Editors’ Choice

The editorial meeting to decide the subject of this year’s special issue of BJOG was uncharacteristically short: the recognition of rapid developments in many areas of both obstetrics and gynaecology meant that the idea of having an issue on ‘Emerging Technologies’ was quickly adopted. The chunky size of this issue confirms that the editors were correct in their assessment. The contributors have submitted a substantial series of absorbing reviews and original papers covering a wide range of subjects, all united by their ‘cutting edge’ theme.

Noninvasive prenatal diagnosis

The search for a reliable way of determining fetal genetic status from an easily obtained maternal blood sample containing fetal material has been a major objective in prenatal diagnosis for many years. The ability to use such material for molecular analysis obviates the need for invasive testing, which not only carries a procedure-related miscarriage rate but also causes parental (and not infrequently physician) anxiety. Early efforts concentrated on identifying the few (and sporadic) fetal cells in the maternal circulation. To increase the proportion of fetal cells in a maternal blood sample, a variety of ingenious enrichment techniques were used, such as fluorescence-activated and magnetic-activated cell sorting, immunostaining with fetal haemoglobin antibodies and others. Nevertheless, obtaining a high enough number of fetal cells for reliable analysis remained a major challenge and the possibility of finding fetal cells left over from a previous pregnancy also created uncertainty. The demonstration of the presence of circulating cell-free fetal nucleic acids in maternal plasma by Lo et al. (Lancet 1997;350:485–7) signalled a major change in research direction, and techniques using fetal DNA are now used routinely in some centres for the determination of fetal sex and rhesus D status. The fetal rhesus D status is correctly identified in almost all cases, and more recently, fetal genotyping of other common rhesus antigens has been reported. On page 144, Geifman-Holtzman et al. present a systematic review of the diagnostic accuracy for fetal rhesus C and E determination from fetal cells or free fetal DNA in maternal blood. They found a total of 369 reported samples tested, and while the overall correct identification of fetal genotype was 96% for rhesus C/c and 98% for rhesus E/e using either fetal cells or fetal DNA, all the incorrect results were from studies where fetal cells were used. When restricting the analysis to the 316 cases where fetal DNA from maternal plasma was used, the fetal genotype was correct in 100% of cases. Nevertheless, the authors argue that due to the small number of alloimmunised pregnancies and the large number of gene and antigen rearrangements that exist, the results should mean further study rather than clinical introduction.

It is often surprising to see that such intricate fetal genotyping is possible, yet using fetal DNA for noninvasive prenatal diagnosis of fetal chromosomal aneuploidies is not currently reliable, especially as these constitute the most common indication for chorionic villus sampling or amniocentesis. On page 152, Lo reviews the technical challenges that explain why this has taken so long to develop and how recent advances in techniques make it likely that safer prenatal diagnosis will be available very soon.

High definition chromosome analysis

Although BJOG does not generally accept case reports, the paper by Choy et al. (page 339) highlights an important innovation with potentially wide applicability. We are using the report as a vehicle to introduce readers to comparative genomic hybridisation (CGH). In this technique, samples are placed on a microchip array in which receptors responding only to specific parts of the genome are attached to an electronic grid through which activation of the receptors can be detected. Array-based CGH prenatal diagnosis may offer a number of advantages over traditional cytogenetic analysis by G banding of stained chromosomes inspected down a microscope. The resolution of the latter is not high and detection of subtle chromosomal rearrangements or microdeletions is not always reliable. However, CGH allows researchers to ‘see’ the chromosomes at a much higher resolution, allowing detailed comparison with parental chromosomes and highlighting any changes. Large databases such as DECIPHER (https://decipher.sanger.ac.uk/) can then be consulted to examine the significance of small aberrations. One major drawback of such technology is that miniscule de novo chromosomal changes are not uncommon and, moreover, may not be associated with an abnormal phenotype. In other words, there is a high chance of finding ‘false-positive’ changes of uncertain significance. Accordingly, the authors call for comprehensive studies into array CGH for prenatal diagnosis before the introduction of such technology into a clinical practice.

Latest developments in stem cell technology

Integration of genetic technology into health care to better understand disease raises the possibility of preventing morbidity and even discovering a cure. In particular, stem cell technology appears to hold significant promise. Stem cells are uncommitted pluripotent immortal cells, which under certain conditions have a unique capacity to proliferate into specialised cells that make up the tissues and organs of the body. These characteristics have brought stem cell biology to the forefront of biomedical science and research. This special issue of BJOG ensures you are up to date with the new developments in this arena and their projected benefits. Stephenson et al. on page 158 outline how human embryonic stem cells, obtained from the inner cell mass of a human preimplantation blastocyst generated during an IVF cycle, can be used for in vitro study of disease pathogenesis, modelling of disease progression and drug development. Gucciardo et al. on page 166 explain how fetal stem cells, derived from the placenta, amniotic membranes and fluid or fetal tissues, and blood might be used therapeutically for various genetic, haemopoietic, neurodegenerative, musculoskeletal and even cardiac disorders as well as for tissue engineering. We are sure that, after reading these two reviews, you will appreciate the potentially immense therapeutic possibilities created through advances in this area. However, as genetic and stem cell technology move from the laboratory to the clinical setting, new ethical, social and regulatory challenges will undoubtedly emerge. Healthcare professionals (in particular reproductive and fetal medicine specialists), ethicists, public health policy makers and society in general need to be prepared to face these challenges. We are likely to need another ‘theme issue’ in this area before too long.

Interesting viewing?

On a more clinical note, healthcare professionals are constantly encouraged to adopt a model of care that emphasises active patient involvement and participation, an approach widely known as ‘patient partnership’. The move towards partnership is designed primarily to improve patients’ experience and is reflected in involving and consulting patients at every level of their care including the provision of comprehensive disease-related healthcare information. The partnership agenda, however, raises important questions. How much does the patient actually want to know? To what extent does the patient want to be involved? And what effect will the information provided have on the patient’s experience and the patient–physician relationship?

The study of Ogden et al. published on page 286 illustrates these issues. In a well-conducted, randomised study, the impact on women of viewing their hysteroscopy on a screen in real time was examined. The results make interesting reading and the related Mini Commentary provided by Prof O’Donovan on page 292 is thought provoking. Traditionally, women are encouraged to watch their procedures ‘live’ on screen to promote patient involvement and to act as a distraction to alleviate pain. Rather contradictorily, the Ogden study showed that those who viewed their procedure ‘live’ had similar perception of procedure-related pain, a smaller decrease in their anxiety levels, were less optimistic about the effectiveness of their treatment and felt their physician was less receptive to them during the procedure compared with those who did not view their procedure on screen. The extent to which the study results can be extrapolated to other obstetric and gynaecological outpatient procedures, such as ultrasound-guided invasive prenatal diagnosis, colposcopy and oocyte retrieval, remains unknown. Clearly, future studies that explore the impact of women viewing such procedures on screen on their overall experience and satisfaction are needed. It is conceivable that individualisation of care according to where each woman places herself on the ‘partnership scale’ will emerge as the optimum approach. Such studies will take time to be completed, so in the interim should we advise our patients that ‘I am about to start your hysteroscopy, please look away now?’ Have a read and decide for yourself ….

Endoscopes, fetoscopes and robots

Three reviews show how similar technologies can be applied in very different settings. Advances in laparoscopic equipment and electronics have led to robotic systems, which allow operations to be conducted from a computer console rather than by standing at the operating table. This offers a number of advantages such as enhanced precision and decreasing surgeon fatigue during long operations. The potential to perform operations over long distances (telesurgery) is of particular interest as it could allow subspecialist input into the care of women without either having to travel long distances. As with any technology under development, there are limitations, and for telesurgery a particular problem remains the time delay (or latency) between movements of the surgeons’ hands and the response of the robot. In their review article Robotic Surgery, Schreuder and Verheijen (page 198) present a detailed account of all the issues surrounding the technique. Although they were not able to identify any randomised studies relating to gynaecology, they have assimilated the available literature not only relating to surgery itself but also to anaesthetic considerations. They ask whether the high cost of such systems can be justified and whether virtual reality simulators can help in training.

Fetal surgery is perhaps an equally media-attracting intervention. After a slow beginning, fetoscopy was almost abandoned as advances in ultrasound technology meant that detailed fetal examination could be noninvasive, and procedures such as fetal blood sampling became achievable using fine needles under real-time ultrasound control. Few indications remained for fetoscopic procedures, and the development of the required highly specialised instruments remained impossible until a team of dedicated fetal medicine specialists obtained a European grant and formed the ‘Eurofetus’ collaboration with an endoscope manufacturer. On page 188, Klaritsch et al. provide a highly useful resource: not only does their paper summarise recent developments in fetoscopic interventions but also forms a catalogue of endoscopic tools that are currently available, gives a list of other equipment that is needed and addresses important practical considerations in the running of such a service.

Finally, Pandis et al. on page 214 discuss the particular challenges of laparoscopic surgery in adolescence and highlight the importance of multidisciplinary team work. This makes not only interesting reading but also allows us to plug the 2010 theme issue ‘The gynaecological and reproductive health problems of puberty and adolescence’. Please do send us your best papers for this issue and remember that although they may be held back a little to make the January 2010 print issue, they will appear in ‘earlyview’ shortly after acceptance. We hope you will agree that the added exposure of inclusion in a theme issue is worth the wait.

It is impossible to cover all our theme issue papers in such a short editorial, and we regret not mentioning in more detail others including advances in MRI to determine blood oxygenation levels (Vincent, on page 240) or diagnose gynaecological malignancies (Booth, on page 300); spooky methods of 3D ultrasound, where the viewer is immersed and can move around in a 3D virtual world (Rousian et al., on page 278); the latest developments on using the powerful tool of proteomics in obstetric and gynaecological research (Horgan et al., on page 173) and how it can be applied in biomarker discovery (e.g. in polycystic ovary syndrome; Atiomo et al., on page 137) or elucidation of the pathophysiological mechanisms of the fetal inflammatory response in relation to amnionitis and preterm birth (Buhimschi, on page 257) and many more. All we can suggest is that you read your BJOG from cover to cover. If you do, you will find bonus material including Mini Commentaries and online videos along the way. We hope you enjoy your theme issue on emerging technologies and learn as much from reading it as we did from editing it!