Healing after Resection of Colonic Endometriosis and Growth Factor-enriched Agents: An Experimental Rat Model.

STUDY OBJECTIVE: To examine the potential beneficial effect of platelet-rich plasma (PRP) and fibrin sealant (TISSEEL; Baxter Healthcare Corporation, Deerfield, IL) on bowel wound healing after shaving of an experimentally induced endometriotic lesion. DESIGN: A single-blind, randomized study (Canadian Task Force classification I). SETTING: A certified animal research facility. ANIMALS: Thirty female Sprague-Dawley rats. INTERVENTIONS: Experimental colonic endometriosis was induced by transplanting endometrial tissue to all animals (first surgery). Thirty rats were then randomized to 1 of 3 groups according to treatment; PRP (group 1, n = 10), fibrin sealant (group 2, n = 10), or no agent (group 3, n = 10) was applied after shaving of the endometriotic nodule (second surgery). MEASUREMENTS AND MAIN RESULTS: Colonic endometriosis was successfully induced in all subjects. Four days after the second surgery, the animals were euthanized, and microscopic evaluation was performed. The pathologist was blinded to the treatment method. Histopathologic analysis revealed that compared with the control group, collagen disposition was found in a significantly higher expression in both the PRP and fibrin sealant groups (p = .011 and p = .011, respectively). Distortion of the integrity of the colon layers was statistically more pronounced in the control group compared with the fibrin sealant group (p = .033), whereas greater new blood vessel formation was observed in the fibrin sealant group compared with the control (p = .023). No histologic evidence of residual or recurrent disease was detected. CONCLUSION: Both PRP and fibrin sealant appear to be safe and associated with improved tissue healing during shaving for the excision of colonic endometriosis, attributed to the enhanced collagen disposition, neovascularization, and protection of the integrity of colon layers. Clinical trials are warranted to confirm the feasibility of PRP and fibrin sealant in the clinical setting.

Corifollitropin alfa compared with follitropin beta in GnRH-antagonist ovarian stimulation protocols in an unselected population undergoing IVF/ICSI.

Recombinant DNA technologies have produced Corifollitropin alfa (CFa) used during IVF/ICSI in order to keep the circulating FSH levels above the threshold necessary to support multi-follicular growth for a week. In this prospective case-control study, we compared 70 participants treated with 150 µg CFa combined with 150 IU of follitropin beta (study group) with 70 subfertile participants with matching baseline characteristics, conforming with the same inclusion criteria and treated with an antagonist protocol using follitropin beta (control group). Live birth was the primary outcome, while secondary outcome measures were IVF/ICSI cycles characteristics, including adverse events and complications. Live birth was determined in reduced rates in the study compared to the control group, reaching statistical significance [6/70 versus 20/70, p = 0.002], as also in the respective number of clinical pregnancies [9/70 versus 23/70, p = 0.005], although the incidence of miscarriage was similar for both groups [6/70 versus 5/70, p > 0.99]. Most of the secondary parameters examined were similar between groups. Logistic regression revealed that protocol and AFC had a direct impact on live birth. Ovarian stimulation with CFa does not seem to constitute an equally effective method as compared with follitropin beta to be offered in a general subfertile population seeking IVF/ICSI treatments.

Endometrial injury for RIF patients undergoing IVF/ICSI: a prospective nonrandomized controlled trial.

To evaluate the effect of endometrial injury on clinical outcomes in subfertile women with repeated implantation failures (RIF) undergoing assisted reproduction. In this prospective nonrandomized controlled trial, 103 subfertile women with RIF were included. Fifty-one underwent endometrial injury through hysteroscopy in the early follicular phase of the previous cycle and 52 underwent the standard protocol without any intervention. Live birth and miscarriage were the primary outcomes. Clinical and in vitro fertilization (IVF) cycle characteristics, were also compared between groups. Both groups were comparable in terms of baseline and cycle characteristics. Live birth rates were significantly higher in the study, compared with the control group (18/51 vs. 8/52, odds ratio (OR) = 0.25; 95% confidence interval (CI) = 0.10-0.64; p = 0.020), although miscarriage rates were similar (7/51 vs. 10/52, OR= 0.25; 95%CI= 0.12-0.66; p = 0.452). The rest of the outcomes parameters were comparable between groups. Logistic regression analysis revealed that endometrial injury and duration of subfertility were independent predictors of live birth after control of other variables (OR = 2.818; 95%CI = 1.044-7.605; p = 0.041 and OR = 0.674; 95%CI = 0.461-0.985, p = 0.042, respectively). Endometrial injury induced through office hysteroscopy in the preceding cycle in subfertile women with RIF improves live birth rates.

Mild versus conventional antagonist ovarian stimulation protocols in expected normal responders undergoing IVF/ICSI: a case-control study.

Mild controlled ovarian hyperstimulation (COH) protocols combining clomiphene citrate (CC) or letrozole with gonadotropins were introduced as an effective alternative of conventional COH in normal responders undergoing IVF/ICSI. In this case-control study, we compared 41 participants treated with a mild stimulation protocol receiving gonadotropins combined with either CC (n = 24) or letrozole (n = 17) with 71 subfertile participants with matching baseline characteristics, conforming with the same inclusion criteria and treated with a conventional antagonist protocol. Live birth was determined in reduced rates in the study group compared to the control group, reaching marginal statistical significance [4/41 versus 19/71, p = 0.050], as also in the respective number of clinical pregnancies [6/41 versus 22/71, p = 0.054], although the incidence of miscarriage was similar for both groups [2/41 versus 5/71, p = 0.714]. Most of the secondary parameters examined, favored the conventional antagonist protocol. There was no difference in any of the outcomes reported between the three different stimulation groups in post-hoc analysis. Mild stimulation regimens with the aid of either CC or letrozole employing GnRH antagonists do not seem to constitute an equally effective method as compared to the conventional antagonist protocol to be offered in good prognosis subfertile women seeking an induced cycle toward IVF/ICSI.

OCT-4 and DAZL expression in precancerous lesions of the human uterine cervix.

AIM: To determine whether octamer-binding transcription factor 4 (OCT-4) and deleted in azoospermia like (DAZL) are expressed among cells with human papilloma virus (HPV) infection and cervical intraepithelial neoplasia (CIN) lesions and quantify their relative expression when compared with normal cervical cultures. METHODS: Cervical cells derived from normal cell cultures, HPV lesions and CIN lesions were cultured in Dulbecco's modified Eagle's medium supplemented with 20% amniotic fluid and 5 ng/mL basic fibroblast growth factor at 37°C and humidified 10% CO2 in air. Real-time polymerase chain reaction (PCR) was carried out using G6PD as a reference. We used REST for statistical analysis of real-time PCR. RESULTS: Whereas DAZL was not expressed either in normal cultures or HPV and CIN lesions, OCT-4 was expressed in all examined cell lines. Moreover its relative expression was significantly upregulated among cultures of HPV-infected cells (RE, 11.003; 95%CI: 0.054-36 704.527, P = 0.042), an observation that was also close to statistical significance among cultures of CIN lesions (P = 0.066). CONCLUSION: The relative expression of OCT-4 is upregulated during the early, preinvasive stages of cervical carcinogenesis. Future studies should investigate its potential as a screening marker and as a possible target of therapy.

The effect of vaginal lubrication on unsatisfactory results of cervical smears.

OBJECTIVE: Speculum lubrication with water-based gels before cervical smear sampling has been investigated and commented on thoroughly during the last decade. The present meta-analysis was based on randomized and quasi-randomized control trials and evaluated its impact on unsatisfactory cytologic results. We also assessed its efficacy in producing lower pain scores during speculum insertion. MATERIALS AND METHODS: We searched MEDLINE (1966- 2013), Scopus (2004-2013), Clinicaltrials.org (1997-2013), Popline (1973-2013), Cochrane Central Register of Controlled Trials (CENTRAL) (1999-2013), and Google Scholar (2004-2013) engines for published randomized control trials, as well as the reference lists from all the included studies. RESULTS: Five randomized trials and 2 quasi-randomized trials were included in the present review involving 8,717 women. Unsatisfactory results based on conventional cytology did not statistically differ among procedures performed with lubricated speculums and those without (odds ratio = 0.94, 95% CI = 0.64-1.37). Consequently, pain scores also did not differ significantly among the 2 groups (odds ratio = -0.37, 95% CI = -1.10 to 0.36). Only 2 studies evaluated unsatisfactory results on liquid-based cytology, precluding firm results. CONCLUSIONS: It seems that speculum lubrication does not interfere with the rates of unsatisfactory results when examination is based on conventional cytology. Conversely, however, the limited number of studies evaluating speculum lubrication on liquid-based cytology precludes firm conclusions.

Fetal alcohol spectrum disorders and cognitive functions of young children.

Fetal alcohol spectrum disorder (FASD) is one of the main causes of mental retardation worldwide. Nearly 1% of children in North America are affected from antenatal exposure to ethanol. Its economic burden in industrialized countries is increasing. It is estimated that, in the United States, 4.0 billion dollars are annually expended in the treatment and rehabilitation of these patients. As a pathologic entity, they present with a broad symptomatology. Fetal alcohol syndrome (FAS) is the most readily recognized clinical manifestation of these disorders. Various factors seem to contribute in the pathogenesis of FASD-related cognitive disorders. During the last 20 years, several potential pretranslational and posttranslational factors have been extensively studied in various experimental animal models. Research has specifically focused on several neurotransmitters, insulin resistance, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, abnormal glycosylation of several proteins, oxidative stress, nutritional antioxidants, and various epigenetic factors. The purpose of the present review is to summarize the clinical manifestations of this disorder during childhood and adolescence and to summarize the possible pathophysiologic and epigenetic pathways that have been implicated in the pathophysiology of FASD.

Electrosurgical bipolar vessel sealing for vaginal hysterectomies.

BACKGROUND: Vascular clamping of the uterine vessels and the ovarian and broad ligaments during vaginal hysterectomies is more difficult than in traditional abdominal hysterectomies. We aimed to assess the efficacy of electrosurgical bipolar vessel sealing systems (EBVS) as an adequate alternative to traditional suturing that could facilitate the accomplishment of securing the vascular pedicles. METHODS: We searched MEDLINE (1966-2013), Scopus (2004-2013), POPLINE (1973-2013), Cochrane Central (1999-2013) and Google Scholar (2004-2013) search engines, along with reference lists from all included studies. RESULTS: Eight randomized trials were selected, including 772 patients. We found that operative duration did not differ significantly among women treated with EBVS and those treated with traditional suture ligation (MD -16.86, 95 % CI -34.77, 1.05). Intraoperative blood loss on the other hand was significantly lower in the EBVS-treated group (MD -49.47, 95 % CI -67.60, -31.35). There were no significant differences in intraoperative complication rates (OR 0.96, 95 % CI 0.46, 2.01), major postoperative complication rates (OR 0.61, 95 % CI 0.29, 1.32) or minor complications (OR 1.63, 95 % CI 0.67, 3.92). CONCLUSION: Our meta-analysis showed that EBVS seem to produce less intraoperative blood loss during vascular clamping, without significantly lowering intraoperative time or complication rate. However, the heterogeneity of included studies preclude firm conclusions. Future studies examine consistently their safety, and cost-effectiveness, and whether the application of such units will enhance the rates of vaginal hysterectomies.

Analgesic options for placement of an intrauterine contraceptive: a meta-analysis.

OBJECTIVE: Several randomised controlled trials have been published in the last few years which evaluated the efficacy of various analgesics in reducing visual analogue (VAS) pain scores during intrauterine device (IUD) placement. Their results seem to be conflicting and inconclusive. METHODS: We searched Medline (1966-2013), Scopus (2004-2013), Clinicaltrials.org (1997-2013), Popline (1973-2013), Cochrane CENTRAL (1999-2013) and Google Scholar (2004-2013) engines for published randomised controlled trials, as well as the reference lists from all electronically retrieved studies. RESULTS: Thirteen studies, involving 1353 women, were finally included in the present meta-analysis. Among the products used, and with respect to their mode of delivery, only paracervical lidocaine was effective in producing lower VAS pain scores related to tenaculum placement (mean difference [MD]: - 20.54; 95% confidence interval [CI]: - 39.92, - 1.15) and IUD insertion (MD: - 28.99; 95% CI: - 53.14, - 4.84). Misoprostol produced higher VAS pain scores for the immediate post-insertion period (MD: 2.83; 95% CI: - 0.79, 6.45) and it caused various side effects. CONCLUSION: Paracervical administration of lidocaine prior to IUD insertion reduces VAS pain scores. In view of the small number of studies assessing its efficacy further studies should confirm our findings.

Searching HPV genome for methylation sites involved in molecular progression to cervical precancer.

Background: Human Papilloma Virus has been considered as the main cause for cervical cancer. In this study we investigated epigenetic changes and especially methylation of specific sites of HPV genome. The main goal was to correlate methylation status with histological grade as well as to determine its accuracy in predicting the disease severity by establishing optimum methylation cutoffs. Methods: In total, sections from 145 cases genotyped as HPV16 were obtained from formalin- fixed, paraffin-embedded tissue of cervical biopsies, conization or hysterectomy specimens. Highly accurate pyrosequencing of bisulfite converted DNA, was used to quantify the methylation percentages of UTR promoter, enhancer and 5' UTR, E6 CpGs 494, 502, 506 and E7 CpGs 765, 780, 790. The samples were separated in different groupings based on the histological outcome. Statistical analysis was performed by SAS 9.4 for Windows and methylation cutoffs were identified by MATLAB programming language. Results: The most important methylation sites were at the enhancer and especially UTR 7535 and 7553 sites. Specifically for CIN3+ (i.e. HSIL or SCC) discrimination, a balanced sensitivity vs. specificity (68.1%, 66.2% respectively) with positive predictive value (PPV) and negative predictive value (NPV) (66.2%, 68.2% respectively) was achieved for UTR 7535 methylation of 6.1% cutoff with overall accuracy 67.1%, while for UTR 7553 a sensitivity 60.9%, specificity 69.0%, PPV=65.6%, NPV=64.5% and overall accuracy=65.0% at threshold 10.1% was observed. Conclusion: Viral HPV16 genome was found methylated in NF-1 binding sites of UTR in cases with high grade disease. Methylation percentages of E6 and E7 CpG sites were elevated at the cancer group.

Estradiol Pretreatment in an Ultrashort GnRH Combined with a GnRH Antagonist Protocol in A Cohort of Poor Responders Undergoing IVF/ICSI: A Case-control Study.

AIM: To provide results of the use of estradiol pretreatment in a combination of an ultrashort gonadotropin-releasing hormone (GnRH) agonist and antagonist protocol, in an attempt to improve the clinical outcomes in "poor responders", according to the Bologna criteria, undergoing in vitro fertilization (IVF). PATIENTS AND METHODS: We applied estradiol pretreatment to 20 participants before the initiation of a combination of an ultrashort GnRH agonist plus an GnRH antagonist protocol followed by high doses of gonadotropins; the control group consisted of 20 subfertile participants with matching age, body mass index (BMI), basal follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH), antral follicle count (AFC) and cause of subfertility, conforming with the same inclusion criteria and treated with a fixed GnRH antagonist protocol. The primary outcome measure was live birth, while the secondary outcomes included embryological and cycle parameters. RESULTS: Live birth was determined in reduced rates in the study compared to the control group (0/20 vs. 3/20, p=0.231) as also in the respective number of clinical pregnancies (2/20 vs. 5/20, p=0.407) and cancellations (10/20 vs. 6/20, p=0.197), but none of these differences reached statistical significance. Also, most of the secondary parameters studied were similar for both groups. CONCLUSION: The study protocol does not seem to constitute an equally effective method compared to the GnRH antagonist protocol in the selected study population. The presented dissimilar results with those reported so far in the literature are possibly attributed to the small sample size and the strict criteria applied when labeling participants as "poor responders".

Double versus single cervical cerclage for the prevention of preterm births.

OBJECTIVE: To evaluate the effectiveness double cervical cerclage in reducing antenatal complications and improve perinatal outcomes. METHODS: We searched Medline, Scopus, Clinicaltrials.org, The Cochrane Central Register of Controlled Trials and Google Scholar search engines. RESULTS: Six studies were included that involved 880 women. Double cerclage was significantly superior to single cerclage in reducing preterm births <34 weeks (734 cases, OR 0.59, 95% CI 0.40, 0.86) and preterm births <28 weeks (645 cases, OR 0.43, 95% CI 0.26-0.73). It also significantly increased the gestational age (380 cases, MD 2.63, 95% CI 0.87, 4.39). However, as a technique, it failed to improve the rates of preterm births <37 weeks (740 cases, OR 0.98, 95% CI 0.72, 1.34) the incidence of chorioamnionitis (740 cases, OR 0.83, 95% CI 0.51, 1.36) and the occurrence of preterm premature rupture of the membranes (796 cases, OR 1.32, 95% CI 0.95, 1.82). CONCLUSIONS: It seems that double cerclage effectively increases the gestational age at delivery and decreases the rates of extremely premature births. However, as a procedure, it does not reduce the incidence of antenatal morbidity or the neonatal death rates. Further research is needed in the field as our meta-analysis is limited by the small number of enrolled studies.

Risk factors for severe perineal lacerations during childbirth.

BACKGROUND: Severe perineal lacerations represent a significant complication of normal labor with a strong impact on quality of life. OBJECTIVES: To identify factors that lead to the occurrence of severe perineal lacerations. SEARCH STRATEGY: We searched MEDLINE, Scopus, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, Google Scholar and reference lists from all included studies. SELECTION CRITERIA: We included prospective and retrospective observational studies. DATA COLLECTION AND ANALYSIS: Predetermined data were collected and analyzed with the Mantel-Haenszel fixed-effects model or the DerSimonian-Laird random-effects model. MAIN RESULTS: The meta-analysis included 22 studies (n=651,934). Women with severe perineal tears were more likely to have had heavier infants (mean difference 192.88 g [95% CI, 139.80-245.96 g]), an episiotomy (OR 3.82 [95% CI, 1.96-7.42]), or an operative vaginal delivery (OR 5.10 [95% CI, 3.33-7.83]). Epidural anesthesia (OR 1.95 [95% CI, 1.63-2.32]), labor induction (OR 1.08 [95% CI, 1.02-1.14]), and labor augmentation (OR 1.95 [95% CI, 1.56-2.44]) were also more common among women with perineal lacerations. CONCLUSIONS: Various factors contribute to the occurrence of perineal lacerations. Future studies should consistently evaluate all examined parameters to determine their possible interrelation.

First versus second stage C/S maternal and neonatal morbidity: a systematic review and meta-analysis.

The rates of cesarean section at full cervical dilatation (second stage cesarean sections) are currently increasing. The purpose of the present study is to compare maternal and neonatal morbidity and mortality among cases offered cesarean section at full dilatation to those offered cesarean section prior to full dilatation. We searched Medline, Scopus, Clinicaltrials.org, Popline, Cochrane CENTRAL, and Google Scholar search engines, along with reference lists from all included studies. The RevMan 5.0 software was used for all analyses. Primary maternal outcomes were defined as death, ICU admission and need for transfusion, while primary neonatal outcomes were defined as death, neonatal unit admission and 5min Apgar score less than 7. Ten studies were finally retrieved involving 23,104 singleton childbearing women (18,160 operated in the first stage and 4944 in the second stage of labor). Second stage cesarean section seems to lead to higher maternal admissions to ICU (OR 7.41, 95% CI 2.47-22.5) and higher transfusion rates (OR 2.60, 95% CI 1.49-2.54). Neonatal death rates were also increased (OR 5.20, 95% CI 2.49-10.85) along with admissions to neonatal unit (OR 1.63, 95% CI 0.91-2.91) and rates of Apgar score less than 7 in 5min (OR 2.77, 95% CI 1.02-7.50). Second stage cesarean section seems to result significantly increased morbidity for both mothers and neonates. It seems that a direct evaluation with forceps and vacuum extractors is imperative in order to establish its place in modern evidence-based practice.

Nodal, Nanog, DAZL and SMAD gene expression in human amniotic fluid stem cells.

The aim of this study was to investigate the expression of Nodal (NODAL Homolog (mouse), Nanog (Nanog Homeobox), DAZL (Deleted in Azoospermia Like) and SMAD (SMAD Family member) genes and their potential role in the regulation of self-renewal in human amniotic fluid-derived stem cells. In this experimental study human amniotic fluid-derived stem cells were analyzed for messenger RNA expression of Nodal. Immunocytochemistry also was performed to determine Nanog and DAZL. SMAD genes expression analysis was performed using cDNA Microarray analysis. Nodal mRNA was positively expressed in all samples of amniotic fluid derived stem cells. Amniotic fluid-derived stem cells showed strong immunoreactivity for molecular markers of undifferentiated human embryonic stem cells including Nanog and DAZL. Among the 8 SMAD genes expressions analyzed SMAD1, SMAD2, SMAD3, SMAD4 and SMAD7 showed positive expression. In conclusion amniotic fluid-derived stem cells seem to express Nodal, Nanog and DAZL and it speculated that the regulation of self-renewal in AFSc could be similar as in human embryonic stem cells.

Acceptance of a post-partum influenza vaccination (cocooning) strategy for neonates in Greece.

Young infants are at increased risk for influenza-associated serious illness, onset of complications, utilization of health-care services, and hospitalization. We investigated the feasibility and acceptance of an influenza vaccination (cocooning) strategy by household contacts implemented in a maternity hospital and the neonatal unit of a pediatric hospital in Athens. A total of 224 mothers (mean age: 30.2 years) who gave birth to 242 neonates were studied. Of them, 165 (73.7%) mothers were vaccinated. Multiple logistic regression revealed that statistically significant factors associated with increased vaccination rates among mothers were: being of Roma origin (p-value=0.002), being an immigrant (p-value=0.025), giving birth to a neonate with birth weight <2500g (p-value=0.012), and residing in a family with ≥4 family members (p-value=0.017). Of the 224 fathers, 125 (55.8%) received the influenza vaccine. Fathers of neonates whose mothers were vaccinated had 6-fold higher vaccination rates compared to fathers of neonates whose mothers refused vaccination (p-value<0.001). Overall, influenza vaccine was administered to 348 (46.9%) of a total of 742 household contacts of the 242 neonates. Upon entering the 2011-2012 influenza season, 51 (22.7%) of 224 families had all household contacts vaccinated against influenza (complete cocoon). Among parents, the statement "I do not want to receive the vaccine" was the prevalent reason for declining influenza vaccination, followed by the misconception "I am not at risk for contacting influenza" (41.1% and 38.2%, respectively).