Abstract
Purpose
The rate of embryonic aneuploidy increases with increasing female age and is the primary cause of lower pregnancy and live birth rates (LBR) in older reproductive age women. This retrospective cohort study evaluates single euploid embryo transfers to determine whether an age-related decline in reproductive efficiency persists.
Methods
A total of 8175 non-donor single embryo transfers (SET) after pre-implantation testing for aneuploidy (PGT-A) and cryopreservation were included. These were divided into five groups by patient age: < 35 years old (n = 3789 embryos transferred), 35–37 (n = 2200), 38–40 (n = 1624), 41–42 (n = 319), and > 42 (n = 243). Implantation rate (IR), clinical pregnancy rate (CPR), and LBR were calculated for each group as a percentage of embryos transferred and compared. CPR was also analyzed as a percentage of implanted pregnancies, and LBR as a percentage of clinical pregnancies, to determine when age has the greatest impact. These results were then adjusted for confounding variables via a multivariate logistic regression model.
Results
Implantation rates negatively correlated with age. After adjusting for confounders, women 38 years or older had a significantly lower IR than those under 35 (OR 0.85, 95%CI 0.73–0.99 for 38–40 years old; 0.69, 0.53–0.91 for 41–42, and 0.69, 0.51–0.94 for > 42). These differences are also apparent in CPR and LBR. The rates of progression to clinical pregnancy and live birth did not differ significantly by age group. Other factors observed to affect IR independently were anti-Müllerian hormone (AMH), day of embryo transfer, and embryo morphology.
Conclusion
While selection of euploid embryos may be effective in overcoming a significant proportion of the age-related decline in reproductive efficiency, a decrease in IR, CPR, and LBR persists even when analyzing only euploid embryo transfers. The observed impact of aging is, therefore, independent of ploidy, as well as of other variables that affect reproductive efficiency. These results indicate that factors other than aneuploidy contribute to reproductive senescence.
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References
Arias E, Xu J, Kochanek KD. United States life tables, 2016. Natl Vital Stat Rep. 2019;68(4):1–66.
Mathews TJ, Hamilton BE. Mean age of mother, 1970-2000. Natl Vital Stat Rep. 2002;51(1):1–13.
Mathews TJ, Hamilton BE. Mean age of mothers is on the rise: United States, 2000-2014. NCHS Data Brief. 2016;232:1–8.
American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and Practice Committee. Female age-related fertility decline. Committee Opinion No. 589. Fertil Steril. 2014;101(3):633–4.
Society for Assisted Reproductive Technology. 2003 Assisted Reproductive Technology National Summary Report.
Society for Assisted Reproductive Technology. 2016 Assisted Reproductive Technology National Summary Report.
Kawwass JF, Monsour M, Crawford S, Kissin DM, Session DR, Kulkarni AD, et al. Trends and outcomes for donor oocyte cycles in the United States, 2000-2010. JAMA. 2013;310(22):2426–34.
Seli E. Ovarian aging. Semin Reprod Med. 2015;33(6):375–6. https://doi.org/10.1055/s-0035-1567817.
Aubert G, Lansdorp PM. Telomeres and aging. Physiol Rev. 2008;88(2):557–79. https://doi.org/10.1152/physrev.00026.2007.
Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14(10):R115. Erratum in: Genome Biol. 2015;16:96. https://doi.org/10.1016/j.contraception.2020.02.011.
Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573–91.
Christiansen L, Lenart A, Tan Q, Vaupel JW, Aviv A, McGue M, et al. DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging Cell. 2016;15(1):149–54.
Perna L, Zhang Y, Mons U, Holleczek B, Saum KU, Brenner H. Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. Clin Epigenetics. 2016;8:64.
Morin SJ, Tao X, Marin D, Zhan Y, Landis J, Bedard J, et al. DNA methylation-based age prediction and telomere length in white blood cells and cumulus cells of infertile women with normal or poor response to ovarian stimulation. Aging (Albany NY). 2018 Dec 8;10(12):3761–73.
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):656–663.e1. https://doi.org/10.1016/j.fertnstert.2019.06.019.
Forman EJ, Hong KH, Franasiak JM, Scott RT Jr. Obstetrical and neonatal outcomes from the BEST Trial: single embryo transfer with aneuploidy screening improves outcomes after in vitro fertilization without compromising delivery rates. Am J Obstet Gynecol. 2014;210(2):157.e1–6. https://doi.org/10.1038/s41598-020-61117-9.
Neal SA, Morin SJ, Franasiak JM, Goodman LR, Juneau CR, Forman EJ, et al. Preimplantation genetic testing for aneuploidy is cost-effective, shortens treatment time, and reduces the risk of failed embryo transfer and clinical miscarriage. Fertil Steril. 2018;110(5):896–904.
Irani M, Zaninovic N, Rosenwaks Z, Xu K. Does maternal age at retrieval influence the implantation potential of euploid blastocysts? Am J Obstet Gynecol. 2019;220:379.e1–7. https://doi.org/10.1097/NRL.0000000000000259.
Franasiak JM, Forman EJ, Patounakis G, Hong KH, Werner MD, Upham KM, et al. Investigating the impact of the timing of blastulation on implantation: management of embryo-endometrial synchrony improves outcomes. Hum Reprod Open. 2018;2018(4):hoy022. https://doi.org/10.1016/j.fertnstert.2019.06.019.
Broekmans FJ. Individualization of FSH doses in assisted reproduction: facts and fiction. Front Endocrinol (Lausanne). 2019;10:181. https://doi.org/10.3389/fendo.2019.00181.
Lensen SF, Wilkinson J, Leijdekkers JA, La Marca A, Mol BWJ, Marjoribanks J, et al. Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI). Cochrane Database Syst Rev. 2018;2:CD012693.
Labarta E, Bosch E, Alamá P, Rubio C, Rodrigo L, Pellicer A. Moderate ovarian stimulation does not increase the incidence of human embryo chromosomal abnormalities in in vitro fertilization cycles. J Clin Endocrinol Metab. 2012 Oct;97(10):E1987–94.
Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999;11(3):307–11.
Treff NR, Su J, Tao X, Levy B, Scott RT Jr. Accurate single cell 24 chromosome aneuploidy screening using whole genome amplification and single nucleotide polymorphism microarrays. Fertil Steril. 2010;94(6):2017–21.
Zimmerman RS, Tao X, Marin D, Werner MD, Hong KH, Lonczak A, et al. Preclinical validation of a targeted next generation sequencing-based comprehensive chromosome screening methodology in human blastocysts. Mol Hum Reprod. 2018;24(1):37–45.
Navot D, Drews MR, Bergh PA, Guzman I, Karstaedt A, Scott RT Jr, et al. Age-related decline in female fertility is not due to diminished capacity of the uterus to sustain embryo implantation. Fertil Steril. 1994;61(1):97–101.
Segal TR, Kim K, Mumford SL, Goldfarb JM, Weinerman RS. How much does the uterus matter? Perinatal outcomes are improved when donor oocyte embryos are transferred to gestational carriers compared to intended parent recipients. Fertil Steril. 2018;110(5):888–95. https://doi.org/10.1016/j.fertnstert.2018.06.015.
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Emre Seli is a consultant for and receives research funding from Foundation for Embryonic Competence.
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Reig, A., Franasiak, J., Scott, R.T. et al. The impact of age beyond ploidy: outcome data from 8175 euploid single embryo transfers. J Assist Reprod Genet 37, 595–602 (2020). https://doi.org/10.1007/s10815-020-01739-0
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DOI: https://doi.org/10.1007/s10815-020-01739-0