Oocyte Cryopreservation Research Articles

Fertility-sparing strategy in a rare case of highly malignant Dicer-1-associated sarcoma of the cervix

IntroductionWe present the rare case of an 18-year-old patient with a Dicer-1 mutation-associated sarcoma of the cervix uteri.CaseThe patient presented with irregular vaginal bleeding in July 2022. The clinical examination showed an exophytic tumor of the cervix, uterus and ovaries were normal in sonogram. The tumor of the cervix was resected, followed by a diagnostic hysteroscopy and abrasion of the uterine cervix and cavity. Hysteroscopy showed normal findings of the cervix and uterus. After diagnosis of a highly malignant Dicer-1 mutation-associated sarcoma of the cervix, cryopreservation of oocytes was realized. Based on the principle of obtaining maximum oncological safety while preserving fertility in this 18-year-old patient, we recommended chemotherapy rather than radiation with its far severe implications on the patient´s reproductive organs. 4 cycles of chemotherapy consisting of doxorubicin and ifosfamide were applied until December 2022. After re-staging in December 2022 via CT scan and MRI, the abdomen and pelvis as well as control hysteroscopy and abrasion were unremarkable. Until now, the patient is tumor free.DiscussionPrimary sarcomas of the cervix are very rare. Recent literature hints towards a distinct DICER-1 sarcoma entity characterized by specific mutational clusters. Limited follow-up data suggested that DICER1-mutant tumors might exhibit a less aggressive clinical course than DICER1-wild-type tumors.ConclusionDecision-making in case of rare histological entities with sparse recommendations in the literature poses a challenge to the treating physician. Treatment strategies should consider oncological safety as well as options of preserving fertility. Gonadotoxic potential of different strategies should be taken into consideration and discussed in detail with the affected patient.

O-234 Indication for fertility preservation in patients with endometriosis

Abstract Endometriosis is a complex gynecological condition that not only causes debilitating symptoms but also significantly impacts fertility. As the disease affects approximately 10% of women of reproductive age, addressing fertility preservation strategies becomes paramount. The conventional treatments for endometriosis, such as medical therapy and surgery, often fail to fully address its adverse effects on ovarian reserve and reproductive potential. Consequently, there is a growing interest in exploring fertility preservation options, particularly oocyte cryopreservation (OOC), for endometriosis patients. Despite the prevalence and impact of endometriosis on fertility, comprehensive data and guidelines specifically tailored to fertility preservation in this population remain scarce. The available evidence suggests that endometriosis, particularly when it involves ovarian endometriomas, is associated with a significant reduction in ovarian reserve, as indicated by lower levels of anti-Müllerian hormone (AMH). Surgical interventions, often necessary for managing endometriosis-related complications, can further compromise ovarian function and diminish fertility prospects. However, recent studies have shed light on the potential benefits of OOC in preserving fertility for endometriosis patients. OOC offers a minimally invasive approach with no impact on ovarian reserve compared to other fertility preservation techniques. Despite the lack of randomized controlled trials, our retrospective data have demonstrated promising outcomes, with a notable number needed to treat (NNT) of 16 for one successful pregnancy. This underscores the significance of discussing and considering OOC as part of the treatment plan for endometriosis patients, especially those at risk of ovarian compromise due to the disease or its management. The decision to pursue fertility preservation through OOC should be made on a case-by-case basis, taking into account various factors such as disease severity, patient age, ovarian reserve, and treatment history. French guidelines recommend considering OOC for endometriosis patients with bilateral ovarian endometriomas larger than 3 cm or those with endometriomas on a single ovary. Initiating fertility preservation discussions early, preferably before surgical intervention, allows patients to make informed decisions regarding their reproductive future. It is crucial to acknowledge the challenges and uncertainties associated with fertility preservation in endometriosis patients. Socio-economic factors, patient preferences, and the lack of clear criteria for selecting candidates for OOC pose significant hurdles. Furthermore, the effectiveness and cost-effectiveness of OOC in this population warrant further investigation. In addition to OOC, alternative fertility preservation options, such as ovarian tissue preservation, could be considered, particularly in cases where ovarian stimulation is not feasible or declined by the patient. However, data on the efficacy and safety of ovarian tissue preservation specifically in endometriosis patients are limited, highlighting the need for further research in this area. In conclusion, fertility preservation, particularly through OOC, holds promise for mitigating the adverse effects of endometriosis on ovarian function and fertility. While uncertainties persist, integrating fertility preservation discussions into the comprehensive management of endometriosis is essential. This ensures that patients are empowered to make informed decisions about their reproductive health and maximizes their chances of achieving desired fertility outcomes despite the challenges posed by endometriosis.

P-028 Pregnancy and perinatal outcomes in male patients with temporary ejaculation failure undergoing assisted reproductive technology

Abstract Study question When temporary ejaculation failure occurs on the oocyte retrieval day, choose surgical sperm retrieval or oocyte cryopreservation? Summary answer TESA-ICSI and oocyte cryopreservation are both relatively efficient and safe way. Embryos have better developmental potential through TESA-ICSI. What is known already Nearly 9% of men among couples who use assisted reproductive technology have temporary ejaculation failure (TEF) on the oocyte retrieval day. If they fail to provide semen sample, the couples may face three choices (1. surgical sperm retrieval; 2. oocyte cryopreservation; 3. canceling the oocyte retrieval). The aim of the study was to compare the impact of testicular sperm aspiration (TESA) or oocyte cryopreservation on the clinical outcomes of intracytoplasmic sperm injection (ICSI) patients with TEF. Study design, size, duration The retrospective study included 345 male patients with TEF in our University-affiliated IVF center from 2015 to 2021. Participants/materials, setting, methods Three hundred and forty-five male patients were divided into two groups. Two hundred patients chose TESA-ICSI (the TESA group), while another 145 patients chose oocyte cryopreservation, waiting for the man’s next successful sperm ejaculation and subsequent ICSI (the frozen oocyte group). We investigated the embryo development, pregnancy and perinatal outcome, and included the data from fresh embryo transfer (ET) cycle. Herein, all patients in the frozen oocyte group received hormone replacement and fresh ET. Main results and the role of chance Firstly, there were no significant difference in the female BMI, FSH, antral follicle count (AFC), AMH, and male semen quality between the two groups. For embryo development, both two groups have the similar normal fertilization rate (71.5% vs 69.7%, P = 0.242). However, the frozen oocyte group has lower rate of Day3 high quality embryo (31.1% vs 49.3%, P < 0.001), available embryo rate (49.8% vs 55.8%, P = 0.043), and available blastocyst rate (18.6% vs 33.7%, P < 0.001). For pregnancy outcome, the clinical pregnancy rate (44.2% vs 50.0%), pregnancy loss rate (4.8% vs 2.9%) and live birth rate (38.5% vs 46.1%) were similar. And there were no significant differences in the rates of Gestational diabetes mellitus, hypertensive disorders of pregnancy, placenta previa and fetal malformation between the two groups. Limitations, reasons for caution This study only included data from fresh embryo cycles, not yet from thawed embryo cycles. Although we presented complete embryo development data for each couple, there may be some bias in pregnancy and perinatal outcomes due to the lack of data from thawed embryo cycles. Wider implications of the findings The present study suggested that TESA-ICSI and oocyte cryopreservation are both relatively efficient and safe way to help the patients encountering TEF. Due to the embryos with better developmental potential through TESA-ICSI, choosing the surgical sperm retrieval might have more have more advantages, and this has to be further verified. Trial registration number REC No. (2023(S142))

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

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

O-084 Outcomes of female fertility preservation with cryopreservation of oocytes or embryos: a population-based study

Abstract Study question What are the reproductive outcomes observed of patients who cryopreserved oocytes or embryos in the context of fertility preservation in the Netherlands? Summary answer After 10 years follow-up, 25.5% of the women used their cryopreserved oocytes or embryos to attempt pregnancy and of these, 34.6% had a live birth. What is known already Fertility preservation through freezing oocytes or embryos is an established treatment for women with a risk of premature ovarian failure (caused by a benign or oncological disease) or physiological age-related fertility decline. Little is known about the success of freezing protocols, utilization rate of oocytes or embryos and live birth rates. Study design, size, duration A retrospective nationwide observational study was performed in the Netherlands. Data were collected between 2017-2019 from all women who cryopreserved oocytes or embryos more than two years ago in the context of fertility preservation in ten out of twelve IVF centers in the Netherlands. Participants/materials, setting, methods In total 1112 women were included in this study. Medical files and patient databases were used to extract data. The study protocol was approved by the medical ethics committee. Main results and the role of chance Fertility preservation cycles are performed increasingly over the years. In the first years (2004-2007) less than 10 cycles per year were performed, which increased to more than 300 cycles per year in ten years’ time (since 2016). Initially embryos were frozen in the context of fertility preservation. In the later years cryopreservation of oocytes became the standard approach. The median number of oocytes cryopreserved was 13 per woman (range 1-52) and of embryos cryopreserved was 6 (range 1-32). Cryopreservation of oocytes versus embryos resulted in a comparable median number of eligible embryos for transfer (3 and 4 embryos respectively). The 5-year utilization rate was 12.3% and 10-year utilization rate was 25.5%. The cumulative clinical pregnancy rate after embryo transfer of cryopreserved oocytes or embryos was 39.2% and the live birth rate was 34.6% per patient. The return rate of those who had fertility preservation due to benign diseases was higher than for the other indications after five years, namely 17.1% (p < 0.05). After ten years the return rates for the other indications increased to similar percentages for all indications. Limitations, reasons for caution The follow-up period varied between patients and not all cryopreserved material was used yet at the end of this study. This might have led to underestimated pregnancy rates. Further, intention-to-treat analysis could not be performed since women who had a fertility preservation procedure without freezing were not included. Wider implications of the findings This study provides data on the reproductive outcomes after fertility preservation. This knowledge can be informative for professionals and future patients to improve counseling and informed decision making regarding ovarian stimulation in the context of fertility preservation. Trial registration number n/a

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

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

O-108 Acceptance rates and reasons for social oocyte cryopreservation among women: systematic review and meta-analysis

Abstract Study question What are the acceptance rates and reasons for social oocyte cryopreservation (SOC) in the general population and healthcare professionals/students according to the current literature. Summary answer Acceptance rates for SOC was 54%. Lack of a partner and coverage of the costs contributed the acceptance with no differences in subgroup analysis. What is known already Oocyte cryopreservation is used for different purposes such as fertility preservation, social reasons and assisted reproductive treatments. In the last 15 years, many studies have been published in the literature examining the reasons and thoughts of women about oocyte freezing in different countries and groups. There is no study that evaluates this body of literature with a general view on social cryopreservation specifically and with the subgroups of the general population and healthcare professionals/students. Study design, size, duration A systematic review and meta-analysis were performed following the PRISMA guidelines after a comprehensive literature search using PubMed, EBSCO MEDLINE complete, Web of Science, ScienceDirect, Scopus and CINAHL databases between July and September 2023. Studies reporting findings about our primary outcomes including acceptance rates and reasons for SOC in general population and healthcare professionals/students were eligible without limitation on the publication year. Participants/materials, setting, methods Two reviewers independently reviewed eligibility and assessed for quality using Joanna Briggs Institute checklists. Totally, 23 studies were included. Data were expressed in risk ratio with a 95% CI using a random effect model. Prevalence estimates were calculated using meta-analysis of the proportion of women who viewed SOC acceptable. Heterogeneity was calculated using CochranQ and I2 statistics. The Q statistic was reported as p values, and the I2 statistic was reported in percentages. Main results and the role of chance In the metaanalysis based on the previous research data; the overall acceptance rate of social oocyte cryopreservation was found to be 54% (95% CI = 46%–62%). In subgroup analysis performed for healthcare professional/students, acceptance rates were not significantly different (95% CI = 0.47-0.61; p > 0.05). Heterogeneity was high for the acceptance rates of SOC (I2=98.64%, τ2=0.78, df = 22; p < 0.001). In subgroup analysis, acceptance rates were evaluated according to the most common reasons for acceptance. Acceptance rates when the cost of SOC is covered was 57% (95% CI = 0.40% - 0.71%, I2 = 98.62%, τ2 =0.88, df = 7; p < 0.001) and this rate was 49 % in the absence of a partner (95% CI = %34 - %64). Heterogeneity was high (I2=%98,81, τ2=0,96, df = 10; p < 0,001). Acceptance rates according to the reasons did not differ significantly in the subgroups for general population and healtcare professionals/students (coverage of cost: 95% CI = 0.59-0.45; p > 0.05; absence of a partner: 95% CI = 0,51-0,55; p > 0,05). Limitations, reasons for caution Some of the included studies had sample sizes that were not large enough to provide sufficient power for reporting on the disposition decision question. Wider implications of the findings Metaanalysis revealed that more than half of the women viewed SOC acceptable, acceptance varied within a wide range and increased in the absence of a partner and covering the cost. Findings of this review underline that affordable oocyte cryopreservation will increase the use of SOC among women of reproductive age. Trial registration number Not applicable

O-182 To err is human, also for those working in ART

Abstract Medically assisted reproduction (MAR) centers combine clinical and technical expertise with a very high complexity. Over the years, MAR centers have undergone increased intricacy due to incorporating laboratory techniques, such as cryopreservation of oocytes and embryos and micromanipulation, embryo culture, and pre-implantation genetic testing. Not only the technicality of the MAR laboratory profession is challenging, but the complexity of each phase has increased over the years; the patient population undergoing treatment has expanded, where not only the intended parents’ gametes are involved but also the utilization of gametes from egg and sperm donors, as well as including a gestational carrier receiving the embryo. These complexities have led to the implementation of rigorous control measures to mitigate the risk of errors. Nevertheless, a zero-risk fertility clinic is an illusion, given the many necessary interventions and manipulations in each treatment cycle. Errors in fertility practice involving gametes or embryos can be devastating to patients and clinical personnel, often raising psychological, legal, ethical, economic, and practical concerns. The most critical cases of risk of harm in MAR procedures involve misidentifying a patient, gamete, or embryo, called ‘mix-up,’ which could lead to dramatic consequences. Although the frequency is low, mix-up cases have been described worldwide. Other adverse events derive from preventable human actions, e.g., overlooking an embryo when carrying out assessments, dropping a dish, incorrect labeling, improper pipetting technique, unusually poor thawing, and inadvertent discard of the sample. Human error cannot be eradicated. In the old view, human error was perceived as the root cause of problems, with individuals being viewed as variables requiring control. Conversely, contemporary perspectives consider human error a symptom of deeper systemic issues. As suggested by the Institute of Medicine in 2000, which published the report “To Err Is Human,” the core of the problem lies not with the fallibility of healthcare personnel but the flawed systems within which they operate. Preventing errors is possible by incorporating safety into system processes and hospital structures. Latent errors are errors that arise due to system inefficiencies. In the context of MAR, these latent conditions can, amongst others, be work-related pressure, high workload, lack of communication between team members, distraction, a suboptimal setup of the lab, a lack of clarity in the procedures, and insufficient time for thorough communication. In the famous Reason’s Swiss cheese theory of error, these latent conditions are weaknesses (or gaps/ holes) in the system’s defense layers. When all the holes from each layer (i.e., policy, planning, design, communication) align, they will permit an error to cause harm. Understanding the theory of human errors and building safety into various layers of care processes in MAR are effective ways of reducing errors rather than blaming sentinel individuals. Errors within MAR centers can be prevented by designing the healthcare system at all levels to make it safer, making it hard for people to do the wrong thing and easy for people to do the right thing.

P-472 Oocyte cryopreservation for social reasons in women ≥ 40 years who decline oocyte donation: anticipated outcomes, myth dispelling, and addressing concerns

Abstract Study question Is oocyte vitrification a reproductive viable alternative for women aged over 40 who decline oocyte donation? Under what specific conditions? Summary answer Oocyte vitrification could be considered as an acceptable alternative in this patient cohort, with patients being adequately informed about the realistic possibilities. What is known already In Argentina, legislation on Assisted Reproduction Technologies endorses assisted reproductive treatments employing women’s own oocytes up to the age of forty-four. This legislative framework has resulted in an increased number of such procedures for women over 40 who decline oocyte donation, as well as a rise in those women in this age group who wish to postpone maternity for social reasons. There are scarce published studies presenting reproductive outcomes using vitrified and thawed autologous oocytes in this specific demographic. Study design, size, duration This retrospective observational study, conducted between January 2008 and December 2023, involved 299 patients aged 40 and above who underwent 356 cycles of autologous oocyte cryopreservation (1.2 cycles per patient). Statistical analysis utilized the InStat GraphPad statistical package, including one-way ANOVA and two-tailed Student’s t-test as required. Participants/materials, setting, methods Eighty-seven patients thawed their oocytes and performed 95 ICSI procedures followed by 75 embryo transfers. The primary outcome was the live birth rate, with secondary outcomes including oocyte survival rate, fertilization rate, implantation rate, clinical pregnancy rate, and miscarriage rate. Vitrification and thawing of oocytes were performed using the Cryotop method. Main results and the role of chance Average age: 41.4± 1.8 years. Average vitrified oocytes: 4.5 ± 3.9 [1-24]. 29.1%(87/299) patients thawed their eggs. Average age at thawing:44.0± 2.7 years [41-50]. Average storage time until use was 2.6 ± 1.9 years. 465 oocytes were thawed (4.9 ± 3.0 oocytes per patient). 31.0% used a donor semen sample and 69% used their partne’s semen sample. Survival rate was 87.1%(405/465). Fertilization rate was 74.3% (301/405). Cleavage rate was 98.0 % (295/301). 78.9% (75/95) of ICSI procedures had embryo transfer (1.9 ± 0.6 embryos per patient). Implantation rate was 8.9% (13/146). Clinical pregnancy rate per transfer was 17.3% (13/75). Miscarriage rate was 23.1% (3/13). Miscarriage rate per transfer was 4.0% (3/75). Live birth rate per transfer was 13.3% (10/75), 11.5% (10/87) per patient who thawed their oocytes and 10.5% (10/95) per ICSI procedure performed. Live birth rate per cryopreserved oocyte was 2.1% (10/465) in the general population and 9.1% (10/110) in those women who achieved at least clinical pregnancy. Women who achieved a healthy live birth had a greater number of vitrified oocytes (7.1 ± 3.1) than those who did not achieve pregnancy (4.9 ± 3.0) (p = 0.02). Limitations, reasons for caution This retrospective study’s conclusions are pertinent to a well-defined group of patients, specifically women aged over 40 who decline oocyte donation and have undergone oocyte vitrification. Wider implications of the findings Despite the absence of an assurance for a live birth through oocyte vitrification in this cohort, offering clear counsel grounded in variables such as the number of retrieved oocytes and age at the moment of cryopreservation allows for informed communication of realistic possibilities for those patients who decline oocyte donation. Trial registration number na

O-085 Oocyte cryopreservation: a comprehensive analysis of live birth rate by age and indication of treatment provides reassurance for young cancer patients

Abstract Study question Does the outcome of oocyte cryopreservation vary across different age groups and treatment indications, i.e. cancer diagnosis, other medical conditions or non medical fertility preservation? Summary answer Live birth rate (LBR) is significantly influenced by a woman's age, although not by indication of treatment. What is known already OC is increasingly applied in assisted reproduction, although little is about the outcomes, including livebirth according to indication. Study design, size, duration Retrospective cohort study analyzing all OC and subsequent warmed oocyte cycles in two fertility centers - Melbourne IVF and the Royal Women’s Hospital, Melbourne, Australia, between the years 2014 to 2022. Participants/materials, setting, methods Women undergoing autologous IVF treatment using vitrified and warmed oocytes. Outcome of stimulation cycles and warmed oocyte cycles were assessed according to women’s age at OCP (≤ 35 years, 35-40 years and ≥ 40 years) and treatment indication- cancer diagnosis, other medical conditions and non medical. Main results and the role of chance 2689 women underwent a total of 3801 cycles of OC, comprising 702 cycles for cancer diagnosis (18.6%), 1146 cycles for other medical (30.5%), and 1953 cycles for non-medical (50.9%). Regardless of indication, younger age groups exhibited a higher median number of mature oocytes: <35 (11, 8-17), 35-40 (9, 6-11), and >40 (6, 3-9) (H(2)=15.1, p < 0.05). Among 582 warmed oocytes cycles, the >40 group demonstrated lower rate cycles with at least one good-quality blastocyst (76.7%) compared to 35-40 (87.1%) and <35 (87.2%), p < 0.05. Cumulative live birth rates (cLBR) were also lower in the >40 age group (14.9%) compared to 35-40 (34.9%) and <35 (46.5%), p < 0.01. When analyzing cycles by indication, patients with cancer had lower oocyte survival rate (80.8% vs 84.8% in other medical and 82.1% in non medical, p < 0.01). Nonetheless, no differences in rate of cycles with at least one good quality embryo rates (cancer diagnosis 87.2%, other medical 82.1% and non medical 89.3%, p = 0.06). Patients with cancer diagnosis had higher clinical miscarriage rate (25%) compared with other medical (7%) and non medical (10.5%), p < 0.01. However, cLBR did not differ between the indication groups (29.7% in cancer diagnosis, 35% in other medical and 38.1% in non medical, p = 0.5. Limitations, reasons for caution Retrospective data collection. Wider implications of the findings Our study offers comprehensive data that may assist patients desiring OC, and provides reassurance that even with a cancer diagnosis, outcomes are as favorable as those having non-medical OC. Given the substantial impact of age, health care providers should, when possible, advise to complete this procedure at a young age. Trial registration number Not applicable

P-371 It’s worth the freeze: outcomes from thawing electively cryopreserved oocytes are comparable in patients with reduced vs normal ovarian reserve at the time of cryopreservation

Abstract Study question For patients coming back to use oocytes derived from elective cryopreservation, does their initial ovarian reserve predict thaw survival, embryos’ developmental milestones and pregnancy success? Summary answer Thaw survival, fertilization rate, embryo development and pregnancy success rates do not vary significantly according to AMH level at initial cryopreservation. What is known already Increasing numbers of patients are electing to cryopreserve oocytes for future use. AMH (Anti Mullerian Hormone) is an ovarian reserve marker often assessed prior to initiation of treatment that predicts response to fertility treatment and the resulting oocyte yield. However, it is not known whether oocytes derived from a patient with compromised ovarian reserve (perhaps over multiple treatment cycles) will fare as well as that of a patient with normal ovarian reserve and a higher per cycle oocyte yield. Our study seeks to shed light on whether a lower initial AMH level negatively impacts the prognosis of the thawed oocytes. Study design, size, duration We included in our retrospective study all oocyte thaw cycles resulting from electively cryopreserved oocytes since 1996 at a single academically affiliated fertility center. 325 patients completed a total of 510 thaw cycles. 315 cycles were excluded from analysis for no AMH information. 6376 oocyte cryopreservation cycles were performed over that timeframe. The primary outcomes were laboratory statistics including oocyte survival, fertilization and embryo blastulation rates, while the secondary outcome was cumulative live birth rates. Participants/materials, setting, methods AMH categories of < 1, 1-2 and > 2 were selected to stratify reduced, low-normal, and normal ovarian reserves, respectively. 70.7% inseminated oocytes with partner sperm while the remaining 29.3% used donor sperm. Mean age at time of oocyte cryopreservation was 36.5 (range 27.5 to 46.2) while mean age at time of oocyte thaw was 39.2 (range 27.7 to 47.5). The statistical analysis was performed using ANOVA for mean comparisons and chi-squared for pregnancy data. Main results and the role of chance Average oocyte yield per cryopreservation cycle was significantly different across AMH groups (7.7 oocytes in AMH < 1, 10.5 oocytes in AMH 1-2, and 17.2 oocytes in AMH > 2, p < 0.01). The number of treatment cycles completed was highest in patients with AMH < 1 at 1.26 cycles. Oocyte survival (mean 89.0%), fertilization rate (mean 75.3%), and blastocyst conversion rate (mean 62.4%) did not vary significantly across AMH groups. Time to oocyte use was not significantly impacted by AMH at the time of initial testing. Those with reduced AMH < 1 came back earlier to utilize the oocytes (787 days), vs 1141 days for patients with AMH 1-2 and 1021 days for patients with AMH > 2. However, this difference was not statistically significant, p = 0.4. The rate of PGT-A euploid embryos did not vary between groups (38.8% in AMH < 1, 45.3% in AMH 1-2, 53.0% in AMH > 2, p = 0.07). Clinical pregnancy, miscarriage rate, and live birth rate in the first transfer cycle was not impacted by AMH. Total cumulative live birth rate was not correlated with AMH (31.6% in AMH < 1, 44.4% in AMH 1-2, 47.8% in AMH > 2, p = 0.48). Limitations, reasons for caution This data was collected at a single fertility center and thus has limited generalizability. 8.0% of patients came back to utilize their oocytes, which varies widely across the published literature. 60.6% of patients did not have AMH assessed as part of their pre-treatment testing and were excluded from analysis. Wider implications of the findings Although reduced ovarian reserve impacts oocyte yield, many studies find no impact on resulting oocyte quality, embryo development and pregnancy success rates. Those with compromised AMH have comparable oocyte thaw outcomes to those with normal ovarian reserve, though more oocyte cryopreservation cycles may be needed to achieve a successful outcome. Trial registration number N/A

O-061 Ovarian cancer and fertility - current understanding

Abstract Introduction Ovarian cancer is a significant health concern worldwide and is the leading cause of death from gynecologic malignancies. While fertility preservation is essential for many young women diagnosed with cancer, concerns have been raised regarding the potential impact of fertility treatments on the risk of ovarian cancer development. 1. Ovarian Cancer Risk Factors Ovarian cancer is a multifactorial disease with various risk factors contributing to its development. A woman has a risk of 1 in 78 of having ovarian cancer in her life time, risk factors include: • Age: Ovarian cancer risk increases with age, with the highest incidence observed in women over 50 years old. About 12.1% of Ovarian Cancer patients are younger than 44 years old. • Family History: Women with a family history of ovarian or breast cancer, especially first-degree relatives, have an increased risk. • BRCA Mutations: Inherited mutations in BRCA1 and BRCA2 genes significantly elevate the risk of ovarian cancer. • Reproductive Factors: Factors such as nulliparity, early menarche, late menopause, and infertility have been associated with an increased risk of ovarian cancer. 2. Fertility Treatments and Ovarian Cancer Risk Understanding the mechanisms underlying ovarian cancer development is crucial for assessing the potential impact of fertility treatments : • Ovulation Hypothesis: The repeated ovulation theory suggests that each ovulatory cycle increases the risk of DNA damage to ovarian epithelial cells, potentially leading to cancer development. The use of fertility drugs to stimulate ovulation, such as clomiphene citrate and gonadotropins, has been studied , the early studies suggested a potential increased risk, more recent evidence has been conflicting, with some studies reporting no association. • In Vitro Fertilization (IVF): Several large-scale studies have investigated the relationship between IVF and ovarian cancer risk found no significant increase in ovarian cancer risk . • Hormonal Influence: Fertility drugs alter hormonal levels, particularly estrogen and progesterone, which may influence ovarian cancer risk. • Selection Bias: Some studies have suggested that the ovarian cancer risk may be confounded by underlying infertility factors rather than the treatments themselves. 3. Clinical Implications and Recommendations • Individual Risk Assessment: Clinicians should assess each patient's individual risk factors for ovarian cancer, including age, family history, and reproductive history, before initiating fertility treatments. • Informed Consent: Patients should be provided with comprehensive information regarding the potential risks and benefits of fertility treatments • Regular Surveillance: Women undergoing fertility treatments should receive regular gynecologic screenings and follow-up care to monitor for any signs or symptoms of ovarian cancer. • Shared Decision Making: Shared decision making between patients and healthcare providers is essential to ensure that treatment decisions align with patients' preferences and values. 4. Fertility Preservation Options • Most therapeutic options for Ovarian Cancer cause infertility, either by premature ovarian failure caused by cytotoxic agents in chemotherapy or surgical approaches that include unilateral or bilateral oophorectomy • In ovarian cancer patients, Oocyte cryopreservation is still the best option and the only one established along with embryo cryopreservation. Fertility preservation surgery can be suggested depending on histology, stage of disease and pre-existing ovarian reserve. • Ovarian tissue cryopreservation will not be an option as long as the risk of reseeding cancer cells is not fully eliminated. 5. Future Directions Advancements in molecular biology and genetics may shed light on the underlying mechanisms of ovarian cancer development and its potential association with fertility treatments. The artificial ovary and in vitro maturation of oocytes is a very attractive option in these patients, but further milestones have to be achieved

P-248 Egg vitrification related to female age: survival and laboratory outcome of 1233 vitrified-thawed oocytes in non-medical autologous use

Abstract Study question Is the female age at retrieval a determinant factor for the viability and potential of the thawed eggs? Summary answer In patients over 40, thawed oocytes display more abnormal fertilization, develop less in extended culture and yield less top quality blastocyst. What is known already Oocyte cryopreservation is a well-established procedure especially since the advent of the vitrification technique. The successful outcomes achieved with vitrification encourage its application in fertility preservation (FP) for medical and non-medical reasons. Besides, the age-related decline in women’s fertility and the oocyte quality negatively affect the outcome of assisted reproduction. Some studies have reported that age at oocyte retrieval strongly influences reproductive prognosis after FP. However, the appropriate age for non-medical FP is still debated. Although oocyte freezing at a younger age is recommended, there should be a balance between a favourable outcome and the cost-effectiveness of the strategy. Study design, size, duration Retrospective study on 166 patients with frozen-thawed oocytes who underwent ICSI during 2021-2023 in a single hospital. Oocyte vitrification had different purposes: banking for poor responders, to limit the number of embryos, and to solve unexpected situations where partner’s semen sample was unavailable. Patients were divided into three groups according to their age at retrieval (Group A ≤ 37 n = 77, Group B 37-40 n = 44, Group C ≥ 40 n = 45). Post-warming survival, fertilization, and embryological data were studied. Participants/materials, setting, methods 1233 oocytes were thawed. The intact oocytes were microinjected 1-2 hours after warming. Embryos were cultured in Sage 1-StepTM to blastocyst stage, and rated on daily basis. Embryo transfer was performed on day 3 or day 5 and remaining blastocysts were frozen on Day 5 or Day 6. Post warming survival, lysis after ICSI, fertilization, embryo development, blastulation rate (BR) and top blastulation rate (TBR), and morphokinetic features were studied in the 3 groups. Main results and the role of chance 84.6% of the 1233 oocytes (vitrified in a high-security closed system) survived the warming process. 1043 eggs were injected and the post-ICSI lysis rate was 11.2%. No significant differences were seen in thawing survival rate in groups A, B and C (85.6% vs. 83.5% vs. 83.8%, p=0.635) nor in the post-ICSI lysis rate (13.1% vs. 7.4% vs. 11.2%, p=0.072). 2PN fertilization rate was similar between the groups (67.8% vs. 61.3% vs. 67.7%, p=0.178) as well as the total number of embryos (303 vs 146 vs 188 p=0.605). However, triploid fertilization rate (3PN) statistically grew with age (2.8% vs. 5.8% vs. 6.5%, p=0.034). Significant differences were also reported in the global abnormal fertilisation rate (1PN+3PN) (6.4% vs 10.3% vs. 13.3%, p= 0.005). BR and TBR were statistically lower after the age of 40 (BR: 61.5% vs. 62.7% vs 40% p<0.001, TBR: 43.3% vs. 47.9% vs. 24.3% p<0.001). Morphokinetic features in the 3 groups were studied (abnormal cleavage pattern, tSB and tB). Overall results were similar between group A and group B but oocyte potential decreases drastically from the age of 40. Limitations, reasons for caution The major limitation of the study is its retrospective nature and the relative small size of each group. As most of patients were transferred during 2023, the pregnancies have not delivered yet so the live birth rate is not mentioned. Wider implications of the findings Studies have reported the impact of age at oocyte retrieval in case of medical FP in cancer and endometriosis. Here we report a negative effect on outcome after the age of 40 in non-medical FP. Patients should be informed that FP is not a certification of a successful outcome. Trial registration number not applicable

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

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

P-221 The efficiency of a PGT-A program is negatively impacted by the utilization of frozen-thawed oocytes in patients of all ages

Abstract Study question Are there any differences in the use of fresh or frozen-thawed oocytes in a PGT-A program? Summary answer While euploidy rates are comparable, the efficiency of a PGT program is adversely impacted when utilizing frozen-thawed oocytes. What is known already Oocyte vitrification has become one of the key assisted reproduction procedures. Some studies have reported rates of embryonic development, clinical pregnancy, and embryo implantation comparable between fresh and cryopreserved oocytes in egg donor patients. Vitrified oocyte accumulation before the blastocyst biopsy is a commonly used strategy in PGT programs to enhance the chances of obtaining a euploid blastocyst with the patient’s own oocytes. Further research is needed to assess the impact of frozen-thawed oocytes on aneuploidy and the efficiency of PGT programs. Study design, size, duration We conducted a retrospective comparison of 777 PGT-A cycles, using either fresh or frozen-thawed oocytes, regarding embryo development (fertilization rates, blastocyst formation, and rates of good-quality blastocysts), PGT outcomes (euploidy and mosaicism rates), and the overall efficiency of the PGT cycle, measured as the number of euploid blastocyst per available mature oocytes, between April 2018 and November 2023. The study groups were stratified based on the age of the patients (≤35 and >35 years old). Participants/materials, setting, methods PGT-A cycles were categorized into two groups: patients who utilized fresh oocytes (n = 641) and those who utilized frozen-thawed oocytes (n = 136). A total of 6,370 fresh oocytes and surviving oocytes from the initially vitrified ones (972 out of 1,153) were fertilized and cultured to the blastocyst stage, at which point biopsies were performed. The biopsied cells were subjected to NGS screening, and statistical data analysis was conducted using the Chi-square test, with significance set at P < 0.05. Main results and the role of chance In the group of patients aged ≤35 years old, significant differences were observed when comparing PGT cycles using fresh or frozen-thawed oocytes in terms of the fertilization rate (78.4% vs. 72.0%), blastocyst formation rate (47.4% vs. 37.7%), and the efficiency of the PGT cycle (24.0% vs. 16.0%), corresponding to a 33.3% reduction in efficiency. No differences were observed between fresh and frozen-thawed oocytes regarding euploidy rate (64.6% vs. 68.4%), mosaicism rate (4.9% vs. 5.1%), and the percentage of good-quality embryos (60.0% vs. 56.1%). Similarly, in patients aged >35 years old, fertilization (81.5% vs. 73.5%), blastocyst formation (40.5% vs. 33.4%), and the efficiency of the PGT cycle (11.7% vs. 7.2%), which correspond to a 38.5% reduction in efficiency, were improved when using fresh oocytes. No differences were observed regarding euploidy (35.6% vs. 35.3%) or mosaicism rate (3.8% vs. 5.3%), and the percentage of good-quality embryos (55.2% vs. 54.7%). The oocyte survival rate was 84.3%. Limitations, reasons for caution Our study is limited by its sample size and retrospective design, as well as the inclusion of a non-selected and general infertile population, which could amplify the impact of confounding variables. Wider implications of the findings We found that the utilization of frozen-thawed oocytes reduces the PGT program efficiency by decreasing fertilization and blastocyst formation rates. This suggests that the oocyte accumulation strategy should be approached with caution. However, vitrification did not lead to an increase in the rates of aneuploidy, mosaicism, or poor-quality blastocysts. Trial registration number NOT APPLICABLE

P-359 Ten years’ experience using cryopreserved oocytes from In Vitro Maturation (IVM) or Controlled Ovarian Hyperstimulation (COH) cycles for fertility preservation in oncologic indications

Abstract Study question Is IVM a relevant option for fertility preservation in cancer patients, considering biological/clinical outcomes post-thawing, compared to COH? Summary answer This study shows that despite a significantly altered embryo morphology within the IVM group, the clinical outcomes remain comparable to those of COH. What is known already Fertility Preservation (FP) techniques are proposed to patients with cancer to provide the possibility of childbearing using their own gametes. Currently, oocyte vitrification after COH is the standard option. IVM serves as an alternative when COH is contraindicated, urgent cancer therapy is required, or in conjunction with ovarian cortex cryopreservation. Limited live births have been reported from frozen-thawed oocytes in IVM cycles of cancer survivors. Scarce data are available for comparing biological/clinical outcomes of frozen-thawed oocytes from IVM versus COH cycles in cancer survivors. Study design, size, duration This bicentric retrospective cohort study aimed to analyze the outcomes of all oocyte warming cycles in 73 cancer survivors having undergone oocyte vitrification for FP after COH and/or IVM. All of them had oocyte retrieval before the administration of gonadotoxic treatment and returned after being cured, with their oncologist agreement, for assisted reproduction treatments, between November 2012 and January 2024. Participants/materials, setting, methods Seventy-seven warming attempts followed by ICSI respectively from 37 COH and 40 IVM cycles were analyzed. Four patients benefited from an IVM and COH cycle. Survival, fertilization, top and good-quality embryos, defined at day-2 respectively as 4 and 3-5 adequate-sized blastomeres, without multinucleation with < 20% of cytoplasmic fragments, implantation, biochemical (hCG>100 UI/mL), clinical (intrauterine sac with fetal heartbeat) and live birth rates were compared using appropriate statistical tests. Main results and the role of chance The mean age and antral follicle count at the time of FP was similar in both groups. The indications for FP were breast cancer (n = 61), hematologic malignancies (n = 7), ovarian cancer (n = 3), other (n = 2). The number of cryopreserved oocytes tended to be higher in the COH group, when compared to the IVM group (8.5±7.3 vs 5.9±4.04; p = 0.16). The mean oocyte maturation rate after IVM was 68.6±23.1%. Oocyte survival, and fertilization rates were similar in COH and IVM groups, respectively (76.4±27.0% vs 76.1±22.0%; p = 0.76) and (67.1±34.3% vs 65.3±25.4%; p = 0.36). We reported a significantly better embryo quality at day-2 in the COH group when compared to the IVM group, with respectively top-quality embryos (44.0±34.2% vs 26.1±33.4%, p = 0,04) and good-quality embryos (62.2±38.0% vs 42.8±40.8%, p = 0.049), and also a significantly higher number of useful embryo in the COH group (2.7±2.6 vs 1.5±1.2, p = 0.03). Regarding clinical outcomes, the results were similar in COH and IVM groups, in terms of implantation rates (12.2±30.4% vs 15.5±35.6%; p = 0.86), biochemical (32.3% (10/31) vs 17.9% (6/28); p = 0.39), clinical pregnancies (25.8% (8/31) vs 17.9% (4/28); p = 0.54), live birth rates ( 25.8% (8/31) vs 14.3% (4/28); p = 0.34). Limitations, reasons for caution Statistical power to compare IVF outcomes after COH and IVM is limited by the few women who returned to use their frozen oocytes. The subjective nature of embryo morphology assessment. Wider implications of the findings This study is the largest evaluating frozen-warmed oocytes from IVM cycles in cancer patients, with 5 live births newly reported. A higher oocyte-yield may be necessary in IVM as the number of useful embryos is significantly lower. Novel approaches are being developed to improve maturation rates following IVM. Trial registration number Not applicable

P-141 Elevating human oocyte vitrification and warming to a new level: fast, efficient, and effective

Abstract Study question Due to the rising trend for oocyte cryopreservation and increasing demand, there is an urgency to make oocyte vitrification and warming protocols more efficient. Summary answer Oocyte vitrification and warming can be done successfully in 4 minutes, reducing the time of commonly used current protocols by up to 25 minutes. What is known already Vitrification and warming of oocytes is widely used in many IVF clinics worldwide and routinely utilized as a dominant technique for fertility preservation and freezing of donor as well as autologous oocytes in many clinical settings. Outcome data using cryopreserved oocytes is comparable to fresh oocytes. However, vitrification and warming of human oocytes can be time consuming. Usually, vitrification of oocytes is done in about 11-16 minutes, and warming requires another 11 minutes. Also, it is a common practice to load not more than 2 oocytes per carrier at time of vitrification. Study design, size, duration From November 2022 to November 2023, 504 germinal vesicles (GV) and 207 metaphase I (MI) oocytes, which did not convert into mature oocytes at day of oocyte retrieval, were vitrified in Vit Kit Freeze (FujiFilm Irvine Scientific, USA), and RapidVit Oocyte (Vitrolife, Sweden). Their survival rates were compared, and as an additional viability indicator, post-warming developmental capabilities were evaluated after 24 and 48hrs of culture in Global High Protein (LifeGlobal, USA). Participants/materials, setting, methods A group of 4 GV or MI oocytes was vitrified at room temperature for 1 minute in Equilibration solution (ES) and 1 minute in Vitrification solution (VS), loaded on a S-Cryolock (Biotech, USA) and then plunged into liquid nitrogen. Warming was done at 37ºC in 0.5M sucrose for 1 minute and Wash solution (WS) for another minute. Post warming, GV and MI oocytes were cultured for developmental evaluation. Statistical significance was defined as P < 0.05. Main results and the role of chance There was no statistically significant difference in the survival rate of GV oocytes between Irvine (209/219; 95.4%), and Vitrolife media (270/285; 94.7%; P = 0.72). The survival of MI oocytes was also comparable and not significantly different between both media; Irvine: 103/106; 97.2%, vs Vitrolife: 96/101; 95.0%; P = 0.43). Because of the similar survival rates of oocytes in both groups, for the developmental potential and conversion rates, oocytes of both groups were combined. Of the 504 GV, 479 survived (95.0%) and after 24hrs of culture, 441 converted to MI (92.1%). After a culture of 48hrs, 56.5% (249/441) converted to metaphase II (MII) oocytes. Combining the vitrified and warmed MI oocytes from both groups, 96.1% (199/207) survived the warming, and after 24hrs of culture, 168 (84.4%) converted to MII oocytes. Vitrification and warming of oocytes at different developmental stages can be done with a short exposure time to hypertonic (ES/VS) and hypotonic (0.5M sucrose) solutions in a total of 4 minutes. Limitations, reasons for caution Immature oocytes were used as study material to evaluate a new protocol with significantly reduced vitrification and warming times. At this moment we cannot provide data on fertilization, embryo development, and blastocyst formation. Wider implications of the findings Oocytes are exposed to less suboptimal temperatures during dehydration and rehydration and help to maintain their developmental potential. Loading 4 oocytes per carrier combined with the decrease in time resulted in increased efficiency. Warming in 0.5M instead of 1M sucrose contributes positively to survival and allows earlier resumption of functionality. Trial registration number not applicable

P-342 Improving consent procedures to increase oocyte donation rates

Abstract Study question Can consent procedures for donation of surplus frozen oocytes be changed to improve donation rates? Summary answer Obtaining informed consent for donation of oocytes after freezing could be improved by adapting new consent procedures used in genomic biomedical research for ART contexts. What is known already The widespread adoption of oocyte cryopreservation has led to a rapid accumulation of oocytes in cryostorage, since the number of people who return to use their eggs remains low. Previous studies show that many people intend to donate their surplus cryopreserved oocytes, but few people actually donate them. Increased rates of donation are required to address chronic shortages of eggs available for both reproductive and research purposes. Study design, size, duration This paper examines whether advances in consent procedures in genomic research and biobanking, such as Dynamic Consent interfaces, could be utilised within the ART context to improve patient experience and oocyte donation rates. Ethical issues with dynamic consent are considered as well as the possible benefits of such a system for potential donors and recipients of oocytes. Participants/materials, setting, methods This paper undertakes ethical analysis of the procedures used for obtaining informed consent in egg freezing for donation of surplus eggs. We consider whether these could be improved and argue that adapting advances in consent procedures, such as dynamic consent interfaces, may help to facilitate donation, with benefits to both donors and recipients. Main results and the role of chance While people freezing eggs often express an intent to donate eggs surplus to their own needs at the start of the freezing process, in few cases does this translate to actual donation. Current processes seek consent for donation at limited times throughout the cryostorage period. Further, some countries such as Australia require that eggs be donated to specific active research projects at the time that eggs are to be relinquished from storage. Factors such as these impede donation and fail to facilitate the initial expressed intent to donate surplus eggs. We hypothesise that consent processes can be improved in ways that may boost rates of donation while still satisfying the requirements of informed consent. Dynamic consent allows continuous review of consent decisions through an online interface. Adaptation of this approach to the context of egg cryopreservation and donation may have several benefits, as continuous communication and review opportunities encourage patient engagement. It may enhance understanding of the need for eggs and increase knowledge of opportunities to donate surplus eggs. While dynamic consent may benefit both potential donors and recipients, careful implementation would be required to ensure compatibility with counselling requirements and other ethical standards for reproductive donation in particular. Limitations, reasons for caution We consider the potential benefits to donors and recipients but do not analyse the costs of implementing such a system of consent for clinics. Further, specific clinics may have consent procedures that differ from the model we use here and may be constrained by regulatory contexts Wider implications of the findings Recent research suggests that cryopreserved oocytes are rarely used or donated. Improving procedures for obtaining informed consent promises to increase rates of donation and improve patient experience. Dynamic consent tools have been widely used in biobanking and genomics research to positive effect but would be novel within the ART context. 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

O-169 Advances in oocyte freezing: implications for donors, recipients, counsellors and clinics

Abstract Much of the attention given to the introduction of oocyte vitrification has focused on the implications for autologous freezing – i.e. freezing by those who wish to store their own eggs for later use. Such debates have considered, for example, the individual motivations of freezers and the ethics and practicalities of state and employer funding. Much less attention has been given to the impact of egg vitrification on the landscape of egg donation. Whilst use of frozen eggs for donation varies by country and clinic, data show that in general the practice is growing; with Spain an early and enthusiastic adopter within Europe. The advent of egg vitrification has led to or accelerated a number of changes in the landscape of donation. More efficient and reliable freezing allows clinics to ‘batch’ eggs and store them for potential use by multiple recipients thereby increasing clinic revenue. Vitrification can also facilitate the creation of a store of eggs and associated donor profiles; providing more choice for recipients at the time of treatment and giving rise to the emergence of commercial egg banks within Europe. There have also been changes to the regulatory landscape catalyzed by the introduction of oocyte vitrification; for example, a recent extension to legal storage periods in the UK in response to the newly established technical potential. In a broader sense, the possibility to vitrify and store eggs has developed at a time when fertility treatment in general is rapidly transforming and commercializing; with the introduction of a range of novel and highly commercialized practices in the same period: e.g. methods of gamete/donor selection which use AI and expanded carrier screening for donors. The management and use of frozen eggs has therefore developed along a different sociotechnical trajectory to that of frozen sperm; acquiring differing meanings, practices and moral, cultural and economic value in the process. In this talk, I draw on data from a recent, large-scale study of egg donation in Europe to consider how oocyte vitrification maybe reshaping the landscape of egg donation. I consider how changing practices associated with vitrification (egg batching and banking, for example) may be reconfiguring how egg donation is constructed and perceived by those involved, as well as how it is regulated. Specifically, I consider the implications that an increase in use of frozen eggs raises for donors, recipients, clinics and their staff, including counsellors.