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Journal of Assisted Reproduction and Genetics
Published in: Journal of Assisted Reproduction and Genetics 10/2019

01-10-2019 | Fluorescence in Situ Hybridization | Assisted Reproduction Technologies

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

Authors: Robert J. Carrasquillo, Taylor P. Kohn, Cengiz Cinnioglu, Carmen Rubio, Carlos Simon, Ranjith Ramasamy, Nasser Al-Asmar

Published in: Journal of Assisted Reproduction and Genetics | Issue 10/2019

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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.
Appendix
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Literature
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
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
3.
Handelsman DJ, Staraj S. Testicular size: the effects of aging, malnutrition, and illness. J Androl. 1985;6(3):144–51.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMedPubMedCentral
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
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.PubMed
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.PubMedPubMedCentral
11.
12.
Curley JP, Mashoodh R, Champagne FA. Epigenetics and the origins of paternal effects. Horm Behav. 2011;59(3):306–14.PubMed
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
14.
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.PubMed
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.PubMed
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
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.PubMed
19.
Toriello HV, Meck JM, PPaG C. Statement on guidance for genetic counseling in advanced paternal age. Genet Med. 2008;10(6):457–60.PubMedPubMedCentral
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.PubMed
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
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.PubMedPubMedCentral
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.PubMedPubMedCentral
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
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.PubMedPubMedCentral
26.
Hare EH, Moran PA. Raised parental age in psychiatric patients: evidence for the constitutional hypothesis. Br J Psychiatry. 1979;134:169–77.PubMed
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.PubMed
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
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.PubMedPubMedCentral
30.
Martin RH. Meiotic chromosome abnormalities in human spermatogenesis. Reprod Toxicol. 2006;22(2):142–7.PubMed
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
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.PubMed
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
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
35.
Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet. 2004;364(9430):273–83.PubMed
36.
Fonseka KG, Griffin DK. Is there a paternal age effect for aneuploidy? Cytogenet Genome Res. 2011;133(2–4):280–91.PubMed
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
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.PubMed
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
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
41.
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
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.PubMed
44.
Griffin DK. The incidence, origin, and etiology of aneuploidy. Int Rev Cytol. 1996;167:263–96.PubMed
45.
Mantel N, Stark CR. Paternal age in Down’s syndrome. Am J Ment Defic. 1967;71(6):1025–7.PubMed
46.
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.PubMedPubMedCentral
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.PubMed
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
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.PubMed
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.PubMedPubMedCentral
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.PubMedPubMedCentral
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.PubMedPubMedCentral
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
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.PubMedPubMedCentral
56.
Templado C, Vidal F, Estop A. Aneuploidy in human spermatozoa. Cytogenet Genome Res. 2011;133(2–4):91–9.PubMed
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.PubMed
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
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
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.PubMed
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
62.
Knapp M, Stiller M, Meyer M. Generating barcoded libraries for multiplex high-throughput sequencing. Methods Mol Biol. 2012;840:155–70.PubMed
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.PubMedPubMedCentral
Metadata
Title
Advanced paternal age does not affect embryo aneuploidy following blastocyst biopsy in egg donor cycles
Authors
Robert J. Carrasquillo
Taylor P. Kohn
Cengiz Cinnioglu
Carmen Rubio
Carlos Simon
Ranjith Ramasamy
Nasser Al-Asmar
Publication date
01-10-2019
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 10/2019
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-019-01549-z

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