Top

Journal of Assisted Reproduction and Genetics

Open Access 02-05-2024 | Infertility | Review

Evaluation of telomere length and telomerase activity on predicting in vitro fertilization treatment outcomes

Authors: Persefoni Fragkiadaki, Elisavet Kouvidi, Anna Angelaki, Dimitra Nikolopoulou, Elena Vakonaki, Aristidis Tsatsakis

Published in: Journal of Assisted Reproduction and Genetics

Abstract

The current article is a literature review aiming to provide an overview of the existing knowledge on the association between telomere length and telomerase activity and in vitro fertilization. Recently, telomeres have been used as an effective biomarker to determine biological age, which may differ from chronological age due to genetic, lifestyle, and environmental factors. Cellular senescence, along with other exogenous and mainly environmental factors, can enhance telomere wear, further shortening their ends and may also affect reproductive aging. IVF is a common fertility treatment caused by female reasons (age, ovulation disorders, damaged or blocked fallopian tubes, endometriosis), male reasons (low sperm quantity or quality), or unexplained infertility. A growing number of studies have proposed a relationship between telomere length and telomerase activity and IVF success and have suggested their use as candidate biomarkers for IVF outcome. Nevertheless, additional studies are necessary to be conducted, in order to clarify the possible implication of telomeres in IVF and to evaluate their possible role as valuable predictors of IVF result.

Victorelli S, Passos JF. Telomeres and cell senescence — size matters not. EBioMedicine. 2017. https://doi.org/10.1016/j.ebiom.2017.03.027.2.

Kosebent EG, Uysal F, Ozturk S. Telomere length and telomerase activity during folliculogenesis in mammals. J Reprod Dev. 2018. https://doi.org/10.1262/jrd.2018-076.

Daios S, et al. Telomere length as a marker of biological aging: a critical review of recent literature. Curr Med Chem. 2022. https://doi.org/10.2174/0929867329666220713123750.

Rocca MS, Foresta C, Ferlin A. Telomere length: lights and shadows on their role in human reproduction. Biol Reprod. 2019. https://doi.org/10.1093/biolre/ioy208.

Anifandis G, et al. Insights into the role of telomeres in human embryological parameters. Opinions Regarding IVF. J Dev Biol. 2021. https://doi.org/10.3390/jdb9040049.

Aitken RJ. The changing tide of human fertility. Hum Reprod. 2022. https://doi.org/10.1093/humrep/deac011.

Choe JS, Archer J, Shanks AL. In Vitro Fertilization. StatPearls, Treasure Island. 2020.

Amini P, et al. Factors associated with in vitro fertilization live birth outcome: a comparison of different classification methods. Int J Fertil Steril. 2021. https://doi.org/10.22074/IJFS.2020.134582.

Wintner EM, et al. Does the transfer of a poor quality embryo together with a good quality embryo affect the In Vitro Fertilization (IVF) outcome? J Ovarian Res. 2017. https://doi.org/10.1186/s13048-016-0297-9.

10.

Cicamodo M, Franciosi F. Acquisition of oocyte competence to develop as an embryo: integrated nuclear and cytoplasmic events. Human Reprod Update. 2018. https://doi.org/10.1093/humupd/dmx040.

11.

Cimadomo D, et al. Impact of maternal age on oocyte and embryo competence. Front Endocrinol (Lausanne). 2018. https://doi.org/10.3389/fendo.2018.00327.

12.

Liu L, Keefe DL. Nuclear origin of aging-associated meiotic defects in senescence-accelerated mice. Biol Reprod. 2004. https://doi.org/10.1095/biolreprod.104.028985.

13.

Wright DL, et al. Characterization of telomerase activity in the human oocyte and preimplantation embryo. Mol Hum Reprod. 2001. https://doi.org/10.1093/molehr/7.10.947.

14.

Liu L, et al. Telomere lengthening early in development. Nat Cell Biol. 2007. https://doi.org/10.1038/NCB1664.

15.

Turner S, Wong HP, Rai J, Hartshorne GM. Telomere lengths in human oocytes, cleavage stage embryos and blastocysts. Mol Hum Reprod. 2010;16:685–94.CrossRefPubMedPubMedCentral

16.

Turner S, Hartshorne GM. Telomere lengths in human pronuclei, oocytes and spermatozoa. Mol Human Reprod. 2013. https://doi.org/10.1093/molehr/gat021.

17.

Keefe DL, et al. Short telomeres in eggs are associated with decreased outcomes following IVF — toward a telomere theory of reproductive aging in women. Am Soc Reprod Med Gen Prize Paper Session. 2003. https://doi.org/10.1016/S0015-0282(03)01803-X.

18.

Keefe DL, 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):1256–60.CrossRefPubMed

19.

Treff N, et al. Telomere DNA deficiency is associated with development of human embryonic aneuploidy. PLoS Genet. 2011. https://doi.org/10.1371/journal.pgen.1002161.

20.

Wang F, et al. The landscape of telomere length and telomerase in human embryos at blastocyst stage. 2023. https://doi.org/10.3390/genes14061200.

21.

Turner K, et al. Direct single-cell analysis of human polar bodies and cleavage-stage embryos reveals no evidence of the telomere theory of reproductive ageing in relation to aneuploidy generation. Cells. 2019. https://doi.org/10.3390/cells8020163.

22.

Turathum B, Gao EM, Chian RC. The function of cumulus cells in oocyte growth and maturation and in subsequent ovulation and fertilization. Cells. 2021. https://doi.org/10.3390/cells10092292.

23.

Wang W, et al. Telomerase activity is more significant for predicting the outcome of IVF treatment than telomere length in granulosa cells. Reproduction (Cambridge, England). 2014. https://doi.org/10.1530/REP-13-0223.

24.

Chen H, et al. Women with high telomerase activity in luteinised granulosa cells have a higher pregnancy rate during in vitro fertilisation treatment. J Assist Reprod Genet. 2011. https://doi.org/10.1007/s10815-011-9600-2.

25.

Cheng EH, et al. Evaluation of telomere length in cumulus cells as a potential biomarker of oocyte and embryo quality. Human Reprod. 2013. https://doi.org/10.1093/humrep/det004.

26.

Yu TN, et al. Assessment of telomere length and mitochondrial DNA copy number in granulosa cells as predictors of aneuploidy rate in young patients. J Clin Med. 2022. https://doi.org/10.3390/jcm11071824.

27.

Hanson BM, et al. Shorter telomere length of white blood cells is associated with higher rates of aneuploidy among infertile women undergoing in vitro fertilization. Fertil Steril. 2021. https://doi.org/10.1016/j.fertnstert.2020.09.164.

28.

Péntek S, et al. Telomere length and telomerase activity of granulosa cells and follicular fluid in women undergoing in vitro fertilization. Antioxidants (Basel, Switzerland). 2023. https://doi.org/10.3390/antiox12020419.

29.

Butts S, et al. Correlation of telomere length and telomerase activity with occult ovarian insufficiency. J Clin Endocrinol Metab. 2009. https://doi.org/10.1210/jc.2008-2269.

30.

Li Y, et al. Telomere length is short in PCOS and oral contraceptive does not affect the telomerase activity in granulosa cells of patients with PCOS. J Assist Reprod Genet. 2017. https://doi.org/10.1007/s10815-017-0929-z.

31.

Xu X, 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. https://doi.org/10.1093/humrep/dew283.

32.

Demanelis K, et al. Determinants of telomere length across human tissues. Science. 2020. https://doi.org/10.1126/science.aaz6876.

33.

Czamanski-Cohen J, et al. Cell-free DNA and telomere length among women undergoing in vitro fertilization treatment. J Assist Reprod Genet. 2015. https://doi.org/10.1007/s10815-015-0581-4

34.

Li Piani, et al. Peripheral mitochondrial DNA, telomere length and DNA methylation as predictors of live birth in in vitro fertilization cycles. PloS one. 2022. https://doi.org/10.1371/journal.pone.0261591.

35.

Vallet-Buisan M, et al. Contribution of semen to early embryo development: fertilization and beyond. Hum Reprod Update. 2023. https://doi.org/10.1093/humupd/dmad006.

36.

Fattet AJ, Chaillot M, Koscinski I. Telomere length, a new biomarker of male (in)fertility? A systematic review of the literature. Genes (Basel). 2023. https://doi.org/10.3390/genes14020425.

37.

Mishra S, et al. Mild oxidative stress is beneficial for sperm telomere length maintenance. World J Methodol. 2016. https://doi.org/10.5662/wjm.v6.i2.163.

38.

Simon L, et al. Clinical significance of sperm DNA damage in assisted reproduction outcome. Hum Reprod. 2010. https://doi.org/10.1093/humrep/deq103.

39.

Robinson L, et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod. 2012. https://doi.org/10.1093/humrep/des261.

40.

Fragkiadaki P, et al. Telomerase activity in pregnancy complications (Review). Mol Med Rep. 2016;14:16–21.CrossRefPubMedPubMedCentral

41.

Vasilopoulos E, et al. The association of female and male infertility with telomere length (Review). Int J Mol Med. 2019. https://doi.org/10.3892/ijmm.2019.4225.

42.

Amir S, et al. Sperm telomere length: diagnostic and prognostic biomarker in male infertility (Review). World Acad Sci J. 2019;1:259–63.

43.

Gentiluomo M, et al. Telomere length and male fertility. Int J Mol Sci. 2021. https://doi.org/10.3390/ijms22083959.

44.

Cariati F, et al. Investigation of sperm telomere length as a potential marker of paternal genome integrity and semen quality. Reprod Biomed Online. 2016. https://doi.org/10.1016/j.rbmo.2016.06.006.

45.

Biron-Shental T, et al. Sub-fertile sperm cells exemplify telomere dysfunction. J Assist Reprod Genet. 2018. https://doi.org/10.1007/s10815-017-1029-9.

46.

Arias-Sosa LA. Understanding the role of telomere dynamics in normal and dysfunctional human reproduction. Reprod Sci. 2019. https://doi.org/10.1177/1933719118804409.

47.

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. Reprod Biol Endocrinol. 2015. https://doi.org/10.1186/s12958-015-0028-x.

48.

Eisenberg DT, Hayes MG, Kuzawa CW. Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants. Proc Natl Acad Sci U S A. 2012;0251–6. https://doi.org/10.1073/pnas.1202092109.

49.

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. https://doi.org/10.1007/s10815-015-0574-3.

50.

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. https://doi.org/10.1371/journal.pgen.0040037.

51.

Berneau SC, et al. Associations of sperm telomere length with semen parameters, clinical outcomes and lifestyle factors in human normozoospermic samples. Andrology. 2020. https://doi.org/10.1111/andr.12734.

52.

Sharqawi M, et al. The impact of lifestyle on sperm function, telomere length, and IVF outcomes. Am J Mens Health. 2022. https://doi.org/10.1177/15579883221119931.

53.

Yuan Y, et al. Sperm telomere length as a novel biomarker of male infertility and embryonic development: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023. https://doi.org/10.3389/fendo.2022.1079966.

54.

Van Opstal J, et al. Male age interferes with embryo growth in IVF treatment. Hum Reprod. 2021. https://doi.org/10.1093/humrep/deaa256.

55.

Lu XM, et al. Effect of advanced paternal age on reproductive outcomes in IVF cycles of non-male-factor infertility: a retrospective cohort study. Asian J Androl. 2023. https://doi.org/10.4103/aja202234.

56.

Yang Q, et al. Effect of paternal overweight or obesity on IVF treatment outcomes and the possible mechanisms involved. Sci Rep. 2016. https://doi.org/10.1038/srep29787.

57.

Yang Q, et al. Sperm telomere length is positively associated with the quality of early embryonic development. Hum Reprod. 2015. https://doi.org/10.1093/humrep/dev144.

58.

Lopes AC, Oliveira PF, Sousa M. Shedding light into the relevance of telomeres in human reproduction and male factor infertility. Biol Reprod. 2019. https://doi.org/10.1093/biolre/ioy215.

59.

Tire B, Ozturk S. Potential effects of assisted reproductive technology on telomere length and telomerase activity in human oocytes and early embryos. J Ovarian Res. 2023. https://doi.org/10.1186/s13048-023-01211-4.

60.

Anifandis G, Messini CI, Dafopoulos K, Messinis IE. Genes and conditions controlling mammalian pre- and post-implantation embryo development. Curr Genomics. 2015. https://doi.org/10.2174/1389202916666141224205025.

61.

Gualtieri R, et al. Sperm oxidative stress during in vitro manipulation and its effects on sperm function and embryo development. Antioxidants (Basel). 2021. https://doi.org/10.3390/antiox10071025.

62.

Simopoulou M, et al. Considerations regarding embryo culture conditions: from media to epigenetics. In vivo. 2018. https://doi.org/10.21873/invivo.11261.

63.

Liu X, et al. The influence of male and female overweight/obesity on IVF outcomes: a cohort study based on registration in Western China. Reprod Health. 2023. https://doi.org/10.1186/s12978-022-01558-9.

64.

Weeg N, et al. The effect of maternal body mass index (BMI) and telomere function on in vitro fertilization (IVF) outcome: a preliminary cohort study. Hum Fertil (Camb). 2020. https://doi.org/10.1080/14647273.2019.1575988.

Title: Evaluation of telomere length and telomerase activity on predicting in vitro fertilization treatment outcomes
Authors: Persefoni Fragkiadaki
Elisavet Kouvidi
Anna Angelaki
Dimitra Nikolopoulou
Elena Vakonaki
Aristidis Tsatsakis
Publication date: 02-05-2024
Publisher: Springer US
Keywords: Infertility
Infertility
Primary Ovarian Insufficiency
Published in: Journal of Assisted Reproduction and Genetics
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-024-03117-6

At a glance: The STEP trials

Springer Medicine

Evaluation of telomere length and telomerase activity on predicting in vitro fertilization treatment outcomes

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content