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Advanced paternal age does not affect embryo aneuploidy following blastocyst biopsy in egg donor cycles

  • Assisted Reproduction Technologies
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Abstract

Purpose

To study the impact of advanced paternal age on embryo aneuploidy.

Methods

This is a multicenter international retrospective case series of couples undergoing assisted reproduction via in vitro fertilization using donor eggs to control for maternal factors and preimplantation genetic testing for aneuploidy via next-generation sequencing at Igenomix reproductive testing centers. The main outcome measure was the prevalence of embryo aneuploidy in egg donor cycles. Semen analysis data was retrieved for a small subset of the male patients.

Results

Data from 1202 IVF/ICSI egg donor cycles using ejaculated sperm (total 6934 embryos) evaluated using PGT-A between January 2016 and April 2018 in a global population across all Igenomix centers were included. No significant association was identified between advancing paternal age and the prevalence of embryo aneuploidy overall and when analyzing for each chromosome. There was also no significant association between advancing paternal age and specific aneuploid conditions (monosomy, trisomy, partial deletion/duplication) for all chromosomes in the genome.

Conclusions

This is the largest study of its kind in an international patient population to evaluate the impact of advancing paternal age on embryo aneuploidy. We conclude there is no specific effect of paternal age on the prevalence of embryo aneuploidy in the context of embryo biopsies from egg donor cycles.

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References

  1. Khandwala YS, Zhang CA, Lu Y, Eisenberg ML. The age of fathers in the USA is rising: an analysis of 168 867 480 births from 1972 to 2015. Hum Reprod. 2017;32(10):2110–6.

    PubMed  Google Scholar 

  2. McPherson NO, Zander-Fox D, Vincent AD, Lane M. Combined advanced parental age has an additive negative effect on live birth rates-data from 4057 first IVF/ICSI cycles. J Assist Reprod Genet. 2018;35(2):279–87.

    PubMed  Google Scholar 

  3. Handelsman DJ, Staraj S. Testicular size: the effects of aging, malnutrition, and illness. J Androl. 1985;6(3):144–51.

    CAS  PubMed  Google Scholar 

  4. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab. 2002;87(2):589–98.

    CAS  PubMed  Google Scholar 

  5. Kidd SA, Eskenazi B, Wyrobek AJ. Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril. 2001;75(2):237–48.

    CAS  PubMed  Google Scholar 

  6. Eskenazi B, Wyrobek AJ, Sloter E, Kidd SA, Moore L, Young S, et al. The association of age and semen quality in healthy men. Hum Reprod. 2003;18(2):447–54.

    CAS  PubMed  Google Scholar 

  7. Brahem S, Mehdi M, Elghezal H, Saad A. The effects of male aging on semen quality, sperm DNA fragmentation and chromosomal abnormalities in an infertile population. J Assist Reprod Genet. 2011;28(5):425–32.

    PubMed  PubMed Central  Google Scholar 

  8. Johnson SL, Dunleavy J, Gemmell NJ, Nakagawa S. Consistent age-dependent declines in human semen quality: a systematic review and meta-analysis. Ageing Res Rev. 2015;19:22–33.

    PubMed  Google Scholar 

  9. Moskovtsev SI, Willis J, Mullen JB. Age-related decline in sperm deoxyribonucleic acid integrity in patients evaluated for male infertility. Fertil Steril. 2006;85(2):496–9.

    CAS  PubMed  Google Scholar 

  10. Broer L, Codd V, Nyholt DR, Deelen J, Mangino M, Willemsen G, et al. Meta-analysis of telomere length in 19,713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect. Eur J Hum Genet. 2013;21(10):1163–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Reichman NE, Teitler JO. Paternal age as a risk factor for low birthweight. Am J Public Health. 2006;96(5):862–6.

    PubMed  PubMed Central  Google Scholar 

  12. Curley JP, Mashoodh R, Champagne FA. Epigenetics and the origins of paternal effects. Horm Behav. 2011;59(3):306–14.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  14. Lian ZH, Zack MM, Erickson JD. Paternal age and the occurrence of birth defects. Am J Hum Genet. 1986;39(5):648–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Orioli IM, Castilla EE, Scarano G, Mastroiacovo P. Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta. Am J Med Genet. 1995;59(2):209–17.

    CAS  PubMed  Google Scholar 

  16. Jones KL, Smith DW, Harvey MA, Hall BD, Quan L. Older paternal age and fresh gene mutation: data on additional disorders. J Pediatr. 1975;86(1):84–8.

    CAS  PubMed  Google Scholar 

  17. Wynn J, King TM, Gambello MJ, Waller DK, Hecht JT. Mortality in achondroplasia study: a 42-year follow-up. Am J Med Genet A. 2007;143A(21):2502–11.

    PubMed  Google Scholar 

  18. Wilkie AO, Slaney SF, Oldridge M, Poole MD, Ashworth GJ, Hockley AD, et al. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet. 1995;9(2):165–72.

    CAS  PubMed  Google Scholar 

  19. Toriello HV, Meck JM, PPaG C. Statement on guidance for genetic counseling in advanced paternal age. Genet Med. 2008;10(6):457–60.

    PubMed  PubMed Central  Google Scholar 

  20. Hemminki K, Kyyrönen P. Parental age and risk of sporadic and familial cancer in offspring: implications for germ cell mutagenesis. Epidemiology. 1999;10(6):747–51.

    CAS  PubMed  Google Scholar 

  21. Yip BH, Pawitan Y, Czene K. Parental age and risk of childhood cancers: a population-based cohort study from Sweden. Int J Epidemiol. 2006;35(6):1495–503.

    PubMed  Google Scholar 

  22. Murray L, McCarron P, Bailie K, Middleton R, Davey Smith G, Dempsey S, et al. Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study. Br J Cancer. 2002;86(3):356–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. D'Onofrio BM, Rickert ME, Frans E, Kuja-Halkola R, Almqvist C, Sjölander A, et al. Paternal age at childbearing and offspring psychiatric and academic morbidity. JAMA Psychiatry. 2014;71(4):432–8.

    PubMed  PubMed Central  Google Scholar 

  24. Reichenberg A, Gross R, Weiser M, Bresnahan M, Silverman J, Harlap S, et al. Advancing paternal age and autism. Arch Gen Psychiatry. 2006;63(9):1026–32.

    PubMed  Google Scholar 

  25. Buizer-Voskamp JE, Laan W, Staal WG, Hennekam EA, Aukes MF, Termorshuizen F, et al. Paternal age and psychiatric disorders: findings from a Dutch population registry. Schizophr Res. 2011;129(2–3):128–32.

    PubMed  PubMed Central  Google Scholar 

  26. Hare EH, Moran PA. Raised parental age in psychiatric patients: evidence for the constitutional hypothesis. Br J Psychiatry. 1979;134:169–77.

    CAS  PubMed  Google Scholar 

  27. Malaspina D, Harlap S, Fennig S, Heiman D, Nahon D, Feldman D, et al. Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry. 2001;58(4):361–7.

    CAS  PubMed  Google Scholar 

  28. Frans EM, Sandin S, Reichenberg A, Lichtenstein P, Långström N, Hultman CM. Advancing paternal age and bipolar disorder. Arch Gen Psychiatry. 2008;65(9):1034–40.

    PubMed  Google Scholar 

  29. Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G, et al. Rate of de novo mutations and the importance of father’s age to disease risk. Nature. 2012;488(7412):471–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Martin RH. Meiotic chromosome abnormalities in human spermatogenesis. Reprod Toxicol. 2006;22(2):142–7.

    CAS  PubMed  Google Scholar 

  31. 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.

    PubMed  Google Scholar 

  32. Zaragoza MV, Jacobs PA, James RS, Rogan P, Sherman S, Hassold T. Nondisjunction of human acrocentric chromosomes: studies of 432 trisomic fetuses and liveborns. Hum Genet. 1994;94(4):411–7.

    CAS  PubMed  Google Scholar 

  33. Sloter E, Nath J, Eskenazi B, Wyrobek AJ. Effects of male age on the frequencies of germinal and heritable chromosomal abnormalities in humans and rodents. Fertil Steril. 2004;81(4):925–43.

    PubMed  Google Scholar 

  34. Tempest HG. Meiotic recombination errors, the origin of sperm aneuploidy and clinical recommendations. Syst Biol Reprod Med. 2011;57(1–2):93–101.

    PubMed  Google Scholar 

  35. Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet. 2004;364(9430):273–83.

    CAS  PubMed  Google Scholar 

  36. Fonseka KG, Griffin DK. Is there a paternal age effect for aneuploidy? Cytogenet Genome Res. 2011;133(2–4):280–91.

    CAS  PubMed  Google Scholar 

  37. Mazzilli R, Cimadomo D, Rienzi L, Capalbo A, Levi Setti PE, Livi C, et al. Prevalence of XXY karyotypes in human blastocysts: multicentre data from 7549 trophectoderm biopsies obtained during preimplantation genetic testing cycles in IVF. Hum Reprod. 2018;33(7):1355–63.

    PubMed  Google Scholar 

  38. Wong IL, Legro RS, Lindheim SR, Paulson RJ, Sauer MV. Efficacy of oocytes donated by older women in an oocyte donation programme. Hum Reprod. 1996;11(4):820–3.

    CAS  PubMed  Google Scholar 

  39. Sauer MV, Kavic SM. Oocyte and embryo donation 2006: reviewing two decades of innovation and controversy. Reprod BioMed Online. 2006;12(2):153–62.

    PubMed  Google Scholar 

  40. Budak E, Garrido N, Soares SR, Melo MA, Meseguer M, Pellicer A, et al. Improvements achieved in an oocyte donation program over a 10-year period: sequential increase in implantation and pregnancy rates and decrease in high-order multiple pregnancies. Fertil Steril. 2007;88(2):342–9.

    PubMed  Google Scholar 

  41. Tapia LG, Rubino P, Ruiz de Assin R, Thiel A, Li X, Kolb B, et al. Advanced paternal age does not affect embryo aneuploidy rate in egg donor cycles [ASRM abstract P-49]. Fertil Steril. 2017;108(3, Supp):e126 https://www.fertstert.org/article/S0015-0282(17)30907-X/abstract. Accessed 27 Aug 2018.

    Google Scholar 

  42. Capelouto SM, Nagy ZP, Shapiro DB, Archer SR, Ellis DP, Smith AK, et al. Impact of male partner characteristics and semen parameters on in vitro fertilization and obstetric outcomes in a frozen oocyte donor model. Fertil Steril. 2018;110(5):859–69.

    PubMed  Google Scholar 

  43. Wagenbichler P, Killian W, Rett A, Schnedl W. Origin of the extra chromosome no. 21 in Down's syndrome. Hum Genet. 1976;32(1):13–6.

    CAS  PubMed  Google Scholar 

  44. Griffin DK. The incidence, origin, and etiology of aneuploidy. Int Rev Cytol. 1996;167:263–96.

    CAS  PubMed  Google Scholar 

  45. Mantel N, Stark CR. Paternal age in Down’s syndrome. Am J Ment Defic. 1967;71(6):1025–7.

    CAS  PubMed  Google Scholar 

  46. Erickson JD. Paternal age and Down syndrome. Am J Hum Genet. 1979;31(4):489–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Lowe X, Eskenazi B, Nelson DO, Kidd S, Alme A, Wyrobek AJ. Frequency of XY sperm increases with age in fathers of boys with Klinefelter syndrome. Am J Hum Genet. 2001;69(5):1046–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Kaarouch I, Bouamoud N, Madkour A, Louanjli N, Saadani B, Assou S, et al. Paternal age: negative impact on sperm genome decays and IVF outcomes after 40 years. Mol Reprod Dev. 2018;85(3):271–80.

    CAS  PubMed  Google Scholar 

  49. De Souza E, Alberman E, Morris JK. Down syndrome and paternal age, a new analysis of case-control data collected in the 1960s. Am J Med Genet A. 2009;149A(6):1205–8.

    PubMed  Google Scholar 

  50. Hatch M, Kline J, Levin B, Hutzler M, Warburton D. Paternal age and trisomy among spontaneous abortions. Hum Genet. 1990;85(3):355–61.

    CAS  PubMed  Google Scholar 

  51. Hook EB, Regal RR. A search for a paternal-age effect upon cases of 47, +21 in which the extra chromosome is of paternal origin. Am J Hum Genet. 1984;36(2):413–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. García-Ferreyra J, Luna D, Villegas L, Romero R, Zavala P, Hilario R, et al. High aneuploidy rates observed in embryos derived from donated oocytes are related to male aging and high percentages of sperm DNA fragmentation. Clin Med Insights Reprod Health. 2015;9:21–7.

    PubMed  PubMed Central  Google Scholar 

  53. García-Ferreyra J, Hilario R, Dueñas J. High percentages of embryos with 21, 18 or 13 trisomy are related to advanced paternal age in donor egg cycles. JBRA Assist Reprod. 2018;22(1):26–34.

    PubMed  PubMed Central  Google Scholar 

  54. 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.

    PubMed  Google Scholar 

  55. Gat I, Tang K, Quach K, Kuznyetsov V, Antes R, Filice M, et al. Sperm DNA fragmentation index does not correlate with blastocyst aneuploidy or morphological grading. PLoS One. 2017;12(6):e0179002.

    PubMed  PubMed Central  Google Scholar 

  56. Templado C, Vidal F, Estop A. Aneuploidy in human spermatozoa. Cytogenet Genome Res. 2011;133(2–4):91–9.

    CAS  PubMed  Google Scholar 

  57. Donate A, Estop AM, Giraldo J, Templado C. Paternal age and numerical chromosome abnormalities in human spermatozoa. Cytogenet Genome Res. 2016;148(4):241–8.

    CAS  PubMed  Google Scholar 

  58. Munné S, Lee A, Rosenwaks Z, Grifo J, Cohen J. Diagnosis of major chromosome aneuploidies in human preimplantation embryos. Hum Reprod. 1993;8(12):2185–91.

    PubMed  Google Scholar 

  59. Munné S, Fragouli E, Colls P, Katz-Jaffe M, Schoolcraft W, Wells D. Improved detection of aneuploid blastocysts using a new 12-chromosome FISH test. Reprod BioMed Online. 2010;20(1):92–7.

    PubMed  Google Scholar 

  60. Mastenbroek S, Twisk M, van Echten-Arends J, Sikkema-Raddatz B, Korevaar JC, Verhoeve HR, et al. In vitro fertilization with preimplantation genetic screening. N Engl J Med. 2007;357(1):9–17.

    CAS  PubMed  Google Scholar 

  61. Twisk M, Mastenbroek S, Hoek A, Heineman MJ, van der Veen F, Bossuyt PM, et al. No beneficial effect of preimplantation genetic screening in women of advanced maternal age with a high risk for embryonic aneuploidy. Hum Reprod. 2008;23(12):2813–7.

    PubMed  Google Scholar 

  62. Knapp M, Stiller M, Meyer M. Generating barcoded libraries for multiplex high-throughput sequencing. Methods Mol Biol. 2012;840:155–70.

    CAS  PubMed  Google Scholar 

  63. Goodrich D, Tao X, Bohrer C, Lonczak A, Xing T, Zimmerman R, et al. A randomized and blinded comparison of qPCR and NGS-based detection of aneuploidy in a cell line mixture model of blastocyst biopsy mosaicism. J Assist Reprod Genet. 2016;33(11):1473–80.

    PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Urology, Beth Israel Deaconess Medical Center, 145 Rosemary Street, C-1, Needham, MA, 02494, USA

    Robert J. Carrasquillo

  2. Igenomix, Valencia, Spain

    Robert J. Carrasquillo, Carmen Rubio, Carlos Simon & Nasser Al-Asmar

  3. Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Taylor P. Kohn

  4. Igenomix USA, Los Angeles, CA, USA

    Cengiz Cinnioglu

  5. Department of Urology, University of Miami Health System, Miami, FL, USA

    Ranjith Ramasamy

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  1. Robert J. Carrasquillo
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  2. Taylor P. Kohn
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  3. Cengiz Cinnioglu
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  4. Carmen Rubio
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  5. Carlos Simon
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  7. Nasser Al-Asmar
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Correspondence to Robert J. Carrasquillo.

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Supplemental Table 1

P values for trends by chromosome and aneuploid condition (PDF 53 kb)

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Carrasquillo, R.J., Kohn, T.P., Cinnioglu, C. et al. Advanced paternal age does not affect embryo aneuploidy following blastocyst biopsy in egg donor cycles. J Assist Reprod Genet 36, 2039–2045 (2019). https://doi.org/10.1007/s10815-019-01549-z

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  • DOI: https://doi.org/10.1007/s10815-019-01549-z

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