To study whether expectant management is an alternative to treatment with systemic MTX in a single dose im regimen in women with an EP and low but plateauing serum hCG concentrations in terms of tubal rupture, future pregnancy, health related quality of life and costs.

Norah M van Mello1*, Femke Mol1, Albert H Adriaanse2, Erik A Boss3, Antonius B Dijkman4, Johannes PR Doornbos5, Mark H Emanuel6, Jaap Friederich7, Loes Leeuw-Harmsen8, Jos P Lips9, Evert JP van Santbrink10, Harold R Verhoeve11, Harry Visser12, Willem M Ankum1, Fulco Veen13, Ben W Mol1 and Petra J Hajenius1

Patients with ectopic pregnancy (EP) and low serum hCG concentrations and women with a pregnancy of unknown location (PUL) and plateauing serum hCG levels are commonly treated with systemic methotrexate (MTX). However, there is no evidence that treatment in these particular subgroups of women is necessary as many of these early EPs may resolve spontaneously. The aim of this study is whether expectant management in women with EP or PUL and with low but plateauing serum hCG concentrations is an alternative to MTX treatment in terms of treatment success, future pregnancy, health related quality of life and costs.

Simultaneously with this trial, another trial is ongoing in the United Kingdom [20]. This placebo controlled trial has a similar objective, uses the same inclusion criteria and interventions (single shot MTX im and expectant management). In the UK trial, however, surgical intervention is installed in both treatment groups if inadequately declining serum hCG concentrations occur after one week of follow up. In our study, these treatment failures are treated with additional MTX injections. In the near future, meta analysis of the results of both trials will provide guidance on the present management dilemmas in women with EP or PUL with low and plateauing serum hCG concentrations.

Recent research suggests that given inter-observer variability in ultrasound measurements

and the greater variation in early embryonic growth than has hitherto been assumed, a more

conservative approach to the diagnosis of early pregnancy loss is warranted.

The studies from Imperial College London, Queen Mary, University of London and the

Katholieke Universiteit Leuven, Belgium published in the November 2011 issue of

Ultrasound in Obstetrics and Gynaecology concluded that current definitions used to

diagnose miscarriage could lead to an incorrect diagnosis and they call for clearer evidence-

based guidance on detecting miscarriage through ultrasound scans.

Having carefully considered these papers, we recommend adoption of the following interim

guidance with immediate effect:

1. Ultrasound diagnosis of miscarriage should only be considered with a mean

gestation sac diameter >/= 25mm (with no obvious yolk sac), or with a fetal pole with

crown rump length >/=7mm (the latter without evidence of fetal heart activity)

2. A transvaginal ultrasound scan should be performed in all cases

3. Where there is any doubt about the diagnosis and/or a woman requests a repeat

scan, this should be performed at an interval of at least one week from the initial scan

before medical or surgical measures are undertaken for uterine evacuation. No

growth in gestation sac size or CRL is strongly suggestive of a non-viable pregnancy

in the absence of embryonic structures.

These revised values for ‘mean gestation sac diameter’ and ‘crown rump length’ do not imply

that previously used values were wrong, nor that diagnosis of miscarriage in the past has

been unsafe, This interim guidance suggests a more cautious approach is warranted,

pending more definitive data becoming available. It extends the criteria included in the

RCOG Green Top Guideline No 25, which recommended a conservative approach with

mean gestation sac diameter <20mm or fetal CRL <6mm.

Christoph Lees MRCOG on behalf of the RCOG Ultrasound Advisory Group

Kim Hinshaw FRCOG Lead author, Green Top Guideline No. 25

Philip Owen FRCOG Chair, RCOG Guidelines Committee

David Richmond FRCOG RCOG Vice President (Standards)

19th October 2011

Notes

The Ultrasound Advisory Group has representation from the Society and College of Radiographers,

International Society of Ultrasound in Obstetrics and Gynecology, British Maternal-Fetal Medicine

Society, British Medical Ultrasound Society and Royal College of Radiologists. This guidance is

endorsed by BMUS, and by the Council of the Society and College of Radiographers.

It was a detailed and varied programme which involved not only a look at where we are at now but actively invited volunteers to engage with us in creating our forthcoming publication.

The afternoon focused on person centered listening and how to ask open ended questions as part of the counselling skills module of our training programme.

The day passed very quickly and for those who could stay on a little, ended after a very pleasant meal at the Watermill Inn. If you have considered volunteering but just not got around to filling out a volunteer interest form, then we want you to know we always have space for one more volunteer. You can download the VIF form here and we’d love to have you on board.

Here are some images of the day.

The Ectopic Pregnancy Trust is thrilled to offer you our new design Charity Christmas cards, for the second year. These high quality cards in three different designs are offered in return for a donation of £4.99 per pack.

Each pack contains 10 quality cards in one of three designs,

1. Bringing Home the Tree: 2. Kings of the Orient: 3. Winter Berries

Every card  has the legend that its purchase has supported The Ectopic Pregnancy Trust. Just as importantly, each one discreetly displays the link to our website and details of how to contact us, so your festive gesture will also promote the organisation among friends, family and colleagues who may in turn be able to direct others to us for the help and support we offer in the future.

Please consider ordering our cards to send in 2011.

Ordering is simple. You do this by making a one off donation for the suggested amount of £4.99 per pack and selecting option AA, from the additional details drop down menu. Then contact us telling us the donation you have made and the quantity of packs you’d like to order and in which designs. We’ll tie up your donation with your order and get them out to you by return.

New for 2011 we also have calendars. These do not carry the EPT logo but do raise income for us and are available for £4.99

We hope you’ll be as delighted with our 2011 designs as we are.

A systematic review of the evidence in the literature (not including new the new data from Imperial college) concludes that the evidence base that has been used to derive the current miscarriage guidelines is based on insufficient data, poor quality studies and so cannot be relied upon in all cases. This view is supported by an opinion paper by Professor Tom Bourne that highlights the problem further and again illustrates that the cut-off values for gestation sac and embryo size may lead to a viable pregnancy being wrongly diagnosed as a miscarriage.

Three papers are also published by the London-Leuven research group based at Imperial College London and the Katholieke University in Leuven, Belgium. These represent the largest study published on the ultrasound based diagnosis of early miscarriage and include over a one thousand women.

The findings of these papers can be summarized into four important points:

1. The current UK guideline used to define miscarriage states an empty gestation sac with mean sac diameter (MSD) of over 20 mm can be classified as miscarriage. The study shows this is associated with a 0.5% risk of misclassifying a viable pregnancy as a miscarriage. The confidence intervals show that at worst the false positive rate at this cut-off could be as high as 3.0%.

2. For an MSD cutoff of 16 mm as used in the USA, the false positive rate for miscarriage is 4.4% and may be as high as 8.4%.

3. Current guidance that an absence of MSD growth may be a sign of miscarriage. The published studies show that this is not the case and that there may be little or absent growth over several days and still a pregnancy can be viable. So an absence of growth in either an embryo or gestation sac is not a definitive sign of miscarriage.

4. There is variation in how different clinicians will measure any given gestation sac or embryo. This is important as it may mean that an MSD measurement of 20 mm may in fact be 16 mm – leading to a higher risk of the pregnancy being misdiagnosed as a miscarriage.

5. The number of pregnancies this may have been affected by this or might be relevant to in the future is not accurately known.

It is very important to put these papers in context for both clinicians and patients. What these papers DO NOT say is that the diagnosis of miscarriage for the vast majority of women who have had or will have a miscarriage is likely to be incorrect. These papers relate to the specific situation where a women undergoes an ultrasound scan and a gestations sac is visualized, but no embryo with a heartbeat is seen. Furthermore they apply to relatively small gestation sacs of under 25 mm. The papers do not suggest there is any problem when a diagnosis of miscarriage is made in the presence of either gestations sacs with an MSD of greater than 25 mm or embryos that are more than 7 mm in size.

However these data are important and show that current criteria for the use of ultrasound to diagnose miscarriage cannot exclude the possibility of misdiagnosis. The authors suggest that the guidance be changed on the basis of this new information in order to avoid the possibility of error.

Accuracy of first-trimester ultrasound in the diagnosis of early embryonic demise: a systematic review. Jeve Y, Rana R, Bhide A, Thangaratinam S. Ultrasound Obstet Gynecol 2011. http://doi.wiley.com/10.1002/uog.10108

Limitations of current definitions of miscarriage using mean gestational sac diameter and crown–rump length measurements: a multicenter observational study. Abdallah Y, Daemen A, Kirk E, Pexsters A, Naji O, Stalder C, Gould D, Ahmed S, Guha S, Syed S, Bottomley C, Timmerman, Bourne T. Ultrasound Obstet Gynecol 2011: http://doi.wiley.com/10.1002/uog.10109

Gestational sac and embryonic growth are not useful as criteria to define miscarriage: a multicenter observational study. Abdallah Y, Daemen A, Guha S, Syed S, Naji O, Pexsters A, Kirk E, Stalder C, Gould D, Ahmed S, Bottomley C, Timmerman D, Bourne T. Ultrasound Obstet Gynecol 2011: http://doi.wiley.com/10.1002/uog.10075

Clinical implications of intra- and interobserver reproducibility of transvaginal sonographic measurements of gestational sac and crown–rump length at 6–9 weeks’ gestation. Pexsters A, Luts J, van Schoubroeck D, Bottomley C, van Calster B, van Huffel S, Abdallah Y, D’Hooghe T, Lees C, Timmerman D, Bourne T. Ultrasound Obstet Gynecol 2011: http://doi.wiley.com/10.1002/uog.8884

For decades experts have been prevented from fully understanding the bacteria as they have been unable to manipulate the genome of chlamydia trachomatis (C. trachomatis).

Now researchers in Southampton have made a significant breakthrough in accessing the chlamydial genome and believe it could pave the way for more effective treatment of the disease.

The research was carried out at the Molecular Microbiology Group at the University of Southampton in conjunction with the department of virology at the Ben-Gurion University of the Negev in Israel.

Professor Ian Clarke, from the University of Southampton, said: “We, together with our colleagues in Israel, discovered that by treating the chlamydia with calcium ions we were able to introduce a piece of foreign DNA.

“This will open up the field of chlamydia research and will enable a better understanding of chlamydial genetics. It could lead to the development of new approaches to chlamydial vaccines and therapeutic interventions.”

Their paper detailing the breakthrough in the study of chlamydia is published in the Public Library of Science journal PLoS Pathogens and carried as a news story in the UK.

The Event will this year be hosted by Les Dennis and promises to be a great night of laughs and music and a time to remember. It will begin with an invitation to light a candle in memory of the babies which have been lost. The concert will then deliver a great line up of talent including Stefan Booth, Belle Humble, Tupele Dorgu (Coronation Street and Waterloo Road) and Lisa Scott Lee (Steps).

The Baby Loss Awareness Campaign  promotes the campaign which highlights the all to common occurrence of baby loss and is a collaboration between 4 sister charities and 1 not for profit organisation: the Miscarriage Association, The Ectopic Pregnancy Trust, SANDS, ARC and Babyloss.com.

The evening is designed to raise your spirits whilst also raising awareness.

Visit the Baby Loss Awareness Campaign website for information about what might be going on in your area

Tickets cost £12  Book your ticket.

The Baby Loss Awareness Campaign is a collaboration of charities and not for profit organisations who facilitate those whose lives have been touched by the loss of a baby during pregnancy or just after birth to unite with others across the UK, to show their support for the Baby Loss Awareness campaign 2011, which focuses on International Pregnancy and Infant Loss Awareness Day on October 15th.

As in previous years, the campaign encourages a number of Wave of Light and other events across the UK. To see if there is an event near you, check out the Official Website of the founding charities and not for profit organisation, at the Baby Loss Campaign Website events page.

Whether you decide to participate in an organised event, quietly light a candle or not, we hope the day passes peacefully for all and that it brings with it another little piece of healing.

So how does an evening of entertainment, champagne, canapés and tastings to kick the Christmas season off to a brilliant start sound? What’s even better; is 100% of ticket sales will go to charity – and you can decide which charity benefits (providing they are registered with theBigGive.org.uk  and of course we hope if you go along, you’ll choose The Ectopic Pregnancy Trust.

For every £50 ticket you purchase, you will receive a £50 charity voucher at the party, to give to any charity registered with theBigGive.org.uk.

So, grab your girlfriend(s) and the boys for that matter, and book some tickets. Tickets will go on sale on the Fortnum and Mason Charity Christmas Party website, at Midday on Monday 19th September.

If you wish to purchase a ticket off-line, please email fortnums@thebiggive.org.uk

Tickets are likely to sell out very quickly so make sure you are first in the queue on the 19th September, to stand a chance of getting a ticket to this wonderfully festive evening out! You can get a reminder first thing on the 19^th September by registering here, http://www.fortnums-christmas.com  so go on, have a fabulous evening out and get in the party mood, on the countdown to Christmas 2011. And if you can’t make it yourself but think you know someone who can, persuade to nominate The Ectopic Pregnancy Trust to benefit from their shopping spree.