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Embryonic Development in Relation to Maternal Age and Conception Probability

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Abstract

Data regarding association between early embryo development and maternal age is limited and inconclusive. This study has two aims: to evaluate differences in the cleavage stage of embryos in young versus advanced maternal age (AMA) women. To compare the early embryonic development of embryos that result in pregnancy versus no pregnancy. A retrospective study of early embryonic development which was recorded and analyzed using time-lapse imaging was conducted. The kinetic markers of time to pronuclei fading (tPNf) and appearance of two to eight cells (t2–t8) were assessed. For embryos cultured to blastocyst, times to morula (tM), start of blastulation (tSB) cavitated, and expanded blastocyst (tB, tEB) were also recorded. A total of 2021 oocytes from 364 intracytoplasmic sperm injection (ICSI) cycles were evaluated, of which 1223 (60.5%) were derived from young patients and 798 (39.5%) from those of AMA. The mean time points to t3, t4, t5, t6, tSB, tB, and tEB were significantly shorter for embryos derived from younger women, as compared to older women (p < 0.05). Overall, women who conceived presented a faster embryonic development, for both age groups. The mean time points of t2 and t8 were significantly shorter in patients who conceived versus not conceived (p < 0.05). We concluded that older women’s age is associated with delayed embryonic development. Embryos that yielded pregnancy cleaved faster compared to those which did not, in both age groups. Thus, when considering which embryo to transfer to women of AMA, selecting the faster-developing embryos may improve the chances of conception.

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References

  1. Mosher WD, Pratt WF. Fecundity and infertility in the United States: incidence and trends. Fertil Steril. 1991;56(2):192–3.

    Article  CAS  Google Scholar 

  2. Mills M, Rindfuss RR, McDonald P, te Velde E, Reproduction E, Society TF. Why do people postpone parenthood? Reasons and social policy incentives. Hum Reprod Update. 2011;17(6):848–60. https://doi.org/10.1093/humupd/dmr026.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Navot D, Bergh PA, Williams MA, Garrisi GJ, Guzman I, Sandler B, et al. Poor oocyte quality rather than implantation failure as a cause of age-related decline in female fertility. Lancet. 1991;337(8754):1375–7. https://doi.org/10.1016/0140-6736(91)93060-m.

    Article  CAS  PubMed  Google Scholar 

  4. Korkmaz C, Tekin YB, Sakinci M, Ercan CM. Effects of maternal ageing on ICSI outcomes and embryo development in relation to oocytes morphological characteristics of birefringent structures. Zygote. 2015;23(4):550–5. https://doi.org/10.1017/S0967199414000197.

    Article  PubMed  Google Scholar 

  5. Cimadomo D, Fabozzi G, Vaiarelli A, Ubaldi N, Ubaldi FM, Rienzi L. Impact of maternal age on oocyte and embryo competence. Front Endocrinol (Lausanne). 2018;9:327. https://doi.org/10.3389/fendo.2018.00327.

    Article  Google Scholar 

  6. Li Q, McKenzie LJ, Matzuk MM. Revisiting oocyte-somatic cell interactions: in search of novel intrafollicular predictors and regulators of oocyte developmental competence. Mol Hum Reprod. 2008;14(12):673–8. https://doi.org/10.1093/molehr/gan064.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bebbere D, Masala L, Albertini DF, Ledda S. The subcortical maternal complex: multiple functions for one biological structure. J Assist Reprod Genet. 2016;33(11):1431–8. https://doi.org/10.1007/s10815-016-0788-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Scott L. The biological basis of non-invasive strategies for selection of human oocytes and embryos. Hum Reprod Update. 2003;9(3):237–49. https://doi.org/10.1093/humupd/dmg023.

    Article  PubMed  Google Scholar 

  9. Baxter Bendus AE, Mayer JF, Shipley SK, Catherino WH. Interobserver and intraobserver variation in day 3 embryo grading. Fertil Steril. 2006;86(6):1608–15. https://doi.org/10.1016/j.fertnstert.2006.05.037.

    Article  PubMed  Google Scholar 

  10. Gardner DK, Meseguer M, Rubio C, Treff NR. Diagnosis of human preimplantation embryo viability. Hum Reprod Update. 2015;21(6):727–47. https://doi.org/10.1093/humupd/dmu064.

    Article  CAS  PubMed  Google Scholar 

  11. Chen AA, Tan L, Suraj V, Reijo Pera R, Shen S. Biomarkers identified with time-lapse imaging: discovery, validation, and practical application. Fertil Steril. 2013;99(4):1035–43. https://doi.org/10.1016/j.fertnstert.2013.01.143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wong C, Chen AA, Behr B, Shen S. Time-lapse microscopy and image analysis in basic and clinical embryo development research. Reprod BioMed Online. 2013;26(2):120–9. https://doi.org/10.1016/j.rbmo.2012.11.003.

    Article  CAS  PubMed  Google Scholar 

  13. Meseguer M, Herrero J, Tejera A, Hilligsoe KM, Ramsing NB, Remohi J. The use of morphokinetics as a predictor of embryo implantation. Hum Reprod. 2011;26(10):2658–71. https://doi.org/10.1093/humrep/der256.

    Article  PubMed  Google Scholar 

  14. Petersen BM, Boel M, Montag M, Gardner DK. Development of a generally applicable morphokinetic algorithm capable of predicting the implantation potential of embryos transferred on Day 3. Hum Reprod. 2016;31(10):2231–44. https://doi.org/10.1093/humrep/dew188.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Alpha Scientists in Reproductive M, Embryology ESIGo. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26(6):1270-1283. doi:10.1093/humrep/der037.

  16. The Boston IVF handbook of infertility: a practical guide for practitioners who care for infertile couples (Reproductive Medicine and Assisted Reproductive Techniques). 3rd ed. Informa Healthcare; 2011.

  17. Akarsu S, Gode F, Isik AZ, Celenk H, Tamer FB, Erkilinc S. Comparison of the morphokinetic parameters of embryos according to ovarian reserve in IVF cycles. Gynecol Endocrinol. 2017;33(9):733–6. https://doi.org/10.1080/09513590.2017.1312327.

    Article  PubMed  Google Scholar 

  18. Akhter N, Shahab M. Morphokinetic analysis of human embryo development and its relationship to the female age: a retrospective time-lapse imaging study. Cell Mol Biol (Noisy-le-grand). 2017;63(8):84-92. doi:10.14715/cmb/2017.63.8.18.

  19. Faramarzi A, Khalili MA, Mangoli E. Correlations between embryo morphokinetic development and maternal age: results from an intracytoplasmic sperm injection program. Clin Exp Reprod Med. 2019;46(3):119–24. https://doi.org/10.5653/cerm.2019.02838.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Warshaviak M, Kalma Y, Carmon A, Samara N, Dviri M, Azem F, et al. The effect of advanced maternal age on embryo morphokinetics. Front Endocrinol (Lausanne). 2019;10:686. https://doi.org/10.3389/fendo.2019.00686.

    Article  Google Scholar 

  21. Lim AS, Tsakok MF. Age-related decline in fertility: a link to degenerative oocytes. Fertil Steril. 1997;68(2):265–71. https://doi.org/10.1016/s0015-0282(97)81513-0.

    Article  CAS  PubMed  Google Scholar 

  22. Schatten H, Sun QY, Prather R. The impact of mitochondrial function/dysfunction on IVF and new treatment possibilities for infertility. Reprod Biol Endocrinol. 2014;12:111. https://doi.org/10.1186/1477-7827-12-111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. de Bruin JP, Dorland M, Spek ER, Posthuma G, van Haaften M, Looman CW, et al. Age-related changes in the ultrastructure of the resting follicle pool in human ovaries. Biol Reprod. 2004;70(2):419–24. https://doi.org/10.1095/biolreprod.103.015784.

    Article  CAS  PubMed  Google Scholar 

  24. Wilding M, Dale B, Marino M, di Matteo L, Alviggi C, Pisaturo ML, et al. Mitochondrial aggregation patterns and activity in human oocytes and preimplantation embryos. Hum Reprod. 2001;16(5):909–17. https://doi.org/10.1093/humrep/16.5.909.

    Article  CAS  PubMed  Google Scholar 

  25. Grondahl ML, Christiansen SL, Kesmodel US, Agerholm IE, Lemmen JG, Lundstrom P, et al. Effect of women’s age on embryo morphology, cleavage rate and competence-A multicenter cohort study. PLoS One. 2017;12(4):e0172456. https://doi.org/10.1371/journal.pone.0172456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Stensen MH, Tanbo T, Storeng R, Byholm T, Fedorcsak P. Routine morphological scoring systems in assisted reproduction treatment fail to reflect age-related impairment of oocyte and embryo quality. Reprod BioMed Online. 2010;21(1):118–25. https://doi.org/10.1016/j.rbmo.2010.03.018.

    Article  PubMed  Google Scholar 

  27. 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 

  28. Mazzilli R, Cimadomo D, Vaiarelli A, Capalbo A, Dovere L, Alviggi E, et al. 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. Fertil Steril. 2017;108(6):961–72 e3. https://doi.org/10.1016/j.fertnstert.2017.08.033.

    Article  PubMed  Google Scholar 

  29. Ubaldi FM, Cimadomo D, Capalbo A, Vaiarelli A, Buffo L, Trabucco E, et al. Preimplantation genetic diagnosis for aneuploidy testing in women older than 44 years: a multicenter experience. Fertil Steril. 2017;107(5):1173–80. https://doi.org/10.1016/j.fertnstert.2017.03.007.

    Article  PubMed  Google Scholar 

  30. Franasiak JM, Forman EJ, Hong KH, Werner MD, Upham KM, Treff NR, et al. The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril. 2014;101(3):656–63 e1. https://doi.org/10.1016/j.fertnstert.2013.11.004.

    Article  PubMed  Google Scholar 

  31. Capalbo A, Hoffmann ER, Cimadomo D, Ubaldi FM, Rienzi L. Human female meiosis revised: new insights into the mechanisms of chromosome segregation and aneuploidies from advanced genomics and time-lapse imaging. Hum Reprod Update. 2017;23(6):706–22. https://doi.org/10.1093/humupd/dmx026.

    Article  CAS  PubMed  Google Scholar 

  32. Kuliev A, Zlatopolsky Z, Kirillova I, Spivakova J, Cieslak JJ. Meiosis errors in over 20,000 oocytes studied in the practice of preimplantation aneuploidy testing. Reprod BioMed Online. 2011;22(1):2–8. https://doi.org/10.1016/j.rbmo.2010.08.014.

    Article  PubMed  Google Scholar 

  33. Fragouli E, Alfarawati S, Spath K, Jaroudi S, Sarasa J, Enciso M, et al. The origin and impact of embryonic aneuploidy. Hum Genet. 2013;132(9):1001–13. https://doi.org/10.1007/s00439-013-1309-0.

    Article  PubMed  Google Scholar 

  34. Minasi MG, Colasante A, Riccio T, Ruberti A, Casciani V, Scarselli F, et al. Correlation between aneuploidy, standard morphology evaluation and morphokinetic development in 1730 biopsied blastocysts: a consecutive case series study. Hum Reprod. 2016;31(10):2245–54. https://doi.org/10.1093/humrep/dew183.

    Article  PubMed  Google Scholar 

  35. Campbell A, Fishel S, Bowman N, Duffy S, Sedler M, Hickman CF. Modelling a risk classification of aneuploidy in human embryos using non-invasive morphokinetics. Reprod BioMed Online. 2013;26(5):477–85. https://doi.org/10.1016/j.rbmo.2013.02.006.

    Article  PubMed  Google Scholar 

  36. Pacella L, Zander-Fox DL, Armstrong DT, Lane M. Women with reduced ovarian reserve or advanced maternal age have an altered follicular environment. Fertil Steril. 2012;98(4):986-94 e1-2. doi:10.1016/j.fertnstert.2012.06.025.

  37. Pinero-Sagredo E, Nunes S, de Los Santos MJ, Celda B, Esteve V. NMR metabolic profile of human follicular fluid. NMR Biomed. 2010;23(5):485–95. https://doi.org/10.1002/nbm.1488.

    Article  CAS  PubMed  Google Scholar 

  38. Meseguer M, Rubio I, Cruz M, Basile N, Marcos J, Requena A. Embryo incubation and selection in a time-lapse monitoring system improves pregnancy outcome compared with a standard incubator: a retrospective cohort study. Fertil Steril. 2012;98(6):1481–9 e10. https://doi.org/10.1016/j.fertnstert.2012.08.016.

    Article  PubMed  Google Scholar 

  39. Basile N, Vime P, Florensa M, Aparicio Ruiz B, Garcia Velasco JA, Remohi J, et al. The use of morphokinetics as a predictor of implantation: a multicentric study to define and validate an algorithm for embryo selection. Hum Reprod. 2015;30(2):276–83. https://doi.org/10.1093/humrep/deu331.

    Article  CAS  PubMed  Google Scholar 

  40. Dal Canto M, Coticchio G, Mignini Renzini M, De Ponti E, Novara PV, Brambillasca F, et al. Cleavage kinetics analysis of human embryos predicts development to blastocyst and implantation. Reprod BioMed Online. 2012;25(5):474–80. https://doi.org/10.1016/j.rbmo.2012.07.016.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. IVF and Infertility Unit, Hillel Yaffe Medical Center, Hadera, Israel

    Oshrit Lebovitz, Mediea Michaeli, Nardin Aslih, Diana Poltov, Daniela Estrada, Yuval Atzmon & Einat Shalom-Paz

  2. Ruth and Bruce Rappaport School of Medicine, Technion, Haifa, Israel

    Oshrit Lebovitz, Nardin Aslih, Daniela Estrada, Yuval Atzmon & Einat Shalom-Paz

  3. Department of Obstetrics and Gynecology, Sheba Medical Center, Ramat-Gan, Israel

    Oshrit Lebovitz

  4. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Oshrit Lebovitz

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Correspondence to Oshrit Lebovitz.

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Lebovitz, O., Michaeli, M., Aslih, N. et al. Embryonic Development in Relation to Maternal Age and Conception Probability. Reprod. Sci. 28, 2292–2300 (2021). https://doi.org/10.1007/s43032-021-00488-4

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