Table 1.
Human studies of ART and cardiovascular effects
| Reference | Cohort | Groups | Number of participants | Age (years) | Inclusion criteria | Findings |
|---|---|---|---|---|---|---|
| Belva et al. 2007 | ICSI group born at Vrije Universiteit Brussel Centre of Reproductive Medicine, 8yrs old between 02/2001–12/2003. | ICSI-only Controls: Age, sex, and maternal education level-matched children from naturally conceived pregnancies |
ICSI: 150 (15 with major congenital malformations) Controls: 147 (5 with major congenital malformations) |
8 | Singleton, caucasian, ≥32 gestation | ICSI children had significantly increased systemic BP compared to controls. |
| Belva et al. 2012a | ICSI group conceived at the UZ Brussel, 14yrs old between 01/2008–03/2011. Controls recruited from local schools. | ICSI-only Controls: Age and sex-matched children from naturally conceived pregnancies |
ICSI: 217 Controls: 223 |
14 | Singleton, caucasian, ≥32 gestation | No differences in resting BP were detected in ICSI children. No differences in BP in response to mild psychological stress was detected in a small subset of ICSI children, after correcting for current characteristics (height, weight, and pubertal stage). |
| Ceelen et al. 2008 | OMEGA Dutch cohort + VU medical center participants born 1986–1995, overlapping with Ceelen et al. 2007. | IVF (ICSI not specified) Controls: Age and sex-matched children conceived by subfertile couples. |
IVF: 225 Controls: 225 |
8–18 | None stated | Systemic BP was higher in IVF children than in control children. |
| Ceelen et al. 2009 | VU medical center participants born 1986–1995 overlapping with Ceelen et al. 2007. | IVF (ICSI not specified) Controls: Age and sex-matched children conceived by subfertile couples. |
IVF: 233 Controls: 233 |
8–18 | Singleton | Increases in systemic BP in IVF children were linked to the amount of weight gain during the 1–3 year-old period. |
| Chen et al. 2014 | Recruited through IVF birth records in South Australia and newspaper advertisements. | IVF Controls: Sex and BMI-matched. |
IVF: 14 Controls: 20 |
Not specified. Mean age±SEM was 21.5±0.6 for IVF and 20.6±0.6 for controls. | Normal birth weight, no medical conditions, no medications interfering with glucose metabolism, no family history of type 2 diabetes or CVD, no smoking, limited alcohol consumption. | Systolic BP was increased in response to three days of overfeeding (increase of 1,250 kcal/day; nutrient composition increased 15% in fat and decreased 15% in carbohydrates, no change in protein composition). |
| Liu et al. 2015 | Recruited from from First Affiliated Hospital of Nanjing Medical University | IVF (ICSI not specified) Controls: Age and sex-matched children from low risk pregnancies |
IVF: 100 Controls: 100 |
5 | None stated. | Alterations in multiple cardiac parameters and increases in left and right MPI in IVF children. No differences in cardiac morphometry. |
| Pontesilli et al. 2015 | Amsterdam ABCD study. Pregnant women were recruited between 01/2003–03/2004. | IVF/ICSI Artificial insemination Ovulation induction Spontaneously conceived after more than 12 months (subfertile) Controls: Spontaneously conceived within 12 months (fertile) |
IVF/ICSI: 28 Artificial insemination: 51 Ovulation induction: 34 Subfertile: 220 Controls: (fertile): 2244 |
5–6 | Singleton, no severe medical conditions. | Systemic BP was higher in ovulation induction and subfertile groups than fertile controls. No differences in BP in IVF/ICSI or artificial insemination groups compared with fertile controls. |
| Rimoldi et al. 2015 | Subset of Scherrer et al. 2012 | IVF/ICSI Controls: Age and sex-matched children from low risk pregnancies |
IVF/ICSI: 21 Controls: 21 |
Not specified. Mean age±SD was 12.0±2.5 for IVF/ICSI and 12.5±2.5 for controls. | Singleton, >37 weeks gestation, normal birth weight >2.5 kg, no pregnancy complications, no acute illness, no medications, no high altitude exposure, no antioxidant supplements. | IVF/ICSI children displayed reduced FMD, increased carotid femoral PWV, and hypoxia-induced pulmonary hypertension, FMD and pulmonary hypertension was improved after 4 weeks of antioxidant treatment. |
| Sakka et al. 2010 | Same as Sakka et al. 2009 | IVF-only Controls: Age and sex-matched children |
IVF: 106 Controls: 68 |
4–14 | Healthy and no medications. | IVF children had higher systemic BP than controls. |
| Scherrer et al. 2012 | Swiss children born 10/2007–04/2010. Control children were recruited by the families of ART children. | IVF/ICSI Naturally-conceived, hormone stimulation Controls: Naturally-conceived age and sex-matched children from low risk pregnancies. |
IVF/ICSI: 65 Naturally-conceived, hormone stimulation: 16 Controls: 57 |
Not specified. Mean age±SD was 11.9±2.3 for IVF/ICSI and 11.1±2.4 for controls. | Singleton, >37 weeks gestation, normal birth weight >2.5 kg, no pregnancy complications, no medications. | FMD of the brachial artery was reduced in IVF/ICSI children. Carotid-femoral PWV and carotid intima-media thickness was increased in IVF/ICSI children. Pulmonary hypertension was induced in IVF/ICSI children at high altitude. No difference in systemic BP. |
| Seggers et al. 2014 | Groningen cohort, born 03/2005–12/2006 | IVF/ICSI IVF/ICSI with no hormone stimulation Controls: children naturally-conceived by subfertile couples |
IVF/ICSI: 63 IVF/ICSI with no hormone stimulation: 52 Controls: 79 |
4 | Singleton | IVF/ICSI children conceived using hormone stimulation had higher systemic BP than IVF/ICSI children without hormone stimulation. No differences in either IVF group when compared to controls. |
| von Arx et al. 2015 | Children examined at the Universities of Bern and Lausanne. Control children were recruited by the families of ART children. | IVF/ICSI Controls: Naturally-conceived age and sex-matched children from low risk pregnancies |
IVF/ICSI: 54 Controls: 54 |
7–18 | Singleton, >37 weeks gestation, normal birth weight >2.5 kg, no pregnancy complications, no medications, no high altitude exposure. | Increased right ventricle end-diastolic area and diastolic dysfunction in IVF/ICSI children. No differences were observed in IVF/ICSI children at low altitude. |
| Xu et al. 2014 | Women’s Hospital, School of Medicine, Zhejiang University born 2003–2007. | Mother with OHSS IVF (ICSI not specified) Mother no OHSS, matched for gestational age and birth weight to IVF-OHSS group Controls: naturally-conceived children matched for gestational age and birth weight to IVF-OHSS group |
Mother with OHSS: 42 Mother no OHSS: 34 Controls: 48 |
3–7 | No maternal history of CVD. | IVF children from mothers with and without OHSS display alterations in heart rate, diastolic function, and FMD compared to controls. Children from mothers with OHSS had severely reduced FMD. No differences in systemic BP. |
BP=blood pressure; BMI=body mass index; CVD=cardiovascular disease; FMD=flow-mediated dilation; ICSI=intracytoplasmic sperm injection; IVF=in vitro fertilization; MPI=myocardial performance index; OHSS=ovarian hyperstimulation syndrome; PWV=pulse wave velocity; SD=standard deviation; SEM=standard error mean.