My research interests can conveniently be divided into 5 broad categories namely pre-eclampsia, fibroid disease, gynaecological surgery and general obstetrics and gynaecology research, and more recently I have established international collaborations.. Below I have described each by topic, included my collaborators and funding sources where appropriate, and key references relating to the work.

Research on Pre-Eclampsia

Topic: Trophoblast Research
Collaboration:
(St George’s, Dept of Biochemistry).
Funding:
The Wellcome Trust –
Brief resume of the research:

The fundamental aim of my basic research has been to attempt to elucidate the regulatory mechanisms involved in human implantation and trophoblastic invasion, as defects in these processes are likely to be the basis of a wide range of pregnancy disorders including pre-eclampsia, intrauterine growth restriction and miscarriage, and perhaps even some cases of subfertility. Ethical constraints and inaccessibility of the site of implantation has rendered studies on human implantation especially difficult. Hence my work in the late-90’s  concentrated on  the development of human models of implantation and trophoblastic invasion – we used DNA transfection technology to establish unlimited supplies of human trophoblast cell lines; and developed a 3-dimensional trophoblast-decidua co-culture explant model for studies of implantation and trophoblastic invasion.

Additional studies of trophoblast phagocytic activity as a potential mechanism of trophoblastic invasion ensued. I believe that phagocytosis is the central mechanism by which trophoblasts invade the maternal decidua, and current and future work is aimed at demonstrating the in-vivo events, and elucidating the regulatory mechanisms. This work came to a halt when my then PhD student / Research Fellow (Dr Mei Choy) left and failure to secure funding meant that I could not immediately replace her and continue with this line of enquiry. However, I am collaborating with Dr Nigel Page, Senior Lecturer at Kingston University (and a former collaborator when he was post-doctoral fellow at Reading University) to resurrect this research as very little advances have occurred in the areas of trophoblastic invasion over the past 5 years.

Topic: Genetic mapping of early pregnancy events
Collaboration:
University of Reading
Funding:
MRC Programme Grant awarded to Professor Lowry.
Brief resume of the research:

To date most pregnancy markers have been identified serendipitously. It is therefore possible that there are other markers of pregnancy that are yet to be discovered which may prove vastly superior to those currently known. We have used RNA finger-printing as a strategy for identifying novel pregnancy markers in disease and health. So far our approach has been to study genes that are switched on or off at various gestations during human pregnancy, starting as early as possible. The studies utilize fetal tissue from pregnancy termination.

This approach has already led us to the identification of NKB as a potential mediator of the pre-eclampsia syndrome. We have also discovered novel tachykinins, and this latter discovery opens up a whole novel area of enquiry which has not existed before, and this may shed new light on the patho-physiology of pre-eclampsia, and indeed other pathologies of pregnancy.

Topic: Skin capillary density in normal and diseased pregnancy
Collaboration:
St George’s, Dept of Clinical Pharmacology.
Funding:
British Heart Foundation – £125k over 2.5 years.
Brief resume of the research:

Women who develop pre-eclampsia during pregnancy are known to be at increased risk of developing cardiovascular disease in later life, including essential hypertension. Reduced capillary density (rarefaction) occurs in association with essential hypertension, and may pre-date the onset of the hypertension. Women who develop pre-eclampsia may have markers that pre-date the onset of the disease, such as abnormal capillary density. We have used intravital capillary video-microscopy to study functional (baseline) and structural (after maximization with venous congestion) skin capillary density in normal pregnancy and in pregnancies complicated by pre-eclampsia. The Research Fellow who conducted this work, Dr Vivek Nama, has created a “normogram” for capillary density in normal pregnancy, and after data analysis we will know if we can use capillary density to predict pre-eclampsia. We are seeking further funding to continue with the studies.

Research on Fibroid Disease

Topic: Clinical research on fibroid disease
Collaboration:
St George’s, Interventional Radiology.
Funding:
None current – imminent submission of major grant application to NIHR
Brief resume of the research:

Fibroids have a cumulative incidence rate by age 49 of 70% in white and more than 80% in black women, and thus are the commonest tumour during reproductive life. Although benign, in 50% of women they cause heavy periods, pelvic pain, pressure symptoms, and may compromise reproduction. They are the commonest indication for hysterectomy in the UK and USA, and therefore have a major impact on women’s health and quality of life, and cost the NHS more than £100m in hysterectomies alone.  Much is unknown about fibroid disease: why they form; the extent to which they compromise reproduction; why some are symptomatic and others quiescent; and best practice in clinical management.  New uterus-preserving treatments such as uterine artery embolization (UAE) and focussed ultrasound surgery have yet to be rigorously evaluated against conventional myomectomy.

My areas of clinical research interest in fibroid disease include the following:

  • UAE versus myomectomy in the treatment of symptomatic fibroids: over the past few years I have collaborated with Professor Anna-Maria Belli (Interventional Radiology) on a programme of research comparing UAE to myomectomy with respect to a clinical, quality of life and economic evaluation. We have published more than 4 papers on some of our work already, and additional papers are in preparation. More importantly, we have proved the feasibility of a larger national trial, and she and I are part of a national group which, following submission of a preliminary application, has been invited to submit a major grant application (£2.5m) to HTA to conduct a national multi-centre trial of UAE versus myomectomy.
  • Optimization of surgical procedures in conventional myomectomy to reduce blood loss, reduce incidence of` adhesions and maximise reproductive potential:  I have developed innovative surgical techniques that lead to significantly reduced blood loss, and therefore enable me to offer myomectomy to women with massive fibroids who would be offered hysterectomy by most gynaecologists – these include the use of subserosal surgicell to seal serosal incisions, and the administration of vasopressin and tranexamic acid to drastically reduce blood loss, as well as the use of pre-myomectomy embolization in Jehova’s Witnesses and in women with previous or potentially very challenging myomectomies. I am currently writing two papers on these innovations, although it is difficult to conduct standard randomized trials because of obvious ethical constraints. I have recently edited a book on fibroid disease which reflects on my interests in fibroid disease.

Topic: Laboratory research on fibroid disease
Collaboration:
Royal Marsden, Sutton.
Funding:
None.
Brief resume of the research:

Although a common tumour, much remains unknown about fibroids: in this relatively new collaboration the principal aim is to establish the genetics and molecular basis of the development of uterine fibroids. We have not yet succeeded in securing funding for this research, but we have started work and already published a paper (see below).

Research involving Gynaecological Surgery

Topic: Hysterectomy: total versus subtotal.
Collaboration:
Mayday University Hospital; University of Sussex.
Funding:
Previously funded by the NHS R&D. None current.
Brief resume of the research:

Historically, the uterus has been regarded as the regulator and controller of important physiological functions, a sexual organ, a source of energy and vitality, and a maintainer of youth and attractiveness. Little wonder therefore that removal of such an organ can and does generate fierce debate and controversy. In the late 80’s and early 90’s arguably the greatest controversy regarding hysterectomy was whether subtotal hysterectomy (when the cervix was conserved) conferred advantages over the total procedure (when the cervix is removed). I secured a £115k grant from the then NHS R&D programme to address the issue, and in October 2002 we published a major paper in the New England Journal of Medicine in which we summarized our key findings. In addition to the publication, the significance of our findings has been recognized by the award of numerous prizes at conferences for “best papers” presented (see “Academic / Research Accolades” page 26 ). This work formed the basis of an MD thesis for my research fellow, Dr Ranee Thakar, which she successfully defended in June 2003. In 2008 we completed a ten-year follow up of the women included in the original study, and have just had a paper published in Obstetrics & Gynecology, and again we were awarded prizes at three international meetings when we presented our findings. By this research we have resolved the controversy of total versus subtotal hysterectomy, and therefore an evidence base for best practice. We have also provided data that has not previously existed on long term outcomes of hysterectomy.

There are still many issues to explore and refine, and our current interest is in optimizing anaesthesia for hysterectomy: in essence we hypothesize that the type of anaesthetic used during open abdominal hysterectomy influences early cognitive function and recovery rates, and to that end we are about to embark on a trial of general anaesthesia versus combined spinal/epidural anaesthesia once we can resolve ethics issues. I am also interested in the issue of why there is such a wide variation in hysterectomy rates between hospitals in one region, between regions and indeed between countries.

Research in General Obstetrics & Gynaecology

Topic: Physical activity as an aid to smoking cessation in pregnancy
Collaboration:
St George’s, Psychology; UCL;  and others
Funding:
Health Technology Assessment – £1.2m over 4 years.
Brief resume of the research:

Smoking during pregnancy is the most important cause of preventable harm to babies and infants.  Stopping smoking reduces this harm and also reduces women’s risks of developing other harmful effects of smoking (e.g. cancer). Smoking cessation counselling can help pregnant smokers to stop but success rates are low and few women attend such treatments. In addition, many pregnant women prefer not to use pharmaceutical aids to smoking cessation. Moderate intensity activity (e.g. brisk walking)  is recommended for nearly all women as part of antenatal care. For non-pregnant women, supervised exercise (e.g. treadmill walking) can help them to stop smoking. Pilot work by the research team has shown that many pregnant women would be happy to join a research study testing exercise added to standard smoking cessation support.

The primary objective of the proposed study is:

1. To compare the efficacy of individual behavioural support plus a physical activity intervention relative to individual behavioural support alone among pregnant women on smoking cessation at the end of pregnancy.

Secondary objectives are:

2. To make comparisons as in 1. above: at four weeks of quitting and six months following the birth.

3. To compare between groups in 1. above: changes in self-reported physical activity levels between baseline and end of treatment and end of pregnancy.

4. To compare between groups in 1, above: during the first week of smoking asbtinence, self-reported tobacco withdrawal symptoms, urges to smoke, perceived stress and self-confidence for quitting smoking.

5. To investigate whether physical activity levels are associated with smoking abstinence at end of pregnancy (or within two weeks of the birth) and six months following the birth.

Topic: Research on postnatal sexual health
Collaboration:
Brunel University; Mayday University Hospital.
Funding:
None current.
Brief resume of the research:

The area of postnatal sexual health is under-researched, and research is under-funded. I have had a major interest in this area for just under a decade now, and via un-funded research collaborations within and out-with St George’s we have published a number of key papers. I am anxious now to seek funding to formalize this research and explore two specific areas: the male perspective on perinatal sexual health, and a more rigorous study of the impact of assisted vaginal delivery on postnatal sexual health. More robust and validated questionnaires and tools (such as more sophisticated endo-anal ultrasound scans) are now available to facilitate research in this area. There is also a growing recognition by funding bodies that this area is under-resourced, which may just render it more likely to secure funding.

Topic: Bacterial vaginosis in human pregnancy.
Collaboration:
St George’s, Genito-Urinary Meidince; St George’s, Obstetrics & Gynaecology.
Funding:
Previously funded by NHS R&D. None current.
Brief resume of the research:

I no longer actively participate in this area of research, which is now the research interest of my former Research Fellow and now consultant colleague Mr Austin Ugwumadu. In collaboration with Dr Phillip Hay (GU Medicine) I supervised Mr Ugwumadu’s research in this area and he was awarded his PhD in 2006. Papers were published in high impact factor journals including the Lancet (see below).

International Collaborations

Collaboration: Bengaluru, India.
Funding:
Current funding from the organization “ARTIST” – see below.
Brief resume of the research:

In 2007 I was appointed Scientific Director of “ARTIST” [Asian Research and Training Institute for Skill Transfer], an organization based in Bengaluru, India, dedicated to the promotion of high quality clinical and laboratory research in India, and subscribing to the philosophy of translational research. I have been instrumental in developing research programmes in areas of particular relevance to obstetrics in India as follows: gestational diabetes and iron deficiency anemia in pregnancy.

Gestational diabetes mellitus: The research on diabetes is currently aimed at optimizing screening and diagnostic tools for gestational diabetes. We have recently submitted a paper to Obstetrics & Gynecology in which we report that the NDDG criteria for the diagnosis of gestational diabetes miss a significant proportion of women warranting treatment, and that the Carpenter & Coulston criteria are a better discriminator, especially in an Indian population where the incidence of gestational diabetes is high (approx 16% versus 3.5% in the West). We are now conducting comparative studies of glucose loads used in the oral glucose tolerance test in pregnancy. In the long term we plan to customize screening and diagnostic criteria to the Indian population.

Iron deficiency anemia in pregnancy: Evidence shows that the Iron and Folic Acid (IFA) programmes introduced some 30 years ago to eradicate iron deficiency anemia (IDA) in pregnancy have failed, as the prevalence of IDA has risen over the past three decades. Our own data based on rural and urban populations confirm this. We have initiated research programmes based on the use of intravenous iron sucrose to eradicate IDA.