Christos Iavazzo

Molecular Mechanisms of Preeclampsia

Preeclampsia is one of the leading causes of maternal morbidity/mortality. The pathogenesis of preeclampsia is still under investigation. The aim of this paper is to present the molecular mechanisms implicating in the pathway leading to preeclampsia.

Polycystic ovarian syndrome and pregnancy outcome

IntroductionPolycystic ovarian syndrome (PCOS) is a common disease of the endocrine system among the women of reproductive age with an incidence ranging from 5 to 10%.MethodThis study is a mini-review of pregnancy and perinatal outcome in women with PCOS.ResultsThe syndrome is associated with increased risk of pregnancy complications such as gestational diabetes, gestational hypertension, preeclampsia, and preterm labor, while no strong association was found with congenital anomalies or spontaneous miscarriages. Furthermore, women with PCOS seem to experience increased risk of cesarean delivery while their newborns face increased perinatal morbidity and mortality. Metformin use seems to reduce the risk of obstetrical complications; however, prospective studies are necessary on the field.ConclusionFurther studies should be organised in order to evaluate the role of PCOS in pregnancy.

Diabetes mellitus and gynecologic cancer: molecular mechanisms, epidemiological, clinical and prognostic perspectives.

IntroductionDiabetes mellitus, the prevalence of which has increased dramatically worldwide, may put patients at a higher risk of cancer. The aim of our study is the clarification of the possible mechanisms linking diabetes mellitus and gynecological cancer and their epidemiological relationship.Materials and MethodsThis is a narrative review of the current literature, following a search on MEDLINE and the Cochrane Library, from their inception until January 2012. Articles investigating gynecologic cancer (endometrial, ovarian, and breast) incidence in diabetic patients were extracted.ResultsThe strong evidence for a positive association between diabetes mellitus and the risk for cancer indicates that energy intake in excess to energy expenditure, or the sequelae thereof, is involved in gynecological carcinogenesis. This risk may be further heightened by glucose which can directly promote the production of tumor cells by functioning as a source of energy. Insulin resistance accompanied by secondary hyperinsulinemia is hypothezised to have a mitogenic effect. Steroid hormones are in addition potent regulators of the balance between cellular differentiation, proliferation, and apoptosis. Inflammatory pathways may also be implicated, as a correlation seems to exist between diabetes mellitus and breast or endometrial carcinoma pathogenesis, although an analogous correlation with ovarian carcinoma is still under investigation. Antidiabetic agents have been correlated with elevated cancer risk, while metformin seems to lower the risk.ConclusionDiabetes mellitus is associated with an elevation in gynecologic cancer risk. Moreover, there are many studies exploring the prognosis of patients with diabetes and gynecological cancer, the outcome and the overall survival in well-regulated patients.

Thermal balloon endometrial ablation: a systematic review

ObjectiveThe aim of our study is to review the role of thermal balloon endometrial ablation (TBEA) as an alternative in treating abnormal uterine bleeding.MethodsArticles relevant to our review and relevant references from the initially identified articles on the field that were archived by May 2007, were retrieved from Pubmed.ResultsSuccess rates ranged from 83 up to 94%, with patient’s satisfaction ranging from 57 up to 94%. Persisted menorrhagia could reach 17% in some studies.ConclusionTBEA is an effective alternative method used in the treatment of menorrhagea which results in a significant reduction in menstrual bleeding and high satisfaction rates. However, a longer follow-up is required to determine the role of such a treatment.

Bakri balloon tamponade for the management of postpartum hemorrhage.

Maternal mortality –0.46 (0.004) –0.36 (0.063) West: –0.63 (0.008) West: –0.69 (0.013) East: –0.24 (0.478) East: 0.04 (0.919) Central: 0.75 (0.246) Central: 0.99 (0.037) Southern: –0.80 (0.101) Southern: –0.67 (0.327) Neonatal mortality –0.39 (0.019) –0.30 (0.119) West: –0.55 (0.027) West: –0.53 (0.079) East: –0.04 (0.912) East: –0.24 (0.539) Central: –0.92 (0.080) Central: –0.98 (0.116) Southern: –0.52 (0.369) Southern: –0.23 (0.773) Early neonatal mortality –0.31 (0.062) –0.22 (0.254) West: –0.47 (0.064) West: –0.44 (0.156) East: –0.08 (0.803) East: –0.26 (0.496) Central: –0.96 (0.034) Central: –0.97 (0.154) Southern: –0.49 (0.401) Southern: –0.18 (0.820) Late neonatal mortality b –0.47 (0.004) –0.39 (0.043) West: –0.59 (0.014) West: –0.55 (0.063) East: 0.05 (0.877) East: –0.11 (0.787) Central: –0.84 (0.156) Central: –0.99 (0.056) Southern: –0.59 (0.295) Southern: –0.37 (0.627)

The role of urocortin in gynecological and obstetrical conditions

AimThe objective of the review is to present the possible role of urocortin, a novel peptide of the corticotrophin releasing factor family, in different conditions of obstetrics and gynecology such as preterm labor, preeclampsia or ovarian steroidogenesis.Method-resultsA MEDLINE search was commenced with the terms “urocortin”, “preterm labor”, “preeclampsia”, “ovary”, “endometrium”, “myometrium”, “placenta”, “plasma”, “amniotic fluid”. Seventy-three articles were found to be relevant on the field and the potential role of urocortin in such conditions is presented.ConclusionAmounting data suggest that urocortin could play a significant role in human reproduction (steroidogenesis in the ovary, maintenance of the placental function and labor). Further investigation on the field is necessary in order to clarify the natural role of this newly identified molecule in the field of obstetrics and gynecology.

Preeclampsia: Molecular Mechanisms, Predisposition, and Treatment

Preeclampsia is a disorder characterised by vascular endothelial dysfunction and vasospasm that occurs after 20 weeks of gestation till 4–6 weeks postpartum. The global incidence of preeclampsia has been estimated at 2–14% of all pregnancies. Despite the advances made in the field, research is still organised to clarify the possible molecular mechanisms or predisposing factors of preeclampsia as well as the treatment options for such a significant disorder. Papers were selected on the basis of fundamental research ideas or reviews in the field. This special issue is comprising of seven papers which are focused on the better understanding of preeclapsia. One of the papers deals with the correlation of preeclampsia with hypoxia, thrombosis, and inflammation. The authors suggest that there is no accurate test for predicting preeclampsia. The role of markers such as sFLT, sEng, products of fetal and placental origin, markers of renal or endothelial damage, or markers of oxidative stress is presented by acting as secondary pathways to the pathophysiological changes that precede the clinical onset of preeclampsia. A combination of such markers is proposed in order to increase the detection accuracy earlier in the pregnancy and hopefully allow for more effective prophylactic strategies. Another paper sought to validate the use of urinary podocyte (podocyturia) as a single diagnostic marker in preeclampsia and in differentiating from other high-risk pregnancy states with similar presentations. The researchers discovered that podocyte loss is present not only in preeclampsia but in other high-risk pregnancy states. In addition, podocyturia was not found in a majority of patients diagnosed with preeclampsia. So, they realized that their findings had relatively low sensitivity and specificity, but they proposed further research regarding the predictive value of podocyturia in preeclampsia in larger studies. The authors of one of the paper investigated whether there is an association between angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism and preeclampsia in 236 pregnant women. They showed that there was significant difference in terms of genotype distribution between preeclampsia and controls, while it was not found any difference in allele frequency for ACE I/D polymorphism. A possible reason for the inconsistency could be the genetic basis that caused different susceptibilities among different populations. Moreover, one paper is mentioning that both women and children exposed to preeclampsia exhibit an adverse vascular phenotype, a propensity to subclinical atherosclerosis, and increased risk of adverse cardiac and vascular events in future life. They suggest that further studies into the mechanisms such as vascular dysfunction underlying the altered cardiovascular phenotype might provide unique insight into pathophysiological or molecular links between preeclampsia and cardiovascular disease which may direct us to novel treatment strategies for both conditions. Improvement in vascular function is also proposed as a valuable intermediate end point in studies aiming to reduce risk in this potentially young and generally asymptomatic population before the onset of clinical disease. F. J. Valenzuela and colleagues have recently reviewed some polymorphisms in important candidate genes involved in different pathogenic mechanisms related to preeclampsia and concluded that various studies in different populations have identified maternal polymorphisms associated with preeclampsia through candidate gene approaches. Luizon and colleagues with a Letter to the Editor add to the paper of F. J. Valenzuela et al. by further referring to candidate genes related to angiogenesis and endothelial dysfunction in preclampsia performed in the Brazilian population. Specifically, genotypes and haplotypes formed by polymorphisms of VEGF, eNOS, and MMP-9, along with an example of the interaction among these genes in the prediction of preeclampsia provide additional information with clinical relevance to its susceptibility. An additional paper is a review of the molecular mechanisms which are contributing to the pathogenesis of preeclampsia. Altered angiogenic balance, systemic inflammation, dysregulation of Renin-Angiotensin system, and placental hypoxia or ischemia are mechanisms leading to the pathogenesis of preeclampsia. However, it is unknown whether the mechanisms act independently or have synergistic effects.

Seven cases of fetal ovarian cysts

⁎ Corresponding author. 38 Seizani Street, Nea Ionia, Athens 14231, Greece. Tel.: +30 6948054119. E-mail address: christosiavazzo@hotmail.com (C. Iavazzo). Fetal ovarian cysts (FOCs) represent 3%–6% of all fetal intraabdominal tumors; they are solitary circumscribed cysts that are either anechoic or septated in the lower abdomen of the female fetus. Differential diagnoses include cystic abnormalities derived from the gastrointestinal tract, bladder, and kidneys [1]. Nussbaum et al. [2] classified FOCs into 2 groups, according to ultrasound findings: simple cysts, which are anechoic and thin-walled lesions; and hemorrhagic cysts, which are septated or have solid contents. Fetal ovarian cysts are follicular or luteal in origin, and usually originate from increased normal follicles during the third trimester [2]. Between January 1, 2006, and December 31, 2009, 7 female fetuses with ovarian cysts were identified at the University of Athens, Aretaieio Hospital, Athens, Greece. The present study was a retrospective investigation of the diagnosis andmanagement of these cases. The Ethics Committee of the study center provided approval. In all cases, diagnosis was made after 32 weeks of gestation. Ultrasound findings were of unilateral, solitary, and sharply circumscribed cysts of the lower abdomen (Figs. 1 and 2). The mean cyst diameter at diagnosis was 37 mm (range 27–61 mm). Five FOCs were simple and 2 were septated. Bilateral FOCs were present in 1 fetus. No other abnormal ultrasound findings were identified. In 6 cases, the cysts regressed spontaneously after birth (Table 1). There was no history of gestational diabetes, hypertension, or pre-eclampsia in any of the cases. Furthermore, no implications were listed, other than ovarian torsion with intracystic hemorrhage after birth in a neonate who underwent laparoscopic adnexectomy. Prenatal diagnosis of FOCs is usually made in the third trimester. In the present case series, the diagnosis was made, on average, at 32+3 weeks. Differential diagnoses included mesenteric and urachal cysts, ectopic hydronephrotic kidneys, intestinal duplication anomalies, cystic teratomas, and intestinal obstruction. The histologic origin of FOCs could be follicular or theca lutein cysts, lymphangiomas, or teratomas. Fetal ovarian cysts greater than50 mmin diameter could be complicated by ovarian torsion, intracystic hemorrhage, intestinal obstruction due to adhesions, and ovarian loss [3]. In utero ultrasound imaging is used to identify complications such as torsion or rupture, although there are no specific ultrasound findings fromwhich ovarian torsion can be diagnosed [4,5]. Postnatally, the cysts can regress spontaneously because of estrogen induction [3]. The therapeutic approach for FOCs depends on the diameter and the echogenicity (the cut-off point for surgical intervention is a diameter greater than 50 mm). Prenatal aspiration of FOCs might be another therapeutic option, although it may lead to chorioamnionitis, preterm labor, or fetal injury. Aspirationwas not performed in the present study. With regard to the timing and method of delivery of fetuses with FOCs, we propose that cesarean delivery is not essential, although it should be considered when there is ovarian torsion so that ovarian function is preserved—especially when there is pulmonary maturation.