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Clinical Utility of Sperm Function Tests in Predicting Male Fertility: A Systematic Review

  • Male Reproduction: Review
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Abstract

Routine semen analysis provides considerable information regarding sperm parameters; however, it is not solely adequate to predict male fertility potential. In the past two decades, several advance sperm function tests have been developed. The present systematic review intends to assess the clinical utility of available advance sperm function tests in predicting the male fertility potential. A systematic literature search was conducted as per PRISMA guidelines using PubMed, MEDLINE, Google Scholar, and Cochrane Library. Different keywords either singly or in combination were used to retrieve the relevant articles related to sperm function tests, male fertility, and pregnancy outcomes. A total of 5169 articles were obtained, out of which 110 meeting the selection criteria were included in this review. The majorly investigated sperm function tests are hypo-osmotic swelling test, acrosome reaction test, sperm capacitation test, hemizona binding assay, sperm DNA fragmentation test, seminal reactive oxygen species test, mitochondrial dysfunction tests, antisperm antibody test, nuclear chromatin de-condensation (NCD) test, etc. The different advance sperm function tests analyse different aspects of sperm function. Hence, any one test may not be helpful to appropriately predict the male fertility potential. Currently, the unavailability of high-quality clinical data, robust thresholds, complex protocols, high cost, etc., are the limiting factors and prohibiting current sperm function tests to reach the clinics. Further multi-centric research efforts are required to fulfil the existing lacunas and pave the way for these tests to be introduced into the clinics.

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Abbreviations

NCD:

Nuclear chromatin de-condensation

ART:

Assisted reproductive techniques

PCBs:

Polychlorinated biphenyls

ROS:

Reactive oxygen species

CASA:

Computer assisted semen analysis

IVF/IUI/ICSI:

In vitro fertilisation/intrauterine insemination/intracytoplasmic sperm injection

ZIAR:

Zona induced acrosome reaction

TUNEL:

Terminal deoxytransferase mediated deoxyuridine triphosphate (dUTP) nick end labelling

TdT:

Terminal deoxyribonucleotide triphosphates

SCSA:

Sperm chromatin structure assay

SCD:

Sperm chromatin dispersion

TB:

Toluidine blue

HOS:

Hypoosmotic swelling test

MAR:

Mixed antiglobulin reaction

IBT:

Immunobead test

DCFDA:

2’,7’–dichlorofluorescin diacetate

ORP:

Oxidation-reduction potential

GM1:

Monosialotetrahexosylganglioside

ZP:

Zona pellucida

HZA:

Hemizona assay

HZI:

Hemizona index

AO:

Acridine orange

DFI:

DNA fragmentation index

HDS:

High DNA stainable cells

ASA:

Antisperm antibodies

RCR:

Respiratory control ratio

MMP:

Mitochondrial membrane potential

JC-1:

Tetraethylbenzimidazolylcarbocyanine iodide

Mt-DNAcn:

Sperm mitochondrial DNA copy number

NBT:

Nitro blue tetrazolium

8-OHdG:

8-Hydroxydeoxyguanosine

SDF:

Sperm DNA fragmentation

RPL:

Recurrent pregnancy loss

ETs:

Embryo transfers

AR:

Acrosome reaction

COH:

Controlled ovarian hyper stimulation

LBR:

Live birth rate

STF:

Sperm function test

References

  1. Mann U, Shiff B, Patel P. Reasons for worldwide decline in male fertility. Curr Opin Urol. 2020;30(3):296–301. https://doi.org/10.1097/MOU.0000000000000745.

    Article  PubMed  Google Scholar 

  2. Sharlip ID, Jarow JP, Belker AM, Lipshultz LI, Sigman M, Thomas AJ, Schlegel PN, Howards SS, Nehra A, Damewood MD, Overstreet JW, Sadovsky R. Best practice policies for male infertility. Fertil Steril. 2002;77(5):873–82. https://doi.org/10.1016/s0015-0282(02)03105-9.

    Article  PubMed  Google Scholar 

  3. Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: a review of literature. J Hum Reprod Sci. 2015;8(4):191–6. https://doi.org/10.4103/0974-1208.170370.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Esteves SC. Novel concepts in male factor infertility: clinical and laboratory perspectives. J Assist Reprod Genet. 2016;33(10):1319–35. https://doi.org/10.1007/s10815-016-0763-8.

  5. Krzastek SC, Farhi J, Gray M, Smith RP. Impact of environmental toxin exposure on male fertility potential. Transl Androl Urol. 2020;9(6):2797–813. https://doi.org/10.21037/tau-20-685.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Durairajanayagam D, Singh D, Agarwal A, Henkel R. Causes and consequences of sperm mitochondrial dysfunction. Andrologia. 2021 Feb;53(1):e13666. https://doi.org/10.1111/and.13666.

    Article  CAS  PubMed  Google Scholar 

  7. Arya D, Balasinor N, Singh D. Varicocoele-associated male infertility: cellular and molecular perspectives of pathophysiology. Andrology. 2022;10(8):1463–83. https://doi.org/10.1111/andr.13278.

    Article  CAS  PubMed  Google Scholar 

  8. Esteves SC. Clinical relevance of routine semen analysis and controversies surrounding the 2010 World Health Organization criteria for semen examination. Int Braz J Urol. 2014;40(4):443–53. https://doi.org/10.1590/S1677-5538.IBJU.2014.04.02.

    Article  PubMed  Google Scholar 

  9. Vasan SS. Semen analysis and sperm function tests: how much to test? Indian J Urol. 2011 Jan;27(1):41–8. https://doi.org/10.4103/0970-1591.78424.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Björndahl L. O-285 The 6th edition of the WHO manual for the examination and processing of human semen: how should it affect our practice? Human Reproduction. 2023;38(Supplement_1):dead093-345.

  11. Douglas C, Parekh N, Kahn LG, Henkel R, Agarwal A. A novel approach to improving the reliability of manual semen analysis: a paradigm shift in the workup of infertile men. World J Mens Health. 2021;39(2):172–85. https://doi.org/10.5534/wjmh.190088.

    Article  PubMed  Google Scholar 

  12. Moody MA, Cardona C, Simpson AJ, Smith TT, Travis AJ, Ostermeier GC. Validation of a laboratory-developed test of human sperm capacitation. Mol Reprod Dev. 2017;84(5):408–22. https://doi.org/10.1002/mrd.22801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Matamoros-Volante A, Moreno-Irusta A, Torres-Rodriguez P, Giojalas L, Gervasi MG, Visconti PE, Treviño CL. Semi-automatized segmentation method using image-based flow cytometry to study sperm physiology: the case of capacitation-induced tyrosine phosphorylation. Mol Hum Reprod. 2018;24(2):64–73.

    Article  CAS  PubMed  Google Scholar 

  14. Liu DY, Baker HW. A simple method for assessment of the human acrosome reaction of spermatozoa bound to the zona pellucida: lack of relationship with ionophore A23187-induced acrosome reaction. Hum Reprod. 1996;11(3):551–7. https://doi.org/10.1093/humrep/11.3.551.

    Article  CAS  PubMed  Google Scholar 

  15. Oehninger S, Morshedi M, Franken D. The hemizona assay for assessment of sperm function. Methods Mol Biol. 2013;927:91–102. https://doi.org/10.1007/978-1-62703-038-0_9.

    Article  CAS  PubMed  Google Scholar 

  16. Glazier DB, Marmar JL, Diamond SM, Gibbs M, Corson SL. A modified acrosome induction test. Arch Androl. 2000;44(1):59–64. https://doi.org/10.1080/014850100262425.

    Article  CAS  PubMed  Google Scholar 

  17. Carver-Ward JA, Jaroudi KA, Hollanders JM, Einspenner M. High fertilization prediction by flow cytometric analysis of the CD46 antigen on the inner acrosomal membrane of spermatozoa. Hum Reprod. 1996;11(9):1923–8. https://doi.org/10.1093/oxfordjournals.humrep.a019518.

    Article  CAS  PubMed  Google Scholar 

  18. Oehninger S, Coddington CC, Scott R, Franken DA, Burkman LJ, Acosta AA, Hodgen GD. Hemizona assay: assessment of sperm dysfunction and prediction of in vitro fertilization outcome. Fertil Steril. 1989;51(4):665–70. https://doi.org/10.1016/s0015-0282(16)60618-0.

    Article  CAS  PubMed  Google Scholar 

  19. Gorczyca W, Bruno S, Darzynkiewicz R, Gong J, Darzynkiewicz Z. DNA strand breaks occurring during apoptosis—their early insitu detection by the terminal deoxynucleotidyl transferase and nick translation assays and prevention by serine protease inhibitors. Int J Oncol. 1992;1:639–48. https://doi.org/10.3892/ijo.1.6.639.

    Article  CAS  PubMed  Google Scholar 

  20. Sharma R, Ahmad G, Esteves SC, Agarwal A. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay using bench top flow cytometer for evaluation of sperm DNA fragmentation in fertility laboratories: protocol, reference values, and quality control. J Assist Reprod Genet. 2016 Feb;33(2):291–300. https://doi.org/10.1007/s10815-015-0635-7.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ostling O, Johanson KJ. Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem Biophys Res Commun. 1984;123(1):291–8. https://doi.org/10.1016/0006-291x(84)90411-x.

    Article  CAS  PubMed  Google Scholar 

  22. Bungum M, Humaidan P, Spano M, Jepson K, Bungum L, Giwercman A. The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination. IVF and ICSI. Hum Reprod. 2004;19(6):1401–8. https://doi.org/10.1093/humrep/deh280.

    Article  CAS  PubMed  Google Scholar 

  23. Fernández JL, Muriel L, Rivero MT, Goyanes V, Vazquez R, Alvarez JG. The sperm chromatin dispersion test: a simple method for the determination of sperm DNA fragmentation. J Androl. 2003 Jan-Feb;24(1):59–66.

    Article  PubMed  Google Scholar 

  24. Erenpreiss J, Jepson K, Giwercman A, Tsarev I, Erenpreisa J, Spano M. Toluidine blue cytometry test for sperm DNA conformation: comparison with the flow cytometric sperm chromatin structure and TUNEL assays. Hum Reprod. 2004;19(10):2277–82. https://doi.org/10.1093/humrep/deh417.

    Article  CAS  PubMed  Google Scholar 

  25. Panner Selvam MK, Agarwal A. A systematic review on sperm DNA fragmentation in male factor infertility: laboratory assessment. Arab J Urol. 2018;16(1):65–76. https://doi.org/10.1016/j.aju.2017.12.001.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Gopalkrishnan K, Hinduja IN, Kumar TC. In vitro decondensation of nuclear chromatin of human spermatozoa: assessing fertilizing potential. Arch Androl. 1991;27(1):43–50. https://doi.org/10.3109/01485019108987650.

    Article  CAS  PubMed  Google Scholar 

  27. Carreras A, Ramirez JP, Mendoza C. Sperm plasma membrane integrity measurement: a combined method. Andrologia. 1992;24(6):335–40. https://doi.org/10.1111/j.1439-0272.1992.tb02665.x.

    Article  CAS  PubMed  Google Scholar 

  28. Rumke PH. The presence of sperm antibodies in the serum of two patients with oligospermia. Vox Sang. 1954;4:135–40.

    Google Scholar 

  29. Andolz P, Bielsa MA, Martínez P, García-Framis V, Benet-Rubinat JM, Egozcue J. Detection of anti-sperm antibodies in serum, seminal plasma and cervical mucus by the immunobead test. Hum Reprod. 1990;5(6):685–9. https://doi.org/10.1093/oxfordjournals.humrep.a137168.

    Article  CAS  PubMed  Google Scholar 

  30. De Almeida M, Soumah A, Jouannet P. Incidence of sperm-associated immunoglobulins in infertile men with suspected autoimmunity to sperm. Int J Androl. 1986;9(5):321–30. https://doi.org/10.1111/j.1365-2605.1986.tb00894.x.

    Article  PubMed  Google Scholar 

  31. Marques M, Sousa AP, Paiva A, Almeida-Santos T, Ramalho-Santos J. Low amounts of mitochondrial reactive oxygen species define human sperm quality. Reproduction. 2014;147(6):817–24. https://doi.org/10.1530/REP-13-0644.

    Article  CAS  PubMed  Google Scholar 

  32. Eruslanov E, Kusmartsev S. Identification of ROS using oxidized DCFDA and flow-cytometry. Methods Mol Biol. 2010;594:57–72. https://doi.org/10.1007/978-1-60761-411-1_4.

    Article  CAS  PubMed  Google Scholar 

  33. Royall JA, Ischiropoulos H. Evaluation of 2',7'-dichlorofluorescin and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells. Arch Biochem Biophys. 1993;302(2):348–55. https://doi.org/10.1006/abbi.1993.1222.

    Article  CAS  PubMed  Google Scholar 

  34. Chai RR, Chen GW, Shi HJ, WS O, Martin-DeLeon PA, Chen H. Prohibitin involvement in the generation of mitochondrial superoxide at complex I in human sperm. J Cell Mol Med. 2017, 21(1):121–9. https://doi.org/10.1111/jcmm.12945.

  35. Ashar FN, Zhang Y, Longchamps RJ, Lane J, Moes A, Grove ML, Mychaleckyj JC, Taylor KD, Coresh J, Rotter JI, Boerwinkle E, Pankratz N, Guallar E, Arking DE. Association of mitochondrial DNA copy number with cardiovascular disease. JAMA Cardiol. 2017;2(11):1247–55. https://doi.org/10.1001/jamacardio.2017.3683.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Li B, Kaushik S, Kalinowski P, Kim B, Gershome C, Ching J, Poburko D. Droplet digital PCR shows the D-Loop to be an error prone locus for mitochondrial DNA copy number determination. Sci Rep. 2018;8(1):11392. https://doi.org/10.1038/s41598-018-29621-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ye W, Tang X, Liu C, Wen C, Li W, Lyu J. Accurate quantitation of circulating cell-free mitochondrial DNA in plasma by droplet digital PCR. Anal Bioanal Chem. 2017;409(10):2727–35. https://doi.org/10.1007/s00216-017-0217-x.

    Article  CAS  PubMed  Google Scholar 

  38. Agarwal A, Roychoudhury S, Bjugstad KB, Cho CL. Oxidation-reduction potential of semen: what is its role in the treatment of male infertility? Ther. Adv Urol. 2016;8(5):302–18. https://doi.org/10.1177/1756287216652779.

    Article  CAS  Google Scholar 

  39. Agarwal A, Qiu E, Sharma R. Laboratory assessment of oxidative stress in semen. Arab J Urol. 2017;16(1):77–86. https://doi.org/10.1016/j.aju.2017.11.008.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Ramu S, Jeyendran RS. The hypo-osmotic swelling test for evaluation of sperm membrane integrity. Methods Mol Biol. 2013;927:21–5. https://doi.org/10.1007/978-1-62703-038-0_3.

    Article  CAS  PubMed  Google Scholar 

  41. McCue PM. Hypo-osmotic swelling test. In Dascanio JJ, McCue PM (eds.) Equine reproductive procedures. Wiley Online Library, 2014;481-482. https://doi.org/10.1002/9781118904398.ch147

  42. Zubair M, Ahmad M, Jamil H. Review on the screening of semen by hypo-osmotic swelling test. Andrologia. 2015 Sep;47(7):744–50. https://doi.org/10.1111/and.12335.

    Article  CAS  PubMed  Google Scholar 

  43. Aitken RJ, Nixon B. Sperm capacitation: a distant landscape glimpsed but unexplored. Mol Hum Reprod. 2013;19(12):785–93. https://doi.org/10.1093/molehr/gat067.

    Article  CAS  PubMed  Google Scholar 

  44. Umehara T, Kawai T, Goto M, Richards JS, Shimada M. Creatine enhances the duration of sperm capacitation: a novel factor for improving in vitro fertilization with small numbers of sperm. Hum Reprod. 2018;33(6):1117–29. https://doi.org/10.1093/humrep/dey081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Aitken RJ, Harkiss D, Knox W, Paterson M, Irvine DS. A novel signal transduction cascade in capacitating human spermatozoa characterised by a redox-regulated, cAMP-mediated induction of tyrosine phosphorylation. J Cell Sci. 1998;111(Pt 5):645–56. https://doi.org/10.1242/jcs.111.5.645.

    Article  CAS  PubMed  Google Scholar 

  46. Davis BK. Timing of fertilization in mammals: sperm cholesterol/phospholipid ratio as a determinant of the capacitation interval. Proc Natl Acad Sci U S A. 1981;78(12):7560–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Baker MA, Hetherington L, Ecroyd H, Roman SD, Aitken RJ. Analysis of the mechanism by which calcium negatively regulates the tyrosine phosphorylation cascade associated with sperm capacitation. J Cell Sci. 2004;117(Pt 2):211–22. https://doi.org/10.1242/jcs.00842.

    Article  CAS  PubMed  Google Scholar 

  48. Krapf D, Arcelay E, Wertheimer EV, Sanjay A, Pilder SH, Salicioni AM, Visconti PE. Inhibition of Ser/Thr phosphatases induces capacitation-associated signaling in the presence of Src kinase inhibitors. J Biol Chem. 2010;285(11):7977–85. https://doi.org/10.1074/jbc.M109.085845.

  49. White DR, Aitken RJ. Relationship between calcium, cyclic AMP, ATP, and intracellular pH and the capacity of hamster spermatozoa to express hyperactivated motility. Gamete Res. 1989;22(2):163–77. https://doi.org/10.1002/mrd.1120220205.

    Article  CAS  PubMed  Google Scholar 

  50. Suarez SS, Ho HC. Hyperactivation of mammalian sperm. Cell Mol Biol (Noisy-le-grand). 2003;49(3):351–6.

    CAS  PubMed  Google Scholar 

  51. Aitken RJ, McLaughlin EA. Molecular mechanisms of sperm capacitation: progesterone-induced secondary calcium oscillations reflect the attainment of a capacitated state. Soc Reprod Fertil Suppl. 2007;63:273–93.

    CAS  PubMed  Google Scholar 

  52. Godbole GB, Modi DN, Puri CP. Regulation of homeobox A10 expression in the primate endometrium by progesterone and embryonic stimuli. Reproduction. 2007;134(3):513–23. https://doi.org/10.1530/REP-07-0234.

    Article  CAS  PubMed  Google Scholar 

  53. Patrat C, Serres C, Jouannet P. The acrosome reaction in human spermatozoa. Biol Cell. 2000;92(3-4):255–66. https://doi.org/10.1016/s0248-4900(00)01072-8.

    Article  CAS  PubMed  Google Scholar 

  54. Liu DY, Baker HW. Acrosome status and morphology of human spermatozoa bound to the zona pellucida and oolemma determined using oocytes that failed to fertilize in vitro. Hum Reprod. 1994;9(4):673–9. https://doi.org/10.1093/oxfordjournals.humrep.a138570.

    Article  CAS  PubMed  Google Scholar 

  55. Liu DY, Baker HW. Disordered acrosome reaction of spermatozoa bound to the zona pellucida: a newly discovered sperm defect causing infertility with reduced sperm-zona pellucida penetration and reduced fertilization in vitro. Hum Reprod. 1994;9(9):1694–700. https://doi.org/10.1093/oxfordjournals.humrep.a138776.

    Article  CAS  PubMed  Google Scholar 

  56. Tesarík J. Comparison of acrosome reaction-inducing activities of human cumulus oophorus, follicular fluid and ionophore A23187 in human sperm populations of proven fertilizing ability in vitro. J Reprod Fertil. 1985;74(2):383–8. https://doi.org/10.1530/jrf.0.0740383.

    Article  PubMed  Google Scholar 

  57. Cross NL, Morales P, Overstreet JW, Hanson FW. Induction of acrosome reactions by the human zona pellucida. Biol Reprod. 1988;38(1):235–44. https://doi.org/10.1095/biolreprod38.1.235.

    Article  CAS  PubMed  Google Scholar 

  58. Brucker C, Lipford GB. The human sperm acrosome reaction: physiology and regulatory mechanisms. An update. Hum Reprod Update. 1995;1(1):51–62. https://doi.org/10.1093/humupd/1.1.51.

    Article  CAS  PubMed  Google Scholar 

  59. Hecht NB. Regulation of ‘haploid expressed genes’ in male germ cells. J Reprod Fertil. 1990;88(2):679–93. https://doi.org/10.1530/jrf.0.0880679.

    Article  CAS  PubMed  Google Scholar 

  60. Oliva R. Protamines and male infertility. Hum Reprod Update. 2006;12(4):417–35. https://doi.org/10.1093/humupd/dml009.

    Article  CAS  PubMed  Google Scholar 

  61. Rogenhofer N, Dansranjavin T, Schorsch M, Spiess A, Wang H, von Schönfeldt V, Cappallo-Obermann H, Baukloh V, Yang H, Paradowska A, Chen B, Thaler CJ, Weidner W, Schuppe HC, Steger K. The sperm protamine mRNA ratio as a clinical parameter to estimate the fertilizing potential of men taking part in an ART programme. Hum Reprod. 2013;28(4):969–78. https://doi.org/10.1093/humrep/des471.

    Article  CAS  PubMed  Google Scholar 

  62. Hamad MF. Quantification of histones and protamines mRNA transcripts in sperms of infertile couples and their impact on sperm’s quality and chromatin integrity. Reprod Biol. 2019;19(1):6–13. https://doi.org/10.1016/j.repbio.2019.03.001.

    Article  PubMed  Google Scholar 

  63. Durmaz A, Dikmen N, Gündüz C, Göker EN, Tavmergen E. Fluctuation of “sperm DNA integrity” in accordance with semen parameters, and it's relationship with infertility. J Assist Reprod Genet. 2014;31(12):1665–71. https://doi.org/10.1007/s10815-014-0364-3.

  64. Zhang Y, Trussell JC, Chohan KR. Detecting and minimizing sperm DNA damage. Semin Reprod Med. 2013;31(4):267–73. https://doi.org/10.1055/s-0033-1345274.

    Article  CAS  PubMed  Google Scholar 

  65. Ribas-Maynou J, García-Peiró A, Fernández-Encinas A, Abad C, Amengual MJ, Prada E, Navarro J, Benet J. Comprehensive analysis of sperm DNA fragmentation by five different assays: TUNEL assay, SCSA, SCD test and alkaline and neutral Comet assay. Andrology. 2013;1(5):715–22. https://doi.org/10.1111/j.2047-2927.2013.00111.x.

    Article  CAS  PubMed  Google Scholar 

  66. Albert O, Reintsch WE, Chan P, Robaire B. HT-COMET: a novel automated approach for high throughput assessment of human sperm chromatin quality. Hum Reprod. 2016;31(5):938–46. https://doi.org/10.1093/humrep/dew030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Enciso M, Alfarawati S, Wells D. Increased numbers of DNA-damaged spermatozoa in samples presenting an elevated rate of numerical chromosome abnormalities. Hum Reprod. 2013;28(6):1707–15. https://doi.org/10.1093/humrep/det077.

    Article  CAS  PubMed  Google Scholar 

  68. Grèze C, Guttmann A, Pons-Rejraji H, Vasson MP, Lornage J, Ouchchane L, Brugnon F. Can the SCD test and terminal uridine nick-end labeling by flow cytometry technique (TUNEL/FCM) be used interchangeably to measure sperm DNA damage in routine laboratory practice? Basic Clin Androl. 2019;26(29):17. https://doi.org/10.1186/s12610-019-0098-2.

    Article  Google Scholar 

  69. Shibahara H, Koriyama J. Methods for direct and indirect antisperm antibody testing. Methods Mol Biol. 2013;927:51–60. https://doi.org/10.1007/978-1-62703-038-0_6.

    Article  CAS  PubMed  Google Scholar 

  70. Pretorius E, Franken DR. The immunobead technique: an indicator of disturbed sperm cervical mucus interaction. Andrologia. 1988;20(1):5–9. https://doi.org/10.1111/j.1439-0272.1988.tb02351.x.

    Article  CAS  PubMed  Google Scholar 

  71. Gatimel N, Moreau J, Isus F, Moinard N, Parinaud J, Leandri RD. Anti-sperm antibodies detection by a modified MAR test: towards a better definition of its indications. Reprod Biomed Online. 2018;37(6):717–23. https://doi.org/10.1016/j.rbmo.2018.09.011.

    Article  CAS  PubMed  Google Scholar 

  72. Harper ME, Bevilacqua L, Hagopian K, Weindruch R, Ramsey JJ. Ageing, oxidative stress, and mitochondrial uncoupling. Acta Physiol Scand. 2004;182(4):321–31. https://doi.org/10.1111/j.1365-201X.2004.01370.x.

    Article  CAS  PubMed  Google Scholar 

  73. Cassina A, Silveira P, Cantu L, Montes JM, Radi R, Sapiro R. Defective human sperm cells are associated with mitochondrial dysfunction and oxidant production. Biol Reprod. 2015 Nov;93(5):119. https://doi.org/10.1095/biolreprod.115.130989.

    Article  CAS  PubMed  Google Scholar 

  74. Kauffman ME, Kauffman MK, Traore K, Zhu H, Trush MA, Jia Z, Li YR. MitoSOX-based flow cytometry for detecting mitochondrial ROS. React Oxyg Species (Apex). 2016;2(5):361–70. https://doi.org/10.20455/ros.2016.865.

    Article  PubMed  Google Scholar 

  75. Espinoza JA, Schulz MA, Sánchez R, Villegas JV. Integrity of mitochondrial membrane potential reflects human sperm quality. Andrologia. 2009;41(1):51–4. https://doi.org/10.1111/j.1439-0272.2008.00878.x.

    Article  CAS  PubMed  Google Scholar 

  76. Malik AN, Czajka A. Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction? Mitochondrion. 2013;13(5):481–92. https://doi.org/10.1016/j.mito.2012.10.011.

    Article  CAS  PubMed  Google Scholar 

  77. Song GJ, Lewis V. Mitochondrial DNA integrity and copy number in sperm from infertile men. Fertil Steril. 2008 Dec;90(6):2238–44. https://doi.org/10.1016/j.fertnstert.2007.10.059.

    Article  CAS  PubMed  Google Scholar 

  78. May-Panloup P, Chrétien MF, Savagner F, Vasseur C, Jean M, Malthièry Y, Reynier P. Increased sperm mitochondrial DNA content in male infertility. Hum Reprod. 2003;18(3):550–6. https://doi.org/10.1093/humrep/deg096.

    Article  PubMed  Google Scholar 

  79. Rosati AJ, Whitcomb BW, Brandon N, Buck Louis GM, Mumford SL, Schisterman EF, Pilsner JR. Sperm mitochondrial DNA biomarkers and couple fecundity. Hum Reprod. 2020;35(11):2619–25. https://doi.org/10.1093/humrep/deaa191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Tian M, Bao H, Martin FL, Zhang J, Liu L, Huang Q, Shen H. Association of DNA methylation and mitochondrial DNA copy number with human semen quality. Biol Reprod. 2014;91(4):101. https://doi.org/10.1095/biolreprod.114.122465. Epub 2014 Sep 10. Erratum in: Biol Reprod. 2015 Mar;92(3):61

    Article  CAS  PubMed  Google Scholar 

  81. Desai N, Sharma R, Makker K, Sabanegh E, Agarwal A. Physiologic and pathologic levels of reactive oxygen species in neat semen of infertile men. Fertil Steril. 2009;92(5):1626–31. https://doi.org/10.1016/j.fertnstert.2008.08.109.

    Article  PubMed  Google Scholar 

  82. Tunc O, Thompson J, Tremellen K. Development of the NBT assay as a marker of sperm oxidative stress. Int J Androl. 2010 Feb;33(1):13–21. https://doi.org/10.1111/j.1365-2605.2008.00941.x.

    Article  CAS  PubMed  Google Scholar 

  83. Kao SH, Chao HT, Chen HW, Hwang TIS, Liao TL, Wei YH. Increase of oxidative stress in human sperm with lower motility. Fertil Steril. 2008;89(5):1183–90. https://doi.org/10.1016/j.fertnstert.2007.05.029.

    Article  CAS  PubMed  Google Scholar 

  84. Shen H, Ong C. Detection of oxidative DNA damage in human sperm and its association with sperm function and male infertility. Free Radic Biol Med. 2000;28(4):529–36. https://doi.org/10.1016/s0891-5849(99)00234-8.

    Article  CAS  PubMed  Google Scholar 

  85. Majzoub A, Arafa M, Mahdi M, Agarwal A, Al Said S, Al-Emadi I, El Ansari W, Alattar A, Al Rumaihi K, Elbardisi H. Oxidation-reduction potential and sperm DNA fragmentation, and their associations with sperm morphological anomalies amongst fertile and infertile men. Arab J Urol. 2018;16(1):87–95. https://doi.org/10.1016/j.aju.2017.11.014.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Homa ST, Vassiliou AM, Stone J, Killeen AP, Dawkins A, Xie J, Gould F, Ramsay JWA. A comparison between two assays for measuring seminal oxidative stress and their relationship with sperm DNA fragmentation and semen parameters. Genes (Basel). 2019;10(3):236. https://doi.org/10.3390/genes10030236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Arslan M, Morshedi M, Arslan EO, Taylor S, Kanik A, Duran HE, Oehninger S. Predictive value of the hemizona assay for pregnancy outcome in patients undergoing controlled ovarian hyperstimulation with intrauterine insemination. Fertil Steril. 2006;85(6):1697–707. https://doi.org/10.1016/j.fertnstert.2005.11.054.

    Article  PubMed  Google Scholar 

  88. Bielsa MA, Andolz P, Gris JM, Martínez P, Egozcue J. Which semen parameters have a predictive value for pregnancy in infertile couples? Hum Reprod. 1994;9(10):1887–90. https://doi.org/10.1093/oxfordjournals.humrep.a138353.

    Article  CAS  PubMed  Google Scholar 

  89. Calvo L, Dennison-Lagos L, Banks SM, Dorfmann A, Thorsell LP, Bustillo M, Schulman JD, Sherins RJ. Acrosome reaction inducibility predicts fertilization success at in-vitro fertilization. Hum Reprod. 1994;9(10):1880–6. https://doi.org/10.1093/oxfordjournals.humrep.a138352.

    Article  CAS  PubMed  Google Scholar 

  90. Esteves SC, Schneider DT, Verza S Jr. Influence of antisperm antibodies in the semen on intracytoplasmic sperm injection outcome. Int Braz J Urol. 2007;33(6):795–802. https://doi.org/10.1590/s1677-55382007000600007.

    Article  PubMed  Google Scholar 

  91. Esteves SC, López-Fernández C, Martínez MG, Silva EA, Gosálvez J. Reliability of the sperm chromatin dispersion assay to evaluate sperm deoxyribonucleic acid damage in men with infertility. Fertil Steril. 2022;117(1):64–73. https://doi.org/10.1016/j.fertnstert.2021.08.045.

    Article  CAS  PubMed  Google Scholar 

  92. Gamzu R, Yogev L, Amit A, Lessing J, Homonnai ZT, Yavetz H. The hemizona assay is of good prognostic value for the ability of sperm to fertilize oocytes in vitro. Fertil Steril. 1994;62(5):1056–9. https://doi.org/10.1016/s0015-0282(16)57073-3.

    Article  CAS  PubMed  Google Scholar 

  93. Hervás I, Pacheco A, Gil Julia M, Rivera-Egea R, Navarro-Gomezlechon A, Garrido N. Sperm deoxyribonucleic acid fragmentation (by terminal deoxynucleotidyl transferase biotin dUTP nick end labeling assay) does not impair reproductive success measured as cumulative live birth rates per donor metaphase II oocyte used. Fertil Steril. 2022;118(1):79–89. https://doi.org/10.1016/j.fertnstert.2022.04.002.

    Article  CAS  PubMed  Google Scholar 

  94. Janssen HJ, Bastiaans BA, Goverde HJ, Hollanders HM, Wetzels AA, Schellekens LA. Antisperm antibodies and in vitro fertilization. J Assist Reprod Genet. 1992;9(4):345–9. https://doi.org/10.1007/BF01203957.

    Article  CAS  PubMed  Google Scholar 

  95. Lin MH, Kuo-Kuang Lee R, Li SH, Lu CH, Sun FJ, Hwu YM. Sperm chromatin structure assay parameters are not related to fertilization rates, embryo quality, and pregnancy rates in in vitro fertilization and intracytoplasmic sperm injection, but might be related to spontaneous abortion rates. Fertil Steril. 2008;90(2):352–9. https://doi.org/10.1016/j.fertnstert.2007.06.018.

    Article  PubMed  Google Scholar 

  96. Meseguer M, Santiso R, Garrido N, García-Herrero S, Remohí J, Fernandez JL. Effect of sperm DNA fragmentation on pregnancy outcome depends on oocyte quality. Fertil Steril. 2011;95(1):124–8. https://doi.org/10.1016/j.fertnstert.2010.05.055.

    Article  CAS  PubMed  Google Scholar 

  97. Franken DR, Burkman LJ, Oehninger SC, Coddington CC, Veeck LL, Kruger TF, Rosenwaks Z, Hodgen GD. Hemizona assay using salt-stored human oocytes: evaluation of zona pellucida capacity for binding human spermatozoa. Gamete Res. 1989;22(1):15–26. https://doi.org/10.1002/mrd.1120220103.

    Article  CAS  PubMed  Google Scholar 

  98. Sallam HN, Farrag A, Agameya AF, El-Garem Y, Ezzeldin F. The use of the modified hypo-osmotic swelling test for the selection of immotile testicular spermatozoa in patients treated with ICSI: a randomized controlled study. Hum Reprod. 2005;20(12):3435–40. https://doi.org/10.1093/humrep/dei249.

    Article  PubMed  Google Scholar 

  99. Sukcharoen N, Keith J, Irvine DS, Aitken RJ. Predicting the fertilizing potential of human sperm suspensions in vitro: importance of sperm morphology and leukocyte contamination. Fertil Steril. 1995;63(6):1293–300. https://doi.org/10.1016/s0015-0282(16)57614-6.

    Article  CAS  PubMed  Google Scholar 

  100. Zorn B, Vidmar G, Meden-Vrtovec H. Seminal reactive oxygen species as predictors of fertilization, embryo quality and pregnancy rates after conventional in vitro fertilization and intracytoplasmic sperm injection. Int J Androl. 2003;26(5):279–85. https://doi.org/10.1046/j.1365-2605.2003.00424.x.

    Article  CAS  PubMed  Google Scholar 

  101. Check JH, Stumpo L, Lurie D, Benfer K, Callan C. A comparative prospective study using matched samples to determine the influence of subnormal hypo-osmotic test scores of spermatozoa on subsequent fertilization and pregnancy rates following in-vitro fertilization. Hum Reprod. 1995 May;10(5):1197–200. https://doi.org/10.1093/oxfordjournals.humrep.a136118.

    Article  CAS  PubMed  Google Scholar 

  102. Tartagni M, Schonauer MM, Cicinelli E, Selman H, De Ziegler D, Petruzzelli F, D'Addario V. Usefulness of the hypo-osmotic swelling test in predicting pregnancy rate and outcome in couples undergoing intrauterine insemination. J Androl. 2002;23(4):498–502.

    Article  PubMed  Google Scholar 

  103. Vogiatzi P, Chrelias C, Cahill DJ, Creatsa M, Vrachnis N, Iliodromiti Z, Kassanos D, Siristatidis C. Hemizona assay and sperm penetration assay in the prediction of IVF outcome: a systematic review. Biomed Res Int. 2013;2013:945825. https://doi.org/10.1155/2013/945825.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Virro MR, Larson-Cook KL, Evenson DP. 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. 2004;81(5):1289–95. https://doi.org/10.1016/j.fertnstert.2003.09.063.

    Article  PubMed  Google Scholar 

  105. Nijs M, Creemers E, Cox A, Franssen K, Janssen M, Vanheusden E, De Jonge C, Ombelet W. Chromomycin A3 staining, sperm chromatin structure assay and hyaluronic acid binding assay as predictors for assisted reproductive outcome. Reprod Biomed Online. 2009;19(5):671–84. https://doi.org/10.1016/j.rbmo.2009.07.002.

    Article  CAS  PubMed  Google Scholar 

  106. Cissen M, Wely MV, Scholten I, Mansell S, Bruin JP, Mol BW, Braat D, Repping S, Hamer G. Measuring sperm DNA fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta-analysis. PLoS One. 2016;11(11):e0165125. https://doi.org/10.1371/journal.pone.0165125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Stanger JD, Vo L, Yovich JL, Almahbobi G. Hypo-osmotic swelling test identifies individual spermatozoa with minimal DNA fragmentation. Reprod Biomed Online. 2010;21(4):474–84. https://doi.org/10.1016/j.rbmo.2010.06.026.

    Article  PubMed  Google Scholar 

  108. McQueen DB, Zhang J, Robins JC. Sperm DNA fragmentation and recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril. 2019;112(1):54–60.e3. https://doi.org/10.1016/j.fertnstert.2019.03.003.

    Article  PubMed  Google Scholar 

  109. Hammadeh ME, Radwan M, Al-Hasani S, Micu R, Rosenbaum P, Lorenz M, Schmidt W. Comparison of reactive oxygen species concentration in seminal plasma and semen parameters in partners of pregnant and non-pregnant patients after IVF/ICSI. Reprod Biomed Online. 2006;13(5):696–706. https://doi.org/10.1016/s1472-6483(10)60661-x.

    Article  CAS  PubMed  Google Scholar 

  110. Ghaleno LR, Valojerdi MR, Hassani F, Chehrazi M, Janzamin E. High level of intracellular sperm oxidative stress negatively influences embryo pronuclear formation after intracytoplasmic sperm injection treatment. Andrologia. 2014;46(10):1118–27. https://doi.org/10.1111/and.12202.

    Article  CAS  PubMed  Google Scholar 

  111. Chen X, Zheng Y, Zheng J, Lin J, Zhang L, Jin J. The progesterone-induced sperm acrosome reaction is a good option for the prediction of fertilization in vitro compared with other sperm parameters. Andrologia. 2019;51(6):e13278. https://doi.org/10.1111/and.13278.

    Article  CAS  PubMed  Google Scholar 

  112. Schill WB. Some disturbances of acrosomal development and function in human spermatozoa. Hum Reprod. 1991;6(7):969–78. https://doi.org/10.1093/oxfordjournals.humrep.a137471.

    Article  CAS  PubMed  Google Scholar 

  113. Plachot M, Mandelbaum J, Junca AM. Acrosome reaction of human sperm used for in vitro fertilization. Fertil Steril. 1984;42(3):418–23. https://doi.org/10.1016/s0015-0282(16)48083-0.

    Article  CAS  PubMed  Google Scholar 

  114. Tello-Mora P, Hernández-Cadena L, Pedraza J, López-Bayghen E, Quintanilla-Vega B. Acrosome reaction and chromatin integrity as additional parameters of semen analysis to predict fertilization and blastocyst rates. Reprod Biol Endocrinol. 2018;16(1):102. https://doi.org/10.1186/s12958-018-0408-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Vujisić S, Lepej SZ, Jerković L, Emedi I, Sokolić B. Antisperm antibodies in semen, sera and follicular fluids of infertile patients: relation to reproductive outcome after in vitro fertilization. Am J Reprod Immunol. 2005;54(1):13–20. https://doi.org/10.1111/j.1600-0897.2005.00274.x.

    Article  PubMed  Google Scholar 

  116. Sukcharoen N, Keith J. The effect of the antisperm auto-antibody-bound sperm on in vitro fertilization outcome. Andrologia. 1995;27(5):281–9. https://doi.org/10.1111/j.1439-0272.1995.tb01106.x.

    Article  CAS  PubMed  Google Scholar 

  117. Kızılay F, Altay B. Sperm function tests in clinical practice. Turk J Urol. 2017;43(4):393–400. https://doi.org/10.5152/tud.2017.96646.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Talwar P, Hayatnagarkar S. Sperm function test. J Hum Reprod Sci. 2015;8(2):61–9. https://doi.org/10.4103/0974-1208.158588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Tournaye H. Management of male infertility by assisted reproductive technologies. Baillieres Best Pract Res Clin Endocrinol Metab. 2000;14(3):423–35. https://doi.org/10.1053/beem.2000.0089.

    Article  CAS  PubMed  Google Scholar 

  120. Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Mens Health. 2014;32(1):1–17. https://doi.org/10.5534/wjmh.2014.32.1.1.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors acknowledge the support from ICMR-National Institute for Research in Reproductive and Child Health. Debarati Sanyal and Deepshikha Arya acknowledge the Indian Academy of Science (Summer Fellowship) and UGC (Junior Research Fellowship), respectively.

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  1. Department of Neuroendocrinology, ICMR-National Institute for Research in Reproductive and Child Health, Parel, Mumbai, 400012, India

    Debarati Sanyal, Deepshikha Arya, Kumari Nishi, Nafisa Balasinor & Dipty Singh

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DS and NB conceived the idea of the systematic review. DS conducted the systematic review and drafted the manuscript. DS and DA crosschecked the review process and organized the manuscript with necessary additions. NB and KN proofread the draft and gave critical inputs. All authors agreed upon the final draft.

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Correspondence to Nafisa Balasinor or Dipty Singh.

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Sanyal, D., Arya, D., Nishi, K. et al. Clinical Utility of Sperm Function Tests in Predicting Male Fertility: A Systematic Review. Reprod. Sci. 31, 863–882 (2024). https://doi.org/10.1007/s43032-023-01405-7

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