Sustainability in the IVF laboratory: recommendations of an expert panel.

The healthcare industry is a major contributor to greenhouse gas emissions. Assisted reproductive technology is part of the larger healthcare sector, with its own heavy carbon footprint. The social, economic and environmental costs of this collective carbon footprint are becoming clearer, as is the impact on human reproductive health. Alpha Scientists in Reproductive Medicine and the International IVF Initiative collaborated to seek and formulate practical recommendations for sustainability in IVF laboratories. An international panel of experts, enthusiasts and professionals in reproductive medicine, environmental science, architecture, biorepository and law convened to discuss the topics of importance to sustainability. Recommendations were issued on how to build a culture of sustainability in the workplace, implement green design and building, use life cycle analysis to determine the environmental impact, manage cryostorage more sustainably, and understand and manage laboratory waste with prevention as a primary goal. The panel explored whether the industry supporting IVF is sustainable. An example is provided to illustrate the application of green principles to an IVF laboratory through a certification programme. The UK legislative landscape surrounding sustainability is also discussed and a few recommendations on 'Green Conferencing' are offered.

Controlled ovarian hyperstimulation (COH) parameters associated with euploidy rates in donor oocytes.

Although oocyte donors are young and are expected to provide a high rate of euploid oocytes, significant differences of euploidy rates for donor embryos exist between different IVF centers (1). Laboratory conditions can lead to differences of euploidy (2,3,4,5,6,7); but, the role of COH has not been investigated. In this study, we investigated whether euploidy rates in the embryos created from donor oocytes are influenced by controlled ovarian hyperstimulation parameters used during assisted reproduction. Euploidy rates in egg donor cycles undergoing PGT-A (N = 423) were examined retrospectively for associations with donor age, gonadotropin doses (dose per day), the fraction of gonadotropin provided by hMG (F(hMG)), days of stimulation, estradiol per mature oocyte on day of trigger, number of mature oocytes retrieved, number of embryos biopsied, incidence of euploidy and physician of record. Differences in euploidy rates between physicians were examined using analysis of variance. The proportion of euploid embryos per donor cycle was examined for associations with COH parameters using pairwise post-hoc comparisons, adjusting for multiple testing. The set of variables from this analysis was then submitted to a principal component analysis. Linear regression analysis was used to assess the relationships between stimulation parameters and the incidence of euploidy (the dependent variable). Euploidy rates and cycle parameters varied significantly among treating physicians. Euploidy rates (expressed as a fraction of biopsied embryos) were associated (p = 0.01) only with the F(hMG) but not with the number of MII retrieved or other variables. On the other hand, the number of euploid embryos (in contrast to the euploidy rate) was associated with the number of MII produced. Donor euploidy rates are significantly associated with the fraction of total gonadotropin comprising human menopausal gonadotropin (or F(hMG)) during controlled ovarian hyperstimulation but are not associated with other cycle parameters. The study provides the first suggestion that patient stimulation parameters can affect the incidence of euploidy in embryos generated through the use of standard assisted reproductive techniques. The study is limited by its retrospective approach and because the aCGH analysis used is less sensitive than more recent NGS technology. Further, it provides a suggestion that the use of hMG is beneficial for obtaining euploid embryos.

Human Reproductive Cell Cryopreservation, Storage, Handling, and Transport: Risks and Risk Management.

Millions of human oocytes and embryos are stored in thousands of locations across the globe. This inventory continues to grow as cryopreservation becomes more successful and more widely applied. The results of studies assessing pregnancy and neonatal outcomes following frozen embryo transfer (FET) have been encouraging, showing lower incidences of small for gestational age neonates and preterm birth compared with fresh transfers. However, many of these studies have also shown that the odds of large for gestational age births and macrosomia are higher after FET. The origin of these conditions remains unclear. Cryostorage presents many potential risks to the cryopreserved cells/tissues, including loss of viability and contamination, but risks are faced also by care providers-for example, injury and financial liability-and by patients-for example, accidental loss of their reproductive tissues, the burden of embryos they no longer wish to use and failing to meet their contractual obligations. Studies are urgently needed to explore and understand all dimensions of cryostorage to help ART clinics develop effective strategies to manage associated risks. The future of cryostorage, as for many other areas of ART and medicine, is automation.

Laser-assisted zona pellucida thinning does not facilitate hatching and may disrupt the in vitro hatching process: a morphokinetic study in the mouse.

STUDY QUESTION: Does laser-assisted zona thinning of cleavage stage mouse embryos facilitate hatching in vitro? SUMMARY ANSWER: No, unlike laser zona opening, zona thinning does not facilitate embryo hatching. WHAT IS KNOWN ALREADY: Artificial opening of the zona pellucida facilitates hatching of mouse and human embryos. Laser-assisted zona thinning has also been used for the purpose of assisted hatching of human embryos but it has not been properly investigated in an animal model; thinning methods have produced inconsistent clinical results. STUDY DESIGN, SIZE, DURATION: Time-lapse microscopy was used to study the hatching process in the mouse after zona opening and zona thinning; a control group of embryos was not zona-manipulated but exposed to the same laser energy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eight-cell CB6F1/J mouse embryos were pooled and allocated to three groups (n = 56 per group): A control group of embryos that were exposed to a dose of laser energy focused outside the zona pellucida (zona intact); one experimental group of embryos in which the zona pellucida was opened by complete ablation using the same total number of pulses as the control group; a second experimental group of embryos in which the zona pellucida was thinned to establish a smooth lased area using the same number of pulses as used in the other two groups. The width of the zona opening was 25 µm and width of the thinned area was 35 µm. Development was monitored by time-lapse microscopy. Overall treatment differences for continuous variables were analyzed by analysis of variance and pairwise comparisons using the Student t-test allowing for unequal variances, while for categorical data, a standard chi-squared test was utilized for all pairwise comparisons. MAIN RESULTS AND THE ROLE OF CHANCE: The frequency of complete hatching was 33.9% in the control group, 94.4% after zona opening, and 39.3% after zona thinning (overall group comparison, P < 0.0001). Overall, 60.7% of the zona-thinned embryos did not complete the hatching process and remained trapped within the zona; when they did hatch, they did not necessarily hatch from the zona-thinned area. Hatching in about one-third of the zona-intact embryos began with breaches at multiple sites by small groups of cells. Likewise, 53.6% of zona-thinned embryos had multiple breaches, always involving an area outside the thinned zone. Zona opening decreased multiple breaching and led to blastocyst escape an average of 14 h earlier than zona-thinned embryos and 5.5 h before control embryos (P = 0.0003). LIMITATIONS, REASONS FOR CAUTION: The experiments presented here were limited to in vitro experiments performed in the mouse. Whether human embryos would behave the same way under similar circumstances is unknown. We postulate that zona thinning is not beneficial in human embryos. WIDER IMPLICATIONS OF THE FINDINGS: The experiments demonstrate that zona thinning is not equivalent to zona opening for assisted hatching. The study provides reason for systematic reviews of assisted hatching trials to take the method of assisted hatching into consideration and not combine the results of zona thinning and zona opening procedures. STUDY FUNDING/COMPETING INTERESTS: Institutional funds were used for the study. No competing interests are declared.

Comprehensive evaluation of contemporary assisted reproduction technology laboratory operations to determine staffing levels that promote patient safety and quality care.

OBJECTIVE: To consider how staffing requirements have changed with evolving and increasingly more complex assisted reproduction technology (ART) laboratory practice. DESIGN: Analysis by four laboratory directors from three different ART programs of the level of complexity and time requirements for contemporary ART laboratory activities to determine adequate staffing levels. SETTING: University-based and private ART programs. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Human resource requirements for ART procedures. RESULT(S): Both complexity and time required for completion of a contemporary ART cycle have increased significantly compared with the same requirements for the "traditional cycle" of the past. The latter required roughly 9 personnel hours, but a contemporary cycle can require up to 20 hours for completion. Consistent with this increase, a quantitative analysis shows that the number of embryologists required for safe and efficient operation of the ART laboratory has also increased. This number depends on not only the volume but also the types of procedures performed: the higher the number of complex procedures, the more personnel required. An interactive Personnel Calculator is introduced that can help determine staffing needs. CONCLUSION(S): The increased complexity of the contemporary ART laboratory requires a new look at the allocation of human resources. Our work provides laboratory directors with a practical, individualized tool to determine their staffing requirements with a view to increasing the safety and efficiency of operations. The work could serve as the basis for revision of the 2008 American Society for Reproductive Medicine (ASRM) staffing guidelines.