P2010/0309-001 WACSClinProc1.

18 Title: Replaces: Description: Target Audience: Key Words: Policy Supported: Ectopic Pregnancy New Guideline Management of first trimester pregnancy complications Midwives and medical officers, QVMU

Pharmacy Manual Safe Handling of Cytotoxic Agents P2010/0475-001 Chemotherapeutic Agent Administration

Purpose: Ectopic pregnancy is a pregnancy outside the uterus. 95% occur in the Fallopian tube. The incidence of ectopic pregnancy is estimated as 1 in 200 pregnancies. Risk Factors: Previous pelvic inflammatory disease Previous tubal surgery Previous ectopic pregnancy Progesterone only pill Intrauterine contraceptive device insitu In vitro fertilisation treatment or assisted fertilisation

Symptoms Not all ectopic pregnancies are symptomatic and display the classic range of clinical signs and symptoms. The diagnosis of ectopic pregnancy should always be considered in any women of reproductive age who complains of abdominal pain. Abdominal pain, vaginal bleeding and amenorrhoea are the most common presenting symptoms, however shoulder tip pain (from free blood irritating the abdominal diaphragm), collapse or hypovolemic shock occur in 20% of cases. Gastrointestinal symptoms may be prominent in ectopic pregnancy, notably diarrhoea and painful defecation.

Assessment PV bleeding +/- abdominal pain Positive pregnancy test Transvaginal USS intrauterine gestational sac not seen, adnexal mass maybe seen, free fluid may be present. Hb
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Antibodies Quantitative HCG

Management Options Medical and surgical treatment are equally successful in women who are haemodynamically stable and have HCG levels <3000IU/L, small tubal diameter and no fetal cardiac activity. Women should be provided with information concerning the advantages and disadvantages of treatment options. Expectant Awaiting spontaneous resolution of confirmed ectopic pregnancy is only acceptable when: HCG levels are low (<1000 IU/L) and declining progressively The tubal mass is less than 2cm in diameter without any recognisable fetal parts Absence of any clinical symptoms Women need to be followed up closely monitoring HCG until levels < 10IU/L

Medical Management Non surgical management with methotrexate may be offered to carefully selected women. Methotrexate is a folic acid antagonist that is widely used for the treatment of neoplasia, severe psoriasis and rheumatoid arthritis. It inhibits DNA synthesis and cell production, primarily in actively proliferating cells such as malignant cells, trophoblasts and fetal cells.

Advantages Good success rates (>80%) in appropriately selected cases Maybe comparable to conservative surgery in terms of subsequent fertility General anaesthetic avoided

Disadvantages Risk of toxicity nausea, stomatitis, bone marrow suppression, pneumonitis, elevated liver enzymes Treatment requires repeated visits to ensure resolution of pregnancy

Indications Clinically stable Able and willing to attend follow-up scans and blood tests Early unruptured ectopic pregnancy HCG less than 3000 IU/L Tubal size less than 3 cm and no fetal cardiac activity on ultrasound Failed surgical treatment Surgery contraindicated or likely to be difficult
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Contraindications Haemodynamic instability Severe immunodeficiency Leucopenia, thrombocytopenia, high concentrations of liver enzymes or serum creatinine High HCG concentration Large ectopic size Fetal cardiac activity Breastfeeding

Registrar/Consultant responsibilities Explain treatment options Written consent Pre treatment bloods HCG, U+E, LFT, FBC Anti D if Rh neg Womens weight and height to calculate body surface area. Single dose Methotrexate 50mg/m2 intramuscularly Advise women that there will be some pain as the pregnancy resolves - paracetamol Avoid intercourse during treatment Use contraception for at least one (3 months) cycle after treatment Avoid alcohol for 7 days Avoid herbal preparation and vitamin supplements containing folate

Follow-up Return to PAC/gynae clinic twice weekly until HCG is falling, then weekly until <10 IU/L. There may be a transient rise in the HCG in the first four days after the injection Consider repeat methotrexate if HCG not decreased by at least 25% on day seven from pre-treatment level. Consider surgical treatment if HCG levels: o o o Show no significant (<50%) fall seven days Plateau Rise after day seven

HCG may fall slowly. Median time to resolution is one month.

Surgical Management Indications for surgical treatment: Ruptured ectopic Haemodynamically unstable Inability or unwillingness to comply with or contraindication to medical treatment
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Failed medical treatment

For women who are haemodynamically unstable: o Resuscitate o o o IV access FBC and X Match Arrange theatre do not delay

Management of tubal pregnancy in the presence of haemodynamic instability should be by the most expedient method. In the presences of a healthy contralateral tube there is no clear evidence that salpingotomy should be used in preference to salpingectomy. A laparoscopic approach to the surgical management of tubal pregnancy in the haemodynamically stable woman is preferable to an open approach depending on the skills of the surgeon.

Follow-up HCG day 3 and day 7 unless salpingectomy performed with confirmation of removal of chorionic villi &/or ectopic. Discharge Discuss risk of residual or recurrent ectopic Gynae clinic appointment in 4 - 6 weeks Discharge letter to general practitioner Social work referral/ contact offered

Written information on early pregnancy loss Attachments Attachment 1 HCG Information Attachment 2 References

Performance Indicators: Evaluation of compliance with guideline to be achieved through medical record audit annually by clinical Quality improvement Midwife WACS Review Date: Annually verified for currency or as changes occur, and reviewed every 3 years via Policy and Procedure working group coordinated by the Clinical and Quality improvement midwife. November 2009 Midwives and medical staff WACS Dr A Dennis Co-Director (Medical) Sue McBeath Co-Director (Nursing & Midwifery) Womens & Childrens Services Sue McBeath Co-Director (Nursing & Midwifery) Womens & Childrens Services

Stakeholders: Developed by:

Dr A Dennis Co-Director (Medical) Womens & Childrens Services Date: 1 December 2007
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ATTACHMENT 1 HCG HCG in a viable pregnancy Mean doubling time for HCG is from 1.4 to 2.1 days in early pregnancy In 85% of viable intrauterine pregnancies HCG rises by 66% every 48 hours during the first 40 days The slowest recorded rise over 48 hours with a viable pregnancy was 53%.

HCG rises at a much slower rate in most but not all ectopic and nonviable intrauterine pregnancies. Diagnostic evaluation TVS diagnostic alone if yolk sac, embryo or embryonic cardiac activity detected The presence of an intrauterine sac is likely to exclude ectopic pregnancy Quantitative HCG Risk of heterotopic pregnancy 1:25 000 except with ART

Discriminatory Zone describes the HCG levels above which the gestational sac can be visualised using ultrasound scan. HCG 1500 2000 IU/L with transvaginal ultrasound (TVS) HCG 5000IU/L with transabdominal ultrasound HCG above the discriminatory zone If TVS doesnt show intrauterine pregnancy but complex adnexal mass then suspect extrauterine pregnancy If no mass then possible multiple pregnancy repeat HCG and TVS in 2 days If HCG is increasing or plateauing then likely ectopic If HCG is decreasing then failed pregnancy (cannot exclude ectopic)

HCG below the discriminatory zone Repeat HCG in 3 days (72 hours allows doubling of HCG) Once HCG reaches 1500 2000 then TVS If HCG doesnt double then pregnancy abnormal Falling HCG indicates failed pregnancy

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ATTACHMENT 2 REFERENCES Hajenius, P, Mol, F, Mol, B, Bossuyt, P, Ankum, W & van der Veen, F. Interventions for tubal ectopic pregnancy Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD000324. DOI: 10.1002/14651858.CD000324.pub2. Royal College of Obstetricians 2004, The management of tubal pregnancy Guideline 21, Online: http://www.rcog.org.uk/files/rcogcorp/GTG21Tubal11022011.pdf Tulandi, T 2007, Clinical manifestations, diagnosis, and management of ectopic pregnancy, UpToDate, Online: http://uptodateonline.com/utd/content/topic.do?topicKey=gen_gyne/8302&selectedTit le=2~98&source=search_result Tulandi, T 2007, Methotrexate therapy of ectopic pregnancy, UpToDate, Online: http://uptodateonline.com/utd/content/topic.do?topicKey=gen_gyne/11036&selectedT itle=5~98&source=search_result Tulandi, T 2007, Surgical treatment of ectopic pregnancy and prognosis for subsequent fertility, UpToDate, Online: http://uptodateonline.com/utd/content/topic.do?topicKey=gyn_surg/5788&selectedTitl e=3~98&source=search_result Tulandi, T 2006, Expectant management of ectopic pregnancy, UpToDate, Online: http://uptodateonline.com/utd/content/topic.do?topicKey=gen_gyne/28942&selectedT urce=search_result

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