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Dai C, Zhang Z, Shan G, et al. Advances in sperm analysis: techniques, discoveries and applications. Nat Rev Urol. 2021;18(8):447-467doi: 10.1038/s41585-021-00472-2.
Dai, C., Zhang, Z., Shan, G., Chu, L. T., Huang, Z., Moskovtsev, S., Librach, C., Jarvi, K., & Sun, Y. (2021). Advances in sperm analysis: techniques, discoveries and applications. Nature reviews. Urology, 18(8), 447-467. https://doi.org/10.1038/s41585-021-00472-2
Dai, Changsheng, et al. "Advances in sperm analysis: techniques, discoveries and applications." Nature reviews. Urology vol. 18,8 (2021): 447-467. doi: https://doi.org/10.1038/s41585-021-00472-2
Dai C, Zhang Z, Shan G, Chu LT, Huang Z, Moskovtsev S, Librach C, Jarvi K, Sun Y. Advances in sperm analysis: techniques, discoveries and applications. Nat Rev Urol. 2021 Aug;18(8):447-467. doi: 10.1038/s41585-021-00472-2. Epub 2021 Jun 01. PMID: 34075227.
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Nat Rev Urol. 2021 Aug;18(8):447-467. doi: 10.1038/s41585-021-00472-2. Epub 2021 Jun 01.

Advances in sperm analysis: techniques, discoveries and applications.

Nature reviews. Urology

Changsheng Dai, Zhuoran Zhang, Guanqiao Shan, Lap-Tak Chu, Zongjie Huang, Sergey Moskovtsev, Clifford Librach, Keith Jarvi, Yu Sun

Affiliations

  1. Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Canada.
  2. CReATe Fertility Centre, Toronto, Canada.
  3. Division of Urology, Mount Sinai Hospital, Toronto, Canada. [email protected].
  4. Department of Surgery, University of Toronto, Toronto, Canada. [email protected].
  5. Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Canada. [email protected].
  6. Institute of Biomaterials & Biomedical Engineering, University of Toronto, Toronto, Canada. [email protected].
  7. Department of Electrical and Computer Engineering, University of Toronto, Toronto, Canada. [email protected].
  8. Department of Computer Science, University of Toronto, Toronto, Canada. [email protected].

PMID: 34075227 DOI: 10.1038/s41585-021-00472-2

Abstract

Infertility affects one in six couples worldwide, and fertility continues to deteriorate globally, partly owing to a decline in semen quality. Sperm analysis has a central role in diagnosing and treating male factor infertility. Many emerging techniques, such as digital holography, super-resolution microscopy and next-generation sequencing, have been developed that enable improved analysis of sperm motility, morphology and genetics to help overcome limitations in accuracy and consistency, and improve sperm selection for infertility treatment. These techniques have also improved our understanding of fundamental sperm physiology by enabling discoveries in sperm behaviour and molecular structures. Further progress in sperm analysis and integrating these techniques into laboratories and clinics requires multidisciplinary collaboration, which will increase discovery and improve clinical outcomes.

© 2021. Springer Nature Limited.

References

  1. Vos, T. et al. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1545–1602 (2016). - PubMed
  2. Agarwal, A. et al. A unique view on male infertility around the globe. Reprod. Biol. Endocrinol. 13, 37 (2015). - PubMed
  3. Skakkebaek, N. E. et al. Male reproductive disorders and fertility trends: influences of environment and genetic susceptibility. Physiol. Rev. 96, 55–97 (2016). - PubMed
  4. Vollset, S. E. et al. Fertility, mortality, migration, and population scenarios for 195 countries and territories from 2017 to 2100: a forecasting analysis for the Global Burden of Disease Study. Lancet 396, 1285–1306 (2020). - PubMed
  5. Carlsen, E. et al. Evidence for decreasing quality of semen during past 50 years. BMJ 305, 609–613 (1992). - PubMed
  6. Levine, H. et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum. Reprod. Update 23, 646–659 (2017). - PubMed
  7. Sripada, S. et al. Trends in Semen Parameters in the Northeast of Scotland. J. Androl. 28, 313–319 (2007). - PubMed
  8. Centola, G. M. et al. Decline in sperm count and motility in young adult men from 2003 to 2013: observations from a U . S . sperm bank. Andrology 4, 270–276 (2016). - PubMed
  9. Virtanen, H. E. & Toppari, J. Semen quality in the 21 st century. Nat. Rev. Urol. 14, 120–130 (2017). - PubMed
  10. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. https://www.who.int/docs/default-source/reproductive-health/srhr-documents/infertility/examination-and-processing-of-human-semen-5ed-eng.pdf?sfvrsn=5227886e_2 (2010). - PubMed
  11. David, S. et al. Sperm morphology, motility, and concentration in fertile and infertile men. N. Engl. J. Med. 345, 1388–1393 (2001). - PubMed
  12. Donnelly, E. T. et al. In vitro fertilization and pregnancy rates: the influence of sperm motility and morphology on IVF outcome. Fertil. Steril. 70, 305–314 (1998). - PubMed
  13. Bartoov, B. et al. Real-time fine morphology of motile human sperm cells is associated with IVF-ICSI outcome. J. Androl. 23, 1–8 (2002). - PubMed
  14. De Vos, A. et al. Influence of individual sperm morphology on fertilization, embryo morphology, and pregnancy outcome of intracytoplasmic sperm injection. Fertil. Steril. 79, 42–48 (2003). - PubMed
  15. Evenson, D. P. The Sperm Chromatin Structure Assay (SCSA) and other sperm DNA fragmentation tests for evaluation of sperm nuclear DNA integrity as related to fertility. Anim. Reprod. Sci. 169, 56–75 (2016). - PubMed
  16. Ramasamy, R., Besada, S. & Lamb, D. J. Fluorescent in situ hybridization of human sperm: Diagnostics, indications, and therapeutic implications. Fertil. Steril. 102, 1534–1539 (2014). - PubMed
  17. Zini, A., San Gabriel, M. & Baazeem, A. Antioxidants and sperm DNA damage: a clinical perspective. J. Assist. Reprod. Genet. 26, 427–432 (2009). - PubMed
  18. Baldi, E., & Muratori, M. Genetic Damage in Human Spermatozoa (Springer, 2014). - PubMed
  19. Zidi-Jrah, I. et al. Relationship between sperm aneuploidy, sperm DNA integrity, chromatin packaging, traditional semen parameters, and recurrent pregnancy loss. Fertil. Steril. 105, 58–64 (2016). - PubMed
  20. Esteves, S. C., Roque, M., Bradley, C. K. & Garrido, N. Reproductive outcomes of testicular versus ejaculated sperm for intracytoplasmic sperm injection among men with high levels of DNA fragmentation in semen: systematic review and meta-analysis. Fertil. Steril. 108, 456–467 (2017). - PubMed
  21. Nosrati, R. et al. Microfluidics for sperm analysis and selection. Nat. Rev. Urol. 14, 707 (2017). - PubMed
  22. Esteves, S. C., Roque, M., Bedoschi, G., Haahr, T. & Humaidan, P. Intracytoplasmic sperm injection for male infertility and consequences for offspring. Nat. Rev. Urol. 15, 1–28 (2018). - PubMed
  23. Adamson, G. D. et al. International committee for monitoring assisted reproductive technology: world report on assisted reproductive technology, 2011. Fertil. Steril. 110, 1067–1080 (2018). - PubMed
  24. Sunderam, S. et al. Assisted reproductive technology surveillance — United States, 2012. Morbidity Mortal. Wkly. Report Surveill. Summaries 64, 1–29 (2015). - PubMed
  25. Wyns, C. et al. ART in Europe, 2016: results generated from European registries by ESHRE. Hum. Reprod. Open 3, hoaa032 (2020). - PubMed
  26. Gnoth, C. et al. Final ART success rates: a 10 years survey. Hum. Reprod. 26, 2239–2246 (2011). - PubMed
  27. Em, S. et al. The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment. Reprod. Biomed. Online 27, 325–337 (2013). - PubMed
  28. Eamer, L. et al. Turning the corner in fertility: high DNA integrity of boundary-following sperm. Lab. Chip 16, 2418–2422 (2016). - PubMed
  29. Parmegiani, L. et al. “Physiologic ICSI”: Hyaluronic acid (HA) favors selection of spermatozoa without DNA fragmentation and with normal nucleus, resulting in improvement of embryo quality. Fertil. Steril. 93, 598–604 (2010). - PubMed
  30. Hoogendijk, C. F., Ph, D., Kruger, T. F., Bouic, P. J. D. & Ph, D. A novel approach for the selection of human sperm using annexin V-binding and flow cytometry. Fertil. Steril. 91, 1285–1292 (2009). - PubMed
  31. Miller, D. et al. Physiological, hyaluronan-selected intracytoplasmic sperm injection for infertility treatment (HABSelect): a parallel, two-group, randomised trial. Lancet 393, 416–422 (2019). - PubMed
  32. Sakkas, D., Ramalingam, M., Garrido, N. & Barratt, C. L. Sperm selection in natural conception: what can we learn from Mother Nature to improve assisted reproduction outcomes? Hum. Reprod. Update 21, 711–726 (2015). - PubMed
  33. Amann, R. P. & Katz, D. F. Andrology lab corner: reflections on CASA after 25 years. J. Androl. 25, 317–325 (2004). - PubMed
  34. Daloglu, M. U. et al. Label-free 3D computational imaging of spermatozoon locomotion, head spin and flagellum beating over a large volume. Light. Sci. Appl. 7, 17111–17121 (2018). - PubMed
  35. Dai, C. et al. Automated non-invasive measurement of single sperm’s motility and morphology. IEEE Trans. Med. Imaging 37, 2257–2265 (2018). - PubMed
  36. Sánchez, V. et al. Oxidative DNA damage in human sperm can be detected by Raman microspectroscopy. Fertil. Steril. 98, 1124–1129 (2012). - PubMed
  37. Nazarenko, R. V., Irzhak, A. V., Pomerantsev, A. L. & Rodionova, O. Y. Confocal Raman spectroscopy and multivariate data analysis for evaluation of spermatozoa with normal and abnormal morphology. A feasibility study. Chemom. Intell. Lab. Syst. 182, 172–179 (2018). - PubMed
  38. Sequencing, W. et al. Probing meiotic recombination and aneuploidy of single sperm cells by whole-genome sequencing. Science 338, 1627–1631 (2012). - PubMed
  39. Tran, Q. T. et al. Chromosomal scan of single sperm cells by combining fluorescence-activated cell sorting and next-generation sequencing. J. Assist. Reprod. Genet. 36, 91–97 (2019). - PubMed
  40. Nosrati, R. et al. Rapid selection of sperm with high DNA integrity. Lab. Chip 14, 1142 (2014). - PubMed
  41. Wagenaar, B. D., Dekker, S., Olthuis, W., Berg, A. V. D. & Segerink, L. I. Towards microfluidic sperm refinement: continuous flow label-free analysis and sorting of sperm cells. Lab. Chip 16, 528–530 (2015). - PubMed
  42. Zaferani, M., Cheong, S. H. & Abbaspourrad, A. Rheotaxis-based separation of sperm with progressive motility using a microfluidic corral system. Proc. Natl Acad. Sci. USA 115, 8272–8277 (2018). - PubMed
  43. Bucar, S. et al. DNA fragmentation in human sperm after magnetic-activated cell sorting. J. Assist. Reprod. Genet. 32, 147–154 (2015). - PubMed
  44. Su, T.-W., Xue, L. & Ozcan, A. High-throughput lensfree 3D tracking of human sperms reveals rare statistics of helical trajectories. Proc. Natl Acad. Sci. USA 109, 16018–16022 (2012). - PubMed
  45. Su, T. W. et al. Sperm trajectories form chiral ribbons. Sci. Rep. 3, 1–8 (2013). - PubMed
  46. Nosrati, R., Driouchi, A., Yip, C. M. & Sinton, D. Two-dimensional slither swimming of sperm within a micrometre of a surface. Nat. Commun. 6, 8703 (2015). - PubMed
  47. Denissenko, P., Kantsler, V., Smith, D. J. & Kirkman-Brown, J. Human spermatozoa migration in microchannels reveals boundary-following navigation. Proc. Natl Acad. Sci. USA 109, 8007–8010 (2012). - PubMed
  48. Chung, J. J. et al. Structurally distinct Ca - PubMed
  49. Frolikova, M., Sebkova, N., Ded, L. & Dvorakova-Hortova, K. Characterization of CD46 and β1 integrin dynamics during sperm acrosome reaction. Sci. Rep. 6, 1–15 (2016). - PubMed
  50. Sutovsky, P., Terada, Y. & Schatten, G. Ubiquitin-based sperm assay for the diagnosis of male factor infertility. Hum. Reprod. 16, 250–258 (2001). - PubMed
  51. Schiza, C. G., Jarvi, K., Diamandis, E. P. & Drabovich, A. P. An emerging role of TEX101 protein as a male infertility biomarker. J. Int. Fed. Clin. Chem. Lab. Med. 25, 9–26 (2014). - PubMed
  52. Huszar, G. Biochemical markers of sperm function: male fertility and sperm selection for ICSI. Reprod. Biomed. Online 7, 462–468 (2003). - PubMed
  53. Louis, G. M. B. et al. Semen quality and time to pregnancy: the longitudinal investigation of fertility and the environment study. Fertil. Steril. 101, 453–462 (2014). - PubMed
  54. Zinaman, M. J., Brown, C. C., Selevan, S. G. & Clegg, E. D. Semen quality and human fertility: a prospective study with healthy couples. J. Androl. 21, 145–153 (2000). - PubMed
  55. Bonde, J. P. E. et al. Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet 352, 1172–1177 (1998). - PubMed
  56. Bungum, M. et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum. Reprod. 22, 174–179 (2007). - PubMed
  57. Duran, E. H., Morshedi, M., Taylor, S. & Oehninger, S. Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study. Hum. Reprod. 17, 3122–3128 (2002). - PubMed
  58. Marques, C. J. et al. Abnormal methylation of imprinted genes in human sperm is associated with oligozoospermia. Mol. Hum. Reprod. 14, 67–73 (2008). - PubMed
  59. Jenkins, T. G. et al. Sperm epigenetics in the study of male fertility, offspring health, and potential clinical applications. Syst. Biol. Reprod. Med. 63, 69–76 (2017). - PubMed
  60. Turner, R. M. Moving to the beat: a review of mammalian sperm motility regulation. Reprod. Fertil. Dev. 18, 25–38 (2005). - PubMed
  61. Gaffney, E. et al. Mammalian sperm motility: observation and theory. Annu. Rev. Fluid Mech. 43, 501–528 (2011). - PubMed
  62. Lindemann, C. B. & Lesich, K. A. Functional anatomy of the mammalian sperm flagellum. Cytoskeleton 73, 652–669 (2016). - PubMed
  63. Piomboni, P., Focarelli, R., Stendardi, A., Ferramosca, A. & Zara, V. The role of mitochondria in energy production for human sperm motility. Int. J. Androl. 35, 109–124 (2012). - PubMed
  64. Vernon, G. G. & Woolley, D. M. Basal sliding and the mechanics of oscillation in a mammalian sperm flagellum. Biophys. J. 87, 3934–3944 (2004). - PubMed
  65. Guzick, D. S. et al. Sperm morphology, motility, and concentration in fertile and infertile men. N. Engl. J. Med. 345, 1388–1393 (2001). - PubMed
  66. Lu, J. C., Huang, Y. F. & Lu, N. Q. Computer‐aided sperm analysis: past, present and future. Andrologia 46, 329–338 (2014). - PubMed
  67. Amann, R. P. & Waberski, D. Computer-assisted sperm analysis (CASA): capabilities and potential developments. Theriogenology 81, 5–17 (2014). - PubMed
  68. Chenouard, N. et al. Objective comparison of particle tracking methods. Nat. Methods 11, 281–289 (2014). - PubMed
  69. Urbano, L., Masson, P., VerMilyea, M. & Kam, M. Automatic tracking and motility analysis of human sperm in time-lapse images. IEEE Trans. Med. Imaging 36, 792–801 (2016). - PubMed
  70. Tomlinson, M. J. et al. Validation of a novel computer-assisted sperm analysis (CASA) system using multitarget-tracking algorithms. Fertil. Steril. 93, 1911–1920 (2010). - PubMed
  71. Agarwal, A., Henkel, R., Huang, C. C. & Lee, M. S. Automation of human semen analysis using a novel artificial intelligence optical microscopic technology. Andrologia 51, 13440 (2019). - PubMed
  72. Menkveld, R. et al. Semen parameters, including WHO and strict criteria morphology, in a fertile and subfertile population: an effort towards standardization of in-vivo thresholds. Hum. Reprod. 16, 1165–1171 (2001). - PubMed
  73. Bijar, A., Benavent, A. P., Mikaeili, M. & Khayati, R. Fully automatic identification and discrimination of sperm’s parts in microscopic images of stained human semen smear. J. Biomed. Sci. Eng. 5, 384–395 (2012). - PubMed
  74. Maree, L., Du Plessis, S. S., Menkveld, R. & Van der Horst, G. Morphometric dimensions of the human sperm head depend on the staining method used. Hum. Reprod. 25, 1369–1382 (2010). - PubMed
  75. Perdrix, A. & Rives, N. Motile sperm organelle morphology examination (MSOME) and sperm head vacuoles: state of the art in 2013. Hum. Reprod. Update 19, 527–541 (2013). - PubMed
  76. Berkovitz, A. et al. The morphological normalcy of the sperm nucleus and pregnancy rate of intracytoplasmic injection with morphologically selected sperm. Hum. Reprod. 20, 185–190 (2005). - PubMed
  77. Setti, A. S., Braga, D. P., Iaconelli, A., Aoki, T. & Borges, E. Twelve years of MSOME and IMSI: a review. Reprod. Biomed. Online 27, 338–352 (2013). - PubMed
  78. Hammoud, I. et al. Selection of normal spermatozoa with a vacuole-free head (×6300) improves selection of spermatozoa with intact DNA in patients with high sperm DNA fragmentation rates. Andrologia 45, 163–170 (2013). - PubMed
  79. Balaban, B. et al. Clinical outcome of intracytoplasmic injection of spermatozoa morphologically selected under high magnification: a prospective randomized study. Reprod. Biomed. Online 22, 472–476 (2011). - PubMed
  80. De Vos, A. et al. Does intracytoplasmic morphologically selected sperm injection improve embryo development? A randomized sibling-oocyte study. Hum. Reprod. 28, 617–626 (2013). - PubMed
  81. Ebner, T., Shebl, O., Oppelt, P. & Mayer, R. B. Some reflections on intracytoplasmic morphologically selected sperm injection. Int. J. Fertil. Steril. 8, 105 (2014). - PubMed
  82. Rougier, N. et al. Changes in DNA fragmentation during sperm preparation for intracytoplasmic sperm injection over time. Fertil. Steril. 100, 69–74 (2013). - PubMed
  83. Vingris, L. et al. Sperm morphological normality under high magnification predicts laboratory and clinical outcomes in couples undergoing ICSI. Hum. Fertil. 18, 81–86 (2015). - PubMed
  84. Dai, C. et al. Automated motility and morphology measurement of live spermatozoa. Andrology https://doi.org/10.1111/andr.13002 (2021). - PubMed
  85. Yin, Z., Kanade, T. & Chen, M. Understanding the phase contrast optics to restore artifact-free microscopy images for segmentation. Med. Image Anal. 16, 1047–1062 (2012). - PubMed
  86. Obara, B., Roberts, M. A., Armitage, J. P. & Grau, V. Bacterial cell identification in differential interference contrast microscopy images. BMC Bioinform. 14, 1–3 (2013). - PubMed
  87. Shaked, N. T. Label-free quantitative imaging of sperm for in-vitro fertilization using interferometric phase microscopy. JFIV Reprod. Med. Genet. 4, 190 (2016). - PubMed
  88. Coppola, G. et al. Digital holographic microscopy for the evaluation of human sperm structure. Zygote 22, 446–454 (2014). - PubMed
  89. Haifler, M. et al. Interferometric phase microscopy for label-free morphological evaluation of sperm cells. Fertil. Steril. 104, 43–47 (2015). - PubMed
  90. Almeling, R. Selling genes, selling gender: Egg agencies, sperm banks, and the medical market in genetic material. Am. Sociol. Rev. 72, 319–340 (2007). - PubMed
  91. Bisht, S., Faiq, M., Tolahunase, M. & Dada, R. Oxidative stress and male infertility. Nat. Rev. Urol. 14, 470–85 (2017). - PubMed
  92. Tang, S. et al. Biallelic mutations in CFAP43 and CFAP44 cause male infertility with multiple morphological abnormalities of the sperm flagella. Am. J. Hum. Genet. 100, 854–864 (2017). - PubMed
  93. Firat-karalar, E. N., Sante, J., Elliott, S. & Stearns, T. Proteomic analysis of mammalian sperm cells identifies new components of the centrosome. J. Cell Sci. 3, 4128–4133 (2014). - PubMed
  94. Coutton, C. et al. Bi-allelic mutations in ARMC2 lead to severe astheno-teratozoospermia due to sperm flagellum malformations in humans and mice. Am. J. Hum. Genet. 104, 331–340 (2019). - PubMed
  95. Zhu, F. et al. Biallelic SUN5 mutations cause autosomal-recessive acephalic spermatozoa syndrome. Am. J. Hum. Genet. 99, 942–949 (2016). - PubMed
  96. Zhu, F. et al. Mutations in PMFBP1 cause acephalic spermatozoa syndrome. Am. J. Hum. Genet. 103, 188–199 (2018). - PubMed
  97. Krausz, C. & Riera-Escamilla, A. Genetics of male infertility. Nat. Rev. Urol. 15, 1–16 (2018). - PubMed
  98. Lewis, S. E. & Simon, L. Clinical implications of sperm DNA damage. Hum. Fertil. 13, 201–207 (2010). - PubMed
  99. Evenson, D. P. Evaluation of sperm chromatin structure and DNA strand breaks is an important part of clinical male fertility assessment. Transl. Androl. Urol. 6, 2–7 (2017). - PubMed
  100. Evenson, D. & Wixon, R. Meta-analysis of sperm DNA fragmentation using the sperm chromatin structure assay. Reprod. Biomed. Online 12, 466–472 (2006). - PubMed
  101. Shamsi, M. B., Imam, S. N. & Dada, R. Sperm DNA integrity assays: Diagnostic and prognostic challenges and implications in management of infertility. J. Assist. Reprod. Genet. 28, 1073–1085 (2011). - PubMed
  102. Mishra, S., Kumar, R., Malhotra, N., Singh, N. & Dada, R. Mild oxidative stress is beneficial for sperm telomere length maintenance. World J. Methodol. 6, 163 (2016). - PubMed
  103. Tremellen, K. Oxidative stress and male infertility — a clinical perspective. Hum. Reprod. Update 14, 243–258 (2008). - PubMed
  104. Lewis, S. E. & Aitken, R. J. DNA damage to spermatozoa has impacts on fertilization and pregnancy. Cell Tissue Res. 322, 33–41 (2005). - PubMed
  105. Kumar, S. B., Chawla, B., Bisht, S., Yadav, R. K. & Dada, R. Tobacco use increases oxidative DNA damage in sperm-possible etiology of childhood cancer. Asian Pac. J. Cancer Prev. 16, 6967–6972 (2015). - PubMed
  106. Vorilhon, S. et al. Accuracy of human sperm DNA oxidation quantification and threshold determination using an 8-OHdG immuno-detection assay. Hum. Reprod. 33, 553–562 (2018). - PubMed
  107. Muratori, M. et al. Investigation on the origin of sperm DNA fragmentation: role of apoptosis, immaturity and oxidative stress. Mol. Med. 21, 109–122 (2015). - PubMed
  108. Ni, K., Spiess, A. N., Schuppe, H. C. & Steger, K. The impact of sperm protamine deficiency and sperm DNA damage on human male fertility: a systematic review and meta‐analysis. Andrology 4, 789–799 (2006). - PubMed
  109. Sakkas, D., Seli, E., Bizzaro, D., Tarozzi, N. & Manicardi, G. C. Abnormal spermatozoa in the ejaculate: abortive apoptosis and faulty nuclear remodelling during spermatogenesis. Reprod. Biomed. Online 7, 428–432 (2003). - PubMed
  110. Virro, M. R., Larson-cook, K. L. & Evenson, D. P. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil. Steril. 81, 1289–1295 (2004). - PubMed
  111. Henkel, R., Hoogendijk, C. F., Bouic, P. J. D. & Kruger, T. F. TUNEL assay and SCSA determine different aspects of sperm DNA damage. Andrologia 42, 305–313 (2010). - PubMed
  112. Sergerie, M., Laforest, G., Bujan, L., Bissonnette, F. & Bleau, G. Sperm DNA fragmentation: threshold value in male fertility. Hum. Reprod. 20, 3446–3451 (2005). - PubMed
  113. Ribeiro, S. et al. Inter- and intra-laboratory standardization of TUNEL assay for assessment of sperm DNA fragmentation. Andrology 5, 477–485 (2017). - PubMed
  114. Mitchell, L. A., Iuliis, G. N. D. & Aitken, R. J. The TUNEL assay consistently underestimates DNA damage in human spermatozoa and is influenced by DNA compaction and cell vitality: development of an improved methodology. Int. J. Androl. 34, 2–13 (2010). - PubMed
  115. Muratori, M., Forti, G. & Baldi, E. Comparing flow cytometry and fluorescence microscopy for analyzing human sperm DNA fragmentation by TUNEL labeling. Cytom. A 73, 785–787 (2008). - PubMed
  116. Cho, C. L. & Agarwal, A. Role of sperm DNA fragmentation in male factor infertility: a systematic review. Arab. J. Urol. 16, 21–34 (2018). - PubMed
  117. Muriel, L. et al. The sperm chromatin dispersion test: a simple method for the determination of sperm DNA fragmentation. J. Androl. 24, 59–66 (2003). - PubMed
  118. Morris, I. D., Ilott, S., Dixon, L. & Brison, D. R. The spectrum of DNA damage in human sperm assessed by single cell gel electrophoresis (Comet assay) and its relationship to fertilization and embryo development. Hum. Reprod. 17, 990–998 (2002). - PubMed
  119. Afanasieva, K. & Sivolob, A. Biophysical chemistry physical principles and new applications of comet assay. Biophys. Chem. 238, 1–7 (2018). - PubMed
  120. Collins, A. R. et al. The comet assay: topical issues. Mutagenesis 23, 143–151 (2008). - PubMed
  121. Olive, P. L. & Banáth, J. P. The comet assay: a method to measure DNA damage in individual cells. Nat. Protoc. 1, 23 (2006). - PubMed
  122. Simon, L. et al. Sperm DNA damage measured by the alkaline Comet assay as an independent predictor of male infertility and in vitro fertilization success. Fertil. Steril. 95, 652–657 (2011). - PubMed
  123. Ribas-Maynou, J. et al. Double stranded sperm DNA breaks measured by comet assay, are associated with unexplained recurrent miscarriage in couples without a female factor. PLoS ONE 7, 44679 (2012). - PubMed
  124. Sanchez, V. et al. Oxidative DNA damage in human sperm can be detected by Raman microspectroscopy. Fertil. Steril. 98, 1124–9 (2012). - PubMed
  125. Angelis, A. De et al. Combined Raman spectroscopy and digital holographic microscopy for sperm cell quality analysis. J. Spectrosc. 2017, 1–15 (2017). - PubMed
  126. Boydston-white, S., Mattha, C., Romeo, M. & Diem, M. A. X. Raman and infrared microspectral imaging of mitotic cells. Appl. Spectrosc. 60, 1–8 (2006). - PubMed
  127. Costa, R. Da, Amaral, S., Redmann, K., Kliesch, S. & Id, S. S. Spectral features of nuclear DNA in human sperm assessed by raman microspectroscopy: effects of UV-irradiation and hydration. PLoS ONE 13, 1–15 (2018). - PubMed
  128. Wang, Y. et al. Prediction of DNA integrity from morphological parameters using a single-sperm DNA fragmentation index assay. Adv. Sci. 6, 1900712 (2019). - PubMed
  129. Barnea, I. et al. Stain-free interferometric phase microscopy correlation with DNA fragmentation stain in human spermatozoa. J. Biophotonics 11, 1–10 (2018). - PubMed
  130. McCallum, C. et al. Deep learning-based selection of human sperm with high DNA integrity. Commun. Biol. 2, 1–100 (2019). - PubMed
  131. Calogero, A. E. et al. Sperm aneuploidy in infertile men. Reprod. Biomed. Online 6, 310–317 (2003). - PubMed
  132. Shi, Q. & Martin, R. H. Aneuploidy in human sperm: a review of the frequency and distribution of aneuploidy, effects of donor age and lifestyle factors. Cytogenet. Cell Genet. 90, 219–226 (2000). - PubMed
  133. Hassold, T. & Hunt, P. To err (meiotically) is human: the genesis of human aneuploidy. Nat. Rev. Genet. 2, 280–291 (2001). - PubMed
  134. Muriel, L. et al. Increased aneuploidy rate in sperm with fragmented DNA as determined by the sperm chromatin dispersion (SCD) test and FISH analysis. J. Androl. 28, 38–49 (2007). - PubMed
  135. Huber, D., Voithenberg, L. V. V. & Kaigala, G. V. Fluorescence in situ hybridization (FISH): History, limitations and what to expect from micro-scale FISH? Micro Nano Eng. 1, 15–24 (2018). - PubMed
  136. Song, S. H. et al. Genome-wide screening of severe male factor infertile patients using BAC-array comparative genomic hybridization (CGH). Gene 506, 248–252 (2012). - PubMed
  137. Karampetsou, E., Morrogh, D. & Chitty, L. Microarray technology for the diagnosis of fetal chromosomal aberrations: which platform should we use? J. Clin. Med. 3, 663–678 (2014). - PubMed
  138. Rubio, C. et al. Use of array comparative genomic hybridization (array-CGH) for embryo assessment: clinical results. Fertil. Steril. 99, 1044–1048 (2013). - PubMed
  139. Patassini, C. et al. Molecular karyotyping of human single sperm by array- comparative genomic hybridization. PLoS ONE 8, 60922 (2013). - PubMed
  140. Xi, R., Kim, T. & Park, P. J. Detecting structural variations in the human genome using next generation sequencing. Brief. Funct. Genomics 9, 405–415 (2011). - PubMed
  141. Koboldt, D. C., Steinberg, K. M., Larson, D. E., Wilson, R. K. & Mardis, E. R. The next-generation sequencing revolution and its impact on genomics. Cell 155, 27–38 (2013). - PubMed
  142. Cheung, S., Parrella, A., Rosenwaks, Z. & Palermo, G. D. Genetic and epigenetic profiling of the infertile male. PLoS ONE 14, e0214275 (2019). - PubMed
  143. Kazda, A. et al. Chromosome end protection by blunt-ended telomeres. Genes Dev. 26, 1703–1713 (2012). - PubMed
  144. Nandakumar, J. & Cech, T. R. Finding the end: recruitment of telomerase to telomeres. Nat. Rev. Mol. Cell Biol. 14, 69–82 (2013). - PubMed
  145. Thilagavathi, J. et al. Analysis of sperm telomere length in men with idiopathic infertility. Arch. Gynecol. Obstet. 287, 803–807 (2013). - PubMed
  146. Yang, Q. et al. Sperm telomere length is positively associated with the quality of early embryonic development. Hum. Reprod. 30, 1876–1881 (2015). - PubMed
  147. Boniewska-Bernacka, E., Pańczyszyn, A. & Cybulska, N. Telomeres as a molecular marker of male infertility. Hum. Fertil. 22, 78–87 (2019). - PubMed
  148. Lafuente, R. et al. Sperm telomere length in motile sperm selection techniques: a qFISH approach. Andrologia 50, e12840 (2018). - PubMed
  149. Turner, S. & Hartshorne, G. M. Telomere lengths in human pronuclei, oocytes and spermatozoa. Mol. Hum. Reprod. 19, 510–518 (2013). - PubMed
  150. Cariati, F. et al. Investigation of sperm telomere length as a potential marker of paternal genome integrity and semen quality. Reprod. Biomed. Online 33, 404–411 (2016). - PubMed
  151. Zhao, F., Yang, Q., Shi, S., Luo, X. & Sun, Y. Semen preparation methods and sperm telomere length: density gradient centrifugation versus the swim up procedure. Sci. Rep. 6, 39051 (2016). - PubMed
  152. Rocca, M. S., Foresta, C. & Ferlin, A. Telomere length: lights and shadows on their role in human reproduction. Biol. Reprod. 100, 305–317 (2019). - PubMed
  153. Jenkins, T. G. & Carrell, D. T. The sperm epigenome and potential implications for the developing embryo. Reproduction 143, 727 (2012). - PubMed
  154. Hammoud, S. S. et al. Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men. Hum. Reprod. 26, 2558–2569 (2011). - PubMed
  155. Denomme, M. M., McCallie, B. R., Parks, J. C., Schoolcraft, W. B. & Katz-Jaffe, M. G. Alterations in the sperm histone-retained epigenome are associated with unexplained male factor infertility and poor blastocyst development in donor oocyte IVF cycles. Hum. Reprod. 32, 2443–2455 (2017). - PubMed
  156. Aston, K. I. et al. Aberrant sperm DNA methylation predicts male fertility status and embryo quality. Fertil. Steril. 104, 1388–1397 (2015). - PubMed
  157. Schrott, R. et al. Sperm DNA methylation altered by tHc and nicotine: vulnerability of neurodevelopmental genes with bivalent chromatin. Sci. Rep. 10, 1–12 (2020). - PubMed
  158. Maamar, M. B. et al. Developmental origins of transgenerational sperm DNA methylation epimutations following ancestral DDT exposure. Dev. Biol. 445, 280–293 (2019). - PubMed
  159. Jenkins, T. G. et al. Intra-sample heterogeneity of sperm DNA methylation. Mol. Hum. Reprod. 21, 313–319 (2015). - PubMed
  160. Keravnou, A. et al. Whole-genome fetal and maternal DNA methylation analysis using MeDIP-NGS for the identification of differentially methylated regions. Genet. Res. 98, 1–9 (2016). - PubMed
  161. Luján, S. et al. Sperm DNA methylation epimutation biomarkers for male infertility and FSH therapeutic responsiveness. Sci. Rep. 9, 1–12 (2019). - PubMed
  162. Oostlander, A. E., Meijer, G. A. & Ylstra, B. Microarray‐based comparative genomic hybridization and its applications in human genetics. Clin. Genet. 66, 488–495 (2004). - PubMed
  163. Houshdaran, S. et al. Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm. PLoS ONE 2, e1289 (2007). - PubMed
  164. Aston, K. I. et al. Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis. Fertil. Steril. 97, 285–292 (2012). - PubMed
  165. Brykczynska, U. et al. Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat. Struct. Mol. Biol. 17, 679 (2010). - PubMed
  166. Steilmann, C. et al. Presence of histone H3 acetylated at lysine 9 in male germ cells and its distribution pattern in the genome of human spermatozoa. Reprod. Fertil. Dev. 23, 997–1011 (2011). - PubMed
  167. Hammoud, S. S. et al. Distinctive chromatin in human sperm packages genes for embryo development. Nature 460, 473–478 (2009). - PubMed
  168. Boissonnas, C., Ph, D. & Jouannet, P. Epigenetic disorders and male subfertility. Fertil. Steril. 99, 624–631 (2013). - PubMed
  169. Hamatani, T. Human spermatozoal RNAs. Fertil. Steril. 97, 275–281 (2012). - PubMed
  170. Pelloni, M. et al. Molecular study of human sperm RNA: ropporin and CABYR in asthenozoospermia. J. Endocrinol. Invest. 41, 781–787 (2018). - PubMed
  171. Gòdia, M. et al. A RNA-Seq analysis to describe the boar sperm transcriptome and its seasonal changes. Front. Genet. 10,, 299 (2019). - PubMed
  172. Wein, S. et al. A computational platform for high-throughput analysis of RNA sequences and modifications by mass spectrometry. Nat. Commun. 11, 1–12 (2020). - PubMed
  173. Kukurba, K. R. & Montgomery, S. B. RNA sequencing and analysis. Cold Spring Harb. Protoc. 2015, 951–969 (2015). - PubMed
  174. Aoki, V. W., Liu, L. & Carrell, D. T. A novel mechanism of protamine expression deregulation highlighted by abnormal protamine transcript retention in infertile human males with sperm protamine deficiency. Mol. Hum. Reprod. 12, 41–50 (2006). - PubMed
  175. Ostermeier, G. C., Miller, D., Huntriss, J. D., Diamond, M. P. & Krawetz, S. A. Delivering spermatozoan RNA to the oocyte. Nature 429, 154 (2004). - PubMed
  176. Rassoulzadegan, M. et al. RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 441, 469–474 (2006). - PubMed
  177. Sone, Y. et al. Nuclear translocation of phospholipase C-zeta, an egg-activating factor, during early embryonic development. Biochem. Biophys. Res. Commun. 330, 690–694 (2005). - PubMed
  178. Fu, Y., Dominissini, D., Rechavi, G. & He, C. Gene expression regulation mediated through reversible m6A RNA methylation. Nat. Rev. Genet. 15, 293 (2014). - PubMed
  179. Chen, Q. et al. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science 351, 397–400 (2016). - PubMed
  180. Zini, A., Finelli, A., Phang, D. & Jarvi, K. Influence of semen processing technique on human sperm DNA integrity. Urology 56, 1081–1084 (2000). - PubMed
  181. Xue, X. et al. Efficacy of swim-up versus density gradient centrifugation in improving sperm deformity rate and DNA fragmentation index in semen samples from teratozoospermic patients. J. Assist. Reprod. Genet. 31, 1161–1166 (2014). - PubMed
  182. Henkel, R. R. & Schill, W. B. Sperm preparation for ART. Reprod. Biol. Endocrinol. 1, 108 (2003). - PubMed
  183. Zaferani, M., Palermo, G. D. & Abbaspourrad, A. Strictures of a microchannel impose fierce competition to select for highly motile sperm. Sci. Adv. 5, 2111 (2019). - PubMed
  184. Li, K. et al. Novel distance — progesterone — combined selection approach improves human sperm quality. J. Transl. Med. 16, 1–10 (2018). - PubMed
  185. Tasoglu, S. et al. Exhaustion of racing sperm in nature-mimicking microfluidic channels during sorting. Small 9, 3374–3384 (2013). - PubMed
  186. Nosrati, R., Graham, P. J., Liu, Q. & Sinton, D. Predominance of sperm motion in corners. Sci. Rep. 6, 1–9 (2016). - PubMed
  187. Zaferani, M., Hon, S. & Abbaspourrad, A. Rheotaxis-based separation of sperm with progressive motility using a microfluidic corral system. Proc. Natl Acad. Sci. USA 115, 8272–8277 (2018). - PubMed
  188. Kaupp, U. B., Kashikar, N. D. & Weyand, I. Mechanisms of sperm chemotaxis. Annu. Rev. Physiol. 70, 93–117 (2008). - PubMed
  189. Huszar, G. et al. Hyaluronic acid binding by human sperm indicates cellular maturity, viability, and unreacted acrosomal status. Fertil. Steril. 79, 1616–1624 (2003). - PubMed
  190. Simopoulou, M. et al. Improving ICSI: a review from the spermatozoon perspective. Syst. Biol. Reprod. Med. 62, 359–371 (2016). - PubMed
  191. Liu, T. et al. Detection of apoptosis based on the interaction between annexin V and phosphatidylserine. Anal. Chem. 81, 2410–2413 (2009). - PubMed
  192. Gil, M., Sar-Shalom, V., Sivira, Y. M., Carreras, R. & Checa, M. A. Sperm selection using magnetic activated cell sorting (MACS) in assisted reproduction: a systematic review and meta-analysis. J. Assist. Reprod. Genet. 30, 479–485 (2013). - PubMed
  193. Galatioto, G. P. et al. May antioxidant therapy improve sperm parameters of men with persistent oligospermia after retrograde embolization for varicocele? World J. Urol. 26, 97–102 (2008). - PubMed
  194. Jun, L. et al. Quantitative analysis of locomotive behavior of human sperm head and tail. Biomed. Eng. IEEE Trans. 60, 390–396 (2013). - PubMed
  195. Zhang, Z. et al. An automated system for investigating sperm orientation in fluid flow. IEEE Int. Conf. Robot. Autom. https://doi.org/10.1109/ICRA.2016.7487551 (2016). - PubMed
  196. Hernandez-Herrera, P., Montoya, F., Rendón-Mancha, J. M., Darszon, A. & Corkidi, G. 3-D human sperm flagellum tracing in low SNR fluorescence images. IEEE Trans. Med. Imaging 37, 2236–2247 (2018). - PubMed
  197. Saggiorato, G. et al. Human sperm steer with second harmonics of the flagellar beat. Nat. Commun. 8, 1–9 (2017). - PubMed
  198. Friedrich, B. M., Riedel-Kruse, I. H., Howard, J. & Julicher, F. High-precision tracking of sperm swimming fine structure provides strong test of resistive force theory. J. Exp. Biol. 213, 1226–1234 (2010). - PubMed
  199. Gade, H., Gaffney, E. A. & Smith, D. J. Nonlinear instability in flagellar dynamics: a novel modulation mechanism in sperm migration? J. R. Soc. Interface 7, 1689–1697 (2010). - PubMed
  200. Zhang, Z. et al. Human sperm rheotaxis: a passive physical process. Sci. Rep. 6, 23553 (2016). - PubMed
  201. Bukatin, A., Kukhtevich, I., Stoop, N., Dunkel, J. & Kantsler, V. Bimodal rheotactic behavior reflects flagellar beat asymmetry in human sperm cells. Proc. Natl Acad. Sci. USA 112, 15904–15909 (2015). - PubMed
  202. Pérez-Cerezales, S. et al. Involvement of opsins in mammalian sperm thermotaxis. Sci. Rep. 5, 16146 (2015). - PubMed
  203. Di Caprio, G. et al. 4D tracking of clinical seminal samples for quantitative characterization of motility parameters. Biomed. Opt. Express 5, 690–700 (2014). - PubMed
  204. Di Caprio, G. et al. Holographic imaging of unlabelled sperm cells for semen analysis: a review. J. Biophotonics 8, 779–789 (2015). - PubMed
  205. Suarez, S. S. & Pacey, A. A. Sperm transport in the female reproductive tract. Hum. Reprod. Update 12, 23–37 (2006). - PubMed
  206. Gadêlha, H., Hernández-Herrera, P., Montoya, F., Darszon, A. & Corkidi, G. Human sperm uses asymmetric and anisotropic flagellar controls to regulate swimming symmetry and cell steering. Sci. Adv. 6, eaba5168 (2020). - PubMed
  207. Elgeti, J., Kaupp, U. B. & Gompper, G. Hydrodynamics of sperm cells near surfaces. Biophys J 99, 1018–1026 (2010). - PubMed
  208. Zhang, X. et al. Lensless imaging for simultaneous microfluidic sperm monitoring and sorting. Lab. Chip 11, 2535 (2011). - PubMed
  209. Bazylewski, P. & Ezugwu, S. A review of three-dimensional scanning near-field optical microscopy (3D-SNOM) and its applications in nanoscale light management. Appl. Sci. 7, 973 (2017). - PubMed
  210. Andolfi, L. et al. The application of scanning near field optical imaging to the study of human sperm morphology. J. Nanobiotechnol. 13, 2 (2015). - PubMed
  211. Chemes, H. E. & Rawe, V. Y. Sperm pathology: a step beyond descriptive morphology. Origin, characterization and fertility potential of abnormal sperm phenotypes in infertile men. Hum. Reprod. Update 9, 405–428 (2003). - PubMed
  212. Xu, J., Tehrani, K. F., Kner, P., States, U. & Avenue, C. Multicolor 3D super-resolution imaging by quantum dot stochastic optical reconstruction microscopy. ACS Nano 9, 2917–2925 (2015). - PubMed
  213. Huang, B., Wang, W., Bates, M. & Zhuang, X. Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy. Science 319, 810–814 (2008). - PubMed
  214. Chung, J. J. et al. CatSperζ regulates the structural continuity of sperm Ca - PubMed
  215. Strünker, T. et al. The CatSper channel mediates progesterone-induced Ca 2+ influx in human sperm. Nature 471, 382–386 (2011). - PubMed
  216. Gervasi, G., Xu, X., Carbajal-Gonzalez, B., Buffone, M. G. & Visconti, P. E. The actin cytoskeleton of the mouse sperm flagellum is organized in a helical structure. J. Cell Sci. 131, 1–9 (2018). - PubMed
  217. Dunleavy, J. E., O’Bryan, M. K., Stanton, P. G. & O’Donnell, L. The cytoskeleton in spermatogenesis. Reproduction 157, 53–72 (2019). - PubMed
  218. Paës, G., Habrant, A. & Terryn, C. Fluorescent nano-probes to image plant cell walls by super-resolution STED microscopy. Plants 7, 1–9 (2018). - PubMed
  219. Aminski, C. L. F. K. Frontiers in structured illumination microscopy. Optica 3, 667–677 (2016). - PubMed
  220. Gustafsson, M. G. Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy. J. Microsc. 198, 82–87 (2000). - PubMed
  221. Dan, D. et al. DMD-based LED-illumination super-resolution and optical sectioning microscopy. Sci. Rep. 3, 1–7 (2013). - PubMed
  222. Chang, B. J., Chou, L. J., Chang, Y. C. & Chiang, S. Y. Isotropic image in structured illumination microscopy patterned with a spatial light modulator. Opt. Express 17, 14710–14721 (2009). - PubMed
  223. Calvi, A. et al. SUN4 is essential for nuclear remodeling during mammalian spermiogenesis. Dev. Biol. 407, 321–330 (2015). - PubMed
  224. Yeh, C. H. et al. SEPT12/SPAG4/LAMINB1 complexes are required for maintaining the integrity of the nuclear envelope in postmeiotic male germ cells. PLoS ONE 10, e0120722 (2015). - PubMed
  225. Miller, M. R. et al. Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone. Science 352, 555–9 (2016). - PubMed
  226. Baker, M. A., Hetherington, L., Ecroyd, H., Roman, S. D. & Aitken, R. J. Analysis of the mechanism by which calcium negatively regulates the tyrosine phosphorylation cascade associated with sperm capacitation. J. Cell Sci. 117, 211–222 (2004). - PubMed
  227. Asquith, K. L., Baleato, R. M., McLaughlin, E. A., Nixon, B. & Aitken, R. J. Tyrosine phosphorylation activates surface chaperones facilitating sperm-zona recognition. J. Cell Sci. 117, 3645–3657 (2004). - PubMed
  228. Awad, H., Khamis, M. M. & El-Aneed, A. Mass spectrometry, review of the basics: ionization. Appl. Spectrosc. Rev. 50, 158–175 (2015). - PubMed
  229. Platt, M. D., Salicioni, A. M., Hunt, D. F. & Visconti, P. E. Use of differential isotopic labeling and mass spectrometry to analyze capacitation-associated changes in the phosphorylation status of mouse sperm proteins. J. Proteome Res. 8, 1431–1440 (2009). - PubMed
  230. Ardito, F., Giuliani, M., Perrone, D., Troiano, G. & Lo Muzio, L. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy. Int. J. Mol. Med. 40, 271–280 (2017). - PubMed
  231. Castillo, J. et al. Proteomic changes in human sperm during sequential in vitro capacitation and acrosome reaction. Front. Cell Dev. Biol. 7, 295 (2019). - PubMed
  232. Drabovich, A. P. et al. Differential diagnosis of azoospermia with proteomic biomarkers ECM1 and TEX101 quantified in seminal plasma. Sci. Transl. Med. 5, 212ra160 (2013). - PubMed
  233. Zerbinati, C. et al. Redox Biology Mass spectrometry pro fi ling of oxysterols in human sperm identi fi es 25- hydroxycholesterol as a marker of sperm function. Redox Biol. 11, 111–117 (2017). - PubMed
  234. Hafiz, P. et al. Predicting implantation outcome of in vitro fertilization and intracytoplasmic sperm injection using data mining techniques. Int. J. Fertil. Steril. 11, 184–190 (2017). - PubMed
  235. Comhaire, F., Messiaen, A. & Decleer, W. A mathematical model predicting the individual outcome of IVF through sperm-analysis: the role of the HaloSpermG2 DNA fragmentation test. Med. Hypotheses 117, 50–53 (2018). - PubMed
  236. Farias-hesson, E. et al. Semi-automated library preparation for high-throughput DNA sequencing platforms. J. Biomed. Biotechnol. 2010, 1–8 (2010). - PubMed
  237. Malm, J. et al. Semi-automated biobank sample processing with a 384 high density sample tube robot used in cancer and cardiovascular studies. Clin. Transl. Med. 4, 27 (2015). - PubMed
  238. Litjens, G. et al. A survey on deep learning in medical image analysis. Med. Image Anal. J. 42, 60–88 (2017). - PubMed
  239. Hicks, S. A. et al. Machine learning-based analysis of sperm videos and participant data for male fertility prediction. Sci. Rep. 9, 1–10 (2019). - PubMed
  240. Sobieranski, A. C. et al. Portable lensless wide-field microscopy imaging platform based on digital inline holography and multi-frame pixel super-resolution. Light. Sci. Appl. 4, 346 (2015). - PubMed
  241. Kanakasabapathy, M. K. et al. An automated smartphone-based diagnostic assay for point-of-care semen analysis. Sci. Transl. Med. 9, 7863 (2017). - PubMed
  242. Carrilho, E., Martinez, A. W. & Whitesides, G. M. Understanding wax printing: a simple micropatterning process for paper-based microfluidics. Anal. Chem. 81, 7091–7095 (2009). - PubMed
  243. Matsuura, K. et al. Paper-based diagnostic devices for evaluating the quality of human sperm. Microfluid. Nanofluidics 16, 857–867 (2014). - PubMed
  244. Nosrati, R., Gong, M. M., Gabriel, C. S., Zini, A. & Sinton, D. Paper-based sperm DNA integrity analysis. Anal. Methods 8, 6260–6264 (2016). - PubMed
  245. Ribas-Maynou, J. et al. Comprehensive analysis of sperm DNA fragmentation by five different assays: TUNEL assay, SCSA, SCD test and alkaline and neutral Comet assay. Andrology 1, 715–722 (2013). - PubMed
  246. Eisenbach, M. & Giojalas, L. Sperm guidance in mammals — an unpaved road to the egg. Nat. Rev. Mol. Cell Biol. 7, 276–285 (2006). - PubMed
  247. Vanderzwalmen, P. et al. Blastocyst development after sperm selection at high magnification is associated with size and number of nuclear vacuoles. Reprod. Biomed. Online 17, 617–627 (2008). - PubMed
  248. Pandiyan, N. et al. in Male Infertility A Clinical Approach (Springer, 2016). - PubMed
  249. Rougier, N. et al. Changes in DNA fragmentation during sperm preparation for intracytoplasmic sperm injection over time. Fertil. Steril. 100, 69–74 (2013). - PubMed
  250. Fink, M. & Taylor, M. A. in A Clinician’ s Guide to Diagnosis Sperm DNA and Chromatin Damage (Springer, 2018). - PubMed
  251. Palermo, G. D., Colombero, L. T., Hariprashad, J. J., Schlegel, P. N. & Rosenwaks, Z. Chromosome analysis of epididymal and testicular sperm in azoospermic patients undergoing ICSI. Hum. Reprod. 17, 570–575 (2002). - PubMed
  252. Lockwood, W. W., Chari, R., Chi, B. & Lam, W. L. Recent advances in array comparative genomic hybridization technologies and their applications in human genetics. Eur. J. Hum. Genet. 14, 139–148 (2006). - PubMed

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