Visual morphology assessment is routinely used for evaluating of embryo quality and selecting human blastocysts for transfer after in vitro fertilization (IVF). However, the assessment produces different results between embryologists and as a result, the success rate of IVF remains low. To overcome uncertainties in embryo quality, multiple embryos are often implanted resulting in undesired multiple pregnancies and complications. Unlike in other imaging fields, human embryology and IVF have not yet leveraged artificial intelligence (AI) for unbiased, automated embryo assessment. We postulated that an AI approach trained on thousands of embryos can reliably predict embryo quality without human intervention. We implemented an AI approach based on deep neural networks (DNNs) to select highest quality embryos using a large collection of human embryo time-lapse images (about 50,000 images) from a high-volume fertility center in the United States. We developed a framework (STORK) based on Google’s Inception model. STORK predicts blastocyst quality with an AUC of >0.98 and generalizes well to images from other clinics outside the US and outperforms individual embryologists. Using clinical data for 2182 embryos, we created a decision tree to integrate embryo quality and patient age to identify scenarios associated with pregnancy likelihood. Our analysis shows that the chance of pregnancy based on individual embryos varies from 13.8% (age ≥41 and poor-quality) to 66.3% (age <37 and good-quality) depending on automated blastocyst quality assessment and patient age. In conclusion, our AI-driven approach provides a reproducible way to assess embryo quality and uncovers new, potentially personalized strategies to select embryos.

Chemokines are a family of small polypeptides which specialize in the attraction of leukocytes. The presence of specific leukocyte subsets at the implantation site is an important element of the complex, and not completely understood, process of embryonic implantation. This report includes the investigation of the in-vivo immunolocalization and hormonal regulation of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and RANTES (regulated upon activation normal T-cell expressed and secreted) in the human endometrium during hormone replacement therapy cycles for oocyte recipients in an IVF programme. In addition, we have analysed the embryonic regulation of these endometrial epithelial chemokines (IL-8 and MCP-1) using an in-vitro model for the apposition phase of human implantation by co-culturing single human embryos until the blastocyst stage with human endometrial epithelial cells (EEC). IL-8 and MCP-1 were immunolocalized in the human endometrium to the glandular and lumenal epithelium as well as to the endothelial cells. RANTES was mainly localized to the stromal compartment and endothelial cells. The immunoreactive levels of endometrial IL-8 and MCP-1 were up-regulated by the administration of progesterone during the receptive phase of the cycle. Furthermore, it was demonstrated that, in vitro, the human blastocyst does not produce measurable amounts of IL-8, MCP-1 or RANTES; however, it does up-regulate EEC IL-8 mRNA expression (P < 0.05) and protein production (P < 0.05), but not IL-8 secretion. The human embryo did not regulate EEC MCP-1 expression. These results provide evidence of hormonal and embryonic regulation of specific endometrial chemokines, suggesting two different but related mechanisms to induce the production of chemokines by the EEC, thus contributing to the attraction of specific leukocyte populations during the peri-implantation phase.

STUDY QUESTION What recommendations can be provided on the approach to and use of time-lapse technology (TLT) in an IVF laboratory? SUMMARY ANSWER The present ESHRE document provides 11 recommendations on how to introduce TLT in the IVF laboratory. WHAT IS KNOWN ALREADY Studies have been published on the use of TLT in clinical embryology. However, a systematic assessment of how to approach and introduce this technology is currently missing. STUDY DESIGN, SIZE, DURATION A working group of members of the Steering Committee of the ESHRE Special Interest Group in Embryology and selected ESHRE members was formed in order to write recommendations on the practical aspects of TLT for the IVF laboratory. PARTICIPANTS/MATERIALS, SETTING, METHODS The working group included 11 members of different nationalities with internationally recognized experience in clinical embryology and basic science embryology, in addition to TLT. This document is developed according to the manual for development of ESHRE recommendations for good practice. Where possible, the statements are supported by studies retrieved from a PUBMED literature search on ‘time-lapse’ and ART. MAIN RESULTS AND THE ROLE OF CHANCE A clear clinical benefit of the use of TLT, i.e. an increase in IVF success rates, remains to be proven. Meanwhile, TLT systems are being introduced in IVF laboratories. The working group listed 11 recommendations on what to do before introducing TLT in the lab. These statements include an assessment of the pros and cons of acquiring a TLT system, selection of relevant morphokinetic parameters, selection of an appropriate TLT system with technical and customer support, development of an internal checklist and education of staff. All these aspects are explained further here, based on the current literature and expert opinion. LIMITATIONS, REASONS FOR CAUTION Owing to the limited evidence available, recommendations are mostly based on clinical and technical expertise. The paper provides technical advice, but leaves any decision on whether or not to use TLT to the individual centres. WIDER IMPLICATIONS OF THE FINDINGS This document is expected to have a significant impact on future developments of clinical embryology, considering the increasing role and impact of TLT. STUDY FUNDING/COMPETING INTEREST(S) The meetings of the working group were funded by ESHRE. S.A. declares participation in the Nordic Embryology Academic Team with meetings sponsored by Gedeon Richter. T.E. declares to have organized workshops for Esco and receiving consulting fees from Ferring and Gynemed and speakers’ fees from Esco and honorarium from Merck and MSD. T.F. received consulting fees from Vitrolife and Laboratoires Genévrier, speakers’ fees from Merck Serono, Gedeon Richter, MSD and Ferring and research grants from Gedeon Richter and MSD. M.M. received sponsorship from Merck. M.M.E. received speakers’ fees from Merck, Ferring and MSD. R.S. received a research grant from ESHRE. G.C. received speakers’ fees from IBSA and Excemed. The other authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER N/A. DISCLAIMER This Good Practice Recommendations (GPR) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and are based on the scientific evidence available at the time of preparation. ESHRE’s GPRs should be used for information 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, ESHRE GPRs do not constitute or imply the endorsement, or favouring of any of the included technologies by ESHRE. †ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.

The in-vitro effects of several concentrations of Ureaplasma urealyticum on the motility, membrane integrity and morphology of washed spermatozoa from healthy donors were studied. A significant reduction in sperm motility and signs of membrane alteration, directly related to U.urealyticum concentration and contact time were observed. Scanning electron microscopy examination showed masses of U. urealyticum attached to the head and middle piece of some of deformed spermatozoa. It is suggested that U.urealyticum is involved in sperm changes leading to male infertility, particularly when there is heavy U. urealyticum colonization or specific infections with this microorganism.

The screening procedure applied to all the candidates sufficiently minimizes any risk to the gamete receiver and the offspring.

Mucins, best known as the major constituent of mucus, are a family of highly glycosylated, high molecular weight (> or = 200 kDa) glycoproteins present on the surface of human epithelial cells. MUC1 has the features of an integral membrane protein. It has an extracellular tandem repeat domain that forms the major part of the core protein, and results in a highly repetitive structure, which is extremely immunogenic. In the protein there is also a proteolytic cleavage site reported in the proximal extracellular domain. The secreted form of MUC1 lacks the cytoplasmic tail, but it is not clear whether this results from alternative splicing or proteolysis and release of the free extracellular domain. The locus of the MUC1 gene is on band 21 of the long arm of chromosome 1 (1q21). Anti-adhesion properties of this mucin are probably the result of the unique structure of the molecule. In mouse uterine epithelium, the homologue MUC1 is regulated with reduced expression in the implantation period, but in humans, expression is high during the peri-implantation period. MUC1 may inhibit the interaction between trophoblast and apical epithelium adhesion molecules at the time of implantation, giving the possibility of forming a uterine barrier for implantation.

As it approaches the maternal surface, the attaching embryo encounters the epithelial glycocalyx, which contains the mucin, MUC1. A high density of MUC1 at the cell surface can inhibit cell adhesion. This raises the possibility of the existence of a uterine barrier to implantation that might allow maternal rejection of poorer quality embryos. To investigate the mechanism of implantation, human embryos were incubated with endometrial epithelial monolayers. Hatched blastocysts were found to attach readily to the epithelial surface. MUC1 was lost from epithelial cells beneath and near to the attached embryo, while normal expression persisted in neighbouring cells.

Fertility societies worldwide responded to the COVID-19 pandemic by recommending that fertility clinics close, or sharply reduce, the clinical operation, leading to a shift in the management of IVF laboratories in three phases: shutdown preparation; maintenance during shutdown; and restart. Each of these phases carries distinct risks that need identification and mitigation, forcing laboratory managers to rethink and adapt their procedures in response to the pandemic. The sudden and unprecedented nature of the pandemic forced laboratory managers from around the world to base decisions on opinion and experience when evidence-based response options were unavailable. These perspectives on pandemic response were presented during a virtual international symposium on COVID-19, held on 3 April 2020, and organized by the London Laboratory Managers' Group. Laboratory managers from seven different countries at different stages of the pandemic (China, Italy, Spain, France, UK, Brazil and Australia) presented their personal experiences to a select audience of experienced laboratory managers from 19 different countries. The intention of this paper is to collect the learnings and considerations from this group of laboratory managers who collaborated to share personal experiences to contribute to the debate surrounding what constitutes good IVF laboratory practice in extraordinary circumstances, such as the COVID-19 pandemic.