Sperm selection in assisted reproductive technology programs using active microfluidic methods based on positive rheotaxis

DOI

https://dx.doi.org/10.18565/aig.2025.86

Makarova N.P., Kapitannikova A.Yu., Sysoeva A.P., Chernyshev V.S., Kalinina E.A., Sukhikh G.T.
Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia

Over the past 50 years, there has been a global decline in the quality of human sperm. Reports suggest that approximately 10-15% of couples worldwide experience difficulties in conceiving, and impaired spermatogenesis is responsible for 30-50% of these cases. The selection of high-quality motile spermatozoa from semen samples is an important step that largely determines the effectiveness of assisted reproductive technologies (ART). A lot of information has been collected in recent years about how sperm move through the female reproductive tract. Microfluidics-based devices make it possible to perform a more appropriate selection of spermatozoa in terms of motility, viability, DNA integrity and morphology, as they provide the opportunity to mimic the natural conditions and obstacles acting on spermatozoa in the natural environment of the female body. Due to the modelling and control of the conditions affecting the semen sample, these devices are able to select spermatozoa with the highest potential for successful fertilization.
This review provides new scientific evidence on the use of the ability of sperm to move against the fluid current during the embryological phase of fertility treatment programs using ART. Novel devices (lab-on-a-chip) that can be successfully integrated into the clinical practice of selecting male gametes by a clinical embryologist are also described. The review includes the data of foreign and Russian articles found in PubMed and e-Library systems published over the last 10 years.
Conclusion: Active microfluidics is a promising area of research for developing sperm selection methods that could improve the effectiveness of assisted reproduction procedures and result in better clinical outcomes.

Authors’ contributions: Makarova N.P. – developing the concept of the article, review and analysis of literature, writing the manuscript; Kapitannikova A.Yu. – review and analysis of literature, writing the manuscript of the article; Sysoeva A.P. – editing the manuscript of the article; Chernyshev V.S. – making critical comments on the article manuscript; Kalinina E.V. – critical review of the article manuscript, making corrections and comments; Sukhikh G.T. – approval of the publication.
Conflicts of interest: Authors declare lack of the possible conflicts of interest.
Funding: The study was performed within the framework of the state assignment 2024-2026 №124020500056-7 “Development of innovative microfluidic chips for selection of male germ cells in programs of infertility treatment by methods of assisted reproductive technologies”, supervised by N.P. Makarova.
For citation: Makarova N.P., Kapitannikova A.Yu., Sysoeva A.P., Chernyshev V.S., Kalinina E.A., Sukhikh G.T.
Sperm selection in assisted reproductive technology programs using
active microfluidic methods based on positive rheotaxis.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (6): 28-36 (in Russian)
https://dx.doi.org/10.18565/aig.2025.86

infertility

assisted reproductive technologies

sperm selection

infertility treatment

pregnancy

ejaculate

spermatozoa

male germ cells

microfluidic technologies

Full text (in Russian)

Ivkosic I.E., Mesic J., Fures R., Hrgovic Z., Bulic L., Brenner E. et al. Infertility - a great challenge of the past, present, and future. Mater. Sociomed. 2025; 37(1): 74-9. https://dx.doi.org/10.5455/msm.2025.37.74-79
Agarwal A., Baskaran S., Parekh N., Cho C.L., Henkel R., Vij S. et al. Male infertility. Lancet. 2021; 397(10271): 319-33. https://dx.doi.org/10.1016/S0140-6736(20)32667-2
Назаренко Т.А., ред. Бесплодный брак: клинические задачи и их решение. М.: МЕДпресс-информ; 2024. 127 с. [Nazarenko T.A., ed. Infertile marriage: clinical problems and their solution. Moscow: MEDpress-inform; 2024. 127 p. (in Russian)].
Tiptiri-Kourpeti A., Asimakopoulos B., Nikolettos N. A narrative review on the sperm selection methods in assisted reproductive technology: out with the new, the old is better? J. Clin. Med. 2025; 14(4): 1066. https://dx.doi.org/10.3390/jcm14041066
Agarwal A., Cho C.L., Majzoub A., Esteves S.C. The Society for Translational Medicine: clinical practice guidelines for sperm DNA fragmentation testing in male infertility. Transl. Androl. Urol. 2017; 6(Suppl. 4): S720-S733. https://dx.doi.org/10.21037/tau.2017.08.06
Дети из чипа: инновационная технология отбора качественных сперматозоидов. Инновационная фармакотерапия. 2024; 1(19): 44-8. [Children from the chip: an innovative technology for selecting high-quality sperm. Innovative pharmacotherapy. 2024; 1(19): 44-8. (in Russian)].
Беляева Л.А., Шурыгина О.В., Тугушев М.Т., Миронов С.Ю. Опыт применения микрожидкостных чипов для сортировки спермы у пациентов с лечением бесплодия. Ульяновский медико-биологический журнал. 2024; 1: 82-90. [Belyaeva L.A., Shurygina O.V., Tugushev M.T., Mironov S.Yu. Using microfluidic sperm sorting chips in patients with infertility. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2024; (1): 82-90. (in Russian)]. https://dx.doi.org/10.34014/2227-1848-2024-1-82-90
Meseguer F., Giménez Rodríguez C., Rivera Egea R., Carrión Sisternas L., Remohí J.A., Meseguer M. Can microfluidics improve sperm quality? A prospective functional study. Biomedicines. 2024; 12(5): 1131. https://dx.doi.org/10.3390/biomedicines12051131
Макарова Н.П., Сысоева А.П., Чернышев В.С., Гаврилов М.Ю., Лобанова Н.Н., Кулакова Е.В., Калинина Е.А. Клиническая и биологическая эффективность использования микрожидкостных чипов для селекции сперматозоидов при лечении бесплодия методами вспомогательных репродуктивных технологий. Акушерство и гинекология. 2024; 11: 138-45. [Makarova N.P., Sysoeva A.P., Chernyshev V.S., Gavrilov M.Yu., Lobanova N.N., Kulakova E.V., Kalinina E.A. Clinical and biological efficacy of microfluidic chips for sperm selection in infertility treatment using assisted reproductive technologies. Obstetrics and Gynecology. 2024; (11): 138-45 (in Russian)]. https://dx.doi.org/10.18565/aig.2024.172
Jahangiri A.R., Ziarati N., Dadkhah E., Bucak M.N., Rahimizadeh P., Shahverdi A. et al. Microfluidics: The future of sperm selection in assisted reproduction. Andrology. 2024; 12(6): 1236-52. https://dx.doi.org/10.1111/andr.13578
Колесов Д.В., Вишнякова П.А., Макарова Н.П., Московцев А.А., Чернышев В.С. Микрофлюидика для вспомогательных репродуктивных технологий. От рождения до активного долголетия: Сборник тезисов докладов II Международного форума геномных и биомедицинских технологий. Сургут: Издательский центр СурГУ; 2024: 9-10. [Kolesov D.V., Vishnyakova P.A., Makarova N.P., Moskovtsev A.A., Chernyshev V.S. Microfluidics for assisted reproductive technologies. From birth to active longevity: Collection of abstracts of reports of the II International Forum of Genomic and Biomedical Technologies. Surgut: Publishing Center of SurSU; 2024: 9-10. (in Russian)].
Патент на полезную модель № 230440U1 Российская Федерация, МПК C12N 5/076, G01N 33/487. Устройство для селекции мужских половых клеток с повышенной оплодотворяющей способностью для использования на эмбриологическом этапе программ лечения бесплодия методами вспомогательных репродуктивных технологий (POSHspermWash). Макарова Н.П., Чернышев В.С., Колесов Д.В., Сухих Г.Т. № 2024120398; заявл. 19.07.2024; опубл. 03.12.2024. [RU230440U1 Russian Federation, IPC C12N 5/076, G01N 33/487. Device for selection of male germ cells with increased fertilization capacity for use at the embryological stage of infertility treatment programs using assisted reproductive technologies (POSHspermWash). Makarova N.P., Chernyshev V.S., Kolesov D.V., Sukhikh G.T. No. 2024120398; appl. 19.07.2024; publ. 03.12.2024. (in Russian)].
Zhou L., Liu H., Liu S., Yang X., Dong Y., Pan Y. et al. Structures of sperm flagellar doublet microtubules expand the genetic spectrum of male infertility. Cell. 2023; 186(13): 2897-2910.e19. https://dx.doi.org/10.1016/j.cell.2023.05.009
Kumar N., Singh A.K. The anatomy, movement, and functions of human sperm tail: an evolving mystery. Biol. Reprod. 2021; 104(3): 508-20. https://dx.doi.org/10.1093/biolre/ioaa213
Tamburrino L., Marchiani S., Muratori M., Luconi M., Baldi E. Progesterone, spermatozoa and reproduction: An updated review. Mol. Cell. Endocrinol. 2020; 516: 110952. https://dx.doi.org/10.1016/j.mce.2020.110952
Mahé C., Zlotkowska A.M., Reynaud K., Tsikis G., Mermillod P., Druart X. et al. Sperm migration, selection, survival, and fertilizing ability in the mammalian oviduct. Biol. Reprod. 2021; 105(2): 317-31. https://dx.doi.org/10.1093/biolre/ioab105
Hirashima T., W P S., Noda T. Collective sperm movement in mammalian reproductive tracts. Semin. Cell Dev. Biol. 2025; 166: 13-21. https://dx.doi.org/10.1016/j.semcdb.2024.12.002
Roldan E.R.S., Teves M.E. Understanding sperm physiology: Proximate and evolutionary explanations of sperm diversity. Mol. Cell. Endocrinol. 2020; 518: 110980. https://dx.doi.org/10.1016/j.mce.2020.110980
Sheibak N., Zandieh Z., Amjadi F., Aflatoonian R. How sperm protects itself: A journey in the female reproductive system. J. Reprod. Immunol. 2024; 163: 104222. https://dx.doi.org/10.1016/j.jri.2024.104222
Cui Z., Wang Y., den Toonder J.M.J. Metachronal motion of biological and artificial cilia. Biomimetics (Basel). 2024; 9(4): 198. https://dx.doi.org/10.3390/biomimetics9040198
Lindemann C.B., Lesich K.A. The many modes of flagellar and ciliary beating: Insights from a physical analysis. Cytoskeleton (Hoboken). 2021; 78(2): 36-51. https://dx.doi.org/10.1002/cm.21656
Raidt J., Werner C., Menchen T., Dougherty G.W., Olbrich H., Loges N.T. et al. Ciliary function and motor protein composition of human fallopian tubes. Hum. Reprod. 2015; 30(12): 2871-80. https://dx.doi.org/10.1093/humrep/dev227
Suarez S.S. Mammalian sperm interactions with the female reproductive tract. Cell Tissue Res. 2016; 363(1): 185-94. https://dx.doi.org/10.1007/s00441-015-2244-2
Tung C.K., Ardon F., Roy A., Koch D.L., Suarez S.S., Wu M. Emergence of upstream swimming via a hydrodynamic transition. Phys. Rev. Lett. 2015; 114(10): 108102. https://dx.doi.org/10.1103/PhysRevLett.114.108102
Hyakutake T., Higashiyama D., Tsuchiya T. Prediction of sperm motion behavior in microfluidic channel using sperm swimming model. J. Biomech. 2024; 176: 112336. https://dx.doi.org/10.1016/j.jbiomech.2024.112336
Shiba K. Regulatory mechanisms for sperm chemotaxis and flagellar motility. Genesis. 2023; 61(6): e23549. https://dx.doi.org/10.1002/dvg.23549
Zhang Z., Liu J., Meriano J., Ru C., Xie S., Luo J. et al. Human sperm rheotaxis: a passive physical process. Sci. Rep. 2016; 6: 23553. https://dx.doi.org/10.1038/srep23553
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. U. S. A. 2015; 112(52): 15904-9. https://dx.doi.org/10.1073/pnas.1515159112
Bukatin A., Denissenko P., Kantsler V. Self-organization and multi-line transport of human spermatozoa in rectangular microchannels due to cell-cell interactions. Sci. Rep. 2020; 10(1): 9830. https://dx.doi.org/10.1038/s41598-020-66803-2
Romero-Aguirregomezcorta J., Sugrue E., Martínez-Fresneda L., Newport D., Fair S. Hyperactivated stallion spermatozoa fail to exhibit a rheotaxis-like behaviour, unlike other species. Sci. Rep. 2018; 8(1): 16897. https://dx.doi.org/10.1038/s41598-018-34973-9
Chinnasamy T., Kingsley J.L., Inci F., Turek P.J., Rosen M.P., Behr B. et al. Guidance and self-sorting of active swimmers: 3D periodic arrays increase persistence length of human sperm selecting for the fittest. Adv. Sci. (Weinh). 2018; 5(2): 1700531. https://dx.doi.org/10.1002/advs.201700531
Dai P., Chen C., Yu J., Ma C., Zhang X. New insights into sperm physiology regulation: Enlightenment from G-protein-coupled receptors. Andrology. 2024; 12(6): 1253-71. https://dx.doi.org/10.1111/andr.13593
Elango K., Kekäläinen J. Putting nose into reproduction: influence of nasal and reproductive odourant signaling on male reproduction. Mol. Reprod. Dev. 2025; 92(1): e70010. https://dx.doi.org/10.1002/mrd.70010
Jikeli J.F., Alvarez L., Friedrich B.M., Wilson L.G., Pascal R., Colin R. et al. Sperm navigation along helical paths in 3D chemoattractant landscapes. Nat. Commun. 2015; 6: 7985. https://dx.doi.org/10.1038/ncomms8985
Yoshida M., Yoshida K. Activation of motility and chemotaxis in the spermatozoa. Reprod. Med. Biol. 2025; 24(1): e12638. https://dx.doi.org/10.1002/rmb2.12638
Pérez-Cerezales S., Laguna-Barraza R., de Castro A.C., Sánchez-Calabuig M.J., Cano-Oliva E., de Castro-Pita F.J. et al. Sperm selection by thermotaxis improves ICSI outcome in mice. Sci. Rep. 2018; 8(1): 2902. https://dx.doi.org/10.1038/s41598-018-21335-8
Shirota K., Yotsumoto F., Itoh H., Obama H., Hidaka N., Nakajima K. et al. Separation efficiency of a microfluidic sperm sorter to minimize sperm DNA damage. Fertil. Steril. 2016; 105(2): 315-21.e1. https://dx.doi.org/10.1016/j.fertnstert.2015.10.023
Huang C.H., Chen C.H., Huang T.K., Lu F., Jen Huang J.Y., Li B.R. Design of a gradient-rheotaxis microfluidic chip for sorting of high-quality sperm with progressive motility. iScience. 2023; 26(8): 107356. https://dx.doi.org/10.1016/j.isci.2023.107356
Danis R.B., Samplaski M.K. Sperm morphology: history, challenges, and impact on natural and assisted fertility. Curr. Urol. Rep. 2019; 20(8): 43. https://dx.doi.org/10.1007/s11934-019-0911-7
El-Sherry T.M., Abdel-Ghani M.A., Abdel Hafez H.K., Abdelgawad M. Rheotaxis of sperm in fertile and infertile men. Syst. Biol. Reprod. Med. 2023; 69(1): 57-63. https://dx.doi.org/10.1080/19396368.2022.2141154
Yaghoobi M., Azizi M., Mokhtare A., Javi F., Abbaspourrad A. Rheotaxis quality index: a new parameter that reveals male mammalian in vivo fertility and low sperm DNA fragmentation. Lab. Chip. 2022; 22(8): 1486-97. https://dx.doi.org/10.1039/d2lc00150k
Romero-Aguirregomezcorta J., Laguna-Barraza R., Fernández-González R., Štiavnická M., Ward F., Cloherty J. et al. Sperm selection by rheotaxis improves sperm quality and early embryo development. Reproduction. 2021; 161(3): 343-52. https://dx.doi.org/10.1530/REP-20-0364
Yaghoobi M., Abdelhady A., Favakeh A., Xie P., Cheung S., Mokhtare A. et al. Faster sperm selected by rheotaxis leads to superior early embryonic development in vitro. Lab. Chip. 2024; 24(2): 210-23. https://dx.doi.org/10.1039/d3lc00737e
Faisal R.M., Ayeleru O.O., Modekwe H.U., Ramatsa I.M. Bibliometric study of plastics microfluidic chip from 1994 to 2022: A review. Heliyon. 2025; 11(2): e42102. https://dx.doi.org/10.1016/j.heliyon.2025.e42102
Zaferani M., Cheong S.H., Abbaspourrad A. Rheotaxis-based separation of sperm with progressive motility using a microfluidic corral system. Proc. Natl. Acad. Sci. U. S. A. 2018; 115(33): 8272-7. https://dx.doi.org/10.1073/pnas.1800819115
Sarbandi I.R., Lesani A., Moghimi Zand M., Nosrati R. Rheotaxis-based sperm separation using a biomimicry microfluidic device. Sci. Rep. 2021; 11: 18327. https://doi.org/10.1038/s41598-021-97602-y
Heidarnejad A., Sadeghi M., Arasteh S., Ghiass M.A. A novel microfluidic device for human sperm separation based on rheotaxis. Zygote. 2025; 33(1): 23-31. https://dx.doi.org/10.1017/S0967199424000467
Banti M., Van Zyl E., Kafetzis D. Sperm preparation with microfluidic sperm sorting chip may improve intracytoplasmic sperm injection outcomes compared to density gradient centrifugation. Reprod. Sci. 2024; 31(6): 1695-704. https://dx.doi.org/10.1007/s43032-024-01483-1
Ahmadkhani N., Saadatmand M., Kazemnejad S., Abdekhodaie M. Qualified sperm selection based on the rheotaxis and thigmotaxis in a microfluidic system. Biomed. Eng. Lett. 2023; 13: 671-80. https://dx.doi.org/10.1007/s13534-023-00294-8
Heydari A., Zabetian Targhi M., Halvaei I., Nosrati R. A novel microfluidic device with parallel channels for sperm separation using spermatozoa intrinsic behaviors. Sci. Rep. 2023; 13: 1185. https://dx.doi.org/10.1038/s41598-023-28315-7
Bouloorchi Tabalvandani M., Javadizadeh S., Badieirostami M. Bio-inspired progressive motile sperm separation using joint rheotaxis and boundary-following behavior. Lab. Chip. 2024; 24(6): 1636-47. https://dx.doi.org/10.1039/d3lc00893b

Received 25.03.2025

Accepted 15.05.2025

Natalya P. Makarova, Dr. Bio. Sci., Leading Researcher at the Department of IVF named after Prof. B.V. Leonov, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, np_makarova@oparina4.ru,
https://orcid.org/0000-0003-1396-7272
Alina Yu. Kapitannikova, Junior Researcher at the Biophotonics Laboratory, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, a_kapitannikova@oparina4.ru, https://orcid.org/0000-0002-0765-773X
Anastasia P. Sysoeva, Clinical Embryologist, Department of IVF named after Prof. B.V. Leonov, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, sysoeva.a.p@gmail.com, https://orcid.org/0000-0002-6502-4498
Vasiliy S. Chernyshev, PhD, Head of the Biophotonics Laboratory, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, v_chernyshev@oparina4.ru https://orcid.org/0000-0003-2372-7037
Elena A. Kalinina, Dr. Med. Sci., Professor, Head of the Department of IVF named after Prof. B.V. Leonov, Academician V.I. Kulakov National Medical Research Center
for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, e_kalinina@oparina4.ru,
https://orcid.org/0000-0002-8922-2878
Gennady T. Sukhikh, Academician of the RAS, Dr. Med. Sci., Professor, Director, Academician V.I. Kulakov National Medical Research Center for Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia, g_sukhikh@oparina4.ru, https://orcid.org/0000-0002-7712-1260

Sperm selection in assisted reproductive technology programs using active microfluidic methods based on positive rheotaxis

Makarova N.P., Kapitannikova A.Yu., Sysoeva A.P., Chernyshev V.S., Kalinina E.A., Sukhikh G.T.

Keywords

References

About the Authors

Similar Articles