• PUL is defined as a positive pregnancy test with no pregnancy visualised on transvaginal scan (TVS) either inside or outside the uterine cavity.

• The presence of an intrauterine gestational sac excludes a PUL and such patients DO NOT need serial bloods.

• On TVS, approximately 88% of pregnancies will be intrauterine, 2% will be visualised as ectopics and 10% will be classified as PUL. Of these 90% will be early IUP or failing PULs / IUPs. Only 10% will be ectopic pregnancies.

• It is important to distinguish the low-risk group (failing PUL and IUPs) from the high-risk group (ectopic). Ectopic pregnancy must be carefully followed through until the diagnosis is made.

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Abbreviations

1.1 To aid health professionals involved in the management of early pregnancy complications with evidence based diagnostic and management approach for Pregnancy of Unknown Location (PUL).

1.2 To optimise patient experience via standardisation of care in early pregnancy management.

2.1 This is defined as a positive pregnancy test with no pregnancy visualised on transvaginal scan (TVS) either inside or outside the uterine cavity.

2.2 This is a heterogeneous group that includes:

a. Complete miscarriage where an intrauterine pregnancy has not been previously visualised.

b. Very early intrauterine pregnancies (IUP) where a sac is not yet visible.

c. Early ectopic pregnancies which are too small to see on TVS.

d. Failing pregnancies undergoing spontaneous resolution – intra or extrauterine.

2.3 The presence of an intrauterine gestational sac excludes a PUL, and such patients DO NOT need serial HCGs.

2.4 On TVS, approximately 88% of pregnancies will be intrauterine, 2% will be visualised as ectopic pregnancy and 10% will be classified as PUL. Of these 90% will be early IUP or failing PULs /IUPs. Only 10% will be ectopic pregnancies.

2.5 It is important to distinguish the low-risk group (failing PUL and IUPs) from the high-risk group (ectopic pregnancy). Potential ectopic pregnancy must be carefully followed through until the diagnosis is made.

2.6 The rate of PUL diagnosis varies from 10- 40% and is dependent on the quality of scanning within a unit. The more ectopic pregnancies that are definitively visualised on TVS, the lower the rate of PULs.

2.7 Once the PUL has been diagnosed:

• Counsel the patient accordingly and provide PUL patient information leaflet.

2.8 Advise the patient:

a. Not to travel

b. To avoid sexual intercourse

c. To return immediately if she experiences a significant increase in abdominal pain.

2.9 Enter patient’s details on the BHCG follow up notebook along with short history to discuss with the consultant and document follow up plan at Frimley Park Hospital.

2.10 Complete a PUL proforma (see Appendix) and keep this in PUL folder if the patient was seen at Wexham Park Hospital.

3.1

• Ensure 0-hour Serum BHCG, Serum Progesterone, FBC & G&S are available.

  • Repeat serum BHCG at 48 hours.

  • If the initial serum BHCG fall from 0 to 48 hours is > 50% then pregnancy test in 2 weeks is advised according to BHCG and US scan finding. Patients are advised to contact EPU if pregnancy test was positive.

• At Frimley Site, BHCG follow up book should be reviewed daily by the EPAU nurse and EPU consultant (admitting consultant when there is no EPU consultant available) and management plans are carried out as per consultant’s advice.

• At Wexham Site, all the blood results should be reviewed by the EPAU clinician on the same day. Consultant covering the UGCC on the day is responsible for reviewing and advising the nurses on the management.

• At Wexham site: If the 0 hour Serum Progesterone is less than 2 in an asymptomatic patient, patients will be advised to repeat the urine pregnancy test in 2 weeks and to contact UGCC if she develops any symptoms or UPT remains positive after 2 weeks.

• The patient is reviewed at regular intervals until a final diagnosis is made and/or the pregnancy resolves spontaneously, defined as ß-hCG <15iu/L.

• Explain to patient that follow-up will include:

  • Clinical assessment

  • Serial ß-hCG measurements

  • Repeat TVS depending on βHCG level and symptoms.

• Perform repeat TV USS immediately if pain develops.

• PUL proforma should be uploaded to EPIC once follow up is complete.

3.2 Persistent PUL, i.e., no significant change in BHCG level without a visualised pregnancy may require treatment with methotrexate. This management should only be instituted by the consultant in charge of the case or the EPAU consultant.

3.3 Anti-D Immunoglobulin is NOT advised for non-sensitised rhesus negative women who are being managed conservatively for an ectopic pregnancy or for PUL, unless felt to be clinically indicated, e.g., signs of intra-peritoneal bleeding.

3.4 An “optimally rising BHCG” does not absolutely exclude an ectopic pregnancy and the patient must be counselled to attend A&E or EPAU immediately if they experience abdominal pain until an intrauterine pregnancy has been demonstrated on ultrasound scan.

3.5 If change in serum BHCG is between a 50% decline and a 63% rise - there should be a high index of suspicion for ectopic pregnancy.

• These high-risk patients should be assessed every 48 hours until diagnosis is confirmed or otherwise. If any patient becomes symptomatic immediate medical review is mandatory.

• If the serum BHCG level decreases more than 50% in 48 hrs. – Likely failing pregnancy even though location is still uncertain.

• If the serum BHCG level increases more than 63% in 48 hrs – Likely to be developing intra uterine pregnancy, however ectopic pregnancy still cannot be excluded.

3.6 Patients that do not attend follow-up as arranged are contacted by telephone. If it is not possible to contact them, a letter/ phone call is made to the patient and her GP highlighting the need for follow up.

3.7 They should be advised that if they experience dizziness, syncope or abdominal pain, they should go directly to A&E and the on call Gynae SpR should be contacted.

3.8 Any PUL patients attending A&E must be reviewed promptly by the on-call team and their management must be discussed with the consultant on call. There should be a low threshold for admission and discussion with the on-call Consultant if there is any doubt about the correct management.

3.9 At Wexham Site, a PUL folder containing names, phone numbers and details of patients being followed up along with PUL proforma can be found in the EPAU. Their notes will be kept in EPAU. This folder should be checked daily by the EPAU nurse/clinician and updated. PUL proforma will be uploaded in EPIC after completion of treatment.

3.10 Expectant Management of PUL is safe if BHCG is low, showing downward trend, the patient is asymptomatic and there was no evidence of haemoperitoneum on scan.

Note

**For medical management, please refer to Ectopic Pregnancy guideline

5.1 The use of S BHCG in the assessment of pregnancies of unknown location (PUL) has resulted in a reduction in hospital admissions and diagnostic laparoscopies for the investigation of possible ectopic pregnancies.

5.2 When serum BHCG should be taken?

• Any women with a diagnosis of PUL on USS.

• Where an ectopic pregnancy has been diagnosed on USS – Serial HCG follow-up may be needed following salpingotomy, medical or conservative management.

• BHCG should be done in suspected cases of Molar pregnancy

5.3 The majority of women above 12 weeks gestation will not require BHCG analysis and therefore this should not be performed until an USS has been carried out, unless there is a high clinical suspicion of an ectopic pregnancy.

5.4 The presence of a gestational sac should exclude a PUL, and such patients do not need serial bloods.

6.1 Progesterone is made by the corpus luteum and the placenta in the early pregnancy. A high progesterone level reflects a normal functioning corpus luteum and placenta of a viable pregnancy

NB 10% of ectopic pregnancies may be viable, and in such cases the progesterone levels may also be high. Consider surgery in these patients.

6.2 A cut off serum progesterone level of 20nmol/L or less, has a positive predictive value of 97% for identifying resolving pregnancies.

6.3 Serum Progesterone will not differentiate ectopic pregnancy from intrauterine pregnancy. However, it is useful in planning the management options for PUL and Ectopic pregnancy.

6.4 Progesterone is to be performed once only. Please do not repeat.

6.5 Progesterone assay is NOT helpful in patients receiving exogenous progesterone (usually IVF/ recurrent miscarriage) patients.

6.6 Progesterone is not indicated when BHCG is requested in suspected molar pregnancies.

7.1 PUL proforma should be completed for all PUL and ectopic pregnancies (100%).

7.2 PUL Leaflet should be given to women who were diagnosed with PUL (100%).

7.3 ALL PUL patients should have 0 hr and 48 hr Serum BHCG levels (100%).

7.4 Anti D prophylaxis should be given within 72 hours to all RH negative women who underwent surgical management of ectopic pregnancy.

7.5 Decision to administer Methotrexate should be taken by Consultant (100%).

• National Institute for Health and Care Excellence [NICE] (2023) Ectopic pregnancy and miscarriage: diagnosis and initial management. NG126. Available at: https://www.nice.org.uk/guidance/ng126 (Accessed: 23 April 2024).

• Banerjee, S. et al. (2001) 'Expectant management of early pregnancies of unknown location: a prospective evaluation of methods to predict spontaneous resolution of pregnancy', BJOG, 108(2), pp. 158-163. Available at: https://doi.org/10.1111/j.1471-0528.2001.00031.x

• Condous, G. et al. (2006) 'Failing pregnancies of unknown location: a prospective evaluation of the human chorionic gonadotrophin ratio', BJOG, 113(5), pp. 521-527. Available at: https://doi.org/10.1111/j.1471-0528.2006.00924.x

• Sagili, H. and Mohamed, K. (2008) 'Pregnancy of unknown location: an evidence-based approach to management', The Obstetrician and Gynaecologist, 10(4), pp. 224-230. Available at: https://doi.org/10.1576/toag.10.4.224.27438

• Hahlin, M et al. (1995) 'The expectant management of early pregnancies of uncertain site', Human Reproduction, 10(5), pp. 1223-1227. Available at: https://doi.org/10.1093/oxfordjournals.humrep.a136123

• National Institute for Health and Care Excellence [NICE] (2008) Routine antenatal anti-D prophylaxis for women who are rhesus D negative. TA156. Available at: https://www.nice.org.uk/guidance/ta156

• Lee, D. et al. (1999) 'Recommendations for the use of anti-D immunoglobulin for Rh prophylaxis', Transfusion Medicine, 9(1), pp. 93-97. Available at: https://doi.org/10.1046/j.1365-3148.1999.009001093.x

• Quereshi, H. et al. (2014) 'BCSH guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn', Transfusion Medicine, 24(1), pp. 8-20. Available at: https://doi.org/10.1111/tme.12091

• Kirk, E. and Bourne, T. (2009) 'Pregnancy of unknown location', Obstetrics, Gynaecology and Reproductive Medicine, 19(3), pp. 80-83. Available at: https://doi.org/10.1016/j.ogrm.2008.11.012

• Association of Early Pregnancy Units (2007) 'AEPU organisational, clinical and supportive guidelines 2007', Archives of Perinatal Medicine, 13(4), pp. 7-28.

• Gamzu, R. et al. (2002) 'Efficacy of methotrexate treatment in extrauterine pregnancies defined by stable or increasing human chorionic gonadotropin concentrations', Fertility and Sterility, 77(4), pp. 761-765. Available at: https://doi.org/10.1016/s0015-0282(01)03256-3

(for information)

Date:

Name

Telephone No

DOB

Hospital No

PUL Category:

1- True PUL.

2- PUL. possible intrauterine pregnancy

3- PUL. Possible incomplete/complete miscarriage

4-PUL. possible Ectopic

Bleeding Score: please ring as appropriate

(based on appearance of sanitary towel, per image below)

Pain Score and location: 0 to 10

0 _____________________________________________________ 10

History: LMP: Amenorrhoea wks:

Biochemistry

Notes

This guideline has been registered with the Trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt, contact a senior colleague or expert. Caution is advised when using guidelines after the review date.

This guideline is for use in Frimley Health NHS Foundation Trust hospitals only. Any use outside this location will not be supported by the Trust and will be at the risk of the individual using it.

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