Ulyanovsk Medico-biological Journal

CLINICAL MEDICINE

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DOI 10.34014/2227-1848-2024-1-82-90

USING MICROFLUIDIC SPERM SORTING CHIPS IN PATIENTS WITH INFERTILITY

L.A. Belyaeva1, O.V. Shurygina1,2, M.T. Tugushev1,2, S.Yu. Mironov1

1Samara State Medical University, Samara, Ministry of Health of the Russian Federation, Russia;

2 Medical Centre Mother and Child, Samara, Russia

 

The purpose of the work is to analyze the effectiveness of the FERTILE microfluidic sperm sorting chip.

Materials and Methods. The technique under consideration is currently experimental. It was used in patients after obtaining voluntary informed consent. A retrospective analysis of medical records of 4 groups of patients was carried out. The patients were divided into 2 experimental and 2 control groups. In total the authors analyzed 54 medical records. The microfluidic sperm sorting chip (FERTILE/FERTILE PLUS CHIP) are intended for the selection of normal mobile spermatozoids, which can be used for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The indicators of preimplantation embryo development in vitro were assessed.

Results. Embryological parameters of infertility treatment using ART were analyzed. Key indicators of preimplantation embryo development (fertilization rate, blastocyst development, embryo cryopreservation) were higher in both experimental groups compared to control ones (standard semen processing). Embryos were obtained by fertilization with sperm which undergone microfluidic sorting. Embryo culture suggests a more physiological nature of gamete separation. During standard ejaculate processing centifugation is used to obtain a fraction of active sperm. However, it negatively affects the cytophysiology of male gametes and causes breaks in the DNA chain in the spermatozoid head.

Conclusion. The authors observed the improvement in embryological parameters of in vitro embryos, which were obtained by means of microfluidic chip-based sperm selection. This method allows us to select cytophysiologically competent sperm and improve the embryo quality without increasing DNA fragmentation rate.

Key words: microfluidics, infertility, assisted reproductive technologies, sperm selection.

 

Conflict of interest. The authors declare no conflict of interest.

Author contributions

Research concept and design: Belyaeva L.A., Shurygina O.V.

Literature search, participation in the research study, data processing: Tugushev M.T.

Statistical data processing: Mironov S.Yu.

Data analysis and interpretation: Belyaeva L.A.

Text writing and editing: Belyaeva L.A.

 

References

  1. De Wagenaar B., Berendsen J.T.W. Microfluidic single sperm entrapment and analysis. Lab Chip. 2015; 15 (5): 1294–1301.

  2. Cho B.S., Schuster T.G., Zhu X., Chang D., Smith G.D., Takayama S. Passively driven integrated microfluidic system for separation of motile sperm. Anal. Chem. 2003; 75 (7): 1671–1675.

  3. Schuster T.G., Cho B., Keller L.M., Takayama S., Smith G.D. Isolation of motile spermatozoa from semen samples using microfluidics. Reprod. Biomed. Online. 2003; 7 (1): 75–81.

  4. Cagla Guler, Sureyya Melil. Sperm Selection and Embryo Development: A Comparison of the Density Gradient Centrifugation and Microfluidic Chip Sperm Preparation Methods in Patients with Astheno-Teratozoospermia. Life (Basel). 2021; 11 (9): 933.

  5. Shan-Shan Tang, Jin-Chun Lu. Analysis of selected sperm samples by a computer-assisted system with high frame rate: A prospective study. Health Sci Rep. 2023; 6 (5): e1217.

  6. Lingling Qiu, Jinxiang Wu. Selection of fertilization strategies for different sperm parameters in vitro fertilization. Ann Transl Med. 2022; 10 (18): 996.

  7. Carrageta D.F., Bernardino R.L., Soveral G., Calamita G., Alves M.G., Oliveira P.F. Aquaporins and male (in)fertility: Expression and role throughout the male reproductive tract. Arch. Biochem. Biophys. 2020; 679: 108222.

  8. Chang-Yu Chen, Tsun-Chao Chiang. Sperm quality assessment via separation and sedimentation in a microfluidic device. Analyst. 2013; 138 (17): 4967–4974.

  9. Pinar Ozcan, Taha Takmaz. Does the use of microfluidic sperm sorting for the sperm selection improve in vitro fertilization success rates in male factor infertility? J Obstet Gynaecol Res. 2021; 47 (1): 382–388.

  10. Huang H., Huang P., Yao D. Enhanced efficiency of sorting sperm motility utilizing a microfluidic chip. Microsystem Technologies. 2015; 23 (2): 305–312.

  11. Quinn M.M., Jalalian L., Ribeiro S., Ona K., Demirci U., Cedars M.I., Rosen M.P. 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 (8): 1388–1393.

  12. Cagla Guler, Sureyya Melil. Sperm Selection and Embryo Development: A Comparison of the injection for unexplained infertility: a prospective, randomized controlled trial. J Assist Reprod Genet. 2019; 36 (3): 403–409.

  13. Smith G.D., Takayama S. Application of microfluidic technologies to human assisted reproduction. Mol. Hum. Reprod. 2017; 23 (4): 257–268. DOI: https://dx.doi.org/10.1093/molehr/gaw076.

  14. Samuel R., Feng H., Jafek A., Despain D., Jenkins T., Gale B. Microfluidic-based sperm sorting & analysis for treatment of male infertility. Transl. Androl. Urol. 2018; 7 (Suppl. 3): 336–347.

  15. Narayanamurthy V., Jeroish Z.E., Bhuvaneshwari K.S., Bayat P., Premkumar R., Samsuri F., Yusoff M.M. Advances in passively driven microfluidics and lab-on-chip devices: a comprehensive literature review and patent analysis. RSC Adv. 2020; 10 (20): 11652–11680.

  16. Manhee Lee, Jin Woo Park. Viscous Cervical Environment-on-a-Chip for Selecting High-Quality Sperm from Human Semen. Biomedicines. 2021; 9 (10): 1439.

  17. Ender Yalcinkaya Kalyan, Seren Can Celik. 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 Andrologia. 2019; 51 (10): e13403.

  18. Molly M. Quinn, Liza Jalalian. 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 (8): 1388–1393.

  19. Zhang X., Khimji I., Gurkan U.A., Safaee H., Catalano P.N., Keles H.O. Lensless imaging for simultaneous microfluidic sperm monitoring and sorting. Lab. Chip. 2011; 11 (15): 2535–2540.

  20. Nasr Esfahani M.H., Deemeh M.R., Tavalaee M., Sekhavati M.H., Gourabi H. Zeta sperm selection improves pregnancy rate and alters sex ratio in male factor infertility patients: A double-blind, randomized clinical trial. Int. J. Fertil. Steril. 2016; 10 (2): 253–260.

Received September 15, 2023; accepted December 4, 2023.

 

Information about the authors

Belyaeva Lidiya Aleksandrovna, Postgraduate Student, Chair of Histology and Embryology, Samara State Medical University, Ministry of Health of the Russian Federation. 443099, Russia, Samara, Chapaevskaya St., 89; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-2095-0452

Shurygina Oksana Viktorovna, Doctor of Medical Sciences, Professor, Chair of Histology and Embryology, Chair of Reproductive Medicine, Clinical Embryology and Genetics, Samara State Medical University, Ministry of Health of the Russian Federation. 443099, Russia, Samara, Chapaevskaya St., 89; Head of the Embryology Laboratory, Medical Centre Mother and Child. 443067, Russia, Samara, Entuziastov St., 29; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/000-0002-3903-4350

Tugushev Marat Talgatovich, Doctor of Medical Sciences, Head of the Chair of Reproductive Medicine, Clinical Embryology and Genetics, Samara State Medical University, Ministry of Health of the Russian Federation. 443099, Russia, Samara, Chapaevskaya St, 89; Chief Physician, Medical Centre Mother and Child. 443067, Russia, Samara, Entuziastov St., 29; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-00002-3328-3217

Mironov Sergey Yur'evich, Postgraduate Student, Chair of Histology and Embryology, Samara State Medical University, Ministry of Health of the Russian Federation. 443099, Russia, Samara, Chapaevskaya St., 89; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-9291-5376

 

For citation

Belyaeva L.A., Shurygina O.V., Tugushev M.T., Mironov S.Yu. Opyt primeneniya mikrozhidkostnykh chipov dlya sortirovki spermy u patsientov s lecheniem besplodiya [Using microfluidic sperm sorting chips in patients with infertility]. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2024; 1: 82–90. DOI: 10.34014/2227-1848-2024-1-82-90 (in Russian).

 

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УДК 57.088.7

DOI 10.34014/2227-1848-2024-1-82-90

ОПЫТ ПРИМЕНЕНИЯ МИКРОЖИДКОСТНЫХ ЧИПОВ ДЛЯ СОРТИРОВКИ СПЕРМЫ У ПАЦИЕНТОВ С ЛЕЧЕНИЕМ БЕСПЛОДИЯ

Л.А. Беляева1, О.В. Шурыгина1,2, М.Т. Тугушев1,2, С.Ю. Миронов1

1 ФГБОУ ВО «Самарский государственный медицинский университет» Минздрава России,
г. Самара, Россия;

2 АО «Медицинская компания ИДК», г. Самара, Россия

 

Цель работы – анализ эффективности использования микрожидкостных чипов для селекции спермы.

Материалы и методы. Методика в настоящее время является экспериментальной и применялась после предварительного получения индивидуального добровольного согласия пациента. Проводился ретроспективный анализ медицинских карт 4 групп пациенток (2 анализируемые, 2 контрольные). Общее число изученных медицинских карт составило 54. Микрожидкостный чип и его модификации (FERTILE/FERTILE PLUS CHIP) предназначены для отбора и селекции нормальных подвижных сперматозоидов для использования в процедурах экстракорпорального оплодотворения (ЭКО), интрацитоплазматической инъекции сперматозоида в яйцеклетку (ИКСИ). Оценивались показатели преимплантационного развития эмбрионов in vitro.

Результаты. Были проанализированы эмбриологические показатели циклов лечения бесплодия методами ВРТ. Ключевые показатели преимплантационного развития эмбрионов: уровень оплодотворения, дорастания до бластоцисты, криоконсервации эмбрионов – были выше в обеих анализируемых группах по сравнению с контрольными группами (со стандартной обработкой спермы). Полученные результаты по культивированию эмбрионов, созданных при оплодотворении сперматозоидами, полученными на основе селекции с помощью микрофлюидных чипов, позволяют предполагать более физиологичный характер сепарации гамет. Центрифугирование при стандартной обработке эякулята для получения фракции активно-подвижных сперматозоидов отрицательно влияет на цитофизиологию мужских гамет и вызывает разрывы в цепочке ДНК в головке сперматозоида.

Выводы. Выявлены тенденции к улучшению эмбриологических показателей культивирования эмбрионов in vitro, полученных при селекции сперматозоидов с помощью микрожидкостных чипов. Данный метод позволяет отбирать цитофизиологически компетентные сперматозоиды, не повышая показатель фрагментации ДНК и улучшая качество эмбрионов.

Ключевые слова: микрофлюидика, бесплодие, вспомогательные репродуктивные технологии, селекция сперматозоидов.

 

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов

Концепция и дизайн исследования: Беляева Л.А., Шурыгина О.В.

Литературный поиск, участие в исследовании, обработка материала: Тугушев М.Т.

Статистическая обработка данных: Миронов С.Ю.

Анализ и интерпретация данных: Беляева Л.А.

Написание и редактирование текста: Беляева Л.А.

 

Литература

  1. De Wagenaar B., Berendsen J.T.W. Microfluidic single sperm entrapment and analysis. Lab Chip. 2015; 15 (5): 1294–1301.

  2. Cho B.S., Schuster T.G., Zhu X., Chang D., Smith G.D., Takayama S. Passively driven integrated microfluidic system for separation of motile sperm. Anal. Chem. 2003; 75 (7): 1671–1675.

  3. Schuster T.G., Cho B., Keller L.M., Takayama S., Smith G.D. Isolation of motile spermatozoa from semen samples using microfluidics. Reprod. Biomed. Online. 2003; 7 (1): 75–81.

  4. Cagla Guler, Sureyya Melil. Sperm Selection and Embryo Development: A Comparison of the Density Gradient Centrifugation and Microfluidic Chip Sperm Preparation Methods in Patients with Astheno-Teratozoospermia. Life (Basel). 2021; 11 (9): 933.

  5. Shan-Shan Tang, Jin-Chun Lu. Analysis of selected sperm samples by a computer-assisted system with high frame rate: A prospective study. Health Sci Rep. 2023; 6 (5): e1217.

  6. Lingling Qiu, Jinxiang Wu. Selection of fertilization strategies for different sperm parameters in vitro fertilization. Ann Transl Med. 2022; 10 (18): 996.

  7. Carrageta D.F., Bernardino R.L., Soveral G., Calamita G., Alves M.G., Oliveira P.F. Aquaporins and male (in)fertility: Expression and role throughout the male reproductive tract. Arch. Biochem. Biophys. 2020; 679: 108222.

  8. Chang-Yu Chen, Tsun-Chao Chiang. Sperm quality assessment via separation and sedimentation in a microfluidic device. Analyst. 2013; 138 (17): 4967–4974.

  9. Pinar Ozcan, Taha Takmaz. Does the use of microfluidic sperm sorting for the sperm selection improve in vitro fertilization success rates in male factor infertility? J Obstet Gynaecol Res. 2021; 47 (1): 382–388.

  10. Huang H., Huang P., Yao D. Enhanced efficiency of sorting sperm motility utilizing a microfluidic chip. Microsystem Technologies. 2015; 23 (2): 305–312.

  11. Quinn M.M., Jalalian L., Ribeiro S., Ona K., Demirci U., Cedars M.I., Rosen M.P. 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 (8): 1388–1393.

  12. Cagla Guler, Sureyya Melil. Sperm Selection and Embryo Development: A Comparison of the injection for unexplained infertility: a prospective, randomized controlled trial. J Assist Reprod Genet. 2019; 36 (3): 403–409.

  13. Smith G.D., Takayama S. Application of microfluidic technologies to human assisted reproduction. Mol. Hum. Reprod. 2017; 23 (4): 257–268. DOI: https://dx.doi.org/10.1093/molehr/gaw076.

  14. Samuel R., Feng H., Jafek A., Despain D., Jenkins T., Gale B. Microfluidic-based sperm sorting & analysis for treatment of male infertility. Transl. Androl. Urol. 2018; 7 (Suppl. 3): 336–347.

  15. Narayanamurthy V., Jeroish Z.E., Bhuvaneshwari K.S., Bayat P., Premkumar R., Samsuri F., Yusoff M.M. Advances in passively driven microfluidics and lab-on-chip devices: a comprehensive literature review and patent analysis. RSC Adv. 2020; 10 (20): 11652–11680.

  16. Manhee Lee, Jin Woo Park. Viscous Cervical Environment-on-a-Chip for Selecting High-Quality Sperm from Human Semen. Biomedicines. 2021; 9 (10): 1439.

  17. Ender Yalcinkaya Kalyan, Seren Can Celik. 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 Andrologia. 2019; 51 (10): e13403.

  18. Molly M. Quinn, Liza Jalalian. 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 (8): 1388–1393.

  19. Zhang X., Khimji I., Gurkan U.A., Safaee H., Catalano P.N., Keles H.O. Lensless imaging for simultaneous microfluidic sperm monitoring and sorting. Lab. Chip. 2011; 11 (15): 2535–2540.

  20. Nasr Esfahani M.H., Deemeh M.R., Tavalaee M., Sekhavati M.H., Gourabi H. Zeta sperm selection improves pregnancy rate and alters sex ratio in male factor infertility patients: A double-blind, randomized clinical trial. Int. J. Fertil. Steril. 2016; 10 (2): 253–260.

Поступила в редакцию 15.09.2023; принята 04.12.2023.

 

Авторский коллектив

Беляева Лидия Александровна – аспирант кафедры гистологии и эмбриологии, ФГБОУ ВО «Самарский государственный медицинский университет» Минздрава России. 443099, Россия, г. Самара, ул. Чапаевская, 89; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-2095-0452

Шурыгина Оксана Викторовна – доктор медицинских наук, профессор кафедры гистологии и эмбриологии, профессор кафедры репродуктивной медицины, клинической эмбриологии и генетики, ФГБОУ ВО «Самарский государственный медицинский университет» Минздрава России. 443099, Россия, г. Самара, ул. Чапаевская, 89; заведующая эмбриологической лабораторией Клинического госпиталя ИДК «Мать и дитя», ОА «Медицинская компания ИДК». 443067, Россия, г. Самара, ул. Энтузиастов, 29; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/000-0002-3903-4350

Тугушев Марат Талгатович – доктор медицинских наук, заведующий кафедрой репродуктивной медицины, клинической эмбриологии и генетики, ФГБОУ ВО «Самарский государственный медицинский университет» Минздрава России. 443099, Россия, г. Самара, ул. Чапаевская, 89; главный врач, АО «Медицинская компания ИДК». 443067, Россия, г. Самара, ул. Энтузиастов, 29; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-00002-3328-3217

Миронов Сергей Юрьевич – соискатель ученой степени кандидата медицинских наук кафедры гистологии и эмбриологии, ФГБОУ ВО «Самарский государственный медицинский университет» Минздрава России. 443099, Россия, г. Самара, ул. Чапаевская, 89; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-9291-5376

 

Образец цитирования

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. DOI: 10.34014/2227-1848-2024-1-82-90.