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A microfluidic sperm-sorting device reduces the proportion of sperm with double-stranded DNA fragmentation

Published online by Cambridge University Press:  27 July 2021

A. Pujol
Affiliation:
Centro de Infertilidad y Reproducción Humana (CIRH)-Eugin Group, Plaça Eguilaz 14, Barcelona 08017, Spain
A. García-Peiró
Affiliation:
CIMAB, C/ Vallcorba1A-3A, Sant Quirze del Valles 08195, Spain
J. Ribas-Maynou
Affiliation:
CIMAB, C/ Vallcorba1A-3A, Sant Quirze del Valles 08195, Spain
R. Lafuente
Affiliation:
Centro de Infertilidad y Reproducción Humana (CIRH)-Eugin Group, Plaça Eguilaz 14, Barcelona 08017, Spain
D. Mataró
Affiliation:
Centro de Infertilidad y Reproducción Humana (CIRH)-Eugin Group, Plaça Eguilaz 14, Barcelona 08017, Spain
R. Vassena*
Affiliation:
Clínica EUGIN-Eugin Group, C/ Balmes 236, Barcelona 08029, Spain
*
Author for correspondence: R. Vassena. Clínica EUGIN-Eugin Group, C/ Balmes 236, Barcelona 08029, Spain. E-mail: rvassena@eugin.es

Summary

Sperm DNA fragmentation can be produced in one (ssSDF) or both (dsSDF) DNA strands, linked to difficulties in naturally achieving a pregnancy and recurrent miscarriages, respectively. The techniques more frequently used to select sperm require centrifugation, which may induce sperm DNA fragmentation (SDF). The objective of this study was to assess whether the microfluidic-based device FertileChip® (now ZyMot®ICSI) can diminish the proportion of sperm with dsSDF. First, in a blinded split pilot study, the semen of nine patients diagnosed with ≥60% dsSDF, was divided into three aliquots: not processed, processed with FertileChip®, and processed with swim up. The three aliquots were all analyzed using neutral COMET for the detection of dsSDF, resulting in a reduction of 46% (P < 0.001) with FertileChip® (dsSDF: 34.9%) compared with the ejaculate and the swim up (dsSDF: 65%). Thereafter, the FertileChip® was introduced into clinical practice and a cohort of 163 consecutive ICSI cycles of patients diagnosed with ≥60% dsSDF was analyzed. Fertilization rate was 75.41%. Pregnancy rates after the first embryo transfer were 53.2% (biochemical), 37.8% (clinical), 34% (ongoing) and the live birth rate was 28.8%. Cumulative pregnancy rates after one (65.4% of patients), two (27.6% of patients) or three (6.4% of patients) transfers were 66% (biochemical), 56.4% (clinical), 53.4% (ongoing) and the live birth rate was 42%. The selection of spermatozoa using Fertile Chip® significantly diminishes the percentage of dsSDF, compared with either the fresh ejaculate or after swim up. Its applicability in ICSI cycles of patients with high dsSDF resulted in good laboratory and clinical outcomes.

Type
Research Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Agarwal, A, Ikemoto, I and Loughlin, KR (1994). Effect of sperm washing on levels of reactive oxygen species in semen. Arch Androl 33, 157–62.CrossRefGoogle ScholarPubMed
Alijotas-Reig, J and Garrido-Gimenez, C (2013). Current concepts and new trends in the diagnosis and management of recurrent miscarriage. Obstet Gynecol Surv 68, 445–66.Google ScholarPubMed
Bach, PV and Schlegel, PN (2016). Sperm DNA damage and its role in IVF and ICSI. Basic Clin Androl 26, 15.CrossRefGoogle ScholarPubMed
Boomsma, CM, Heineman, MJ, Cohlen, BJ and Farquhar, C (2007). Semen Preparation Techniques for Intrauterine Insemination. The Cochrane Database of Systematic Reviews, CD004507.CrossRefGoogle Scholar
Casanovas, A, Ribas-Maynou, J, Lara-Cerrillo, S, Jimenez-Macedo, AR, Hortal, O, Benet, J, Carrera, J and García-Peiró, A (2019). Double-stranded sperm DNA damage is a cause of delay in embryo development and can impair implantation rates. Fertil Steril 111, 699707.e1.CrossRefGoogle ScholarPubMed
Cuevas Saiz, I, Carme Pons Gatell, M, Vargas, MC, Delgado Mendive, A, Rives Enedáguila, N, Moragas Solanes, M, Canal, BC, López, JT, Bonet, AB and Hurtado de Mendoza Acosta, MV (2018). The Embryology Interest Group: updating ASEBIR’s morphological scoring system for early embryos, morulae and blastocysts. Med Reprod Embriol Clín 5, 4254.Google Scholar
Esbert, M, Pacheco, A, Vidal, F, Florensa, M, Riqueros, M, Ballesteros, A, Garrido, N and Calderón, G (2011). Impact of sperm DNA fragmentation on the outcome of IVF with own or donated oocytes. Reprod Biomed Online 23, 704–10.Google ScholarPubMed
Gardner, DK and Schoolcraft, WB (1999). Towards reproductive certainty: Infertility and genetics beyond. In: Jansen, R and Mortimer, D (eds), In Vitro Culture of Human Blastocysts, pp. 378–88. Carnforth, UK: Parthenon Publishing Group.Google ScholarPubMed
Jan, SZ, Hamer, G, Repping, S, de Rooij, DG, van Pelt, AM and Vormer, TL (2012). Molecular control of rodent spermatogenesis. Biochim Biophys Acta 1822, 1838–50.CrossRefGoogle ScholarPubMed
Lange, J, Pan, J, Cole, F, Thelen, MP, Jasin, M and Keeney, S (2011). ATM controls meiotic double-strand break formation. Nature 479(7372), 237–40.CrossRefGoogle ScholarPubMed
Lara-Cerrillo, S, Ribas-Maynou, J, Rosado-Iglesias, C, Lacruz-Ruiz, T, Benet, J and García-Peiró, A (2021). Sperm selection during ICSI treatments reduces single- but not double-strand DNA break values compared to the semen sample. J Assist Reprod Genet 38, 1187–96.CrossRefGoogle ScholarPubMed
Lattes, K, Checa, MA, Vassena, R, Brassesco, M and Vernaeve, V (2017). There is no evidence that the time from egg retrieval to embryo transfer affects live birth rates in a freeze-all strategy. Hum Reprod 32, 368–74.CrossRefGoogle Scholar
Muratori, M, Tarozzi, N, Carpentiero, F, Danti, S, Perrone, FM, Cambi, M, Casini, A, Azzari, C, Boni, L, Maggi, M, Borini, A and Baldi, E (2019). Sperm selection with density gradient centrifugation and swim up: effect on DNA fragmentation in viable spermatozoa. Sci Rep 9, 7492.CrossRefGoogle ScholarPubMed
Parrella, A, Keating, D, Cheung, S, Xie, P, Stewart, JD, Rosenwaks, Z and Palermo, GD (2019). A treatment approach for couples with disrupted sperm DNA integrity and recurrent ART failure. J Assist Reprod Genet 36, 2057–66.CrossRefGoogle ScholarPubMed
Pujol, A, García, D, Obradors, A, Rodríguez, A and Vassena, R (2018). Is there a relation between the time to ICSI and the reproductive outcomes? Hum Reprod 33, 797806.Google Scholar
Quinn, MM, Jalalian, L, Ribeiro, S, Ona, K, Demirci, U, Cedars, MI and Rosen, MP (2018). 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 33, 1388–93.Google ScholarPubMed
Ribas-Maynou, J, García-Peiró, A, Abad, C, Amengual, MJ, Navarro, J and Benet, J (2012a). Alkaline and neutral comet assay profiles of sperm DNA damage in clinical groups. Hum Reprod 27, 652–8.CrossRefGoogle ScholarPubMed
Ribas-Maynou, J, García-Peiró, A, Fernández-Encinas, A, Amengual, MJ, Prada, E, Cortés, P, Navarro, J and Benet, J (2012b). Double stranded sperm DNA breaks, measured by comet assay, are associated with unexplained recurrent miscarriage in couples without a female factor. PLoS ONE, 7, e44679.CrossRefGoogle ScholarPubMed
Ribas-Maynou, J, García-Peiró, A, Fernández-Encinas, A, Abad, C, Amengual, MJ, Prada, E, Navarro, J and Benet, J (2013). Comprehensive analysis of sperm DNA fragmentation by five different assays: TUNEL assay, SCSA, SCD test and alkaline and neutral comet assay. Andrology 1, 715–22.CrossRefGoogle ScholarPubMed
Ribas-Maynou, J, Fernández-Encinas, A, García-Peiró, A, Prada, E, Abad, C, Amengual, MJ, Navarro, J and Benet, J (2014a). Human semen cryopreservation: a sperm DNA fragmentation study with alkaline and neutral comet assay. Andrology 2, 83–7.CrossRefGoogle ScholarPubMed
Ribas-Maynou, J, Gawecka, JE, Benet, J and Ward, WS (2014b). Double-stranded DNA breaks hidden in the neutral comet assay suggest a role of the sperm nuclear matrix in DNA integrity maintenance. Mol Hum Reprod 20, 330–40.CrossRefGoogle ScholarPubMed
Samuel, R, Feng, H, Jafek, A, Despain, D, Jenkins, T and Gale, B (2018). Microfluidic-based sperm sorting and analysis for treatment of male infertility. Trans Androl Urol 7(Suppl 3), S336–47.CrossRefGoogle ScholarPubMed
SEF (2018) (Sociedad Española de la Fertilidad). Retrieved from https://www.registrosef.com/ Google Scholar
Shirota, K, Yotsumoto, F, Itoh, H, Obama, H, Hidaka, N, Nakajima, K and Miyamoto, S (2016). Separation efficiency of a microfluidic sperm sorter to minimize sperm DNA damage. Fertil Steril 105, 315–21, e311.CrossRefGoogle ScholarPubMed
Simon, L and Lewis, SE (2011). Sperm DNA damage or progressive motility: which one is the better predictor of fertilization in vitro? System Biol Reprod Med 57, 133–8.Google ScholarPubMed
Smith, GD and Takayama, S (2017). Application of microfluidic technologies to human assisted reproduction. Mol Hum Reprod 23, 257–68.Google ScholarPubMed
Suarez, SS and Wu, M (2017). Microfluidic devices for the study of sperm migration. Mol Hum Reprod 23, 227–34.Google Scholar
Tasoglu, S, Safaee, H, Zhang, X, Kingsley, JL, Catalano, PN, Gurkan, UA, Nureddin, A, Kayaalp, E, Anchan, RM, Maas, RL, Tüzel, E and Demirci, U (2013). Exhaustion of racing sperm in nature-mimicking microfluidic channels during sorting. Small 9, 3374–84.CrossRefGoogle ScholarPubMed
Tremellen, K (2008). Oxidative stress and male infertility—A clinical perspective. Hum Reprod Update 14, 243–58.CrossRefGoogle Scholar
Tvrdá, E, López-Fernández, C, Sánchez-Martín, P and Gosálvez, J (2018). Sperm DNA fragmentation in donors and normozoospermic patients attending for a first spermiogram: Static and dynamic assessment. Andrologia Epub ahead of print.Google Scholar
Vaughan, DA and Sakkas, D (2019). Sperm selection methods in the 21st century. Biol Reprod 101, 1076–82.CrossRefGoogle ScholarPubMed
World Health Organization (2010). WHO Laboratory manual for the examination and processing of human semen (5th edn). Geneva: World Health Organization.Google Scholar
Wyns, C, Bergh, C, Calhaz-Jorge, C, De Geyter, Ch, Kupka, MS, Motrenko, T, Rugescu, I, Smeenk, J, Tandler-Schneider, A, Vidakovic, S and Goossens, V (2020). ART in Europe, 2016: results generated from European registries by ESHRE European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod Open 2020, hoaa032.CrossRefGoogle Scholar
Yildiz, K and Yuksel, S (2019). Use of microfluidic sperm extraction chips as an alternative method in patients with recurrent in vitro fertilisation failure. J Assist Reprod Genet 36, 1423–9.CrossRefGoogle ScholarPubMed