Evaluating the association of ART in advanced maternal age and SCAD: a systematic review

Abstract Background European maternal age is increasing. Advanced maternal age (AMA) is defined as pregnancy occurring above 35 years of age at the time of delivery; further subcategorised into very advanced maternal age (VAMA) when aged over 40 years, and extremely advanced maternal age (EAMA), over 45 years. AMA often requires assisted reproductive technology (ART) to conceive and sustain the pregnancy. The association of Spontaneous coronary artery dissection (SCAD) following ART needs further evaluation. Purpose This systematic review aims to evaluate the risk of SCAD in those of VAMA and EAMA, who underwent ART, with the view to help inform clinical guidelines and risk stratification strategies, for cardiovascular complications in this unique patient population. Methods PRISMA guidelines were used to perform a systematic review of Pubmed, Embase, Scopus, EBSCOhost and Cochrane databases. Articles published between January 2015, and February 2025 were included. The search yielded 50 studies, of which 11 were considered suitable for abstract review. Only 3 met our inclusion criteria. Results A single retrospective study identified 54 patients diagnosed with pregnancy-related SCAD, with a mean age of ≥ 35 years, 28% of whom underwent ART. Data was collected from 2010-2017, yet with therapeutic advancements, increasingly AMA cohorts are being offered ART. Although small cohort sizes limit the universality of these findings. The 2 additional studies agreed that both female sex hormones and ART are significant risk factors for the pathogenesis of SCAD. Heightened susceptibility to microvascular dysfunction mediated by oestrogen-induced metalloprotease activity, contributes to vessel fragility and predisposes individuals to SCAD. Conclusion(s) The triad of haemodynamic shift, ART and AMA create the ‘perfect storm’ within the maternal coronaries. Pregnancy increases vascular shear stress and cardiac output. ART is associated with decreased collagen synthesis, elastic fibre fragmentation and increased inflammatory infiltrate. The added strain of labour, particularly repeated Valsalva manoeuvres, further exacerbates this triad. Layering these factors onto an already vulnerable cardiovascular system compounds the risk of SCAD, yet no studies to date have examined the risk of SCAD in VAMA, or EAMA undergoing ART. Further research is essential to refine SCAD risk assessment in pregnancy, especially concerning ART. This systematic review highlights a significant research gap. Prospective studies are warranted to provide more comprehensive and up-to-date data on SCAD in mothers of AMA who have undergone ART to determine whether cardiac risk factors should be a consideration when assessing the safety and feasibility of these reproductive interventions.PRISMA