Dataset Information

PCSK9 and Lp(a) levels of children born after assisted reproduction technologies.

ABSTRACT:

Purpose

Proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipoprotein (a) (Lp[a]) levels are associated with cardiovascular risk. To investigate PCSK9 and Lp(a) levels of children born after assisted reproduction technologies (ART) compared with naturally conceived (NC) controls.

Methods

In this exposure-matched cohort study, 73 racial-, sex-, and age-matched children (mean age 98?±?35 months) of ART (intracytoplasmic sperm injection [ICSI] n =?33, classic in vitro fertilization [IVF] n =?40) and 73 NC children were assessed. Blood lipid profile, including PCSK9 and Lp(a) levels, was measured. Children were grouped according to age (ResultsIn the overall population, PCSK9 levels were related to total cholesterol, low-density lipoprotein, and systolic blood pressure, while Lp(a) levels were related to age, apolipoprotein-B, birth weight, height, waist-to-hip ratio, insulin resistance, insulin, and high-sensitivity C-reactive protein. No significant differences were observed regarding lipid biomarkers between ART and NC children. However, a significant interaction was found between age groups and conception method (p ConclusionsWe show that PCSK9 levels increase with age in ART children, indicating a gradual deterioration of lipidemic profile that could lead to increased cardiovascular risk. Moreover, our results indicate that ART method may be of importance given that classic IVF is associated with higher levels of Lp(a).

SUBMITTER: Vlachopoulos C

PROVIDER: S-EPMC6603255 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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PCSK9 and Lp(a) levels of children born after assisted reproduction technologies.

Vlachopoulos Charalambos C Kosteria Ioanna I Sakka Sophia S Gkourogianni Alexandra A Terentes-Printzios Dimitrios D Koutagiar Iosif I Skoumas Ioannis I Miliou Antigoni A Papassotiriou Ioannis I Gardikioti Vasiliki V Loutradis Dimitrios D Chrousos George G Kanaka-Gantenbein Christina C Tousoulis Dimitrios D

Journal of assisted reproduction and genetics 20190511 6

<h4>Purpose</h4>Proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipoprotein (a) (Lp[a]) levels are associated with cardiovascular risk. To investigate PCSK9 and Lp(a) levels of children born after assisted reproduction technologies (ART) compared with naturally conceived (NC) controls.<h4>Methods</h4>In this exposure-matched cohort study, 73 racial-, sex-, and age-matched children (mean age 98 ± 35 months) of ART (intracytoplasmic sperm injection [ICSI] n = 33, classic in vitro fertili ...[more]

PMID: 31079266

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Project description:Study questionAre there more de novo mutations (DNMs) present in the genomes of children born through medical assisted reproduction (MAR) compared to spontaneously conceived children?Summary answerIn this pilot study, no statistically significant difference was observed in the number of DNMs observed in the genomes of MAR children versus spontaneously conceived children.What is known alreadyDNMs are known to play a major role in sporadic disorders with reduced fitness such as severe developmental disorders, including intellectual disability and epilepsy. Advanced paternal age is known to place offspring at increased disease risk, amongst others by increasing the number of DNMs in their genome. There are very few studies reporting on the effect of MAR on the number of DNMs in the offspring, especially when male infertility is known to be affecting the potential fathers. With delayed parenthood an ongoing epidemiological trend in the 21st century, there are more children born from fathers of advanced age and more children born through MAR every day.Study design, size, durationThis observational pilot study was conducted from January 2015 to March 2019 in the tertiary care centre at Radboud University Medical Center. We included a total of 53 children and their respective parents, forming 49 trios (mother, father and child) and two quartets (mother, father and two siblings). One group of children was born after spontaneous conception (n = 18); a second group of children born after IVF (n = 17) and a third group of children born after ICSI combined with testicular sperm extraction (ICSI-TESE) (n = 18). In this pilot study, we also subdivided each group by paternal age, resulting in a subgroup of children born to younger fathers (<35 years of age at conception) and older fathers (>45 years of age at conception).Participants/materials, setting, methodsWhole-genome sequencing (WGS) was performed on all parent-offspring trios to identify DNMs. For 34 of 53 trios/quartets, WGS was performed twice to independently detect and validate the presence of DNMs. Quality of WGS-based DNM calling was independently assessed by targeted Sanger sequencing.Main results and the role of chanceNo significant differences were observed in the number of DNMs per child for the different methods of conception, independent of parental age at conception (multi-factorial ANOVA, f(2) = 0.17, P-value = 0.85). As expected, a clear paternal age effect was observed after adjusting for method of conception and maternal age at conception (multiple regression model, t = 5.636, P-value = 8.97 × 10-7), with on average 71 DNMs in the genomes of children born to young fathers (<35 years of age) and an average of 94 DNMs in the genomes of children born to older fathers (>45 years of age).Limitations, reasons for cautionThis is a pilot study and other small-scale studies have recently reported contrasting results. Larger unbiased studies are required to confirm or falsify these results.Wider implications of the findingsThis pilot study did not show an effect for the method of conception on the number of DNMs per genome in offspring. Given the role that DNMs play in disease risk, this negative result is good news for IVF and ICSI-TESE born children, if replicated in a larger cohort.Study funding/competing interest(s)This research was funded by the Netherlands Organisation for Scientific Research (918-15-667) and by an Investigator Award in Science from the Wellcome Trust (209451). The authors have no conflicts of interest to declare.Trial registration numberN/A.

Project description:Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the human reproductive system in both genders, but no comprehensive analysis of the potential relationship between vitamin D status and Assisted Reproduction Technologies (ART) outcomes is currently available. On this basis, the purpose of this systematic review and meta-analysis was to perform an in-depth evaluation of clinical studies assessing whether vitamin D status of patients undergoing ART could be related to cycle outcome variables. This issue is of interest considering that vitamin D deficiency is easily amenable to correction and oral vitamin D supplementation is cheap and without significant side effects. Surprisingly, no studies are currently available assessing vitamin D status among male partners of couples undergoing ART, while seven studies on vitamin D status of women undergoing controlled ovarian hyperstimulation (COH) for ART were found and included in the review. Results show that vitamin D deficiency is highly prevalent among women undergoing COH, ranging from 21% to 31% across studies conducted in Western countries and reaching 75-99% in Iranian studies. Data on vitamin D deficiency (25-hydroxyvitamin D serum levels <20 ng/ml) in relation to ART outcomes could be extracted from three studies and included in the meta-analysis, yielding a common risk ratio (RR) of 0.89 (95% CI 0.53-1.49) and showing a lower but not statistically significant likelihood of clinical pregnancy for vitamin-D-deficient women compared with vitamin-D-sufficient patients. In conclusion, there is insufficient evidence to support the routine assessment of vitamin D status to predict the clinical pregnancy rate in couples undergoing ART. The partly conflicting results of the available studies, potentially explaining the lack of statistical significance for a negative influence of vitamin D deficiency on clinical pregnancy rate, are likely secondary to confounders and insufficient sample size, and further larger cohort and randomised controlled studies are required.

Project description:BackgroundThe association between assisted reproductive technologies (ARTs) and the body mass index (BMI) of children remains controversial. Confounding by morbidity and other factors associated with parental infertility may have biased studies comparing children born after ART with children born after no treatment. We investigated the associations between different fertility treatments and BMI in children at age 5 to 8 years, adjusting for and stratifying by causes of parental infertility.Methods and findingsThis Danish cohort study included 327,301 children born between 2007 and 2012 (51% males, median age at follow-up 7 years). Of these, 13,675 were born after ART, 7,728 were born after ovulation induction with or without intrauterine insemination [OI/IUI], and 305,898 were born after no fertility treatments. Using the International Obesity Task Force (IOTF) standards, we defined overweight (BMI ≥ IOTF-25) and obesity (BMI ≥ IOTF-30). We compared children born after ART versus OI/IUI; intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilization (IVF); and frozen-thawed versus fresh embryo transfer and estimated crude and adjusted prevalences of children with overweight or obesity at age 5 to 8 years, prevalence odds ratios (PORs), and differences in mean BMI z-scores. Adjustment was performed using stabilized inverse probability of treatment weights, including parity, year of conception, parental causes of infertility, age, educational level, comorbidities, maternal country of origin, BMI, and smoking as covariates. The crude prevalence of obesity was 1.9% in children born after ART, 2.0% in those born after OI/IUI, and 2.7% in those born after no fertility treatment. After adjustment, children born after ART and OI/IUI had the same prevalence of being overweight (11%; POR 1.00, 95% confidence interval [CI] 0.91 to 1.11; p = 0.95) or obese (1.9%; POR 1.01, 95% CI 0.79 to 1.29; p = 0.94). Comparison of ICSI with conventional IVF yielded similar pattern (POR 0.95, 95% CI 0.83 to 1.07; p = 0.39 for overweight and POR 1.16, 95% CI 0.84 to 1.61; p = 0.36 for obesity). Obesity was more prevalent after frozen-thawed (2.7%) than fresh embryo transfer (1.8%) (POR 1.54, 95% CI 1.09 to 2.17; p = 0.01). The associations between fertility treatments and BMI were only modestly different in subgroups defined by the cause of infertility. Study limitations include potential residual confounding, restriction to live births, and lack of detailed technical information about the IVF procedures.ConclusionsWe found no association with BMI at age 5 to 8 years when comparing ART versus OI/IUI or when comparing ICSI versus conventional IVF. However, use of frozen-thawed embryo transfer was associated with a 1.5-fold increased risk of obesity compared to fresh embryo transfer. Despite an elevated relative risk, the absolute risk difference was low.

Project description:BackgroundPrevious research has documented that children conceived through medically assisted reproduction (MAR) are at increased risk of poor birth outcomes, such as low birthweight (LBW), which are risk factors for stunted longer-term cognitive development. However, parents who undergo MAR to conceive have, on average, advantaged socioeconomic backgrounds which could compensate for the negative effects of being born LBW. Previous studies have not analysed whether the negative effects of LBW are attenuated among MAR conceived children.MethodsWe draw on the UK Millennium Cohort Study (sweeps 1-6) which contains a sub-sample of (N = 396) MAR-conceived children. The dependent variable measures cognitive ability at around ages 3, 5, 7, 11 and 14. We examine the cognitive development of four groups of children: MAR-conceived low birthweight (MAR LBW); MAR-conceived non-low birthweight (MAR NLBW); naturally conceived low birthweight (NC LBW); naturally conceived non-low birthweight (NC NLBW). We estimate the two following linear regression models for each sweep: (i) a baseline model to examine the unadjusted association between cognitive development and low birthweight by mode of conception; and (ii) a model adjusted by socio-demographic family characteristics.ResultsIn baseline models, MAR LBW children [age 3: β = 0.021, 95% confidence interval (CI): -0.198, 0.241; age 5: β = 0.21, 95% CI: 0.009, 0.418; age 7: β = 0.163, 95% CI: -0.148, 0.474; age 11: β = 0.003, 95% CI: -0.318, 0.325; age 14: β = 0.156, 95% CI: -0.205, 0.517], on average perform similarly in cognitive ability relative to NC NLBW at all ages, and display higher cognitive scores than NC LBW children until age 7. When we account for family characteristics, differences are largely attenuated and become close to zero at age 14.ConclusionsDespite the higher incidence of LBW among MAR compared with NC children, they do not seem to experience any disadvantage in their cognitive development compared with naturally conceived children. This finding is likely explained by the fact that, on average, MAR children are born to socioeconomically advantaged parents.

Dataset Information

PCSK9 and Lp(a) levels of children born after assisted reproduction technologies.

Purpose

Methods

Publications

PCSK9 and Lp(a) levels of children born after assisted reproduction technologies.

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