Clinical Outcome Using the Q300™ Device in a Reproductive Laboratory Environment: an open-label, non-controlled and non-randomized study

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This open-label, non-controlled, non-randomized preprint assessed usability and preliminary clinical outcomes of the Q300™ optical imaging device for sperm selection in an ART (ICSI) setting at Barzilai Medical Center, enrolling 34 couples prospectively and comparing their laboratory and pregnancy-related outcomes to a parallel control group of 42 couples treated without the device. Prepared sperm (using density gradients and swim-up) were imaged by the Q300 to verify morphological compliance with WHO 2021 criteria before microinjection, and outcomes were evaluated against Vienna Consensus ART laboratory KPIs, including fertilization, day-2/day-3 embryo development, blastulation, and pregnancy rates. The study reported improvements in day-3 embryo development, blastulation, and cumulative pregnancy rates, while the authors acknowledge a major limitation that the design was non-randomized and non-controlled and the data are preliminary. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match related to infertility/IVF outcomes rather than endometriosis-specific mechanisms.

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Clinical Outcome Using the Q300™ Device in a Reproductive Laboratory Environment: an open-label, non-controlled and non-randomized study | 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 Research Article Clinical Outcome Using the Q300™ Device in a Reproductive Laboratory Environment: an open-label, non-controlled and non-randomized study Yulia Michailov, Eden Amsalem, Natalia Umanski, Valeria Tamadaev, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6293579/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Jun, 2025 Read the published version in Reproductive Biology and Endocrinology → Version 1 posted 11 You are reading this latest preprint version Abstract Background Infertility affects a significant portion of the global population, with male factor infertility contributing to nearly half of all cases. The success of assisted reproductive technologies (ART), such as in vitro fertilization (IVF), depends on selecting high-quality sperm with optimal motility, morphology, and DNA integrity. The Q300™ device for sperm selection offers a revolutionary approach to enhancing these parameters. Utilizing an advanced optical imaging system, the Q300™ isolates the morphologically compliant sperm cells sperm for injection into the oocytes. This study aims to assess the usability and preliminary clinical outcome of the Q300™ device under "real-life conditions" in a fertility laboratory setting. Methods Preliminary clinical data collected from Barzilai Medical Center with or without using the technology was compared to the Key Performance Indicators (KPI) for ART laboratories according to the Vienna Consensus. Results The data suggests that the Q300™ significantly improved day-3 embryo development, blastulation, and cumulative pregnancy rates. Conclusions By offering a more refined and efficient selection process, the Q300™ has the potential to redefine clinical practice in infertility treatment, providing patients with a higher likelihood of achieving successful outcomes. Trial registration: NCT06232720 https://clinicaltrials.gov/study/NCT06232720 . Date of registration: 15 Feb 2023. Date of enrollment of first subject: 20 August 2023. ART OTA Sperm selection ICSI Blastocyst. BACKGROUND Infertility is a growing concern for couples worldwide, affecting millions and often leading to emotional and psychological stress [ 1 ]. While advances in reproductive medicine, such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), have provided hope to many, the success of these treatments heavily relies on selecting the healthiest sperm [ 2 – 3 ]. Traditional sperm selection methods, though effective to a degree, often lack precision in distinguishing between viable and non-viable sperm at a microscopic level. The sperm selection during ICSI is primarily based on manual and subjective morphological assessment and needs to be standardized for uniformity and concomitance between embryologists [ 4 ]. Advanced sperm selection techniques employ methods to enhance the accuracy and efficiency of selecting high-quality sperm. By focusing on key parameters such as motility, DNA integrity, and overall health, [ 5 ] these technologies aim to improve fertilization rates, embryo quality [ 6 ] and ultimately the chances of a successful pregnancy [ 3 ]. Recent breakthroughs in sperm selection technology are poised to revolutionize infertility treatment. These innovations leverage cutting-edge techniques. Magnetic-activated cell sorting (MACS) employs a column containing annexin V microbeads that bind to the phosphatidylserine that is expressed in apoptotic sperm. An absence of a beneficial effect of MACS on pregnancy was confirmed by recent studies [ 7 – 9 ]. A microfluidics system, which contains micrometer-sized channels that enable sperm preparation without the need for centrifugation, appears to improve total motile sperm count, morphology, and DNA integrity [ 10 – 12 ], although it has yielded controversial results. Some studies presented positive effects of using microfluidics on live birth rate (LBR) [ 13 ], but others failed to support this conclusion [ 14 ]. Intracytoplasmic morphologically selected sperm injection (IMSI) involves the observation and selection of sperm based on the absence of vacuoles in the sperm head using high magnification (> 6000x) [ 15 ]. The latest reviews and meta-analysis showed that IMSI does not improve LBR [ 16 – 18 ]. Emerging technologies such as artificial intelligence (AI) and machine learning have gained traction recently. These technologies can assess progressive motility parameters to aid embryologists in sperm selection without causing damage or exposing the sperm to chemical stains [ 5 – 6 ]. One of the newest techniques is the use of the Q300™ device, which is an advanced optical imaging system designed for 3D morphological analysis of individual sperm [ 19 ]. This technology employs quantitative phase microscopy and principles of holographic imaging, enabling precise 3D refractive index measurement of live and motile sperm cells [ 20 ]. The device images live and motile sperm cells intended for subsequent injection into an oocyte for fertilization in ICSI procedures and provides users with an automatic, objective, and recorded 3D morphological analysis of each individual sperm cell that the embryologist previously determined as normal and elected to inspect further. The device enables virtual staining, hence, label-free sperm visualization as if the cell were chemically stained, but without using actual staining [ 21 – 22 ]. The morphological assessment is compared in real-time to world Health organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen (WHO, 2021) criteria [ 23 ] or other established sperm-assessment criteria that the in vitro fertilization (IVF) lab may choose. While the Q300 device aids the clinical embryologist in selecting sperm cells, the embryologist can make the final decision. This intervention aims to develop superior-quality embryos and achieve a successful pregnancy and live birth. In a previous multi-center double-blind study, in which the evaluation of the sperm by the Q300™ system was compared to evaluation by chemical staining [ 24 ], the agreement between the QPM and the reference method was adequate with 85.2% sensitivity and 71.5% accuracy, however, the repeatability of the measurements was up to 10× better when using the Q300™ system [ 24 ]. Another significant study finding revealed that less than 25% of the sperm cells chosen for ICSI through manual selection met the morphological criteria suggested by WHO 2021, despite this method being the current gold standard. This assessment was conducted by the same embryologists after the cells were fixated, stained, and analyzed offline at high digital magnification. This finding highlights the importance of improving the technology and techniques to identify the best sperm cell for injection into the oocyte. This study aims to evaluate both the usability and the initial clinical outcomes associated with the Q300™ device when used under real-world conditions in a fertility laboratory setting. The assessment focuses on understanding how effectively the device can be integrated into routine laboratory workflows, as well as its potential impact on clinical outcomes in assisted reproductive technology (ART). To achieve this, preliminary clinical data was collected from Barzilai Medical Center, where ART procedures were conducted both with and without using the Q300™ device. These datasets were then analyzed and compared against established Key Performance Indicators (KPIs) for ART laboratories, as outlined in the Vienna Consensus [ 25 ]. The Vienna Consensus provides standardized benchmarks for evaluating ART laboratory performance, ensuring that the study findings are assessed in the context of internationally recognized quality metrics. By comparing clinical outcomes with and without the Q300™ device, the study aims to determine whether the technology contributes to improvements in key ART success parameters. The primary endpoints include fertilization, embryo development on day 2 and day 3, blastocyst and good blastocyst development rates. The secondary endpoint consists of pregnancy outcomes. METHODS Objectives : 34 couples intended for ICSI, meeting specific inclusion and exclusion criteria (Table 1) were prospectively enrolled from the clinic's patients. The limitations for eligibility were female age ≤ 40, availability of fresh or frozen ejaculated motile sperm, and presence of motile sperm at the time of sperm selection for ICSI. There was no restriction on the number of previous IVF/ICSI cycles per couple. Table 1: Inclusion and exclusion criteria for participant selection. Sperm Collection: Fresh semen samples were collected by masturbation after 2–5 days of abstinence . The sample was allowed to liquefy at room temperature or 37°C for 20–30 minutes . Sperm Preparation: For sperm preparation, the gradient of density and swim-up technique were used. For the gradient of density, gradient layers of 80% and 40% were used. The sample was centrifuged at 500g for 20 minutes and washed using a multipurpose handling medium (MHM). The supernatant was discarded, and the pellet was resuspended in a small volume (20–50 µL) of sperm washing medium for the swim-up. Sperm selection: Prepared sperm were transferred to a microdroplet of polyvinylpyrrolidone (PVP) solution in the ICSI dish for selection . Each sperm cell selected by the embryologist was imaged using the Q300 device before microinjection to ensure morphological compliance. Initially, sperm cells were selected based on progressive motility and morphology. These cells were then imaged by the Q300 device to assess their morphological compliance according to WHO 2021 criteria. ICSI Procedure: Selected sperm were subsequently microinjected by electrohydraulic injectors (RI Integra micromanipulator, Cooper Surgical, Cooper Surgical, USA). Non-compliant sperm cells were discarded . The ICSI procedure was performed as per standard protocols. Embryo culture and vitrification: The oocytes were cultured in an Embryoscope by using continuous single culture-NX complete medium (CSCM -NXC) (Irvine Scientific, California, USA) to the day 3 or blastocyst stage and transferred or cryopreserved by using a Kitazato vitrification kit (Kitazato, Japan) . Embryo thawing: Embryos or blastocysts were thawed using a Kitazato warming kit (Kitazato, Japan) and transferred to the CSCM- NXC dish. Embryo transfer: Embryo transfer was performed using transabdominal ultrasound guidance employing a soft transfer catheter (Wallace, Cooper Surgical, USA) . RESULTS 34 couples were recruited for the study from Barzilai Medical Center. Laboratory data collected from these 34 couples using the Q300™ was compared to the parallel results of a control group of 42 couples without using the Q300™ who met the inclusion and exclusion criteria, and was also compared to the KPIs for ART laboratories based on the Vienna Consensus (Table 2 ). The average age of females undergoing treatment was similar in both groups (33 vs. 34 years). The average number of oocytes per couple was slightly lower in the Q300™ group (7.82 vs. 8.45), but this difference was not statistically significant ( p = 0.62). There were no significant differences in sperm parameters between the groups, including sperm volume (3.04 mL vs. 3.3 mL, p = 0.53), Sperm concentration (32.2 vs. 25.45 million cells/mL, p = 0.42), and sperm motility (57.5% vs. 44.8%, p = 0.16). Among the Q300™ group, 61 sperm cells were classified as "green" (matching WHO criteria), and 205 were classified as "yellow" (borderline quality). The percentage of injected cells relative to total sperm evaluated using the Q300™ device was 40.9% (266/650) (Table 2 ). This finding highlights the difficulty of the embryologist in finding the appropriate sperm cell for the injection. Table 2 A comparison of clinical data between patients using Q300™ and patients in the control group. Parameter Q300™ Group Control Group P Value Enrolled couples 34 42 Female average age 34 33 Number of oocytes 266 355 Average number of oocytes per couple 7.82 8.45 p = 0.62 Sperm volume [mL] 3.3 (0.2–6.5) 3.04 (0.5–6.5) p = 0.53 Sperm concentration [million cells / mL] 32.2 (1.8–180) 25.45 (1.1–150) p = 0.42 Sperm motility [%] 57.5 (5-100) 44.8 (5–89) p = 0.16 Total number of sperm injected 266 355 Total number of fully-compliant (a.k.a “green”) sperms injected 61 Number of borderline compliant (a.k.a “yellow”) sperm cells injected 205 % injected cells vs. Q300™ evaluated cells 266/650 (40.9%) Fertilization and Embryo Development Rates The fertilization rate was comparable between the control group and the Q300™ group, with rates of 81.6% and 77.8%, respectively ( p = 0.65) (Vienna consensus competency: ≥ 65%) (Table 3 ). This difference was not statistically significant despite a slightly lower fertilization rate in the Q300™ group. For Day 2 embryo development, the Q300™ group exhibited a slightly higher development rate (95.5%) compared to the control group (91.3%), although the difference was not statistically significant ( p = 0.29). By Day 3, the embryo development rate showed a more pronounced improvement in the Q300™ group (91.7%) relative to the control group (84.3%), with this trend nearing statistical significance ( p = 0.05). The blastocyst development rate demonstrated a favorable trend in the Q300™ group (54.3%) compared to the control group (43.2%), though this difference was not statistically significant ( p = 0.056). Similarly, the rate of good-quality blastocyst development was slightly higher in the Q300™ group (36.9%) versus the control group (31.5%) (Vienna consensus competency: ≥ 30%), but this difference did not reach statistical significance ( p = 0.16). The usable embryo rate per couple was slightly higher in the Q300™ group (59.1%) compared to the control group (54.8%), but this difference was not statistically significant ( p = 0.20). Pregnancy Outcomes The cumulative pregnancy rate per retrieval significantly improved in the Q300™ group, reaching 65% compared to 34.1% in the control group ( p < 0.05). Table 3 Comparison of Q300™ results to control group results and KPIs for ART laboratories based on the Vienna Consensus. Parameter Q300™ Group Control Group P Value Vienna Consensus Number of injected oocytes 266 355 Total fertilization rate (total number of fertilizations per group divided by total number of oocytes injected per group) 77.8% (208/266) 81.6% (290/355) p = 0.65 ≥ 65% Day 2 embryo development rate 95.5% (173/181) 91.3% (265/290) p = 0.29 Day 3 embryo development rate 91.7% (166/181) 84.3% (232/275) p = 0.05 Blastocyst development rate 54.3% (56/103) 43.2% (48/111) p = 0.056 > 40% Good blastocyst development rate 36.9% (38/103) 31.5% (35/111) p = 0.16 > 30% Total usable embryos rate per couple (out of the number of fertilized oocytes) 59.1% (123/208) 54.8% (159/290) p = 0.2 Cumulative pregnancy rate per retrieval 65% (20/31) 34.1% (14/41) p < 0.05 Miscarriage rate (out of total pregnancies) 20% (4/20) 14% (2/14) p = 0.67 DISSCUSION Infertility impacts a considerable number of couples worldwide, with male factor infertility being a major contributor to conception difficulties [ 26 ]. ICSI is an advanced ART procedure designed to address infertility cases primarily caused by male factors [ 27 ]. This technique involves the direct injection of a single sperm into an oocyte to enhance fertilization. In cases of male-factor infertility, ICSI has been shown to increase the likelihood of successful fertilization and pregnancy significantly [ 28 ]. Research has consistently shown that sperm morphology is critical in determining fertilization and pregnancy success in ICSI procedures [ 29 ]. Standardizing traditional sperm selection methods is essential to ensure uniformity and accuracy among embryologists [ 4 ]. The integration of emerging technologies into clinical practice expands the range of tools available to fertility specialists, offering renewed hope to couples struggling with infertility. Furthermore, this innovative 3D imaging tool lays the groundwork for AI-driven sperm selection, potentially introducing new criteria and improving standardization in sperm analysis and selection. The introduction of Q300™ technology allowed for a more precise and objective assessment of sperm morphology, enabling embryologists to select the most viable sperm cells with greater accuracy than with conventional methods. This technique enhances sperm selection through virtual staining and automated evaluation of internal organelles, following WHO 2021 guidelines, without chemical staining. By prioritizing the healthiest and most viable sperm for fertilization, Q300™ technology aims to improve embryo quality and increase implantation success rates. This study included 34 couples using QART compared to 42 couples without using QART. The baseline characteristics, including female age and sperm parameters, were similar between the two groups, ensuring that outcome differences were likely attributable to the sperm selection method rather than confounding variables. A critical observation for consideration was embryologists' difficulty in manually identifying high-quality sperm for ICSI. The Q300™ device classified only 40.9% of the embryologist-selected sperm as suitable for injection, underscoring the challenge of selecting optimal sperm cells by simple embryologist observation, the current gold standard. Similar results were shown in a previous study by Michailov et al.,2023 [ 24 ]. Despite this, fertilization rates remained comparable between groups (81.6% vs. 77.8%, p = 0.65), aligning with Vienna Consensus competency benchmarks (≥ 65%). Embryo development rates exhibited positive trends in favor of the Q300™ group. Although Day 2 embryo development rates were similar between groups, Day 3 development rates were higher in the Q300™ group (91.7% vs. 84.3%, p = 0.05). Blastocyst development rates also trended favorably (54.3% vs. 43.2%, p = 0.056), suggesting a potential benefit of enhanced sperm selection on embryo quality. Likewise, the rate of good-quality blastocysts was slightly higher in the Q300™ group (36.9% vs. 31.5%), surpassing the Vienna Consensus competency threshold (≥ 30%), though not reaching statistical significance ( p = 0.16). The most striking result was the significantly improved cumulative pregnancy rate per retrieval in the Q300™ group (65% vs. 34.1%, p < 0.05). This suggests that refined sperm selection using the Q300™ technology may contribute to higher implantation success and overall pregnancy rates. The increased rate of usable embryos per couple (59.1% vs. 54.8%, p = 0.20) further supports the potential of Q300™ to enhance ART outcomes. While the results are promising, it is essential to acknowledge certain limitations. The study was conducted on a relatively small sample size, and while trends indicate potential benefits, many findings did not reach statistical significance. More extensive, multi-center trials are necessary to validate these outcomes and determine the reproducibility of Q300™ sperm selection technology in broader clinical settings. Furthermore, long-term follow-up of pregnancies and live birth outcomes will provide essential insights into the safety and efficacy of this approach. In conclusion, this study is the first to explore the impact of using a new type of sperm cell imaging and selection workstation, utilizing quantitative phase imaging to acquire and analyse the structure of live and motile human sperm cells. The Q300™ calculates WHO morphological parameters and presents them to the operator in real time, enabling objective and quantitative sperm selection during ICSI. This study was intended to provide an understanding of the practical usability and early clinical impact of using the Q300™ device in the IVF laboratory. Moreover, this study aimed to help design future, statistically powered RCTs that will further explore the impact of the Q300™ on laboratory and clinical results of ICSI procedures. The initial data suggests favourable outcomes, improving day-3 embryo development, blastocyst formation, and cumulative pregnancy rates. Further research is necessary to identify the patient subgroups that can benefit the most from this system. Additionally, validating and statistically powering the outcome measures in future studies is crucial. In the next generation of the product, incorporating an objective selection based on sperm motility may further improve its functionality. CONCLUSION This technique has the potential to improve the trends in embryo development and significantly increase pregnancy rates, thereby enhancing the success of reproductive treatments. Future research should focus on optimizing its application and evaluating its role in standardizing sperm selection criteria to improve reproductive outcomes. Abbreviations ART -assisted reproductive technologies IVF -in vitro fertilization ICSI- intracytoplasmic sperm injection KPI- Key Performance Indicators MACS- Magnetic-activated cell sorting LBR- live birth rate IMSI-Intracytoplasmic morphologically selected sperm injection AI artificial intelligence Declarations DATA AVAILABILITY The datasets generated during and/or analyzed during the current study are not publicly available but may be made available upon reasonable request to the corresponding author. ETHICS STATEMENT The studies involving humans were approved by Helsinki Committee Barzilai Medical Center. Chairman Professor Amos Katz. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. AUTHOR CONTRIBUTIONS YM: Conceptualization, Data curation, Methodology, Writing – original draft. SF: Conceptualization, Writing – review & editing. BS-R: Supervision, Writing – review & editing FUNDING The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article. ACKNOWLEDGMENTS Part of this manuscript's content has been presented at the European Society Of Human Reproduction and Embryology (ESHRE) Annual Meeting 2024. (P-043: Preliminary Clinical Outcome Using the Q300™ Device in a Reproductive Laboratory Environment). 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Cite Share Download PDF Status: Published Journal Publication published 10 Jun, 2025 Read the published version in Reproductive Biology and Endocrinology → Version 1 posted Editorial decision: Revision requested 29 Apr, 2025 Reviews received at journal 28 Apr, 2025 Reviews received at journal 26 Apr, 2025 Reviewers agreed at journal 21 Apr, 2025 Reviewers agreed at journal 18 Apr, 2025 Reviews received at journal 04 Apr, 2025 Reviewers agreed at journal 31 Mar, 2025 Reviewers invited by journal 29 Mar, 2025 Editor assigned by journal 26 Mar, 2025 Submission checks completed at journal 26 Mar, 2025 First submitted to journal 24 Mar, 2025 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. 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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-6293579","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":442027431,"identity":"2e861448-ef70-4ca0-ae31-d63a56a0a1f9","order_by":0,"name":"Yulia Michailov","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYFAC5oYDDGwSIMYBICEhQ4QWRpgWtgSQFh6itABVgxg8BmCSoAaDG4mNB36UWSRub+/5/OpGjQUPA/vhoxsIaGk42HNOInHOmbPbrHOOAR3Gk5Z2g5CWA7xtEokzJHK3GeewAbVI8JgR1HLwL1hLzjPjnH9EajkMsSWH+XFuGxFaJM88bDgsc07CeAbPMTPm3D4JHjZCfuE7nnz445uyOtkZ7M2PP+d8q5PjZz98DK8WhQMINjhCIXGED8g3INjMHwipHgWjYBSMgpEJAK6sTKzMLZvPAAAAAElFTkSuQmCC","orcid":"","institution":"Barzilai Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Yulia","middleName":"","lastName":"Michailov","suffix":""},{"id":442027432,"identity":"7cd9c3f5-9cdc-4233-92a6-f9d02ee1ba59","order_by":1,"name":"Eden Amsalem","email":"","orcid":"","institution":"Barzilai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Eden","middleName":"","lastName":"Amsalem","suffix":""},{"id":442027433,"identity":"21f201fe-824f-4f3f-ba60-c9e7a9349e21","order_by":2,"name":"Natalia Umanski","email":"","orcid":"","institution":"Barzilai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Natalia","middleName":"","lastName":"Umanski","suffix":""},{"id":442027434,"identity":"8d7b3369-9155-4d4b-90e0-13ca7cb1f2e2","order_by":3,"name":"Valeria Tamadaev","email":"","orcid":"","institution":"Barzilai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Valeria","middleName":"","lastName":"Tamadaev","suffix":""},{"id":442027435,"identity":"41ea2b7b-f02c-4e7b-b03b-d809ee7709c4","order_by":4,"name":"Shevach Friedler","email":"","orcid":"","institution":"Barzilai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Shevach","middleName":"","lastName":"Friedler","suffix":""},{"id":442027436,"identity":"20c91779-7c1e-4071-9c22-8ba2ca2d9f07","order_by":5,"name":"Bozhena Saar-Ryss","email":"","orcid":"","institution":"Barzilai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Bozhena","middleName":"","lastName":"Saar-Ryss","suffix":""}],"badges":[],"createdAt":"2025-03-24 09:08:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6293579/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6293579/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12958-025-01424-w","type":"published","date":"2025-06-10T15:57:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84726555,"identity":"4ff515aa-b5aa-4371-bf02-be7b6599e696","added_by":"auto","created_at":"2025-06-16 16:06:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":562850,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6293579/v1/f26f2e4e-d8be-4b8d-ad3f-3d42699d979d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Outcome Using the Q300™ Device in a Reproductive Laboratory Environment: an open-label, non-controlled and non-randomized study","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eInfertility is a growing concern for couples worldwide, affecting millions and often leading to emotional and psychological stress [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. While advances in reproductive medicine, such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), have provided hope to many, the success of these treatments heavily relies on selecting the healthiest sperm [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Traditional sperm selection methods, though effective to a degree, often lack precision in distinguishing between viable and non-viable sperm at a microscopic level. The sperm selection during ICSI is primarily based on manual and subjective morphological assessment and needs to be standardized for uniformity and concomitance between embryologists [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdvanced sperm selection techniques employ methods to enhance the accuracy and efficiency of selecting high-quality sperm. By focusing on key parameters such as motility, DNA integrity, and overall health, [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] these technologies aim to improve fertilization rates, embryo quality [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and ultimately the chances of a successful pregnancy [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecent breakthroughs in sperm selection technology are poised to revolutionize infertility treatment. These innovations leverage cutting-edge techniques. Magnetic-activated cell sorting (MACS) employs a column containing annexin V microbeads that bind to the phosphatidylserine that is expressed in apoptotic sperm. An absence of a beneficial effect of MACS on pregnancy was confirmed by recent studies [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA microfluidics system, which contains micrometer-sized channels that enable sperm preparation without the need for centrifugation, appears to improve total motile sperm count, morphology, and DNA integrity [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], although it has yielded controversial results. Some studies presented positive effects of using microfluidics on live birth rate (LBR) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], but others failed to support this conclusion [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIntracytoplasmic morphologically selected sperm injection (IMSI) involves the observation and selection of sperm based on the absence of vacuoles in the sperm head using high magnification (\u0026gt;\u0026thinsp;6000x) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The latest reviews and meta-analysis showed that IMSI does not improve LBR [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEmerging technologies such as artificial intelligence (AI) and machine learning have gained traction recently. These technologies can assess progressive motility parameters to aid embryologists in sperm selection without causing damage or exposing the sperm to chemical stains [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOne of the newest techniques is the use of the Q300\u0026trade; device, which is an advanced optical imaging system designed for 3D morphological analysis of individual sperm [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This technology employs quantitative phase microscopy and principles of holographic imaging, enabling precise 3D refractive index measurement of live and motile sperm cells [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The device images live and motile sperm cells intended for subsequent injection into an oocyte for fertilization in ICSI procedures and provides users with an automatic, objective, and recorded 3D morphological analysis of each individual sperm cell that the embryologist previously determined as normal and elected to inspect further. The device enables virtual staining, hence, label-free sperm visualization as if the cell were chemically stained, but without using actual staining [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The morphological assessment is compared in real-time to world Health organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen (WHO, 2021) criteria [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] or other established sperm-assessment criteria that the in vitro fertilization (IVF) lab may choose. While the Q300 device aids the clinical embryologist in selecting sperm cells, the embryologist can make the final decision. This intervention aims to develop superior-quality embryos and achieve a successful pregnancy and live birth.\u003c/p\u003e \u003cp\u003eIn a previous multi-center double-blind study, in which the evaluation of the sperm by the Q300\u0026trade; system was compared to evaluation by chemical staining [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], the agreement between the QPM and the reference method was adequate with 85.2% sensitivity and 71.5% accuracy, however, the repeatability of the measurements was up to 10\u0026times; better when using the Q300\u0026trade; system [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Another significant study finding revealed that less than 25% of the sperm cells chosen for ICSI through manual selection met the morphological criteria suggested by WHO 2021, despite this method being the current gold standard. This assessment was conducted by the same embryologists after the cells were fixated, stained, and analyzed offline at high digital magnification. This finding highlights the importance of improving the technology and techniques to identify the best sperm cell for injection into the oocyte.\u003c/p\u003e \u003cp\u003eThis study aims to evaluate both the usability and the initial clinical outcomes associated with the Q300\u0026trade; device when used under real-world conditions in a fertility laboratory setting. The assessment focuses on understanding how effectively the device can be integrated into routine laboratory workflows, as well as its potential impact on clinical outcomes in assisted reproductive technology (ART).\u003c/p\u003e \u003cp\u003eTo achieve this, preliminary clinical data was collected from Barzilai Medical Center, where ART procedures were conducted both with and without using the Q300\u0026trade; device. These datasets were then analyzed and compared against established Key Performance Indicators (KPIs) for ART laboratories, as outlined in the Vienna Consensus [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The Vienna Consensus provides standardized benchmarks for evaluating ART laboratory performance, ensuring that the study findings are assessed in the context of internationally recognized quality metrics.\u003c/p\u003e \u003cp\u003eBy comparing clinical outcomes with and without the Q300\u0026trade; device, the study aims to determine whether the technology contributes to improvements in key ART success parameters. The primary endpoints include fertilization, embryo development on day 2 and day 3, blastocyst and good blastocyst development rates. The secondary endpoint consists of pregnancy outcomes.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cu\u003eObjectives\u003c/u\u003e: 34 couples intended for ICSI, meeting specific inclusion and exclusion criteria (Table 1) were prospectively enrolled from the clinic\u0026apos;s patients. The limitations for eligibility were female age \u0026le; 40, availability of fresh or frozen ejaculated motile sperm, and presence of motile sperm at the time of sperm selection for ICSI. There was no restriction on the number of previous IVF/ICSI cycles per couple.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003eInclusion and exclusion criteria for participant selection.\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" style=\"width: 816px; height: 440.622px;\" width=\"816\" height=\"440.622\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eSperm Collection:\u003c/u\u003e Fresh semen samples were collected by masturbation after 2\u0026ndash;5 days of abstinence\u003cspan dir=\"RTL\"\u003e.\u0026nbsp;\u003c/span\u003eThe sample was allowed to liquefy at room temperature or 37\u0026deg;C for 20\u0026ndash;30 minutes\u003cspan dir=\"RTL\"\u003e.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eSperm Preparation:\u003c/u\u003e For sperm preparation, the gradient of density and swim-up technique were used. \u0026nbsp;For the gradient of density, gradient layers of 80% and 40% were used. The sample was centrifuged at 500g for 20 minutes and washed using a multipurpose handling medium (MHM). The supernatant was discarded, and the pellet was resuspended in a small volume (20\u0026ndash;50 \u0026micro;L) of sperm washing medium for the swim-up.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eSperm selection:\u003c/u\u003e Prepared sperm were transferred to a microdroplet of polyvinylpyrrolidone (PVP) solution in the ICSI dish for selection\u003cspan dir=\"RTL\"\u003e.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eEach sperm cell selected by the embryologist was imaged using the Q300 device before microinjection to ensure morphological compliance. Initially, sperm cells were selected based on progressive motility and morphology. These cells were then imaged by the Q300 device to assess their morphological compliance according to WHO 2021 criteria.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eICSI Procedure:\u003c/u\u003e Selected sperm were subsequently microinjected by electrohydraulic injectors (RI Integra micromanipulator, Cooper Surgical, Cooper Surgical, USA). Non-compliant sperm cells were discarded\u003cspan dir=\"RTL\"\u003e.\u003c/span\u003e The ICSI procedure was performed as per standard protocols.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eEmbryo culture and vitrification:\u003c/u\u003e The oocytes were cultured in an Embryoscope by using continuous single culture-NX complete medium (CSCM -NXC) (Irvine Scientific, California, USA) to the day 3 or blastocyst stage and transferred or cryopreserved by using a Kitazato vitrification kit (Kitazato, Japan)\u003cspan dir=\"RTL\"\u003e.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eEmbryo thawing:\u003c/u\u003e Embryos or blastocysts were thawed using a Kitazato warming kit (Kitazato, Japan) and transferred to the CSCM- NXC dish.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eEmbryo transfer:\u003c/u\u003e Embryo transfer was performed using transabdominal ultrasound guidance employing a soft transfer catheter (Wallace, Cooper Surgical, USA)\u003cspan dir=\"RTL\"\u003e.\u003c/span\u003e\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e34 couples were recruited for the study from Barzilai Medical Center. Laboratory data collected from these 34 couples using the Q300\u0026trade; was compared to the parallel results of a control group of 42 couples without using the Q300\u0026trade; who met the inclusion and exclusion criteria, and was also compared to the KPIs for ART laboratories based on the Vienna Consensus (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe average age of females undergoing treatment was similar in both groups (33 vs. 34 years).\u003c/p\u003e \u003cp\u003eThe average number of oocytes per couple was slightly lower in the Q300\u0026trade; group (7.82 vs. 8.45), but this difference was not statistically significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.62).\u003c/p\u003e \u003cp\u003eThere were no significant differences in sperm parameters between the groups, including sperm volume (3.04 mL vs. 3.3 mL, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.53), Sperm concentration (32.2 vs. 25.45\u0026nbsp;million cells/mL, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.42), and sperm motility (57.5% vs. 44.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.16).\u003c/p\u003e \u003cp\u003eAmong the Q300\u0026trade; group, 61 sperm cells were classified as \"green\" (matching WHO criteria), and 205 were classified as \"yellow\" (borderline quality).\u003c/p\u003e \u003cp\u003eThe percentage of injected cells relative to total sperm evaluated using the Q300\u0026trade; device was 40.9% (266/650) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This finding highlights the difficulty of the embryologist in finding the appropriate sperm cell for the injection.\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\u003eA comparison of clinical data between patients using Q300\u0026trade; and patients in the control group.\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\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQ300\u0026trade; Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnrolled couples\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale average age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of oocytes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e355\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage number of oocytes per couple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSperm volume [mL]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003cp\u003e(0.2\u0026ndash;6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.04\u003c/p\u003e \u003cp\u003e(0.5\u0026ndash;6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSperm concentration\u003c/p\u003e \u003cp\u003e[million cells / mL]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.2\u003c/p\u003e \u003cp\u003e(1.8\u0026ndash;180)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.45\u003c/p\u003e \u003cp\u003e(1.1\u0026ndash;150)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSperm motility [%]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.5\u003c/p\u003e \u003cp\u003e(5-100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.8\u003c/p\u003e \u003cp\u003e(5\u0026ndash;89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal number of sperm injected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e355\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal number of fully-compliant (a.k.a \u0026ldquo;green\u0026rdquo;) sperms injected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of borderline compliant (a.k.a \u0026ldquo;yellow\u0026rdquo;) sperm cells injected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e% injected cells vs. Q300\u0026trade; evaluated cells\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e266/650 (40.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eFertilization and Embryo Development Rates\u003c/h3\u003e\n\u003cp\u003eThe fertilization rate was comparable between the control group and the Q300\u0026trade; group, with rates of 81.6% and 77.8%, respectively (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.65) (Vienna consensus competency: \u0026ge; 65%) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). This difference was not statistically significant despite a slightly lower fertilization rate in the Q300\u0026trade; group.\u003c/p\u003e \u003cp\u003eFor Day 2 embryo development, the Q300\u0026trade; group exhibited a slightly higher development rate (95.5%) compared to the control group (91.3%), although the difference was not statistically significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.29). By Day 3, the embryo development rate showed a more pronounced improvement in the Q300\u0026trade; group (91.7%) relative to the control group (84.3%), with this trend nearing statistical significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eThe blastocyst development rate demonstrated a favorable trend in the Q300\u0026trade; group (54.3%) compared to the control group (43.2%), though this difference was not statistically significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.056). Similarly, the rate of good-quality blastocyst development was slightly higher in the Q300\u0026trade; group (36.9%) versus the control group (31.5%) (Vienna consensus competency: \u0026ge; 30%), but this difference did not reach statistical significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.16).\u003c/p\u003e \u003cp\u003eThe usable embryo rate per couple was slightly higher in the Q300\u0026trade; group (59.1%) compared to the control group (54.8%), but this difference was not statistically significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.20).\u003c/p\u003e\n\u003ch3\u003ePregnancy Outcomes\u003c/h3\u003e\n\u003cp\u003eThe cumulative pregnancy rate per retrieval significantly improved in the Q300\u0026trade; group, reaching 65% compared to 34.1% in the control group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Q300\u0026trade; results to control group results and KPIs for ART laboratories based on the Vienna Consensus.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQ300\u0026trade; Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVienna Consensus\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of injected oocytes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e355\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal fertilization rate (total number of fertilizations per group divided by total number of oocytes injected per group)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77.8%\u003c/p\u003e \u003cp\u003e(208/266)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81.6%\u003c/p\u003e \u003cp\u003e(290/355)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay 2 embryo development rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95.5%\u003c/p\u003e \u003cp\u003e(173/181)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91.3%\u003c/p\u003e \u003cp\u003e(265/290)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay 3 embryo development rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91.7%\u003c/p\u003e \u003cp\u003e(166/181)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84.3%\u003c/p\u003e \u003cp\u003e(232/275)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlastocyst development rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.3%\u003c/p\u003e \u003cp\u003e(56/103)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.2%\u003c/p\u003e \u003cp\u003e(48/111)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.056\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;40%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGood blastocyst development rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.9%\u003c/p\u003e \u003cp\u003e(38/103)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.5%\u003c/p\u003e \u003cp\u003e(35/111)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;30%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal usable embryos rate per couple (out of the number of fertilized oocytes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.1%\u003c/p\u003e \u003cp\u003e(123/208)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.8%\u003c/p\u003e \u003cp\u003e(159/290)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCumulative pregnancy rate per retrieval\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65% (20/31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.1% (14/41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiscarriage rate (out of total pregnancies)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20% (4/20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14% (2/14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"DISSCUSION","content":"\u003cp\u003eInfertility impacts a considerable number of couples worldwide, with male factor infertility being a major contributor to conception difficulties [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. ICSI is an advanced ART procedure designed to address infertility cases primarily caused by male factors [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. This technique involves the direct injection of a single sperm into an oocyte to enhance fertilization. In cases of male-factor infertility, ICSI has been shown to increase the likelihood of successful fertilization and pregnancy significantly [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eResearch has consistently shown that sperm morphology is critical in determining fertilization and pregnancy success in ICSI procedures [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Standardizing traditional sperm selection methods is essential to ensure uniformity and accuracy among embryologists [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The integration of emerging technologies into clinical practice expands the range of tools available to fertility specialists, offering renewed hope to couples struggling with infertility. Furthermore, this innovative 3D imaging tool lays the groundwork for AI-driven sperm selection, potentially introducing new criteria and improving standardization in sperm analysis and selection.\u003c/p\u003e \u003cp\u003eThe introduction of Q300\u0026trade; technology allowed for a more precise and objective assessment of sperm morphology, enabling embryologists to select the most viable sperm cells with greater accuracy than with conventional methods. This technique enhances sperm selection through virtual staining and automated evaluation of internal organelles, following WHO 2021 guidelines, without chemical staining. By prioritizing the healthiest and most viable sperm for fertilization, Q300\u0026trade; technology aims to improve embryo quality and increase implantation success rates.\u003c/p\u003e \u003cp\u003eThis study included 34 couples using QART compared to 42 couples without using QART. The baseline characteristics, including female age and sperm parameters, were similar between the two groups, ensuring that outcome differences were likely attributable to the sperm selection method rather than confounding variables.\u003c/p\u003e \u003cp\u003eA critical observation for consideration was embryologists' difficulty in manually identifying high-quality sperm for ICSI. The Q300\u0026trade; device classified only 40.9% of the embryologist-selected sperm as suitable for injection, underscoring the challenge of selecting optimal sperm cells by simple embryologist observation, the current gold standard. Similar results were shown in a previous study by Michailov et al.,2023 [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Despite this, fertilization rates remained comparable between groups (81.6% vs. 77.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.65), aligning with Vienna Consensus competency benchmarks (\u0026ge;\u0026thinsp;65%).\u003c/p\u003e \u003cp\u003eEmbryo development rates exhibited positive trends in favor of the Q300\u0026trade; group. Although Day 2 embryo development rates were similar between groups, Day 3 development rates were higher in the Q300\u0026trade; group (91.7% vs. 84.3%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05). Blastocyst development rates also trended favorably (54.3% vs. 43.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.056), suggesting a potential benefit of enhanced sperm selection on embryo quality. Likewise, the rate of good-quality blastocysts was slightly higher in the Q300\u0026trade; group (36.9% vs. 31.5%), surpassing the Vienna Consensus competency threshold (\u0026ge;\u0026thinsp;30%), though not reaching statistical significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.16).\u003c/p\u003e \u003cp\u003eThe most striking result was the significantly improved cumulative pregnancy rate per retrieval in the Q300\u0026trade; group (65% vs. 34.1%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). This suggests that refined sperm selection using the Q300\u0026trade; technology may contribute to higher implantation success and overall pregnancy rates. The increased rate of usable embryos per couple (59.1% vs. 54.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.20) further supports the potential of Q300\u0026trade; to enhance ART outcomes.\u003c/p\u003e \u003cp\u003eWhile the results are promising, it is essential to acknowledge certain limitations. The study was conducted on a relatively small sample size, and while trends indicate potential benefits, many findings did not reach statistical significance. More extensive, multi-center trials are necessary to validate these outcomes and determine the reproducibility of Q300\u0026trade; sperm selection technology in broader clinical settings. Furthermore, long-term follow-up of pregnancies and live birth outcomes will provide essential insights into the safety and efficacy of this approach.\u003c/p\u003e \u003cp\u003eIn conclusion, this study is the first to explore the impact of using a new type of sperm cell imaging and selection workstation, utilizing quantitative phase imaging to acquire and analyse the structure of live and motile human sperm cells. The Q300\u0026trade; calculates WHO morphological parameters and presents them to the operator in real time, enabling objective and quantitative sperm selection during ICSI.\u003c/p\u003e \u003cp\u003eThis study was intended to provide an understanding of the practical usability and early clinical impact of using the Q300\u0026trade; device in the IVF laboratory. Moreover, this study aimed to help design future, statistically powered RCTs that will further explore the impact of the Q300\u0026trade; on laboratory and clinical results of ICSI procedures. The initial data suggests favourable outcomes, improving day-3 embryo development, blastocyst formation, and cumulative pregnancy rates. Further research is necessary to identify the patient subgroups that can benefit the most from this system. Additionally, validating and statistically powering the outcome measures in future studies is crucial. In the next generation of the product, incorporating an objective selection based on sperm motility may further improve its functionality.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis technique has the potential to improve the trends in embryo development and significantly increase pregnancy rates, thereby enhancing the success of reproductive treatments. Future research should focus on optimizing its application and evaluating its role in standardizing sperm selection criteria to improve reproductive outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eART -assisted reproductive technologies\u003c/p\u003e\n\u003cp\u003eIVF -in vitro fertilization\u003c/p\u003e\n\u003cp\u003eICSI- intracytoplasmic sperm injection\u003c/p\u003e\n\u003cp\u003eKPI- Key Performance Indicators\u003c/p\u003e\n\u003cp\u003eMACS- Magnetic-activated cell sorting\u003c/p\u003e\n\u003cp\u003eLBR- live birth rate\u003c/p\u003e\n\u003cp\u003eIMSI-Intracytoplasmic morphologically selected sperm injection\u003c/p\u003e\n\u003cp\u003eAI artificial intelligence\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eDATA AVAILABILITY\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are not publicly available but may be made available upon reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003eETHICS STATEMENT\u003c/p\u003e\n\u003cp\u003eThe studies involving humans were approved by Helsinki Committee Barzilai Medical Center. Chairman Professor Amos Katz. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.\u003c/p\u003e\n\u003cp\u003eAUTHOR CONTRIBUTIONS\u003c/p\u003e\n\u003cp\u003eYM: Conceptualization, Data curation, Methodology, Writing – original draft. SF: Conceptualization, Writing – review \u0026amp; editing. BS-R: Supervision, Writing – review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eFUNDING\u003c/p\u003e\n\u003cp\u003eThe author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003eACKNOWLEDGMENTS\u003c/p\u003e\n\u003cp\u003ePart of this manuscript's content has been presented at the European Society Of Human Reproduction and Embryology (ESHRE) Annual Meeting 2024. (P-043: Preliminary Clinical Outcome Using the Q300™ Device in a Reproductive Laboratory Environment).\u003c/p\u003e\n\u003cp\u003eCONFLICT OF INTEREST\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBraverman AM, Davoudian T, Levin IK, Bocage A, Wodoslawsky S. Depression, anxiety, quality of life, and infertility: a global lens on the last decade of research. Fertil Steril. 2024;121(3):379\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaldini D, Ferri D, Baldini GM, Lot D, Catino A, Vizziello D, Vizziello G. Sperm Selection for ICSI: Do We Have a Winner? Cells. 2021;17(12):3566.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCariati F, Orsi MG, Bagnulo F, Del Mondo D, Vigilante L, De Rosa M, Sciorio R, Conforti A, Fleming S, Alviggi C. Advanced Sperm Selection Techniques for Assisted Reproduction. J Pers Med. 2024;4(7):726.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgarwal A, Sharma R, Gupta S, Finelli R, Parekh N, Panner Selvam MK, Henkel R, Durairajanayagam D, Pompeu C, Madani S, et al. Sperm Morphology assessment in the era of intracytoplasmic sperm injection: Reliable results require focus on standardization, quality control, and training. World J Men\u0026rsquo;s Health. 2022;40:347\u0026ndash;60. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5534/wjmh.210054\u003c/span\u003e\u003cspan address=\"10.5534/wjmh.210054\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVaughan DA, Sakkas D. Sperm selection methods in the 21st century. In Gardner DK, editor. Biol Reprod, 2019;101:1076\u0026ndash;1082.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMendizabal-Ruiz G, Chavez-Badiola A, Aguilar Figueroa I, Martinez Nu\u0026ntilde;o V, Flores-Saiffe Farias A, Valencia-Murilloa R, Drakeley A, Garcia-Sandoval JP, Cohen J. Computer software (SiD) assisted real-time single sperm selection associated with fertilization and blastocyst formation. Reprod Biomed Online. 2022;45:703\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLepine S, McDowell S, Searle LM, Kroon B, Glujovsky D, Yazdani A. Advanced sperm selection techniques for assisted reproduction. Cochrane Database Syst Rev. 2019;7:Cd010461.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGil JM, Herv\u0026aacute;s I, Navarro-Gomezlechon A, Quintana F, Amor\u0026oacute;s D, Pacheco A, Gonz\u0026aacute;lez-Ravina C, Rivera-Egea R, Garrido N. Cumulative live birth rates in donor oocyte ICSI cycles are not improved by magnetic-activated cell sorting sperm selection. Reprod biomed online. 2022;44:677\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNorozi-Hafshejani M, Tavalaee M, Najafi MH, Shapour F, Arbabian M, Nasr-Esfahani MH. MACS-DGC versus DGC Sperm Wash Procedure: Comparing Clinical Outcomes in Couples with Male Factor Infertility Undergoing ICSI: A Clinical Trial Study. Fertil Steril. 2022;16:17\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGode F, Bodur T, Gunturkun F, Gurbuz AS, Tamer B, Pala I, Isik AZ. Comparison of microfluid sperm sorting chip and density gradient methods for use in intrauterine insemination cycles. Fertil Steril. 2019;112:842\u0026ndash;e848841.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGode F, G\u0026uuml;rb\u0026uuml;z AS, Tamer B, Pala I, Isik AZ. The Effects of Microfluidic Sperm Sorting, Density Gradient and Swim up Methods on Semen Oxidation Reduction Potential. Urol J. 2020;17:397\u0026ndash;401.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQuinn MM, Jalalian L, Ribeiro S, Ona K, Demirci U, Cedars MI, Rosen MP. Microfluidic sorting selects sperm for clinical use with reduced DNA damage compared to density gradient centrifugation with swim-up in split semen samples. Hum Reprod. 2018;33:1388\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAydın Ş, Bulgan Kılı\u0026ccedil;dağ E, \u0026Ccedil;ağlar Ayta\u0026ccedil; P, \u0026Ccedil;ok T, Şimşek E, Haydardedeoğlu B. Prospective randomized controlled study of a microfluidic chip technology for sperm selection in male infertility patients. Andrologia. 2022;54:e14415.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSrinivas S, Donthi S, Mettler AD, Tolani AD, Deenadayal M. Does Choosing Microfluidics for Sperm Sorting Offer an Advantage to Improve Clinical Pregnancies in Donor Egg Recipients? J Hum Reprod Scien. 2022;15:143\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBartoov B, Berkovitz A, Eltes F. Selection of spermatozoa with normal nuclei to improve the pregnancy rate with intracytoplasmic sperm injection. New Eng J Med. 2001;345:1067\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTeixeira DM, Hadyme Miyague A, Barbosa MA, Navarro PA, Raine-Fenning N, Nastri CO, Martins WP. Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction. Coc Dat Syst Rev. 2020;2:Cd010167.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuran-Retamal M, Morris G, Achilli C, Gaunt M, Theodorou E, Saab W, Serhal P, Seshadri S. Live birth and miscarriage rate following intracytoplasmic morphologically selected sperm injection vs intracytoplasmic sperm injection: An updated systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2020;99:24\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcDowell S, Kroon B, Ford E, Hook Y, Glujovsky D, Yazdani A. Advanced sperm selection techniques for assisted reproduction. The Coc Dat of System Rev.2014: Cd010461.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarnea I, Karako L, Mirsky SK, Levi M, Balberg M, Shaked NT. Stain-free interferometric phase microscopy correlation with DNA fragmentation stain in human spermatozoa. J Biophotonics. 2018;11:e201800137.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDardikman G, Mirksy S, Barnea I, Shaked NT. High-resolution 4-D acquisition of freely swimming human sperm cells without staining. Sci Adv. 2020;6:14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNygate YN, Levi M, Mirsky SK, Turko NA, Rubin M, Barnea I, Dardikman-Yoffe G, Haifler M, Shalev A, Shaked NT. Holographic virtual staining of individual biological cells. Proc Natl Acad Sci. 2020;117:9223\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBen-Yehuda K, Mirsky SK, Levi M, Barnea I, Meshulach I, Kontente S, Benvaish D, Cur-Cycowicz R, Nygate YN, Shaked NT. Simultaneous morphology, motility, and fragmentation analysis of live individual sperm cells for male fertility evaluation. Adv Intell Syst. 2022;4:2100200.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 6th ed. WHO Press; Geneva, Switzerland. 2021. (accessed on 3 December 2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichailov Y, Nemerovsky L, Ghetler Y, Finkelstein M, Schonberger O, Wiser A, Raziel A, Saar-Ryss B, et al. Stain-Free Sperm Analysis and Selection for Intracytoplasmic Sperm Injection Complying with WHO Strict Normal Criteria. Biomedicines. 2023;23(10):11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine. The Vienna consensus: report of an expert meeting on the development of ART laboratory performance indicators. RBMO. 2017;35(5):494\u0026ndash;510.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEisenberg ML, Esteves SC, Lamb DJ, Hotaling JM, Giwercman A, Hwang K. Cheng YS Male infertility. Nat Rev Dis Primers. 2023;14(1):49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e[27] Palermo G. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992;340:17\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO\u0026rsquo;Neill CL, Chow S, Rosenwaks Z, Palermo GD. Development of ICSI. Reproduction. 2018;156:F51\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGiudice F, Del, Belladelli F, Chen T, Glover F, Mulloy EA, Kasman AM, et al. The association of impaired semen quality and pregnancy rates in assisted reproduction technology cycles: Systematic review and meta-analysis. Andrologia [Internet]. 2022;54(6):e14409.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"reproductive-biology-and-endocrinology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"rbej","sideBox":"Learn more about [Reproductive Biology and Endocrinology](http://rbej.biomedcentral.com)","snPcode":"12958","submissionUrl":"https://submission.nature.com/new-submission/12958/3","title":"Reproductive Biology and Endocrinology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"ART, OTA, Sperm selection, ICSI, Blastocyst.","lastPublishedDoi":"10.21203/rs.3.rs-6293579/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6293579/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eInfertility affects a significant portion of the global population, with male factor infertility contributing to nearly half of all cases. The success of assisted reproductive technologies (ART), such as in vitro fertilization (IVF), depends on selecting high-quality sperm with optimal motility, morphology, and DNA integrity. The Q300\u0026trade; device for sperm selection offers a revolutionary approach to enhancing these parameters. Utilizing an advanced optical imaging system, the Q300\u0026trade; isolates the morphologically compliant sperm cells sperm for injection into the oocytes. This study aims to assess the usability and preliminary clinical outcome of the Q300\u0026trade; device under \"real-life conditions\" in a fertility laboratory setting.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePreliminary clinical data collected from Barzilai Medical Center with or without using the technology was compared to the Key Performance Indicators (KPI) for ART laboratories according to the Vienna Consensus.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe data suggests that the Q300\u0026trade; significantly improved day-3 embryo development, blastulation, and cumulative pregnancy rates.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eBy offering a more refined and efficient selection process, the Q300\u0026trade; has the potential to redefine clinical practice in infertility treatment, providing patients with a higher likelihood of achieving successful outcomes.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003eNCT06232720 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://clinicaltrials.gov/study/NCT06232720\u003c/span\u003e\u003cspan address=\"https://clinicaltrials.gov/study/NCT06232720\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Date of registration: 15 Feb 2023. 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