ProfessorTom Bourne, Ph.D., FRCOG

International Ovarian Tumor Analysis Trial (IOTA)
The International Ovarian Tumor Analysis (IOTA) group was founded in 1999 by Dirk Timmerman, Lil Valentin and Tom Bourne. Its first aim was to develop standardized terminology. In 2000, IOTA published a consensus statement on terms, definitions and measurements to describe the sonographic features of adnexal masses, which is now widely used. IOTA now covers a multitude of studies examining many aspects of gynecological ultrasonography within a network of contributing centers throughout the world. Over 30,000 adnexal masses have now been included in the study. Tom Bourne can be seen being interviewed about diagnosing ovarian cancer below.

Having agreed on standardized terminology, the principal IOTA investigators from different centers prospectively collected a large cohort of patients with a persistent adnexal mass. Accurate preoperative discrimination between benign and malignant adnexal masses is known to be of pivotal value in clinical practice. Research has focused on the development of predictive models to estimate the risk of malignancy.

IOTA developed easy descriptors and simple rules that can be used in up to 80% of adnexal masses to correctly classify them as benign or malignant. They were prospectively and externally validated, and proved to have very good performances, close to that of subjective assessment of an expert sonographer. Moreover, they maintain performance in the hands of users with different levels of ultrasound experience. IOTA subsequently published the ADNEX-model - the first predictive multi-class model that is able to differentiate between four subgroups of malignant tumors. This has now been incorporated into a user friendly APP and embedded in to several manufacturers ultrasound machines to enable clinicians to use this easily in the clinic.

Currently IOTA is engaged in several new studies. The group is investigating the long-term behavior of expectantly managed adnexal pathology (IOTA phase 5). This will answer important questions about complications and malignant transformation in masses that are left in situ. Studies are being carried out to determine the best second stage test for masses that are difficult to classify by the existing models, for instance by MRI (IOTA-MRI). Other studies focus on the identification of new potential biomarkers (trans-IOTA) to be incorporated in diagnostic models.

Today there are over 50 clinical units contributing to IOTA studies, nearly every continent is represented. The group is multidisciplinary and involves gynecologists, radiologists, oncologists as well as physicists and biologists. The group believes that good communication between all these disciplines is how ideas can be turned into improvements for patients.

The Ph.D. fellow responsible for this project is Dr Nina Cooper. She is specifically running pIOTA examining cysts in pregnancy and MyIOTA - establishing diagnostic criteria and management for cysts in Womens under the age of 18.


ASSESSMENT OF BIOMARKERS IN PREGNANCY OF UNKNOWN LOCATION AND ECTOPIC PREGNANCY (ABPEP)


A pregnancy of unknown location (PUL) is a phenomenon in early pregnancy where a woman has a positive pregnancy test but we cannot see where the pregnancy is with an ultrasound scan. The concern is that we may be missing an ectopic pregnancy (a potentially dangerous situation where the pregnancy is not in the womb).

Streamlining care for these patients

The management of women with a PUL or an ectopic pregnancy can be prolonged and variable. We now know many PUL and ectopic pregnancies can be managed safely with an expectant (a wait and see) approach and not everyone will require medical or surgical intervention. We are carrying out research that assesses a mathematical model which helps us provide individualised care and see which women are suitable for this approach. We are incorporating these models into user friendly APP's to make the use of these models user friendly.

Monitoring pregnancy of unknown location (PUL) and ectopic pregnancy without visiting the clinic

Currently, monitoring for both these conditions requires blood tests that must be taken at an early pregnancy clinic. We are developing a novel technique using urine rather than blood sample analysis that may result in fewer visits to the clinic.

Looking at novel biomarkers for PUL and ectopic pregnancy patients

We are also carrying out research looking for new hormones or markers in blood, urine or vaginal swab samples which may assist us in treating women with a PUL or ectopic pregnancy. This could lead to fewer blood tests, scans and visits to the Early Pregnancy Unit for women, which we know can be emotionally demanding.

Approved study number: 14/NS/1078- NRES Committee North Scotland

The post doctoral. fellow responsble for this project is Dr Chris Kyriacou.

THE PSYCHOLOGICAL IMPACT OF EARLY PREGNANCY EVENTS

Early pregnancy losses are common, with miscarriage affecting 25% of women who have been pregnant by 39 years of age. They are unique in encompassing both bereavement and a personal clinical pathology. For this reason, an understanding of the emotional implications for the woman cannot easily be extrapolated from our understanding of other illness behaviour or grief reactions.

Grief, to different degrees, and depending on the circumstances of the loss, in response to the loss of a potential child and imminent parenthood, is perhaps inevitable. Some level of anxiety relating to ones future ability to procreate is also an anticipated response.

However, small-scale projects thus far have demonstrated that pregnancy losses are also recognized precipitants of longer-term psychological disorder, including anxiety, depression and post-traumatic stress.

This research project, supported by Imperial College Healthcare Charity, assesses the frequency and severity of psychological morbidity in women, and their partners and in comparison to a control group of women with healthy early pregnancies. We use self-report questionnaires, which are sent to participants 1, 3 and 9 months after a loss. By collating demographic and clinical data, we aim to assess for risk factors predicting psychological sequelae. With a better understanding of their impact, clinical management strategies may be tailored to address the womans emotional as well as physical needs. There would also be the potential to better target support and counseling.

As of the start of May 2015, we had recruited just over 600 women across 3 sites (St Mary's, Queen Charlotte's and Chelsea & Westminster). The next stage of the project is to validate the results from the self-report questionnaires by performing interviews on a portion of respondents.

The clinical research Ph.D fellow responsible for this project is Dr Nina Parker.

PREDICTING ADVERSE PREGNANCY OUTCOME FROM EARLY PREGNANCY (EPOS)

In a recent meta-analysis by the ESHRE early pregnancy special interest group it has been suggested that bleeding and pain in early pregnancy may be associated with a significant risk of later complications in pregnancy including intra-uterine growth restriction (IUGR), pregnancy induced hypertension and pre-term labour. These data are retrospective and the characterisation of the events described is suboptimal. For example, the term bleeding in pregnancy could mean anything from a single spot of blood to heavy bleeding and passing large clots. There were no attempts to quantify pain or duration of episodes of pain and bleeding. Similarly the presence of sub-chorionic haematoma has been related to both miscarriage and premature labour. However the relative importance of the size, location and timing of these lesions is largely not known.

There is a clear need to prospectively evaluate the long-term impact of events in early pregnancy. The clinical relevance of such a study is that women can be selected as being at risk and so offered appropriate fetal surveillance and potential early intervention when necessary. For example, those identified at risk of pre-term birth may be offered surveillance of the length of their cervix, as well as being given vaginal progesterone. However, it is clearly inappropriate and would create a vast amount of work with associated costs if all women who suffered an early pregnancy complication were offered serial scans. We urgently need to understand which early pregnancy events represent a risk to the fetus in later pregnancy and direct any surveillance strategies towards those women selected to be at risk.

The EPOS study has been designed to address these issues. We aim to assess the risk of miscarriage in pregnancies complicated by events in the first trimester as well as evaluate their impact on the longer term pregnancy outcomes. Using this information we will develop a risk prediction model to aid in risk stratification and therefore planning of clinical care. The addition of biomarker information may contribute to such a model to aid prediction of outcomes.

The official National Institutes of Health definition of a biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker can be used for diagnosis of a disease, identification of individuals at risk for disease prevention, as a potential drug target, or as a potential marker for a drug response or to predict outcome. Therefore the role of identifying potential biomarkers has greatly increased, particularly as these have not previously been assessed thoroughly in early pregnancy. These can aid diagnosis, assess severity, help in monitoring of conditions and possibly aid in response to treatment. Biomarkers within the context of this study may help in the metabolic and microbiological mapping of pregnancies and aid in the development of a risk model and therefore increase its sensitivity and specificity.

The high throughout of a diverse selection of patients at Queen Charlottes & Chelsea Hospital has enabled the study to thus far be successful in recruiting over 600 participants. Each participant is recruited in early pregnancy, from as early as 5 weeks gestation, and scanned every 2 weeks in the first trimester. Then a routine dating and anomaly scan is performed. Following this an additional third trimester growth scan is performed. Data with regards to patient demographics, symptoms, ultrasound scan findings and pregnancy outcome is collected. In addition to this, samples of blood, urine and a vaginal swab are taken at a minimum of three and maximum of six time points throughout pregnancy. The aim of this is to create a longitudinal metabolic map of pregnancies as well as identifying potential biomarkers for adverse pregnancy outcome, such as miscarriage, pre-term birth and pre-eclampsia.

The clinical research Ph.D. fellow responsible for this project is Dr Margot Pikovsky

DOCTORS VIEWS AND EXPERIENCES OF THE MEDICAL COMPLAINTS SYSTEM (the IMPACT study)

Since the recommendations from the Shipman inquiry have been implemented, the number of formal complaints being investigated by the GMC has doubled. There has been recent media coverage highlighting a rise in complaint of 23% in just one year.

There is also a view that there are significantly more informal and formal internal investigations held in response to complaints raised about doctors both from patients and colleagues.

There is little or no information on the impact of these changes on individual doctors and on the way they practice medicine. Whilst the process aims to protect patients, the end result on balance may be doctors who have been made unwell and who practice medicine more defensively. It is therefore important that we better understand these issues, both for patients and doctors.

We are interested in investigating

i) the psychological impact of different levels of inquiry for the individual doctor

ii) how the process of being investigated for a complaint affects future practice

iii) whether those who have been subject to a complaint think they have been treated reasonably and fairly and

iv) ways of predicting those who are particularly at risk of getting into difficulty so that support can be offered at an earlier stage. We hope that these findings will be used to steer future policy. At the conclusion of the study, we will publish a report which will be available to all participants.

The first paper from this study can be read by clicking on the following link. The paper was associated with significant media interest both in the UK and elsewhere