Oxidative stress and female infertility: the role of follicular fluid soluble receptor of advanced glycation end-products (sRAGE) in women with endometriosis.

Oxidative Stress (OS) relates to the pathophysiology of endometriosis by activation of the inflammation process in the ovary, abdomen, peritoneum and endometrium. Advanced Glycation end-products (AGEs) cause oxidative damage to the follicles of the ovary. This study aims to investigate the correlation of follicular fluid soluble receptor of AGEs (FF sRAGE) with fertility-related parameters in infertile women with endometriosis. From January 2012 to July 2015 twenty-four women diagnosed with mild to moderate endometriosis aged 28-38 years underwent assisted reproduction. sRAGE levels measured in FF were related to lifestyle factors, sociodemographic characteristics, gynaecological and obstetric parameters, hormonal status and fertilization. sRAGE was inversely associated with BMI (r = -0.503, p = 0.012). No significant association of sRAGE with age (p = 0.714) or alcohol consumption (p = 0.882) was found. Pearson's r correlation coefficient revealed that sRAGE was positively associated with serum AMH (r = 0.518, p = 0.009), FF AMH (r = 0.630, p = 0.001), number of follicles >15mm (r = 0.601, p = 0.002), total number of follicles aspirated (r = 0.698, p < 0.001), total number of MII oocytes obtained, (r = 0.757, p < 0.001) and the number of embryos with good embryo scoring (suitable for ET) (r = 0.522, p = 0.009). It seems that measurement of FF RAGE might be a useful predictive marker for IVF success in infertile women with endometriosis undergoing assisted reproduction.

Expression of Delta Like Ligand 4 (DLL4) in endometrial carcinomas and tumor vasculature.

PURPOSE: Delta like ligand 4 (DLL4) is a transmembrane ligand of the Notch Signalling pathway, that regulates blood vessel sprouting and maturation. We investigated the expression of DLL4 in endometrial cancer. METHODS: DLL4 was assessed in the plasma (with ELISA) and tissues (with immunohistochemistry) 33 patients with endometrial cancer, treated with radical hysterectomy for stage I endometroid carcinoma. The angiogenic activity (AA) of endometrial cancer was quantified by assessing the CD31+ microvessel density (MVD) in the invading tumor front. Vascular maturation index (VMI), defined as the percentage of CD31+ microvessels expressing DLL4, was calculated as the ratio of the CD31+ MVD to the DLL4+ MVD. RESULTS: The angiogenic activity was directly related with the histological grade (p=0.01). The VMI ranged from 0.1 to 0.7 (median 0.34). The concentration of DLL4 in the plasma ranged from 55-81pg/ml (mean 62.8) before, and dropped to 55-62 (mean 58.2) after hysterectomy (p<0.05). DLL4 was also expressed by cancer cells in 17/33 cases. No correlation between DLL4-related parameters with histopathological variables was noted. CONCLUSION: This pilot study shows that DLL4 is overexpressed in endometrial cancer cells, vasculature and is also elevated in the plasma of a fraction of patients before surgery. The percentage of DLL4+ vessels in the penetrating sample ranged from 10-70%, indicating a large difference in the quality of angiogenesis produced between the endometrial tumors of the same histological type and differentiation.

The Influence of Sexual Behavior and Demographic Characteristics in the Expression of HPV-Related Biomarkers in a Colposcopy Population of Reproductive Age Greek Women.

Despite the significant scientific evolution in primary and secondary cervical cancer prevention in the battle started by George Papanicolaou in the previous century, global cervical cancer mortality rates remain disappointing. The widespread implementation of HPV-related molecular markers has paved the way to tremendous developments in cervical cancer screening, with the transition from cytological approach to the more accurate and cost-effective HPV testing modalities. However, the academic audience and different health systems have not yet adopted a universal approach in screening strategies, and even artificial intelligence modalities have been utilized from the multidisciplinary scientific armamentarium. Combination algorithms, scoring systems as well as artificial intelligent models have been so far proposed for cervical screening and management. The impact of sexual lifestyle inherently possesses a key role in the prevalence of HPV-related biomarkers. This study aimed to investigate any possible influence of sexual behavior and demographic characteristics in the expression of HPV-related biomarkers in a colposcopy population from October 2016 to June 2017, and corroborated the determining role of age at fist intercourse; the older the age, the lower the probability for DNA positivity. Multivariate analysis illustrated additionally that a number of sexual partners exceeding 4.2 was crucial, with women with ≤5 partners being approximately four times less likely to harbor a positive HPV DNA test (p < 0.0001). Similarly, a reported partner change during the last year before HPV DNA assessment contributed to 2.5 times higher odds for DNA positivity (p = 0.0006). From this perspective, the further development and validation of scoring systems quantifying lifestyle factors that could reflect cervical precancer risk seems paramount.

Maternal and paternal age at birth and the risk of breast cancer in Greek women: a case-control study.

PURPOSE: To investigate the possible association between maternal and paternal age and breast cancer in Greek women. METHODS: This study enrolled 238 women with breast cancer and 153 healthy women as control group. All participants were examined clinically and with breast ultrasound and those older than 40 years, also with digital mammography. RESULTS: A statistically significant positive correlation was observed between the age of the father (x2=52.985, p<0.001) and the mother (x2=34.838, p=0.001). More specifically, in breast cancer patients, the majority of their mothers (45.4%) was over 30 years of age and their fathers' age (48.3%) was over 37 years of age. CONCLUSIONS: Our study found that as the age of the father and mother increases, the incidence of breast cancer increases in parallel. Further studies with larger number of patients are necessary in order to clarify the real role of parental age as a risk factor of breast cancer.

Cervical Pathology Following HPV Vaccination in Greece: A 10-year HeCPA Observational Cohort Study.

BACKGROUND: In Greece the population-level impact of HPV vaccination is unknown due to lack of official registries. This study presents in a pragmatic frame the comparison of cervical pathology data between HPV-vaccinated and unvaccinated women referred for colposcopy. PATIENTS AND METHODS: This is an observational prospective cohort study performed in 7 academic Obstetrics and Gynaecology Departments across Greece between 2009-2019. Cases were women that had completed HPV vaccination before coitarche and were referred for colposcopy due to abnormal cytology. For each vaccinated woman an unvaccinated matched control was selected. RESULTS: A total of 849 women who had been vaccinated before coitarche and 849 unvaccinated controls were recruited. The combination of cytological, colposcopic and molecular findings necessitated treatment in only a single case among vaccinated (0.1%) and in 8.4% among unvaccinated. CONCLUSION: HPV vaccination at a proper age can markedly reduce development of severe cervical precancers and consequently the need for treatment, as well as their long-term related obstetrical morbidity.

Management of malignant and borderline phyllodes tumors of the breast: our experience.

PURPOSE: Phyllodes breast tumors (PT) range from benign lesions to malignant ones that may give distant metastasis. Preoperative diagnosis is difficult, while the treatment of borderline and malignant disease remains controversial. METHODS: Eighteen patients in 3 clinics were included in the study. Lumpectomy with large margins was performed in 15 patients, while mastectomy was performed in 3 patients. Lymph node excision was carried out in 3 patients with malignant tumors. Radiation therapy (RT) was delivered after a second lumpectomy in cases of local recurrence. Chemotherapy was used only in 2 patients with aggressive recurrent tumors. RESULTS: Borderline behavior was reported in 4 patients. Lumpectomy was performed in these cases, with local recurrence in 2 of them. Malignant behavior was reported in 14 patients. Lumpectomy was performed in 10 patients and mastectomy in 3. Local recurrence was reported in 5 cases and in 2 patients recurrence after a 2nd operation was also reported. CONCLUSIONS: Borderline PT were treated conservatively and the prognosis was excellent, while malignant subtypes needed mastectomy in about 25% of the cases, The local recurrence rate was high, but the disease free survival (DFS) and the overall survival (OS) were also very high (94%).

Genetic variations in the SULF1 gene alter the risk of cervical cancer and precancerous lesions.

Human papillomavirus (HPV) infection alone is not sufficient to explain the development of cervical cancer. Genetic variants have been linked to the development of precancerous lesions and cervical cancer. In this study, we aimed to evaluate the association of 10 single nucleotide polymorphisms (SNPs) of the Fas cell surface death receptor (FAS), trinucleotide repeat containing 6C (TNRC6C), transmembrane channel like 8 (TMC8), DNA meiotic recombinase 1 (DMC1), deoxyuridine triphosphatase (DUT), sulfatase 1 (SULF1), 2'-5-oligoadenylate synthetase 3 (OAS3), general transcription factor IIH subunit 4 (GTF2H4) and interferon gamma (IFNG) genes with susceptibility to precancerous lesions and cervical cancer. In total, 608 female participants, consisting of 199 patients with persistent low-grade precancerous lesions (CIN1), 100 with high-grade precancerous lesions (CIN2/3), 17 patients with cervical cancer and 292 healthy controls, were enrolled in this study. SNPs were tested for associations with each of the above-mentioned cervical group lesions or when considering an overall patient group. A significant difference for rs4737999 was observed between the controls and the overall patient group considering the recessive mode of inheritance [odds ratio (OR), 0.48; 95% confidence interval (CI), 0.24-0.96; P=0.033]. This effect was even stronger on the risk of CIN1 lesions. Carriers of the rs4737999 AA genotype were almost 3-fold less likely of having low grade lesions compared to the other genotypes. On the whole, this study provides evidence of an influence of the SULF1 gene rs4737999 SNP in the development of precancerous lesions/cervical cancer.

Overcoming heparin resistance in pregnant women with antithrombin deficiency: a case report and review of the literature.

BACKGROUND: The risk of thromboembolic events during pregnancy in patients with antithrombin deficiency is increased. Preventing thromboembolic events during pregnancy in the case of antithrombin deficiency is still a matter of concern. CASE PRESENTATION: We present a case of a 19-year-old primigravida Greek Pomak woman, who was diagnosed as having congenital antithrombin deficiency. She had a history of recurrent miscarriages and a family history of thrombosis. She was managed with adjusted doses of low molecular weight heparin throughout her pregnancy, with regular anti-Xa and antithrombin level monitoring. Prior to delivery and for 4 days after delivery she received human antithrombin III concentrate. She delivered a small for gestational age baby with no other complications. She required an increased dose of heparin due to heparin resistance. CONCLUSIONS: Antithrombin deficiency is associated with an increased risk of venous thromboembolic events with a 50% risk of thromboembolic events before the 50th year of life. It is a rare condition, so data concerning the optimal management during pregnancy are limited. The selection of patients who should receive low molecular weight heparin prophylaxis as well as dose intensity and monitoring are discussed. In our patient a conventional low molecular weight heparin dose proved to be inadequate at least at the laboratory level.

Comparative Evaluation of Arabin Pessary and Cervical Cerclage for the Prevention of Preterm Labor in Asymptomatic Women with High Risk Factors.

OBJECTIVE: Preterm labor is one of the most significant obstetric problems associated with high rate of actual and long-term perinatal complications. Despite the creation of scoring systems, uterine activity monitoring, cervical ultrasound and several biochemical markers, the prediction and prevention of preterm labor is still a matter of concern. The aim of this study was to examine cervical findings for the prediction and the comparative use of Arabin pessary or cerclage for the prevention of preterm birth in asymptomatic women with high risk factors for preterm labor. MATERIAL AND METHODS: The study group was composed of singleton pregnancies (spontaneously conceived) with high risk factors for preterm labor. Cervical length, dilatation of the internal cervical os and funneling, were estimated with transvaginal ultrasound during the first and the second trimesters of pregnancy. RESULTS: Cervical funneling, during the second trimester of pregnancy, was the most significant factor for the prediction of preterm labor. The use of Arabin cervical pessary was found to be more effective than cerclage in the prolongation of pregnancy. CONCLUSION: In women at risk for preterm labor, the detection of cervical funneling in the second trimester of pregnancy may help to predict preterm labor and to apply the appropriate treatment for its prevention. Although the use of cervical pessary was found to be more effective than cerclage, more studies are needed to classify the effectiveness of different methods for such prevention.

Predictive value of fetal scalp pH and base excess for fetal acidosis and poor neonatal outcome.

OBJECTIVE: The objective of this study is to assess retrospectively the predictive value of fetal scalp pH and base excess (BE) for fetal acidosis and poor neonatal outcome in term, low-risk, spontaneous deliveries with suspicious or pathological intrapartum cardiotocography (CTG) tracings. METHODS: Umbilical artery pH and BE values obtained immediately after delivery and Apgar score were the outcomes under consideration. Statistics included receiver-operating characteristic curve (ROC) and multiple logistic regression analysis. RESULTS: Four hundred and six deliveries were included in the study. Scalp pH < 7.20 predicted umbilical pH ≤7.1 with 64.3% sensitivity and 92.9% specificity (p < .001). The corresponding positive-predictive value (PPV) was 24.3% and the negative-predictive value (NPV) was 98.6%. Scalp BE ≤ -7 mmol/l (a cut-off value provided by ROC curve analysis) predicted Apgar score ≤ 7 at 5 min with 61.9% sensitivity and 91.7% specificity (p < .001). The corresponding PPV and NPV were 29.5 and 97.7%, respectively. Neither scalp pH nor BE was significantly associated with umbilical BE values. Infants with intrapartum BE ≤ -7 mmol/l were 30 times on an average more likely to get a low Apgar score, independently of intrapartum pH values. CONCLUSION: Our study supports the consideration of both scalp pH and BE values, when fetal blood sampling (FBS) is used.

Retraction: Human Papilloma Virus' Life Cycle and Carcinogenesis.

[This retracts the article , PMID: 28465751.].

Ovarian reserve after fibroid embolization in premenopausal women.

OBJECTIVE: To investigate the effect of uterine artery embolization (UAE) for fibroids on ovarian pool of premenopausal women. STUDY DESIGN: Prospective case control study. MATERIAL AND METHODS: One-hundred and twenty premenopausal women, aged between 40 and 50 years, who underwent UAE for symptomatic uterine fibroids and the same number of women, aged between 40 and 50 years, with symptomatic uterine fibroids, who were not offered treatment were recruited for this study. Hormonal status and ovarian reserve were evaluated by means of anti-Müllerian hormone (AMH) and follicle stimulating hormone (FSH) pre-procedural, three months, six months and 12 months after UAE. RESULTS: No statistically significant decrease was noted in AMH values 12 months post procedure and no statistical significant alterations in AMH values between the two groups. CONCLUSIONS: Even though the study results may not be able to confirm the preservation of ovarian reserve and normal menstruation after UAE in premenopausal women, it should be considered as a friendly to normal menstruation treatment option of symptomatic fibroids.

Paraaortic lymphadenectomy in intermediate to high risk uterine endometrioid cancer : a retrospective evaluation.

PURPOSE: To investigate the impact on survival of paraaortic lymph node dissection (PALND) added to pelvic lymph node dissection (PLND) in patients with intermediate to high-risk endometrioid endometrial cancer (EC ). Surgical parameters and perioperative morbidity have been explored as well. METHODS: We retrospectively identified all eligible patients that received LND as part of their primary treatment at a single institution from January 2000 to December 2010. Survival curves for overall (OS), disease-specific (DSS) and disease-free (DFS) survival were plotted by the Kaplan-Meier method and compared by the log-rank test. Cox proportional hazards regression was used for multivariable analysis for OS and DSS. RESULTS: 93 patients underwent PLND plus PALND in their initial operation (PALND group) and 177 patients underwent PLND only (no-PALND group). Patients in the non-PALND group were older, more obese and had higher rates of comorbidities. The median number of PLN and PALN retrieved were 26 and 13 respectively. Isolated PALN metastasis was seen in 2 (2.1%) patients. PALND was associated with longer operative time, higher transfusion rate and longer hospital stay. PALND group had a benefit in OS (p=0.033), which did not persist in DSS or DFS. Furthermore, the type of LND did not significantly improve either OS or DSS according to the multivariate analysis results. CONCLUSION: PALND had no therapeutic value per se in women with intermediate to high risk endometrioid tumors and the improvement seen in OS should rather be attributed to the better medical status of women who received PALND.

Contraceptive behaviour of Christian and Muslim teenagers at the time of abortion and post-abortion in Thrace, Greece.

OBJECTIVES: The aims of the study were to compare the contraceptive behaviour of Christian and Muslim adolescents who had an abortion in Thrace, Greece, and to examine whether extensive contraceptive counselling at the time of abortion modified their subsequent contraceptive practices. METHODS: Adolescents, aged 14-19 years, who had undergone an elective abortion in our department, were included in a prospective 12-year study. Extensive contraceptive counselling was offered before discharge from the hospital. Attitudes to contraception were assessed by means of a simple questionnaire at the time of abortion and at 1-year follow-up. RESULTS: The study population comprised of 95 Christian Orthodox adolescents (Group A) and 79 Muslim adolescents (Group B). At the time of abortion, contraceptive behaviour differed significantly between the two groups (p = .004). Contraceptive methods used in Group A in comparison with Group B were as follows: oral contraceptives (27.4% vs. 12.7%), condoms (22.1% vs. 38.0%), interrupted coitus (18.9% vs. 20.3%), periodic abstinence (16.8% vs. 25.3%) and emergency contraception (14.7% vs. 3.8%). The commonest source of information on contraception in Group A was the gynaecologist (17.9%) and family planning clinic (15.8%), whereas in Group B it was the individual's partner (25.3%) and parents (16.4%). Contraceptive behaviour was significantly modified in both groups at post-abortion follow-up (both p < .001). The original difference between the groups, however, persisted (p = .006). In Group A, oral contraceptives were the dominant method (48.4%), followed by condoms (30.5%), whereas in Group B, the order was still the reverse (24.1% and 46.8%, respectively). CONCLUSION: Cultural differences significantly affect the contraceptive behaviour. Nevertheless, interventions that promote contraception can still be successful in different populations.

Inherited thrombophilia and reproductive disorders.

Apart from its established role in the pathogenesis of venous thromboembolism (VTE), inherited thrombophilia has been proposed as a possible cause of pregnancy loss and vascular gestational complications. There is a lot of controversy in the literature on the relationship between inherited prothrombotic defects and these obstetric complications. This is a review of the literature on inherited thrombophilia and reproductive disorders. Factor V Leiden, prothrombin G20210A mutation, and protein S deficiency seem to be associated with late and recurrent early pregnancy loss, while their impact on other pregnancy complications is conflicting. No definite association has been established between protein C and antithrombin deficiency and adverse pregnancy outcome, primarily due to their low prevalence. Screening is suggested only for women with early recurrent loss or late pregnancy loss. Anticoagulant treatment during pregnancy should be considered for women with complications who were tested positive for thrombophilia.

Genotoxic effect of tocolytic drug ritodrine in combination with smoking during pregnancy.

OBJECTIVE: Tocolytic drugs are used widely in order to prevent preterm birth. Ritodrine, is the only food and drug administration (FDA) approved drug for tocolytic use. We estimated the cytogenetic effect of ritodrine administered as maternal therapy, alone or in combination with smoking, in women and their neonates. METHODS: Lymphocyte and fibroblasts cultures were evaluated and three indices were analyzed; sister chromatid exchanges (SCEs), proliferation rate index (PRI) and mitotic index (MI) as well as average generation time (AGT) and population doubling time (PDT). Campothacin (CPT-11) was used as a positive control. RESULTS: Administration of ritodrine up to a month revealed significant reduction of SCEs/cell in neonates in the presence or absence of the mutagenic agent. A statistical significant increase on SCEs, for mothers and neonates, was noticed in neonate's lymphocytes when tocolytic therapy was over a month. Ritodrine revealed a cytoprotective action against smoking when the two factors were combined, but the synergistic action of ritodrine with smoking increased genotoxicity, cytostaticity and cytotoxicity of neonates after long administration (1-3 months). CONCLUSIONS: The time-depended genotoxic, cytostatic and cytotoxic action of ritodrine alone or in combination with smoking suggests that its administration should not exceed the time period of a month.

Human Papilloma Virus' Life Cycle and Carcinogenesis.

RATIONALE: Considering that the loss of cell cycle and apoptosis control constitutes a central event in human papilloma virus' (HPV)-mediated carcinogenesis, the reason of this study is to insight to the HPV life cycle. OBJECTIVE: The purpose of the study is to analyze the HPV molecular biology and cervical cancer association. METHODS AND RESULTS: Brief review of current literature on the HPV life cycle and cervical carcinogenesis. DISCUSSION: Among the HPV associated cancers, cervical cancer still ranks number two in the global cancer incidence of women. A central component of the association between HPV and cervical carcinogenesis is the ability of HPV to persist in the lower genital tract for long periods of time without being cleared because of its evasion mechanisms.

Evaluation of the effect of natural and emotional stress of labor on lactation and breast-feeding.

BACKGROUND: The amount of stress experienced by both the mother and fetus during labor and delivery varies considerably and is likely to be different in primiparous and multiparous women as well as in those who receive analgesia during labor and those who do not receive. OBJECTIVE: In this study, we explored relations between stress during birth experience and lactogenesis of 100 women, who experienced vaginal delivery in Department of Obstetrics and Gynecology of University Hospital of Alexandroupolis. METHOD: Stress hormones (cortisol and glucose) were measured in serum (cord and maternal blood) immediately after delivery. Moreover, breast-feeding frequency on day 4, the time when the subjects first felt fullness in the breasts, milk volume on day 4 postpartum and duration of labor were recorded. Also, we recorded maternal exhaustion score during labor and positive and negative affects, posttraumatic stress score and mother-infant bonding rate, with the use of questionnaires. RESULTS: There were significant intercorrelations among the outcome variables. Mothers who experienced pain, exhaustion and negative feelings in a stressful and long labor had delayed onset of lactation. CONCLUSIONS: These results indicate that primiparity, long labor, stress to the mother and fetus during labor and delivery, negative affects and high score of posttraumatic stress are risk factors for delayed lactogenesis.

The effect of the use of a new type of partogram on the cesarean section rates.

OBJECTIVE: To assess the contribution of a new type of partogram, used in labor monitoring, in caesarean section rates. MATERIAL AND METHODS: The study included term singleton uncomplicated pregnancies divided into two groups. Two types of partogram were used in labor monitoring. In the first group, the classical WHO partogram (A) was used. In the second group, a new type of partogram, in which cervical dilatation and the position of descending head (B) (one line) were estimated and reported, was used. The labor duration and caesarean section rates were calculated and compared in the two groups. RESULTS: A statistically significant decrease in labor duration (from the initiation of the active phase of labor to the delivery time) (dt1+dt2+dt3) (p<0.001, A: median: 318.4±10.4 min, B: 246.56±8.28 min) and in caesarean section rates was noted (p<0.001, A: 89 vs B: 49). CONCLUSION: The new type of partogram seems to have potential benefits such as reducing the incidence of prolonged labor and decreasing the caesarean section rates.