0.01), and after removing the cancelled cases (p < 0.05). Limitations, reasons for caution The main limitation lies in the retrospective nature of the study. However, since each patient is her own control (Paired study), it gives an added value. Wider implications of the findings COCP before COH in PPOS cycles could have detrimental effects on oocyte yield, reducing the efficacy and efficiency of egg donation programs. This could be extended to social freezing programs in normo-responders patients, in which the probability of future pregnancy is closely linked to the number of good oocytes vitrified. Trial registration number Not Applicable

P-452 Economic impact of antagonist stimulation protocol vs progestin primed stimulation protocol in oocyte donor program A retrospective study

Abstract Study question Is the cost per oocyte lower in antagonist ovarian stimulation protocol vs progestin primed ovarian stimulation protocol in oocyte donation program? Summary answer The cost per oocyte is lower in progestin primed stimulation protocol in oocyte donation program What is known already 1. The use of progesterone during ovarian stimulation is effective in blocking the LH surge, and it does not affect the number of oocytes collected or the quality of the embryos obtained. Progestins can be used orally and are less expensive than GnRH analogues. These new regimens enable more flexibility and are interesting but their medical and economic significance remains to be demonstrated. Study design, size, duration Calculation of cost-effectiveness ratios (cost per mature oocyte achieved) using data derived from retrospective clinical practice in a large egg donor program of a single University Hospital between 2011 and 2021 5677 egg donor cycles identified from the electronic medical records database were eligible. Participants/materials, setting, methods Donors fulfilled national legal and medical-guide requirements, 18- 35 y.o, regular menstrual cycles, BMI 18-30 Kg/m2, no relevant medical history and normal karyotype. They were divided into 2 groups(4subgroups): Antagonist FSH stimulation group(subcategory recombinant and biosimilar FSH) and Progestin primed FSHstimulation group(subcategory recombinant and biosimilar FSH). Demographic data were collected and compared between groups. The cost per unit of gonadotrophin, progestin and antagonist was calculated according to the manufacturer’s sale price. Main results and the role of chance The mean age of women recruited into the study was 26,5 years. The distribution into the different study groups was as follows: 1.1. 3155 (55,6%) in recombinant FSH antagonists group (FSHrA), Mean days stimulation 9,17-antagonists 4,91; mature eggs:13,62 2.2. 1489 (26,2%) in biosimilar recombinant FSH antagonist group (FSHrbA), Mean days: stimulation 9,17-antagonists 5,28; mean mature eggs: 13,37 3.3. 187 (3%) in recombinant FSH progestin primed group (FSHrPP), Mean days stimulation 9,26-desogestrel 23; mean mature eggs: 12,54 4.4. 846 (14,9%) in biosimilar recombinant FSH progestin primed group(FSHrbPP). Mean days stimulation 9,07-desogestrel 24; Mean mature eggs: 13,78 According to clinical outcomes in oocyte donor, we did not find statistical differences neither in the mean of days of stimulation nor in mature eggs collected in each treatment group but there is a higher rate in the range of 0-4 mature eggs collected in Progestin primed group. The costs for each drug were as follows: 0,33-0,382€ per unit of recombinant FSH; 0,299-0,33€ per unit of recombinant biosimilar FSH; 25,85€ per unit of Ganirelix; 0,14 per unit of Desogestrel. In conclusion, cost savings can be achieved using FSH progestin primed treatment. The cost per mature oocyte is 52,59€ compared with 58,25€ per oocyte in FSH antagonist group. Limitations, reasons for caution Cancellations before reaching pickup are not contemplated,they may increase the total cost of the cycle. Although the days of stimulation are equivalent in the different groups, the cost of visits including the costs of nursing, infrastructure, patient care time and consumables might be different between the groups. Wider implications of the findings Progestins can present an effective option for egg donation programs in terms of cost Trial registration number not applicable

P-178 Time to hatching: the most predictive morphokinetic parameter for embryo implantation in machine learning algorithms following time-lapse incubation and blastocyst transfer in oocyte-donation programs

Abstract Study question Which is the most predictive parameter when machine learning (ML) is applied to a known implantation database (KID) of day 5 embryo transfer database in an egg donation program? Summary answer Time to hatching (tiHB) is the most predictive embryonic parameter when machine learning algorithms were used on reproductive data in an oocyte donation program. What is known already Artificial intelligence is becoming an encouraging tool in medicine, also in ART, where the amount of data generated in the IVF lab has dramatically increase, favored by time-lapse technology. Numerous embryo selections algorithms based on logistic regressions have been developed for predicting blastocyst formation and implantation potential, but with machine learning, we can train algorithms and connect different morphological and morphokinetic embryo parameters with implantation or even live birth embryo potential. The aim of this study was to test machine learning algorithms and to identify predictive embryonic morphokinetic parameters when comparing the different models generated after machine learning analysis. Study design, size, duration Retrospective analysis of 405 embryos in a KID obtained after 392 embryo-transfers (13 double and 379 single-ET) performed in an oocyte donation program in 4 fertility clinics (year 2021). Recipientś average age: 42.2±4.2 years. The embryos were cultured in Global® Total® culture medium in Geri® (Genea Biomedx) time-lapse incubators after ICSI until embryo transfer at blastocyst stage. Only sperm samples >1x106 spermatozoa/ml were included. All parameters were registered by one single trained senior embryologist. Participants/materials, setting, methods Thirty-five variables were initially analyzed: classic morphokinetic markers, time intervals (including total thinning time before hatching: tiHB-tFB and total blastulation time before hatching: tiHB-Tcav) and morphological measurements (blastocyst and inner cell mass diameter 110h post-injection). Eighty percent of the data was used for model training and 20% was reserved for model validation. Twelve supervised and unsupervised predictive machine learning models were developed. The software used to carry out the analysis was SPSS (v20.0) R (4.0.5). Main results and the role of chance The basic characteristics of the embryo population were similar. From the 405 embryos transferred, 216 blastocysts came from vitrified oocytes (53.3%). The implantation rate was 57.03% (231 gestational sacs) and the miscarriage rate was 16.8%. The classification-supervised algorithms applied included binary logistic regression, neural networks, support vector machines, neighborhood-based methods, classification trees, boosting and bagging methods. The algorithms were optimized by minimizing the AUC. Cluster analysis (unsupervised) was also performed. In the 6 best predictive models, the variables with the highest relevance were tiHB (hatching initiation time), tiHB-tFB and tiHB-tcav: variables related to hatching initiation. Furthermore, in the cluster analysis, these three variables appeared grouped in the same cluster. From the blastocysts population that implanted, 57.6% (133/231) were initiating hatching, while from those embryos that did not, only 42.3% (74/174) began the hatching process. Other variables such as the diameter of the transferred blastocyst, which we assumed to be valuable as an objective morphological parameter, did not show a high predictive capacity in the models obtained. Blastocyst average diameter of implanting blastocysts was 157.9±24.9 µm and non-implanting was 153.9±26.1 µm. Limitations, reasons for caution Morphology and morphokinetic parameters require subjective annotation and thus might have intrinsic intra-reader variability. Our findings need to be validated prospectively. Wider implications of the findings Time to blastocyst hatching appears to have significative impact in most ML predictive models. Hatching-related variables seems to have predictive power. Despite numerous variables influencing IVF outcome (intrinsic and extrinsic to embryo development) ML and AI approaches may improve the prioritization of the most viable embryo favoring single embryo transfer. Trial registration number 2021ibmad001

P-165 Which are the determining factors influencing the success rate of egg donation programs with imported vitrified oocytes?

Abstract Study question Which are the determining factors influencing the success rate of egg donation programs with imported vitrified oocytes? Summary answer Number of oocytes available after warming, male BMI and semen characteristics are critical parameters influencing reproductive results of oocyte donation programs with imported vitrified oocytes What is known already The use of vitrified oocytes from foreign banks and the performance of ICSI using fresh sperm from the recipient's partner is a widely used method of heterologous fertilisation. Recent evidence has questioned the overall effectiveness of this approach: vitrification and warming may reduce the number of oocytes available for insemination, resulting in a lower rate of live births per cycle. Recent studies have attempted to define the right clinical strategy to improve the effectiveness of oocyte vitrification cycles, stressing the importance of the number of imported oocytes (8-9 oocytes) and transfer to the blastocyst stage. Study design, size, duration Observational longitudinal cohort study of 431 cycles of oocyte donation conducted between January 2015 and February 2019. A total of 398 couples (mean female age: 43.2 ± 3.5, 28-50 years; mean male age: 44.7 ± 6.1, 28-73 years) underwent an IVF cycle with imported donated vitrified oocytes (mean donor age: 25.2 ± 3.5, 19-34 years). All consecutive oocyte donation cycles conducted at the centre for Reproductive Medicine of the European Hospital in Rome were included. Participants/materials, setting, methods In order to assess which factors are associated with the various outcomes, uni-and multi-variable analyses were conducted. In the multivariable analyses, variables that showed a p value<0.1 in the univariable analyses were included in the final model. The results were presented as Odds Ratio (OR). The corresponding 95% Confidence Interval (95% CI) was also exposed. A p value <0.05 was considered statistically significant. All analyses were performed with STATA v16.1 statistical software. Main results and the role of chance A univariate analysis was carried out showing that among the demographic characteristics studied, the only one that proved significantly able to influence the outcome of the pregnancy test was male BMI. In 49% of unsuccessful cycles, the male BMI was above 25 (p = 0.03). The correlation is confirmed when comparing cycle outcomes in couples with normal/underweight vs overweight/obese men (p = 0.03). The relationship between female or donor BMI and treatment outcome, however, was not statistically significant. The day on which embryo transfer is performed affects the outcome of the cycle: transferring on day 2 compared to day 5 reduces the probability of clinical pregnancy (ET in day 2= positive clinical pregnancy in 4/16 (25%); ET in day 3= 158/307 (51.4%); ET in day 5=40/67 (59.7%). The relationship between male BMI classes and sperm parameters was studied: the distribution of concentration is different in the 3 BMI groups (p = 0.011); in particular, obese men have a significantly lower concentration than normal-weight men (p = 0.006 after Bonferroni correction). There were no statistically significant differences in volume (P = 0.722), morphology (p = 0.100) and motility (p = 0.179), although there was a downward trend in motility, with a reduction in obese subjects compared to normal weight. Limitations, reasons for caution This is an observational study and our findings are in contrast with previous studies which do not show any correlation between male partner BMI categories and reproductive outcomes in egg donation programs. Wider implications of the findings Our study shows that the number of oocytes available after warming, male BMI, semen characteristics and blastocyst transfer are critical parameters able to influence the reproductive outcomes of egg donation programs with imported vitrified oocytes. Trial registration number Not applicable

P-722 Ending the anonymity of egg donors in shared donation programs could reduce the number of participants

Abstract Study question Loss of egg donor anonymity could affect shared donation programs in Brazil? Summary answer Yes. Approximately 20% of the women who participated in this study would drop out of the program, especially those with higher incomes. What is known already The Brazilian Federal Council of Medicine seems to be increasingly flexible with regard to maintaining mandatory secrecy on the identity of donors. The resolution regarding assisted reproduction techniques, approved in 2021, concerns the possibility of donation between family members, up to fourth degree relatives. The possibility to know and have access to this identity or even the search for half-brothers can be a reality in many countries for children born through access to reproductive technology but the opinion or behaviour of this population about the presence or absence of anonymity is limited to a few studies. Study design, size, duration Women (n = 800) who applied for enrolment in the shared egg donation program at a private IVF clinic were invited to participate in an electronic survey developed using the online Survio® tool. The invitation to participate was sent by email from June to November 2021. 279 women (34.8%, 20-35 years) responded to the survey. Participants/materials, setting, methods The information was obtained through questioning and gaining information about: socioeconomic profile of the donors, their motives, ambivalence in relation to the sharing of eggs and feelings about a possible end of anonymity. Thereafter, answers given to 10 specific questions were recorded. Furthermore, a correlation analysis was performed to assess the relationship between acceptance of the end of donor anonymity and various study parameters. Main results and the role of chance Approximately 61% of patients would want to become egg donors for two reasons: to reduce IVF costs and to help another woman. However, significantly younger women want to be part of the egg donation program just to reduce their treatment costs (P < 0.05). Approximately 71% of women do not want any contact with the child born from their eggs; 69% of them would not like to meet the recipients and 75% would not like to meet the child, even if only the recipient had become pregnant. If donors lost a child, they would not even want to meet the child who was born with their donated eggs (76%). Most participants also responded that they would be in the program even if the anonymity was not maintained (80%). However, women with higher income would drop out of the program if donor anonymity was not maintained (56.3%) compared to women with lower income (13.5%;P < 0.001). Limitations, reasons for caution Confounding variables related to the male partner's opinion cannot be excluded. Studies with larger samples are needed to confirm these findings. Wider implications of the findings A possible end to the anonymity of egg donors in Brazil would pose numerous challenges to the current practice of gamete donation. These concerns give rise to a broad discussion in society about how best to safeguard and promote the interests of donor-conceived children and protect the rights of donors. Trial registration number Not applicable.

P-245 Cumulative live birth rates in egg donation regarding the origin of oocytes (fresh or cryopreserved oocytes) in unsynchronized cycles

Abstract Study question Is there a difference in cumulative live birth rates between the two groups of fresh or cryopreserved donor oocytes? Summary answer In egg donation cumulative live birth rates achieved with fresh donor oocytes are similar to those with cryopreserved donor oocytes. What is known already The improvement techniques of cryopreservation of gametes and embryos with vitrification has played an important role in ART and Oocyte Donation Programs. Oocyte donation is a worldwide established method for women with premature ovarian failure, those with repeated (IVF) failure, or those who have inherited genetic abnormalities. The increasing use of Oocyte cryopreservation has improved the outcomes and the success rates. However, cryopreserved-donated oocytes have been still achieved lower live birth rates in comparison to fresh donor oocytes. Study design, size, duration This study was carried out in Assisting Nature IVF Unit from January 2015 to December 2020. 191 recipient’s cycles were examined for the cumulative live birth outcomes according to the origin of oocytes. Group A include cycles with fresh donor oocytes from the retrieval day and Group B include cycles with cryopreserved donor oocytes. Participants/materials, setting, methods 191 recipient cycles participated in the study. Group A (n = 133) received fresh donor eggs in which the formed blastocysts were cryopreserved and then were thawed for the first embryotransfer (ET). Acceptors in Group B (n = 58) received cryopreserved donor eggs and carried out a fresh embryotransfer. The rest of formed blastocysts were cryopreserved and thawed in the next ET. All acceptors transferred at most two embryos and they occurred maximum 3 embryotransfers in egg donation. Main results and the role of chance In Group A 755 fresh donor oocytes were utilized when in Group B were 269 cryopreserved oocytes. Fertilization (87% Group A, 84% Group B) and blastulation rates (70% Group A and 65% Group B) were similar between two groups. Cumulatively the live birth rate in Group A was 61% (1st ET: 51,1%, 2nd ET: 9%, 3rd ET: 0,9%). Acceptors with a failure in the first ET carried out a second ET or in the third ET with cryopreserved blastocysts. In Group B acceptors achieved 59% live birth rates (1st ET: 50%, 2nd ET: 9%). Some acceptors after the failure of the first ET carried out a second ET and delivered a healthy baby. There was not observed significant difference in live birth rate between two groups. The vitrification and warming stages in oocyte cryopreservation has been dramatically improved in recent years and therefore in our study seems to have equal live birth rates as in the fresh oocytes in egg donation program. Limitations, reasons for caution Large scale studies are required with further investigation with more equal number of studied patients between groups. Moreover, information regarding sperm quality parameters, embryos quality or endometrium should be considered. Wider implications of the findings Acceptors should be reassured that the origin of oocytes does not have impact in the likelihood of becoming pregnant. Trial registration number NONE

P-276 Embryo development of fresh versus vitrified metaphase II oocytes in low prognosis patients: a retrospective sibling-oocyte monocentric study

Abstract Study question Do fresh and vitrified/warmed oocytes have the same developmental potential in low prognosis patients defined by POSEIDON criteria? Summary answer Embryos derived from vitrified/warmed oocytes show lower competence for embryo development when compared to those obtained from fresh oocytes in low prognosis patients. What is known already The strategy of oocyte accumulation has been proposed for the management of low-prognosis patients with the aim to increase the number of oocytes available for fertilization and further the number of embryos. The effect of oocyte vitrification/warming on the embryo developmental potential has mainly been studied in oocyte donation programs. Investigations on sibling-oocyte failed to show difference in the morphological embryo development, but the evaluation stopped after 2-3 days of embryo culture. In addition, morphokinetic evaluation revealed delayed development of embryos derived from vitrified oocytes, from the first cleavage to the time of blastulation. Study design, size, duration Single-center sibling-oocyte retrospective monocentric study including low-prognosis patients, defined by POSEIDON criteria, who had undergone an accumulation of oocyte strategy for managing their infertility, between November 2013 and January 2021. Only patients presenting fresh and vitrified/warmed oocytes at the time of insemination were analyzed for the sibling-oocyte comparison. Main study outcomes were fertilization, cleavage, blastulation rates, day-2 and day-5 embryo quality, and the rate of embryos available for transfer/cryopreservation. Participants/materials, setting, methods Forty-five patients were included, with a mean age of 34.8 ± 3.4 years. Oocyte vitrification/warming was performed using the Cryotop method. Top-quality and good-quality embryos were defined at day-2 respectively as 4 and 3-5 adequate-sized blastomeres, without multinucleation and containing <20% of cytoplasmic fragmentation, and at day-5 according to Gardner and Schoolcraft’s classification, top ≥B4 (AB/BA/AA) and good ≥ B3BB. Statistical analyses used mixed effects logistic regression to take into account the sibling-oocyte design. Main results and the role of chance A total of 656 oocytes were inseminated, 225 fresh and 431 vitrified/warmed oocytes. The oocyte survival rate after warming was 82%, 95%CI [76-87%]. There was no difference between fresh and vitrified/warmed oocytes groups regarding the degeneration rate following ICSI (5.0% vs 4.8% respectively, p = 0.95), the fertilization rate (74.6% vs 71.4% respectively, p = 0.42) or the cleavage rate on day-2 (98.3% vs 95.4% respectively, p = 0.15). However, the embryo development was significantly different from day 2, with higher day 2 top-quality and good-quality embryos rates in the fresh oocytes group when compared to the vitrified/warmed oocytes group (top-quality: 38.3% vs 24.8% respectively, p = 0.01; good-quality 58.0% vs 45.2% respectively, p = 0.02). The same results were observed on blastocysts when extended culture was decided, with a higher blastulation rate in the fresh oocyte group (56.7% vs 31.7% respectively, p < 0.001) and higher top-quality and good-quality day 5 blastocyst rate (top-quality: 23.4% vs 5.6% respectively, p = 0.01; good-quality 23.9% vs 7.9%, p = 0.01).The rate of embryos available for transfer/cryostorage was similar in both groups (40,7 % vs 38,8 %, p = 0,71). The cumulative live-birth rate was 33,3% (4/45 from vitrified oocytes group, 5/45 from fresh oocytes group, 6/45 from mixed oocytes group). Limitations, reasons for caution The retrospective nature of the study, on a limited number of limited number of patients represents an inherent limitation. Embryo assessment was subjective, the evaluator knowing the oocyte’s source group. The impact of the morphological alterations observed in embryos derived from vitrified/warmed oocytes need to be confirmed with clinical outcomes. Wider implications of the findings The majority of studies comparing fresh and vitrified/warmed oocytes were performed in egg-donation programs. This study focuses on low-prognosis patients, who reflect perhaps more the patients who consult in ART centers. Further prospective studies are needed to confirm our findings. Trial registration number Not applicable

O-070 Double stimulation in egg donors: is an adequate strategy to optimize the gamete donation program?

Abstract Study question Is double stimulation (DuoStim) a viable strategy to optimize the performance of the egg donation program? Summary answer Carrying out two consecutive stimulations in the gamete donation program allows the number of donations to be increased, optimizing its efficiency while maintaining donor safety. What is known already DouStim (double stimulation) consists of two successive ovarian stimulations in the follicular and ensuing luteal phase with two oocyte retrievals at the end of both ovarian stimulations. This non-conventional strategy, developed to retrieve the greatest number of oocytes in the shortest possible time, was designed initially to optimize clinical outcomes in poor ovarian response, but double stimulation could be useful in patients with a good prognosis such as oocyte donors to optimize the program efficacy. Study design, size, duration Prospective and observational analysis performed in IVI Madrid between September and December 2019. Participants underwent the same stimulation protocol in the follicular phase and for luteal phase stimulation. The study was approved by an Institutional Review Board (1903-MADR-034-AR) and all women provided written informed consent. Participants/materials, setting, methods Follicular and luteal-phase stimulation was the same for all the donors; daily tablet of 10 mg of acetate of medroxyprogesterone (AMP) from first day of stimulation, 225 IU/day recombinant FSH and triggering with 0.1 mg GnRH agonist. To analyze the differences in clinical results between both phases of the cycle, independent donations were made after each oocyte retrieval. Statistical analyses were performed using the Statistical Package for Social Sciences 19.0 (IBM Corporation, Armonk, NY, USA). Main results and the role of chance We included 60 egg donors for a total of 88 recipients who received oocytes retrieved in both the follicular and luteal phases. Although the number of oocytes and metaphase II was significantly higher in the follicular phase compared to the luteal one, 19.8 ± 2.0 vs. 13.3 ± 2.2 oocytes, p < 0.001 and 16.4 ± 1.8 vs. 11.5 ± 2.1 MII, p < 0.001, then this disparity in the results disappears since the rate of usable blastocyst is similar with the same proportion of frozen embryos in both stimulation phases (4.0 ± 0.6 vs. 4.4 ± 0.8, p = 0.451). According to the clinical results, we did not observe significant differences between the follicular and the luteal phase neither for the implantation rate (69.8% vs. 66.1%, p = 0.783), nor for the clinical pregnancy rate (71.2% vs. 66.7%), confirming the possibility of being able to make independent donations of each of the stimulated phases without affecting the chances of success. Limitations, reasons for caution This is an observational study and thus possible confounders cannot be completely excluded. More data are needed to draw firm conclusions and it will be critical to increase the sample size to check if the results observed in this work remains in the general population Wider implications of the findings As far as we know, this is the first study in which a double stimulation protocol is applied in oocyte donors. The fact of being able to increase the number of donations in the same stimulation cycle allows us to improve the efficiency of the egg donation program. Trial registration number Not apply

P-098 Male age does not affect sperm motility rate after thawing and laboratory outcomes of transnational oocyte donation programs

Abstract Study question Can outcomes of transnational egg donation treatments, which involves the shipping of cryopreserved partner semen, be affected by advanced paternal age? Summary answer Male age does not affect percentage of motile spermatozoa after thawing. Advanced paternal age does not affect IVF laboratory outcomes of transnational egg donation treatments What is known already Studies on advanced paternal age are limited and a clear definition of advanced paternal age is still missing. The separation between advanced paternal and maternal age effects is hampered by the collinearity of maternal age with paternal age, since older males are often associated with older women. Many studies have focused on egg donation treatments, to overcome this problem. However, these studies reported conflicting results, such as a putative effect of advanced paternal age on ICSI outcomes, while some others not. This study analyzes paternal age in transnational egg donation program, which involves the shipping of cryopreserved partner semen Study design, size, duration A multicentric retrospective cohort study involving 101 couples and 327 blastocysts was performed from June 2018 up to December 2021. Two Italian IVF centers involved a Spanish center to perform a transnational fresh oocyte donation program. The aim of the study was to analyze the putative effect of male age on (i) semen parameters, (ii) fertilization rate and (iii) blastocyst rate. Participants/materials, setting, methods Donations of both male and female gametes were excluded. We performed sperm cryopreservation of the male partner of the recruited couples. Frozen samples were shipped with a authorized courier, which certified the safety of the whole procedure. The day of donor’s egg retrieval, semen samples were thawed and ICSI was performed on fresh donated oocytes. Resulted blastocysts were vitrified and shipped to the centers where the frozen embryo transfers in the recipient patients were performed. Main results and the role of chance The mean of male partners age was 42.6 ± 6.5 (min 26- max 63). Overall fertilization rate was 81.6% (686/840), and blastocyst rate was 47.6% (327/686). Male age was analyzed as a continuous variable and divided into five groups calculated for 5-year intervals. No differences in terms of fertilization rates nor blastocysts rates were found (85.3% and 43.7% for <35-years; 84.7% and 54.0% for 36-39-years; 79.7% and 44.2% for 40-44-years; 89.6 and 48.1% for 45-49-years; 74.5% and 56.5 for >50-years). Although advanced paternal age has been correlated to the decrease of most of sperm parameters, in the present study we found that only progressive rapid motility was significantly affected by advanced paternal age (coefficient -0.261 , P = 0.009). To evaluate the predictive value of advanced paternal age and sperm parameters on fertilization and blastocysts formation, we performed a multiple linear regression analysis. We found that sperm parameters and male age in our sample are not predictive of the number of fertilized oocytes nor the number of obtained blastocysts. Importantly for the setting of the study, the percentage of progressive motile sperm at the thawing was not influenced by paternal age. Limitations, reasons for caution The main limitation of the study is the small sample size, which might mask the paternal age effect on the sperm parameters, as the volume, which tend to decrease in the classes of age, but did not reached the statistical significance. The multicentric nature of the study represent a strength Wider implications of the findings The discomfort for couples that need oocyte donation in countries where there is a low availability of egg donors is often underestimated. This study demonstrate that, independently of male age, the shipping of frozen sperm and the ICSI of freshly donated oocytes represent a valid option for these couples. Trial registration number not applicable

'Gift with a price tag': Nigerian egg donors' knowledge, experiences and motivations.

Research around the world has indicated that the demand for egg donation has grown considerably among young females. This study qualitatively examines the knowledge, experiences, and motivations of young egg donors at a Nigerian health facility. In-depth interviews were conducted in Igbo and English with consenting thirty-one egg donors attending a fertil-ity clinic in Anambra State, south-eastern Nigeria. Data were collected and analysed to generate themes with the aid of NVivo 10 software. Three themes were identified from the participants' motivations and include (a) monetary (93.6%), (b) altruistic (3.2%), and (c) both monetary and altruistic reasons (3.2%). Findings highlighted that the differences were based on a variety of reasons in Nigeria. All the participants were literate and single, and the majority received payment. The majority (77.4%) of those who received payment mentioned that the payment was not worth the donation program. The participants preferred to be anonymous because they had not discussed their donation with their family members, and the non-acceptance of egg donation program by the Nigerian society. Given that the market for egg donation has become a common method of infertility management in Nigeria, our findings have important implications for practices, policy actions, and future research.