Expression of neuronal markers in the endometrium of women with and those without endometriosis.

STUDY QUESTION: How do the expression patterns of neuronal markers differ in the endometrium of women with and without endometriosis? SUMMARY ANSWER: The neuronal markers, PGP9.5, NGFp75 and VR1, are expressed in the endometrium at levels that do not differ between women with and without endometriosis. WHAT IS KNOWN ALREADY: Aberrant neuronal growth within the uterus may contribute to abnormal fertility and uterine dysfunction. However, controversy still exists as to whether aberrant innervation in the endometrium is associated with gynaecological pathology such as endometriosis. This may reflect the use of subjective methods such as histology to assess the innervation of the endometrium. We, therefore, employed a quantitative method, western blotting, to study markers of endometrial innervation in the presence and absence of endometriosis. STUDY DESIGN, SIZE, DURATION: This study included 45 women undergoing laparoscopic examination for the diagnosis of endometriosis. Endometrial samples were analysed by western blot for the expression of neuronal and neurotrophic markers, PGP9.5, VR1 and NGFp75. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Endometrial pipelle biopsies were obtained from patients with (n = 20, study group) and without (n = 25, control group) endometriosis. Tissue was analysed by immunohistochemistry and western blot analysis for the expression of pan-neuronal marker, PGP9.5, sensory nociceptive marker, TPVR1, and low-affinity neurotrophic growth factor receptor, NGFRp75. MAIN RESULTS AND THE ROLE OF CHANCE: PGP9.5, NGFp75 and VR1 were expressed in the endometrium of women, independent of the presence of endometriosis. Furthermore, the expression level of PGP9.5, VR1 and NGFp75 did not alter between the two cohorts of women. LIMITATIONS, REASONS FOR CAUTION: Studies of this nature are subject to the heterogeneous nature of patient population and tissue samples despite attempts to standardize these parameters. Hence, further studies using similar methodology will be required to confirm our results. WIDER IMPLICATIONS OF THE FINDINGS: Our results highlight that sensory neuronal markers are present in women with and without endometriosis. Future work will assess what the targets of the endometrial nerves are and investigate their function, their impact on endometrial biology and, in particular, whether aberrant neuronal function, rather than the mere presence of neuronal function, could be the root cause of subfertility and/or pain affecting many endometriosis sufferers. Our results do not, however, confirm the previous paradigm of increased innervation in the endometrium of women with endometriosis, nor the use of nerve cell detection from pipelle biopsies to diagnose endometriosis.

To close or not to close? A systematic review and a meta-analysis of peritoneal non-closure and adhesion formation after caesarean section.

Many gynaecologists do not currently close the peritoneum after caesarean section (CS). Recently, several studies examining adhesion formation after repeat CS appear to favour closure of the peritoneum after caesarean section. We performed a systematic review of the current available evidence with regard to the long-term outcome, mainly in terms of adhesion formation after closure versus non-closure of peritoneum during CS. We undertook a literature search between January 1995 and February 2008 using MEDLINE, Pubmed, EMBASE, Cochrane central controlled trials register and Cochrane pregnancy and childbirth group trials register. We also had searched all the references cited in the relevant studies. Both English and non-English language papers were included. Prospective studies which compared peritoneal closure versus non-closure during CS in terms of adhesion formation were included. Studies were included if they had a primary objective to examine adhesion formation in a repeat caesarean section, had a clear study design, had an adhesion scoring system, excluded patients who had adhesions in the primary caesarean section or interim surgeries after the primary caesarean section, and had no usage of anti-adhesion agents in the primary caesarean section. Retrospective studies which were performed by case-notes review alone, were excluded. Eleven studies were identified via our search strategy. Five were retrospective and six were prospective. Out of the eleven studies, three satisfied the inclusion criteria and were included (n=249); two studies were follow-ups of RCTs and one was not randomised. Out of 249 women included in the analysis, 110 had peritoneal closure during CS whereas the other 139 did not have peritoneal closure. Meta-analysis was performed using the two randomised studies plus (i) the unadjusted estimate from the non-randomised study and (ii) the reported adjusted estimate, adjusted for baseline differences in the groups. Non-closure of the peritoneum during CS resulted in a significantly increased likelihood of adhesion formation in both meta-analyses--OR (95% CI): (i) 2.60 (1.48-4.56) and (ii) 4.23 (2.06-8.69). This systematic review has demonstrated that according to current data in the literature, there is some evidence to suggest that non-closure of the peritoneum after caesarean section is associated with more adhesion formation compared to closure.

Can formal education and training improve the outcome of instrumental delivery?

OBJECTIVE(S): The primary objective was to examine the effect of formal education and training on instrumental delivery with respect to its success rate and associated neonatal and maternal morbidity. The secondary objective was to determine factors that could influence the success rate of instrumental delivery. STUDY DESIGN: Prospective case-control study with historical controls set in a teaching hospital in Sheffield. The prospective group included all women who had instrumental deliveries between 1 November 1999 and 29 February 2000. The control group included all women who delivered between 1 February 1997 and 1 February 1998. An educational package involving formal postgraduate training and self-directed learning were introduced in the time period between the prospective and the control groups. Medical notes were reviewed in the historical controls. For both the control and prospective groups, the following patient characteristics were recorded: maternal age, parity, whether or not onset of labour was induced, use of oxytocin in the second stage of labour, delay in the second stage, operator grade, vaginal findings at delivery and the use of epidural analgesia. RESULTS: The overall failure rate was not different in the prospective group (16%) compared with the control group (18.5%). However, the introduction of an educational package was associated with significant decrease in maternal morbidity associated with cervical, severe labial and high vaginal tears (Odds Ratio (OR) 0.29, CI 0.09-0.97) and neonatal morbidity associated with admission to SCBU (OR 0.72, CI 0.02-0.60), severe neonatal scalp injury (OR 0.14, CI 0.02-0.98) and facial injuries (OR 0.02, CI 0.01-0.04). The factors identified to affect the success of instrumental deliveries were: OP and OT positions of the baby at delivery (OR 0.28, CI 0.17-0.44) and inexperienced operators (OR 0.11, CI 0.02-0.58). CONCLUSION: In this study, formal education and training of medical staff did not influence the success rate of instrumental delivery but was associated with improved safety for both mother and baby.

The correlation of adhesions and peritoneal fluid cytokine concentrations: a pilot study.

BACKGROUND: Intra-abdominal adhesion formation and reformation after surgery is a significant cause of morbidity. The greatest problem after the surgical removal of adhesions is their reformation. We examined the concentrations of interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha in the peritoneal fluid throughout the 48 h post-operative period following adhesiolysis, and correlated the results to the extent of adhesion reformation. METHODS: Peritoneal fluid, collected from eight patients following laparoscopy and again at 12, 36 and 48 h after surgery, was analysed using enzyme-linked immunosorbent assay (IL-1 and IL-6) and bioassay (TNF-alpha). At 48 h, a second look laparoscopy was performed to inspect the pelvis for adhesion formation/reformation. RESULTS: Three patients had adhesion reformation >10% at 48 h after surgery. The mean adhesion score 48 h after adhesiolysis was 5 (range 0-17). The mean reduction in adhesion score was 88% (range 83-100%). Newly formed adhesions were filmy, relatively soft and avascular in nature. Adhesion reformation of >10% was associated with (i) high concentrations of IL-6 at 12 h (P < 0.01) and (ii) high concentrations of IL-1 at 48 h (P < 0.001). CONCLUSIONS: Results from this preliminary study suggest that future treatment strategies for adhesion prevention could be aimed at the control of cellular mediators in the peritoneal fluid during the initial adhesion formation period.

IL-1, IL-6 and TNF-alpha concentrations in the peritoneal fluid of women with pelvic adhesions.

BACKGROUND: Pelvic adhesions are a significant cause of morbidity and are associated with infertility and pain. The three pro-inflammatory cytokines interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha are involved in adhesion formation/reformation. METHODS: The concentration of these three cytokines was examined in the peritoneal fluid of women undergoing laparoscopy, in order to examine the factors affecting their concentrations, with specific reference to the presence or absence of adhesions. RESULTS: We found that the concentration of TNF-alpha in the peritoneal fluid was significantly correlated to the menstrual cycle day (P < 0.01), with increasing concentration as the menstrual cycle progressed from the follicular to the luteal phase. In contrast, IL-1 and IL-6 levels did not show any variation throughout the menstrual cycle. Increased TNF-alpha was found in patients with pelvic adhesions compared with those with normal pelvis; the concentration of TNF-alpha was highest in mild compared with severe adhesions. In contrast, IL-1 concentration was higher in the presence of severe adhesions. IL-6 levels were significantly correlated with the grade of endometriosis (P < 0.05), but there were no significant correlations of either TNF-alpha or IL-1 concentrations with the various grades of endometriosis. CONCLUSION: The exact role of TNF-alpha and IL-1 in adhesion formation is still unknown, but the results from this study suggest that their concentration in the peritoneal fluid is associated with the degree of adhesions present.

Peritoneal healing and adhesion formation/reformation.

Intra-abdominal adhesion formation and reformation after surgery is a cause of significant morbidity, resulting in infertility and pain. The understanding of the pathogenesis of adhesion formation and reformation especially at the cellular and molecular level can help to further develop more effective treatments for the prevention of adhesion formation and reformation. Following an injury to the peritoneum, fibrinolytic activity over the peritoneal surface decreases, leading to changes in the expression and synthesis of various cellular mediators and in the remodelling of the connective tissue. The cellular response to peritoneal injury and adhesion formation and reformation are reviewed. Analysis of the available literature data on the cellular mediators in the peritoneal fluid showed variation in results from different investigators. The potential sources of variability and error are examined. It is still unclear if there is significant individual variation in the peritoneal response to injury.

The changing nature of elective laparoscopic surgery: a review over a 7 year period in a reproductive surgery unit.

There was a significant increase in the number of laparoscopic procedures performed in the Reproductive and Surgery Unit at the Jessop Hospital for Women over the 7 year period from 1991 to 1997. The three most common procedures were adhesiolysis/salpingo-ovariolysis, treatment of endometriosis and ovarian drilling, which together constituted over 80% of all cases. The duration of surgery and the complexity of the cases gradually increased with time. The determinants of patients staying overnight after laparoscopic surgery in decreasing order of importance were: (i) whether they had undergone surgery in the morning or in the afternoon; (ii) the operating time; and (iii) the number of entry ports used. Most (75%) of the laparoscopic procedures were performed or supervised directly by a consultant. In this study period the major complication rate was 0.7%.

Management of anti-Rhesus-D antibodies in pregnancy: a review from 1994 to 1998.

OBJECTIVE: To review our management of anti-Rhesus-D antibodies in pregnancy over a 5-year period in order to assess possible changes in the management or prognosis which may have developed with time. METHOD: Retrospective analysis of prospectively collected data from 31 pregnancies with maternal anti-D levels >4 IU/ml and in which the fetus was Rhesus positive. RESULTS: There were a total of 30 amniocenteses, 8 cordocenteses, and 54 fetal blood transfusions performed. When undertaken as the first procedure, the mean gestational age at amniocentesis was 30 weeks as compared with 25 weeks for fetal blood sampling/transfusion (p < 0.05). The median anti-D level at the first procedure was 24 IU/ml for amniocentesis and 64 IU/ml for fetal blood sampling. Of the 54 blood transfusions, 43 were intravascular, 4 were intraperitoneal, and 7 transfusions were both intravascular and intraperitoneal. CONCLUSIONS: Intravascular as opposed to intraperitoneal transfusions were found to be the main method of transfusion in the later years in this study, a finding which was expected with improved sonographic equipment. Apart from this, management and prognosis of anti-D red cell isoimmunisation in pregnancy have remained relatively stable since the 1980s. Amniocentesis was useful in the management of such pregnancies, especially as an initial procedure in the cases with a lower initial anti-D level. In this series 90% of the fetuses requiring blood transfusion, but were without hydrops, survived, whereas this was about 70%, if they had become hydropic (this latter figure was reduced by 2 hydropic deaths before 20 weeks' gestation in the same very severely affected woman).

Peritoneal closure--to close or not to close.

Peritoneal closure is a controversial issue among obstetricians and gynaecologists. This article reappraises the issue of peritoneal closure. We conducted a thorough literature search using Medline, Pubmed and Embase as well as a hand-search for all references quoted in the relevant papers. The routine non-closure of the peritoneum reduces operation time by an average of 6 min. Most studies showed no difference in the other outcome measures including infection/febrile episodes, analgesic/anaesthetics requirement, bowel function restoration, post-operative stay and adhesion formation. There are insufficient data concerning adhesion formation. In conclusion, apart from a slightly shorter operation time associated with non-closure of the peritoneum, many studies showed no difference in short-term morbidity in the closure and the non-closure group. More studies are needed to examine the long-term morbidity associated with the closure or the non-closure of the peritoneum.

Obstetric and neonatal outcome in women with a history of recurrent miscarriage: a cohort study.

Obstetric and neonatal outcomes of women who had a history of recurrent miscarriage were compared with a control population from 1 January 1992 to 30 June 1998. Amongst a total of 162 pregnancies which progressed beyond 24 weeks gestation in women with a history of recurrent miscarriage, there were four perinatal deaths and 16 babies were admitted to the special care baby unit. The rates of preterm delivery (13%), small-for-gestational-age (13%), perinatal loss (2.5%) and Caesarean section (36%) were significantly (P < 0.05) higher than those of the control group (3.9, 2.1, 1 and 16.7% respectively). The ratio of male to female babies was equal. There was no significant difference in the incidence of hypertension or diabetes between the two groups. Patients with recurrent miscarriage represent a population at high risk of obstetric problems and close surveillance in the antenatal period is therefore required.

Coagulation activation, fibrinolysis and inhibitors in neonates.

Enhanced coagulation activation with reduced antithrombin III (ATIII) activity was seen in healthy neonates. Although systemic tissue plasminogen activator (t-PA) and urokinase-like plasminogen activator (u-PA) levels showed no significant differences from normal adults, enhanced fibrinolysis was indicated by elevated D-dimer and low plasminogen levels in the neonates in this study. Enhanced fibrinolysis observed was countered by elevated plasminogen activator inhibitor-I (PAI-1) levels, a trend similar to that observed in the amniotic fluid during labour. The elevated PAI-1 level seen in neonates may have a beneficial effect in preventing haemorrhage in the neonatal period. The haemostatic and fibrinolytic mechanisms studied in normal pregnancy neonates were similar to neonates born to gestational diabetes mellitus (GDM) mothers. Further studies need to include neonates with poor outcome and low Apgar score to assess their haemostatic status.