Comparison of embryologist stress, somatization, and burnout reported by embryologists working in UK HFEA-licensed ART/IVF clinics and USA ART/IVF clinics.

STUDY QUESTION: What is the prevalence of occupational stress, somatization, and burnout reported by UK and US, embryologists and the impact of work conditions on these well-being outcomes? SUMMARY ANSWER: Surveyed UK and US embryologists reported moderate perceived stress, low somatic symptom severity, high levels of burnout, and overall stressful work conditions, but with differences that could be due to country-specific occupational and employment characteristics. WHAT IS KNOWN ALREADY?: Spanish, UK, US, and international surveys have identified high levels of occupational stress, somatization, burnout, and occupational health issues among embryologists. These issues have been attributed to embryologists' occupational challenges and work conditions. STUDY DESIGN, SIZE, DURATION: A cross-sectional web-based survey was sent to 253 embryologists working in UK ART/IVF clinics and 487 embryologists working in US ART/IVF clinics. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants self-reported their stress levels, somatization, burnout, and work conditions. Proportions across the Perceived Stress Scale (PSS), Patient Health Questionnaire (PHQ-15), Maslach Burnout Inventory-General Survey (MBI-GS), a single-item work unit grade (A-F), and customized occupational and sociodemographic questionnaires were calculated using descriptive statistics. Welch's t-test was utilized to compare PSS and PHQ-15 scores between groups. Risk ratios were calculated using log-binomial regression for all models except for levels of anxiety related to performing cryostorage tasks, for which Poisson models were used. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 50.6% (128) of the embryologists in the UK and 50.1% (244) in the US completed the survey. Both groups self-reported moderate PSS and low PHQ-15 scores, although fewer UK embryologists scored high on the MBI cynicism dimension than their US colleagues (43% UK vs 60% US embryologists, P < 0.05). The UK and US embryologists did not differ on the MBI exhaustion dimension with both scoring high for exhaustion (59% UK vs 62% US). Although 81% and 80% of UK and US embryologists, respectively, reported working overtime, more embryologists in the UK reported being adequately compensated. Increasing levels of anxiety-related to cryostorage showed a dose-dependent increased risk of burnout on at least two MBI-GS dimensions only in the UK group, and, a dose-dependent likelihood of higher PSS and PHQ-15 scores in both groups. LIMITATIONS, REASONS FOR CAUTION: Since the two groups were surveyed 9 months apart and were self-reporting, the study is limited by the differences in responsibilities, scheduling, and workload specific to the time of year. WIDER IMPLICATIONS OF THE FINDINGS: Work-related health issues and occupational challenges shared by UK and US embryologists could be addressed by organizational enhancements and technology. Lower levels of stress and burnout among UK embryologists might be due to the HFEA-provided structure/certainty. STUDY FUNDING/COMPETING INTEREST(S): This study was supported without any external funding by TMRW Life Sciences Inc., which is developing and commercializing an automated platform for embryology. M.G.C. and M.S.L. are full-time employees and stockholders/shareholders with TMRW Life Sciences, and A.M. of Novavax, Inc. was an employee of TMRW Life Sciences. G.P. is a consultant for TMRW Life Sciences. The remaining authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: NCT05326802; NCT05708963.

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.

The Internet of Things in assisted reproduction.

The Internet of Things (IoT) is a network connecting physical objects with sensors, software and internet connectivity for data exchange. Integrating the IoT with medical devices shows promise in healthcare, particularly in IVF laboratories. By leveraging telecommunications, cybersecurity, data management and intelligent systems, the IoT can enable a data-driven laboratory with automation, improved conditions, personalized treatment and efficient workflows. The integration of 5G technology ensures fast and reliable connectivity for real-time data transmission, while blockchain technology secures patient data. Fog computing reduces latency and enables real-time analytics. Microelectromechanical systems enable wearable IoT and miniaturized monitoring devices for tracking IVF processes. However, challenges such as security risks and network issues must be addressed through cybersecurity measures and networking advancements. Clinical embryologists should maintain their expertise and knowledge for safety and oversight, even with IoT in the IVF laboratory.

Cryostorage management of reproductive cells and tissues in ART: status, needs, opportunities and potential new challenges.

Among the wide range of procedures performed by clinical embryologists, the cryopreservation of reproductive cells and tissues represents a fundamental task in the daily routine. Indeed, cryopreservation procedures can be considered a subspecialty of medically assisted reproductive technology (ART), having the same relevance as sperm injection or embryo biopsy for preimplantation genetic testing. However, although a great deal of care has been devoted to optimizing cryopreservation protocols, the same energy has only recently been spent on developing and implementing strategies for the safe and reliable storage and transport of reproductive specimens. Herein, we have summarized the content of the available guidelines, the risks, the needs and the future perspectives regarding the management of cryopreservation biorepositories used in ART.

The in vitro fertilization laboratory: teamwork and teaming.

Delivery of fertility treatment involves both teamwork within a discipline as well as teaming across multiple work areas, such as nursing, administrative, laboratory, and clinical. In contrast to small autonomous centers, the in vitro fertilization (IVF) laboratory team in large clinics must function both as a team with many members and a constellation of teams to deliver seamless, safe, and effective patient-centered care. Although this review primarily focuses on teamwork within the IVF laboratory, which comprises clinical laboratory scientists and embryologists who perform both diagnostic and therapeutic procedures, it also discusses the laboratory's wider role with other teams of the IVF clinic, and the role of teaming (the ad hoc creation of multidisciplinary teams) to function highly and address critical issues.

Vitrifying multiple embryos in different arrangements does not alter the cooling rate.

Vitrification is the most common method of cryopreservation of gametes in fertility clinics due to its improved survival rates compared to slow freezing techniques. For the Open Cryotop® vitrification device, the number of oocytes, or embryos, mounted onto a single device can vary. In this work, a mathematical model is developed for the cooling of oocytes and embryos (samples). The model is solved computationally, to investigate whether varying the number of samples mounted onto the Open Cryotop® affects the cooling rates, and consequently the survival rates, of vitrified samples. Several realistic spatial arrangements of samples are examined, determining their temperature over time. In this way we quantify the effect of spatial arrangement on the cooling rate. Our results indicate that neither the spatial arrangement nor the number of mounted samples has a large effect on cooling rates, so long as the volume of the cryoprotectant remains minimal. The time taken for cooling is found to be on the order of half a second, or less, regardless of the spatial arrangement or number of mounted samples. Hence, rapid cooling can be achieved for any number or arrangement of samples, as long as device manufacturer guidelines are adhered to.

Comparison of 36 assisted reproduction laboratories monitoring environmental conditions and instrument parameters using the same quality-control application.

RESEARCH QUESTION: Assisted reproduction laboratories record instrument performance periodically. No standardized guidelines have been produced for this activity despite mandatory auditing systems in several countries. This study of 36 laboratories in 12 different countries was conducted to assess differences and similarities between quality assurance programmes using an adaptable cloud-based quality-control app for instrument monitoring. DESIGN: A total of 36 deidentified IVF laboratories that subscribed to the same quality-assurance application were studied. Data were evaluated based on instrument types allocated to 10 domains: incubators, gas tanks, warming surfaces, refrigerators and freezers, cryo-storage, environment, water purification, peripheral equipment, checklists and miscellaneous. RESULTS: The incubator domain constituted the greatest proportion of parameters (35%), followed by surface warming instruments at 15%. Most incubator O2 readings were monitored between 4.5 and 5.5%, and between 5.5 and 6.5% for CO2. The altitude of the laboratory was poorly correlated with the CO2 setting. Incubator display and measured values of gases and temperature by built-in sensors vary considerably compared with third-party sensors. A quality-control diligence score or mean average data points was calculated for each laboratory. This score is independent of number of instruments or laboratory size. Higher scores were associated with laboratories in countries with government regulations and mandatory auditing systems. CONCLUSIONS: Major differences exist in instrument monitoring practices among laboratories. Although incubator monitoring is the largest domain, many other sensitive instruments are diligently monitored by most laboratories. International standardization and guidelines are needed.

Morphokinetic parameters of early embryo development via time lapse monitoring and their effect on embryo selection and ICSI outcomes: a prospective cohort study.

PURPOSE: To compare the outcomes of embryos selected via time lapse monitoring (TLM) versus those selected with conventional methods of selection in subfertile women undergoing ICSI. METHODS: The study population (239 women) was classified into two groups, based on the monitoring method used: Group 1 (TLM) and Group 2 (conventional monitoring). Groups were compared according to the clinical and ICSI cycle characteristics and reproductive outcomes, while transfers were performed at day 2 or 3. Subgroup analyses were performed, in women of both groups according to age and clinical parameters, and in embryos of Group 1 based on their cellular events. RESULTS: There was a statistically significant difference between the two study groups with regard to the outcome parameters, favoring Group 1 and especially in women >40 years of age. No differences were found in subgroup analyses in participants of both groups, regarding the stimulation protocol used, number of the oocytes retrieved and type of subfertility, while in Group 1 the percentages of "in range" cellular events were higher in certain divisions in ages 35-40, non-smokers, and the GnRH-agonist group, and in embryos that resulted in pregnancy. CONCLUSION: Morphokinetic parameters of early embryo development via TLM are related to the characteristics of subfertile patients and associated with ICSI outcomes.

Real-time PCR for single-cell genotyping in sickle cell and thalassemia syndromes as a rapid, accurate, reliable, and widely applicable protocol for preimplantation genetic diagnosis.

Sickle-cell and beta-thalassemia syndromes are priority genetic diseases for prevention programs involving population screening with the option of prenatal diagnosis for carrier couples. Preimplantation genetic diagnosis (PGD) represents a specialized alternative to prenatal diagnosis and is most appropriately used for couples with an unsuccessful reproductive history and/or undergoing assisted reproduction. However, clinical application of PGD has been hindered by difficulties in reliably transferring molecular diagnostic protocols to the single-cell level. We standardized and validated a protocol involving first-round multiplex PCR, amplifying the region of the beta-globin gene containing most of the common disease mutations world-wide and two unlinked microsatellite markers (GABRB3 and D13S314), followed by: 1) analysis of beta-globin genotypes with real-time PCR and 2) microsatellite sizing to exclude chance contamination. The protocol was standardized on 100 single lymphocytes from a beta-thalassemia heterozygote, including 15 artificially contaminated samples, the latter demonstrated through microsatellite analysis. PCR failure and allele drop-out (ADO) were observed in one (uncontaminated) sample each (1.2%). A pilot study in six clinical PGD cycles with five different beta-globin genotype interactions achieved results (in 5-6 hr) in 46 out of 50 single blastomeres (92%), all concordant with results from an established PGD method applied simultaneously; microsatellite analysis detected only parental alleles, excluding contamination. Beta-globin genotypes were also confirmed in two blastomeres through prenatal diagnosis (twin pregnancy), and in 11 out of 12 spare embryos, revealing one incident of ADO. Overall, the protocol proved to be sensitive, accurate, reliable, rapid, and applicable for many genotype interactions, with internal monitoring of contamination, thus fulfilling all requirements for clinical PGD application.

An evaluation of PGD in clinical genetic services through 3 years application for prevention of beta-thalassaemia major and sickle cell thalassaemia.

PGD represents an alternative within prenatal diagnosis services, which avoids terminating affected on-going pregnancies. In Greece, prevention programmes for haemoglobinopathies, including the option of prenatal diagnosis, are well established. Following optimization of a single-cell genotyping strategy (designed to be applicable for the majority of beta-thalassaemia major or sickle thalassaemia genotype interactions) along with close collaboration with an IVF unit, we integrated the option of PGD for at-risk couples with a problematic reproductive history. A total of 59 couples requesting PGD were counselled, of whom 41 initiated 63 PGD cycles. Following standard assisted reproduction treatment for oocyte retrieval, 20 cycles were cancelled (too few oocytes and/or poor quality embryos), but in 43 cycles single blastomeres were biopsied from 3 day embryos and genotyped (total 302). Diagnosis was achieved for 236 embryos, and 100 of 125 unaffected embryos were transferred. Sixteen pregnancies were established, although six were lost within the first trimester. Ten pregnancies underwent second trimester prenatal diagnosis, with nine pregnancies (13 babies: six singletons, two twins and one triplet) confirmed unaffected, although one singleton was a PGD misdiagnosis and terminated. The triplet pregnancy was selectively reduced to twins, and nine pregnancies went to term, with 12 healthy babies born. This report highlights advantages, limitations and approaches towards improvement when incorporating PGD within genetic services for a common recessive disease.

Multiplex sequence variation detection throughout the CFTR gene appropriate for preimplantation genetic diagnosis in populations with heterogeneity of cystic fibrosis mutations.

Cystic fibrosis (CF) is one of the most important genetic diseases requiring prevention programmes. Preimplantation genetic diagnosis (PGD) represents an alternative to prenatal diagnosis, and is especially appropriate for couples with an unsuccessful reproductive history. For clinical application, protocols must be optimized to minimize PCR failure, allelic drop-out (ADO) and contamination, while simultaneously detecting a wide spectrum of CF genotypes. We have developed a flexible multiplex PCR protocol allowing analysis of sequence variations in any combination amongst seven CFTR gene exons (4, 10, 11, 13 in two parts, 14b, 17b and 21) by nested PCR and denaturing gradient gel electrophoresis analysis, along with analysis of a fluorescently labelled intragenic microsatellite (IVS8CA). The experiments were carried out on 390 single lymphocytes from three CF patients, one heterozygote and one non-CF individual. PCR efficiency of the exons ranged from 90 to 100%, and ADO from 0 to 3.8%. IVS8CA was co-amplified with a PCR efficiency of 92.4 and 10.8% ADO. The present method overcomes the need for separate assays for each CFTR gene mutation. Additionally, it facilitates analysis of any informative linked polymorphic sequence variation (within the seven exons) along with analysis of a microsatellite, which is useful (when informative) for minimizing misdiagnosis and/or indirect diagnosis. This method proved robust and flexible for diagnosing diverse CF genotype combinations in single cells.