Sperm telomere length in donor samples is not related to ICSI outcome

Abstract

Purpose

Variations in sperm telomere length (STL) have been associated with altered sperm parameters, poor embryo quality, and lower pregnancy rates, but for normozoospermic men, STL relevance in IVF/ICSI is still uncertain. Moreover, in all studies reported so far, each man’s STL was linked to the corresponding female partner characteristics. Here, we study STL in sperm donor samples, each used for up to 12 women, in order to isolate and determine the relationship between STL and reproductive outcomes.

Methods

Relative STL was determined by qPCR in 60 samples used in a total of 676 ICSI cycles. Univariable and multivariable statistical analyses were used to study the STL effect on fertilization rate; embryo morphology; biochemical, clinical, and ongoing pregnancy rates; and live birth (LB) rates.

Results

The average STL value was 4.5 (relative units; SD 1.9; range 2.4–14.2). Locally weighted scatterplot smoothing regression and the rho-Spearman test did not reveal significant correlations between STL and the outcomes analyzed. STL was not different between cycles resulting or not in pregnancy and LB (Mann-Whitney U test, p > 0.05). No significant effect of STL on reproductive outcomes was found, with the OR for each unit increase in STL (95% CI) of 0.94 (0.86–1–04), 0.99 (0.9–1.09), 0.98 (0.89–1.09), and 0.93 (0.8–1.06) for biochemical, clinical, and ongoing pregnancy and LB, respectively. The multilevel analysis confirmed that the effect of STL on fertilization; biochemical, clinical, and ongoing pregnancy; and LB was not significant (p > 0.05).

Conclusion

After addressing STL independently from female variables, results show that STL measurement is not useful to predict reproductive outcomes in ICSI cycles using donor semen.

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

Fig. 1
Fig. 2

References

  1. 1.

    O'Sullivan RJ, Karlseder J. Telomeres: protecting chromosomes against genome instability. Nat Rev Mol Cell Biol. 2010;11(3):171–81. https://doi.org/10.1038/nrm2848.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345(6274):458–60. https://doi.org/10.1038/345458a0.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Liu L, Blasco M, Trimarchi J, Keefe D. An essential role for functional telomeres in mouse germ cells during fertilization and early development. Dev Biol. 2002;249(1):74–84.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Kalmbach KH, Fontes Antunes DM, Dracxler RC, Knier TW, Seth-Smith ML, Wang F, et al. Telomeres and human reproduction. Fertil Steril. 2013;99(1):23–9. https://doi.org/10.1016/j.fertnstert.2012.11.039.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Ozturk S. Telomerase activity and telomere length in male germ cells. Biol Reprod. 2015;92(2):53. https://doi.org/10.1095/biolreprod.114.124008.

    Article  PubMed  Google Scholar 

  6. 6.

    Kimura M, Cherkas LF, Kato BS, Demissie S, Hjelmborg JB, Brimacombe M, et al. Offspring’s leukocyte telomere length, paternal age, and telomere elongation in sperm. PLoS Genet. 2008;4(2):e37. https://doi.org/10.1371/journal.pgen.0040037.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Aston KI, Hunt SC, Susser E, Kimura M, Factor-Litvak P, Carrell D, et al. Divergence of sperm and leukocyte age-dependent telomere dynamics: implications for male-driven evolution of telomere length in humans. Mol Hum Reprod. 2012;18(11):517–22. https://doi.org/10.1093/molehr/gas028.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Ferlin A, Rampazzo E, Rocca MS, Keppel S, Frigo AC, De Rossi A, et al. In young men sperm telomere length is related to sperm number and parental age. Hum Reprod. 2013;28(12):3370–6. https://doi.org/10.1093/humrep/det392.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Turner S, Hartshorne GM. Telomere lengths in human pronuclei, oocytes and spermatozoa. Mol Hum Reprod. 2013;19(8):510–8. https://doi.org/10.1093/molehr/gat021.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Kozik A, Bradbury EM, Zalensky A. Increased telomere size in sperm cells of mammals with long terminal (TTAGGG)n arrays. Mol Reprod Dev. 1998;51(1):98–104. https://doi.org/10.1002/(SICI)1098-2795(199809)51:1<98::AID-MRD12>3.0.CO;2-Q.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Antunes DM, Kalmbach KH, Wang F, Dracxler RC, Seth-Smith ML, Kramer Y, et al. A single-cell assay for telomere DNA content shows increasing telomere length heterogeneity, as well as increasing mean telomere length in human spermatozoa with advancing age. J Assist Reprod Genet. 2015;32(11):1685–90. https://doi.org/10.1007/s10815-015-0574-3.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Kawanishi S, Oikawa S. Mechanism of telomere shortening by oxidative stress. Ann N Y Acad Sci. 2004;1019:278–84. https://doi.org/10.1196/annals.1297.047.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Ling X, Zhang G, Chen Q, Yang H, Sun L, Zhou N, et al. Shorter sperm telomere length in association with exposure to polycyclic aromatic hydrocarbons: results from the MARHCS cohort study in Chongqing, China and in vivo animal experiments. Environ Int. 2016; https://doi.org/10.1016/j.envint.2016.08.001.

  14. 14.

    Thilagavathi J, Venkatesh S, Dada R. Telomere length in reproduction. Andrologia. 2013;45(5):289–304. https://doi.org/10.1111/and.12008.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Hansen ME, Hunt SC, Stone RC, Horvath K, Herbig U, Ranciaro A, et al. Shorter telomere length in Europeans than in Africans due to polygenetic adaptation. Hum Mol Genet. 2016; https://doi.org/10.1093/hmg/ddw070.

  16. 16.

    Yang Q, Zhao F, Dai S, Zhang N, Zhao W, Bai R, et al. Sperm telomere length is positively associated with the quality of early embryonic development. Hum Reprod. 2015;30(8):1876–81. https://doi.org/10.1093/humrep/dev144.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Rocca MS, Speltra E, Menegazzo M, Garolla A, Foresta C, Ferlin A. Sperm telomere length as a parameter of sperm quality in normozoospermic men. Hum Reprod. 2016;31(6):1158–63. https://doi.org/10.1093/humrep/dew061.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Cariati F, Jaroudi S, Alfarawati S, Raberi A, Alviggi C, Pivonello R, et al. Investigation of sperm telomere length as a potential marker of paternal genome integrity and semen quality. Reprod BioMed Online. 2016;33(3):404–11. https://doi.org/10.1016/j.rbmo.2016.06.006.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Yan J, Wu K, Tang R, Ding L, Chen ZJ. Effect of maternal age on the outcomes of in vitro fertilization and embryo transfer (IVF-ET). Sci China Life Sci. 2012;55(8):694–8. https://doi.org/10.1007/s11427-012-4357-0.

    Article  PubMed  Google Scholar 

  20. 20.

    Cardozo ER, Karmon AE, Gold J, Petrozza JC, Styer AK. Reproductive outcomes in oocyte donation cycles are associated with donor BMI. Hum Reprod. 2016;31(2):385–92. https://doi.org/10.1093/humrep/dev298.

    CAS  PubMed  Google Scholar 

  21. 21.

    Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002;30(10):e47.

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Coroleu B, Barri PN, Carreras O, Belil I, Buxaderas R, Veiga A, et al. Effect of using an echogenic catheter for ultrasound-guided embryo transfer in an IVF programme: a prospective, randomized, controlled study. Hum Reprod. 2006;21(7):1809–15. https://doi.org/10.1093/humrep/del045.

    Article  PubMed  Google Scholar 

  23. 23.

    de Frutos C, Lopez-Cardona AP, Fonseca Balvis N, Laguna-Barraza R, Rizos D, Gutierrez-Adan A, et al. Spermatozoa telomeres determine telomere length in early embryos and offspring. Reproduction. 2016;151(1):1–7. https://doi.org/10.1530/REP-15-0375.

    PubMed  Google Scholar 

  24. 24.

    Keefe DL, Franco S, Liu L, Trimarchi J, Cao B, Weitzen S, et al. Telomere length predicts embryo fragmentation after in vitro fertilization in women—toward a telomere theory of reproductive aging in women. Am J Obstet Gynecol. 2005;192(4):1256–1260; discussion 60-1. https://doi.org/10.1016/j.ajog.2005.01.036.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Keefe DL, Liu L, Marquard K. Telomeres and aging-related meiotic dysfunction in women. Cell Mol life Sci: CMLS. 2007;64(2):139–43. https://doi.org/10.1007/s00018-006-6466-z.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Cheng EH, Chen SU, Lee TH, Pai YP, Huang LS, Huang CC, et al. Evaluation of telomere length in cumulus cells as a potential biomarker of oocyte and embryo quality. Hum Reprod. 2013;28(4):929–36. https://doi.org/10.1093/humrep/det004.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Xu X, Chen X, Zhang X, Liu Y, Wang Z, Wang P, et al. Impaired telomere length and telomerase activity in peripheral blood leukocytes and granulosa cells in patients with biochemical primary ovarian insufficiency. Hum Reprod. 2017;32(1):201–7. https://doi.org/10.1093/humrep/dew283.

    PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Francesc Figueras and Désirée Garcia for the statistical analysis support.

Funding

This work was supported by the intramural funding of Clinica EUGIN and by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia (GENCAT 2015 DI 049) to M. T-M. and by Erasmus+ Programme to E.B.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Rita Vassena.

Ethics declarations

Ethical approval

Permission to conduct this study was obtained from the local Ethical Committee for Clinical Research. All procedures performed were in accordance with the ethical standards of the institutional research committees and with the 1964 Helsinki declaration, as revised in 2013.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Supplementary Figure 1
figure3

Correlation between STL (RU) and sperm concentration (million/mL) (A), sperm motility (% A + B) (B) and sperm donor age (years) (C). n = 60 samples. (GIF 18 kb)

Supplementary Figure 2
figure4

Locally Weighted Scatterplot Smoothing (LOWESS) regression of STL (RU) against embryo morphological score (A), fertilization rate (B), abnormal fertilization rate (C), pregnancy rates (biochemical (D), clinical (E), and ongoing (F)), and live birth rate (G). (GIF 97 kb)

Supplementary Table 1

(DOCX 15 kb)

Supplementary Table 2

(DOCX 13 kb)

Supplementary Table 3

(DOCX 39 kb)

High-Resolution Image (TIFF 439 kb)

High-Resolution Image (TIFF 821 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Torra-Massana, M., Barragán, M., Bellu, E. et al. Sperm telomere length in donor samples is not related to ICSI outcome. J Assist Reprod Genet 35, 649–657 (2018). https://doi.org/10.1007/s10815-017-1104-2

Download citation

Keywords

  • IVF/ICSI
  • Embryo morphology
  • Sperm telomere length
  • Live birth