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Association of Early Pregnancy Units
‘Maintaining standards in early pregnancy care’ GUIDELINES
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All women with early pregnancy problems will have prompt access to a Early Pregnancy Assessment Unit
that provides efficient management, counselling and access to appropriate At all times women will be supported in making informed choices
about their care and management.
The Association of Early Pregnancy Units Executive Committee have set out
a 10 point Charter for service provision and these include: 1. Referral Guidelines and Operational Policy that are clear to patient.
2. Recognition of Patient choice in management.
3. Dedicated area with quiet room for breaking bad news.
4. Availability of facility and opening hours.
5. Competence at Scanning
6. Same day Serum HCG Service.
7. Written information leaflets for patient care
8. Acknowledgement of patient privacy and dignity
9. Bereavement counselling availability
10. Free pregnancy testing
Contents
Guidelines for Service Organisation

II Clinical Guidelines

Incomplete miscarriage Missed miscarriage Management of Pregnancy of Unknown Location (PUL)
III Supportive
Guidelines
Support and follow-up after a miscarriage Disposal of fetal remains (< 24 weeks) and funeral services Guidelines for Service Organisation
It should be located in a dedicated area. The surroundings should be pleasant and comfortable with toilets near at hand.
Access


The gold standard is to have a unit open seven days a week from 8.00am until 5.00 pm The minimum requirement would be to have a unit open for five days, mornings only from Monday to Friday. Patient access to AEPU Website (earlypregnacy.org.uk) will give details of nearest EPU to patient within UK and contact number.
Facilities


A simple system of sensitive urine pregnancy testing should be available in the unit There should be access to ß-hCG assay with results within 24 hours Rhesus grouping and Anti-D should be considered if gestation is >12 weeks It is important to bear in mind that some patients may require other gynaecological
Staffing

Varies between the units. Minimum requirement would be: Attitude of the staff involved should be caring and sympathetic Clear and consistent verbal and written information Initial support and informal counselling should be provided by all health professionals involved There should be access to formal counselling sessions where necessary (this may be needed Referral Guidelines
Who may be referred:

 Women in first trimester who have had a positive pregnancy test
intrauterine contraceptive device in-situ  Women with a non-viable pregnancy diagnosed in ante-natal booking clinic.  Women between 13-20 weeks, with pain and/or bleeding, either restricted access to only inpatients or open to all outpatient referrals depending on the resources of a unit
 Post evacuation/termination with persistent bleeding.
Sources of Referral
 Primary Care Doctors
 Accident & Emergency Departments  Wards  Nurse Led Primary Care Drop In Centres  Self referral
Referral Procedure

Referral booking is via Co-ordinator between 9 am and 5 pm and via the Gynae SHO/Senior Gynae nurse
at night.
 The appointment book or Electronic Diary should be available on gynae ward after 5.00pm. to enter
 Details of patient’s name, address, date of birth, name of GP and reason for referral should be noted  GPs to be advised to tell the patients that : as it is an emergency clinic the appointment time cannot be guaranteed and delays are likely  GPs to be encouraged to send a letter either with the patient or by fax A patient information leaflet on what to expect should be available in the waiting area. Caution
Women referred to the unit are, by definition, stable and can be given an appointment for the next
working day.
Women who are unwell, bleeding heavily or in whom an ectopic pregnancy is suspected should be
admitted through the usual channels and not asked to wait for an appointment on the unit. There will also
be a proportion of women who are frightened by the loss or who are socially and geographically isolated
and prefer admission.
II Clinical
Guidelines

Guidelines for General Patient Management
 A brief history is taken on the standardised proforma in accordance with RCOG/RCG guidelines
Previous obstetric history, LMP, pregnancy test in this pregnancy  Clinical examination should be considered if appropriate  Transvaginal scan (TVU) is performed if less than 7-8 weeks and also in some circumstances at more than 8 weeks, with patient option to see what is seen on the screen  Patient’s wishes should be respected if strongly declines a TVS  A clear explanation should be given by the Gynaecologist/Sonographer performing the scan as to the  Appropriate pictures are taken for the patient’s records. Pictures are not usually given to patients in  All items on the proforma should be checked  A plan of management should be formulated based on the guidelines  A pregnancy test should be performed if a pregnancy is not clearly visible  Consideration for a ß-hCG assay should be given if a pregnancy test is positive  Support should be given where the pregnancy is non-viable and a second, independent observer must confirm the diagnosis. A quiet room should be available  Follow up should be arranged before the woman leaves the clinic  Appropriate written advice and telephone numbers for contact should be given RCOG Guidelines for Rh Prophylaxis


Confirmed miscariage: Anti-D immunoglobulin should be given to all non-sensitised Rh negative
women who miscarry after 12 weeks, whether complete or incomplete and to those who miscarry below
12 weeks when the uterus is evacuated (either surgically or medically).
Threatened miscarriage: Anti-D should be given to all non-sensitised Rh negative women with
threatened miscarriage after 12 weeks. Routine administration of anti-D is not required below 12 weeks
when the fetus is viable, unless the bleeding is heavy or associated with abdominal pain.
Ectopic pregnancy: All Rh negative women with ectopic pregnancies whether managed surgically or
medically should be given anti-D. The recommended dose before 20 weeks of pregnancy is 250IU.
Documentation from the EPAU should clearly state whether or not anti-D was given in the
Clinic.


Reference:
Use of anti-D immunoglobulin for Rh prophylaxis. RCOG ‘Green –top’ Guideline no. 22,
1999.
Guidelines on Record keeping and Data Collection

Until such time as computer based records are developed in the early pregnancy assessment units, data
should be maintained in hand-written registers.
Accurate record keeping is needed to ensure that pregnancy outcome is recorded with sufficient detail and
that feedback is comprehensive.
The training of appropriate support staff to maintain high standards of record-keeping should be
encouraged.
----------------------------------------------------------------------------------------------------------------
Guidance on maintaining Registers

The monitoring of the management protocols in terms of acceptance and outcome can only be achieved
through maintaining accurate registers. The following issues are important to establish the diagnosis and
its management.
1.
All first visit scans should be given a diagnosis and grouped under respective diagnostic groups,
such as:
Viable pregnancy or Threatened miscarriage if associated with bleeding,
Complete Miscarriage,
Incomplete Miscarriage,
Missed Miscarriage,
Ectopic Pregnancy,
Those scans that do not fit into any of the above diagnostic categories because a gestation sac is either too small or not visible, should be grouped under: EGS (early gestational sac) with/without YS (yolk sac), when no embryo is visible and Pregnancy of Unknown Location (PUL) if an intrauterine or extrauterine pregnancy can not be demonstrated on scan. 3. Pregnancy of unknown location (PUL): At a subsequent scan when a diagnosis becomes possible they are placed under the respective groups as mentioned above. A pregnancy, which does not fit into any of the above diagnostic groups, is still classified as Pregnancy of unknown location (PUL). Scans that are performed after a diagnosis has been allocated to an individual patient so as to avoid counting the same patient twice in a diagnostic category. All Incomplete/Missed miscarriages should be further grouped according to the method of treatment and their outcome recorded. All ectopic pregnancies should be grouped according to the method of treatment and Monthly statistics should be entered on a Data sheet. Guidelines for Scanning
RCOG Criteria

If the gestation sac has a mean diameter greater than 20mm, with no evidence of an embryo or yolk sac,
this is highly suggestive of a silent miscarriage.
If the embryo has a crown rump length greater than 6mm, with no evidence of heart pulsations, this is
highly suggestive of a silent miscarriage.
When the mean gestation sac is less than 20mm or the crown rump length is less than 6mm a repeat
examination should be performed at least one week later both to assess growth of the gestation sac and
embryo and to establish whether heart activity exists.
If the gestation sac is smaller than expected for gestational age the possibility of incorrect dates should
always be considered, especially in the absence of clinical features suggestive of a threatened miscarriage.
In all of the above instances a repeat scan should be undertaken in 7 days. This is necessary to confirm
the diagnosis. A second independent observer needs to confirm the findings of pregnancy loss if fetal
death is apparent.
All scans should be performed by experienced personnel.
The following individuals are suitably trained to perform ultrasound:
Radiographers/midwives with the Diploma in Medical Ultrasound (DMU)/PGDip
Radiologists with ultrasound training and experience as recommended by the Royal College of
Radiologists.
Obstetricians and Radiologists who have completed the joint obstetric ultrasound training scheme of the
Royal College of Obstetricians and Gynaecologists and The Royal College of Radiologists, or
alternatively who have appropriate experience and training in obstetric ultrasound.
All personnel should have appropriate peer review of their ultrasound practice.
Information should be recorded including:

number of sacs and mean gestation sac diameter regularity of the outline of sac and its location extra uterine observations – ovaries, adnexal mass, fluid in the Pouch of Douglas (P.O.D.) Guidelines for Ultrasound Features of Early Pregnancy

Gestational age
Anatomical landmarks
Comments

pregnancies have an intrauterine pseudo GS Results from approximation of d. capsularis and d. vera. May be present in one third ectopics. Confirms viability (97% of embryos with CA have a normal outcome). GSD Gestational sac diameter DDS Double decidual sign IUP Intrauterine pregnancy Guidelines for Ultrasound Features of Early Pregnancy and Management
Ultrasound appearance
Intrauterine gestation sac
Reassure and rescan at later date depending on scan availability (See References) Gestational Sac
Rescan 1 week later If no change on second scan discuss management (see under management of non-viable pregnancy) Crown Rump Length
(CRL) <6mm
Fetal Heart Activity (FH) not
demonstrated
If no change on second scan discuss management (see under management of non-viable pregnancy) Empty uterus
pregnancy. Give contact numbers if any pain. Empty uterus
Adnexal mass
Fluid in POD
Pain

Empty uterus
Follow up with serial ß-hCG (see guidelines for ß-hCG assay) Endometrium/tissue diameter Complete miscarriage later, if bleeding persists
Endometrium/tissue diameter Incomplete miscarriage Pregnancy of Unknown
Location (PUL)

Adequate time should be allowed for women to make decisions. It is imperative to know that
patients will vary in their response to information at the time. If not receptive rescan should be
arranged for one week. If the patient displays clear understanding and wishes to know about
further management appropriate choices to be given
Embryos with: CRL smaller than expected or no growth noticed after one week, tend to be
chromosomally abnormal.
References:
1. Guidance on ultrasound procedures in Early Pregnancy. Standing joint committee on obstetric ultrasound of RCR/RCOG.
2. Philipp T, Philipp K, Reiner A, Beer F, Kalousek DK. Embryosopic and cytogenetic analysis of 233 missed abortions: factors involved in the pathogenesis of developmental defects of early pregnancies. Human Reproduction, 2003, 18, 1724-32. 3. Johns J, Hyett J, Jauniaux E. Obstetric outcome after threatened miscarriage with or without a haematoma on ultrasound. Obstetrics and Gynaecology, 2003, 102, 483-7. Guidelines for Viable Intra-Uterine Pregnancy

A normally sited gestation sac with clearly identified cardiac activity
Over 90% of women in whom fetal heart activity is detected at 8 weeks will not miscarry (Brigham et al,
1999)
At least 25% of all pregnancies threaten to miscarry.
A threatened miscarriage is one in which:
- the women bleeds a little from the vagina - cervical os is closed - there is little abdominal pain and - pregnancy is still viable. All women attending EPAU receive a contact number Women will go back to GP for referral to ANC via the usual method Follow up appointment may be required in the following situations significant vaginal bleeding and patient refusing to be admitted for reassurance at patient’s request because of previous miscarriages

The Embryonic heart rate:
Theoretically, cardiac activity should always be evident when the embryo is over 2mm. However, in
around 5-10% of embryos between 2 and 4 mm, it can not be demonstrated. Perform a follow up scan
within one week.

Bradycardia has been found in pregnancies that subsequently aborted. However, a single observation of
slow heart rate does not necessarily predict subsequent death and in later pregnancy can be associated
with maternal autoimmine disease (RO positive) and congenital heart block. Follow-up is therefore
essential.
Reference: Brigham S, Conlon C, Farquharson RG. A longitudinal of pregnancy outcome following idiopathic recurring
miscarriage. Human Reproduction, 1999, 14, 2868-71.
Guidelines for Management of Non-viable Pregnancy

1. Incomplete
Miscarriage

Endometrial thickness <15mm in longitudinal
diagnosed as “Complete miscarriage” ref ¹. Advise to report if bleeding persists longer than 2/52 Conservative method should be offered as an option provided the bleeding is not heavy. Rescan 1- 2 weeks later. Alternatively, medical management may be offered if patient is not willing to wait. Or, surgical evacuation is arranged if a patient has a strong preference for it. If infected tissue is present in the uterine cavity Surgical evacuation under antibiotic cover. Missed Miscarriage (early embryonic / fetal demise)
Always offer choices of conservative, medical and surgical methods of management If patient chooses Conservative management, rescan 1-2 weeks later, if necessary follow up with further rescans at 1-2 week intervals. medical management should be offered if patient is not willing to wait. Surgical method should be reserved for those who: change their mind during the course of conservative management
Studies suggest that, 10% women who miscarry fall into categories with unstable vital signs or infected
tissue2 . Since the introduction of TVS, ‘missed miscarriage’ and ‘anembryonic pregnancy’(absent fetal
echo) are felt to reflect different aspects or stages of the same clinical process.
References:
1. Rulin MC et al. The reliability of ultrasonography in the management of spontaneous abortion, clinically thought to be
complete: a prospective study. Am J Obstet Gynaecol 1993; 168 (1): 12-5 2. Ballagh SA et al. Is curettage needed for uncomplicated incomplete spontaneous abortion? Am J Obstet Gynecol 1998; Guidelines for Conservative Management of Non-viable Pregnancy

Conservative management may be continued as long as the patient is willing, provided there are no signs
of infection such as:
Success rates are higher with prolonged follow-up. However if patient requests a surgical or medical method at any stage it should be arranged. Give patient a contact number to ring if there are any problems. If necessary, arrange further rescans 1-2 weeks later until a diagnosis of complete miscarriage is made. The duration may be as long as 6-8 weeks sometimes. Most women prefer a conservative approach. Women need to be given a thorough explanation and all their questions and doubts should be satisfactorily answered before they leave the clinic. Reassurance that the infection rate is low at approximately 3% (MIST Trial, 2004). Go through the information leaflet and explain what to expect and how to deal with it. Conservative management requires:  Thorough explanation  Satisfactory answers to their questions  Reassurance with regards to infection that it is less in comparison with surgical ERPC  Follow up appointment two weeks later  ‘Patient information leaflet’ Guidelines for Medical Management of Non-viable Pregnancy
The drugs used for medical management of induced abortion include an antiprogresterone, mifepristone
(200mg) with a prostaglandin such as gemeprost or Misoprostol.
The conventional prostaglandin E1 analogue used for abortion procedures is gemeprost, and is effective in
95% of cases in combination with mifepristone at <63 days of amenorrheoa. The alternative E1 analgue, misoprostol may be given orally or vaginally and is most effective if administered vaginally (95% versus
87% respectively)(ElRefaey et al, 1995). The main advantages over gemeprost are that it does not require
refrigeration, it is cheaper and can be administered orally or vaginally.
The medical approach has implications for patients safety as it avoids the need for an anaesthetic and
surgical instrumentation.
The morbidity in those treated medically was lower than in those requiring surgery (1.7% verses
6.6%)(Hinshaw, 1997).
Contraindications to medical management
Absolute: adrenal
haemoglobinopathies or anticoagulant therapy non steroidal anti-inflammatory drug ingestion in previous 48 hours
Varying rates of efficacy have been quoted with medical management in non-viable pregnancies. The
efficacy is greatest for those pregnancies of less than 10 weeks or with a sac diameter of less than 24mm
(92 – 94%) (DeJonge et al, 1995).
References:
1. El-Refaey et al. Induction of abortion with mifeprestone (RU 486) and oral or vaginal misoprostol. N Engl J Med 2. Hinshaw HKS. Medical management of miscarriage. In Grudzinkas TG, O’Brien PMS, editors. Problems in early pregnancy: advances in diagnosis and management. London: RCOG press, 1997; 284-95. 3. De Jonge EJM et al. Randomised clinical trial of medical evacuation and surgical curettage for incomplete
Prostaglandin regimens – Incomplete miscarriage

Different prostaglandin regimens for use in incomplete miscarriage include the following:
 Gemeprost 1mg vaginally
 Misoprostol 800ug (4 x 200 ug tabs) vaginally
Prostaglandin regimens - Missed miscarriage

 Mifepristone 200mg orally followed 36 – 48 hours later by cevagem 1mg vaginally
 Mifepristone 200mg orally followed 36 – 48 hours later by misoprostol 800ug (4 x 200ug tabs)
 Since progesterone levels are low in non-viable pregnancy mifepristone may be avoided and
Procedure

Take consent for mifepristone and PG +/- surgical evacuation Prescribe and give mifepristone 200mg orally. Advice the patient to inform the hospital if she
vomits shortly after administration of the mifepristone.
In the case of a pregnancy occurring with an IUCD in-situ, the device should be removed before administration of mifepristone. Arrange admission 48 hours later.
Inform the patient regarding the length of stay on the ward. Observe for three- six hours after administration of prostaglandin and discharge if clinically well. < 9 weeks on scan get only one insertion of prostaglandin > 9 weeks on scan get 3 hourly PG X 5 Prescribe PG (Misoprostol 800ug tabs/Cervagem 1mg) vaginally and Metronidazole 1G PR in the Drug chart. Prescribe Doxycycline 100mg bd for 10 days with co-dydramol 2 tabs qds for one week to take home after the procedure (antichlamydial prophylaxis). Inform that in case of heavy bleeding ERPC may be required and therefore to be prepared to stay overnight if necessary Women may or may not pass POC while on the ward. They should be advised of what to expect when they go home and not referred to EPAU for a scan before their follow up appointment. Any products that are obtained should be sent for histological examination Give contact telephone numbers for EPAU/Gynae ward Guidelines for Surgical Evacuation of Non-viable Pregnancy

Surgical evacuation should be preferably managed on a day case basis unless there is heavy bleeding.
Alternatively, if the patient needs to be admitted to Gynae ward arrange with the ward.
Have a unit protocol for admission system with a clear patient pathway description.
Give the patient information on admission procedure including appropriate patient information leaflet(s).
Explain the surgical procedure and obtain written consent with Doctor familiar with procedure. Mention
rare anaesthetic and uncommon surgical risks involved such as uterine perforation (1%), cervical tears,
intra-abdominal trauma (0.1%), intrauterine adhesions, haemorrhage and infection.
Arrange for a FBC and blood grouping. Anti-D immunoglobulin should be given to all non- sensitised
Rh negative women undergoing surgical evacuation.
All at risk women (usually women under the age of 25 years) undergoing surgical evacuation for
miscarriage should be screened for Chlamydia trachomatis.¹
Alternatively prescribe prophylactic doxycycline 100 mg bd for 10 days and Metronidazole 1G PR to
women undergoing surgical evacuation.
Ensure that products of conception are seen at evacuation.
The RCOG study group² recommended that all tissue obtained at a surgical evacuation for miscarriage
should be sent for histology examination. The reasons are:
to exclude ectopic if chorionic tissue is found on histology
A follow-up appointment is usually not required after a surgical evacuation.
Give patient information on “What you may need to know after a miscarriage”.
References:
1. Royal college of Obstetricians and Gynaecologists. The Management of Early Pregnancy Loss. Green Top Guideline No.
25. London: RCOG Press; 2000 and 2003
2. Recommendations from the 33rd RCOG Study Group. In Grudzinkas TG, O’Brien PMS, editors. Problems in early
pregnancy: advances in diagnosis and management. London: RCOG press, 1997. 327-31
Guidelines for beta-hCG Measurements
Urine Measurements
The urine test is simple and reliable enough to be used routinely to establish whether or not a woman is
pregnant. A rapid and simple test is available in the unit.
Serum measurements
Measurement of hCG in serum permits more accurate quantification which may be useful in the
following:

1. Screening in women at high risk of ectopic pregnancy
2. Determining the appropriate treatment for women with suspected ectopic pregnancy
3. Monitoring during expectant management or medical management of women with ectopic pregnancy
4. Evaluation of conservative surgical treatment of ectopic pregnancy

Serum hCG levels double approximately every two days in early (<8 weeks) normal intrauterine
pregnancy; a lesser increase (<66% over 48 hours) is associated with ectopic pregnancy and miscarriage.2
To find out whether or not a pregnancy is normal or pathological, the two useful clinical concepts of hCG
measurement are the hCG doubling time and the discriminatory hCG level.
HCG doubling time
It refers to the time taken for the hCG level to double its original value. A beta-hCG value of
<5 IU/L is considered to be the non pregnant value.
The doubling time is particularly useful in early pregnancy i.e. before 5.5 weeks or when the plasma hCG
level is <5000IU/L. As pregnancy progresses the doubling time also lengthens.
However 15% of normal pregnancies will have abnormal doubling time and 13% of ectopic pregnancies
will have a normal doubling time 3.
Caution
1. In multiple pregnancy the hCG level would be a little higher, requiring an extra two or three days for
2. The possibility of a heterotopic pregnancy should be kept in mind (1 in 3000 cases of spontaneous conceptions and between 1% to 3% of assisted conceptions). Discriminatory hCG level
It refers to a defined level of hCG above which the gestational sac of an intrauterine pregnancy should be
visible on ultrasound. In women with an hCG result above the discriminatory level, but absence of an
intrauterine gestational sac on ultrasound, ectopic pregnancy is a distinct possibility.
With the use of high resolution transvaginal ultrasound the discriminatory level has been reported to be
around 1000IU/L IRP 4. However the American Fertility Society suggested that in practice the level
ought to be around 2400IU/L.
The discriminatory level may vary in different units and depends on three factors:
the experience of the person performing the ultrasound
It usually lies between 1000 – 2400IU/L.
A diagnosis of ectopic pregnancy is more likely whenever intrauterine pregnancy is not detected by
ultrasound at serum hCG concentration above 2400IU/L.
References
1.
Recommendations for clinical practice arising from 33rd RCOG Study Group. Problems of Early Pregnancy – Advances in Diagnosis and Management, 1997. Kader et al. (1981) Discriminating hCG zone: Its use in the Sonographic evaluation for ectopic pregnancy, Obstet Gynecol 58, 156-61 Ling and Stovall (1994) Update on the diagnosis and management of ectopic pregnancy, Advances in Obstetrics and Gynaecology, 1, pp 55-83. Chicago:Mosby Year Book, Inc Caeciatore et al. (1990) Diagnosis of Ectopic Pregnancy by Vaginal Ultrasonography in Combination with a discriminatory serum hCG levl of 1000IU/L (IRP). BJOG 97, 904-8. Management of Pregnancy of Unknown Location (PUL)
Definition
No evidence of intrauterine or extrauterine pregnancy in women with a positive pregnancy test.
Initial assessment

the presence of risk factors for ectopic pregnancy (See under ectopic pregnancy)
Give appropriate information to patient. Explain the need for further follow up
Follow up

 Close surveillance with Serum hCG measurements every 2-3 days
 See guidelines for beta hCG
 Repeat TVS when beta hCG 1,000 IU/L or one week later
 Provide support
 Follow up until:
Pregnancy of unknown location (PUL) – Perhaps resolving Management of PUL Scan result following TVS
Ultrasound
Pattern of change of
Management
hCG level after 48
hours

If hCG < 1000 repeat hCG 48 hours later Adnexal findings + or - Diagnosis: Ectopic Pregnancy of unknown location – resolving Guidelines on the Management of Ectopic Pregnancy
Ectopic pregnancy affects 1:80 pregnancies. Evidence suggests that the incidence of ectopic pregnancies has been rising. While this increase is for the most part real, early diagnosis also plays a role by identifying ectopic pregnancies that would have resolved. In the U.K the incidence has doubled from 4.9 to 11.1 per 1000 pregnancies from 1973 - 1999, while mortality has decreased from 16.4 per 10,000 cases. During the last triennium (1997 -1999) ectopic pregnancies accounted for 12.2% of all direct maternal deaths and remained the leading cause of death in the first trimester. The availability of sensitive and specific radio-immunoassays of β-human chorionic gonadotrophin (β-hCG) and high resolution transvaginal ultrasound (TVS) allow early detection of ectopic pregnancies. Studies on β-hCG dynamics provide evidence that 85% of viable intra-uterine will show a 66% rise in β-hCG levels in every 48 hr period in the first 40 days of gestation. Conversely only 13% of ectopic pregnancies will show a 66% rise. A rise of < 50% is almost always associated with a non-viable pregnancy. An intra-uterine pregnancy sac should be seen on abdominal scan with a β-hCG level of 6500 IU/ml or on TVS at 1000 -2000 IU/ml. Based on audit data LWH uses 1500 IU/ml as the level we expect to see an intra-uterine gestation sac on TV scan. The classical surgical approach for an ectopic pregnancy is by open laparotomy. Four randomly controlled trials (RCT) have reported the results of comparisons between this traditional approach and laparoscopic tubal surgery. The laparoscopic approach was associated with significantly less blood loss, lower analgesia requirements, shorter hospital stay and quicker postoperative recovery time. The subsequent intrauterine pregnancy rate (IUP) was 70% after laparoscopic surgery compared to 55% after laparotomy. The recurrent ectopic rate was also lower 5% compared to 16.6%, but this incidence of persistent trophoblastic tissue was increased. A laparoscopic approach is superior to a laparotomy in terms of recovery from surgery,
Subsequent intra-uterine pregnancy rate and recurrent ectopic rate but is associated with a higher risk
of persistent trophoblast. (This is a Grade A recommendation)
The wider use of laparoscopic surgery must be tempered by its use only in appropriate situations by In cases of haemorrhagic shock or where the surgeon has inadequate experience at operative
laparoscopy, traditional rapid laparotomy is preferred. (This is a grade A recommendation)
In a meta-analysis of 40 studies the IUP rate after tubal conservation was 46% compared to 44% After tubal excision. The repeat ectopic rate was respectively 15% and 10%. Similarly in an important meta-analysis of nine good quality comparative studies Yao and Tulandi reported no significant difference in the IUP between salpingostomy and salpingectomy. Failure to completely remove the ectopic occurred in 4.8% - 11% of salpingostomy cases. In contrast almost no cases of persistence Salpingectomy is to be preferred to salpingostomy when the contralateral tube is healthy as it is
associated with lower rates of persistent trophoblast and subsequent repeat ectopic whilst having
similar IUP rates. (This is a grade B recommendation).
Non-surgical management is now available for certain cases of ectopic pregnancy. Not all ectopic pregnancies progress and pose a risk to the mother. Spontaneous resolution is well documented. However the risk of rupture in a woman with an ectopic pregnancy exists until the β-hCG level has fallen to < 10iu/l. Expectant management requires frequent hospitalisation and/or follow-up and with poor efficacy is NOT RECOMMENDED practice at this hospital
In selected cases methotrexate is an effective alternative to surgery. Methotrexate is a folic acid-antagonist (anti-metabolite) which prevents the growth of rapidly dividing cells by interfering with DNA synthesis. It can be administered systematically (IV, IM or orally). Three trials have reported the use of Methotrexate in a single dose of 50mg/m² body surface area IM and these reported a resorption rate of 92% and subsequent IUP rate of 58% with a recurrent ectopic rate of The incidence of side- effects after methotrexate is related to both the dose and mode of administration. Side effects encountered include stomatitis, alopecia, haematosalpinx and impairment of tubal mucosa. Methotrexate pneumonitis and neutropenia have also been described. Failure of Methotrexate therapy is more likely to occur with high hCG levels (32% if initial level > 10,000iu.) with large tubal diameters and with fetal cardiac activity. These restrictions limit the general It is important to have a high index of suspicion for ectopic pregnancy, because the patient may not
be symptomatic until rupture occurs, or on the other hand the patient may experience vague and mild symptoms early in the course of the disease. In addition the clinical presentation and natural course of an Risk Factors. Are present in 25 - 50% of patients with an ectopic pregnancy. They include history of
 Previous pelvic inflammatory disease.  Conceiving with IUCD or on the progesterone only pill. Symptoms.
 GIT symptoms - diarrhoea or pain on defecation 3. Adnexal mass with cervical excitation tenderness The classic symptoms and signs such as severe abdominal pain and hypotension are associated with advanced or ruptured ectopic pregnancy. Laparotomy with appropriate resuscitation is the treatment
of choice for haemodynamically-compromised patients with ruptured ectopic pregnancy
Investigations
1. Pregnancy tests.
All patients with a history of suspected ectopic should have a pregnancy test. If the check mate is negative an ICON should be performed as local evidence suggests this test is more sensitive. A NEGATIVE pregnancy test essentially excludes a pregnancy in more than 99% of cases (although a chronic ectopic pregnancy may be present). Therefore, if clinical suspicion of ectopic pregnancy persists in the presence of a negative pregnancy test and the ultrasound examination is not helpful, then serum β-hCG should be measured serially to establish diagnosis. (See inconclusive ultrasound findings) 2. Ultrasound examination :-
Should be arranged as soon as possible. If the patient is in significant discomfort she should be admitted to await scan the following day. If she is clinically stable with no discomfort she may be allowed home to await scan. Direct contact number for the emergency room should be given and the patient asked to attend at any time if her condition deteriorates. : - Ultrasound features suggestive of an ectopic pregnancy are.
 An empty uterus – with or without thickened endometrium.  An ectopic sac with or without heart beat. (Don’t forget ectopics at other sites such as cervix or ovary.) Utility of serum β-hCG in patients with non-specific ultrasound findings. If the ultrasound findings are non-specific. Follow diagnostic algorithm for ectopic pregnancy. However Arrange laparoscopy if clinical features worsen at any stage.
Laparoscopy remains the gold standard for the diagnosis of ectopic pregnancy, although this approach has a false negative rate of 3-4% and a false positive rate of 5%. Management Management of ruptured ectopic with collapse.  ABC of resuscitation ( see resuscitation guidelines.)  Get help; call SPR 1 –3, SPR 4 –5 on call and anaesthetist.  Site two IV lines ( at least 16g), commence Iv fluids (crystalloid) give facial oxygen and insert  Send blood for FBC Clotting screen and cross-match at least 4 units of blood.  Continue fluid resuscitation and ensure intensive monitoring of haemodynamic state whilst awaiting  Do not wait for BP and pulse to normalise prior to transfer.  Pfannensteil incision , locate tube directly and clamp.  Assess bloods consider CVP / HDU discuss with anaesthetist.  Record operative findings pay close attention to the state of the remaining tube.  Anti –D to be given to Rhesus negative women. Surgical management of non-acute ectopic.
 Inform SPR 1-3 of admission and following consultation arrange laparoscopy.  If possible a doctor with appropriate skills for laparoscopic salpingectomy should perform the  Assess the condition of the other tube.  Perform salpingectomy or salpingostomy. Record operative findings pay close attention to the state of remaining tube. If salpingostomy performed follow up with weekly β-hCG until measurements return to While trophoblast remains in the tube it has the capacity to rupture. We recommend weekly β- hCG. If not falling a single dose of Methotrexate 50mg/m2 can be given or repeat surgery. Guidelines for the Medical treatment of Ectopic Pregnancy.
Patient selection.
Inclusion criteria.
 The patient should be haemodynamically stable.  No Fetal Heart activity demonstrated.  Patient fully understands and will be compliant with regular follow-up until Bhcg returns to normal.  Patient is aware of potential side-effects.  Case reviewed by SpR 4/5 or consultant  Agrees to avoid pregnancy for 4 months post treatment. Exclusion Criteria.
 Pre-existing severe medical condition or disorder.  Any abnormality on LFT U&E or FBC.  Any known renal or hepatic abnormality.  Any known contra-indication to methotrexate.  Patient is taking NSAID, Diuretics tetracycline group drugs and is unwilling or unable to stop  Patient not willing to return for follow-up.  Patient unwilling to wait 4 months before trying to conceive again.  Presence of co-existing intra-uterine pregnancy. Treatment Schedule.
 Pre-treatment bloods for β-hCG U&E LFT and FBC.  Prescribe Methotrexate 50mg/m as once only dose.  Order methotrexate from pharmacy (get back from RLH same day if ordered before 12.  Methotrexate to be IM into the gluteal region by a doctor. Patient follow-up and monitoring.
 Day 4 before 11 00hrs Routine observations. Β-hCG  Day 7 before 11 00hrs Routine observations. FBC β-hCG LFT,s  Day 14 before 11 00hrs Routine observations. FBC β-hCG  Day 21,28,35 until β-hCG is <10 i.u/l If between day 4 and Day 7 the β-hCG does not fall by 15% the dose of Methorexate should be repeated. (50mg/m).The injection should be given into the opposite Gluteal after confirming normal LFT on Day 7. Day 4 and Day 7 tests should be repeated on Day 11 and 14 if a second dose of Methotrexate is given. The β-hCG can take several weeks to fall to normal. If β-hCG continues to rise of levels become static despite two doses of methorexate. Laparoscopy should  She may experience some pain in the abdomen as the pregnancy resolves.  She may take simple analgesia for this pain Paracetamol / cocodamol. If this not sufficient to contact  To stay in the area till follow-up complete.  To avoid intercourse till follow-up complete.  Patient should be given 24 hour contact number for the emergency room. Patients who have had medical or surgical management of an ectopic pregnancy should be offered a follow-up appointment. In future pregnancies a scan can be performed in the Early Pregnancy Assessment Unit at 6 weeks to confirm the site of the pregnancy. Heterotrophic pregnancy.
This is a very rare occurrence, however with the increased use of assisted reproduction the incidence has  There is no role for medical management.  Laparoscopic salpingectomy is the treatment of choice. Guidelines revised and updated by Dr Joanne Topping and Mr John Kirwan July 2003  Department of Health. Report on Confidential Enquiries into maternal Deaths in the United kingdom 1997 -1999  Stovall TG, Ling FW. Ectopic pregnancy: Diagnostic and therapeutics algorithms minimising surgical intervention. J Reprod Med 1993; 38: 807-812.
 Yao M, Tulandi T. Current status of surgical and non-surgical management of ectopic pregnancy. Fertil Steril 1997; 67: 421-433
 Royal College of Obstetricians and Gynaecologists. Guideline on the management of tubal pregnancies. RCOG  Glock JL, et al Efficacy and safety of single-dose methotrexate in the treatment of ectopic pregnancy. Fertil Steril 1994; 62: 716 – 721.
Algorithm For management of Suspected Ectopic.
Ectopic sac.
Or empty uterus with
Intra-uterine gestation
adenexal mass or free
DISCHARGE
BHCG <1500IU/L
Repeat in 48
Falling BHCG
Trophoblast in regression
Follow to normal
Abnormal BHCG rise
laparoscopy



Guidelines on the Management of Women with
Recurrent Miscarriage

Definition: Recurrent miscarriage (RM) is defined as loss of three or more consecutive
pregnancies although most authorities would accept two consecutive fetal losses.
Prevalence: Based on an incidence of spontaneous miscarriage of 15 %, the risk of RM should
be 0.4% - but it is double this at 1%. This suggests that for some couples there is an underlying
cause for their RM.
Primary RM: Where women who have no successful pregnancies.
Secondary RM: Where women miscarry repetitively after a successful pregnancy or pregnancies
Investigation Protocols for recurrent miscarriage (RM) (for patients’ information)
See website: earlypregnancy.org.uk or lwh.org.uk (look under Miscarriage Clinic)

1. Unknown or Idiopathic.
In 50% of cases of recurrent miscarriage no cause is found ¹ ² ³. Most women who have two or three miscarriages
have nothing wrong with them that will cause them to miscarry every pregnancy. Their miscarriages are caused by
random factors just as women who miscarry only once. This is the reason why tests and investigations are rarely
undertaken before three consecutive miscarriages. Any drug treatment in this group would be empirical. The
mainstay of management of these patients is based upon emotional support supplemented by ultrasound scan in early
pregnancy, which gives “success rates” of between 70-80%4 5. Even at or above the age of forty, there is still a 50%
chance of a successful pregnancy (Brigham et al, 1999). Couples can obtain a predicted success rate for future
pregnancy by using the following table:
Predicted probability of a successful pregnancy by age and previous
miscarriage history.(95% confidence interval)
_________________________________________________________________ _________________________________________________________________ 20
2. Genetic and Chromosomal
A high proportion of early miscarriages would be found to have a chromosomal abnormality.
In less than 3% of cases, either the woman or her partner may possess abnormal chromosomes which they happen to
repeatedly pass on to the fetus. This can be tested by taking blood samples from both partners for chromosomal
analysis. It usually takes 4-6 weeks to get the results. If a chromosomal abnormality is found in a parent, referral to a
clinical geneticist may be necessary. The chances of a successful subsequent pregnancy will depend on the type of
chromosomal abnormality. The most common condition causing recurrent miscarriages is a balanced or reciprocal
translocation. In this condition the chromosomes although being of the correct number are arranged differently.
3. Abnormalities of the uterus (womb) or cervix (neck of the womb).
Abnormalities in the shape of the uterus occur in probably less than 5% of women with recurrent miscarriages.
Uterine abnormalities such as a bicornuate uterus (double uterus), unicornuate uterus, septate uterus or fibroid uterus
may be detected on detailed ultrasound scan or hysteroscopy (telescopic examination through the vagina and neck of
the womb). It is not clear whether there is any benefit in surgical correction of the abnormalities.
Cervical weakness (formerly known as incompetence) may be acquired eg from previous surgery or following birth.
It causes painless dilatation of the cervix and rupture of the membranes (breaking of waters) in mid pregnancy. It
may be detected by transvaginal ultrasound scan in the midtrimester starting at 14-16 weeks. If the diagnosis is made,
a stitch is usually put in the cervix to prevent opening of the cervix.
4. Infection
The continuing emergence of Bacterial Vaginosis as a cause of RM is widely accepted (Oakeshott et al, 2002). Other
rare infections involved include Rubella (German Measles), Toxoplasmosis, Listeria and Parvovirus.
5. Hormonal
Imbalance of hormones such as progesterone and human chorionic gouadotrophin (hCG) have been suggested as a
cause of miscarriage. However there is scientific evidence of benefit from hCG support but no support for injections
of progesterone.
Some women with recurrent miscarriage have polycystic ovaries (PCO) in which there are multiple small cysts
within the ovary causing an abnormal hormone balance and this may cause recurrent miscarriage by interfering with
successful implantation of the fertilised egg.
6. Thrombophilia or blood clotting abnormalities
Normally the blood becomes slightly thicker during pregnancy, but in some women the blood is found to clot more
easily due to the presence of certain antibodies called Antiphospholipid antibodies. These blood clots in the placental
blood vessels may decrease the blood flow to the baby resulting in miscarriage. Antiphospholipid antibodies are
present in 15% of women with recurrent miscarriage. The main type of antiphospholipid antibodies are Lupus
Anticoagulant and Anticardiolipin antibody. The association between phospholipid antibodies and recurrent
miscarriage is referred to as Antiphospholipid Syndrome (APS) (Branch and Khamashta, 2003).
For a diagnosis of PAPS to be made one should have two positive tests at least six weeks apart, one positive result
may be due to viral or other infection. Various treatments are available including low dose aspirin alone (75mg) or
aspirin plus heparin.
Management:
Individual units may have their own protocols for management of women with RM
(www.earlypregnancy.org.uk). The aim is to make all health professionals providing early
pregnancy care to be aware of the current approach to this problem.
Preliminary work up
The mainstay of management of patients with idiopathic RM is based upon emotional support
supplemented by ultrasound scan in early pregnancy, which gives “success rates” of between 70-
Above the age of forty, there is still a 50% chance of a successful pregnancy (Brigham et al, 1999) as the two main determining factors are maternal age and number of previous consecutive losses.  Patients should not be subjected to tests without a proper plan of further follow-up and  It is important for both partners to be aware of what is going to happen, encourage  Care should be streamlined, and tests should not be merely done to reassure the patient  Reassure the couple that all known factors for RM will be explored. Give explanation of all the tests before taking blood samples.  Routine testing for inherited clotting disorders is not recommended  Discus the treatments that are available (it prepares the couple for their further  Discuss lifestyle and about preconceptual care.  Encourage them to talk about their fears and anxieties.  Arrange for a six-week follow-up appointment for the couple to see a specialist.  Advise to contact their GP for referral to EPAU if they should achieve a pregnancy and arrange an ultrasound scan at six weeks gestation and thereafter fortnightly for maternal assurance until seen in the antenatal booking clinic
Medical consultation:
 In all couples with a history of Recurrent miscarriage Cytogenetic analysis of the products of conception should be performed if the next pregnancy fails  Routine screening for thyroid and Diabetes in early pregnancy loss is uninformative  Give results of the tests  Discuss possible treatment options Live birth rate in Antiphospholipid syndrome: with 75 mg aspirin alone >70% with aspirin and low molecular weight heparin >70%  Give detailed information about the treatment regime that they will need in a future pregnancy: - aspirin +/- heparin is started as soon as pregnancy is diagnosed. - both are continued until delivery and thereafter postnatally for 6 weeks if obese or Caesarean section or previous thrombosis history.  hCG is recommended for women with oligomenorrhoea (periods more than 35 days apart) from the time of positive serum HCG until 12 weeks gestation. General Advice ♦Smoking and alcohol intake are thought to be associated with a higher rate of miscarriage. ♦There is no association between the use of computers and miscarriage ♦The Department of Health suggests that all women planning a pregnancy should have 400 µgms of folic acid before pregnancy until approximately 12 weeks gestation. ♦It is advisable to avoid close contact with sheep and horses during lambing. ♦Avoid contact with cat’s litter References:
1. Stirrat GM 1990 Recurrent miscarriage; definition and epidemiology. Lancet 348: 1402-6
2. Quenby and Farquharson 1993 Predicting recurring miscarriage-What is important? Obstet Gynecol 82: 132-8
3. Stray-Pederson et al 1984 Etiological factors and subsequent performance in 195 couples with a prior history of
habitual abortion. Am J Obstet Gynecol 148: 140-6 4. Liddel et al 1991, Recurrent miscarriage: Outcome after supportive care in early pregnancy. Aus NZ J Obstet 5. Clifford et al 1997 Future pregnancy outcome in unexplained recurrent first trimester miscarriage. Human 6. Brigham S, Conlon C, Farquharson RG. A longitudinal study of pregnancy outcome following idiopathic recurring miscarriage. Human Reproduction, 1999, 14, 2868-71. 7. Oakeshott P, Hay P, Hay S, Steinke F, Rink E, Kerry S. Association between bacterial vaginosis or chlamydial infection and miscarriage before 16 weeks gestation. BMJ, 2002, 325, 1334-6. 8. RCOG Green Top Guideline on Recurring Miscarriage (No 17), RCOG Press, October 2003. 9. Branch W and Khamashta M. Antiphospholipid Syndrome: Obstetric Diagnosis, Management and Controversies., Obstetrics and Gynecology, 2003, 101, 1333-44. Guidelines on the Management of Gestational Trophoblastic disease

Incidence:
Need for chemotherapy: in partial mole (0.5%) in Ultrasound features in trophoblastic disease
Diagnosis
Uterine cavity filled with homogeneous central Complex mass with multiple echo free spaces in Twin sacs, one viable fetus and the other complex Ovaries: Soap bubble or spoke-wheel appearance of the ovaries in upto 50% of cases
Colour flow imaging can be helpful in demonstrating avascular nature of the mass.
Explain the diagnosis and the need for follow-up in a screening centre.
A twin pregnancy with a partial mole may proceed after appropriate counselling. However if
complications such as pre-eclampsia and haemorrhage develop, termination of pregnancy may be
indicated.
Investigations:
FBC, blood group and thyroid function tests
hCG measurements. hCG levels are enormously raised.
Chest x-ray if any chest symptoms

Review with hCG results.
Arrange for surgical evacuation on DSU/ Gynae ward.
Give patient information leaflets on:
- Admission to Day Surgery Unit or Gynae ward - Understanding Hydatidiform Mole Treatment:
Surgical evacuation is the treatment of choice. Because of the lack of fetal parts, a suction curette
of 12 mm is usually sufficient to evacuate complete molar pregnancies.
Routine repeat evacuation is not warranted. It may be recommended in selected cases. In such
cases consultation with the screening centre should be sought.
Avoid:
 Medical evacuation, since mifepristone increases the sensitivity of the uterus to
 Cervical preparation prior to surgical evacuation  Oxytocic agents, until evacuation of the mole is completed. If patient is experiencing significant haemorrhage prior to evacuation use of oxytocics will be necessary.
Histological examination:
All products of conception obtained after evacuation should be sent for histopathological
examination.
Follow-up:
Arrange for follow-up in two weeks.
Advice on future pregnancies and contraception:
- not to use COC until hCG levels have reverted - not to conceive until the hCG level has been normal for six months or follow-up has been completed (whichever is the sooner)
Complete and despatch Molar Pregnancy registration form for the RCOG Trophoblast Disease
Surveillance Units in London (Charing Cross), Sheffield (Weston Park) or Dundee (Ninewells).

COC: Combined oral contraceptive pill
III Supportive Guidelines

Guidelines for support, follow up and counselling
There has been a definite move over the last 10 years to manage miscarriage problems with
greater sensitivity and understanding. Medical, nursing and ulltrasonography staff should be
trained in counselling skills, support techniques and other issues around problems in early
pregnancy. It is recognised that in pregnancy, ultrasonic diagnosis, repeated testing and the
uncertainties of the outcome may lead to substantial anxiety in the women under care. (1)

Support
All women attending the EPAU are offered a contact number following their initial referral.
Literature is available regarding the various scenarios that are possible to consolidate verbal
information.
1. What is threatened miscarriage? 2. Inconclusive Scan 3. Pregnancy loss – What happens next? 4. Conservative management of miscarriage 5. Medical management of miscarriage 6. Surgical management of miscarriage 7. What you may need to know after a miscarriage. 8. Ectopic pregnancy 9. Medical treatment of ectopic pregnancy 10. Surgical treatment of ectopic pregnancy 11. Understanding hydatidiform mole 12. What is an Early Pregnancy Assessment Unit 13. Recurrent miscarriage
Patient information leaflet no. 7 ‘What you may need to after a miscarriage’, provides
information on various questions that these women may have after a miscarriage. It tells them
about annual remembrance service held by hospital chaplains.

Follow up
A routine follow-up appointment is not given after the completion of the treatment of
miscarriage. Nevertheless all women are given local contact numbers along with the appropriate
leaflets which contain various telephone numbers. Women who contact the unit are given the
support and advice they need but those who require formal counselling will be referred to the
counsellors.
Women with a diagnosis of ectopic pregnancy treated surgically are generally given a follow-up
appointment in the gynae outpatient.

Counselling

Women have different abilities and mechanisms to cope with a pregnancy loss. A good number
of them will come out of the grieving process. It is only a small number of them that will require
formal counselling by the counsellors. Generally, those who require formal counselling would
need more than one visit.
Counselling is also provided to staff should this be deemed necessary, in acknowledgement of
the sometime stressful nature of the work.
(Refer to – Midwifery Counselling Service: Operational Policy for more details)
Support Organisations:
1. Miscarriage Association
C/o Clayton Hospital Wakefield West Yorkshire WF1 3JS Tel. 01924 200799 11, Millside Riverdale Buckinghamshire SL8 5EB Tel. 01494 765001 Alexandra House Oldham Terrace, Acton London W3 6NH Maternity unit The Hillingdon Hospital Pield Heath Road, Uxbridge, Middlesex UB8 3NN Tel. 01895 238025 5. Royal College of Obstetricians and Gynaecologists, 27 Sussex Place, Regents Park, London NW1 4RG www.rcog.org.uk for links Guidelines for Disposal of Fetal remains and Funeral services

(before 24 weeks)
- NHS Management executive issued guidelines on the disposal of all fetal material - Guidelines said that disposal should be done in a sensitive way, irrespective of how This guidance needs a lot to be desired. It urges a significant cultural change within the NHS. Until recently the majority of tissue from early pregnancy loss < 24 weeks (including TOP) was being incinerated along with clinical waste. This practise was felt to be totally unacceptable and fetal remains are now being disposed of in a sensitive and dignified manner in light of Bristol Inquiry recommendations ( Kennedy Report). Does it apply to all fetal remains is the next question? Five areas have been identified involved in the disposal of fetal remains. 1. Delivery suite 2. Gynaecology ward 3. Day theatre 4. Main theatre 5. Genetics 6. Histology department 7. EPAU All these products of conception are taken for a blessing common to all religions, this is done once every week or monthly in the main chapel. Women may ask and wish to know about the actual disposal of fetal remains. When asked women should be informed of what happens to the fetal remains and be given choices on how their fetal remains could be disposed. Histology department POC are normally disposed of in a macerator. If fetal parts are identified the container is kept separately and labelled with a green label. There is no dignified mechanism in place to dispose fetal remains obtained from Evacuation of retained products of conception (ERPCs). Products obtained from ERPCs are not collected for disposal in the same sensitive manner. Each Hospital Trust should have in place a clear system and protocol for the sensitive disposal of fetal remains. A Book of Remembrance should be made available in the hospital. There is no funeral under 24 weeks. However parents who wish to arrange a funeral are given all the required support and advice. A better understanding of the women’s faith makes the women feel more comfortable and also helps the staff in giving out right advice and opinion suitable to her needs keeping her religious background in view. The bodies or remains of babies born dead before 24 weeks gestation have no legal status and as such there is no legal requirements for their disposal to be registered. Nevertheless a central Register or Book of Remembrance is maintained in which the entries can be made by the parents. There are memorial services for loved and lost babies held annually by the hospital chaplains. The mechanism in place in a given hospital should be outlined in the Guidelines

Source: http://earlypregnancy.org.uk/prof/documents/AEPUGuidelines2004.pdf