Cardiovascular health of 9-year-old IVF offspring is not associated with IVF but with parental subfertility

Study question: Does the in vitro procedure, ovarian hyperstimulation or subfertility affect blood pressure (BP) of 9-year-old IVF children born to subfertile couples? Summary answer: Our study demonstrates that the higher BP in 9-year-old children born to subfertile couples is not due to IVF-procedures but is associated with couples' subfertility. What is known already: Possible long-term effects of IVF on child health and development have been studied relatively little. This is surprising, as it is known that environmental conditions may influence embryonic and fetal development which may result in health related problems in later life. Some studies suggested that IVF adversely affects BP at school age. Yet, it is unclear which component of IVF attributes to this potentially less favourable BP. Study design, size, duration: A prospective assessor blinded study of two groups of children followed from birth onwards: the Groningen Assisted Reproductive Technology (ART) cohort-study and the Long-Chain PolyUnsaturated Fatty Acids (LCPUFA) study. In total 449 children were assessed at the age of 9. Participants/materials, setting, methods: We evaluated cardiovascular health, focusing on BP (in mmHg and percentiles), and heartrate of 57 children born following controlled ovarian hyperstimulation-IVF (COH-IVF); 47 children born after modified natural cycle-IVF (MNC-IVF); and 65 children who were conceived naturally to subfertile couples. Cardiovascular parameters were measured multiple times on one day. Similar data of a reference group (n = 279) of children born to fertile couples of the LCPUFA-study were available. Main results and the role of chance: BP was similar in the COH-IVF, MNC-IVF and Sub-NC groups. This allowed us to pool the groups to form a subfertile group (n = 169). The subfertile group had a higher systolic blood pressure percentile (SBP, mean [σ]: 60.7 [19.2]), diastolic blood pressure percentile (DBP, 62.5 [18.8]) and heart rate (81.5 [9.9]) than the fertile reference group: SBP (56.3 [24.5]); DBP (55.8 [23.3]) and heart rate (77.0 [9.7]). In the adjusted analyses the subfertile group still had a higher SBP percentile (adjusted B [95%CI]: 7.86 [2.16-13.55]); a higher DBP percentile (7.64 [2.20-13.08]); and a higher heart rate (7.40 [4.96-9.85]). Limitations, reasons for caution: Larger study groups are necessary to draw firm conclusions regarding ovarian hyperstimulation and the in vitro procedure. Another limitation is that all blood pressure measurements were performed on one day. Wider implications of the findings: Our findings are in line with other studies describing less favourable cardiovascular outcomes in IVF offspring. Our study suggests that the higher BP and heart rate is not due to procedures of IVF but due to parental subfertility. The findings may have important implications for the counselling of subfertile couples.