Impact of advanced maternal age on assisted reproductive technology outcomes: biological mechanisms, clinical implications and management strategies
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20262153Keywords:
Advanced maternal age, Assisted reproductive technology, In vitro fertilization, Frozen embryo transferAbstract
Delayed childbearing has increased the number of women of advanced maternal age (AMA) seeking assisted reproductive technology (ART). AMA, defined as ≥35 years, is linked to reduced ovarian reserve, poor oocyte quality, and higher pregnancy risks. Despite advances in IVF, ICSI and frozen embryo transfer (FET), maternal age remains a key factor affecting success rates. This review summarizes the biological changes associated with reproductive aging and their impact on ART outcomes such as implantation, pregnancy rates, miscarriage and perinatal outcomes. Literature shows that aging leads to mitochondrial dysfunction, chromosomal abnormalities and reduced embryo quality, resulting in lower pregnancy and live birth rates and higher miscarriage rates in women ≥35 years. While FET may improve uterine conditions, it cannot fully overcome the decline in oocyte quality. AMA is also associated with increased risks such as hypertension, gestational diabetes and preterm birth. In conclusion, advanced maternal age significantly affects ART outcomes, and careful patient counselling and individualized treatment strategies are essential to improve success rates.
References
Martin JA, Hamilton BE, Ventura SJ, Menacker F, Park MM, Sutton PD. Births: final data for 2001. Natl Vital Stat Rep. 2002;51(2):1-102.
Dicker D, Feldberg D, Samuel N, Goldman JA. Age and pregnancy rates in in vitro fertilization. J In Vitro Fert Embryo Transf. 1991;8:141-4.
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.
Hochler H, Lipschuetz M, Suissa-Cohen Y, Weiss A, Sela HY, Yagel S, et al. The impact of advanced maternal age on pregnancy outcomes: a retrospective multicenter study. J Clin Med. 2023;12(17):5696.
Wennberg AL, Opdahl S, Bergh C, Aaris Henningsen AK, Gissler M, Romundstad LB, et al. Effect of maternal age on maternal and neonatal outcomes after assisted reproductive technology. Fertil Steril. 2016;106(5):1142-9.
Hull MG, Glazener CM, Kelly NJ, Conway DI, Foster PA, Hinton RA, et al. The age-related decline in female fecundity: a quantitative controlled study of implanting capacity and survival of individual embryos after in vitro fertilization. Fertil Steril. 1996;65(4):783-90.
Fuchs F, Monet B, Ducruet T, Chaillet N, Audibert F. Effect of maternal age on the risk of preterm birth: a large cohort study. PLoS One. 2018;13(1):e0191002.
Dulitzki M, Soriano D, Schiff E, Chetrit A, Mashiach S, Seidman DS. Effect of very advanced maternal age on pregnancy outcome and rate of cesarean delivery. Obstet Gynecol. 1998;92(6):935-9.
David MS, Vintejoux E, Kucharczak F, Brouillet S, Rougier N, Huberlant S. Impact of caesarean section on pregnancy outcomes in ART after transfer of one or more frozen blastocysts. J Gynecol Obstet Hum Reprod. 2024;53(1):102692.
Lass A, Croucher C, Duffy S, Dawson K, Margara R, Winston RM. One thousand initiated cycles of in vitro fertilization in women ≥40 years of age. Fertil Steril. 1998;70(6):1030-4.
Simpson JL. Genetic programming in ovarian development and oogenesis. In: Treatment of the Postmenopausal Woman. Academic Press; 2007:29-47.
Schwartz D, Mayaux MJ. CECOS Federation. Female fecundity as a function of age: results of artificial insemination in 2193 nulliparous women with azoospermic husbands. N Engl J Med. 1982;306(7):404-6.
Capalbo A, Hoffmann ER, Cimadomo D, Ubaldi FM, Rienzi L. Human female meiosis revised: new insights into chromosome segregation and aneuploidies. Hum Reprod Update. 2017;23(6):706-22.
Petracchi F, Igarzabal ML, Gadow EC. Cytogenetic analysis of first trimester pregnancy loss. Int J Gynecol Obstet. 2008;104(3):243-4.
Spandorfer SD, Davis OK, Barmat LI, Chung PH, Rosenwaks Z. Relationship between maternal age and aneuploidy in IVF pregnancy loss. Fertil Steril. 2004;81(5):1265-9.
Dai R, Chen Y, Liu Y, Li Y, Wang H, Li J, et al. Effect of maternal age on spontaneous abortion during the first trimester. J Matern Fetal Neonatal Med. 2018;31(14):1824-9.
Hassold T, Chiu D. Maternal age-specific rates of numerical chromosome abnormalities. Hum Genet. 1985;70:11-7.
Magnus MC, Wilcox AJ, Morken NH, Weinberg CR, Haberg SE. Role of maternal age and pregnancy history in risk of miscarriage. BMJ. 2019;364:l869.
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. Fertil Steril. 2014;101(3):656-63.
Heffner LJ. Advanced maternal age—how old is too old? N Engl J Med. 2004;351(19):1927-9.
Nelson SM, Lawlor DA. Predicting live birth and adverse outcomes in IVF. PLoS Med. 2011;8(1):e1000386.
Fitzpatrick KE, Tuffnell D, Kurinczuk JJ, Knight M. Pregnancy at very advanced maternal age. BJOG. 2017;124(7):1097-106.
Secomandi L, Borghesan M, Velarde MC, Demaria M. Cellular senescence in female reproductive aging. Hum Reprod Update. 2022;28(2):172-89.
Storeide O, Veholmen M, Eide M, Bergsjo P, Sandvei R. Incidence of ectopic pregnancy. Acta Obstet Gynecol Scand. 1997;76(4):345-9.
Mikwar M, MacFarlane AJ, Marchetti F. Mechanisms of oocyte aneuploidy with advanced maternal age. Mutat Res Rev Mutat Res. 2020;785:108320.
Reddy KR, Asif M, Deotale G, Shanmuga Priya VG. Artificial intelligence in embryo selection: Enhancing precision and overcoming traditional limitations in vitro fertilization. Int J Reprod Contracept Obstet Gynecol. 2026;15:789-97.
Li Q, Wei X, Zeng W, Lin Y. Impact of IVF-ET on obstetric and perinatal outcomes in advanced maternal age women. Placenta. 2025;167:55-62.
Volsa AM, Hoffmann ER, Ross PJ, Canovas S. Epitranscriptomic modifications in embryonic development: insights into natural and ART-induced mechanisms and implications. Hum Reprod Update. 2026;32(2):181-205.
Zhang JT, Lee R, Sauer MV, Ananth CV. Risks of placental abruption and preterm delivery in patients undergoing assisted reproduction. JAMA Netw Open. 2024;7(7):e2420970.
Chen L, Dong Q, Weng R. Maternal and neonatal outcomes of dichorionic twin pregnancies achieved with assisted reproductive technology: meta-analysis of contemporary data. J Assist Reprod Genet. 2024;41(3):581-9.
Downloads
Published
How to Cite
Issue
Section
