{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:16:54Z","timestamp":1792718214557,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>This study aimed to compare sperm parameters and reproductive outcomes after sperm selection using microfluidic chips versus conventional techniques (swim-up\/density gradients). A systematic review and meta-analysis were performed after the extraction of relevant data from thirty-nine studies that met the inclusion criteria. Mean difference or odds ratio was calculated for each outcome. The analysis revealed that sperm selection using microfluidics yields lower sperm DNA fragmentation (MD = \u22129.98 [\u221213.19, \u22126.76], p &lt; 0.00001), increased progressive motility (MD = 14.50 [7.84, 21.71], p = 0.04), total motility (MD = 10.68 [6.04, 15.31], p &lt; 0.00001) and morphology (MD = 1.41 [0.67, 2.16], p = 0.0002). Significant differences were also found in the fertilization rate\/MII oocyte microinjected (OR = 1.22 [1.01, 1.46], p = 0.04), implantation rate\/embryo transfer (ET) (OR = 4.51 [1.42, 14.37], p = 0.01), clinical pregnancy\/ET (OR = 1.73 [1.22, 2.45], p = 0.002), ongoing pregnancy\/ET (OR = 1.99 [1.03, 3.83], p = 0.04), live birth rate\/first cycle (OR = 1.59 [1.12, 2.24], p = 0.009) and per all embryo transfer (OR = 1.65 [1.06, 2.55], p = 0.03). No significant differences were found in embryo euploidy\/number of biopsied blastocysts (OR = 1.34 [0.88, 2.04], p = 0.77), biochemical pregnancy\/ET (OR = 1.23 [0.84, 1.80], p = 0.29), miscarriage rate\/cycle (OR = 0.84 [0.54, 1.31], p = 0.35) and per pregnancy (OR = 0.71 [0.50, 1.02], p = 0.07), live birth rate\/first embryo transfer (OR = 1.60 [0.80, 3.22], p = 0.18) and per concluded cycle (OR = 1.03 [0.53, 2.00], p = 0.92). To summarize, microfluidics may offer a beneficial approach in certain situations, particularly for patients with elevated sperm DNA fragmentation (SDF) levels. However, its integration into routine clinical practice cannot be justified yet in terms of cost-effectiveness. Additional research is needed to provide more comprehensive data on reproductive outcomes, especially live birth rates, which remain the ultimate goal of assisted reproductive technologies.<\/jats:p>","DOI":"10.3390\/biology14070792","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T10:45:08Z","timestamp":1751366708000},"page":"792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Sperm Selection Using Microfluidic Techniques Significantly Decreases Sperm DNA Fragmentation (SDF), Enhancing Reproductive Outcomes: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7648-2585","authenticated-orcid":false,"given":"Alma","family":"Gisbert Iranzo","sequence":"first","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), Avenida Fernando Abril Martorell, 106\u2014Torre A, Planta 1\u00aa, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2905-922X","authenticated-orcid":false,"given":"Marina","family":"Cano-Extremera","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), Avenida Fernando Abril Martorell, 106\u2014Torre A, Planta 1\u00aa, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Herv\u00e1s","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), Avenida Fernando Abril Martorell, 106\u2014Torre A, Planta 1\u00aa, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Falquet Guillem","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), Avenida Fernando Abril Martorell, 106\u2014Torre A, Planta 1\u00aa, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Gil Juli\u00e1","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), Avenida Fernando Abril Martorell, 106\u2014Torre A, Planta 1\u00aa, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1687-1279","authenticated-orcid":false,"given":"Ana","family":"Navarro-Gomezlechon","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), Avenida Fernando Abril Martorell, 106\u2014Torre A, Planta 1\u00aa, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Mar\u00eda","family":"Pacheco-Rend\u00f3n","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), Avenida Fernando Abril Martorell, 106\u2014Torre A, Planta 1\u00aa, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8271-5218","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Garrido","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), Avenida Fernando Abril Martorell, 106\u2014Torre A, Planta 1\u00aa, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e188","DOI":"10.1016\/j.fertnstert.2021.07.516","article-title":"Comparison of Microfluidic Sperm Sorting (Mfss) versus Physiological Intracytoplasmic Sperm Injection (Picsi) Versus Density Gradient in High DNA Fragmentation Index Sperm Samples","volume":"116","author":"Nayar","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.ijgo.2013.09.005","article-title":"The changing prevalence of infertility","volume":"123","author":"Petraglia","year":"2013","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Huang, J.Y.J., and Rosenwaks, Z. (2014). Assisted reproductive techniques. Human Fertility: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-4939-0659-8_8"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e137","DOI":"10.1016\/j.fertnstert.2021.07.380","article-title":"A Sperm Selection Technique to Improve Embryo Ploidy","volume":"116","author":"Keating","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1017\/S0967199421000484","article-title":"A microfluidic sperm-sorting device reduces the proportion of sperm with double-stranded DNA fragmentation","volume":"30","author":"Pujol","year":"2022","journal-title":"Zygote"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/andr.12724","article-title":"An update on clinical and surgical interventions to reduce sperm DNA fragmentation in infertile men","volume":"8","author":"Esteves","year":"2020","journal-title":"Andrology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s10815-013-9962-8","article-title":"Sperm selection using magnetic activated cell sorting (MACS) in assisted reproduction: A systematic review and meta-analysis","volume":"30","author":"Gil","year":"2013","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e296","DOI":"10.1016\/j.fertnstert.2023.08.862","article-title":"Live Birth Rate After Using Microfluidic Sperm Separation Device for Sperm Preparation in All In-Vitro Fertilization (Ivf) and Intracytoplasmic Sperm Injection (Icsi) Cycles","volume":"120","author":"Kothamasu","year":"2023","journal-title":"Fertil. Steril."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"ESHRE Add-ons Working Group, Lundin, K., Bentzen, J.G., Bozdag, G., Ebner, T., Harper, J., Le Clef, N., Moffett, A., Norcross, S., and Polyzos, N.P. (2023). Good practice recommendations on add-ons in reproductive medicine. Hum. Reprod., 38, 2062\u20132104.","DOI":"10.1093\/humrep\/dead184"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00404-022-06618-w","article-title":"Microfluidic chips as a method for sperm selection improve fertilization rate in couples with fertilization failure","volume":"306","author":"Mirsanei","year":"2022","journal-title":"Arch. Gynecol. Obs."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1007\/s10815-019-01543-5","article-title":"A treatment approach for couples with disrupted sperm DNA integrity and recurrent ART failure","volume":"36","author":"Parrella","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_12","first-page":"QC14","article-title":"Frequency of sperm DNA fragmentation according to selection method: Comparison and relevance of a microfluidic device and a swim-up procedure","volume":"9","author":"Kishi","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e294","DOI":"10.1016\/j.fertnstert.2023.08.857","article-title":"Microfluidic-Based Sperm Selection: Effect on Sperm DNA Fragmentation and Embryo Development","volume":"120","author":"Bastida","year":"2023","journal-title":"Fertil. Steril."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1093\/humrep\/deac099","article-title":"Microfluidic preparation of spermatozoa for ICSI produces similar embryo quality to density-gradient centrifugation: A pragmatic, randomized controlled trial","volume":"37","author":"Quinn","year":"2022","journal-title":"Hum. Reprod."},{"key":"ref_15","unstructured":"Review Manager (RevMan) (2024, March 12). Version 5.4. The Cochrane Collaboration, 2020. Available online: https:\/\/revman.cochrane.org\/."},{"key":"ref_16","first-page":"e13403","article-title":"Does a microfluidic chip for sperm sorting have a positive add-on effect on laboratory and clinical outcomes of intracytoplasmic sperm injection cycles? A sibling oocyte study","volume":"51","author":"Okan","year":"2019","journal-title":"Andrologia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4919","DOI":"10.1136\/bmj.i4919","article-title":"ROBINS-I: A tool for assessing risk of bias in non-randomized studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1080\/19396368.2020.1837994","article-title":"Microfluidic sperm selection yields higher sperm quality compared to conventional method in ICSI program: A pilot study","volume":"67","author":"Anbari","year":"2021","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e14623","DOI":"10.1111\/and.14623","article-title":"Microfluidic devices employing chemo- and thermotaxis for sperm selection can improve sperm parameters and function in patients with high DNA fragmentation","volume":"54","author":"Doostabadi","year":"2022","journal-title":"Andrologia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.fertnstert.2019.06.037","article-title":"Comparison of microfluid sperm sorting chip and density gradient methods for use in intrauterine insemination cycles","volume":"112","author":"Gode","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_23","first-page":"397","article-title":"The effects of microfluidic sperm sorting, density gradient and swim-up methods on semen oxidation reduction potential","volume":"17","author":"Gode","year":"2020","journal-title":"Urol. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.fertnstert.2024.02.021","article-title":"The impact of microfluidics sperm processing on blastocyst euploidy rates compared with density gradient centrifugation: A sibling oocyte double-blinded prospective randomized clinical trial","volume":"122","author":"Godiwala","year":"2024","journal-title":"Fertil. Steril."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1016\/j.fertnstert.2023.08.379","article-title":"MICROFLUIDIC SELECTION ENHANCES CRYOSURVIVAL OF SPERMATOZOA","volume":"120","author":"Kocur","year":"2023","journal-title":"Fertil. Steril."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e126","DOI":"10.1016\/j.fertnstert.2020.08.375","article-title":"Uperior Sperm Selection? Microfluidic Sperm Sorting Improves Euploid Embryo Ongoing Pregnancy Rate Compared to Density Gradient Centrifugation","volume":"114","author":"Palmerola","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1093\/humrep\/deae045","article-title":"Microfluidic sperm sorting selects a subpopulation of high-quality sperm with a higher potential for fertilization","volume":"39","author":"Sheibak","year":"2024","journal-title":"Hum. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1007\/s10815-022-02504-1","article-title":"Embryologic outcomes among patients using a microfluidics chip compared to density gradient centrifugation to process sperm: A paired analysis","volume":"39","author":"Godiwala","year":"2022","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1016\/j.fertnstert.2023.05.009","article-title":"A Double-Blinded Prospective Randomized Trial Comparing Euploidy Rates Among Embryos Created from Sibling Oocytes Injected with Sperm Processed by Microfluidics or by Density Gradient Centrifugation","volume":"120","author":"Godiwala","year":"2023","journal-title":"Fertil. Steril."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e334","DOI":"10.1016\/j.fertnstert.2021.07.902","article-title":"Novel sperm capacitation system based on microfluidics, the path to automation","volume":"116","author":"Meseguer","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.fertnstert.2015.10.023","article-title":"Separation efficiency of a microfluidic sperm sorter to minimize sperm DNA damage","volume":"105","author":"Shirota","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1002\/adhm.201400058","article-title":"Selection of functional human sperm with higher DNA integrity and fewer reactive oxygen species","volume":"3","author":"Asghar","year":"2014","journal-title":"Adv. Healthc. Mater."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zaha, I., Naghi, P., Stefan, L., Bunescu, C., Radu, M., Muresan, M.E., Sandor, M., Sachelarie, L., and Huniadi, A. (2023). Comparative Study of Sperm Selection Techniques for Pregnancy Rates in an Unselected IVF\u2013ICSI Population. J. Pers. Med., 13.","DOI":"10.3390\/jpm13040619"},{"key":"ref_34","first-page":"e14415","article-title":"Prospective randomized controlled study of a microfluidic chip technology for sperm selection in male infertility patients","volume":"54","year":"2022","journal-title":"Andrologia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1007\/s43032-021-00784-z","article-title":"Does Microfluidic Sperm Sorting Affect Embryo Euploidy Rates in Couples with High Sperm DNA Fragmentation?","volume":"29","author":"Keskin","year":"2022","journal-title":"Reprod. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1111\/andr.13362","article-title":"Can a sperm selection technique improve embryo ploidy?","volume":"11","author":"Kocur","year":"2023","journal-title":"Andrology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e331","DOI":"10.1016\/j.fertnstert.2020.08.897","article-title":"Microfluidic sperm sorting vs. density gradient: A preliminary analysis examining embryo grade and pregnancy outcomes in ivf-icsi cycles using varying sperm selection methods","volume":"114","author":"Pavlovic","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e283","DOI":"10.1016\/j.fertnstert.2021.07.761","article-title":"Does zym\u014dt sperm separation improve embryo development outcomes when applied to all infertility patients compared to density gradient washing or surgically attained sperm?","volume":"116","author":"Schiewe","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41378-023-00501-7","article-title":"Sperm quality metrics were improved by a biomimetic microfluidic selection platform compared to swim-up methods","volume":"9","author":"Vasilescu","year":"2023","journal-title":"Microsyst. Nanoeng."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1007\/s10815-019-01480-3","article-title":"Use of microfluidic sperm extraction chips as an alternative method in patients with recurrent in vitro fertilisation failure","volume":"36","author":"Yildiz","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"46","DOI":"10.31083\/j.ceog5003046","article-title":"Comparison of reproductive outcomes in ICSI cycles using sperm chip technique and density gradient technique in men with normal semen analysis","volume":"50","author":"Kar","year":"2023","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/jog.14539","article-title":"Does the use of microfluidic sperm sorting for the sperm selection improve in vitro fertilization success rates in male factor infertility?","volume":"47","author":"Ozcan","year":"2021","journal-title":"J. Obs. Gynaecol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s10815-018-1375-2","article-title":"Effects of the microfluidic chip technique in sperm selection for intracytoplasmic sperm injection for unexplained infertility: A prospective, randomized controlled trial","volume":"36","author":"Yetkinel","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Escud\u00e9-Logares, L., Serrano-Novillo, C., Uroz, L., Galindo, A., and M\u00e1rquez, C. (2024). Advanced Paternal Age: A New Indicator for the Use of Microfluidic Devices for Sperm DNA Fragmentation Selection. J. Clin. Med., 13.","DOI":"10.3390\/jcm13020457"},{"key":"ref_45","first-page":"100338","article-title":"Microfluidic sperm sorting improves ICSI outcomes in patients with increased values of Double-Strand Breaks in sperm DNA","volume":"21","year":"2023","journal-title":"Rev. Int. Androl."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.1039\/D3LC00037K","article-title":"Development of a novel cervix-inspired tortuous microfluidic system for efficient, high-quality sperm selection","volume":"23","author":"Dadkhah","year":"2023","journal-title":"Lab Chip"},{"key":"ref_47","first-page":"85","article-title":"Comparison of In-House Microfluidic Device and Centrifuge-Based Method Efficacy in Sperm Preparation for Assisted Reproductive Technology","volume":"24","author":"Phairatana","year":"2023","journal-title":"J. Reprod. Infertil."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1093\/humrep\/dey239","article-title":"Microfluidic sorting selects sperm for clinical use with reduced DNA damage compared to density gradient centrifugation with swim-up in split semen samples","volume":"33","author":"Quinn","year":"2018","journal-title":"Hum. Reprod."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/7\/792\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:02:17Z","timestamp":1760032937000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/7\/792"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":48,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["biology14070792"],"URL":"https:\/\/doi.org\/10.3390\/biology14070792","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]}}}