Professor Ian Symonds

Background: Ageing, socioeconomic level, obesity, fertility, relaxed natural selection and urbanization have been postulated as the risk factors of ovarian cancer (OC56). We sought to identify which factor plays the most significant role in predicting OC56 incidence rate worldwide. Methods: Bivariate correlation analysis was performed to assess the relationships between country-specific estimates of ageing (measured by life expectancy), GDP PPP (Purchasing power parity), obesity prevalence, fertility (indexed by the crude birth rate), opportunity for natural selection (Ibs) and urbanization. Partial correlation was used to compare contribution of different variables. Fisher A-to-Z was used to compare the correlation coefficients. Multiple linear regression (Enter and Stepwise) was conducted to identify significant determinants of OC56 incidence. ANOVA with post hoc Bonferroni analysis was performed to compare differences between the means of OC56 incidence rate and residuals of OC56 standardised on fertility and GDP respectively between the six WHO regions. Results: Bivariate analyses revealed that OC56 was significantly and strongly correlated to ageing, GDP, obesity, low fertility, Ibs and urbanization. However, partial correlation analysis identified that fertility and ageing were the only variables that had a significant correlation to OC56 incidence when the other five variables were kept statistically constant. Fisher A-to-Z revealed that OC56 had a significantly stronger correlation to low fertility than to ageing. Stepwise linear regression analysis only identified fertility as the significant predictor of OC56. ANOVA showed that, between the six WHO regions, multiple mean differences of OC56 incidence were significant, but all disappeared when the contributing effect of fertility on OC56 incidence rate was removed. Conclusions: Low fertility may be the most significant determining predictor of OC56 incidence worldwide.

Background: Cord drainage in the third stage of labour involves unclamping the previously clamped and separated umbilical cord and allowing the blood from the placenta to drain freely into an appropriate receptacle. Currently there are no systematic reviews of the effects of placental cord drainage on the management of the third stage of labour. Objectives: The objective of this review was to assess the specific effects of placental cord drainage on the third stage of labour, with or without the prophylactic use of oxytocics. Search strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2005), CINAHL (1982 to December 2004) and the National Research Register (December 2004). We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 16 July 2009 and added the results to the awaiting classification section. Selection criteria: Randomised trials involving placental cord drainage as a variable within the package of interventions as part of the management of the third stage of labour. Data collection and analysis: Two review authors independently assessed the quality of trials and extracted data. Main results: Two studies met our inclusion criteria in terms of quality and relevance. Cord drainage could impact the third stage of labour as the results show a statistically significant reduction in the length of third stage of labour (one trial, n = 147, weighted mean difference (minutes) -5.46, 95% confidence interval (CI) -8.02 to -2.90). In the incidence of retained placenta at 30 minutes after birth (one trial, n = 477, relative risk 0.28, 95% CI 0.10 to 0.73) a significant difference was found, but this should be interpreted with caution due to potential intervention bias. Authors' conclusions: It is difficult to draw conclusions from such a small number of studies, especially where the review outcomes were presented in a variety of formats. However, there does appear to be some potential benefit from the use of placental cord drainage in terms of reducing the length of the third stage of labour. More research is required to investigate the impact of cord drainage on the management of the third stage of labour. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Aims: To compare the effectiveness of thermal balloon ablation (TBA) and levonorgestrel intrauterine system (LNG-IUS) in the management of idiopathic menorrhagia and changes in pictorial blood loss assessment chart (PBAC) scores in patients who had failed on oral medical treatment. Methods: Phase III, single-centre, open randomised controlled trial. Following full screening and evaluation of 104 women, 33 were randomised to TBA and 33 to LNG-IUS. Primary outcomes were changes in PBAC scores from baseline to 12 months. Secondary outcomes were changes in haemoglobin and serum ferritin, at six.months, continuation with treatment and hysterectomy rates at two years and changes in PBAC scores at three, six and nine months. Results: All patients randomised had a PBAC score of =120. At all assessment times, median PBAC scores were less than baseline, the greatest reductions being seen at 12 months for both treatments. When the median PBAC for the LNG-IUS (26 (0-68)) was significantly different to the median PBAC for the TBA cohort (62 (0-142)) P<0.001. Irregular bleeding problems were the most common reason for discontinuation of the LNG-IUS and resulted in more women (39.8%) seeking other treatment by two years than the TBA (23.1%) (P<0.05) and more undergoing a hysterectomy (20.7% vs 13.3%, respectively) (p>0.05). Patient acceptability of the LNG-IUS and TBA was similar at 12 and 24.months in terms of their perceived satisfaction of effect on menorrhagia. Conclusions: Both TBA and LNG-IUS achieved significant decreases in PBAC scores, with those for the LNG-IUS being significantly greater at 12 months. However, prolonged days of bleeding resulted in fewer women continuing with the LNG-IUS at two years. © 2007 The AuthorsJournal compilation © 2007 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

OBJECTIVES: Pre-eclampsia (PE) is associated with an increased incidence of cardiovascular disease in later life. Daughters of PE mothers have an increased risk of developing the disease; recent epidemiological data suggest a (grand)paternal contribution. We have directly studied the parents of 673 women with stringently defined PE in relation to their daughters' disease. METHODS: (Grand)parental medical history, current medication and blood pressure (using an Omron 705 automated monitor) were recorded, with obstetric history for the grandmother, including directly verified pregnancy hypertension. RESULTS: The age of the 649 participating grandmothers was 55.5 ± 7.5 years (mean ± SD) and that of the 542 participating grandfathers was 58.0 ± 7.3 years. Essential hypertension (EHT) requiring therapy was present in 23.4% of the grandmothers and 22.8% of the grandfathers. Patients had moderate to severe PE; a quarter were delivered before 34 weeks' gestation. A third of the babies had birthweights below the third centile; the perinatal mortality rate was 2.1%. Grandpaternal absolute systolic pressures and EHT status were highly significant determinants of maternal systolic pressure during gestation (F = 11.8, P < 0.001; F = 8.91, P = 0.003, respectively); maternal body mass index (BMI) had less effect. A similar, less marked, pattern was seen for diastolic pressure (F = 6.01, P = 0.014; F = 11.50, P < 0.0001). Grandmaternal EHT did not influence her daughter's systolic or diastolic pressure (P > 0.2 for both). CONCLUSIONS: A paternal, but not maternal, history of EHT is associated with increased risks of non-pregnant hypertension in the children, the risk being greater in daughters than sons. Pregnancy may unveil or exacerbate this effect, possibly reflecting underlying endothelial vulnerability. © 2007 Lippincott Williams & Wilkins, Inc.

The Genetics of Pre-Eclampsia (GOPEC) collaboration aims to identify genetic factors in U.K. families affected by pre-eclampsia. A number of genetic studies have reported associations with pre-eclampsia, but attempts to replicate these findings have yielded inconsistent results. We describe the results of extensive genotyping of seven candidate genes previously reported as conferring susceptibility to pre-eclampsia. Six hundred fifty-seven women affected by pre-eclampsia and their families were genotyped at 28 single-nucleotide polymorphisms in the genes encoding angiotensinogen, the angiotensin receptors, factor V Leiden variant, methylene tetrahydrofolate reductase, nitric oxide synthase, and TNFa. Genotypes were analyzed by the transmission/disequilibrium test. Genotype risk ratios (GRRs) associated with maternal genotypes had a range of 0.70-1.16; GRRs associated with fetal genotypes had a range of 0.72-1.11. No GRR achieved the prespecified criteria for statistical significance (posterior probability >.05). We conclude that none of the genetic variants tested in this large study of strictly defined pre-eclamptic pregnancies confers a high risk of disease. The results emphasize the importance of conducting rigorously designed studies of adequate size to provide precise genetic risks with narrow confidence intervals, if overreporting of falsepositive results is to be avoided.

In the past, the mainstay of surgical treatment of menorrhagia was hysterectomy. This is an effective form of treatment in terms of outcome but it does carry a degree of morbidity and prolonged convalescence. Endometrial ablation techniques were initially developed using the urological resectoscope, and recently, simpler methods have been developed to strive to obtain high patient satisfaction rates with less associated morbidity. This article looks at the considerations in the development of these new treatments, as well as medical treatment options such as the use of intra-uterine progestogens. © 2004 Elsevier Ltd. All rights reserved.

Over the course of the last two decades hysteroscopy with endometrial biopsy has begun to replace dilation and curettage as the method of choice for the diagnosis of endometrial carcinoma. In the majority of women this can be performed as an outpatient procedure with no loss in diagnostic accuracy. Transvaginal ultrasound measurement of endometrial thickness provides a highly sensitive and less invasive alternative means of assessing the endometrium but has a low positive predictive value for cancer, especially in women taking hormone replacement therapy. The cut-off value used to define normality needs to take into account patient age and ethnic origin. Ultrasound screening may not be suitable for women taking tamoxifen and those with recurrent or late-onset abnormal uterine bleeding.

A first-class maternity service requires effective team working and opportunities for multiprofessional learning. However, it has been found that collaboration and cohesive working between doctors and midwives is not always evident. This paper describes the context for a unique merger of two academic departments, obstetrics/gynaecology and midwifery, with a view to enhancing interprofessional collaboration in teaching and research. Although interprofessional learning, particularly at undergraduate level, can be difficult to design and implement it is argued that it is necessary to enhance multiprofessional teamwork. It was found that a staged programme of action is needed to develop and evaluate curricular initiatives in interprofessional learning. Whilst learning about and valuing each other's roles is as important as sharing curriculum content it can involve an element of risk and considerable resources. Pilot work locally suggests that it is well worth the time and effort involved but long-term success will be dependent upon staff commitment and evaluation of the process as well as the outcomes.

Hysteroscopic examination of the endometrium can be carried out as an outpatient procedure with no loss in diagnostic accuracy and at considerably lower cost than when done as a day-case. Cervical dilation is required in less than 20% of cases and only one-third of patients require local anaesthetic. Over 90% of women find the procedure acceptable and report minimal discomfort. Approximately 50% of women will have some abnormality identified at hysteroscopy of whom 1-2% will have endometrial malignancy. Twenty per cent of patients require subsequent hysteroscopic surgery under general anaesthetic, mostly for the removal of benign lesions. The initial capital investment required to establish a new service is small when compared to the long-term savings on the cost per patient procedure.

Laparoscopy is increasingly being replaced by transvaginal ultrasound and quantitative serum human chorionic gonadotrophin (hCG) measurement in the diagnosis of suspected ectopic pregnancy. For haemodynamically-stable patients, laparoscopic treatment is associated with less morbidity and lower costs than laparotomy. The rate of successful intrauterine pregnancy is higher following linear salpingotomy than salpingectomy. However, conservative surgery also appears to be associated with higher rates of recurrent ectopic pregnancy and is more likely to be complicated by persistent trophoblastic tissue. Medical treatment with local or systemic injection of methotrexate is a suitable alternative for selected patients.

A total of 39 patients with suspected primary (n = 17) or recurrent/residual (n = 22) ovarian carcinoma were investigated by pelvic magnetic resonance imaging (MRI) and immunoscintigraphy using the monoclonal antibody OC-125 labelled with Indium-111. The results of the imaging studies were compared with surgical evaluation and pathological examination of resected material in each case. In patients with suspected primary tumours, the sensitivity and specificity of MRI for the diagnosis of ovarian carcinoma was 37.5 and 66 per cent respectively, and for immunoscintigraphy 75 and 22 per cent. In patients with suspected recurrent disease, the sensitivity and specificity were 88 and 40 per cent for MRI and 82 and 60 per cent for immunoscintigraphy, compared with serum CA125 levels which had a sensitivity of 81 per cent and specificity of 50 per cent. The predictive value of a positive result was 83 per cent for MRI, 87 per cent for immunoscintigraphy and 81 per cent for serum CA125, with a negative predictive value of 50 per cent for all three techniques. These techniques are proving to be the main imaging methods for the assessment of patients with ovarian carcinoma, however, both techniques showed limitations in the detection of very small volume disease and were no more sensitive than serum CA125 in the detection of recurrence.

Monoclonal antibodies recognising a number of antigens are used in the diagnosis and treatment of ovarian carcinoma. Conventional histology and cytology can be supplemented by immunohistology. Antigens shed from tumours are routinely measured in patients sera by monoclonal based assays to monitor disease progression. Radiolabelled antibodies can be used to localise tumour in vivo by gamma camera imaging or intraoperatively using a hand held probe. Antibodies conjugated to radionuclides have been successfully used in the treatment of patients with small volume residual disease and malignant serous effusions. © 1992.

Urinary mucins which express determinants for the anti-breast carcinoma monoclonal antibody, NCRC-11 (IgM), closely resemble the mammary mucins found in milk fat globules and carcinomas. An IgG3 monoclonal antibody, C595, was prepared against urinary mucins isolated on a NCRC-11 antibody affinity column, and this ¿second generation¿ antibody was shown to have a very similar pattern of reactivity to the original NCRC-11 antibody. By immunohistology, the profile of reactivity of both antibodies with tumour and normal tissue specimens was virtually identical. Both antibodies reacted with epithelial mucins isolated from breast tumours or normal urine using an NCRC-11 antibody affinity column, although the antibodies were unreactive with other antigen preparations. Heterologous immunoradiometric assays (¿sandwich¿ tests) confirmed that NCRC-11 and C595 epitopes were co-expressed on the same molecule. C595 antibodies inhibited the binding of radiolabelled NCRC-11 antibodies to antigen, suggesting that the two epitopes were in close topographical proximity. The protein core of the mammary mucins has recently been shown to consist predominantly of a repeated 20 amino acid sequence (Gendler et al., 1988). Peptides with this complete sequence and small fragments were synthesised, and the C595 antibody was found to recognise an epitope within this repeat. The ability to identify and synthesise monoclonal antibody-defined determinants, as well as those in the adjacent or overlapping sequences within the protein core of epithelial mucins, is viewed as a strategy for facilitating the production of antibodies of new and novel specificity to complement the panels of existing anti-breast cancer reagents. © The MacMillan Press Ltd., 1990.

Well organised cervical screening programmes have reduced the mortality from cervical cancer by up to 50% in the developed world. Despite this, questions remain over: high false negative rates; the role of Human Papillama Virus (HPV) testing; and the management of low grade abnormalities. In contrast, the value of mass screening for ovarian cancer remains unproven, although current screening methods can detect early stage disease in asymptomatic individuals. Breast screening does appear to be associated with a reduction in mortality in the long term but paradoxically may increase death rates in young women in the short term. Testing for sexually transmitted infections is effective in reducing morbidity, but tends to be selective at present because of concerns over the cost and psychosocial implications of general, population screening. © 2003 Elsevier Ltd. All rights reserved.

Screening is one of the most often discussed areas of gynaecology today. In this chapter, after a brief review of WHO criteria for a screening programme and relevant statistical terms, the pros and cons of screening are considered. Its role in gynaecological cancers, genetic conditions and chlamydial infection is discussed. Ultrasound and multimodal screening can detect ovarian cancer in asymptomatic women, but there is insufficient evidence on whether screening improves outcome including mortality for women in any risk group. BRCA 1 and 2 screening is offered to women with families in which two or more first-degree relatives are affected by ovarian or premenopausal breast cancer. This gives a 65% chance of identifying a mutation. We have considered some of the interesting developments in cervical screening like PAPNET, thin prep and HPV testing. After discussing some of the controversies in breast cancer screening programmes, the case for introduction of chlamydia screening is debated. © 2001 Harcourt Publishers Ltd.