Skip to main content

Advertisement

Log in

Male Age and Progressive Sperm Motility Are Critical Factors Affecting Embryological and Clinical Outcomes in Oocyte Donor ICSI Cycles

  • Male Reproduction: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

This retrospective cohort study aimed to explore whether paternal age and semen quality parameters affect the embryological and clinical outcomes of ICSI with oocyte donation. A total of 339 oocyte donation (OD)-ICSI cycles were categorized into four groups according to the semen parameter profiles of the male counterparts: normozoospermia (NS, n = 184), oligozoospermia (OS, n = 41), asthenozoospermia (AS, n = 50), and oligoasthenozoospermia (OAS, n = 64). The effect of age, total sperm count, and progressive motility was separately analyzed for reproductive outcomes and compared between the study groups: fertilization, blastulation, and top-quality embryo rate, biochemical and clinical pregnancy, live birth, and miscarriage. A negative correlation between male age and fertilization rate was observed (rs =  − 0.23, p < 0.0001), while male age was a significant factor for biochemical pregnancy (p = 0.0002), clinical pregnancy (p = 0.0017), and live birth (p = 0.0038). Reduced total sperm count and lowered progressive motility led to poorer fertilization rates (rs = 0.19 and 0.35, respectively, p < 0.0001) and affected embryo quality (rs = 0.13, p = 0.02, and rs = 0.22, p < 0.0001, respectively). OD-ICSI cycles with asthenozoospermia had significantly lowered success rates in biochemical pregnancy, clinical pregnancy, and live birth (p < 0.05). Our study demonstrated that both advanced male age and reduced progressive motility of spermatozoa exert a significant negative influence on the outcome of assisted reproduction, even in controlled procedures with gamete selection and optimization such as in OD-ICSI. Improvement in treatment strategies and male fertility evaluation requires incorporation of such evidence to obtain better prognosis towards personalized management.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

The data contained in this article will be shared on reasonable request to the corresponding author.

Code Availability

Not applicable.

References

  1. Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012;9:e1001356.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015;21:411–26.

    Article  PubMed  Google Scholar 

  3. Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. ReprodBiolEndocrinol. 2015;13:37.

    Google Scholar 

  4. Palermo G, Joris H, Devroey P, Van Steirteghem A. Pregnancies after intracytoplasmic sperm injection of a single spermatozoon into an oocyte. Lancet. 1992;340:17–8.

    Article  CAS  PubMed  Google Scholar 

  5. De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, Scaravelli G, Smeenk J, Vidakovic S, Goossens V, European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2014: results generated from European registries by ESHRE: the European IVF-monitoring consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod. 2018;33:1586–601.

    Article  PubMed  Google Scholar 

  6. Setti AS, Braga DPAF, Iaconelli Junior A, Borges JE. Increasing paternal age and ejaculatory abstinence length negatively influence the intracytoplasmic sperm injection outcomes from egg-sharing donation cycles. Andrology. 2020;8(3):594–601.

    Article  CAS  PubMed  Google Scholar 

  7. Alberts B, Johnson AD, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell. New York: Taylor and Francis Group:Garland Science; 2015.

    Google Scholar 

  8. Esteves SC. Clinical relevance of routine semen analysis and controversies surrounding the 2010 World Health Organization criteria for semen examination. IntBraz J Urol. 2014;40:433–53.

    Google Scholar 

  9. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010.

    Google Scholar 

  10. Lotti F, Maggi M. Ultrasound of the male genital tract in relation to male reproductive health. Hum Reprod Update. 2015;21:56–83.

    Article  PubMed  Google Scholar 

  11. Oehninger S, Franken DR, Ombelet W. Sperm functional tests. FertilSteril. 2014;102:1528–33.

    Google Scholar 

  12. Agarwal A, Cho CL, Esteves SC. Should we evaluate and treat sperm DNA fragmentation? CurrOpinObstet Gynecol. 2016;28:164–71.

    Google Scholar 

  13. Krzastek SC, Smith RP, Kovac JR. Future diagnostics in male infertility: genomics, epigenetics, metabolomics and proteomics. TranslAndrol Urol. 2020;9:S195-205.

    Google Scholar 

  14. Frattarelli JL, Miller KA, Miller BT, Elkind-Hirsch K, Scott RT Jr. Male age negatively impacts embryo development and reproductive outcome in donor oocyte assisted reproductive technology cycles. FertilSteril. 2008;90:97–103.

    Google Scholar 

  15. Girsh E, Katz N, Genkin L, Girtler O, Bocker J, Bezdin S, Barr I. Male age influences oocyte-donor program results. J Assist Reprod Genet. 2008;25:137–43.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Luna M, Finkler E, Barritt J, Bar-Chama N, Sandler B, Copperman AB, Grunfeld L. Paternal age and assisted reproductive technology outcome in ovum recipients. FertilSteril. 2009;92:1772–5.

    Google Scholar 

  17. Bartolacci A, Pagliardini L, Makieva S, Salonia A, Papaleo E, Viganò P. Abnormal sperm concentration and motility as well as advanced paternal age compromise early embryonic development but not pregnancy outcomes: a retrospective study of 1266 ICSI cycles. J Assist Reprod Genet. 2018;35:1897–903.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Koppers B, Gassner P, Meschede D, Horst J, Behre HM, Nieschlag E. Prognostic value of male diagnostic profiles in intracytoplasmic sperm injection (ICSI). Int J Androl. 1998;21:227–32.

    Article  CAS  PubMed  Google Scholar 

  19. Capelouto SM, Nagy ZP, Shapiro DB, Archer SR, Ellis DP, Smith AK, Spencer JB, Hipp HS. Impact of male partner characteristics and semen parameters on in vitro fertilization and obstetric outcomes in a frozen oocyte donor model. FertilSteril. 2018;110:859–69.

    Google Scholar 

  20. Borges E Jr, Setti AS, Braga DP, Figueira RC, Iaconelli A Jr. Total motile sperm count has a superior predictive value over the WHO 2010 cut-off values for the outcomes of intracytoplasmic sperm injection cycles. Andrology. 2016;4:880–6.

    Article  PubMed  Google Scholar 

  21. Chapuis A, Gala A, Ferrières-Hoa A, Mullet T, Bringer-Deutsch S, Vintejoux E, Torre A, Hamamah S. Sperm quality and paternal age: effect on blastocyst formation and pregnancy rates. Basic ClinAndrol. 2017;27:2.

    Google Scholar 

  22. Mariappen U, Keane KN, Hinchliffe PM, Dhaliwal SS, Yovich JL. Neither male age nor semen parameters influence clinical pregnancy or live birth outcomes from IVF. Reprod Biol. 2018;18:324–9.

    Article  PubMed  Google Scholar 

  23. Mansour RT, Aboulghar MA, Serour GI, Amin YM, Ramzi AM. The effect of sperm parameters on the outcome of intracytoplasmic sperm injection. FertilSteril. 1995;64:982–6.

    CAS  Google Scholar 

  24. Nagy ZP, Liu J, Joris H, Verheyen G, Tournaye H, Camus M, Derde MC, Devroey P, Van Steirteghem AC. The result of intracytoplasmic sperm injection is not related to any of the three basic sperm parameters. Hum Reprod. 1995;10:1123–9.

    Article  CAS  PubMed  Google Scholar 

  25. Oehninger S, Veeck L, Lanzendorf S, Maloney M, Toner J, Muasher S. Intracytoplasmic sperm injection: achievement of high pregnancy rates in couples with severe male factor infertility is dependent primarily upon female and not male factors. FertilSteril. 1995;64:977–81.

    CAS  Google Scholar 

  26. Svalander P, Jakobsson AH, Forsberg AS, Bengtsson AC, Wikland M. The outcome of intracytoplasmic sperm injection is unrelated to “strict criteria” sperm morphology. Hum Reprod. 1996;11:1019–22.

    Article  CAS  PubMed  Google Scholar 

  27. Nagy ZP, Verheyen G, Tournaye H, Van Steirteghem AC. Special applications of intracytoplasmic sperm injection: the influence of sperm count, motility, morphology, source and sperm antibody on the outcome of ICSI. Hum Reprod. 1998;13:143–54.

    Article  PubMed  Google Scholar 

  28. Mercan R, Lanzendorf SE, Mayer J Jr, Nassar A, Muasher SJ, Oehninger S. The outcome of clinical pregnancies following intracytoplasmic sperm injection is not affected by semen quality. Andrologia. 1998;30:91–5.

    Article  CAS  PubMed  Google Scholar 

  29. Mercan R, Oehninger S, Muasher SJ, Toner JP, Mayer J Jr, Lanzendorf SE. Impact of fertilization history and semen parameters on ICSI outcome. J Assist Reprod Genet. 1998;15:39–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lee SH, Song H, Park YS, Koong MK, Song IO, Jun JH. Poor sperm quality affects clinical outcomes of intracytoplasmic sperm injection in fresh and subsequent frozen-thawed cycles: potential paternal effects on pregnancy outcomes. FertilSteril. 2009;91:798–804.

    Google Scholar 

  31. Mazzilli R, Cimadomo D, Vaiarelli A, Capalbo A, Dovere L, Alviggi E, Dusi L, Foresta C, Lombardo F, Lenzi A, Tournaye H, Alviggi C, Rienzi L, Ubaldi FM. Effect of the male factor on the clinical outcome of intracytoplasmic sperm injection combined with preimplantation aneuploidy testing: observational longitudinal cohort study of 1,219 consecutive cycles. FertilSteril. 2017;108:961-72.e3.

    Google Scholar 

  32. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191–4.

    Article  Google Scholar 

  33. National Authority for Medically Assisted Reproduction (EAIYA). Legal framework for assisted reproduction in Greece (last accessed November 14th, 2020). http://eaiya.gov.gr/law-fek/. Accessed 16 Feb 2021.

  34. Menkveld R, Stander FS, Kotze TJ, Kruger TF, van Zyl JA. The evaluation of morphological characteristics of human spermatozoa according to stricter criteria. Hum Reprod. 1990;5:586–92.

    Article  CAS  PubMed  Google Scholar 

  35. Gardner DK, Schoolcraft WB. In vitro culture of human blastocysts. In: Jansen R, Mortimer D, editors. Toward reproductive certainty: fertility and genetics beyond. London: Parthenon Publishing; 1999. p. 378–88.

    Google Scholar 

  36. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, Rienzi L, Sunde A, Schmidt L, Cooke ID, Simpson JL, van der Poel S. The international glossary on infertility and fertility care, 2017. Hum Reprod. 2017;32:1786–801.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Derijck AA, Van der Heijden GW, Ramos L, Giele M, Kremer JA, De Boer P. Motile human normozoospermic and oligozoospermic semen samples show a difference in double-strand DNA break incidence. Hum Reprod. 2007;22:2368–76.

    Article  PubMed  Google Scholar 

  38. Sharma R, Agarwal A, Rohra VK, Assidi M, Abu-Elmagd M, Turki RF. Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring. ReprodBiolEndocrinol. 2015;13:35.

    Google Scholar 

  39. Paulson RJ, Milligan RC, Sokol RZ. The lack of influence of age on male fertility. Am J Obstet Gynecol. 2001;184:816–24.

    Article  Google Scholar 

  40. Duran EH, Dowling-Lacey D, Bocca S, Stadtmauer L, Oehninger S. Impact of male age on the outcome of assisted reproductive technology cycles using donor oocytes. Reprod Biomed Online. 2010;20(6):848–56.

    Article  CAS  PubMed  Google Scholar 

  41. Ghuman NK, Mair E, Pearce K, Choudhary M. Does age of the sperm donor influence live birth outcome in assisted reproduction? Hum Reprod. 2016;31:582–90.

    Article  CAS  PubMed  Google Scholar 

  42. Morris G, Mavrelos D, Theodorou E, Campbell-Forde M, Cansfield D, Yasmin E, Sangster P, Saab W, Serhal P, Seshadri S. Effect of paternal age on outcomes in assisted reproductive technology cycles: systematic review and meta-analysis. FertilSteril Rev. 2020;1:16–34.

    Google Scholar 

  43. Alio AP, Salihu HM, McIntosh C, August EM, Weldeselasse H, Sanchez E, Mbah AK. The effect of paternal age on fetal birth outcomes. Am J Mens Health. 2012;6(5):427–35.

    Article  PubMed  Google Scholar 

  44. Van Opstal J, Fieuws S, Spiessens C, Soubry A. Male age interferes with embryo growth in IVF treatment. Hum Reprod. 2020:deaa256. https://doi.org/10.1093/humrep/deaa256.

  45. de La Rochebrochard E, Thonneau P. Paternal age: are the risks of infecundity and miscarriage higher when the man in aged 40 years or over? Rev EpidemiolSantePublique. 2005;53:S47-55.

    Google Scholar 

  46. Whitcomb BW, Turzanski-Fortner R, Richter KS, Kipersztok S, Stillman RJ, Levy MJ, Levens ED. Contribution of male age to outcomes in assisted reproductive technologies. FertilSteril. 2011;95:147–51.

    Google Scholar 

  47. Verheyen G, Tournaye H, Staessen C, De Vos A, Vandervorst M, Van Steirteghem A. Controlled comparison of conventional in-vitro fertilization and intracytoplasmic sperm injection in patients with asthenozoospermia. Hum Reprod. 1999;14:2313–9.

    Article  CAS  PubMed  Google Scholar 

  48. Zuccarello D, Ferlin A, Cazzadore C, Pepe A, Garolla A, Moretti A, Cordeschi G, Francavilla S, Foresta C. Mutations in dynein genes in patients affected by isolated non-syndromic asthenozoospermia. Hum Reprod. 2008;23:1957–62.

    Article  CAS  PubMed  Google Scholar 

  49. Martínez-Heredia J, de Mateo S, Vidal-Taboada JM, Ballescà JL, Oliva R. Identification of proteomic differences in asthenozoospermic sperm samples. Hum Reprod. 2008;23:783–91.

    Article  PubMed  Google Scholar 

  50. Saraswat M, Joenväärä S, Jain T, Tomar AK, Sinha A, Singh S, Yadav S, Renkonen R. Human spermatozoa quantitative proteomic signature classifies normo- and asthenozoospermia. Mol Cell Proteomics. 2017;16:57–72.

    Article  CAS  PubMed  Google Scholar 

  51. Parinaud J, Vieitez G, Moutaffian H, Richoilley G, Milhet P. Relationships between motility parameters, morphology and acrosomal status of human spermatozoa. Hum Reprod. 1996;11:1240–3.

    Article  CAS  PubMed  Google Scholar 

  52. Egeberg Palme DL, Rehfeld A, Bang AK, Nikolova KA, Kjærulff S, Petersen MR, Jeppesen JV, Glensbjerg M, Juul A, Skakkebæk NE, Ziebe S, Jørgensen N, Almstrup K. Viable acrosome-intact human spermatozoa in the ejaculate as a marker of semen quality and fertility status. Hum Reprod. 2018;33:361–71.

    Article  PubMed  Google Scholar 

  53. Xu F, Zhu H, Zhu W, Fan L. Human sperm acrosomal status, acrosomal responsiveness, and acrosin are predictive of the outcomes of in vitro fertilization: a prospective cohort study. Reprod Biol. 2018;18:344–54.

    Article  PubMed  Google Scholar 

  54. Cejudo-Roman A, Pinto FM, Subirán N, Ravina CG, Fernández-Sánchez M, Pérez-Hernández N, Pérez R, Pacheco A, Irazusta J, Candenas L. The voltage-gated sodium channel nav1.8 is expressed in human sperm. PLoS One. 2013;8:e76084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ren D, Navarro B, Perez G, Jackson AC, Hsu S, Shi Q, Tilly JL, Clapham DE. A sperm ion channel required for sperm motility and male fertility. Nature. 2001;413:603–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Quill TA, Ren D, Clapham DE, Garbers DL. A voltage-gated ion channel expressed specifically in spermatozoa. ProcNatlAcadSci USA. 2001;98:12527–31.

    Article  CAS  Google Scholar 

  57. Collodel G, Capitani S, Baccetti B, Pammolli A, Moretti E. Sperm aneuploidies and low progressive motility. Hum Reprod. 2007;22:1893–8.

    Article  CAS  PubMed  Google Scholar 

  58. Meseguer M, Martínez-Conejero JA, O’Connor JE, Pellicer A, Remohí J, Garrido N. The significance of sperm DNA oxidation in embryo development and reproductive outcome in an oocyte donation program: a new model to study a male infertility prognostic factor. FertilSteril. 2008;89:1191–9.

    Google Scholar 

  59. Chen C, Hu JCY, Neri QV, Rosenwaks Z, Palermo GD. Kinetic characteristics and DNA integrity of human spermatozoa. Hum Reprod. 2011;19:i30.

    Google Scholar 

  60. Palermo GD, Neri QV, Monahan D, Kocent J, Rosenwaks Z. Development and current applications of assisted fertilization. FertilSteril. 2012;97:248–59.

    Google Scholar 

  61. Duran EH, Morshedi M, Taylor S, Oehninger S. Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study. Hum Reprod. 2002;17:3122–8.

    Article  CAS  PubMed  Google Scholar 

  62. Ozmen B, Caglar GS, Koster F, Schopper B, Diedrich K, Al-Hasani S. Relationship between sperm DNA damage, induced acrosome reaction and viability in ICSI patients. Reprod Biomed Online. 2007;15:208–14.

    Article  CAS  PubMed  Google Scholar 

  63. Høst E, Lindenberg S, Smidt-Jensen S. DNA strand breaks in human spermatozoa: correlation with fertilization in vitro in oligozoospermic men and in men with unexplained infertility. Acta ObstetGynecol Scand. 2000;79:189–93.

    Google Scholar 

  64. Carrell DT, Liu L, Peterson CM, Jones KP, Hatasaka HH, Erickson L, Campbell B. Sperm DNA fragmentation is increased in couples with unexplained recurrent pregnancy loss. Arch Androl. 2003;49:49–55.

    Article  CAS  PubMed  Google Scholar 

  65. Merino G, Carranza-Lira S, Murrieta S, Rodriguez L, Cuevas E, Morán C. Bacterial infection and semen characteristics in infertile men. Arch Androl. 1995;35:43–7.

    Article  CAS  PubMed  Google Scholar 

  66. Tomaiuolo R, Veneruso I, Cariati F, D’Argenio V. Microbiota and human reproduction: the case of male infertility. High Throughput. 2020;9:10.

    Article  CAS  PubMed Central  Google Scholar 

  67. World Health Organization. Laboratory manual for the examination of human semen and semen-cervical mucus interaction. 2nd ed. Cambridge: Cambridge University Press; 1993.

    Google Scholar 

  68. Legro RS, Wong IL, Paulson RJ, Lobo RA, Sauer MV. Recipient’s age does not affect pregnancy outcome after oocyte donation. AJOG. 1995;172:96–100.

    Article  CAS  Google Scholar 

  69. Paulson RJ, Hatch IE, Lobo RA, Sauer MV. Cumulative conception and live birth rates after oocyte donation: implications regarding endometrial receptivity. Hum Reprod. 1997;12:835–9.

    Article  CAS  PubMed  Google Scholar 

  70. Ashkenazi J, Dicker D, Feldberg D, Goldman JA. Fresh versus frozen thawed semen for initial and late insemination in IVF-ET cycles. Eur J ObstetGynecolReprod Biol. 1991;42:115–7.

    CAS  Google Scholar 

  71. Lansac J, Thepot F, Mayaux MJ, Czyglick F, Wack T, Selva J, Jalbert P. Pregnancy outcome after artificial insemination or IVF-ET with frozen semen donor: a collaborative study of the French CECOS Federation on 21597 pregnancies. Eur J ObstetGynecolReprod Biol. 1997;74:223–8.

    CAS  Google Scholar 

  72. Marcus-Braun N, Braun G, Potashnik G, Har-Vardi I. Effect of cryopreservation on quality and fertilization capacity of human sperm. Eur J ObstetGynecolReprod Biol. 2004;116:63–6.

    CAS  Google Scholar 

  73. Eastick J, Venetis C, Cooke S, Storr A, Susetio D, Chapman M. Is early embryo development as observed by time-lapse microscopy dependent on whether fresh or frozen sperm was used for ICSI? A cohort study. J Assist Reprod Genet. 2017;34:733–40.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We owe a heartfelt thanks to Associate Professor Mara Simopoulou for discussing important scientific context and for her supportive advice and to the Medical and Paramedical staff of the Assisted Reproduction Unit “IVF Athens” for their valuable support and contribution in the successful conduction of all the included ART cycles.

Author information

Authors and Affiliations

Authors

Contributions

Paraskevi Vogiatzi conceived the study. The study was designed by Paraskevi Vogiatzi, Abraham Pouliakis, Maria Sakellariou, Aikaterini Athanasiou, and Adamantios Athanasiou. Data collection and analysis were performed by Paraskevi Vogiatzi, Abraham Pouliakis, Maria Sakellariou, Aikaterini Athanasiou, and Adamantios Athanasiou. The first draft of the manuscript was written by all authors, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Paraskevi Vogiatzi.

Ethics declarations

Ethics Approval

The study was approved by the Research and Ethics Committee of the Reproductive Center (EVD 0701/2020) and has been conducted in accordance with the ethical standards of the National Authority for Medically Assisted Reproduction and with the 1964 Helsinki Declaration and its later amendments.

Consent to Participate

Throughout the study and especially during data acquisition and analysis, anonymity was strictly preserved by an initial assignment of an exclusive code for each participant, with no other identifying characteristics recorded. Patients received extensive consultation on the procedures to be followed, and written consent was obtained by all participants on treatment.

Consent for Publication

Not applicable, no identifying information about participants is contained on the manuscript or in data collection and analysis performed.

Conflict of Interest

The authors declare no competing interests.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 1269 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vogiatzi, P., Pouliakis, A., Sakellariou, M. et al. Male Age and Progressive Sperm Motility Are Critical Factors Affecting Embryological and Clinical Outcomes in Oocyte Donor ICSI Cycles. Reprod. Sci. 29, 883–895 (2022). https://doi.org/10.1007/s43032-021-00801-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-021-00801-1

Keywords

Navigation