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STUDY QUESTION To what extent can genotype analysis aid in the classification of (mosaic) aneuploid embryos diagnosed through copy number analysis of a trophectoderm (TE) biopsy? SUMMARY ANSWER In a small portion of embryos, genotype analysis revealed signatures of meiotic or uniform aneuploidy in those diagnosed with intermediate copy number changes, and signatures of presumed mitotic or putative mosaic aneuploidy in those diagnosed with full copy number changes. WHAT IS KNOWN ALREADY Comprehensive chromosome screening (CCS) for preimplantation genetic testing has provided valuable insights into the prevalence of (mosaic) chromosomal aneuploidy at the blastocyst stage. However, diagnosis of (mosaic) aneuploidy often relies solely on (intermediate) copy number analysis of a single TE biopsy. Integrating genotype information allows for independent assessment of the origin and degree of aneuploidy. Yet, studies aligning both datasets to predict (putative mosaic) aneuploidy in embryos remain scarce. STUDY DESIGN, SIZE, DURATION A single TE biopsy was collected from 1560 embryos derived from 221 couples tested for a monogenic disorder (n = 218) or microdeletion-/microduplication syndrome (n = 3). TE samples were subjected to both copy number and genotyping analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Copy number and SNP genotyping analysis were conducted using GENType. Unbalanced chromosomal anomalies ≥10 Mb (or ≥20 Mb for copy number calls <50%) were classified by degree, based on low-range intermediate (LR, 30–50%), high-range intermediate (HR, 50–70%) or full (>70%) copy number changes. These categories were further subjected to genotyping analysis to ascertain the origin (and/or degree) of aneuploidy. For chromosomal gains, the meiotic division of origin (meiotic I/II versus non-meiotic or presumed mitotic) was established by studying the haplotypes. The level of monosomy (uniform versus putative mosaic) in the biopsy could be ascertained from the B-allele frequencies. For segmental aneuploidies, genotyping was restricted to deletions. MAIN RESULTS AND THE ROLE OF CHANCE Of 1479 analysed embryos, 24% (n = 356) exhibited a whole-chromosome aneuploidy, with 19% (n = 280) showing full copy number changes suggestive of uniform aneuploidy. Among 258 embryos further investigated by genotyping, 95% of trisomies with full copy number changes were identified to be of meiotic origin. For monosomies, a complete loss of heterozygosity (LOH) in the biopsy was observed in 97% of cases, yielding a 96% concordance rate at the embryo level (n = 248/258). Interestingly, 4% of embryos (n = 10/258) showed SNP signatures of non-meiotic gain or putative mosaic loss instead. Meanwhile, 5% of embryos (n = 76/1479) solely displayed HR (2.5%; n = 37) or LR (2.6%; n = 39) intermediate copy number changes, with an additional 2% showing both intermediate and full copy number changes. Among embryos with HR intermediate copy number changes where genotyping was feasible (n = 25/37), 92% (n = 23/25) showed SNP signatures consistent with putative mosaic aneuploidy. However, 8% (n = 2/25) exhibited evidence of meiotic trisomy (9%) or complete LOH in the biopsy (7%). In the LR intermediate group, 1 of 33 (3%) genotyped embryos displayed complete LOH. Furthermore, segmental aneuploidy was detected in 7% of embryos (n = 108/1479) (or 9% (n = 139) with added whole-chromosome aneuploidy). These errors were often (52%) characterized by intermediate copy number values, which closely aligned with genotyping data when examined (94–100%). LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The findings were based on single TE biopsies and the true extent of mosaicism was not validated through embryo dissection. Moreover, evidence of absence of a meiotic origin for a trisomy should not be construed as definitive proof of a mitotic error. Additionally, a genotyping diagnosis was not always attainable due to the absence of a recombination event necessary to discern between meiotic II and non-meiotic trisomy, or the unavailability of DNA from both parents. WIDER IMPLICATIONS OF THE FINDINGS Interpreting (intermediate) copy number changes of a single TE biopsy alone as evidence for (mosaic) aneuploidy in the embryo remains suboptimal. Integrating genotype information alongside the copy number status could provide a more comprehensive assessment of the embryo's genetic makeup, within and beyond the single TE biopsy. By identifying meiotic aberrations, especially in presumed mosaic embryos, we underscore the potential value of genotyping analysis as a deselection tool, ultimately striving to reduce adverse clinical outcomes. STUDY FUNDING/COMPETING INTEREST(S) L.D.W. was supported by the Research Foundation Flanders (FWO; 1S74621N). M.B. K.T. F.V.M. S.J. A.V.T. V.S. D.S. A.D. and S.S. are supported by Ghent University Hospital. B.M. was funded by Ghent University. The authors have no conflicts of interest. [ABSTRACT FROM AUTHOR]

Hormonal treatments and surgical interventions practiced with the aim to affirm gender identity in transgender and gender diverse patients may impact their future reproductive ability, family building, and family planning options. Whereas it is recommended by international guidelines to discuss the potential risks of infertility and to present fertility preservation (FP) options to transgender individuals and their families prior to initiating any of these treatments, many barriers still remain. Further, transgender and gender diverse individuals often experience barriers to accessing contraception, abortion, pre-conception care, and comprehensive perinatal care. In this review we summarize the current literature on reproductive healthcare issues reported in transgender people including fertility issues, fertility preservation (FP), contraception, pregnancy and lactation and perinatal health. A narrative literature search of major databases (Pubmed, Medline, PsycInfo, Google Scholar, Web of Science) was conducted. Given the paucity and heterogeneity of studies, summative review tactics were not available. The literature was critically reviewed by international experts in the field with focus on the impact of gender-affirming medical interventions on future fertility, current FP options and reproductive health issues in transgender people. The current literature supports that transgender and gender diverse individuals may wish to have genetically related children in the future, rendering the issue of FP relevant to this patient group. The cryopreservation of mature gametes is an efficacious option for FP for post-pubertal adolescents and adults. It is recommended to discuss these options at time of planning for gender-affirming hormonal therapy (GAHT) or engaging with other gender-affirming procedures that can limit future fertility. Discontinuation of GAHT may allow individuals to undergo FP later, but data are limited and there is the concern of symptoms and consequences of stopping GAHT. For pre-pubertal and early pubertal children, FP options are limited to the cryopreservation of gonadal tissue. At present the tissue can become functional only after re-transplantation, which might be undesirable by transgender individuals in the future. Preconception counseling, prenatal surveillance, perinatal support, contraceptive, and pregnancy termination related healthcare need to be meaningfully adapted for this patient population, and many knowledge gaps remain. Specialized FP reproductive healthcare for transgender and gender diverse individuals is in early evolution. Research should be conducted to examine effects of medical interventions on fertility, timing of FP, gamete preservation and outcome of the fertility treatments. Strategies to inform and educate transgender and gender diverse patients can lead to optimization of reproductive care and counseling and decision making of FP for this population. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What information and support should be offered to donors, intended parents and donor-conceived people, in general and in consideration of the availability of direct-to-consumer genetic testing and matching services? SUMMARY ANSWER For donors, intended parents and donor-conceived offspring, recommendations are made that cover information needs and informed consent, psychosocial implications and disclosure. WHAT IS KNOWN ALREADY Trends indicate that the use of donor-assisted conception is growing and guidance is needed to help these recipients/intended parents, the donors and offspring, navigate the rapidly changing environment in which donor-assisted conception takes place. STUDY DESIGN, SIZE, DURATION A working group (WG) collaborated on writing recommendations based, where available, on evidence collected from a literature search and expert opinion. Draft recommendations were published for stakeholder review and adapted where relevant based on the comments received. PARTICIPANTS/MATERIALS, SETTING, METHODS Papers retrieved from PUBMED were included from 1 January 2014 up to 31 August 2020, focusing on studies published since direct-to-consumer genetic testing has become more widespread and accessible. The current paper is limited to reproductive donation performed in medically assisted reproduction (MAR) centres (and gamete banks): donation outside the medical context was not considered. MAIN RESULTS AND THE ROLE OF CHANCE In total, 32 recommendations were made for information provision and support to donors, 32 for intended parents and 27 for donor-conceived offspring requesting information/support. LIMITATIONS, REASONS FOR CAUTION The available evidence in the area of reproductive donation is limited and diverse with regards to the context and types of donation. General conclusions and recommendations are largely based on expert opinion and may need to be adapted in light of future research. WIDER IMPLICATIONS OF THE FINDINGS These recommendations provide guidance to MAR centres and gamete banks on good practice in information provision and support but should also be considered by regulatory bodies and policymakers at a national and international level to guide regulatory and legislative efforts towards the protection of donors and donor-conceived offspring. STUDY FUNDING/COMPETING INTEREST(S) The development of this good practice paper was funded by European Society of Human Reproduction and Embryology (ESHRE), covering expenses associated with the WG meetings, the literature searches and dissemination. The WG members did not receive any payment. The authors have no conflicts of interest to declare. DISCLAIMER This document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and where relevant based on the scientific evidence available at the time of preparation. The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. †ESHRE pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the recommended management for medically assisted reproduction (MAR) in patients with a viral infection or disease, based on the best available evidence in the literature? SUMMARY ANSWER The ESHRE guideline on MAR in patients with a viral infection/disease makes 78 recommendations on prevention of horizontal and vertical transmission before, during and after MAR, and the impact on its outcomes, and these also include recommendations regarding laboratory safety on the processing and storage of gametes and embryos testing positive for viral infections. WHAT IS KNOWN ALREADY The development of new and improved anti-viral medications has resulted in improved life expectancy and quality of life for patients with viral infections/diseases. Patients of reproductive age are increasingly exploring their options for family creation. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for the development of ESHRE guidelines. After the formulation of nine key questions for six viruses (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human papilloma virus, human T-lymphotropic virus I/II and Zika virus) by a group of experts, literature searches and assessments were performed. Papers published up to 2 November 2020 and written in English were included in the review. Evidence was analyzed by female, male or couple testing positive for the virus. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. There were 61 key questions to be answered by the guideline development group (GDG), of which 12 were answered as narrative questions and 49 as PICO (Patient, Intervention, Comparison, Outcome) questions. A stakeholder review was organized after the finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE This guideline aims to help providers meet a growing demand for guidance on the management of patients with a viral infection/disease presenting in the fertility clinic. The guideline makes 78 recommendations on prevention of viral transmission before and during MAR, and interventions to reduce/avoid vertical transmission to the newborn. Preferred MAR treatments and interventions are described together with the effect of viral infections on outcomes. The GDG formulated 44 evidence-based recommendations—of which 37 were formulated as strong recommendations and 7 as weak—33 good practice points (GPP) and one research only recommendation. Of the evidence-based recommendations, none were supported by high-quality evidence, two by moderate-quality evidence, 15 by low-quality evidence and 27 by very low-quality evidence. To support future research in the field of MAR in patients with a viral infection/disease, a list of research recommendations is provided. LIMITATIONS, REASONS FOR CAUTION Most interventions included are not well-studied in patients with a viral infection/disease. For a large proportion of interventions, evidence was very limited and of very low quality. More evidence is required for these interventions, especially in the field of human papilloma virus (HPV). Such future studies may require the current recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides clinicians with clear advice on best practice in MAR for patients with a viral infection/disease, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in the field. STUDY FUNDING/COMPETING INTEREST(S) The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive any financial incentives, all work was provided voluntarily. A.D. reports research fees from Ferring and Merck, consulting fees from Ferring, outside the submitted work. C.P. reports speakers fees from Merck and MSD outside the submitted work. K.T. reports speakers fees from Cooper Surgical and Ferring and consultancy fees as member of the advisory board BioTeam of Ferring, outside the submitted work. The other authors have no conflicts of interest to declare. DISCLAIMER This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.) [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is it possible to define a set of performance indicators (PIs) for clinical work in ART, which can create competency profiles for clinicians and for specific clinical process steps? SUMMARY ANSWER The current paper recommends six PIs to be used for monitoring clinical work in ovarian stimulation for ART, embryo transfer, and pregnancy achievement: cycle cancellation rate (before oocyte pick-up (OPU)) (%CCR), rate of cycles with moderate/severe ovarian hyperstimulation syndrome (OHSS) (%mosOHSS), the proportion of mature (MII) oocytes at ICSI (%MII), complication rate after OPU (%CoOPU), clinical pregnancy rate (%CPR), and multiple pregnancy rate (%MPR). WHAT IS KNOWN ALREADY PIs are objective measures for evaluating critical healthcare domains. In 2017, ART laboratory key PIs (KPIs) were defined. STUDY DESIGN, SIZE, DURATION A list of possible indicators was defined by a working group. The value and limitations of each indicator were confirmed through assessing published data and acceptability was evaluated through an online survey among members of ESHRE, mostly clinicians, of the special interest group Reproductive Endocrinology. PARTICIPANTS/MATERIALS, SETTING, METHODS The online survey was open for 5 weeks and 222 replies were received. Statements (indicators, indicator definitions, or general statements) were considered accepted when ≥70% of the responders agreed (agreed or strongly agreed). There was only one round to seek levels of agreement between the stakeholders. Indicators that were accepted by the survey responders were included in the final list of indicators. Statements reaching less than 70% were not included in the final list but were discussed in the paper. MAIN RESULTS AND THE ROLE OF CHANCE Cycle cancellation rate (before OPU) and the rate of cycles with moderate/severe OHSS, calculated on the number of started cycles, were defined as relevant PIs for monitoring ovarian stimulation. For monitoring ovarian response, trigger and OPU, the proportion of MII oocytes at ICSI and complication rate after OPU were listed as PIs: the latter PI was defined as the number of complications (any) that require an (additional) medical intervention or hospital admission (apart from OHSS) over the number of OPUs performed. Finally, clinical pregnancy rate and multiple pregnancy rate were considered relevant PIs for embryo transfer and pregnancy. The defined PIs should be calculated every 6 months or per 100 cycles, whichever comes first. Clinical pregnancy rate and multiple pregnancy rate should be monitored more frequently (every 3 months or per 50 cycles). Live birth rate (LBR) is a generally accepted and an important parameter for measuring ART success. However, LBR is affected by many factors, even apart from ART, and it cannot be adequately used to monitor clinical practice. In addition to monitoring performance in general, PIs are essential for managing the performance of staff over time, and more specifically the gap between expected performance and actual performance measured. Individual clinics should determine which indicators are key to the success in their organisation based on their patient population, protocols, and procedures, and as such, which are their KPIs. LIMITATIONS, REASONS FOR CAUTION The consensus values are based on data found in the literature and suggestions of experts. When calculated and compared to the competence/benchmark limits, prudent interpretation is necessary taking into account the specific clinical practice of each individual centre. WIDER IMPLICATIONS OF THE FINDINGS The defined PIs complement the earlier defined indicators for the ART laboratory. Together, both sets of indicators aim to enhance the overall quality of the ART practice and are an essential part of the total quality management. PIs are important for education and can be applied during clinical subspecialty. STUDY FUNDING/COMPETING INTEREST(S) This paper was developed and funded by ESHRE, covering expenses associated with meetings, literature searches, and dissemination. The writing group members did not receive payment. Dr G.G. reports personal fees from Merck, MSD, Ferring, Theramex, Finox, Gedeon-Richter, Abbott, Biosilu, ReprodWissen, Obseva, PregLem, and Guerbet, outside the submitted work. Dr A.D. reports personal fees from Cook, outside the submitted work; Dr S.A. reports starting a new employment in May 2020 at Vitrolife. Previously, she has been part of the Nordic Embryology Academic Team, with meetings were sponsored by Gedeon Richter. The other authors have no conflicts of interest to declare. DISCLAIMER This document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and where relevant based on the scientific evidence available at the time of preparation. The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. Furthermore, ESHREs recommendations do not constitute or imply the endorsement, recommendation, or favouring of any of the included technologies by ESHRE. [ABSTRACT FROM AUTHOR]

Study Question: Can risks associated with novelties in assisted reproduction technologies (ARTs) be assessed in a systematic and structured way?Summary Answer: An ART-specific risk assessment tool has been developed to assess the risks associated with the development of novelties in ART (EuroGTP II-ART).What Is Known Already: How to implement new technologies in ART is well-described in the literature. The successive steps should include testing in animal models, executing pre-clinical studies using supernumerary gametes or embryos, prospective clinical trials and finally, short- and long-term follow-up studies on the health of the offspring. A framework categorizing treatments from experimental through innovative to established according to the extent of the studies conducted has been devised. However, a systematic and standardized methodology to facilitate risk evaluation before innovations are performed in a clinical setting is lacking.Study Design, Size, Duration: The EuroGTP II-ART risk assessment tool was developed on the basis of a generic risk assessment algorithm developed for tissue and cell therapies and products (TCTPs) in the context of the project 'Good Practices for demonstrating safety and quality through recipient follow-up European Good Tissue and cells Practices II (EuroGTP II)'. For this purpose, a series of four meetings was held in which eight ART experts participated. In addition, several tests and simulations were undertaken to fine-tune the final tool.Participants/materials, Setting, Methods: The three steps comprising the EuroGTP II methodology were evaluated against its usefulness and applicability in ART. Ways to improve and adapt the methodology into ART risk assessment were agreed and implemented.Main Results and the Role Of Chance: Assessment of the novelty (Step 1), consisting of seven questions, is the same as for other TCTPs. Practical examples were included for better understanding. Identification of potential risks and consequences (Step 2), consisting of a series of risks and risk consequences to consider during risk assessment, was adapted from the generic methodology, adding more potential risks for processes involving gonadic tissues. The algorithm to score risks was also adapted, giving a specific range of highest possible risk scores. A list of strategies for risk reduction and definition of extended studies required to ensure effectiveness and safety (Step 3) was also produced by the ART experts, based on generic EuroGTP II methodology. Several explanations and examples were provided for each of the steps for better understanding within this field.Limitations, Reasons For Caution: A multidisciplinary team is needed to perform risk assessment, to interpret results and to determine risk mitigation strategies and/or next steps required to ensure the safety in the clinical use of novelties.Wider Implications Of the Findings: This is a dynamic tool whose value goes beyond assessment of risk before implementing a novel ART in clinical practice, to re-evaluate risks based on information collected during the process.Study Funding/ Competing Interest(s): This study was called EUROGTP II and was funded by the European Commission (Grant agreement number 709567). The authors declare no competing interests concerning the results of this study. [ABSTRACT FROM AUTHOR]

STUDY QUESTION To evaluate the implementation of the coding systems in medically assisted reproduction (MAR) centres in the European Union (EU). SUMMARY ANSWER Our data show that a significant number of MAR centres use the Single European Code (SEC), but it also shows certain limitations to the coding. WHAT IS KNOWN ALREADY Traceability and identification of tissue and cells used for clinical application are extremely important as it is one of the key aspects of quality and safety both for the donors and the recipients. Patients as well as tissues and cells move across the European continent and far beyond, hence a uniform coding system was very much needed. The coding of tissues and cells from human origin was already embedded in the EU directives 2004/23/EC. The use of the Single European Code (SEC) on tissues and cells was enforced in 2017 for tissues and cells distributed within the EU or exported from the EU. The SEC ensures standardization within the EU, allowing the integration of the two existing codes (ISBT-128 and Eurocode) within the SEC structure. Likewise, in the MAR field, the SEC was launched in order to ensure the traceability of reproductive tissues and cells. Gametes and embryos from partner donation as well as reproductive cells and tissues of allogeneic donation were excluded from the SEC as long as they remain in the centre of origin. STUDY DESIGN, SIZE, DURATION A cross-sectional survey aimed to gain insight into the use of SEC by MAR centres was conducted between 5 November and 15 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS The online survey was distributed among the ESHRE members. MAIN RESULTS AND THE ROLE OF CHANCE The survey results highlight the strengths and weaknesses in the practical use of the SEC. The data from the survey showed that the SEC code is something that is known in the MAR field. Our data showed that over half of the respondents were using the SEC in their centre. On the other hand, there is also criticism about the use of SEC in MAR, especially that the added value for traceability and identification in ART is found to be rather limited. LIMITATIONS, REASONS FOR CAUTION The survey response rate was rather low (4.84%). The view of the use of SEC discussed in this paper still provides insight into the use of the SEC in several MAR centres. WIDER IMPLICATIONS OF THE FINDINGS The survey highlights some knowledge gaps concerning coding. This information can be used to develop tools to increase knowledge of the SEC. STUDY FUNDING/COMPETING INTEREST(S) There was no external funding for this study. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Study Question: To what extent can genotype analysis aid in the classification of (mosaic) aneuploid embryos diagnosed through copy number analysis of a trophectoderm (TE) biopsy?, Summary Answer: In a small portion of embryos, genotype analysis revealed signatures of meiotic or uniform aneuploidy in those diagnosed with intermediate copy number changes, and signatures of presumed mitotic or putative mosaic aneuploidy in those diagnosed with full copy number changes., What Is Known Already: Comprehensive chromosome screening (CCS) for preimplantation genetic testing has provided valuable insights into the prevalence of (mosaic) chromosomal aneuploidy at the blastocyst stage. However, diagnosis of (mosaic) aneuploidy often relies solely on (intermediate) copy number analysis of a single TE biopsy. Integrating genotype information allows for independent assessment of the origin and degree of aneuploidy. Yet, studies aligning both datasets to predict (putative mosaic) aneuploidy in embryos remain scarce., Study Design Size Duration: A single TE biopsy was collected from 1560 embryos derived from 221 couples tested for a monogenic disorder (n = 218) or microdeletion-/microduplication syndrome (n = 3). TE samples were subjected to both copy number and genotyping analysis., Participants/materials Setting Methods: Copy number and SNP genotyping analysis were conducted using GENType. Unbalanced chromosomal anomalies ≥10 Mb (or ≥20 Mb for copy number calls <50%) were classified by degree, based on low-range intermediate (LR, 30-50%), high-range intermediate (HR, 50-70%) or full (>70%) copy number changes. These categories were further subjected to genotyping analysis to ascertain the origin (and/or degree) of aneuploidy. For chromosomal gains, the meiotic division of origin (meiotic I/II versus non-meiotic or presumed mitotic) was established by studying the haplotypes. The level of monosomy (uniform versus putative mosaic) in the biopsy could be ascertained from the B-allele frequencies. For segmental aneuploidies, genotyping was restricted to deletions., Main Results and the Role of Chance: Of 1479 analysed embryos, 24% (n = 356) exhibited a whole-chromosome aneuploidy, with 19% (n = 280) showing full copy number changes suggestive of uniform aneuploidy. Among 258 embryos further investigated by genotyping, 95% of trisomies with full copy number changes were identified to be of meiotic origin. For monosomies, a complete loss of heterozygosity (LOH) in the biopsy was observed in 97% of cases, yielding a 96% concordance rate at the embryo level (n = 248/258). Interestingly, 4% of embryos (n = 10/258) showed SNP signatures of non-meiotic gain or putative mosaic loss instead. Meanwhile, 5% of embryos (n = 76/1479) solely displayed HR (2.5%; n = 37) or LR (2.6%; n = 39) intermediate copy number changes, with an additional 2% showing both intermediate and full copy number changes. Among embryos with HR intermediate copy number changes where genotyping was feasible (n = 25/37), 92% (n = 23/25) showed SNP signatures consistent with putative mosaic aneuploidy. However, 8% (n = 2/25) exhibited evidence of meiotic trisomy (9%) or complete LOH in the biopsy (7%). In the LR intermediate group, 1 of 33 (3%) genotyped embryos displayed complete LOH. Furthermore, segmental aneuploidy was detected in 7% of embryos (n = 108/1479) (or 9% (n = 139) with added whole-chromosome aneuploidy). These errors were often (52%) characterized by intermediate copy number values, which closely aligned with genotyping data when examined (94-100%)., Large Scale Data: N/A., Limitations Reasons for Caution: The findings were based on single TE biopsies and the true extent of mosaicism was not validated through embryo dissection. Moreover, evidence of absence of a meiotic origin for a trisomy should not be construed as definitive proof of a mitotic error. Additionally, a genotyping diagnosis was not always attainable due to the absence of a recombination event necessary to discern between meiotic II and non-meiotic trisomy, or the unavailability of DNA from both parents., Wider Implications of the Findings: Interpreting (intermediate) copy number changes of a single TE biopsy alone as evidence for (mosaic) aneuploidy in the embryo remains suboptimal. Integrating genotype information alongside the copy number status could provide a more comprehensive assessment of the embryo's genetic makeup, within and beyond the single TE biopsy. By identifying meiotic aberrations, especially in presumed mosaic embryos, we underscore the potential value of genotyping analysis as a deselection tool, ultimately striving to reduce adverse clinical outcomes., Study Funding/competing Interests: L.D.W. was supported by the Research Foundation Flanders (FWO; 1S74621N). M.B., K.T., F.V.M., S.J., A.V.T., V.S., D.S., A.D., and S.S. are supported by Ghent University Hospital. B.M. was funded by Ghent University. The authors have no conflicts of interest., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Study Question: Is it possible to define a set of performance indicators (PIs) for clinical work in ART, which can create competency profiles for clinicians and for specific clinical process steps?, Summary Answer: The current paper recommends six PIs to be used for monitoring clinical work in ovarian stimulation for ART, embryo transfer, and pregnancy achievement: cycle cancellation rate (before oocyte pick-up (OPU)) (%CCR), rate of cycles with moderate/severe ovarian hyperstimulation syndrome (OHSS) (%mosOHSS), the proportion of mature (MII) oocytes at ICSI (%MII), complication rate after OPU (%CoOPU), clinical pregnancy rate (%CPR), and multiple pregnancy rate (%MPR)., What Is Known Already: PIs are objective measures for evaluating critical healthcare domains. In 2017, ART laboratory key PIs (KPIs) were defined., Study Design Size Duration: A list of possible indicators was defined by a working group. The value and limitations of each indicator were confirmed through assessing published data and acceptability was evaluated through an online survey among members of ESHRE, mostly clinicians, of the special interest group Reproductive Endocrinology., Participants/materials Setting Methods: The online survey was open for 5 weeks and 222 replies were received. Statements (indicators, indicator definitions, or general statements) were considered accepted when ≥70% of the responders agreed (agreed or strongly agreed). There was only one round to seek levels of agreement between the stakeholders.Indicators that were accepted by the survey responders were included in the final list of indicators. Statements reaching less than 70% were not included in the final list but were discussed in the paper., Main Results and the Role of Chance: Cycle cancellation rate (before OPU) and the rate of cycles with moderate/severe OHSS, calculated on the number of started cycles, were defined as relevant PIs for monitoring ovarian stimulation. For monitoring ovarian response, trigger and OPU, the proportion of MII oocytes at ICSI and complication rate after OPU were listed as PIs: the latter PI was defined as the number of complications (any) that require an (additional) medical intervention or hospital admission (apart from OHSS) over the number of OPUs performed. Finally, clinical pregnancy rate and multiple pregnancy rate were considered relevant PIs for embryo transfer and pregnancy. The defined PIs should be calculated every 6 months or per 100 cycles, whichever comes first. Clinical pregnancy rate and multiple pregnancy rate should be monitored more frequently (every 3 months or per 50 cycles). Live birth rate (LBR) is a generally accepted and an important parameter for measuring ART success. However, LBR is affected by many factors, even apart from ART, and it cannot be adequately used to monitor clinical practice. In addition to monitoring performance in general, PIs are essential for managing the performance of staff over time, and more specifically the gap between expected performance and actual performance measured. Individual clinics should determine which indicators are key to the success in their organisation based on their patient population, protocols, and procedures, and as such, which are their KPIs., Limitations Reasons for Caution: The consensus values are based on data found in the literature and suggestions of experts. When calculated and compared to the competence/benchmark limits, prudent interpretation is necessary taking into account the specific clinical practice of each individual centre., Wider Implications of the Findings: The defined PIs complement the earlier defined indicators for the ART laboratory. Together, both sets of indicators aim to enhance the overall quality of the ART practice and are an essential part of the total quality management. PIs are important for education and can be applied during clinical subspecialty., Study Funding/competing Interests: This paper was developed and funded by ESHRE, covering expenses associated with meetings, literature searches, and dissemination. The writing group members did not receive payment.Dr G.G. reports personal fees from Merck, MSD, Ferring, Theramex, Finox, Gedeon-Richter, Abbott, Biosilu, ReprodWissen, Obseva, PregLem, and Guerbet, outside the submitted work. Dr A.D. reports personal fees from Cook, outside the submitted work; Dr S.A. reports starting a new employment in May 2020 at Vitrolife. Previously, she has been part of the Nordic Embryology Academic Team, with meetings were sponsored by Gedeon Richter. The other authors have no conflicts of interest to declare., Disclaimer: This document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and where relevant based on the scientific evidence available at the time of preparation.The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type.Furthermore, ESHREs recommendations do not constitute or imply the endorsement, recommendation, or favouring of any of the included technologies by ESHRE., (© The Author(s) 2021. Published by Oxford University Press.)

Study Question: To evaluate the implementation of the coding systems in medically assisted reproduction (MAR) centres in the European Union (EU)., Summary Answer: Our data show that a significant number of MAR centres use the Single European Code (SEC), but it also shows certain limitations to the coding., What Is Known Already: Traceability and identification of tissue and cells used for clinical application are extremely important as it is one of the key aspects of quality and safety both for the donors and the recipients. Patients as well as tissues and cells move across the European continent and far beyond, hence a uniform coding system was very much needed. The coding of tissues and cells from human origin was already embedded in the EU directives 2004/23/EC. The use of the Single European Code (SEC) on tissues and cells was enforced in 2017 for tissues and cells distributed within the EU or exported from the EU. The SEC ensures standardization within the EU, allowing the integration of the two existing codes (ISBT-128 and Eurocode) within the SEC structure. Likewise, in the MAR field, the SEC was launched in order to ensure the traceability of reproductive tissues and cells. Gametes and embryos from partner donation as well as reproductive cells and tissues of allogeneic donation were excluded from the SEC as long as they remain in the centre of origin., Study Design Size Duration: A cross-sectional survey aimed to gain insight into the use of SEC by MAR centres was conducted between 5 November and 15 December 2018., Participants/materials Setting Methods: The online survey was distributed among the ESHRE members., Main Results and the Role of Chance: The survey results highlight the strengths and weaknesses in the practical use of the SEC. The data from the survey showed that the SEC code is something that is known in the MAR field. Our data showed that over half of the respondents were using the SEC in their centre. On the other hand, there is also criticism about the use of SEC in MAR, especially that the added value for traceability and identification in ART is found to be rather limited., Limitations Reasons for Caution: The survey response rate was rather low (4.84%). The view of the use of SEC discussed in this paper still provides insight into the use of the SEC in several MAR centres., Wider Implications of the Findings: The survey highlights some knowledge gaps concerning coding. This information can be used to develop tools to increase knowledge of the SEC., Study Funding/competing Interests: There was no external funding for this study. The authors declare that they have no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)