Medically Assisted Reproduction Research Articles

Reflecting sex, social class and race inequalities in reproduction? Study of the gender representations conveyed by 38 fertility centre websites in 8 European countries

BackgroundFertility centre websites are a key sources of information on medically assisted reproduction (MAR) for both infertile people and the general public. As part of a global fertility market, they are also a window to attract potential future patients. They give formal and practical information but in the way the information is displayed, they also convey social representations, and in particular, gender representation in its intersectional dimension. The objective is to analyse the sex, class and race representations regarding reproduction and parenthood that are embedded in the content of fertility centre websites in eight European countries.MethodsThe 5 most visible fertility centres that appeared in the first places on Internet search were selected for each country under study, except for one country which has only three fertility centres. In total, 38 fertility centre websites were considered for a thematic analysis using an iterative approach and a comprehensive perspective.ResultsEach centre details its services and techniques according to the legal provisions in force in its country. However, on all the websites studied, the fertility centres demonstrate a strong gendered representation. The logos generally depict women or parts of their bodies, as do the photos, which mainly show white women with light eyes. The description of the causes of infertility and the techniques offered by the centres also highlights gender differences. Sperm donation, where MAR is reserved for heterosexual couples, is included among the techniques for women with the comment that it will enable them to fulfil their dream of becoming mothers.ConclusionsMAR, and through it the project of having a child and procreative work, is presented as a matter for white, cisgender and heterosexual women, thus fueling stratified reproduction and limiting reproductive justice. The research team formulated guidelines for fertility centres to encourage them to adopt a more inclusive approach in terms of sex, social class and race, so that the diversity of infertile people feel involved and welcome in these centres, to avoid misperceptions about infertility in the general population and to reinforce autonomy and justice in reproductive matters.

Alignment, Anticipation, Adaptation, or Lagging Behind? Age‐Based Regulations in Assisted Reproduction and Late Fertility

AbstractThis paper focuses on age restrictions on access to infertility treatments and eligibility for their public reimbursement, exploring their relevancy in contexts of rising late birth rates (40+). I explore how age‐based reimbursement policies for in vitro fertilization treatments have responded to these fertility trends in 27 high‐income countries and in which regulatory frameworks for medically assisted reproduction (MAR) very late births (45+) have particularly increased. First, I show that while age limits for treatment reimbursement are well aligned with the prevalence of late fertility in some national contexts, in most countries, strict age restrictions are lagging behind the rise in late births. In others, pronatalist policies have prompted permissive age criteria or law revisions, anticipating or adapting to rising trends in late births. Second, the rise in very late births has been limited in some contexts with strict age‐based rules. However, the analysis suggests that the impact of MAR on very late births may also be influenced by contextual factors other than regulations.

EuMAR stakeholder engagement: an analysis of medically assisted reproduction (MAR) data collection practices in EU countries†.

What are the current national medically assisted reproduction (MAR) data collection systems across EU Member States, and how can these countries contribute to a unique, cycle-by-cycle registry for the European Monitoring of Medically Assisted Reproduction (EuMAR) project? The study identified significant variation in MAR data collection practices across Member States, with differences in data types, collection methods, and reporting requirements; the EuMAR project emerges as an opportunity to enhance data standardization and improve MAR data collection in the EU. There is a need for new approaches in MAR data collection that include long-term and cross border follow-up. The EuMAR project intends to establish a unified, cycle-by-cycle registry of data on MAR treatments in EU countries, from which accurate cumulative outcomes can be calculated. This cross-sectional study involved a survey and interviews with stakeholders from 26 EU Member States conducted in 2023 over a period of seven months. Representatives from national competent authorities and professional associations involved in MAR data collection in EU countries were invited to complete the survey and interviewed to assess current data flows, information requirements, and their interest in the EuMAR project. Half of the participating countries reported having a national MAR registry with cycle-by-cycle data (n = 13), while 31% reported having a national registry with aggregated data (n = 8) and 19% reported having no national registry (n = 5). Of the countries with a national cycle-by-cycle registry, eight countries collect identifiable data, five countries collect pseudonymized data, and one country collects fully anonymized data. Informed consent is required in 10 countries. The main advantages that participants expected from a European registry like EuMAR were the possibility of obtaining national statistics in the absence of a national registry and improving the calculation of cumulative outcomes. The results of the study are based on self-reported data, which may be subject to bias, however, the validity of the collected information was verified with different means, including follow-up calls for clarifications and sharing final transcript reports. The feasibility of the proposed data flow models will be tested in a pilot study. Despite the heterogeneity of data collection practices across EU countries, the results show that stakeholders have high expectations of the benefits that the EuMAR registry can bring, namely the improvement of data consistency, cross-border comparability, and cumulative live birth rates, leading to better information for patients, health care providers and policy makers. The EuMAR project was co-founded by ESHRE and the European Commission (101079865-EuMAR-EU4H-2021-PJ2). No competing interests were declared. N/A.

Medically assisted reproduction (MAR) with sperm donation: Comparison of the profiles and medical pathways of unmarried women and women in heterosexual couples

Research questionThe legislation allowing unmarried women to undergo medically assisted reproduction (MAR) with sperm donation was adopted in France on August 2, 2021. This major advancement, and its impact on French society, led us to a closer examination of the requests made by unmarried women and the outcomes of ART attempts. DesignA retrospective single center cohort study was conducted in a fertility center in Paris, France. All unmarried women and women in heterosexual couple seeking for MAR using sperm donation between September 2021 and October 2022 were included. Medical and socio-demographic data, as well as details and outcomes of MAR attempts were analyzed until October 31, 2023. ResultsTwo hundred seventy-two unmarried women and 76 women in heterosexual couple were included. Results were compared between the two groups. Unmarried women were significantly older, with a significant decrease in anti-Müllerian hormone (AMH) and antral follicle count (AFC). They also exhibited a higher prevalence of gynecological pathologies associated with infertility, such as endometriosis. Unmarried women were more likely to work in intermediate occupations, whereas women in heterosexual couple more often had employee status. Among unmarried women who had undergone at least one MAR attempt by October 31, 2023, significantly lower cumulative early and ongoing pregnancy rates were observed. ConclusionsFemale age appears to play a major role in the likehood of pregnancy and live birth. It is therefore crucial to inform women initiating the process of MAR with sperm donation that success is not guaranteed.

Medically Assisted Reproduction and Partnership Stability

AbstractDespite the increasing use of medically assisted reproduction (MAR) in modern societies, there is limited evidence on whether conceiving with MAR or remaining involuntarily childless after MAR is associated with partnership stability. While older age, the more advantaged socioeconomic position of women undergoing MAR and their strong fertility intentions could lead to higher partnership stability, the experience of infertility and undergoing MAR may have an opposite effect, especially if couples remain involuntarily childless. Using data on Finnish nulliparous couples from 1995–2017 (N = 149,884) and event‐history models, we compare the risk of separation of couples who remained childless after MAR (N = 3871), who conceived through MAR (N = 14,474), who conceived naturally without MAR (N = 167,962) or with a prior history of MAR (N = 2273). Couples who remained childless after MAR had a higher risk of separation than couples who conceived with MAR or naturally. The higher risk of separation decreased over time since the discontinuation of treatments but persisted over the longer term. There were no differences in the risk of separation between couples who conceived with MAR or naturally. The results suggest that involuntary childlessness after MAR is associated with an increased risk of separation while undergoing MAR/experiencing infertility does not seem to play a role.

Challenges for the legislation enabling egg donation in Switzerland.

Switzerland is one of the most restrictive countries in Europe when it comes to the regulation of egg donation in medically assisted reproduction (MAR). Indeed, even after the introduction of modifications to the law regulating reproductive medicine allowing embryo culture, embryo freezing, and preimplantation genetic testing, egg donation has remained completely forbidden. The absolute ban on egg donation is heavily discussed in academia, society, and politics. After many failed attempts, this prohibition is now on its way to be lifted, after agreement was reached in the legislative institutions. The forthcoming legalisation of egg donation raises, however, several questions on how some aspects of this practice will be regulated. In this contribution, we briefly review the reasons why a ban on egg donation has been present for so long in Switzerland, to then analyse two issues raised by the commitment to lift this ban. First, we reflect on the question of whether the new legislation should introduce chronological age limits for access to heterologous MAR. Second, we consider how the practice of egg sharing could be regulated once egg donation is legal.

Azoospermia: Etiology, Diagnosis and Management

Male infertility is on the rise over the past few years, and azoospermia is one of the most common causes. It has two primary subtypes: non-obstructive azoospermia (NOA), where the spermatogenesis is hindered, and obstructive azoospermia (OA), when there appears to be a ductal obstruction while spermatogenesis is normal. Azoospermia is characterised by the absence of sperm in two or more ejaculates. Making the azoospermic man have his own biological child is now becoming a reality with the advent of TESE and ICSI procedures, followed by the latest advancements like the combination of imaging studies, Full-Field Optical Coherence Tomography (FFOCT), stem cell therapy, platelet-rich plasma therapy, and gene therapy, which are emerging as newer tools for effective treatment. The key aim of this article is to highlight the concept of azoospermia and focus on its evaluation and management through present-day developments in andrology and medically assisted reproduction (MAR). A detailed literature review is performed through Pubmed, Science Direct, the Online Library, and Scopus.

The clinical effectiveness of the Mind/Body Program for Infertility on wellbeing and assisted reproduction outcomes: a randomized controlled trial in search for active ingredients.

Does the Mind/Body Program for Infertility (MBPI) perform better, due to certain distinctive elements, than a partly matched support group in improving the wellbeing and medically assisted reproduction (MAR) outcomes of women with elevated distress levels in a clinical setting? While robust enhancements occurred in the wellbeing overall, the cognitive behavioural and formalized stress management elements of the MBPI allowed a significantly stronger improvement in trait anxiety, but not in other mental health and MAR outcomes, compared with a support group. Mind-body psychological programmes adjacent to MAR have been found to improve women's mental states and possibly increase chances of pregnancy. However, not enough is known about the programme's effectiveness among patients with elevated distress levels in routine clinical settings, nor is it clear which of its particular ingredients are specifically effective. A pre-post design, single-centre, randomized controlled trial was performed between December 2019 and October 2022 (start and end of recruitment, respectively). The sample size (n = 168) was calculated to detect superiority of the MBPI in improving fertility-related quality of life. Randomization was computer-based, with random numbers concealing identities of patients until after allocation. The trial was conducted at a large university teaching hospital. A total of 168 patients were randomly assigned to the mind-body (MBPI) group (n = 84) and the fertility support (FS) control group (n = 84). Patients received a 10-week, 135-min/week group intervention, with the FS group following the same format as the MBPI group, but with a less restricted and systematic content, and without the presumed effective factors. The number of patients analysed was n = 74 (MBPI) and n = 68 (FS) for post-intervention psychological outcomes, and n = 54 (MBPI) and n = 56 (FS) for pregnancy outcomes at a 30-month follow-up. Significant improvements occurred in both groups in all psychological domains (adjusted P < 0.001), except for treatment-related quality of life. Linear mixed-model regression analysis did not reveal significantly greater pre-post improvements in the MBPI group than in the FS group in fertility-related quality of life (difference in differences (DD) = 4.11 [0.42, 7.80], d = 0.32, adjusted P = 0.124), treatment-related quality of life (DD = -3.08 [-7.72, 1.55], d = -0.20, adjusted P = 0.582), infertility-specific stress (DD = -2.54 [-4.68, 0.41], d = -0.36, adjusted P = 0.105), depression (DD = -1.16 [3.61, 1.29], d = -0.13, adjusted P = 0.708), and general stress (DD = -0.62 [-1.91, 0.68], d = -0.13, adjusted P = 0.708), but it did show a significantly larger improvement in trait anxiety (DD = -3.60 [-6.16, -1.04], d = -0.32, adjusted P = 0.042). Logistic regression showed no group effect on MAR pregnancies, spontaneous pregnancies, or live births. The follow-up only covered MAR-related medical outcomes and no psychological variables, and their rates were not equal in the two groups. Biological factors other than age, aetiology, and duration of infertility may have confounded the study results. Loss to follow-up was between 5% and 10%, which may have led to some bias. The psychologically and medically heterogeneous sample, the normal clinical setting and the low attrition rate all raise the external validity and generalizability of our study. The MBPI works not only in controlled conditions, but also in routine MAR practice, where it can be introduced as a cost-effective, low-intensity psychological intervention, within the framework of stepped care. More studies are needed to further identify its active ingredients. The authors received no financial support for the research, authorship, and/or publication of this article. The authors have no conflict of interest to disclose. ClinicalTrials.gov NCT04151485. 5 November 2019. 15 December 2019.

L’accès aux services de fertilité pour les femmes lesbiennes, bisexuelles ou pansexuelles et les personnes queer, trans ou non-binaires : une revue rapide des écrits scientifiques

&lt;p&gt;Introduction: Lesbian, bisexual, and pansexual (LBP) women as well as transgender, queer, and non-binary individuals (TQNB) often rely on medically assisted reproduction (MAR) to build their families, but do not always have access to these services. Currently, there appears to be no literature that comprehensively reviews, from an ecosystemic perspective, the main factors determining LBP women's and TQNB people's access to MAR.&lt;/p&gt;&lt;p&gt;Objective: This rapid review aims to identify, from an ecosystemic perspective, the factors described in the scientific literature as influencing LBP women's and TQNB people's access to MAR.&lt;/p&gt;&lt;p&gt;Methods: A literature search using 11 search engines identified 22 articles presenting results of recent empirical studies (2018-2023) using various methodologies. Relevant results were subjected to thematic analysis, and identified factors were classified within an ecosystemic model.&lt;/p&gt;&lt;p&gt;Results: The identified factors are (1) at the microsystemic level, support from the social network and healthcare personnel; (2) at the exosystemic level, healthcare personnel's awareness of sexual and gender diversity, adequacy of information and documentation, organizational logic of fertility services, cost of services, legislation; (3) at the macrosystemic level, heterocisnormativity as a cross-cutting influence.&lt;/p&gt;&lt;p&gt;Discussion and conclusion: To ensure access to MAR for LBP women and TQNB people, a comprehensive and multi-level approach is necessary. Suggestions for health practices and public policies are proposed.&lt;/p&gt;

Are you aware of your citations? A cross-sectional survey on improper citations of retracted articles in assisted reproduction

Are authors aware when they have cited a retracted paper in their manuscripts in the medically assisted reproduction (MAR) field? A cross-sectional study based on an online survey was conducted to acquire information on the citation pattern from corresponding authors who had cited a retracted article. A dataset of retracted articles in the MAR field was collected from PubMed and Retraction Watch. A complete list of published articles that cited each retracted article was retrieved. The survey was distributed via e-mail to corresponding authors who had cited a retracted paper in their study. The survey revealed a significant lack of awareness among authors, with 78.7% unaware that they had cited retracted articles. This lack of awareness was attributed to insufficient notification mechanisms within research databases and journals, alongside a reliance on previously stored copies of manuscripts. A notable finding was that reference checks were typically performed by a single author, with no instances of retraction concerns raised during the peer-review process. Only a small fraction (17.8%) of respondents reported verifying retraction notices on both journal websites and scientific databases. Correcting publications that contain references which are subsequently retracted is significant for systematic reviews, meta-analyses and guidelines. Citations of retracted articles perpetuate erroneous scientific data, but assessing the accuracy of citations requires considerable effort. Proper notification of retraction status and cross-checking of citations can help to prevent errors.

O-210 DNA methylation signature of monozygotic twinning: investigating the relationship with medically assisted reproduction, higher-order gestations, and common genetic variants

Abstract Study question To study a DNA methylation signature of monozygotic twins in relation to medically assisted reproduction (MAR), higher-order gestations, and genome-wide common genetic variants. Summary answer Monozygotic twinning and MAR show largely distinct DNA methylation signatures. Monozygotic triplets, like monozygotic twins, carry a comparable but stronger DNA methylation signature. What is known already Monozygotic twins arise when a zygote or embryo splits during pre-implantation stages of development. Higher-order monozygotic multiples including triplets have been hypothesized to arise from multiple consecutive splitting events. The underlying mechanisms are unknown. Some studies have reported a higher rate of monozygotic twins born after the use of medically-assisted reproductive technologies. We recently identified a DNA methylation signature in blood samples from adult monozygotic twins, which showed strong replication across cohorts and in buccal samples from children. This signature consists of 834 differentially methylated locations, enriched for loci with a role in embryonic processes, cell adhesion, and metastable epi-alleles. Study design, size, duration We compared buccal DNA methylation profiles of 934 naturally conceived monozygotic twins to 43 monozygotic twins conceived after IVF/ICSI (mean age=9). We generated monozygotic twinning DNA methylation scores in an independent buccal dataset (59 triplets, 198 twins, and 119 siblings of twins, mean age=15). A genome-wide association study (GWAS) on the DNA methylation score was performed in two datasets from the Netherlands Twin Register (NTR) (1: Blood, N = 2841, mean age=37, 2: Buccal, N = 1150, mean age=10). Participants/materials, setting, methods DNA methylation was assessed with Illumina arrays (450k/EPIC). To study the relationship between DNA methylation and MAR, we performed an epigenome-wide association study (EWAS) of MAR in monozygotic twins. We applied our previously developed DNA-methylation based predictor (trained on blood methylation data from twins using elastic net regression) to novel buccal methylation data from multiples including triplets. GWAS analysis was performed in gcta using --fastGWA-mlm correcting for 10 genetic ancestry PCs and genotype platform. Main results and the role of chance Through EWAS, we identified 29 differentially methylated CpGs in buccal cells from monozygotic twins conceived after MAR compared to naturally conceived monozygotic twins (after Bonferroni correction), of which 8 were previously identified in an EWAS meta-analysis of IVF on cord blood from singletons at birth. None of the 834 CpGs detected in our previous EWAS meta-analysis of monozygotic twinning were associated with MAR, suggesting that they are connected to natural monozygotic twinning. The monozygotic twinning epigenetic signature showed similar performance in buccal DNA methylation data from monozygotic twins as previously observed (81% of monozygotic twins correctly classified). Sensitivity was highest for monozygotic triplets (90% correctly classified), but specificity remains moderate (66% of DZ twins correctly predicted, 53% of non-twins correctly predicted). GWAS analysis of blood 450k array data identified three genome-wide significant loci. The top SNP (rs76157694, MAF=0.25) maps to TBX4; an embryonic transcription factor primarily known for its role in hindlimb development. This finding is consistent with our previous results of MZ-differentially methylated positions being enriched within TBX4 binding motifs. GWAS analysis of the buccal EPIC array data identified no genome-wide significant loci. We are planning a GWAS meta-analysis together with the Genetics of DNA methylation consortium. Limitations, reasons for caution Our research provides compelling hints towards an epigenomic event in monozygotic multiples, but whether the signature represents a cause, effect, or a byproduct of monozygotic twinning remains to be established. In ongoing research, we study the signature in pre- and perinatal tissues from twins (Dutch Fetal biobank and PANDA biobank). Wider implications of the findings The methylation signature may serve as a biomarker to retrospectively diagnose if a person was conceived as monozygotic twin, providing novel opportunities to examine links between vanishing monozygotic twin syndrome and certain congenital disorders. Examples include Beckwith-Wiedemann Syndrome and Amyoplasia (∼10-fold higher frequency of monozygotic twins among patients). 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.

O-120 The role of CatSper in male infertility - from bench to bedsite and back

Abstract Infertility is on the rise, but the underlying causes still remain mostly unknown. In fact, for about one third of infertile men, semen parameters are within reference limits. This so called ‘unexplained male infertility’ seems to rest on elusive functional defects of the sperm undetectable by semen analysis, precluding early diagnosis of the infertility and evidence-based treatment by medically assisted reproduction (MAR). As a result, affected couples often experience failed MAR attempts, subjecting the ‘healthy’ female to recurring medical risks. We set out to gain insight into the pathomechanisms underlying unexplained male infertility. To this end, we systematically assessed the function of the sperm-specific multisubunit CatSper-channel complex in sperm of 2,300 men undergoing a fertility workup at our center, using a simple motility-based ‘CatSper-Test’ combined with [Ca2+]i fluorimetric and electrophysiological recordings. Thereby, we identified a group of men with normal semen parameters, but defective CatSper function. These men or couples failed to conceive naturally and upon MAR via intrauterine insemination and in vitro fertilization. Intracytoplasmic sperm injection (ICSI) was, ultimately, required to conceive a child. We revealed that the defective CatSper function was caused by variations in CATSPER genes. Moreover, we unveiled that CatSper-deficient human sperm were unable to undergo hyperactive motility and, therefore, failed to penetrate the egg coat. Thus, we provide the experimental evidence that sperm hyperactivation is required for human fertilization, explaining the infertility of CatSper-deficient men and need of ICSI for medically assisted reproduction. Finally, our study also revealed that defective CatSper function and ensuing failure to hyperactivate represents the most common cause of unexplained male infertility known thus far and that this sperm channelopathy can readily be diagnosed, enabling future evidence-based treatment of affected couples.

O-179 From secrecy to transparency: The journey of donor identity in reproductive medicine in Portugal

Abstract Thanks to significant medical advancements in reproductive medicine, people have more opportunities to achieve their parenthood goals. Third-party reproduction allows individuals and couples who might not otherwise be able to conceive to have the chance to build their family, thanks to the availability of donor gametes and gestational surrogacy. Gamete donation policy in Europe varies by country, raising ethical and legal concerns. In recent years, shifts from anonymity towards openness in donor legislation have occurred in several countries. Globally, in the last decade, there has been an increase in the number of families created using egg, sperm or embryo donation. The number of IVF/ICSI cycles using donor eggs or sperm in Portugal totalled 1890 in 2019 and 54 in 2020 (an unusual year due to the Covid-19 pandemic). In Portugal, the first medically assisted reproduction (MAR) law was approved in 2006, and gamete donations were anonymous. Ten years later, in 2016, Portugal’s MAR legal framework changed, and access to MAR was broadened to all women, independent of their marital status and sexual orientation. Therefore, treatment with donor sperm, oocytes, and embryos became available to recipients, including heterosexual couples, lesbian couples, and single women. In 2018, there was another change in the law and gamete donations became non-anonymous. In Portugal, identity-release donation allows the donor to remain anonymous to the intended parents during treatment (although they may have access to some non-identifying information about the donor). Nevertheless, the child can request the National Council for Medically Assisted Reproduction access to the donor’s personal information (full name) once they turn 18. Considering this legal framework, the number of previous donors who were contacted and asked whether they would maintain their donation despite the non-anonymity was residual. The identity-release framework did not seem to have affected the number of donations either. Donations are more frequent in private clinics than in the Portuguese public gamete bank, and this leads to waiting lists that can reach two years for a treatment involving oocytes or sperm donation. In this context, efforts to increase gamete donation, particularly in the National Health Service, are crucial. A study is currently being conducted in Portugal to pinpoint the main reasons why people do not consider being gamete donors. Preliminary results in a sample comprising 297 participants (82.2% females), with a mean age of 25.43 (SD = 7.88) years old and a mean of 14.09 (SD = 2.06) years of education, revealed that 73 (24.6%) stated that they would not consider being a donor because of the non-anonymity and 39 (13.2%) indicated that they would not consider becoming a donor due to concerns about being contacted in the future and requested responsibilities. These results may contribute to informing future initiatives aiming at promoting awareness on the topic of gamete donation. Another relevant topic is secrecy, which refers to parents not disclosing information to their offspring or their social group about donated gametes’ conception. Disclosing is recommended as an ongoing process, preferably when the child is young. This disclosure process may benefit from counselling or other support resources (e.g., children’s books, patients’ associations).

O-121 Assisted Reproductive Technology (ART) in Europe 2021 and development of a strategy of vigilance: Preliminary results generated from European registers by the ESHRE EIM Consortium

Study question What are the reported data on cycles in ART, IUI and fertility preservation interventions in 2021 as compared to previous years and what are the main trends over the years? Summary answer The 25th ESHRE report on ART and IUI shows a progressive increase in reported treatment cycle numbers in Europe, a small decrease in the number of transfers (IVF + ICSI) with more than one embryo with a trend to decreasing multiple delivery rates, outcomes for IUI cycles are similar to previous years. What is known already Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been collected, analyzed by the European IVF-monitoring Consortium (EIM) and reported in 23 manuscripts published in Human Reproduction and Human Reproduction Open. Study design, size, duration Yearly collection of European medically assisted reproduction (MAR) data by EIM for ESHRE. The data on treatments performed between January 1 and December 31, 2021, in 34 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations. Participants/materials, setting, methods In all 1155 clinics offering ART services in 34 countries reported a total of 910 470 treatment cycles, involving 115 567 with IVF, 346 183 with ICSI, 311 487 with frozen embryo replacement (FET), 62 694 with preimplantation genetic testing (PGT), 69 883 with egg donation (ED), 246 with IVM of oocytes and 4410 cycles with frozen oocyte replacement (FOR). European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 1242 institutions offering IUI in 29 and 21 countries, respectively. A total of 139 350 treatments with IUI-H and 45 532 treatments with IUI-D were included. A total of 28 692 fertility preservation (FP) interventions from 15 countries including oocyte, ovarian tissue, semen and testicular tissue banking in pre-and post-pubertal patients were reported. Main results and the role of chance In total, 1155 IVF clinics participated (81.4% of registered clinics in the participating countries). Next to these also 1242 IUI units reported their data. In the 34 reporting countries, after IVF the clinical pregnancy rates (PR) per aspiration and per transfer in 2021 were similar to those observed in 2020 (26.2% and 43.3% versus 25.4% and 40.9%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2020 (23.9% en 45.7% versus 25.2% and 45.3%). Also after FET with own embryos, the PR per thawing is stabilizing, 35.0% in 2020 and 36.2% in 2021. After ED the PR per fresh embryo transfer was slightly increased to 53.1% (51.3% in 2020) and per FOR 45.5% (43.9% in 2020). In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and ≥4 embryos in 60.2%, 34.8%, 1.8% and 0.2% of all treatments, respectively (corresponding to 57.9%, 37.5%, 2.1% and 0.2% in 2020). This resulted in a proportion of singleton, twin and triplet DRs of 90.4%, 9.5% and 0.1%, respectively (compared to 88.9%, 10.9% and 0.2%, respectively in 2020). Treatments with FER in 2021 resulted in twin and triplet DR of 7.0% and 0.1%, respectively (versus 7.9% and 0.1% in 2020). After IUI, the DRs remained similar at 9.2% after IUI-H (8.8% in 2020) and at 14.0% after IUI-D (12.5% in 2020). Twin and triplet DRs after IUI-H were 7.4% and 0.2%, respectively (in 2020: 7.9% and 0.4%) and 5.9% and 0.2% after IUI-D (in 2020: 5.7% and 0.1%). The majority of FP interventions included the cryopreservation of oocytes (n= 11 966 from 15 countries) and of ejaculated sperm (n=14 688 from 15 countries). Limitations, reasons for caution As the methods of data collection and levels of completeness of reported data vary among European countries, the results should be interpreted with caution. For this abstract, some countries were not able to provide adequate data about the number of centers and initiated cycles and deliveries. Wider implications of the findings The 25th ESHRE report on ART and IUI shows a continuous increase of reported treatment numbers and MAR-derived live births in Europe. Being already the largest data collection on MAR in Europe, continuous efforts to stimulate data collection and reporting strive for future quality control and completeness of the data and offer higher transparency and vigilance in the field of reproductive medicine.

P-330 The impact of adenomyosis on pregnancy outcomes, from conception to birth- a systematic review and meta-analysis

Abstract Study question What is the impact of adenomyosis and its phenotypes on spectrum of outcomes ranging from conception to birth? Summary answer Adenomyosis has a negative impact on implantation with reduced clinical pregnancy and live birth rate and increased risk of miscarriage and perinatal morbidity. What is known already Current evidence, including meta-analyses, on the impact of adenomyosis on reproductive outcomes is conflicting. There are data suggesting that adenomyosis has a negative impact on pregnancy outcomes whereas some studies have suggested that adenomyosis appears inert, with no impact on reproductive functions. A wide variation has been observed in the baseline population, type of Assisted Reproductive Technology (ART) stimulation protocol, number, order and type of ART cycles across the pooled observational studies. Alongside, there may be a spectrum of adenomyosis characteristics like the disease type, location, severity, and presence of coexisting endometriosis, resulting in heterogeneity and our interpretation of evidence. Study design, size, duration For this systematic review and meta-analysis, a comprehensive search was conducted in MEDLINE, EMBASE, CINAHL Plus, Web of Science Core Collection, Clinicaltrials.gov and WHO ICTRP from inception until January 2024 with no language restriction. Observational studies were included with participants as women with natural and/or medically assisted reproduction (MAR) conception, exposure as adenomyosis diagnosed on imaging, histology or using WHO International Classification of Disease 10th edition (ICD-10) code (N80.0) and comparator as women without adenomyosis. Participants/materials, setting, methods Data was included from 51 observational studies for the meta-analysis of pregnancy and obstetric outcomes. ROBINS-E tool (Risk Of Bias In Non-randomized Studies-of Exposure) was be used to assess the risk of bias. Odds ratio (OR) from individual studies were pooled using random-effects model to summarise the estimate for dichotomous outcomes with 95% confidence interval (CI) and mean differences for continuous outcomes. This was supplemented by sensitivity analyses. Clinical heterogeneity was assessed with I² statistics. Main results and the role of chance Women with adenomyosis had reduced odds of implantation (OR = 0.78; CI: 0.72-0.86), lower clinical pregnancy (OR = 0.87; CI: 0.82-0.92), higher miscarriage (OR = 1.51; CI: 1.44-1.58), and lower live birth (OR = 0.56; CI: 0.50-0.63) compared to those without. Both, diffuse and focal adenomyosis were associated with lower live birth (OR = 0.56; CI: 0.45-0.72; diffuse and OR = 0.56; CI: 0.45-0.70; focal). The miscarriage risk was higher in junctional zone adenomyosis (OR = 4.04; CI: 1.17-13.94) compared to outer myometrium adenomyosis. The negative impact of adenomyosis was evident in subgroups of women undergoing donor oocyte cycles (OR = 0.62; CI: 0.50-0.76; live birth and OR = 1.83; CI: 1.26-2.66; miscarriage) and first ART cycle (OR = 0.55; CI: 0.48-0.65; live birth and OR = 2.16 CI: 1.72-2.71; miscarriage). Conversely, those with euploid embryo transfer, had a higher odds of miscarriage (OR = 1.90; CI:1.05-3.43) with no significant impact on live birth (OR = 0.78; CI: 0.52-1.19). The impact continued perinatally, including pre-eclampsia (OR = 1.32; CI: 1.23-1.41), small for gestational age (OR = 1.323; CI:1.25-1.40), placenta previa (OR = 3.99, CI: 3.53-4.51), caesarean section (OR = 1.97; CI:1.89-2.05), and low Apgar scores (OR = 0.911; CI:0.88-0.96). Limitations, reasons for caution The inherent heterogeneity among the included observational studies was high; however, subgroup analyses for type of ART cycle, number, and order of ART cycle and by phenotype of adenomyosis had low heterogeneity. This warrants caution when interpreting pooled outcome estimates for pregnancy and obstetric outcomes across general population of women. Wider implications of the findings Adenomyosis has a direct and negative impact on fertility and pregnancy outcomes by virtue of impaired implantation and trophoblastic function. Hence, adenomyosis needs to be factored in when counselling women about the success of MAR cycles and requires closer monitoring in pregnancy as a high-risk pregnancy. Trial registration number not applicable

O-058 Newly identified female mutations causing oocyte maturation defect and embryo developmental arrest

Abstract Female infertility is a complex issue affecting a significant number of women. In the United States, among married women aged 15–49 years with no prior births, approximately one in five (19%) were unable to get pregnant after one year of trying. In addition, approximately one in four (26%) women in this group had difficulty getting pregnant or carrying a pregnancy to term. For women under 35 years of age, infertility is defined as a lack of success within one year, while for women aged 35 and older, it is within six months. Various factors, such as genetic, endocrine, physiological, anatomical, and immunological irregularities within the reproductive system, can affect a woman's chances of achieving pregnancy and delivering a healthy child. Among these factors, oocyte maturation is an important prerequisite for successful fertilization and subsequent embryonic development. In Medically Assisted Reproduction (MAR), the meiotic maturation of oocytes is induced by human chorionic gonadotropin (hCG) injection, which mimics the natural endogenous luteinizing hormone (LH) surge during the menstrual cycle. Although it is common for a few oocytes to remain immature despite ovarian stimulation and hCG administration, generally, immature oocytes have the competency to spontaneously mature in vitro. However, oocyte maturation is a sophisticated process involving multiple genes or protein molecules. Therefore, pathogenic variations in the genomic sequence or functional defects in any molecule that affects meiosis may lead to impaired oocyte maturation. While complete failure of all oocytes to mature in vivo is extremely rare, understanding the molecular aetiology of oocyte maturation is crucial for addressing infertility issues related to this process and improving fertility outcomes. The transition from the cleavage to the blastocyst stage often represents a significant bottleneck, with nearly 10% of fertilized eggs arrested at the cleavage stages. Developmental arrest of the preimplantation embryo is characterized by the cessation of cellular division for at least 24 h. Various factors originating from both embryonic and parental sources contribute to arrest of early stage embryo development. The genetic roots of developmental arrest were examined by considering both the parental causes of infertility and factors within the embryo. Examination revealed shared elements, regardless of the source of origin. Chromosomal abnormalities, abnormal preimplantation development, and monogenic variations have been reported to cause embryonic developmental arrests. Recently, deficiencies in oocyte maturation and embryo development have been categorized as part of the oocyte/zygote/embryo arrest (OZEMA) phenotype in the Online Mendelian Inheritance in Man (OMIM) database. A latest extensive review of monogenic causes associated with female infertility identified 23 genes with a total of 27 gene disease relationships (GDRs) for the OZEMA phenotype. Seventeen GDRs were classified as having at least moderate evidence of involvement in OZEMA, in addition to ten GDRs with less substantial evidence. Several additional genes were subsequently identified. This presentation will provide an overview of gene defects linked to the OZEMA phenotype, discuss the current status and future prospects of pre-MAR screening of females with OZEMA, and assess a novel workflow for modern genetic diagnosis to maximize the benefit of the patient.

P-700 Modelling individual follicle growth rates during ovarian stimulation in medically assisted reproduction cycles to enable prediction of final follicle profiles

Abstract Study question Can the growth of individual follicles during ovarian stimulation in medically assisted reproduction (MAR) cycles be modelled to enable prediction of final follicle profiles? Summary answer Mean follicle growth rate is 1.35 mm per day. Our model reliably forecasts follicle size profiles on the final scan within ±2mm with 75.1% accuracy. What is known already Follicle growth rates during ovarian stimulation are believed to be linear with various mean growth rates reported between 1 to 4 mm per day. Follicles are believed to grow faster during ovarian stimulation than in the natural menstrual cycle. The change in mean follicle size was 1.69 mm per day with ovarian stimulation in 131 MAR cycles, and 1.4 mm per day in 50 natural cycles. However, there are only very limited data using individual follicle sizes to model follicle growth to enable prediction of future follicle size profiles. Study design, size, duration We conducted a retrospective cohort study of 12,950 patients from 11 European clinics (2005-2023). First IVF/ICSI cycles with at least three follicles and two scans were analysed. Using 8,564 cycles with scans one or two days apart, 98,029 follicles were modelled to estimate follicle growth rates per day. Stratification by age, weight, total antral follicle count (AFC), initial FSH dose, and suppressant protocol was performed. Predictive modelling was conducted using 39,698 scans including 434,082 follicles. Participants/materials, setting, methods Assessment of Follicle Growth: Follicles were ranked and the difference in corresponding follicle sizes over consecutive scans estimated, and the impact of baseline characteristics evaluated. Prediction of follicle size profile on final scan: A kernel density estimator and random forest model were developed using the same training data. Both approaches estimated future follicle growth from the initial scan. The two predictions were combined using maximum-likelihood adjustments. Generalisation error was estimated using independent test data. Main results and the role of chance The mean growth rate of individual follicles was 1.350 mm per day (95% CI 1.346 – 1.353 mm per day), which was lower than the previously reported mean follicle growth rate during ovarian stimulation (1.7 mm per day). The large number of patient-cycles and follicles assessed enabled a precise estimate of follicle growth per day during ovarian stimulation. Age, total AFC, initial FSH dose, bodyweight, and suppressant protocol had no statistically significant effect on the estimated mean growth rate. Using only the follicle sizes from the initial scan during ovarian stimulation, our model had 75.1% accuracy for predicting follicle sizes on the final scan within ±2mm. Including follicle size data from the first two scans improved the accuracy of the model to predict the follicle sizes on the final scan to 80.4%. In a confirmatory analysis, we cross-validated our findings across each of 11 individual clinics, and similar estimates for the generalisation error as for the standard test/train split were maintained, suggesting suitable generalisability of these findings. Limitations, reasons for caution A key simplifying assumption in this study is that follicles demonstrate monotonic growth patterns. Specifically, the relative ordering of follicle sizes is preserved over the entire cycle. This assumption enables straightforward extraction of growth statistics from the observed data but assumes that follicles do not regress in size. Wider implications of the findings We have used a large high-quality dataset, allied to advanced modern machine learning techniques, to precisely estimate follicle growth rates during ovarian stimulation, and use this to reliably predict future follicle size profiles during ovarian stimulation. This supports the design, personalisation, streamlining and success of future assisted conception cycles. Trial registration number None

P-093 The effect of antioxidant supplementation on sperm quality in infertile men: a randomized placebo-controlled clinical trial

Abstract Study question Is sperm quality improved in infertile men after administration for three months of a combination of antioxidants as compared to placebo? Summary answer Administration in infertile men for three months of a combination of antioxidants as compared to placebo does not improve sperm quality. What is known already In infertile men, limited evidence exists to support treatment with a combination of antioxidants for improving sperm quality. A recent Cochrane meta-analysis suggested that treatment of these patients with combinations of antioxidants as compared to placebo or no treatment results in an increase in sperm motility (MD + 12.71 95%CI +11.33 to + 14.08, 7 studies, 684 patients), while no beneficial effect was observed on DNA fragmentation index (DFI) and on the probability of live birth. Nevertheless, combinations of antioxidants are widely used in clinical practice at present. Study design, size, duration This randomized placebo-controlled trial evaluated the effect of a combination of antioxidants on sperm motility (primary outcome). Secondary outcomes were sperm concentration, morphology, DFI and levels of reactive oxygen species (ROS). For this purpose, 79 infertile men, were randomized, using a computer-generated randomization list, between 2019-2022, to receive either a combination of antioxidants (n = 40) or placebo (n = 39) for three months. This was a quadruple-blind trial (participants, clinicians, outcome assessors, data analyst). Participants/materials, setting, methods Sperm variables were evaluated according to WHO criteria, ROS levels by the detection of 8-hydroxy-2-deoxy-guanosine peroxidation product on sperm and DFI by flow cytometry. For all outcomes, the changes between treatment initiation and completion were assessed in both the antioxidant and the placebo groups and compared statistically. Values are expressed as mean (95%CI of the mean) and statistical significance was set at p = 0.05. Main results and the role of chance Nine patients dropped out from the study, since they did not perform the second sperm analysis for personal reasons and thus did not complete the study process. No differences were observed between the antioxidants and the placebo group regarding male age {mean difference (MD) -1.3 years, 95%CI -1.4 to + 4.1}, smoking (antioxidants: 41.6%, 95%CI 25.5 to 59.2 vs placebo: 43.5%, 95%CI 27.8 to 60.3), exercise (antioxidants: 45.4%, 95%CI 28.1 to 63.6 vs placebo: 16.1%, 95%CI 5.4 to 33.7) and primary infertility (antioxidants: 82.3%, 95%CI 65.4 to 93.2 vs placebo: 85.7%, 95%CI 69.7 to 95.1). No statistically significant differences were observed in infertile men who received a combination of antioxidants or placebo, between the changes of pre and post treatment values, regarding sperm motility (-3.5%, 95%CI: -13 to + 5.9, p = 0.742), concentration (-1.9%, 95%CI: -15.7 to + 11.8, p = 0.0.77), morphology (-0.10%, 95%CI: -0.8 to 0.6, p = 0.793), DFI (0.2%, 95%CI: -3.8 to + 4.4, p = 0.891) and levels of ROS (-1.2%, 95%CI: -3.2 to + 0.8, p = 0.231). No side effects were reported in antioxidants combination treated patients for the duration of follow-up. Limitations, reasons for caution The current RCT did not explicitly include men with abnormal DFI, limiting the extrapolation of the results obtained in this group of patients. Moreover, it was not designed to evaluate the probability of pregnancy either spontaneously or after Medically Assisted Reproduction (MAR). Wider implications of the findings The current study does not support the use of antioxidants for enhancing male infertility. Future relevant studies should focus on identifying the optimal population and duration of treatment. Trial registration number NCT04256278

P-759 Safety and quality of MAR (medically assisted reproduction) provisions in Spain in response to adaptative regulation during a public health emergency: a national registry analysis

Abstract Study question Did the level of quality and the safety of MAR treatments change in response to the restrictive medical care regulations during the COVID emergency? Summary answer All assessed markers of PMA treatment quality and safety were maintained, indicating a robust quality structure of the Spanish PMA medical system. What is known already Acute public health stressors can affect the provision of effective and safe care in specific healthcare areas, as operational constrains are put in place and resource allocation is shifted to emerging areas of need. During 2020, Spain was heavily affected by the COVID pandemic, and the provision of PMA was constrained both in time and scope for several months. Here, we examine the results of these constrains on the quality and safety of PMA treatments performed in the country through the comparative analysis of pre- and post- emergency national data. Study design, size, duration This retrospective study includes aggregate registry data from 316 PMA centers in Spain, representing 100% of reported IVF/ICSI treatments in the country. Data refer to treatments performed in 2019, 2020 and 2021.Treatment data were compared on an intention to treat basis (ITT) whenever possible. Participants/materials, setting, methods A total of 48.123, 40.453 and 49.734 IVF/ICSI treatments with own oocytes were initiated in 2019, 2020 and 2021 respectively. Oocyte donor stimulation were 15.807, 12.001, and 13.287, respectively. Safety markers analyzed were: oocytes collected (donation), multiple pregnancies and births, complications of treatment requiring hospitalization. Indicators of efficacy were pregnancy and live birth rates, with and without PGT-A, on an ITT basis. Data were compared by ANOVA or t-test. A p &amp;lt; 0.05 was considered significant. Main results and the role of chance The ratio between transfers and clinical results in IVF/ICSI cycles with own eggs, according to treatment intention, has remained stable in both pregnancies [34.4-34.8%] and deliveries [24.7-25.7%] between 2019, 2020 and 2021 Births with multiple fetuses were 11.3%, 9.4% and 8.7% respectively. Live births from PGT-A cycles were 22.4% in 2019 and 23.0% in 2020. The results of cycles with donor eggs remained stable in both pregnancies [56.7-58.7%] and deliveries [43.3-44.2%] between 2019, 2020 and 2021. Births with multiple fetuses were 10.7%, 9.8% and 8.2% respectively. Births of higher order than twins were anecdotal. Complications requiring hospital admission have remained at 0.20% - 0.026% of total treatments, with ovarian hyperstimulation and hemorrhages being the most frequent. Limitations, reasons for caution The aggregate nature of data did not allow for a more in depth associative analysis. Wider implications of the findings The analyzed indicators have remained within the expected ranges, suggesting a low impact of the COVID measures on the operational quality and safety of the TRA units. Trial registration number NA