Advanced maternal age and ART-conceived pregnancies

It is a Friday in the antenatal clinic. A 41-year-old G1 at 11 weeks' gestation, conceived by ICSI after seven years of infertility, sits across from you with a notebook full of questions. She has been told by her fertility clinic that she is "high risk", and she wants to know what that means. The honest answer is that she carries the stacked risk of age, of subfertility, and of ART — three risk factors that are biologically real but that, taken together, still end in a healthy live birth for the large majority of women. The skill the fellowship candidate brings is to counsel her without minimising, and to surveil her without medicalising her. This topic is that skill.^[1][6]

Overview and definition

Two related but distinct populations share this topic. Advanced maternal age (AMA) is conventionally defined as 35 years or older at the estimated date of delivery; very advanced maternal age (VAMA) is 45 years or older. Assisted reproductive technology (ART) refers to fertility treatments in which both eggs and sperm are handled outside the body — IVF and ICSI — and is distinct from ovulation induction and controlled ovarian stimulation without IVF.^[1][4]

The two populations overlap heavily, because the demographic shift driving older motherhood is the same shift driving ART use — and the modern ART population is increasingly a singleton population after elective single embryo transfer (eSET). The exam-relevant point is that the excess risk of the ART singleton persists even after eSET, indicating an intrinsic effect of the conception method or the underlying infertility.^[6]

The fundamental framing: in any given patient, distinguish three separate risk contributions — age, subfertility, and ART. They are not interchangeable, and the counselling and surveillance differ for each.^[6]

References13ShowHide

1. [1]Reddy UM, Ko CW, Willinger M Maternal age and the risk of stillbirth throughout pregnancy in the United States Am J Obstet Gynecol, 2006.PMID 16949411
2. [2]Stillbirth Collaborative Research Network Writing Group Association between stillbirth and risk factors known at pregnancy confirmation JAMA, 2011.PMID 22166606
3. [3]Davies MJ, Moore VM, Willson KJ, et al. Reproductive technologies and the risk of birth defects N Engl J Med, 2012.PMID 22559061
4. [4]Pandey S, Shetty A, Hamilton M, et al. Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis Hum Reprod Update, 2012.PMID 22611174
5. [5]Lazaraviciute G, Kauser M, Bhattacharya S, et al. A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously Hum Reprod Update, 2014.PMID 24961233
6. [6]Luke B Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies Am J Obstet Gynecol, 2017.PMID 28322775
7. [7]Luke B, Brown MB, Wantman E, et al. Risk of severe maternal morbidity by maternal fertility status: a US study in 8 states Am J Obstet Gynecol, 2019.PMID 30321527
8. [8]Westvik-Johari K, Lawlor DA, Romundstad LB, et al. Risk of stillbirth and neonatal death in singletons born after fresh and frozen embryo transfer: cohort study from the Committee of Nordic Assisted Reproduction Technology and Safety Fertil Steril, 2023.PMID 36567207
9. [9]Ginström Ernstad E, Spangmose AL, Opdahl S, et al. Perinatal and maternal outcome after vitrification of blastocysts: a Nordic study in singletons from the CoNARTaS group Hum Reprod, 2019.PMID 31687765
10. [10]Fall CH, Sachdev HS, Osmond C, et al. Association between maternal age at childbirth and child and adult outcomes in the offspring: a prospective study in five low-income and middle-income countries (COHORTS collaboration) Lancet Glob Health, 2015.PMID 25999096
11. [11]Pinborg A, Loft A, Nyboe Andersen A Neonatal outcome in a Danish national cohort of 8602 children born after in vitro fertilization or intracytoplasmic sperm injection: the role of twin pregnancy Acta Obstet Gynecol Scand, 2004.PMID 15488125
12. [12]Zaat TR, Kostova EB, Korsen P, et al. Obstetric and neonatal outcomes after natural versus artificial cycle frozen embryo transfer and the role of luteal phase support: a systematic review and meta-analysis Hum Reprod Update, 2023.PMID 37172270
13. [13]Zhang H, Wang W Risk factors and adverse pregnancy outcomes in older pregnant women with hypertensive disorders of pregnancy J Obstet Gynaecol Res, 2022.PMID 35596590