Themistoklis Dagklis

Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy

BACKGROUND Administration of conventional antithrombotic treatment (low-dose aspirin plus low-molecular weight heparin [LDA+LMWH]) for obstetric antiphospholipid syndrome (APS) does not prevent life-threatening placenta insufficiency-associated complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR) in 20% of patients. Statins have been linked to improved pregnancy outcomes in mouse models of PE and APS, possibly due to their protective effects on endothelium. Here, we investigated the use of pravastatin in LDA+LMWH-refractory APS in patients at an increased risk of adverse pregnancy outcomes. METHODS We studied 21 pregnant women with APS who developed PE and/or IUGR during treatment with LDA+LMWH. A control group of 10 patients received only LDA+LMWH. Eleven patients received pravastatin (20 mg/d) in addition to LDA+LMWH at the onset of PE and/or IUGR. Uteroplacental blood hemodynamics, progression of PE features (hypertension and proteinuria), and fetal/neonatal outcomes were evaluated. RESULTS In the control group, all deliveries occurred preterm and only 6 of 11 neonates survived. Of the 6 surviving neonates, 3 showed abnormal development. Patients who received both pravastatin and LDA+LMWH exhibited increased placental blood flow and improvements in PE features. These beneficial effects were observed as early as 10 days after pravastatin treatment onset. Pravastatin treatment combined with LDA+LMWH was also associated with live births that occurred close to full term in all patients. CONCLUSION The present study suggests that pravastatin may improve pregnancy outcomes in women with refractory obstetric APS when taken at the onset of PE or IUGR until the end of pregnancy.

Nandrolone abuse decreases anxiety and impairs memory in rats via central androgenic receptors

Anabolic androgenic steroids (AASs) affect areas of the central nervous system, which are involved in emotional and cognitive responses such as sexuality, anxiety, and memory. In the present study we imitated the abuse of AASs by administering high doses of the AAS nandrolone decanoate (ND) to rats. Thereafter rats were exposed to an elevated plus-maze and an olfactory social memory test to evaluate their anxiety-like and cognitive behaviour. To reveal whether these emotional and cognitive changes evoked by ND were caused via direct activation of androgenic receptors (ARs) in the brain, the AR antagonist flutamide (FL) was administered intracerebroventricularly (i.c.v.). Male rats were randomly divided in four groups, one group received 15 mg/kg ND subcutaneously, once daily for 6 wk (ND group). In the second group, in addition to ND, a daily dose of 5 microg FL was injected i.c.v. also for 6 wk (ND+FL group). The third group of rats received only FL and in the control group the vehicle was injected. The ND group clearly spent more time investigating the open arms in the maze test and recognizing the juvenile during the olfactory social memory test in comparison to the control group. In the ND+FL group rats showed similar emotional behaviour and cognitive ability to that of the control group. Injection of FL alone did not affect either anxiety or memory. These results indicate that repeated, high-dose administration of ND decreases anxiety and impairs memory in rats via direct activation of central ARs.

Clinical Improvement and Successful Pregnancy in a Preeclamptic Patient With Antiphospholipid Syndrome Treated With Pravastatin

The clinical hallmarks of the antiphospholipid syndrome (APS) are thrombosis and adverse obstetric outcomes. Women with APS have a higher incidence of preeclampsia.1 Currently, treatment of APS focuses on anticoagulation therapy, treatment mostly given empirically and often ineffective. Similarly, treatment for preeclampsia remains symptomatic and also ineffective. Studies in animal models support the hypothesis that pravastatin may be an effective therapy to prevent pregnancy complications in APS and in preeclampsia.2–5 Here, we describe a patient, with a previous history of preeclampsia, thrombosis, and APS, presenting with preeclampsia at 23 weeks’ gestation in her second pregnancy that was treated with pravastatin, which resulted in marked clinical improvement and successful pregnancy outcome. A 30-year-old woman with no previous medical history had a first pregnancy complicated with early preeclampsia with bilateral notching (22 weeks and 0 days) and hypertension and edema at 24 weeks, leading to a still birth at week 26. She developed deep vein thrombosis 2 days postpartum. Based on her history of deep vein thrombosis, early preeclampsia, and twice positive lupus anticoagulant, with an interval of 3 months between the tests, the patient was diagnosed with APS. The patient received therapeutic doses of low-molecular-weight heparin for 3 months and prophylactic doses while trying to conceive again. Her blood pressure and proteinuria remained normal. Ten months later, she got pregnant and was started on intermediate doses of enoxaparin (0.6 OD) and aspirin (100 mg OD). Blood pressure …

GnRH antagonist versus long GnRH agonist protocol in poor IVF responders: a randomized clinical trial.

OBJECTIVE To compare the efficacy of the long GnRH agonist and the fixed GnRH antagonist protocols in IVF poor responders. STUDY DESIGN This was a randomized controlled trial performed in the Iakentro IVF centre, Thessaloniki, from January 2007 to December 2011, concerning women characterised as poor responders after having 0-4 oocytes retrieved at a previous IVF cycle. They were assigned at random, using sealed envelopes, to either a long GnRH agonist protocol (group I) or a GnRH antagonist protocol (group II). RESULTS Overall 364 women fulfilled the inclusion criteria and were allocated to the two groups: finally 330 participated in our trial. Of these, 162 were treated with the long GnRH agonist protocol (group I), and 168 with the fixed GnRH antagonist protocol (group II). Numbers of embryos transferred and implantation rates were similar between the two groups (P=NS). The overall cancellation rate was higher in the antagonist group compared to the agonist group, but the difference was not significant (22.15% vs. 15.2%, P=NS). Although clinical pregnancy rates per transfer cycle were not different between the two groups (42.3% vs. 33.1%, P=NS), the clinical pregnancy rate per cycle initiated was significantly higher in the agonist compared to the antagonist group (35.8% vs. 25.6%, P=0.03). CONCLUSIONS Although long GnRH agonist and fixed GnRH antagonist protocols seem to have comparable pregnancy rates per transfer in poor responders undergoing IVF, the higher cancellation rate observed in the antagonist group suggests the long GnRH agonist protocol as the first choice for ovarian stimulation in these patients.

Parameters affecting latency period in PPROM cases: a 10-year experience of a single institution

Abstract Objective: To investigate the association of epidemiological and pregnancy-related parameters with the latency period achieved in cases of preterm premature rupture of membranes (PPROM). Method: A retrospective study was performed enrolling cases admitted in high-risk pregnancy unit (HRPU) with PPROM between 24 + 0 and 36 + 6 gestational week during 2002–2011. Cases with vaginal bleeding at admission, co-existing maternal or fetal pathology, placenta praevia, previous interventions in cervix or uterus, triplets or higher order pregnancies were excluded. Epidemiological parameters and latency period between admission due to PPROM and delivery were recorded. Obstetrical complications, mode of delivery, and neonatal morbidity parameters were also studied. A multivariate regression model was used to correlate latency period with epidemiological and pregnancy-related risk factors. Results: Overall, there were 319 cases of PPROM admitted, of which 303 (94.9%) met inclusion criteria. Median latency period was 5.2 d. The latency interval exceeded 48 h in 65.0% of cases (197/303). Emergency cesarean was demanded in 20.2% of cases, chorioamnionitis was diagnosed in 7.5% while 76.1% of neonates were admitted in neonatal intensive care unit. Higher gestational week at admission was associated with shorter latency interval (p < 0.001), twin pregnancy with shorter latency interval (p = 0.02), while latency interval was significantly lower in cases complicated with chorioamnionitis (p = 0.048). Conclusion: Gestational week at PPROM, twin gestation and chorioamnionitis are factors significantly affecting latency interval.

Serum vaspin levels in women with and without gestational diabetes mellitus during pregnancy and postpartum.

Although vaspin is regarded an insulin-sensitizing adipokine, its role in gestational diabetes mellitus (GDM) is currently unknown. We aimed to evaluate serum vaspin levels and their correlation with insulin resistance in women with and without GDM. Forty-four women with GDM [GDM Group - 20 managed with diet only (GDM-diet) and 24 with diet plus insulin (GDM-insulin)] and 44 age-matched pregnant women with normal glucose tolerance (Control Group) were studied. Serum glucose, lipids, uric acid, insulin and vaspin were measured at the 2nd and 3rd trimester of pregnancy and postpartum. The quantitative insulin sensitivity check index (QUICKI) and homeostasis model of assessment-insulin resistance (HOMA-IR) were calculated. Circulating vaspin levels decreased significantly postpartum in all groups (p<0.001), but did not differ between GDM or GDM Subgroups and Control Group in any time point. At the 3rd trimester of pregnancy vaspin was positively correlated to insulin (p=0.022), HOMA-IR (p=0.016) and triglycerides (p=0.033) and negatively correlated to QUICKI (p=0.016) in the GDM women, but not in the Controls. These correlations were not observed at the 2nd trimester or postpartum. Vaspin, in contrast to HOMA-IR, could not independently predict GDM in binary logistic regression. In patients with GDM, insulin treatment did not affect vaspin levels. In conclusion, our data suggest that vaspin levels gradually decrease from the 2nd trimester to postpartum; however, decreases are similar between women with or without GDM. Serum vaspin cannot independently predict GDM and it is not affected by the degree of glucose metabolism deregulation or the exogenous administration of insulin.

Common features and differences of the hypothalamic-pituitary-gonadal axis in male and female.

Abstract Male and female reproductive axis, comprised of hypothalamus, pituitary and gonads, present common features and differences, discussed in this review. These include the way hypothalamus regulates pituitary function, and the way pituitary, in turn, affects gonadal function. Finally, age plays an important role in axis regulation, in both genders. Chinese abstract 男性与女性的生殖轴均由下丘脑、垂体、性腺组成，本文将阐述它们间存在的相似与不同之处，包括下丘脑对垂体的调控以及垂体作为应答对性腺的作用。最后，年龄是影响男女性腺轴调节的重要因素。

Factors implicated in the initiation of human parturition in term and preterm labor: a review.

Abstract After accommodating the pregnancy for an average of 40 weeks, the uterus expels the fetus, the placenta and the membranes through the birth canal in a process named parturition. The absolute sequence of events that trigger and sustain human parturition are not yet fully clarified. Evidence suggests that spontaneous preterm and term labor seem to share a common inflammatory pathway. However, there are several other factors being involved in the initiation of human parturition. Placental corticotropin releasing hormone production seems to serve as a placental clock that might be set to ring earlier or later determining the duration of pregnancy and timing of labor. Estrogens do not cause contractions but their properties seem to capacitate uterus to coordinate and enhance contractions. Cytokines, prostaglandins, nitric oxide and steroids seem also to induce ripening by mediating remodeling of the extracellular matrix and collagen. Infection and microbe invasion resulting in chorioamnionitis also represents a common cause of early preterm labour. This review provides an overview of all these factors considered to be implicated in the initiation of human parturition. Chinese abstract 在调节平均40周的妊娠后,子宫通过产道排出胎儿，胎盘和胎膜的过程称为分娩。触发和维持人类分娩的绝对事件序列仍未完全阐明。有证据表明，自发早产和足月产似乎都遵循一条同样的炎症通路。然而，仍有一些其他的因素与人类分娩的触发有关。胎盘促肾上腺激素释放激素的产生似乎充当胎盘时钟的作用，时钟响的时间可能会设定的早或晚，决定了孕期的时长和分娩的时间。雌激素并不造成宫缩，但是它的性质可使子宫协调而加强宫缩。细胞因子、前列腺素、一氧化氮和类固醇似乎通过重塑细胞外基质和胶原来同样促进成熟。感染和微生物入侵所导致的绒毛膜羊膜炎也是常见的早产原因之一。这篇综述提供了与人类分娩的相关因素的概述。

Operator experience reduces the risk of second trimester amniocentesis-related adverse outcomes

OBJECTIVE To investigate the impact of operator experience on amniocentesis-related adverse outcomes. STUDY DESIGN Retrospective study of mid-trimester amniocenteses performed by the same operator on singleton pregnancies in a single private institution during 1994-2007. Outcomes were hemorrhagic or dark amniotic fluid aspiration, insufficient volume aspiration, repeated puncture and fetal loss. Rates were estimated annually, as well as for every 10% of procedures up to the total number. The association of each outcome with epidemiological aspects was also examined. RESULTS In total, 5913 amniocenteses were performed. The overall rate of adverse outcomes was 5.4%. The total adverse outcome rate reduced from 10.2% in the first 10% of cases to 3.0% in the last 10% (P=.001). The rate of hemorrhagic fluid gradually decreased from 4.4% to 1.5% (P=.05) over the same intervals. The fetal loss rate was also reduced from 0.5% during the first half to 0.3% in the second half of the study period (P=NS). Logistic regression analysis indicated no significant correlations between adverse outcomes with any of epidemiological parameters of women undergoing amniocentesis. CONCLUSION Operator experience has a beneficial impact on preventing procedure-related adverse outcomes.

Amniocentesis-related adverse outcomes in diamniotic twins: is there a difference compared to singleton pregnancies?

OBJECTIVE To investigate whether diamniotic twin gestations are at increased risk of amniocentesis-related adverse outcomes compared to singleton pregnancies. STUDY DESIGN This was a retrospective study of mid-trimester amniocenteses performed during the period 1993-2009. Cases were divided in two groups, one including singleton (Group 1) and the other diamniotic twin pregnancies (Group 2). All amniocentesis-related adverse outcomes were reviewed, including aspiration of insufficient amniotic fluid, aspiration of hemorrhagic amniotic fluid, repeated puncture and miscarriage. The incidence of these adverse outcomes was compared between the two groups. RESULTS In total, 6270 cases were included in the study (Group 1, n=6150 and Group 2, n=120). Advanced maternal age was the main indication for amniocentesis in both singleton and twin pregnancies. There was no difference in the incidence of insufficient sample aspiration (0.2% in singletons vs. 0.0% in twins, P=NS), in the incidence of blood-stained amniotic fluid (3.7% in singletons vs. 4.6% in twins, P=NS), in the rate of need for second attempt (2.1% in singletons vs. 1.7% in twins, P=NS) or in the miscarriage rate (0.24% in singletons vs. 0% in twins). CONCLUSION In our experience, the incidence of amniocentesis-related adverse outcomes is not increased in diamniotic twins compared to singleton pregnancies.