Perinatal outcomes in pregnancies with very and extremely advanced maternal age: An Italian multicenter retrospective cohort study

Introduction: Pregnancies at very and extremely advanced maternal age (VAMA, 45–49 years and EAMA, ≥50 years) are increasingly common, particularly regarding the influence of assisted reproductive technology (ART), yet their obstetric and perinatal outcomes remain underexplored. This study aimed to investigate maternal and neonatal outcomes in singleton pregnancies among women aged ≥45 years, with a specific focus on ART conception and oocyte source. Material and Methods: This multicenter retrospective cohort study included women aged ≥45 years with singleton pregnancies delivered ≥22 weeks' gestation between 2016 and 2022 across five Italian academic hospitals. Pregnancies were categorized by mode of conception (spontaneous conception [SC] vs. ART), and ART pregnancies were further stratified by oocyte origin (homologous [ART-HO] vs. heterologous [ART-HE]). Multivariable logistic regression was used to evaluate associations between mode of conception and obstetric outcomes, adjusting for key confounders. Results: Among 557 included pregnancies, 495 (88.9%) involved women aged 45–49 years, and 62 (11.1%) women aged ≥50. Compared to SC, ART pregnancies were associated with higher adjusted odds of cesarean delivery (aOR 4.20, 95% CI 2.99–4.92; p < 0.001) and postpartum hemorrhage (aOR 2.72, 95% CI 1.75–4.23; p < 0.001). No significant differences in neonatal outcomes were observed. In the ART subgroup analysis, ART-HE was associated with increased odds of gestational diabetes (aOR 1.97, 95% CI 1.10–3.55; p = 0.024) and manual placental removal (aOR 10.45, 95% CI 1.23–88.46; p = 0.031) compared to ART-HO. Conclusions: ART pregnancies in women ≥45 years are associated with increased maternal morbidity, particularly when involving heterologous oocytes. These findings underscored the need for tailored counseling and multidisciplinary perinatal care in this growing population.