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Ubaldi FM, Cimadomo D, Vaiarelli A, et al. Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment. Front Endocrinol (Lausanne). 2019;10:94doi: 10.3389/fendo.2019.00094.
Ubaldi, F. M., Cimadomo, D., Vaiarelli, A., Fabozzi, G., Venturella, R., Maggiulli, R., Mazzilli, R., Ferrero, S., Palagiano, A., & Rienzi, L. (2019). Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment. Frontiers in endocrinology, 1094. https://doi.org/10.3389/fendo.2019.00094
Ubaldi, Filippo Maria, et al. "Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment." Frontiers in endocrinology vol. 10 (2019): 94. doi: https://doi.org/10.3389/fendo.2019.00094
Ubaldi FM, Cimadomo D, Vaiarelli A, Fabozzi G, Venturella R, Maggiulli R, Mazzilli R, Ferrero S, Palagiano A, Rienzi L. Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment. Front Endocrinol (Lausanne). 2019 Feb 20;10:94. doi: 10.3389/fendo.2019.00094. eCollection 2019. PMID: 30842755; PMCID: PMC6391863.
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Front Endocrinol (Lausanne). 2019 Feb 20;10:94. doi: 10.3389/fendo.2019.00094. eCollection 2019.

Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment.

Frontiers in endocrinology

Filippo Maria Ubaldi, Danilo Cimadomo, Alberto Vaiarelli, Gemma Fabozzi, Roberta Venturella, Roberta Maggiulli, Rossella Mazzilli, Susanna Ferrero, Antonio Palagiano, Laura Rienzi

Affiliations

  1. Clinica Valle Giulia, G.en.e.r.a. Centers for Reproductive Medicine, Rome, Italy.
  2. Department of Experimental and Clinical Medicine, University Magna Græcia of Catanzaro, Catanzaro, Italy.
  3. Andrology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
  4. Department of Gynecological, Obstetrical and Reproductive Sciences, University of Campania Luigi Vanvitelli, Caserta, Italy.

PMID: 30842755 PMCID: PMC6391863 DOI: 10.3389/fendo.2019.00094

Abstract

Advanced maternal age (AMA; >35 year) is associated with a decline in both ovarian reserve and oocyte competence. At present, no remedies are available to counteract the aging-related fertility decay, however different therapeutic approaches can be offered to women older than 35 year undergoing IVF. This review summarizes the main current strategies proposed for the treatment of AMA: (i) oocyte cryopreservation to conduct fertility preservation for medical reasons or "social freezing" for non-medical reasons, (ii) personalized controlled ovarian stimulation to maximize the exploitation of the ovarian reserve in each patient, (iii) enhancement of embryo selection via blastocyst-stage preimplantation genetic testing for aneuploidies and frozen single embryo transfer, or (iv) oocyte donation in case of minimal/null residual chance of pregnancy. Future strategies and tools are in the pipeline that might minimize the risks of AMA through non-invasive approaches for embryo selection (e.g., molecular analyses of leftover products of IVF, such as spent culture media). These are yet challenging but potentially ground-breaking perspectives promising a lower clinical workload with a higher cost-effectiveness. We also reviewed emerging experimental therapeutic approaches to attempt at restoring maternal reproductive potential, e.g., spindle-chromosomal complex, pronuclear or mitochondrial transfer, and chromosome therapy.

Keywords: advanced maternal age; embryo selection; oocyte cryopreservation; oocyte donation; ovarian stimulation; single embryo transfer

References

  1. Reprod Biomed Online. 2017 Dec;35(6):678-684 - PubMed
  2. Hum Reprod Update. 2013 Jan-Feb;19(1):26-36 - PubMed
  3. Mitochondrion. 2011 Sep;11(5):797-813 - PubMed
  4. Gynecol Endocrinol. 2016;32(1):1-5 - PubMed
  5. J Clin Endocrinol Metab. 2005 Jul;90(7):4399-404 - PubMed
  6. Nature. 2004 Mar 11;428(6979):145-50 - PubMed
  7. Hum Reprod Update. 2014 Jan-Feb;20(1):124-40 - PubMed
  8. J Clin Endocrinol Metab. 2002 Apr;87(4):1907-8 - PubMed
  9. Cell Tissue Res. 2013 Nov;354(2):593-607 - PubMed
  10. Obstet Gynecol. 2006 Nov;108(5):1084-8 - PubMed
  11. Fertil Steril. 2012 Sep;98(3):644-9 - PubMed
  12. Mol Hum Reprod. 2010 Dec;16(12):944-9 - PubMed
  13. Fertil Steril. 2017 May;107(5):1098-1106 - PubMed
  14. Reprod Biomed Online. 2014 Dec;29(6):684-91 - PubMed
  15. Nat Med. 2012 Feb 26;18(3):413-21 - PubMed
  16. F1000Res. 2013 Nov 12;2:240 - PubMed
  17. Fertil Steril. 2018 Mar;109(3):429-436 - PubMed
  18. Fertil Steril. 2013 Jan;99(1):37-43 - PubMed
  19. Lancet. 2018 May 5;391(10132):1842-1852 - PubMed
  20. Reproduction. 2017 Jul;154(1):R23-R35 - PubMed
  21. Nature. 1990 Apr 19;344(6268):768-70 - PubMed
  22. Hum Reprod. 2015 Jan;30(1):81-7 - PubMed
  23. Fertil Steril. 2017 Sep;108(3):407-415.e11 - PubMed
  24. Reprod Biol Endocrinol. 2014 Nov 24;12:111 - PubMed
  25. Hum Reprod. 2016 May;31(5):977-85 - PubMed
  26. Gynecol Endocrinol. 2016 Jul;32(7):577-80 - PubMed
  27. Hum Reprod. 2019 Jan 01;34(1):181-192 - PubMed
  28. Fertil Steril. 2014 Mar;101(3):656-663.e1 - PubMed
  29. PLoS One. 2014 Apr 25;9(4):e96237 - PubMed
  30. Reprod Biomed Online. 2014 May;28(5):548-51 - PubMed
  31. Reprod Biomed Online. 2017 Jan;34(1):32-37 - PubMed
  32. PLoS One. 2015 Oct 15;10(10):e0140779 - PubMed
  33. Fertil Steril. 2014 Dec;102(6):1692-9.e6 - PubMed
  34. Hum Reprod. 2016 Feb;31(2):370-6 - PubMed
  35. Hum Reprod. 2016 Jan;31(1):199-208 - PubMed
  36. Clin Endocrinol (Oxf). 2016 May;84(5):720-8 - PubMed
  37. Nature. 2010 May 6;465(7294):82-5 - PubMed
  38. Fertil Steril. 2015 Mar;103(3):662-8 - PubMed
  39. Hum Reprod Update. 2015 Nov-Dec;21(6):727-47 - PubMed
  40. DNA Res. 2015 Oct;22(5):331-42 - PubMed
  41. J Assist Reprod Genet. 2016 Oct;33(10):1279-1286 - PubMed
  42. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD000099 - PubMed
  43. Fertil Steril. 2014 Jul;102(1):108-115.e1 - PubMed
  44. Curr Opin Obstet Gynecol. 2017 Jun;29(3):153-159 - PubMed
  45. Fertil Steril. 2015 May;103(5):1136-43 - PubMed
  46. Trends Endocrinol Metab. 2014 Jan;25(1):5-7 - PubMed
  47. Hum Reprod Update. 2011 Nov-Dec;17(6):848-60 - PubMed
  48. Hum Reprod. 2015 Sep;30(9):2097-106 - PubMed
  49. Hum Reprod Update. 2001 Jul-Aug;7(4):428-35 - PubMed
  50. Science. 2015 Apr 3;348(6230):36-8 - PubMed
  51. Curr Opin Endocrinol Diabetes Obes. 2016 Dec;23(6):458-464 - PubMed
  52. Fertil Steril. 2017 May;107(5):1173-1180 - PubMed
  53. Hum Reprod. 2017 Sep 1;32(9):1802-1811 - PubMed
  54. Dev Biol. 2006 Oct 1;298(1):149-54 - PubMed
  55. Fertil Steril. 2004 Jun;81(6):1713-4 - PubMed
  56. J Mol Cell Biol. 2011 Apr;3(2):132-41 - PubMed
  57. Maturitas. 2013 Nov;76(3):279-83 - PubMed
  58. Gynecol Endocrinol. 2016;32(1):74-7 - PubMed
  59. Hum Reprod. 2011 Oct;26(10):2593-7 - PubMed
  60. J Assist Reprod Genet. 2016 Aug;33(8):971-80 - PubMed
  61. Fertil Steril. 2018 Oct;110(5):870-879.e5 - PubMed
  62. Hum Reprod. 2011 Feb;26(2):480-90 - PubMed
  63. Fertil Steril. 2016 Aug;106(2):244-50 - PubMed
  64. Mol Hum Reprod. 2014 Mar;20(3):271-81 - PubMed
  65. Reprod Sci. 2018 Jul;25(7):980-982 - PubMed
  66. J Obstet Gynaecol Can. 2018 Mar;40(3):356-368 - PubMed
  67. Fertil Steril. 2011 Mar 1;95(3):1031-6 - PubMed
  68. Differentiation. 2008 Oct;76(8):843-56 - PubMed
  69. Hum Reprod Update. 2016 Jan-Feb;22(1):2-22 - PubMed
  70. Stem Cells Dev. 2011 Aug;20(8):1451-64 - PubMed
  71. Fertil Steril. 2018 Apr;109(4):644-664 - PubMed
  72. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12580-5 - PubMed
  73. Stem Cells. 2013 Nov;31(11):2538-50 - PubMed
  74. Fertil Steril. 2017 Oct;108(4):585-591 - PubMed
  75. Hum Reprod. 2018 Aug 1;33(8):1442-1448 - PubMed
  76. BJOG. 2014 Mar;121 Suppl 1:49-56 - PubMed
  77. Fertil Steril. 2013 Jul;100(1):100-7.e1 - PubMed
  78. Hum Reprod. 2017 Jan;32(1):112-118 - PubMed
  79. BJOG. 2016 Aug;123(9):1471-80 - PubMed
  80. Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11907-11912 - PubMed
  81. Sci Rep. 2017 Jul 12;7(1):5210 - PubMed
  82. Science. 2012 Nov 16;338(6109):971-5 - PubMed
  83. Fertil Steril. 2009 Nov;92(5):1520-4 - PubMed
  84. J Assist Reprod Genet. 2017 Apr;34(4):487-493 - PubMed
  85. Hum Reprod. 2009 Aug;24(8):1786-810 - PubMed
  86. Am J Obstet Gynecol. 2014 Feb;210(2):157.e1-6 - PubMed
  87. Fertil Steril. 2017 Jan;107(1):220-228.e5 - PubMed
  88. Hum Reprod. 2018 Jan 1;33(1):58-64 - PubMed
  89. Fertil Steril. 2016 Feb;105(2):459-66.e2 - PubMed
  90. Reprod Biol Endocrinol. 2005 May 05;3:17 - PubMed
  91. Hum Genet. 2017 Jul;136(7):805-819 - PubMed
  92. Biomed Res Int. 2016;2016:7193075 - PubMed
  93. Fertil Steril. 2018 Sep;110(4):661-670.e1 - PubMed
  94. Hum Reprod. 2011 Aug;26(8):2129-39 - PubMed
  95. Fertil Steril. 2014 Dec;102(6):1613-8 - PubMed
  96. Eur J Hum Genet. 2015 Jul;23(7):901-6 - PubMed
  97. Reproduction. 2012 Apr;143(4):469-76 - PubMed
  98. BJOG. 2016 Jun;123(7):1097-105 - PubMed
  99. J Assist Reprod Genet. 2016 Jul;33(7):893-7 - PubMed
  100. Hum Reprod Update. 2017 Mar 1;23(2):139-155 - PubMed
  101. Curr Opin Obstet Gynecol. 2018 Jun;30(3):155-162 - PubMed
  102. Reprod Sci. 2016 Dec;23(12):1612-1615 - PubMed
  103. Arch Gynecol Obstet. 2013 May;287(5):1017-21 - PubMed
  104. J Ovarian Res. 2014 Feb 25;7:25 - PubMed
  105. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005070 - PubMed
  106. PLoS One. 2018 May 10;13(5):e0197262 - PubMed
  107. Hum Reprod Update. 2017 Sep 1;23(5):560-579 - PubMed
  108. BJOG. 2017 Mar;124(4):561-572 - PubMed
  109. Mol Hum Reprod. 1998 Mar;4(3):269-80 - PubMed
  110. Fertil Steril. 2015 May;103(5):1194-1201.e2 - PubMed
  111. Hum Reprod. 2018 Apr 1;33(4):745-756 - PubMed
  112. Fertil Steril. 2010 Feb;93(2):397-404 - PubMed
  113. Hum Reprod. 2014 Jun;29(6):1173-81 - PubMed
  114. Reprod Biol Endocrinol. 2014 Feb 20;12:17 - PubMed
  115. Fertil Steril. 2013 Sep;100(3):624-30 - PubMed
  116. Hum Reprod. 2010 Nov;25(11):2678-84 - PubMed
  117. JBRA Assist Reprod. 2017 Dec 01;21(4):336-342 - PubMed
  118. Mol Hum Reprod. 2010 Aug;16(8):590-600 - PubMed
  119. New Bioeth. 2018 Apr;24(1):57-73 - PubMed
  120. Front Endocrinol (Lausanne). 2018 Jun 14;9:317 - PubMed
  121. Eur J Obstet Gynecol Reprod Biol. 1996 Feb;64(2):175-8 - PubMed
  122. EMBO Mol Med. 2015 Oct 15;7(11):1465-79 - PubMed
  123. Mol Hum Reprod. 2016 Oct;22(10):704-718 - PubMed
  124. Fertil Steril. 2014 Jan;101(1):105-11 - PubMed
  125. J Assist Reprod Genet. 2015 Aug;32(8):1195-6 - PubMed
  126. Int J Mol Sci. 2017 Jul 22;18(7): - PubMed
  127. Hum Reprod Update. 2017 Mar 1;23(2):211-220 - PubMed
  128. Hum Reprod. 2017 Mar 1;32(3):492-498 - PubMed
  129. Bioethics. 2009 Jan;23(1):47-58 - PubMed
  130. Hum Reprod. 2015 Nov;30(11):2519-26 - PubMed
  131. Hum Reprod. 2018 Sep 1;33(9):1767-1776 - PubMed
  132. Fertil Steril. 2015 Nov;104(5):1145-52.e1-5 - PubMed
  133. Cell. 2005 Jul 29;122(2):303-15 - PubMed
  134. Hum Reprod Update. 2016 Nov;22(6):725-743 - PubMed
  135. Int J Dev Biol. 2012;56(10-12):841-52 - PubMed
  136. Curr Opin Obstet Gynecol. 2017 Feb;29(1):59-63 - PubMed
  137. Fertil Steril. 2017 Jan;107(1):27-31 - PubMed
  138. JAMA. 2013 Dec 11;310(22):2426-34 - PubMed
  139. Fertil Steril. 2016 Jun;105(6):1452-3 - PubMed
  140. Fertil Steril. 2015 Feb;103(2):317-22 - PubMed
  141. Hum Reprod. 1999 Nov;14(11):2681-6 - PubMed
  142. Cryobiology. 2017 Oct;78:119-127 - PubMed
  143. Hum Reprod. 2018 Mar 1;33(3):464-473 - PubMed
  144. Fertil Steril. 2012 May;97(5):1108-14.e1 - PubMed
  145. Front Endocrinol (Lausanne). 2018 Jun 29;9:327 - PubMed
  146. Hum Reprod. 2015 Dec;30(12):2703-7 - PubMed
  147. Proc Natl Acad Sci U S A. 2012 Jul 3;109(27):E1858-67 - PubMed
  148. Arch Gynecol Obstet. 2013 May;287(5):1039-44 - PubMed
  149. Hum Reprod. 2017 Apr 1;32(4):725-732 - PubMed
  150. N Engl J Med. 2015 Nov 19;373(21):2089-90 - PubMed
  151. Mol Hum Reprod. 2001 Jan;7(1):49-55 - PubMed
  152. Fertil Steril. 2016 Mar;105(3):755-764.e8 - PubMed
  153. Semin Reprod Med. 2015 Nov;33(6):410-21 - PubMed
  154. Hum Reprod Update. 2014 Nov-Dec;20(6):808-21 - PubMed
  155. Hum Reprod. 2011 Jul;26(7):1768-74 - PubMed
  156. Fertil Steril. 2016 Nov;106(6):1312-1318 - PubMed
  157. Fertil Steril. 2012 Apr;97(4):870-5 - PubMed
  158. Fertil Steril. 2015 Aug;104(2):418-25 - PubMed
  159. Nature. 2009 Sep 17;461(7262):367-72 - PubMed
  160. Dev Biol. 2007 Jun 1;306(1):112-20 - PubMed
  161. Reprod Biol Endocrinol. 2018 Mar 9;16(1):22 - PubMed
  162. Health Psychol. 2008 Sep;27(5):604-15 - PubMed
  163. Hum Reprod Update. 2012 Jan-Feb;18(1):29-43 - PubMed
  164. Hum Reprod. 2004 Jul;19(7):1548-53 - PubMed
  165. Mol Cell Endocrinol. 2017 Apr 15;445:74-84 - PubMed
  166. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8585-90 - PubMed
  167. Aging (Albany NY). 2009 Dec 12;1(12):971-8 - PubMed
  168. Hum Reprod. 2016 Aug;31(8):1653-61 - PubMed
  169. Semin Reprod Med. 2002 Feb;20(1):63-74 - PubMed
  170. Fertil Steril. 2018 Aug;110(3):467-475.e2 - PubMed
  171. Nat Med. 2015 Oct;21(10):1114-6 - PubMed
  172. Hum Reprod. 2018 Jul 1;33(7):1342-1354 - PubMed
  173. Mol Hum Reprod. 2009 May;15(5):271-7 - PubMed
  174. Fertil Steril. 2015 Dec;104(6):1503-12 - PubMed
  175. Reprod Biomed Online. 2017 Apr;34(4):345-353 - PubMed
  176. Hum Reprod Update. 2012 Jan-Feb;18(1):73-91 - PubMed
  177. Fertil Steril. 2010 Feb;93(3):762-8 - PubMed
  178. Curr Biol. 2011 Apr 26;21(8):651-7 - PubMed
  179. J Obstet Gynaecol Can. 2011 Nov;33(11):1165-1175 - PubMed
  180. Hum Reprod. 1998 Oct;13(1O):2857-68 - PubMed
  181. Reprod Biol Endocrinol. 2011 Feb 16;9:25 - PubMed
  182. Genome Biol. 2017 Nov 24;18(1):224 - PubMed
  183. Fertil Steril. 2016 Jan;105(1):225-35.e1-3 - PubMed
  184. Stem Cells Int. 2017;2017:7610414 - PubMed
  185. Fertil Steril. 2017 May;107(5):1122-1129 - PubMed
  186. Arch Gynecol Obstet. 2015 Mar;291(3):657-62 - PubMed
  187. Fertil Steril. 2017 Jul;108(1):62-71.e8 - PubMed
  188. Expert Opin Biol Ther. 2002 Apr;2(4):361-70 - PubMed
  189. Hum Reprod. 1994 Mar;9(3):538-42 - PubMed
  190. Fertil Steril. 2016 Jun;105(6):1488-1495.e1 - PubMed
  191. Fertil Steril. 2016 Mar;105(3):548-559 - PubMed
  192. Hum Reprod. 2017 Nov 1;32(11):2153-2158 - PubMed
  193. Hum Reprod Update. 2017 Nov 1;23(6):706-722 - PubMed
  194. Reprod Biol Endocrinol. 2014 Sep 26;12:94 - PubMed
  195. Nature. 2013 Aug 15;500(7462):296-300 - PubMed
  196. Science. 2009 Nov 13;326(5955):948-52 - PubMed
  197. Obstet Gynecol. 2007 Nov;110(5):1050-8 - PubMed
  198. Bioethics. 2009 Jan;23(1):39-46 - PubMed
  199. Hum Reprod. 2013 Aug;28(8):2298-307 - PubMed
  200. Nat Cell Biol. 2009 May;11(5):631-6 - PubMed
  201. Hum Reprod. 2015 Aug;30(8):1850-60 - PubMed
  202. Hum Reprod Update. 2009 Sep-Oct;15(5):573-85 - PubMed
  203. Fertil Steril. 2018 May;109(5):908-918.e2 - PubMed
  204. J Assist Reprod Genet. 2016 Nov;33(11):1473-1480 - PubMed
  205. Hum Reprod Update. 2011 Jul-Aug;17(4):454-66 - PubMed
  206. Hum Reprod. 2003 Feb;18(2):455-7 - PubMed
  207. Acta Obstet Gynecol Scand. 2003 Jan;82(1):48-52 - PubMed
  208. J Clin Oncol. 2013 Jul 1;31(19):2500-10 - PubMed
  209. Reprod Biomed Online. 2012 Apr;24(4):424-32 - PubMed
  210. Fertil Steril. 2018 Jan;109(1):77-83 - PubMed

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