An ESHG-ESHRE survey on the current practice of expanded carrier screening in medically assisted reproduction.

STUDY QUESTION: What is the current practice and views on (expanded) carrier screening ((E)CS) among healthcare professionals in medically assisted reproductive (MAR) practices in Europe? SUMMARY ANSWER: The findings show a limited support for ECS with less than half of the respondents affiliated to centres offering ECS, and substantial variation in practice between centres in Europe. WHAT IS KNOWN ALREADY: The availability of next-generation sequencing, which enables testing for large groups of genes simultaneously, has facilitated the introduction and expansion of ECS strategies, currently offered particularly in the private sector in the context of assisted reproduction. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey evaluating practice and current views among professionals working in MAR practice in different European countries was designed using the online SurveyMonkey tool. The web-based questionnaire included questions on general information regarding the current practice of (E)CS in MAR and questions on what is offered, to whom the test is offered, and how it is offered. It consisted mostly of multiple-choice questions with comment boxes, but also included open questions on the respondents' attitudes/concerns relevant to (E)CS practice, and room to upload requested files (e.g. guidelines and gene panels). In total, 338 responses were collected from 8 February 2022 to 11 April 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: The online survey was launched with an invitation email from the ESHRE central office (n = 4889 emails delivered) and the European Society of Human Genetics (ESHG) central office (n = 1790 emails delivered) sent to the ESHRE and ESHG members, and by social media posts. The survey was addressed to European MAR centres or gamete banks and to centres located in non-European countries participating in the European IVF-monitoring Consortium. Two reminder emails were sent. After exclusion of 39 incomplete responses received (e.g. only background information), 299 respondents from 40 different countries were included for analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 42.5% (127/299) of respondents were affiliated to centres offering ECS. The perceived responsibility to enable prospective parents to make informed reproductive decisions and preventing suffering/burden for parents were the main reasons to offer ECS. A single ECS panel is offered by nearly 45% (39/87 received answers) of the centres offering ECS, 25.3% (22/87) of those centres offer a selection of ECS panels, and 29.9% (26/87) offer whole exome sequencing and a large in silico panel. Different ranges of panel sizes and conditions were included in the ECS panel(s) offered. Most of the respondents (81.8%; 72/88 received answers) indicated that the panels they offer are universal and target the entire population. Pathogenic variants (89.7%; 70/78 received answers), and to a lesser extent, likely pathogenic variants (64.1%%; 50/78 received answers), were included in the ECS report for individuals and couples undergoing MAR with their own gametes. According to 87.9% (80/91 received answers) of the respondents, patients have to pay to undergo an ECS test. Most respondents (76.2%; 61/80 received answers) reported that counselling is provided before and after the ECS test. Preimplantation genetic testing, the use of donor gametes, and prenatal diagnostic testing were the three main reproductive options discussed with identified carrier couples. The main reason, according to the respondents, for not offering ECS in their centre, was the lack of professional recommendations supporting ECS (52.5%; 73/139 received answers) and the high cost for couples or reimbursement not being available (49.6%; 69/139). The challenges and moral dilemmas encountered by the respondents revolved mainly around the content of the offer, including the variants classification and the heterogeneity of the panels, the counselling, and the cost of the test. LIMITATIONS, REASONS FOR CAUTION: Although the total number of respondents was acceptable, the completion rate of the survey was suboptimal. In addition, the heterogeneity of answers to open-ended questions and the ambiguity of some of the answers, along with incomplete responses, posed a challenge in interpreting survey results. It is also plausible that some questions were not easily understood by the respondents. For this reason, response and non-response bias are acknowledged as further limitations of the survey. WIDER IMPLICATIONS OF THE FINDINGS: The results of this survey could aid in identifying potential challenges or areas for improvement in the current practice of ECS in the MAR field and contribute to the discussion on how to address them. The results underline the need to stimulate a more knowledge-based debate on the complexity and the pros and cons of a possible implementation of ECS in MAR. STUDY FUNDING/COMPETING INTEREST(S): All costs relating to the development process were covered from European Society of Human Reproduction and Embryology and European Society of Human Genetics funds. There was no external funding of the development process or manuscript production. A.C. is full-time employee of Juno Genetics. L.H. declared receiving a research grant during the past 36 months from the Netherlands Organisation for Health Research and Development. She has also participated in a Health Council report of the Netherlands on preconception carrier screening and collaborated with the VSOP Dutch Genetic Alliance (patient umbrella organization on rare and genetic disorders). L.H. and C.v.E. are affiliated with Amsterdam University Medical Centre, a hospital that offers ECS in a non-commercial setting. R.V. received honoraria for presentations from Merck Academy and is unpaid board member of the executive committee of the Spanish Fertility Society. The other authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

ESHRE guideline: number of embryos to transfer during IVF/ICSI†.

STUDY QUESTION: Which clinical and embryological factors should be considered to apply double embryo transfer (DET) instead of elective single embryo transfer (eSET)? SUMMARY ANSWER: No clinical or embryological factor per se justifies a recommendation of DET instead of eSET in IVF/ICSI. WHAT IS KNOWN ALREADY: DET is correlated with a higher rate of multiple pregnancy, leading to a subsequent increase in complications for both mother and babies. These complications include preterm birth, low birthweight, and other perinatal adverse outcomes. To mitigate the risks associated with multiple pregnancy, eSET is recommended by international and national professional organizations as the preferred approach in ART. STUDY DESIGN, SIZE, DURATION: The guideline was developed according to the structured methodology for development and update of ESHRE guidelines. Literature searches were performed in PUBMED/MEDLINE and Cochrane databases, and relevant papers published up to May 2023, written in English, were included. Live birth rate, cumulative live birth rate, and multiple pregnancy rate were considered as critical outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Based on the collected evidence, recommendations were discussed until a consensus was reached within the Guideline Development Group (GDG). A stakeholder review was organized after the guideline draft was finalized. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 35 recommendations on the medical and non-medical risks associated with multiple pregnancies and on the clinical and embryological factors to be considered when deciding on the number of embryos to transfer. These recommendations include 25 evidence-based recommendations, of which 24 were formulated as strong recommendations and one as conditional, and 10 good practice points. Of the evidence-based recommendations, seven (28%) were supported by moderate-quality evidence. The remaining recommendations were supported by low (three recommendations; 12%), or very low-quality evidence (15 recommendations; 60%). Owing to the lack of evidence-based research, the guideline also clearly mentions recommendations for future studies. LIMITATIONS, REASONS FOR CAUTION: The guideline assessed different factors one by one based on existing evidence. However, in real life, clinicians' decisions are based on several prognostic factors related to each patient's case. Furthermore, the evidence from randomized controlled trials is too scarce to formulate high-quality evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides health professionals with clear advice on best practice in the decision-making process during IVF/ICSI, based on the best evidence currently available, and recommendations on relevant information that should be communicated to patients. 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, the literature searches, and the dissemination of the guideline. The guideline group members did not receive payment. DPB declared receiving honoraria for lectures from Merck, Ferring, and Gedeon Richter. She is a member of ESHRE EXCO, and the Mediterranean Society for reproductive medicine and the president of the Croatian Society for Gynaecological Endocrinology and Reproductive Medicine. CDG is the past Chair of the ESHRE EIM Consortium and a paid deputy member of the Editorial board of Human Reproduction. IR declared receiving reimbursement from ESHRE and EDCD for attending meetings. She holds an unpaid leadership role in OBBCSSR, ECDC Sohonet, and AER. KAR-W declared receiving grants for clinical researchers and funding provision to the institution from the Swedish Cancer Society (200170F), the Senior Clinical Investigator Award, Radiumhemmets Forskningsfonder (Dnr: 201313), Stockholm County Council FoU (FoUI-953912) and Karolinska Institutet (Dnr 2020-01963), NovoNordisk, Merck and Ferring Pharmaceuticals. She received consulting fees from the Swedish Ministry of Health and Welfare. She received honoraria from Roche, Pfizer, and Organon for chairmanship and lectures. She received support from Organon for attending meetings. She participated in advisory boards for Merck, Nordic countries, and Ferring. She declared receiving time-lapse equipment and grants with payment to institution for pre-clinical research from Merck pharmaceuticals and from Ferring. SS-R received research funding from Roche Diagnostics, Organon/MSD, Theramex, and Gedeo-Richter. He received consulting fees from Organon/MSD, Ferring Pharmaceuticals, and Merck Serono. He declared receiving honoraria for lectures from Ferring Pharmaceuticals, Besins, Organon/MSD, Theramex, and Gedeon Richter. He received support for attending Gedeon Richter meetings and participated in the Data Safety Monitoring Board of the T-TRANSPORT trial. He is the Deputy of ESHRE SQART special interest group. He holds stock options in IVI Lisboa and received equipment and other services from Roche Diagnostics and Ferring Pharmaceuticals. KT declared receiving payment for honoraria for giving lectures from Merck Serono and Organon. She is member of the safety advisory board of EDQM. She holds a leadership role in the ICCBBA board of directors. ZV received reimbursement from ESHRE for attending meetings. She also received research grants from ESHRE and Juhani Aaltonen Foundation. She is the coordinator of EHSRE SQART special interest group. 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 judgement 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 https://www.eshre.eu/Guidelines-and-Legal).

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma.

The standard surgical treatment of endometrial carcinoma, consisting of total hysterectomy with bilateral salpingo-oophorectomy, drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) provide comprehensive information on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment.A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE), and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment (patient selection, tumor clinicopathological characteristics, treatment, special issues) in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts from across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified by a systematic search, was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives.

Simultaneous modal phase and group velocity matching in microstructured optical fibers for second harmonic generation with ultrashort pulses.

Optical fibers provide a favorable medium for nonlinear optical processes owing to the small mode field size and concurrently high optical intensity combined with the extended interaction lengths. Second harmonic generation (SHG) is one of those processes that has been demonstrated in silica glass optical fibers. Since silica is centrosymmetric, generating SHG in an optical fiber requires poling of the glass. In addition and when one wants to use ultrashort pulses for SHG, achieving both phase and group velocity matching is crucial. Although fibers that feature either modal phase velocity or group velocity matching for SHG have been reported, the possibility of simultaneous modal phase and group velocity matching was never reported before. In this paper we address this challenge, and for the first time to our knowledge, we show that it is feasible to do so with silica microstructured optical fibers featuring at least one ring of air holes in the cladding and a heavily Germanium doped core (above 25 mol.%) by exploiting the LP01(ω) and LP02(2ω) modes at 1.06 µm pump and 0.53 µm second harmonic wavelengths. This finding can greatly impact applications requiring waveguide based SHG generation with ultrashort pulses, including microscopy, material characterization and nonlinear imaging.

Endometriosis Classification Systems: An International Survey to Map Current Knowledge and Uptake.

OBJECTIVE: In the field of endometriosis, several classification, staging and reporting systems have been developed, but do clinicians routinely use these classification systems, which system do they use and what are the clinicians' motivations? DATA SOURCES: A cross-sectional study was performed to gather data on the current use of endometriosis classification systems, problems encountered and interest in a new simple surgical descriptive system for endometriosis. Of particular focus were three systems most commonly used: the Revised American Society for Reproductive Medicine (rASRM) classification, the Endometriosis Fertility Index (EFI), and the ENZIAN classification. Data were analysed by SPSS. A survey was designed using the online SurveyMonkey tool consisting of 11 questions concerning three domains-participants background, existing classification systems and intentions with regards to a new classification system for endometriosis. Replies were collected between 15 May and 1 July 2020. METHODS OF STUDY SELECTION: na TABULATION, INTEGRATION AND RESULTS: The final dataset included the replies of 1178 clinicians, including surgeons, gynecologists, reproductive endocrinologists, fertility specialists and sonographers, all managing women with endometriosis in their clinical practice. Overall, 75.5% of the professionals indicate that they currently use a classification system for endometriosis. The rASRM classification system was the best known and used system, the EFI system and ENZIAN system were known by a majority of the professionals but used by only a minority. The lack of clinical relevance was most often selected as a problem with using any system. The findings of the survey suggest that clinicians worldwide are open to using a new classification system for endometriosis that can achieve standardized reporting, and is clinically relevant and simple. The findings therefore support future initiatives for the development of a new descriptive system for endometriosis and provide information on user expectations and conditions for universal uptake of such a system. CONCLUSION: Even with a high uptake of the existing endometriosis classification systems (rASRM, ENZIAN and EFI), most clinicians managing endometriosis would like a new simple surgical descriptive system for endometriosis.

Outcomes of SARS-CoV-2 infected pregancies after medically assisted reproduction.

STUDY QUESTION: What is the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the outcome of a pregnancy after medically assisted reproduction (MAR)? SUMMARY ANSWER: Our results suggest that MAR pregnancies are not differentially affected by SARS-CoV-2 infection compared to spontaneous pregnancies. WHAT IS KNOWN ALREADY: Information on the effects of coronavirus disease 2019 (COVID-19) on pregnancy after MAR is scarce when women get infected during MAR or early pregnancy, even though such information is vital for informing women seeking pregnancy. STUDY DESIGN, SIZE, DURATION: Data from SARS-CoV-2 affected MAR pregnancies were collected between May 2020 and June 2021 through a voluntary data collection, organised by the European Society of Human Reproduction and Embryology (ESHRE). PARTICIPANTS/MATERIALS, SETTING, METHODS: All ESHRE members were invited to participate to an online data collection for SARS-CoV-2-infected MAR pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: The dataset includes 80 cases from 32 countries, including 67 live births, 10 miscarriages, 2 stillbirths and 1 maternal death. An additional 25pregnancies were ongoing at the time of writing. LIMITATIONS, REASONS FOR CAUTION: An international data registry based on voluntary contribution can be subject to selective reporting with possible risks of over- or under-estimation. WIDER IMPLICATIONS OF THE FINDINGS: The current data can be used to guide clinical decisions in the care of women pregnant after MAR, in the context of the COVID-19 pandemic. STUDY FUNDING/COMPETING INTEREST(S): The authors acknowledge the support of ESHRE for the data registry and meetings. J.S.T. reports grants or contracts from Sigrid Juselius Foundation, EU and Helsinki University Hospital Funds, outside the scope of the current work. The other authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The calm after the storm: re-starting ART treatments safely in the wake of the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic created a significant impact on medically assisted reproduction (MAR) services. ESHRE decided to mobilize resources in order to collect, analyse, monitor, prepare and disseminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) knowledge specifically related to ART and early pregnancy. This article presents the impact of the SARS-CoV-2 pandemic focusing on reproductive healthcare. It details the rationale behind the guidance prepared to support MAR services in organizing and managing the re-start of treatments or in case of any future wave of COVID-19 disease. The guidance includes information on patient selection and informed consent, staff and patient triage and testing, adaptation of ART services, treatment planning and code of conduct. The initiatives detailed in this article are not necessarily COVID-specific and such action plans could be applied effectively to manage similar emergency situations in different areas of medicine, in the future.

Inverse model for ultrashort pulse amplification in semiconductor optical amplifiers.

To describe ultrashort pulse amplification in semiconductor optical amplifiers (SOAs), several models have been developed that calculate the amplified output pulse as a function of the input. Because of the many processes at play in SOAs (band filling, carrier heating, spectral hole burning, two-photon absorption, and the associated free-carrier absorption), it is challenging to predict which input is needed to generate a targeted output. In this Letter, we construct a generic inverse SOA model that calculates the required input pulse including its shape and phase to obtain a desired output. This inverse model will enable a more efficient and well-targeted design of SOA-based photonic systems, while also allowing better quality and performance control.

An International Terminology for Endometriosis, 2021.

OBJECTIVE: Different classification systems have been developed for endometriosis, using different definitions for the disease, the different subtypes, symptoms and treatments. In addition, an International Glossary on Infertility and Fertility Care has been published in 2017 by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) in collaboration with other organisations. An international working group convened over the development of a classification or descriptive system for endometriosis. As a basis for such system, a terminology for endometriosis was considered a condition sine qua non. The aim of the current study was to develop a set of terms and definitions be prepared on endometriosis that would be the basis for standardization in disease description, classification and research. DATA SOURCES: The working group listed a number of terms relevant to be included in the terminology, documented currently used and published definitions, and discussed and adapted them until consensus was reached within the working group. Following stakeholder review, further terms were added, and definitions further clarified. Although definitions were collected through published literature, the final set of terms and definitions is to be considered consensus-based. After finalization of the first draft, the members of the international societies and other stakeholders were consulted for feedback and comments, which lead to further adaptations. METHODS OF STUDY SELECTION: na TABULATION, INTEGRATION, AND RESULTS: A list of 49 terms and definitions in the field of endometriosis is presented, including a definition for endometriosis and its subtypes, different locations, interventions, symptoms and outcomes. Endometriosis is defined as a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process. CONCLUSION: The current paper outlines a list of 49 terms and definitions in the field of endometriosis. The application of the defined terms aims to facilitate harmonization in endometriosis research and clinical practice. Future research may require further refinement of the presented definitions.

Endometriosis Classification, Staging and Reporting Systems: A Review on the Road to a Universally Accepted Endometriosis Classification.

OBJECTIVE: In the field of endometriosis, several classification, staging and reporting systems have been developed. Which endometriosis classification, staging and reporting systems have been published and validated for use in clinical practice? DATA SOURCES: A systematic PUBMED literature search was performed. Data were extracted and summarized. METHODS OF STUDY SELECTION: na TABULATION, INTEGRATION AND RESULTS: Twenty-two endometriosis classification, staging and reporting systems have been published between 1973 and 2021, each developed for specific, and different, purposes. There still is no international agreement on how to describe the disease. Studies evaluating the different systems are summarized showing a discrepancy between the intended and the evaluated purpose, and a general lack of validation data confirming a correlation with pain symptoms or quality of life for any of the current systems. A few studies confirm the value of the ENZIAN system for surgical description of deep endometriosis. With regards to infertility, the endometriosis fertility index has been confirmed valid for its intended purpose. CONCLUSION: Of the 22 endometriosis classification, staging and reporting systems identified in this historical overview, only a few have been evaluated for the purpose for which they were developed. The literature search was limited to PUBMED. Unpublished classification, staging or reporting systems, or those published in books were not considered. It can be concluded that there is no international agreement on how to describe endometriosis or how to classify it, and that most classification/staging systems show no or very little correlation with patient outcomes. This overview of existing systems is a first step in working towards a universally accepted endometriosis classification.

3D direct laser writing of microstructured optical fiber tapers on single-mode fibers for mode-field conversion.

We present a design and fabrication approach for 3D printed polymer microstructured optical fiber tapers on standard single-mode glass fibers for efficient and compact mode-field conversion. This paves the way towards complex functionalized fiber tips for various applications, like sensors and beam shaping components, currently limited by the mode-field size and distribution of standard optical fibers. In this paper, we demonstrate the potential of mode-field converting tapers for relaxing the misalignment tolerance in fiber-to-fiber connections and maximizing the coupling efficiency in fiber-to-chip connections. We demonstrate a mode-field diameter expansion ratio of 1.7 and reduction ratio of 3 and show that our microstructured tapers achieve a comparable performance in coupling efficiency as their step-index counterparts, while providing greater robustness.

Evaluating risk, safety and efficacy of novel reproductive techniques and therapies through the EuroGTP II risk assessment tool.

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.

Measurement of the soliton number in guiding media through continuum generation.

No general approach is available yet to measure directly the ratio between chromatic dispersion and the nonlinear coefficient, and hence the soliton number for a given optical pulse, in an arbitrary guiding medium. Here we solve this problem using continuum generation. We experimentally demonstrate our method in polarization-maintaining and single-mode fibers with positive and negative chromatic dispersion. Our technique also offers new opportunities to determine the chromatic dispersion of guiding media over a broad spectral range while pumping at a fixed wavelength.

Comparison and appraisal of (inter)national recurrent pregnancy loss guidelines.

Investigations and treatment options of recurrent pregnancy loss (RPL) differ internationally. This manuscript reviews the similarities and differences between international guidelines. The European Society of Human Reproduction and Embryology (ESHRE) guideline (2017), the American Society for Reproductive Medicine (ASRM) Committee Opinion (2013) and the Royal College of Obstetricians and Gynaecologists (RCOG) guideline (2011) were appraised using the AGREE II criteria. The guidelines were checked for definitions, risk factors, investigations and therapeutic options. The guidelines agreed on acquired thrombophilia analysis. All guidelines agreed on a regimen for the treatment of antiphospholipid antibody syndrome consisting of aspirin and heparin, but only the ESHRE guideline specified the order of starting these medications. Treatment of thrombophilia and uterine anomalies was advised against; all guidelines recommended supportive care for unexplained RPL. The guidelines did not agree on the definition of RPL and differed in investigations regarding lifestyle, karyotype analysis of parents and/or pregnancy tissue, and the diagnostic tool for uterine anomalies. All three guidelines indicate an association between lifestyle and RPL; the ESHRE recommends health behaviour changes. Couples suffering from RPL should be informed about possible investigations and treatment options, and whether those are evidence-based. It is important for clinicians to realize that the guidelines differ internationally.

Opportunities for visible supercontinuum light generation in integrated diamond waveguides.

We numerically show the advantages of using diamond-on-insulator (DOI) waveguides to design compact supercontinuum (SC) light sources for the visible (VIS) wavelength range. We conclude that the DOI platform is more suitable than silicon nitride waveguides for tailoring the dispersion in such a way that a zero-dispersion wavelength (ZDW) is obtained in the VIS, as is required to achieve efficient VIS SC generation (SCG). After designing a DOI waveguide that features a ZDW at ∼600 nm, we exploit it to numerically obtain a smooth SC ranging from 453 nm to 1030 nm above the -30 dB point after propagation over 4 mm. Our result extends beyond the state-of-the-art shortest VIS wavelengths induced by SCG in integrated waveguides, while using ∼26 times lower input energy and a shorter waveguide length, thus showcasing the potential of the DOI platform for on-chip VIS SC light sources.

Towards an analytical framework for tailoring supercontinuum generation.

A fully analytical toolbox for supercontinuum generation relying on scenarios without pulse splitting is presented. Furthermore, starting from the new insights provided by this formalism about the physical nature of direct and cascaded dispersive wave emission, a unified description of this radiation in both normal and anomalous dispersion regimes is derived. Previously unidentified physics of broadband spectra reported in earlier works is successfully explained on this basis. Finally, a foundry-compatible few-millimeters-long silicon waveguide allowing octave-spanning supercontinuum generation pumped at telecom wavelengths in the normal dispersion regime is designed, hence showcasing the potential of this new analytical approach.

Revised guidelines for good practice in IVF laboratories (2015).

STUDY QUESTION: Which recommendations can be provided by the European Society of Human Reproduction and Embryology Special Interest Group (ESHRE SIG) Embryology to support laboratory specialists in the organization and management of IVF laboratories and the optimization of IVF patient care? SUMMARY ANSWER: Structured in 13 sections, the guideline development group formulated recommendations for good practice in the organization and management of IVF laboratories, and for good practice of the specific procedures performed within the IVF laboratory. WHAT IS KNOWN ALREADY: NA. STUDY DESIGN, SIZE, DURATION: The guideline was produced by a group of 10 embryologists representing different European countries, settings and levels of expertise. The group evaluated the document of 2008, and based on this assessment, each group member rewrote one or more sections. Two 2-day meetings were organized during which each of the recommendations was discussed and rewritten until consensus within the guideline group was reached. After finalizing the draft, the members of the ESHRE SIG embryology were invited to review the guideline. PARTICIPANTS/MATERIALS, SETTING, METHODS: NA. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides recommendations on the general organization of an IVF laboratory (staffing and direction, quality management, laboratory safety), and on the specific aspects of the procedures performed in IVF laboratories (Identification of patients and traceability of their reproductive cells, consumables, handling of biological material, oocyte retrieval, sperm preparation, insemination of oocytes, scoring for fertilization, embryo culture and transfer, and cryopreservation). A last section provides recommendations regarding an Emergency plan for IVF laboratories. LIMITATIONS, REASONS FOR CAUTION: Evidence on most of the issues described is scarce, and therefore it was decided not to perform a formal search for and assessment of scientific evidence. However, recommendations published in the EUTCD and relevant and recent documents, manuals and consensus papers were taken into account when formulating the recommendations. WIDER IMPLICATIONS OF THE FINDINGS: Despite the limitations, the guideline group is confident that this document will be helpful to directors and managers involved in the management and organization of IVF laboratories, but also to embryologists and laboratory technicians performing daily tasks. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings. The guideline group members did not receive payment. Dr Coticchio reports speaker's fees from IBSA and Cook, outside the submitted work; Dr Lundin reports grants from Vitrolife, personal fees from Merck Serono, non-financial support from Unisense, outside the submitted work; Dr. Rienzi reports personal fees from Merck Serono, personal fees from MSD, grants from GFI, outside the submitted work; the other authors had nothing to disclose. TRIAL REGISTRATION NUMBER: NA.

Laser ablation- and plasma etching-based patterning of graphene on silicon-on-insulator waveguides.

We present a new approach to remove monolayer graphene transferred on top of a silicon-on-insulator (SOI) photonic integrated chip. Femtosecond laser ablation is used for the first time to remove graphene from SOI waveguides, whereas oxygen plasma etching through a metal mask is employed to peel off graphene from the grating couplers attached to the waveguides. We show by means of Raman spectroscopy and atomic force microscopy that the removal of graphene is successful with minimal damage to the underlying SOI waveguides. Finally, we employ both removal techniques to measure the contribution of graphene to the loss of grating-coupled graphene-covered SOI waveguides using the cut-back method.

Adjoint-enabled optimization of optical devices based on coupled-mode equations.

In this work, we propose a method for designing optical devices described by coupled-mode equations. Following a commonly applied optimization strategy, we combine gradient-based optimization algorithms with an adjoint sensitivity analysis of the coupled-mode equations to obtain an optimization scheme that can handle a large number of design parameters. To demonstrate this adjoint-enabled optimization method, we design a silicon-on-insulator Raman wavelength converter. As structure, we consider a waveguide constructed from a series of interconnected and adiabatically-varying linear tapers, and treat the width at each interconnection point, the waveguide length, and the pump-Stokes frequency difference as independent design parameters. Optimizing with respect to these 1603 parameters results in an improvement of more than 10 dB in the conversion efficiency for a waveguide length of 6.28 cm and frequency difference 187 GHz below the Raman shift as compared to a converter designed by the conventional phase-matching design rule and operating at perfect Raman resonance. The increase in conversion efficiency is also accompanied by a more than 7 dB-improvement in the Stokes amplification. Hence, the adjoint-enabled optimization allows us to identify a more efficient method for achieving Raman conversion than conventional phase-matching. We also show that adjoint-enabled optimization significantly improves design robustness. In case of the Raman converter example, this leads to a sensitivity with respect to local variations in waveguide width that is several orders of magnitude smaller for the optimized design than for the phase-matched one.

Design of large scale plasmonic nanoslit arrays for arbitrary mode conversion and demultiplexing.

We present an iterative design method for the coupling and the mode conversion of arbitrary modes to focused surface plasmons using a large array of aperiodically randomly located slits in a thin metal film. As the distance between the slits is small and the number of slits is large, significant mutual coupling occurs between the slits which makes an accurate computation of the field scattered by the slits difficult. We use an accurate modal source radiator model to efficiently compute the fields in a significantly shorter time compared with three-dimensional (3D) full-field rigorous simulations, so that iterative optimization is efficiently achieved. Since our model accounts for mutual coupling between the slits, the scattering by the slits of both the source wave and the focused surface plasmon can be incorporated in the optimization scheme. We apply this method to the design of various types of couplers for arbitrary fiber modes and a mode demultiplexer that focuses three orthogonal fiber modes to three different foci. Finally, we validate our design results using fully vectorial 3D finite-difference time-domain (FDTD) simulations.