A Multi-Center Evaluation of a Novel IVF Cryostorage Device in an Active Clinical Setting

A Multi-Center Evaluation of a Novel IVF Cryostorage Device in an Active Clinical Setting | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A Multi-Center Evaluation of a Novel IVF Cryostorage Device in an Active Clinical Setting Michael Collins, Jessica Bailey, Jordan Tremont, Natalee Laasch, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4189762/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Aug, 2024 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Purpose To evaluate the safety, function, and integration of a novel automated software-guided cryostorage system in an active IVF laboratory setting. Methods The Investigational Device (ID) was installed at 3 IVF laboratories (sites: α, β, and γ). A total of 15 embryologists were trained to use the ID. Mock patient specimens containing mirrored live patient data were handled using the ID. Temperature readings were recorded every minute. Successful identification, storage, and retrieval of patient specimens by the ID were evaluated. To assess an LN 2 pressure builder, the frequency of use and events of workflow interruption were logged. Student’s t-test was used to determine statistical significance. Results The ID was in active use for 164 days total. During this time, 329 mock patient egg and embryo cohorts were handled by the ID. The mean ± SD temperatures during active use were: α, -176.57 ± 1.83 O C; β, -178.21 ± 2.75 O C; γ, -178.98 ± 1.74 and did not differ significantly. The highest recorded temperatures were: α, -165.14 O C; β, -157.41 O C; γ, -164.45 O C. A total of 1064 automation transactions on 409 specimen vessels were performed. Data was managed on 1501 eggs and embryos. The ID did not lose or misplace any specimen data or vessels, and no specimen was exposed to a detrimental (>-150 O C) temperature excursion. Over the 25 LN 2 pressure builder usages during 99 total days, there was 1 occurrence where usage interrupted workflow due to a lack of LN 2 pressure. Conclusions The ID has advantages over the current manual-based cryostorage systems, including radio frequency identification (RFID) tracking, automation of manual tasks, and software guidance to ensure accurate specimen storage and retrieval. The results of this study indicate that the ID can be easily integrated into active IVF laboratories. Health sciences/Health occupations Health sciences/Health care/Occupational health cryostorage automation embryo digital chain of custody IVF Figures Figure 1 Figure 2 Introduction There is increasing demand for the cryostorage of human reproductive specimens [ 1 – 12 ]. Human reproductive specimen cryostorage handling remains intensely manual [ 13 ]. Specimens are manually retrieved from storage with variability in handling [ 14 ]. Specimen identification and location commonly rely on written or transcribed records and labels without the benefit of advanced software identification and tracking [ 14 ]. Routine cryostorage equipment includes liquid Nitrogen (LN 2 ) Dewars that store specimens at a single level and occupy increasing laboratory space [ 1 , 15 ]. Modern assisted reproductive technology (ART) facilities arduously monitor cryostorage equipment stability and integrity with minimal software oversight [ 13 , 15 ]. Embryologists have reported signs of fatigue, stress, anxiety, and burnout under current laboratory operating conditions [ 13 , 16 – 21 ]. Anxiety is known to be specifically associated with cryostorage working conditions [ 16 – 21 ], which may impact fidelity of the manual process. Embryologists working with manual cryostorage operations could benefit from the adoption of automation and software assistance within the laboratory setting [ 17 – 19 ]. Cryopreserved specimen mis-labeling errors, although rare, are known to occur [ 22 ]. The variability in specimen identification and handling, along with the reliance on non-digital identification and data handling, is likely to contribute to these rare occurrences of specimen mix-up and error [ 13 ]. It is believed that this similarly contributes to the fatigue, stress, anxiety, and burnout experienced by embryologists in cryostorage working conditions. The present study evaluates a novel IVF specimen cryostorage system (Investigational Device – ID). The study objective is to evaluate the safety, function, and integration of the ID in an active clinical setting. The ID includes automation intended to support embryologists and their working conditions by eliminating or reducing many manual tasks and facilitating specimen identification into, during, and from storage. The ID couples automation with specifically designed software to (1) provide active oversight of environmental conditions, (2) ensure proper equipment function, (3) enable an auditable digital chain of custody, and (4) lessen variability of specimen identification and retrieval from storage. Materials and Methods Investigational Device The ID (Fig. 1 ) consists of a cryostorage tank, temperature and environmental sensors, RFID readers, automation, an LN 2 pressure builder (Apollo®, Cryotherm GmbH & Co. KG, Kirchen (Sieg), Germany), and software. The cryostorage tank is a vacuum-insulated 250L liquid nitrogen storage vessel. The tank stores up to 1383 CryoBeacons (Fig. 2 ) in 2 levels of racks suspended in the vapor phase of LN 2 . CryoBeacons are specimen receptacles designed to hold common commercially available reproductive health cryodevices with vitrified reproductive specimens. CryoBeacons are maintained below − 150 O C during storage through the cooling effect of the LN 2 vapor. The CryoBeacons are RFID-tagged receptacles. The ID has multiple RFID antennae to identify CryoBeacons, determine location, and distinguish the desired CryoBeacon from others in close proximity. All CryoBeacons are identified via the RFID tag at least twice during specimen deposit and withdrawal from the ID. CryoBeacons are submerged in LN 2 in specifically designed carriers that are placed into the ID by trained embryologist operators. The embryologist interfaces with the ID through an iris scanner and a touchscreen control. Once placed into the ID automation moves the desired CryoBeacon from the LN 2 carrier to the storage location in the tank. Specimen cryogenic temperature is maintained during movement by residual LN 2 in the CryoBeacon during movement. The ID confirms that the CryoBeacon has sufficient LN 2 to maintain specimen thermal integrity before movement. Should automation fail during movement, an emergency LN 2 feed line floods the CryoBeacon. The emergency LN 2 feed requires 35 psi supply. The ID will not operate if 35 psi is not measured. To ensure 35 psi, the LN 2 pressure builder is part of the ID and evaluated in this study. The ID is controlled by custom-designed software including ivfOS™. The software functions to control access to registered users, ensure correct placement and location of CryoBeacons, control automation, read and log data from temperature and environmental sensors, enable offsite monitoring of safety and operations, and maintain an auditable digital chain of custody of specimens. Study Sites and Study Conduct The ID was installed at three study sites (α, β, and γ). All three sites had experience with automated cryostorage equipment, but not the ID. A total of 15 embryologists (4 at α and γ, 7 at β) were trained to use the ID and participated in the study. To evaluate the integration, function, and safety of the ID in an active IVF laboratory, mock patient freeze cohorts consisting of blank CryoBeacons (CryoBeacons without cryodevices) were registered with the software and deposited into the ID for storage. No live specimens were used in this evaluation. Live patient specimen data was mirrored in ivfOS™. The patient’s live specimens and data were handled throughout the study by the site using their individual manual processes and procedures. Five patient cohorts (all eggs or embryos from a single oocyte retrieval even if there were multiple days of freezing) were deposited per day (exclusive of weekends) throughout the 30-day study period. One hundred patient cohorts per study site were targeted. Following the first week of the study, on each weekday, 1 patient specimen from a cohort deposited a week earlier was retrieved and thawed (reported as thawed in ivfOS™). Similarly, if any patient’s live specimen(s) were thawed the blank CryoBeacon was retrieved from the ID and the specimen(s) were reported as thawed. This ensured that the retrieval and return of CryoBeacons for further storage of remaining specimens was evaluated. To evaluate specimen safety during storage, temperature readings from a resistance temperature detector (RTD) near the specimen storage level in the tank were recorded every minute. The software allows for the printing of cryodevice labels. The cryodevice labels are linked to the patient’s data record and the assigned CryoBeacon(s). Since there were no cryodevices used in the evaluation, the labels were adhered to a paper data record for each patient cohort. At the conclusion of the study, any remaining CryoBeacons were retrieved from the ID. The physical CryoBeacons were then matched to the inventory for the ID in ivfOS™ and the physical labels on the paper data records. Any discrepancy between the three databases was investigated for the root cause to determine if the fault was due to the ID or human error. To evaluate the integration of the LN 2 pressure builder into a busy IVF laboratory, the frequency of use and workflow interruptions were logged. Included in the log were questions if the use was expected or unexpected, if it disrupted work or was planned, and if the embryologist was able to complete the planned task they were performing. Statistical Analysis and Ethics Student’s t-test and descriptive statistics were used to evaluate temperatures. Counts of misplaced, misidentified, or lost specimen receptacles were used to evaluate the digital chain of custody. The study protocol was reviewed and approved to be exempt from IRB oversight (Pro00067860, Center for IRB Intelligence (CIRBI) Platform, Advarra, Columbia, MD). Results The ID was in active use for 164 days total (36, 68, 30; α, β, γ, respectively). During this time, 329 mock patient egg and embryo cohorts (56, 173, 100) were handled by the ID. Site β conducted a preliminary study using the same protocol, without the LN 2 pressure builder, prior to initiation of sites α and γ. Site α is a satellite laboratory with smaller patient volume than sites β and γ. The mean ± SD temperatures during active use were: α, -176.57 ± 1.83 O C; β, -178.21 ± 2.75 O C; γ, -178.98 ± 1.74 and did not differ significantly. The highest recorded temperatures were: α, -165.14 O C; β, -157.41 O C; γ, -164.45 O C (Table 1 ). Table 1 No specimens tracked by the device were exposed to a detrimental temperature excursion (> -150°C) throughout the 164 combined days of active use. Site α β Γ Mean ± SD temperatures during active use -176.6 ± 1.8°C -178.2 ± 2.8°C -178.9 ± 1.7°C Highest recorded temperatures -165.1°C -157.4°C -164.5°C A total of 1064 automation transactions on 409 specimen vessels were performed. Data was managed on 1501 eggs and embryos. The ID did not lose or misplace any specimen data or vessels, and no specimen was exposed to a detrimental (>-150 O C) temperature excursion (Table 2 ). Table 2 No specimens or specimen data tracked by the device were lost or misplaced; A total of 1064 automated transactions and 1501 specimen data were handled. Site α β Γ Mock Patient Cohorts 56 173 100 Lost or Misplaced Specimens 0 0 0 The LN 2 pressure builder requires periodic filling (~ every 3 days, depending on use). Each site chose to use the LN 2 pressure builder with different determination factors, frequencies, and time of day. Site α used the pressure builder 10 times over 36 days, while β used the system 6 times over 33 days and γ 9 times over 30 days. Over the 25 LN 2 pressure builder usages during 99 total days, there was 1 occurrence where usage interrupted workflow due to a lack of LN 2 pressure. Discussion There is an increasing demand for fertility services, including cryostorage of reproductive health specimens [ 1 – 12 ]. It is believed that this increasing workload is leading to high levels of stress, fatigue, burnout, and anxiety regarding cryostorage operations reported by embryologists [ 13 , 16 – 21 ]. However, even with the increasing number of IVF cycles compounding issues, cryostorage operations still commonly rely on handwritten labels and paper ledgers to track, locate, identify, deposit, and retrieve specimens, in addition to manual regulation of cryostorage equipment function and environmental conditions [ 1 , 13 – 14 ]. The introduction and adoption of technological improvements, including dedicated software management, is lagging in IVF cryostorage operations [ 15 ]. Embryologists working in IVF cryostorage facilities spend an inordinate amount of time doing fatiguing work [ 13 ]. It is believed this is a result of the current cryostorage equipment design and lack of automation and software. Embryologists in the UK and US report a desire for technological improvements in cryostorage operations [ 17 – 19 ]. This report is the evaluation of the safety, function, and integration of an ID for reproductive health specimen cryostorage. The ID combines software with automation. These features function together to provide a robust digital chain of custody with oversight of equipment function to help ensure specimen integrity and operator safety. The ID functioned as intended during the study period. The paramount concern with specimen integrity is temperature excursions beyond the devitrification temperature that may harm or destroy them [ 23 – 25 ]. During the 164 days of use in an active clinical setting there was not a temperature excursion that would have placed a specimen in jeopardy. To function correctly and provide for a digital chain of custody, the software and automation of the ID must work together. In this study, the ID did not lose, misplace, or misidentify any specimen receptacle. Even though the study sites chose to integrate the ID, especially the LN 2 pressure builder, in different ways, the data support that the LN 2 pressure builder does not disrupt the workflows of busy IVF laboratories. In summary, the ID is easily integrated into IVF laboratories, functions as designed, and is safe for specimens and trained operators. There are benefits of the specific ergonomic design, that limit physical strain, such as the need to bend over, lift heavy objects, or stand on stools and ladders [ 13 ]. These design benefits, when coupled with the accurate specimen identification and location from the digital chain of custody, should improve embryologist working conditions and the reported levels of cryostorage-related anxiety [ 17 – 19 ]. Using software to monitor specimen and environmental conditions and labware function eliminates the need for written records and ledgers and allows for analytics to improve laboratory operations. Declarations Disclosures Michael G. Collins Ph.D., Robert Woodhull, Ellen Stringfellow and Ashley Souza are all fulltime employees of TRMW Life Sciences. Author Contribution M.C. designed the experiment, oversaw data collection and analysis, wrote the main manuscript text. All authors contributed to the concept of the study. All authors reviewed and approved the manuscript. J.B., J.T., N.L., C.M., A.D., J.M., A.L., S.P., E.K., R.S., and L.R. conducted the experiment. R.W., E.S. and A.S. provided logistical support for equipment, training on appropriate use and oversight during data collection. Acknowledgement We thank Mr. Gustavo Hernandez-Furio, an undergraduate intern with TMRW Life Sciences and a sophomore at Columbia University's School of Engineering & Applied Science for help with the data organization in this study. We also thank Ms. Julia Stork, an undergraduate intern with TMRW Life Science and a senior at Northwestern University, for her help in coordinating the manuscript, author correspondence, data analysis, and editing tasks associated with this article. References Alikani M. Cryostorage of human gametes and embryos: a reckoning. Reprod. Biomed. Online . 2018; 37(1): 1-3. https://doi.org/10.1016/j.rbmo.2018.05.004 Alikani M., Parmegiani L. Human reproductive cell cryopreservation, storage, handling, and transport: risks and risk management. Semin. Reprod. Med. 2018; 36 :265–272. https://doi.org/10.1055/s-0038-1676849. Alikani M., Go K.J., McCaffrey C., McCulloh D.H. Comprehensive evaluation of contemporary assisted reproduction technology laboratory operations to determine staffing levels that promote patient safety and quality care . Fertil. Steril. 2014; 102 :1350–1356. https://doi.org/10.1016/j.fertnstert.2014.07.1246. Campbell A., Gardner D.K., Meseguer M., Miller K.A., Montag M., Palermo G.D. Cheung S., Keating D., Xie P., Rosenwaks Z., Rienzi L., Innocenti F., Cimadomo D., Ubaldi F.M., Sakkas D., Tucker M.J., Nel-Themaat L., Simon C. In vitro fertilization and andrology laboratory in 2030: expert visions. Fertil. Steril. 2021; 116 :4–12. https://doi.org/10.1016/j.fertnstert.2021.05.088 Canosa S., Maggiulli R., Cimadomo D., Innocenti F., Fabozzi G., Gennarelli G., Revelli A., Bongioanni F., Vaiarelli A., Ubaldi F.M., Rienzi L., Palmer G.A., Nijs M. Cryostorage management of reproductive cells and tissues in ART: status, needs, opportunities and potential new challenges. Reprod. Biomed. Online. 2023; 47 :103252. https://doi.org/10.1016/j.rbmo.2023.06.007. Go K.J. A subspecialty of the assisted reproductive technologies: cryogenic inventory maintenance. J. Assist. Reprod. Genet. 2019; 36(1) :15–17. https://doi.org/10.1007/s10815-018-1378-z. Niederberger C., Pellicer A., Cohen J., Gardner D.K., Palermo G.D., O'Neill C.L., Chow S., Rosenwaks Z., Cobo A., Swain J.E., Schoolcraft W.B., Frydman R., Bishop L.A., Aharon D., Gordon C., New E., Decherney A., Tan S.L., Paulson R.J., Goldfarb J.M., Brännström M., Donnez J., Silber S., Dolmans M.M., Simpson J.L., Handyside A.H., Munné S., Eguizabal C., Montserrat N., Izpisua Belmonte J.C., Trounson A., Simon C., Tulandi T., Giudice L.C., Norman R.J., Hsueh A.J., Sun Y., Laufer N., Kochman R., Eldar-Geva T., Lunenfeld B., Ezcurra D., D'Hooghe T., Fauser B.C.J.M., Tarlatzis B.C., Meldrum D.R., Casper R.F., Fatemi H.M., Devroey P., Galliano D., Wikland M., Sigman M., Schoor R.A., Goldstein M., Lipshultz L.I., Schlegel P.N., Hussein A., Oates R.D., Brannigan R.E., Ross H.E., Pennings G., Klock S.C., Brown S., Van Steirteghem A., Rebar R.W., LaBarbera A.R.. Forty years of IVF. Fertil. Steril. 2018; 110: 185-324.e5. https://doi.org/10.1016/j.fertnstert.2018.06.005. Rienzi L., Fauser B. Future challenges for clinical embryologists . Reprod. Biomed. Online. 2021; 43 :973–975. https://doi.org/10.1016/j.rbmo.2021.10.001 Rinehart L.A. Storage, transport, and disposition of gametes and embryos: legal issues and practical considerations. Fertil. Steril. 2021; 115 :274–281. https://doi.org/10.1016/j.fertnstert.2020.11.025. Simione F., Sharp T. Best practices for storing and shipping cryopreserved cells . In Vitro Cell. Dev. Biol. Anim . 2017; 53 :888–895. https://doi.org/10.1007/s11626-017-0214-6. Simon C., Campbell A., Gardner D.K., Meseguer M., Miller K.A., Montag M., Palermo G.D., Cheung S., Keating D., Xie P., Rosenwaks Z., Rienzi L., Innocenti F., Cimadomo D., Ubaldi F.M., Sakkas D., Tucker M.J., Nel-Themaat L. In vitro fertilization and andrology laboratories in 2030. Fertil. Steril. 2021; 116 :2–3. https://doi.org/10.1016/j.fertnstert.2021.05.089. Erratum in: Fertil. Steril . 2021; 116 :917. Tomlinson M.J. Safe storage of gametes and embryos: no time for complacency. Semin. Reprod. Med. 2018; 36 :289–298. https://doi.org/10.1055/s-0039-1678596 Collins M.G., Venier W., Salhia A., Beltsos, A., Lee J.A., Copperman A.B., Bailey J. Sakkas D., Broussard A. Working with fatigue: assessment of cryomanagement conditions in IVF biorepositories. Fertil. Steril. 2022; 118(4) supplement: E124 https://doi.org/10.1016/j.fertnstert.2022.08.368. Gupta R., Venier W., Salhia A., Beltsos A., Lee J.A., Briton-Jones C., Copperman A.B., Bailey J., Sakkas D., Collins M.G. "A collaborative assessment to measure variance in cryospecimen retrieval methods across multiple IVF clinics." Fertil. Steril. 2021; 116(3) : E377. https://doi.org/10.1016/j.fertnstert.2021.07.1013 Moutos C.P., Lahham R., Phelps J.Y. Cryostorage failures: a medicolegal review. J. Assist. Reprod. Genet . 2019; 36(6) :1041-1048. https://doi.org/10.1007/s10815-019-01478-x López-Regalado M.L., Olvera C., Martínez L., Castilla J.A. Embryologists’ health: a nationwide online questionnaire. J. Assist. Reprod. Genet. 2014; 31 :1587–1597. https://doi.org/10.1007/s10815-014-0352-7. Murphy A., Baltimore H., Lapczynski M., Proctor G., Meyer E.C., Glynn T., Domar A., Collins M.G. Embryologist burnout: physical and psychological symptoms and occupational challenges currently reported by U.S. embryologists. Fertil. Steril. 2022; 118(4) supplement: E66. https://doi.org/10.1016/j.fertnstert.2022.08.205. Murphy A., Lapczynski M., Proctor G., Glynn T., Domar A., Gameiro S., Palmer G., Collins M.G. 2023. Comparison of embryologist stress, fatigue, and burnout currently reported by U.K. and U.S embryologists. Fertil. Steril. 2023; 120(4) supplement: E265. https://doi.org/10.1016/j.fertnstert.2023.08.779. Murphy A., Lapczynski M., Proctor G., Meyer, E.C., Glynn T., Domar A., Gameiro S., Palmer G., Collins M. The occupational challenges reported by UK embryologists: stress, fatigue, and burnout. Hum. Repr. 2023; 38(1) supplement : dead093.906. https://doi.org/10.1093/humrep/dead093.906. Palmer G., Tully B., Angle M., Sadruddin S., Howles C., Elliott T., Szvetecz S., Nagy ZP, Cohen J. Occupational demands and resultant stress of reproductive scientists: Outcomes from an international survey. Fertility 2022, January 5–8, ACC Liverpool, UK 2022. Priddle H., Pickup S., Hayes C.; Association of Reproductive and Clinical Scientists (ARCS). Occupational health issues experienced by UK embryologists: informing improvements in clinical reproductive science practice. Hum. Fertil. 2022; 25 :608–617. https://doi.org/10.1080/14647273.2021.1871782. Nesbit C., Blanchette Porter M., Esfandiari N. Catastrophic human error in assisted reproductive technologies: a systematic review. J. Patient. Saf. 2022; 18 : E267–E274. https://doi.org/10.1097/PTS.0000000000000763. Campbell L.D., Astrin J.J., DeSouza Y., Giri J., Patel A.A., Rawley-Payne M., Rush A., Sieffert N. The 2018 revision of the ISBER best practices: summary of changes and the editorial team's development process. Biopreserv. Biobank . 2018; 16(1) :3-6. https://doi.org/10.1089/bio.2018.0001 Mochida K., Hasegawa A., Li M.W., Fray M.D., Kito S., Vallelunga J.M., Lloyd K.K., Yoshiki A., Obata Y., Ogura A. High osmolality vitrification: a new method for the simple and temperature-permissive cryopreservation of mouse embryos. PLoS One. 2013; 8(1) : E49316. https://doi.org/10.1371/journal.pone.0049316 Sansinena M., Santos M.V., Taminelli G., Zaritky N. Implications of storage and handling conditions on glass transition and potential devitrification of oocytes and embryos. Theriogenology. 2014; 82(3) :373-8. https://doi.org/10.1016/j.theriogenology.2014.04.003 Additional Declarations Competing interest reported. Michael G. Collins Ph.D., Robert Woodhull, Ellen Stringfellow and Ashley Souza are all fulltime employees of TRMW Life Sciences. Cite Share Download PDF Status: Published Journal Publication published 16 Aug, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 21 May, 2024 Reviews received at journal 20 May, 2024 Reviews received at journal 09 May, 2024 Reviewers agreed at journal 27 Apr, 2024 Reviewers agreed at journal 25 Apr, 2024 Reviewers invited by journal 25 Apr, 2024 Editor assigned by journal 25 Apr, 2024 Editor invited by journal 10 Apr, 2024 Submission checks completed at journal 09 Apr, 2024 First submitted to journal 29 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4189762","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":285501523,"identity":"4062a10e-f0c3-4553-9672-628d6c9df09d","order_by":0,"name":"Michael Collins","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsUlEQVRIiWNgGAWjYDACZgY2IGkhR7IWCWMeUuwBa0nsIVq9bjvzswc/KiTS94udfSbBUHHProGQFrPDbOaGPWckcnuk080kGM4UJxOhhYdNgrcNpCWN7QZjW0IyQYeBtEj+/SeRzkOSFmneBokEmBY7IrSwmUnLHJMw7Lmdxv4j4UxCAmEt5w8/k3xTYyPPPjuN2eBDRYI9QS2oAGhFYgOJehgYSLVlFIyCUTAKRgAAAPNXMqqhgUgrAAAAAElFTkSuQmCC","orcid":"","institution":"TMRW Life Sciences","correspondingAuthor":true,"prefix":"","firstName":"Michael","middleName":"","lastName":"Collins","suffix":""},{"id":285501524,"identity":"c6e1be47-04d7-4346-aa59-8d39b7148f9d","order_by":1,"name":"Jessica Bailey","email":"","orcid":"","institution":"Boston IVF – The Eugin Group","correspondingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"","lastName":"Bailey","suffix":""},{"id":285501525,"identity":"ac5bc2a6-ecff-4047-83f4-a7709059190a","order_by":2,"name":"Jordan Tremont","email":"","orcid":"","institution":"Boston IVF – The Eugin Group","correspondingAuthor":false,"prefix":"","firstName":"Jordan","middleName":"","lastName":"Tremont","suffix":""},{"id":285501526,"identity":"6e26d43a-a65f-4a20-9345-03ea6497d68a","order_by":3,"name":"Natalee Laasch","email":"","orcid":"","institution":"Boston IVF – The Eugin Group","correspondingAuthor":false,"prefix":"","firstName":"Natalee","middleName":"","lastName":"Laasch","suffix":""},{"id":285501527,"identity":"56f29016-1e0f-4df3-a7ea-8fb1b23bb1d8","order_by":4,"name":"Cali McDonough","email":"","orcid":"","institution":"Boston IVF – The Eugin Group","correspondingAuthor":false,"prefix":"","firstName":"Cali","middleName":"","lastName":"McDonough","suffix":""},{"id":285501528,"identity":"3a5a3af0-c5af-4659-8046-b3ad3f440fa6","order_by":5,"name":"Andrea Dufault","email":"","orcid":"","institution":"Boston IVF – The Eugin Group","correspondingAuthor":false,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Dufault","suffix":""},{"id":285501529,"identity":"166293f4-9bb5-4413-9616-219e1e1dcf3e","order_by":6,"name":"Jessica Martin","email":"","orcid":"","institution":"Boston IVF – The Eugin Group","correspondingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"","lastName":"Martin","suffix":""},{"id":285501530,"identity":"2152c9da-0478-43c3-97fc-89f62610d317","order_by":7,"name":"Albert Li","email":"","orcid":"","institution":"Reproductive Medicine Associates of New York","correspondingAuthor":false,"prefix":"","firstName":"Albert","middleName":"","lastName":"Li","suffix":""},{"id":285501531,"identity":"e5944184-eb99-489d-9c5b-728a56a94454","order_by":8,"name":"Stefan Pitts","email":"","orcid":"","institution":"Reproductive Medicine Associates of New York","correspondingAuthor":false,"prefix":"","firstName":"Stefan","middleName":"","lastName":"Pitts","suffix":""},{"id":285501532,"identity":"5f73453c-f469-4163-83d3-8a941a0e94c1","order_by":9,"name":"Emma Kontaxis","email":"","orcid":"","institution":"Reproductive Medicine Associates of New York","correspondingAuthor":false,"prefix":"","firstName":"Emma","middleName":"","lastName":"Kontaxis","suffix":""},{"id":285501533,"identity":"3fb5a126-ffb1-4890-abd5-cba516aca3d9","order_by":10,"name":"Richard Slifkin","email":"","orcid":"","institution":"Reproductive Medicine Associates of New York","correspondingAuthor":false,"prefix":"","firstName":"Richard","middleName":"","lastName":"Slifkin","suffix":""},{"id":285501534,"identity":"fdebc0ed-7b01-47d9-9165-b684693f4d59","order_by":11,"name":"Joseph Lee","email":"","orcid":"","institution":"Reproductive Medicine Associates of New York","correspondingAuthor":false,"prefix":"","firstName":"Joseph","middleName":"","lastName":"Lee","suffix":""},{"id":285501535,"identity":"475ddaac-5f9a-411b-99a4-dc7f4ffb2813","order_by":12,"name":"Laura Reed","email":"","orcid":"","institution":"Colorado Center for Reproductive Medicine","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"Reed","suffix":""},{"id":285501536,"identity":"1e2aa790-d7f8-418f-9301-a53c4b61dc47","order_by":13,"name":"Jason Swain","email":"","orcid":"","institution":"Colorado Center for Reproductive Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jason","middleName":"","lastName":"Swain","suffix":""},{"id":285501537,"identity":"0d82eae5-8ead-4e84-b1e9-02243ed6cd99","order_by":14,"name":"William Schoolcraft","email":"","orcid":"","institution":"Colorado Center for Reproductive Medicine","correspondingAuthor":false,"prefix":"","firstName":"William","middleName":"","lastName":"Schoolcraft","suffix":""},{"id":285501538,"identity":"b5b343c6-313b-4bee-80e4-4f4b4d2c5c59","order_by":15,"name":"Ellen String","email":"","orcid":"","institution":"TMRW Life Sciences","correspondingAuthor":false,"prefix":"","firstName":"Ellen","middleName":"","lastName":"String","suffix":""},{"id":285501539,"identity":"4b9d70be-c819-41f5-90bc-b1102c8624c8","order_by":16,"name":"Robert Woodhull","email":"","orcid":"","institution":"TMRW Life Sciences","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"","lastName":"Woodhull","suffix":""},{"id":285501540,"identity":"ea7b76e6-e4f8-470c-9602-39ecff7fcee7","order_by":17,"name":"Ashley Souza","email":"","orcid":"","institution":"TMRW Life Sciences","correspondingAuthor":false,"prefix":"","firstName":"Ashley","middleName":"","lastName":"Souza","suffix":""}],"badges":[],"createdAt":"2024-03-29 21:29:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4189762/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4189762/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-69877-4","type":"published","date":"2024-08-16T15:57:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":53879015,"identity":"733ac927-3cb7-4b3f-ae53-a5b50f292377","added_by":"auto","created_at":"2024-04-01 17:05:22","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":784598,"visible":true,"origin":"","legend":"\u003cp\u003eInvestigational Device: a novel automated software-guided cryostorage system.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4189762/v1/ad75d395e9e88e8391d61b6e.jpeg"},{"id":53879024,"identity":"2cda112c-63f7-4111-8d3c-137104517bc0","added_by":"auto","created_at":"2024-04-01 17:05:25","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":151954,"visible":true,"origin":"","legend":"\u003cp\u003eCryoBeacons: RFID tagged vessels submersed in LN\u003csub\u003e2\u003c/sub\u003e for cryopreservation and storage.of specimens.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4189762/v1/46d00b7f16d0a2f0d4e5a36c.jpeg"},{"id":63071974,"identity":"5254a7f9-591a-483e-932e-873e9626c338","added_by":"auto","created_at":"2024-08-22 20:10:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1373017,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4189762/v1/3cd077fe-88ca-4a59-a67f-da18c9847c90.pdf"}],"financialInterests":"Competing interest reported. Michael G. Collins Ph.D., Robert Woodhull, Ellen Stringfellow and Ashley Souza are all fulltime employees of TRMW Life Sciences.","formattedTitle":"\u003cp\u003eA Multi-Center Evaluation of a Novel IVF Cryostorage Device in an Active Clinical Setting\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThere is increasing demand for the cryostorage of human reproductive specimens [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Human reproductive specimen cryostorage handling remains intensely manual [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Specimens are manually retrieved from storage with variability in handling [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Specimen identification and location commonly rely on written or transcribed records and labels without the benefit of advanced software identification and tracking [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRoutine cryostorage equipment includes liquid Nitrogen (LN\u003csub\u003e2\u003c/sub\u003e) Dewars that store specimens at a single level and occupy increasing laboratory space [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Modern assisted reproductive technology (ART) facilities arduously monitor cryostorage equipment stability and integrity with minimal software oversight [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Embryologists have reported signs of fatigue, stress, anxiety, and burnout under current laboratory operating conditions [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Anxiety is known to be specifically associated with cryostorage working conditions [\u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], which may impact fidelity of the manual process. Embryologists working with manual cryostorage operations could benefit from the adoption of automation and software assistance within the laboratory setting [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCryopreserved specimen mis-labeling errors, although rare, are known to occur [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The variability in specimen identification and handling, along with the reliance on non-digital identification and data handling, is likely to contribute to these rare occurrences of specimen mix-up and error [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. It is believed that this similarly contributes to the fatigue, stress, anxiety, and burnout experienced by embryologists in cryostorage working conditions.\u003c/p\u003e \u003cp\u003eThe present study evaluates a novel IVF specimen cryostorage system (Investigational Device \u0026ndash; ID). The study objective is to evaluate the safety, function, and integration of the ID in an active clinical setting. The ID includes automation intended to support embryologists and their working conditions by eliminating or reducing many manual tasks and facilitating specimen identification into, during, and from storage. The ID couples automation with specifically designed software to (1) provide active oversight of environmental conditions, (2) ensure proper equipment function, (3) enable an auditable digital chain of custody, and (4) lessen variability of specimen identification and retrieval from storage.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eInvestigational Device\u003c/h2\u003e \u003cp\u003eThe ID (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e consists of a cryostorage tank, temperature and environmental sensors, RFID readers, automation, an LN\u003csub\u003e2\u003c/sub\u003e pressure builder (Apollo\u0026reg;, Cryotherm GmbH \u0026amp; Co. KG, Kirchen (Sieg), Germany), and software. The cryostorage tank is a vacuum-insulated 250L liquid nitrogen storage vessel. The tank stores up to 1383 CryoBeacons (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) in 2 levels of racks suspended in the vapor phase of LN\u003csub\u003e2\u003c/sub\u003e. CryoBeacons are specimen receptacles designed to hold common commercially available reproductive health cryodevices with vitrified reproductive specimens. CryoBeacons are maintained below \u0026minus;\u0026thinsp;150\u003csup\u003eO\u003c/sup\u003eC during storage through the cooling effect of the LN\u003csub\u003e2\u003c/sub\u003e vapor.\u003c/p\u003e \u003cp\u003eThe CryoBeacons are RFID-tagged receptacles. The ID has multiple RFID antennae to identify CryoBeacons, determine location, and distinguish the desired CryoBeacon from others in close proximity. All CryoBeacons are identified via the RFID tag at least twice during specimen deposit and withdrawal from the ID.\u003c/p\u003e \u003cp\u003eCryoBeacons are submerged in LN\u003csub\u003e2\u003c/sub\u003e in specifically designed carriers that are placed into the ID by trained embryologist operators. The embryologist interfaces with the ID through an iris scanner and a touchscreen control. Once placed into the ID automation moves the desired CryoBeacon from the LN\u003csub\u003e2\u003c/sub\u003e carrier to the storage location in the tank. Specimen cryogenic temperature is maintained during movement by residual LN\u003csub\u003e2\u003c/sub\u003e in the CryoBeacon during movement. The ID confirms that the CryoBeacon has sufficient LN\u003csub\u003e2\u003c/sub\u003e to maintain specimen thermal integrity before movement. Should automation fail during movement, an emergency LN\u003csub\u003e2\u003c/sub\u003e feed line floods the CryoBeacon. The emergency LN\u003csub\u003e2\u003c/sub\u003e feed requires 35 psi supply. The ID will not operate if 35 psi is not measured. To ensure 35 psi, the LN\u003csub\u003e2\u003c/sub\u003e pressure builder is part of the ID and evaluated in this study.\u003c/p\u003e \u003cp\u003eThe ID is controlled by custom-designed software including ivfOS\u0026trade;. The software functions to control access to registered users, ensure correct placement and location of CryoBeacons, control automation, read and log data from temperature and environmental sensors, enable offsite monitoring of safety and operations, and maintain an auditable digital chain of custody of specimens.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy Sites and Study Conduct\u003c/h2\u003e \u003cp\u003eThe ID was installed at three study sites (α, β, and γ). All three sites had experience with automated cryostorage equipment, but not the ID. A total of 15 embryologists (4 at α and γ, 7 at β) were trained to use the ID and participated in the study.\u003c/p\u003e \u003cp\u003eTo evaluate the integration, function, and safety of the ID in an active IVF laboratory, mock patient freeze cohorts consisting of blank CryoBeacons (CryoBeacons without cryodevices) were registered with the software and deposited into the ID for storage. No live specimens were used in this evaluation. Live patient specimen data was mirrored in ivfOS\u0026trade;. The patient\u0026rsquo;s live specimens and data were handled throughout the study by the site using their individual manual processes and procedures. Five patient cohorts (all eggs or embryos from a single oocyte retrieval even if there were multiple days of freezing) were deposited per day (exclusive of weekends) throughout the 30-day study period. One hundred patient cohorts per study site were targeted. Following the first week of the study, on each weekday, 1 patient specimen from a cohort deposited a week earlier was retrieved and thawed (reported as thawed in ivfOS\u0026trade;). Similarly, if any patient\u0026rsquo;s live specimen(s) were thawed the blank CryoBeacon was retrieved from the ID and the specimen(s) were reported as thawed. This ensured that the retrieval and return of CryoBeacons for further storage of remaining specimens was evaluated. To evaluate specimen safety during storage, temperature readings from a resistance temperature detector (RTD) near the specimen storage level in the tank were recorded every minute.\u003c/p\u003e \u003cp\u003eThe software allows for the printing of cryodevice labels. The cryodevice labels are linked to the patient\u0026rsquo;s data record and the assigned CryoBeacon(s). Since there were no cryodevices used in the evaluation, the labels were adhered to a paper data record for each patient cohort. At the conclusion of the study, any remaining CryoBeacons were retrieved from the ID. The physical CryoBeacons were then matched to the inventory for the ID in ivfOS\u0026trade; and the physical labels on the paper data records. Any discrepancy between the three databases was investigated for the root cause to determine if the fault was due to the ID or human error.\u003c/p\u003e \u003cp\u003eTo evaluate the integration of the LN\u003csub\u003e2\u003c/sub\u003e pressure builder into a busy IVF laboratory, the frequency of use and workflow interruptions were logged. Included in the log were questions if the use was expected or unexpected, if it disrupted work or was planned, and if the embryologist was able to complete the planned task they were performing.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis and Ethics\u003c/h2\u003e \u003cp\u003eStudent\u0026rsquo;s t-test and descriptive statistics were used to evaluate temperatures. Counts of misplaced, misidentified, or lost specimen receptacles were used to evaluate the digital chain of custody.\u003c/p\u003e \u003cp\u003e The study protocol was reviewed and approved to be exempt from IRB oversight (Pro00067860, Center for IRB Intelligence (CIRBI) Platform, Advarra, Columbia, MD).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe ID was in active use for 164 days total (36, 68, 30; α, β, γ, respectively). During this time, 329 mock patient egg and embryo cohorts (56, 173, 100) were handled by the ID. Site β conducted a preliminary study using the same protocol, without the LN\u003csub\u003e2\u003c/sub\u003e pressure builder, prior to initiation of sites α and γ. Site α is a satellite laboratory with smaller patient volume than sites β and γ.\u003c/p\u003e \u003cp\u003eThe mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD temperatures during active use were: α, -176.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83\u003csup\u003eO\u003c/sup\u003eC; β, -178.21\u0026thinsp;\u0026plusmn;\u0026thinsp;2.75\u003csup\u003eO\u003c/sup\u003eC; γ, -178.98\u0026thinsp;\u0026plusmn;\u0026thinsp;1.74 and did not differ significantly. The highest recorded temperatures were: α, -165.14\u003csup\u003eO\u003c/sup\u003eC; β, -157.41\u003csup\u003eO\u003c/sup\u003eC; γ, -164.45\u003csup\u003eO\u003c/sup\u003eC (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNo specimens tracked by the device were exposed to a detrimental temperature excursion (\u0026gt; -150\u0026deg;C) throughout the 164 combined days of active use.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSite\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eα\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eΓ\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD temperatures during active use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-176.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-178.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-178.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHighest recorded temperatures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-165.1\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-157.4\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-164.5\u0026deg;C\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA total of 1064 automation transactions on 409 specimen vessels were performed. Data was managed on 1501 eggs and embryos. The ID did not lose or misplace any specimen data or vessels, and no specimen was exposed to a detrimental (\u0026gt;-150\u003csup\u003eO\u003c/sup\u003eC) temperature excursion (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNo specimens or specimen data tracked by the device were lost or misplaced; A total of 1064 automated transactions and 1501 specimen data were handled.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSite\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eα\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eΓ\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMock Patient Cohorts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e173\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLost or Misplaced Specimens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe LN\u003csub\u003e2\u003c/sub\u003e pressure builder requires periodic filling (~\u0026thinsp;every 3 days, depending on use). Each site chose to use the LN\u003csub\u003e2\u003c/sub\u003e pressure builder with different determination factors, frequencies, and time of day. Site α used the pressure builder 10 times over 36 days, while β used the system 6 times over 33 days and γ 9 times over 30 days. Over the 25 LN\u003csub\u003e2\u003c/sub\u003e pressure builder usages during 99 total days, there was 1 occurrence where usage interrupted workflow due to a lack of LN\u003csub\u003e2\u003c/sub\u003e pressure.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThere is an increasing demand for fertility services, including cryostorage of reproductive health specimens [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. It is believed that this increasing workload is leading to high levels of stress, fatigue, burnout, and anxiety regarding cryostorage operations reported by embryologists [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, even with the increasing number of IVF cycles compounding issues, cryostorage operations still commonly rely on handwritten labels and paper ledgers to track, locate, identify, deposit, and retrieve specimens, in addition to manual regulation of cryostorage equipment function and environmental conditions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The introduction and adoption of technological improvements, including dedicated software management, is lagging in IVF cryostorage operations [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEmbryologists working in IVF cryostorage facilities spend an inordinate amount of time doing fatiguing work [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. It is believed this is a result of the current cryostorage equipment design and lack of automation and software. Embryologists in the UK and US report a desire for technological improvements in cryostorage operations [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis report is the evaluation of the safety, function, and integration of an ID for reproductive health specimen cryostorage. The ID combines software with automation. These features function together to provide a robust digital chain of custody with oversight of equipment function to help ensure specimen integrity and operator safety.\u003c/p\u003e \u003cp\u003eThe ID functioned as intended during the study period. The paramount concern with specimen integrity is temperature excursions beyond the devitrification temperature that may harm or destroy them [\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. During the 164 days of use in an active clinical setting there was not a temperature excursion that would have placed a specimen in jeopardy.\u003c/p\u003e \u003cp\u003eTo function correctly and provide for a digital chain of custody, the software and automation of the ID must work together. In this study, the ID did not lose, misplace, or misidentify any specimen receptacle. Even though the study sites chose to integrate the ID, especially the LN\u003csub\u003e2\u003c/sub\u003e pressure builder, in different ways, the data support that the LN\u003csub\u003e2\u003c/sub\u003e pressure builder does not disrupt the workflows of busy IVF laboratories.\u003c/p\u003e \u003cp\u003eIn summary, the ID is easily integrated into IVF laboratories, functions as designed, and is safe for specimens and trained operators. There are benefits of the specific ergonomic design, that limit physical strain, such as the need to bend over, lift heavy objects, or stand on stools and ladders [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These design benefits, when coupled with the accurate specimen identification and location from the digital chain of custody, should improve embryologist working conditions and the reported levels of cryostorage-related anxiety [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Using software to monitor specimen and environmental conditions and labware function eliminates the need for written records and ledgers and allows for analytics to improve laboratory operations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDisclosures \u003c/h2\u003e\n\u003cp\u003eMichael G. Collins Ph.D., Robert Woodhull, Ellen Stringfellow and Ashley Souza are all fulltime employees of TRMW Life Sciences.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.C. designed the experiment, oversaw data collection and analysis, wrote the main manuscript text. All authors contributed to the concept of the study. All authors reviewed and approved the manuscript. J.B., J.T., N.L., C.M., A.D., J.M., A.L., S.P., E.K., R.S., and L.R. conducted the experiment. R.W., E.S. and A.S. provided logistical support for equipment, training on appropriate use and oversight during data collection.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank Mr. Gustavo Hernandez-Furio, an undergraduate intern with TMRW Life Sciences and a sophomore at Columbia University's School of Engineering \u0026amp; Applied Science for help with the data organization in this study. We also thank Ms. Julia Stork, an undergraduate intern with TMRW Life Science and a senior at Northwestern University, for her help in coordinating the manuscript, author correspondence, data analysis, and editing tasks associated with this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlikani M. Cryostorage of human gametes and embryos: a reckoning. \u003cem\u003eReprod. Biomed. Online\u003c/em\u003e. 2018; \u003cstrong\u003e37(1):\u003c/strong\u003e1-3. https://doi.org/10.1016/j.rbmo.2018.05.004\u003c/li\u003e\n\u003cli\u003eAlikani M., Parmegiani L. Human reproductive cell cryopreservation, storage, handling, and transport: risks and risk management. \u003cem\u003eSemin. Reprod. Med. \u003c/em\u003e2018; \u003cstrong\u003e36\u003c/strong\u003e:265\u0026ndash;272. https://doi.org/10.1055/s-0038-1676849.\u003c/li\u003e\n\u003cli\u003eAlikani M., Go K.J., McCaffrey C., McCulloh D.H. Comprehensive evaluation of contemporary assisted reproduction technology laboratory operations to determine staffing levels that promote patient safety and quality care\u003cstrong\u003e. \u003c/strong\u003e\u003cem\u003eFertil. Steril.\u003c/em\u003e 2014; \u003cstrong\u003e102\u003c/strong\u003e:1350\u0026ndash;1356. https://doi.org/10.1016/j.fertnstert.2014.07.1246.\u003c/li\u003e\n\u003cli\u003eCampbell A., Gardner D.K., Meseguer M., Miller K.A., Montag M., Palermo G.D. Cheung S., Keating D., Xie P., Rosenwaks Z., Rienzi L., Innocenti F., Cimadomo D., Ubaldi F.M., Sakkas D., Tucker M.J., Nel-Themaat L., Simon C. In vitro fertilization and andrology laboratory in 2030: expert visions. \u003cem\u003eFertil. Steril.\u003c/em\u003e 2021; \u003cstrong\u003e116\u003c/strong\u003e:4\u0026ndash;12. https://doi.org/10.1016/j.fertnstert.2021.05.088\u003c/li\u003e\n\u003cli\u003eCanosa S., Maggiulli R., Cimadomo D., Innocenti F., Fabozzi G., Gennarelli G., Revelli A., Bongioanni F., Vaiarelli A., Ubaldi F.M., Rienzi L., Palmer G.A., Nijs M. Cryostorage management of reproductive cells and tissues in ART: status, needs, opportunities and potential new challenges. \u003cem\u003eReprod. Biomed. Online.\u003c/em\u003e 2023; \u003cstrong\u003e47\u003c/strong\u003e:103252. https://doi.org/10.1016/j.rbmo.2023.06.007.\u003c/li\u003e\n\u003cli\u003eGo K.J. A subspecialty of the assisted reproductive technologies: cryogenic inventory maintenance. \u003cem\u003eJ. Assist. Reprod. Genet.\u003c/em\u003e 2019; \u003cstrong\u003e36(1)\u003c/strong\u003e:15\u0026ndash;17. https://doi.org/10.1007/s10815-018-1378-z.\u003c/li\u003e\n\u003cli\u003eNiederberger C., Pellicer A., Cohen J., Gardner D.K., Palermo G.D., O\u0026apos;Neill C.L., Chow S., Rosenwaks Z., Cobo A., Swain J.E., Schoolcraft W.B., Frydman R., Bishop L.A., Aharon D., Gordon C., New E., Decherney A., Tan S.L., Paulson R.J., Goldfarb J.M., Br\u0026auml;nnstr\u0026ouml;m M., Donnez J., Silber S., Dolmans M.M., Simpson J.L., Handyside A.H., Munn\u0026eacute; S., Eguizabal C., Montserrat N., Izpisua Belmonte J.C., Trounson A., Simon C., Tulandi T., Giudice L.C., Norman R.J., Hsueh A.J., Sun Y., Laufer N., Kochman R., Eldar-Geva T., Lunenfeld B., Ezcurra D., D\u0026apos;Hooghe T., Fauser B.C.J.M., Tarlatzis B.C., Meldrum D.R., Casper R.F., Fatemi H.M., Devroey P., Galliano D., Wikland M., Sigman M., Schoor R.A., Goldstein M., Lipshultz L.I., Schlegel P.N., Hussein A., Oates R.D., Brannigan R.E., Ross H.E., Pennings G., Klock S.C., Brown S., Van Steirteghem A., Rebar R.W., LaBarbera A.R.. Forty years of IVF. \u003cem\u003eFertil. Steril. \u003c/em\u003e2018; \u003cstrong\u003e110:\u003c/strong\u003e185-324.e5. https://doi.org/10.1016/j.fertnstert.2018.06.005. \u003c/li\u003e\n\u003cli\u003eRienzi L., Fauser B. Future challenges for clinical embryologists\u003cem\u003e. Reprod. Biomed. Online.\u003c/em\u003e 2021; \u003cstrong\u003e43\u003c/strong\u003e:973\u0026ndash;975. https://doi.org/10.1016/j.rbmo.2021.10.001\u003c/li\u003e\n\u003cli\u003eRinehart L.A. Storage, transport, and disposition of gametes and embryos: legal issues and practical considerations. \u003cem\u003eFertil. Steril.\u003c/em\u003e 2021; \u003cstrong\u003e115\u003c/strong\u003e:274\u0026ndash;281. https://doi.org/10.1016/j.fertnstert.2020.11.025.\u003c/li\u003e\n\u003cli\u003eSimione F., Sharp T. Best practices for storing and shipping cryopreserved cells\u003cem\u003e. In Vitro Cell. Dev. Biol. Anim\u003c/em\u003e. 2017; \u003cstrong\u003e53\u003c/strong\u003e:888\u0026ndash;895. https://doi.org/10.1007/s11626-017-0214-6.\u003c/li\u003e\n\u003cli\u003eSimon C., Campbell A., Gardner D.K., Meseguer M., Miller K.A., Montag M., Palermo G.D., Cheung S., Keating D., Xie P., Rosenwaks Z., Rienzi L., Innocenti F., Cimadomo D., Ubaldi F.M., Sakkas D., Tucker M.J., Nel-Themaat L. In vitro fertilization and andrology laboratories in 2030. \u003cem\u003eFertil. Steril.\u003c/em\u003e 2021; \u003cstrong\u003e116\u003c/strong\u003e:2\u0026ndash;3. https://doi.org/10.1016/j.fertnstert.2021.05.089. Erratum in: \u003cem\u003eFertil. Steril\u003c/em\u003e. 2021; \u003cstrong\u003e116\u003c/strong\u003e:917.\u003c/li\u003e\n\u003cli\u003eTomlinson M.J. Safe storage of gametes and embryos: no time for complacency. \u003cem\u003eSemin. Reprod. Med.\u003c/em\u003e 2018; \u003cstrong\u003e36\u003c/strong\u003e:289\u0026ndash;298. https://doi.org/10.1055/s-0039-1678596\u003c/li\u003e\n\u003cli\u003eCollins M.G., Venier W., Salhia A., Beltsos, A., Lee J.A., Copperman A.B., Bailey J. Sakkas D., Broussard A. Working with fatigue: assessment of cryomanagement conditions in IVF biorepositories. \u003cem\u003eFertil. Steril. \u003c/em\u003e2022; \u003cstrong\u003e118(4) supplement:\u003c/strong\u003e E124 https://doi.org/10.1016/j.fertnstert.2022.08.368.\u003c/li\u003e\n\u003cli\u003eGupta R., Venier W., Salhia A., Beltsos A., Lee J.A., Briton-Jones C., Copperman A.B., Bailey J., Sakkas D., Collins M.G. \u0026quot;A collaborative assessment to measure variance in cryospecimen retrieval methods across multiple IVF clinics.\u0026quot; \u003cem\u003eFertil. Steril. \u003c/em\u003e2021; \u003cstrong\u003e116(3)\u003c/strong\u003e: E377. https://doi.org/10.1016/j.fertnstert.2021.07.1013\u003c/li\u003e\n\u003cli\u003eMoutos C.P., Lahham R., Phelps J.Y. Cryostorage failures: a medicolegal review. \u003cem\u003eJ. Assist. Reprod. Genet\u003c/em\u003e. 2019; \u003cstrong\u003e36(6)\u003c/strong\u003e:1041-1048. https://doi.org/10.1007/s10815-019-01478-x\u003c/li\u003e\n\u003cli\u003eL\u0026oacute;pez-Regalado M.L., Olvera C., Mart\u0026iacute;nez L., Castilla J.A. Embryologists\u0026rsquo; health: a nationwide online questionnaire. \u003cem\u003eJ. Assist. Reprod. Genet.\u003c/em\u003e 2014; \u003cstrong\u003e31\u003c/strong\u003e:1587\u0026ndash;1597. https://doi.org/10.1007/s10815-014-0352-7.\u003c/li\u003e\n\u003cli\u003eMurphy A., Baltimore H., Lapczynski M., Proctor G., Meyer E.C., Glynn T., Domar A., Collins M.G. Embryologist burnout: physical and psychological symptoms and occupational challenges currently reported by U.S. embryologists. \u003cem\u003eFertil. Steril.\u003c/em\u003e 2022; \u003cstrong\u003e118(4) supplement:\u003c/strong\u003e E66. https://doi.org/10.1016/j.fertnstert.2022.08.205.\u003c/li\u003e\n\u003cli\u003eMurphy A., Lapczynski M., Proctor G., Glynn T., Domar A., Gameiro S., Palmer G., Collins M.G. 2023. Comparison of embryologist stress, fatigue, and burnout currently reported by U.K. and U.S embryologists. \u003cem\u003eFertil. Steril.\u003c/em\u003e 2023; \u003cstrong\u003e120(4) supplement: \u003c/strong\u003eE265. https://doi.org/10.1016/j.fertnstert.2023.08.779.\u003c/li\u003e\n\u003cli\u003eMurphy A., Lapczynski M., Proctor G., Meyer, E.C., Glynn T., Domar A., Gameiro S., Palmer G., Collins M. The occupational challenges reported by UK embryologists: stress, fatigue, and burnout. \u003cem\u003eHum. Repr.\u003c/em\u003e 2023; \u003cstrong\u003e38(1)\u003c/strong\u003e\u003cstrong\u003esupplement\u003c/strong\u003e: dead093.906. https://doi.org/10.1093/humrep/dead093.906.\u003c/li\u003e\n\u003cli\u003ePalmer G., Tully B., Angle M., Sadruddin S., Howles C., Elliott T., Szvetecz S., Nagy ZP, Cohen J. Occupational demands and resultant stress of reproductive scientists: Outcomes from an international survey. \u003cem\u003eFertility \u003c/em\u003e2022, January 5\u0026ndash;8, ACC Liverpool, UK 2022.\u003c/li\u003e\n\u003cli\u003ePriddle H., Pickup S., Hayes C.; Association of Reproductive and Clinical Scientists (ARCS). Occupational health issues experienced by UK embryologists: informing improvements in clinical reproductive science practice. \u003cem\u003eHum. Fertil.\u003c/em\u003e 2022; \u003cstrong\u003e25\u003c/strong\u003e:608\u0026ndash;617. https://doi.org/10.1080/14647273.2021.1871782.\u003c/li\u003e\n\u003cli\u003eNesbit C., Blanchette Porter M., Esfandiari N. Catastrophic human error in assisted reproductive technologies: a systematic review. \u003cem\u003eJ. Patient. Saf.\u003c/em\u003e 2022; \u003cstrong\u003e18\u003c/strong\u003e: E267\u0026ndash;E274. https://doi.org/10.1097/PTS.0000000000000763. \u003c/li\u003e\n\u003cli\u003eCampbell L.D., Astrin J.J., DeSouza Y., Giri J., Patel A.A., Rawley-Payne M., Rush A., Sieffert N. The 2018 revision of the ISBER best practices: summary of changes and the editorial team\u0026apos;s development process. \u003cem\u003eBiopreserv. Biobank\u003c/em\u003e. 2018; \u003cstrong\u003e16(1)\u003c/strong\u003e:3-6. https://doi.org/10.1089/bio.2018.0001\u003c/li\u003e\n\u003cli\u003eMochida K., Hasegawa A., Li M.W., Fray M.D., Kito S., Vallelunga J.M., Lloyd K.K., Yoshiki A., Obata Y., Ogura A. High osmolality vitrification: a new method for the simple and temperature-permissive cryopreservation of mouse embryos. PLoS One. 2013; \u003cstrong\u003e8(1)\u003c/strong\u003e: E49316. https://doi.org/10.1371/journal.pone.0049316\u003c/li\u003e\n\u003cli\u003eSansinena M., Santos M.V., Taminelli G., Zaritky N. Implications of storage and handling conditions on glass transition and potential devitrification of oocytes and embryos. Theriogenology. 2014; \u003cstrong\u003e82(3)\u003c/strong\u003e:373-8. https://doi.org/10.1016/j.theriogenology.2014.04.003\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"cryostorage, automation, embryo, digital chain of custody, IVF","lastPublishedDoi":"10.21203/rs.3.rs-4189762/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4189762/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo evaluate the safety, function, and integration of a novel automated software-guided cryostorage system in an active IVF laboratory setting.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe Investigational Device (ID) was installed at 3 IVF laboratories (sites: α, β, and γ). A total of 15 embryologists were trained to use the ID. Mock patient specimens containing mirrored live patient data were handled using the ID. Temperature readings were recorded every minute. Successful identification, storage, and retrieval of patient specimens by the ID were evaluated. To assess an LN\u003csub\u003e2\u003c/sub\u003e pressure builder, the frequency of use and events of workflow interruption were logged. Student\u0026rsquo;s t-test was used to determine statistical significance.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe ID was in active use for 164 days total. During this time, 329 mock patient egg and embryo cohorts were handled by the ID. The mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD temperatures during active use were: α, -176.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83\u003csup\u003eO\u003c/sup\u003eC; β, -178.21\u0026thinsp;\u0026plusmn;\u0026thinsp;2.75\u003csup\u003eO\u003c/sup\u003eC; γ, -178.98\u0026thinsp;\u0026plusmn;\u0026thinsp;1.74 and did not differ significantly. The highest recorded temperatures were: α, -165.14\u003csup\u003eO\u003c/sup\u003eC; β, -157.41\u003csup\u003eO\u003c/sup\u003eC; γ, -164.45\u003csup\u003eO\u003c/sup\u003eC. A total of 1064 automation transactions on 409 specimen vessels were performed. Data was managed on 1501 eggs and embryos. The ID did not lose or misplace any specimen data or vessels, and no specimen was exposed to a detrimental (\u0026gt;-150\u003csup\u003eO\u003c/sup\u003eC) temperature excursion. Over the 25 LN\u003csub\u003e2\u003c/sub\u003e pressure builder usages during 99 total days, there was 1 occurrence where usage interrupted workflow due to a lack of LN\u003csub\u003e2\u003c/sub\u003e pressure.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe ID has advantages over the current manual-based cryostorage systems, including radio frequency identification (RFID) tracking, automation of manual tasks, and software guidance to ensure accurate specimen storage and retrieval. The results of this study indicate that the ID can be easily integrated into active IVF laboratories.\u003c/p\u003e","manuscriptTitle":"A Multi-Center Evaluation of a Novel IVF Cryostorage Device in an Active Clinical Setting","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-01 17:05:12","doi":"10.21203/rs.3.rs-4189762/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-21T08:03:49+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-21T01:17:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-09T11:02:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"182633d4-c747-4d11-92a8-7552e2ffaa50","date":"2024-04-27T15:50:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"46678fc2-254b-4231-abec-3b65a856f4fe","date":"2024-04-25T10:45:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-25T05:14:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-25T05:12:02+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-04-10T05:42:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-10T02:39:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-03-29T21:14:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dfeffd38-73b9-4f36-abed-ae42bf104980","owner":[],"postedDate":"April 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":30099452,"name":"Health sciences/Health occupations"},{"id":30099453,"name":"Health sciences/Health care/Occupational health"}],"tags":[],"updatedAt":"2024-08-22T19:52:07+00:00","versionOfRecord":{"articleIdentity":"rs-4189762","link":"https://doi.org/10.1038/s41598-024-69877-4","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-08-16 15:57:58","publishedOnDateReadable":"August 16th, 2024"},"versionCreatedAt":"2024-04-01 17:05:12","video":"","vorDoi":"10.1038/s41598-024-69877-4","vorDoiUrl":"https://doi.org/10.1038/s41598-024-69877-4","workflowStages":[]},"version":"v1","identity":"rs-4189762","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4189762","identity":"rs-4189762","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}