Dimitrios Loutradis

Absence of insulin resistance and low-grade inflammation despite early metabolic syndrome manifestations in children born after in vitro fertilization

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.

Euthyroid Hyperthyrotropinemia in Children Born after in Vitro Fertilization

CONTEXT Assisted reproduction techniques are now commonly used. Although classic in vitro fertilization (IVF) started almost 30 yr ago, few long-term systematic prospective studies of children conceived with assisted reproduction have been performed. OBJECTIVE Our objective was to investigate thyroid function in children conceived after IVF vs. naturally conceived controls. POPULATIONS AND METHODS A total of 106 children conceived after classic IVF and 68 naturally conceived controls, aged 4-14 yr, were studied. All children were thoroughly examined, and serum T(3), T(4), TSH, anti-thyroid peroxidase, and anti-thyroglobulin antibodies were measured. A second TSH determination and a thyroid ultrasound were performed for TSH higher than 5 microIU/ml, and children were considered to have persistent hyperthyrotropinemia, if the TSH elevation was confirmed. RESULTS Seven IVF children but none of the controls had persistent elevations of circulating TSH, suggesting euthyroid hyperthyrotropinemia or subclinical primary hypothyroidism (P = 0.044). TSH was significantly higher in the IVF group than in controls (P = 0.046), whereas no significant differences in the concentrations of T(3) or T(4) were observed. None of the children had detectable circulating antithyroid antibodies in either group. CONCLUSIONS A significant elevation of serum TSH compatible with a mild TSH resistance of the thyroid were found in IVF children compared with controls. This was not due to the presence of antithyroid autoantibodies. We suggest that this might represent a slight epigenetic developmental abnormality related to the preimplantation manipulation of the embryo. Further studies are needed to confirm these findings and to better determine their etiopathogenesis and clinical significance.

Gender dimorphic increase in RBP-4 and NGAL in children born after IVF: an epigenetic phenomenon?

In vitro fertilisation (IVF) has been widely used during the last decades. Recent studies demonstrated some alterations in IVF childrens metabolic profile compared with controls. The recently reported lipocalins retinol‐binding protein 4 (RBP‐4) and neutrophil gelatinase‐associated lipocalin (NGAL), as well as visfatin, which are associated with glucose intolerance and could help in the early detection of metabolic abnormalities, have not been studied in IVF children as yet. We studied the lipocalins RBP‐4 and NGAL as well as visfatin in children born after IVF.

Prelabor cesarean delivery and early-onset acute childhood leukemia risk.

The long-term impact of cesarean delivery (CD) on the health of the offspring is being explored methodically. We sought to investigate the effect of birth by (a) prelabor and (b) during-labor CD on the risk of early-onset (⩽3 years) acute lymphoblastic leukemia (ALL), specifically of its prevailing precursor B (B-ALL) subtype. A total of 1099 incident cases of ALL (957 B-ALL), 131 of acute myeloid leukemia (AML), and their 1 : 1 age-matched and sex-matched controls, derived from the Nationwide Registry for Childhood Hematological Malignancies (1996–2013), were analyzed using multivariate regression models. A null association was found between prelabor and/or during labor CD and either ALL (B-ALL) or AML in the 0–14 age range. By contrast, birth by CD increased significantly the risk of early-onset ALL [odds ratioCD (ORCD)=1.57, 95% confidence interval (CI): 1.10–2.24] mainly on account of prelabor CD (ORprelaborCD=1.66, 95% CI: 1.13–2.43). The respective figures were even higher for the early-onset precursor B-ALL (ORCD=1.66, 95% CI: 1.15–2.40 and ORprelaborCD=1.79, 95% CI: 1.21–2.66), whereas no association emerged for early-onset AML. Prelabor CD, which deprives exposure of the fetus/infant to the presumably beneficial effect of stress hormones released in both vaginal labor and during labor CD, was associated exclusively with an increased risk of early-onset ALL, particularly the precursor B-ALL subtype. If confirmed, these adverse long-term outcomes of CD may point to re-evaluation of prelabor CD practices and prompt scientific discussion on the best ways to simulate the effects of vaginal delivery, such as a precesarean induction of labor.

Human Chorionic Gonadotropin: The Pregnancy Hormone and More

To thoroughly review the uses of human chorionic gonadotropin (hCG) related to the process of reproduction and also assess new, non-traditional theories. Review of the international literature and research studies. hCG and its receptor, LH/CGR, are expressed in numerous sites of the reproductive tract, both in gonadal and extra-goanadal tissues, promoting oocyte maturation, fertilization, implantation and early embryo development. Moreover, hCG seems to have a potential role as an anti-rejection agent in solid organ transplantation. Future research needs to focus extensively on the functions of hCG and its receptor LH/CGR, in an effort to reveal known, as well as unknown clinical potentials.

Parental alcohol consumption and risk of leukemia in the offspring: a systematic review and meta-analysis

Parental alcohol consumption before and during pregnancy has been linked to adverse outcomes in the offspring including leukemogenesis. We, therefore, aimed to systematically assess and quantitatively synthesize published data on the association of paternal consumption during preconception and maternal consumption during pregnancy with leukemia risk in childhood (0–14 years). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed (until February 2016) and the reference lists of the relevant studies. Observational studies examining the association between parental alcohol consumption and childhood leukemia were considered eligible. Data extracted from 39 case–control studies (over 16 000 leukemia cases and 30 000 controls) were pooled and summary-effect estimates were calculated. Subgroup analyses were carried out by main acute leukemia type [lymphoblastic or myeloid), cytogenetics/genetic polymorphisms, and specific alcohol beverages. We found a statistically significant dose–response association of any level of maternal alcohol consumption compared with nondrinking during pregnancy exclusively with acute myeloid leukemia (AML) [odds ratio (OR)moderate consumption: 1.64, 95% confidence intervals (CIs): 1.23–2.17 and ORhigh consumption: 2.36, 95% CI: 1.60–3.49]. In contrast, no association of paternal preconception consumption with any leukemia type was noted. In beverage-specific analyses, only a positive association of maternal wine drinking with childhood AML was found, which was more pronounced in analyses including only studies on infant leukemia (ORwine: 2.12, 95% CI: 1.16–3.90). The largest ever meta-analysis shows a sizeable, statistically significant dose–response association of maternal alcohol consumption during index pregnancy with AML risk. Future research exploring the role of genetic polymorphisms is anticipated to shed light on the underlying pathophysiology.

The Impact of Genetics Profile (Gene Polymorphisms) in Obese Non- PCOS Women Entering an IVF/ICSI Program

Data concerning the effects of increased body mass index (BMI) on ovarian and pregnancy outcome are rich, but the results are rather controversial. Regarding pharmacogenetics, gene polymorphisms of hormonal receptor genes, such as Estrogen Receptor alpha (ESR1), Estrogen Receptor beta (ESR2) and FSH receptor (FSHR) genes, are associated with ovarian stimulation and pregnancy outcome and may constitute a useful tool for ART experts for the prediction of this outcome. The aim of this study is to track differences in the distribution of gene polymorphisms among obese non-PCOS and non-obese patients concerning three distinct genes which are involved in the ovarian stimulation mechanism: PvuII polymorphism of ESR1 gene, RsaI polymorphism of ESR2 gene and Ser680Asn variation of FSHR gene, using restriction fragment length polymorphism analysis and real-time polymerase chain reaction. A total of 151 normally ovulating female patients underwent IVF or ICSI. Interestingly, the pregnancy rate in the BMI≥30 kg/m² group was higher in a statistically significant way (40.9% versus 17.8%, p=0.023). The obese patients of this study were in need of increased total FSH dose in order to achieve a satisfactory oocyte number (p<0.001) and needed more days of stimulation (p=0.002), but also presented lower basal FSH levels (p=0.032), which may explain, to an extend, the better pregnancy outcome. Concerning the polymorphisms of ESR1, ESR2 and FSHR genes, we did not observe differences in the genotype distribution when we compared the obese non-PCOS population with the non-obese population. Thus, obesity does not constitute an additional indication to perform a genetic analysis before entering an IVF/ICSI program.

Posterior Deep Infiltrating Endometriotic Nodules: Operative Considerations according to Lesion Size, Location, and Geometry, during One's Learning Curve

We conducted this prospective cohort study to standardize our laparoscopic technique of excision of posterior deep infiltrating endometriosis (DIE) nodules, according to their size, location, and geometry, including 36 patients who were grouped, according to principal pelvic expansion of the nodule, into groups with central (group 1) and lateral (group 2) lesions, and according to nodule size, into ≤2 cm (group A) and >2 cm (group B) lesions, respectively. In cases of group 1 the following operative steps were more frequently performed compared to those of group 2: suspension of the rectosigmoid, colpectomy, and placement of bowel wall reinforcement sutures. The opposite was true regarding suspension of the adnexa, systematic ureteric dissection, and removal of the diseased pelvic peritoneum. When grouping patients according to nodule size, almost all of the examined parameters were more frequently applied to patients of group B: adnexal suspension, suspension of the rectosigmoid, systematic ureteric dissection, division of uterine vein, colpectomy, and placement of bowel wall reinforcement sutures. Nodule size was the single most important determinant of duration of surgery. In conclusion, during the building-up of ones learning curve of laparoscopic excision of posterior DIE nodules, technique standardization is very important to avoid complications.

Chorionic Villus Sampling in Assisted Versus Spontaneous Conception Twins.

Purpose To compare the outcome of chorionic villus sampling (CVS) in twin pregnancies following assisted reproduction technology (ART) versus twins that have been conceived spontaneously. Materials and Methods Retrospective analysis of dichorionic twin pregnancies that underwent CVS between 1986 and 2013 at our department which is a tertiary center for fetal medicine. 32 twin pregnancies after ART and 130 spontaneously conceived twin pregnancies, which underwent CVS, were analyzed. Results No difference was observed in the pregnancy loss rate between the two groups (0 % in the ART group vs. 3 % in the spontaneous twins group). The rate of preterm delivery before 28 weeks was higher in the ART group (18.8 %) compared to the control group (1.6 %). The perinatal mortality rate was similar in the two groups. Conclusion The pregnancy loss rate following CVS is similar in ART twins and in spontaneous twins. However, the risk of prematurity before 28 weeks is significantly higher in the ART group.