Cardiometabolic Differences in Children Born After in Vitro Fertilization: Follow-Up Study (original) (raw)
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Reproductive biomedicine online, 2014
The effects of artificial reproductive techniques and subfertility on cardiovascular and metabolic profiles of children aged 5-6 years were investigated using data from the Amsterdam Born Children and their Development study. Of the 2577 children, 34 were conceived through ovulation induction, 51 through artificial insemination and 28 through IVF or intracytoplasmic sperm injection (ICSI). Two hundred and twenty children were born to couples who conceived after more than 12 months and 2244 were born to couples who conceived within 12 months of unprotected intercourse ('subfertile' and 'fertile', respectively). At the age of 5-6 years, fasting glucose levels were higher among children conceived through ovulation induction and IVF-ICSI compared with those of children of fertile couples (adjusted difference: ovulation induction: 0.4 mmol/l, 95% CI 0.2 to 0.6; IVF-ICSI: 0.2 mmol/l, 95% CI 0.0 to 0.5). Blood pressure was higher in children of subfertile couples compared w...
Human Reproduction, 2017
Are the in vitro procedure, ovarian hyperstimulation or a combination of these two associated with blood pressure (BP) of 9-year-old IVF children born to subfertile couples? SUMMARY ANSWER: Our study demonstrates that ovarian hyperstimulation and the in vitro procedure are not associated with BP values in 9-year-old children born to subfertile couples. 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 foetal development which may result in health related problems in later life. Some studies suggested that IVF is associated with higher BP at preschool age. Yet, it is unclear whether this may be also true for older children and if so, which component of IVF, i.e. the ovarian hyperstimulation, the embryo culture or a combination of these, attributes to this potentially less favourable BP. STUDY DESIGN, SIZE, DURATION: The Groningen Assisted Reproductive Technology cohort-study is a prospective assessor-blinded study of children followed from before birth onwards. In total, 170 children were assessed at the age of 9 years. The attrition rate up until the 9-year-old assessment was 21%. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated cardiovascular health, focusing on BP (in mmHg and the internationally recognized percentiles of the US National High BP Education Program), heart rate and anthropometrics of 57 children born following controlled ovarian hyperstimulation-IVF/ICSI (COH-IVF/ICSI); 47 children born after modified natural cycle-IVF/ICSI (MNC-IVF/ICSI); and 66 children who were conceived naturally by subfertile couples (Sub-NC). Cardiovascular parameters were measured multiple times on one day. In addition, anthropometric data, including BMI and skinfold thickness, were collected. MAIN RESULTS AND THE ROLE OF CHANCE: Systolic BP in mmHg did not differ between the COH-IVF/ICSI (mean 106.9, SD 6.7), MNC-IVF/ICSI (mean 104.8, SD 5.9) and Sub-NC (mean 106.3, SD 5.3) groups. In addition, systolic BP percentiles did not differ between the groups: COH-IVF/ICSI (mean 62.4, SD 20.2); MNC-IVF/ICSI (mean 56.3, SD 19.3); and Sub-NC (mean 62.3, SD17.8). Also, after adjustment for confounders BP in the three groups was similar. Heart rate and anthropometric values in the three groups did not differ.
Objective: To evaluate cardiovascular and metabolic features of offspring conceived by in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI). Design: Literature review and meta-analysis. Setting: Not applicable. Patient(s): Offspring from IVF-ICSI versus natural conception. Intervention(s): None. Main Outcome Measure(s): Systolic and diastolic blood pressure (SBP and DBP), cardiovascular function, body mass index (BMI), and lipid and glucose profiles. Result(s): We included 19 studies that had recruited 2,112 IVF-ICSI and 4,096 naturally conceived offspring, ranging from childhood to early adulthood. The blood pressure levels of IVF-ICSI offspring were statistically significantly higher than those of naturally conceived offspring (weighted mean differences and confidence intervals: 1.88 mm Hg [95% CI, 0.27, 3.49] for SBP and 1.51 mm Hg [95% CI, 0.33, 2.70] for DBP). In addition, cardiac diastolic function was suboptimal and vessel thickness was higher among IVF-ICSI offspring. Compared with the metabolism of naturally conceived offspring, IVF-ICSI offspring displayed comparable BMI, lower low-density lipoprotein cholesterol levels, and higher fasting insulin levels. Conclusion(s): Children conceived by IVF-ICSI manifested a minor yet statistically significant increase in blood pressure without the clustering of increased BMI or impaired lipid metabolism by early adulthood. Our findings indicate a risk of cardiovascular disease among IVF-ICSI offspring, which calls for longer-term follow-ups and further investigation.
Human Reproduction, 2014
Does ovarian hyperstimulation, the in vitro procedure, or a combination of these two negatively influence blood pressure (BP) and anthropometrics of 4-year-old children born following IVF? Higher systolic blood pressure (SBP) percentiles were found in 4-year-old children born following conventional IVF with ovarian hyperstimulation compared with children born following IVF without ovarian hyperstimulation. Increasing evidence suggests that IVF, which has an increased incidence of preterm birth and low birthweight, is associated with higher BP and altered body fat distribution in offspring but the underlying mechanisms are largely unknown. We performed a prospective, assessor-blinded follow-up study in which 194 children were assessed. The attrition rate up until the 4-year-old assessment was 10%. We measured BP and anthropometrics of 4-year-old singletons born following conventional IVF with controlled ovarian hyperstimulation (COH-IVF, n = 63), or born following modified natural cycle IV (MNC-IVF, n = 52), or born to subfertile couples who conceived naturally (Sub-NC, n = 79). Both IVF and ICSI were performed. Primary outcome measures were the SBP percentiles and diastolic BP (DBP) percentiles. Anthropometric measures included triceps and subscapular skinfold thickness. Several multivariable regression analyses were applied in order to correct for subsets of confounders. The value 'B' is the unstandardized regression coefficient. SBP percentiles were significantly lower in the MNC-IVF group (mean 59, SD 24) than in the COH-IVF (mean 68, SD 22) and Sub-NC groups (mean 70, SD 16). The difference in SBP between COH-IVF and MNC-IVF remained significant after correction for current, early life and parental characteristics (B: 14.09; 95% confidence interval (CI): 5.39-22.79), whereas the difference between MNC-IVF and Sub-NC did not. DBP percentiles did not differ between groups. After correction for early life factors, subscapular skinfold thickness was thicker in the COH-IVF group than in the Sub-NC group (B: 0.28; 95% CI: 0.03-0.53). Larger study groups are necessary to draw firm conclusions. An effect of gender or ICSI could not be properly investigated as stratifying would further reduce the sample size. We corrected for the known differences between MNC-IVF and COH-IVF but it is possible that the groups differ in additional, more subtle parental characteristics. In addition, we measured BP on 1 day only, had no control group of children born to fertile couples (precluding investigating effects of the underlying subfertility) and included singletons only. As COH-IVF is associated with multiple births we may have underestimated cardiometabolic problems after COH-IVF. Finally, multivariable regression analysis does not provide clear insight in the causal mechanisms and we have performed further explorative analyses. Our findings are in line with other studies describing adverse effects of IVF on cardiometabolic outcome but this is the first study suggesting that ovarian hyperstimulation, as used in IVF treatments, could be a causative mechanism. Perhaps ovarian hyperstimulation negatively influences cardiometabolic outcome via changes in the early environment of the oocyte and/or embryo that result in epigenetic modifications of key metabolic systems that are involved in BP regulation. Future research needs to assess further the role of ovarian hyperstimulation in poorer cardiometabolic outcome and investigate the underlying mechanisms. The findings emphasize the importance of cardiometabolic monitoring of the growing number of children born following IVF. The authors have no conflicts of interest to declare. The study was supported by the University Medical Center Groningen, the Cornelia Foundation and the school for Behavioral- and Cognitive Neurosciences. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report.
Fertility and Sterility, 2010
Objective: To investigate the metabolic profile, traditional adipokines, and indices of insulin resistance and low-grade inflammation in children born as a result of IVF compared with spontaneously conceived controls. Design: Cross-sectional, case-control study. Setting: IVF Section of the First Department of Obstetrics and Gynecology and the First Department of Pediatrics of the University of Athens. Patient(s): One hundred six children conceived after classic IVF and 68 age-matched spontaneously conceived controls, aged 4-14 years. Intervention(s): Children underwent physical examination and morning fasting samples were collected. Main Outcome Measure(s): Lipid profile, circulating fasting glucose, insulin, leptin, adiponectin, high-sensitivity interleukin-6, and high-sensitivity C-reactive protein were determined and the fasting glucose-to-insulin ratio was calculated. Result(s): Children born as a result of classic IVF had significantly higher systolic and diastolic blood pressures (BP) and triglycerides than controls. These BP differences remained significant even after correction for birth size and multiple births. No significant differences in biochemical indices of insulin resistance, circulating adipokines, and inflammatory markers were detected before or after these same corrections. Conclusion(s): Despite an increase of BP, children born as a result of IVF have no biochemical evidence of insulin resistance, including fasting glucose-to-insulin ratio and circulating adipokines, or low-grade chronic inflammation. However, the long-term impact of periconceptual manipulations should be closely monitored.
Human Reproduction, 2016
Is the maternal cardiovascular (CV) risk profile associated with human embryonic growth trajectories and does the mode of conception affect this association? summary answer: This small study suggests that the maternal CV risk profile is inversely associated with first trimester embryonic growth trajectories in in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) pregnancies, but not in spontaneously conceived pregnancies. what is known already: Maternal high-blood pressure and smoking affect placental function, accompanied by increased risk of fetal growth restriction and low-birthweight. Mothers who experience pregnancies complicated by fetal growth restriction are at increased risk of CV disease in later life. study design, size, duration: In a prospective periconception birth cohort conducted in a tertiary hospital, 111 singleton ongoing pregnancies with reliable pregnancy dating, no pre-existing maternal disease and no malformed live borns were investigated. participants/materials, settings, methods: Spontaneously conceived pregnancies with a reliable first day of the last menstrual period and a regular menstrual cycle of 25-31 days only (n ¼ 66) and IVF/ICSI pregnancies (n ¼ 45) were included. Women underwent weekly three-dimensional ultrasound scans (3D US) from 6-to 13-week gestational age. To estimate embryonic growth, serial crown-rump length (CRL) measurements were performed using the V-Scope software in a BARCO I-Space. Maternal characteristics and CV risk factors were collected by self-administered questionnaires. The CV risk profile was created based on a score of risk factors, including maternal age, body-mass index, CV disease in the family, diet and smoking. Quartiles of the CV risk score were calculated. Associations between the CV risk score and embryonic growth were assessed using square root transformed CRL in multivariable linear mixed model analyses. IVF/ICSI treatment in relation with CV risk factors substantiate the importance of more investigation into differences in sensitivity of endometrial, endothelial, placental and embryonic tissues.
Childhood cardiovascular health and subfertility: the Bogalusa Heart Study
Pediatric Research
BACKGROUND: Although childhood cardiovascular risk can contribute to adult cardiovascular disease, and fertility and adult cardiovascular health are linked, the association between early-life cardiovascular risk and female infertility has not been studied. METHODS: A total of 1799 women participated in the Babies substudy of the Bogalusa Heart Study. Systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, glucose, and insulin were age-standardized and examined as predictors of self-reported fertility difficulties using multivariable logistic regression with adjustment for confounders. Polycystic ovarian syndrome (PCOS) was assessed via a report of diagnosis and symptoms, using a validated questionnaire. RESULTS: Women with a history of PCOS were more likely to report fertility difficulties. Childhood and adolescent cardiovascular risk factors were generally not associated with fertility indicators, although childhood LDL (aOR 1.38 per one-SD increase, 0.97-1.96) and total cholesterol (aOR 1.49, 1.06-2.11) were raised in those who never became pregnant. Pre-pregnancy risk SBP (overall fertility, aOR 1.49, 1.00-2.23) and glucose levels (ever tried but unable, aOR 2.65, 1.39-5.06) were associated with an increased risk of some infertility indicators. These results were largely unaffected by exclusion of women with PCOS. CONCLUSION: Some childhood and pre-pregnancy cardiovascular risk factors are associated with adult subfertility.
The Journal of Pediatrics, 2000
Objective: To investigate associations between maternal diabetes and blood pressure (BP), obesity, impaired glucose tolerance, and serum lipids in offspring and whether these parameters correlate with metabolism during pregnancy. Study design: Body mass index, BP, serum glucose, and insulin during an oral glucose tolerance test, and lipid concentrations were measured in 99 offspring of diabetic mothers (ODN1) and 80 members of a control group. Results: ODNI were more obese (body mass index 22.5 _+ 5.6 vs 20.5 ± 4.0 kg/m 2) and had higher systolic (8 mm Hg) and mean arterial BP (4 mm Hg) but similar diastolic BP compared with the control group. ODM had higher 2-hour glucose (6.6 _+ 1.5 vs 5.7 _* 0.9 mmol/L) and insulin (580 ± 54d vs 577 +_ 259 pmol/L) concentrations but lower fasting concentrations of low-denslty llpoproteln (2.5~ _+ 0.67 vs 2.82 ± 0.70 mmol/L) and total cholesterol (4.0l ~+ 0.80 vs 4.40 ± 0.78 retool/L). In both groups bo w mass index, triglycerides, and fasting and 2-hour glucose concentrations showed correlations with BP measurements. Fasting insulin was correlated with BP readings only in the ODM. Correlations were found between second-and thlrd-trimester maternal fiee fatty acid concentrations and diastolic and mean arterial BP. Thlrd-trimester ~-hydroxvbutyrate was correlated with mean arterial BE Conclusions: In ODNI, abnormalities in weight and glucose tolerance are associated with abnormal maternal metabolism. Higher BP is an additional abnormality associated with fetal overnutrition.
Hypertensive pregnancy complications in poor and normal responders after in vitro fertilization
Fertility and Sterility, 2010
Objective: To investigate whether women pregnant after a poor response in IVF have pregnancy-induced hypertension and preeclampsia more frequently than women with pregnancies after a normal response in IVF. Poor response to ovarian stimulation for IVF reflects advanced ovarian aging, which may be associated with early vascular aging. This may become apparent in an increased incidence of hypertensive pregnancy complications in pregnancies achieved after poor response in IVF. Design: Patient-control study. Setting: Tertiary Fertility Center. Patient(s): One hundred fifty poor (three oocytes or fewer) and 150 normal responders (8-12 oocytes) pregnant after IVF-intracytoplasmic sperm injection (ICSI), matched for age, type of infertility, dose of recombinant FSH, singleton or twin pregnancy, and IVF or ICSI treatment. Intervention(s): None. Main Outcome Measure(s): Primary end points were birth weight of the neonate and the incidence of pregnancyrelated hypertensive disorders. Secondary end points were duration of pregnancy, type of delivery, and live birth of the neonate. Result(s): Poor and normal responders did not have significantly different incidences in pregnancy-related hypertensive disorders, nor did their neonates differ significantly in birth weight. Moreover, duration of pregnancy, type of delivery, and live birth ratios were similar in both poor and normal responders. Conclusion(s): From this matched control study we were unable to confirm our hypothesis, that women pregnant after a poor response in IVF have pregnancy-induced hypertension and preeclampsia more frequently than women with pregnancies after a normal response in IVF. These results do not support a vascular etiology of poor response.