Early Pregnancy Bleeding

CLINICAL

Carol Breeze

Background wenty to forty per cent of A speculum examination must be pregnant women will experience performed and any products of conception Twenty to forty per cent of pregnant T bleeding during the first trimester (POC) removed from the cervical os. These women will experience bleeding during of pregnancy.1 The major causes patients may require urgent transfer to the the first trimester. Initial presentation are miscarriage (10–20% of clinical operating theatre for a suction curettage, is usually to the general practitioner. pregnancies) and ectopic pregnancy laparoscopy or laparotomy. Complications of miscarriage, including (1–2%).2 Bleeding in the very early In the haemodynamically stable patient, threatened miscarriage and ectopic weeks of pregnancy may be related to a more detailed assessment can be pregnancy, are the most common endometrial implantation. Rarer causes undertaken in the community setting. diagnoses. The failure to diagnose include cervical and vaginal lesions (eg an ectopic pregnancy may have life- History threatening consequences for a woman. malignancy, cervical ectropion, polyps, infection) and uterine infection. Gestational It is important to assess the likely Objectives trophoblastic disease should always be gestational age of the pregnancy, the considered, particularly in the setting of an amount of blood loss and any associated The aim of this article is to review abnormally raised serum human chorionic pain symptoms. Syncope, chest pain and the history, examination findings, gonadotropin (hCG) or suggestive shortness of breath may point to anaemia investigations and management options ultrasound findings. Establishing the site from significant blood loss, and shoulder for miscarriage and ectopic pregnancy. of the pregnancy is vital, as failure to tip pain may be associated with intra- correctly diagnose an ectopic can have abdominal bleeding. Discussion potentially life-threatening consequences. Risk factors for ectopic pregnancy include:1 Early pregnancy bleeding is a very • current use of an intrauterine device distressing symptom for which a woman Assessment (IUD) or the minipill seeks reassurance that she has an The initial assessment of a woman with • pregnancy as a result of assisted ongoing pregnancy. It is not always vaginal bleeding in early pregnancy must reproduction possible to make a diagnosis at the first first consider haemodynamic stability and • a past history of pelvic infection or presentation. In some cases, the need the degree of pain or bleeding. Immediate sexually transmissible infections (STIs) for follow-up investigations or referral transfer to the emergency department is or tubal surgery to a gynaecologist is required. As necessary in a haemodynamically unstable • previous ectopic pregnancy.1 healthcare providers, we should continue patient. It is important to recognise that Cervical smear history is relevant, to review and update our knowledge young women may suffer significant blood particularly if any abnormal bleeding has in the management of this common loss before any signs of haemodynamic also been occurring outside of pregnancy. presentation in order to optimise our care instability are evident. Certain medical conditions, such as poorly of these patients. The most likely diagnoses of a controlled diabetes and thyroid disease, haemodynamically unstable patient are associated with an increased risk of with early pregnancy bleeding are a miscarriage.3 ruptured ectopic pregnancy an incomplete miscarriage with ‘cervical shock’ Examination (parasympathetic stimulation caused by Following initial assessment for any products in the cervical os leading to evidence of haemodynamic instability hypotension and bradycardia) or massive and anaemia, abdominal examination haemorrhage secondary to miscarriage. may reveal areas of tenderness, guarding

or rigidity, and signs of distension. The experienced sonographer. On transvaginal based on the absence of evidence of an fundus will be palpable above the ultrasound (TVS), a gestational sac will IUP on TVS. Table 1 gives examples of a symphysis pubis when the uterus reaches usually be visible from four weeks and discriminatory hCG of 2000 IU/L, with the size appropriate for a 12-week three days after the last menstrual period,5 TVS findings and recommendations for gestation. It may be palpable earlier than assuming the dates are correct and management. this in the case of a multiple pregnancy, menstrual cycle is regular (Figure 1). gestational trophoblastic disease (GTD), or A non-viable pregnancy is diagnosed Pregnancy of unknown if other pelvic or uterine masses such as on ultrasound under either or both of the location fibroids or ovarian cysts are present. following circumstances: If there are no signs on a TVS of an Speculum examination is performed to • no live fetus visible in a gestational sac intra- or extra-uterine pregnancy, and assess the amount and origin of ongoing where the mean sac diameter (MSD) is no obvious retained POC are seen, the bleeding. The vagina and cervix should be >25 mm pregnancy is defined as a pregnancy of inspected for other causes of bleeding • visible fetal pole with a crown rump unknown location (PUL). Under these (eg polyps). Tissue present in the open length (CRL) of >7 mm, with no circumstances, the three possible cervical os must always be removed fetal heart activity after a period of scenarios are:5 and should be sent for histopathological observation of at least 30 seconds.5 • intrauterine pregnancy examination to confirm retained POC. If there is any doubt regarding the viability • ectopic pregnancy Bimanual examination allows assessment of the fetus, a second opinion or a review • failed PUL. of uterine size, dilatation of the cervical scan in one week is recommended. If a When interpreting the scan result of a os, pelvic tenderness and cervical motion gestational sac is not visible in the uterus, woman with a PUL, there is evidence that tenderness. the adnexa should be carefully examined serum hCG levels at zero and 48 hours are Pelvic and cervical motion tenderness for evidence of an ectopic pregnancy helpful in diagnosis of the ectopic location.5 need immediate further investigation and (Figure 2). An adnexal mass is the most Until the location is determined, a discussion with a specialist. common ultrasound finding in ectopic woman with a PUL could have an ectopic pregnancies, present in >88% of cases.6 pregnancy. It is therefore important to Investigations The discriminatory zone is the serum re‑assess the woman if symptoms change. A combination of ultrasound assessment hCG level above which a gestational sac Women who have a plateauing hCG, or and measurement of serum hCG is should be visualised on TVS. In most new or worsening clinical symptoms, required to determine the location and institutions, this is set at 1500 or 2000 require referral for specialist assessment. viability of an early pregnancy when the IU/L, although a number of variables, Clinical symptoms may necessitate woman has presented with bleeding. including skill of the sonographer and admission to hospital while further Testing for maternal blood group and quality of the ultrasound, can alter the investigations are undertaken. antibody status will determine the need level. Below the hCG discriminatory zone, for Rh D immunoglobulin administration. the diagnosis of a non-viable pregnancy Management of miscarriage Serum hCG levels rise exponentially can be made solely on the basis of an Several terms are used to describe up to six to seven weeks of gestation, inappropriately rising hCG. Above the clinical scenarios around the process of increasing by at least 66% every 48 discriminatory zone, the diagnosis is miscarriage. These are defined in Table 2. hours.4 Following repeat measurements separated by 48–72 hours, a falling hCG is consistent with a non-viable pregnancy, but does not indicate whether the pregnancy is a failed intrauterine pregnancy (IUP), or an involuting ectopic. Plateaued or very slow to rise levels of hCG (<50% in 48 hours) are suggestive of an ectopic or non-viable intrauterine pregnancy.3 However, it should be noted that an apparently appropriately rising hCG is found in 21% of ectopic pregnancies.3 Ultrasonography for pregnancy Figure 1. Gestational sac within uterine cavity assessment in the first trimester should on TVS Figure 2. Ectopic pregnancy on TVS be performed transvaginally by an

284 AFP VOL.45, NO.5, MAY 2016 © The Royal Australian College of General Practitioners 2016 EARLY PREGNANCY BLEEDING CLINICAL

Threatened miscarriage is treated highly effective for medical evacuation options for the treatment of miscarriage. expectantly. There is a 2.6 times increased of the uterus given either vaginally or It showed comparable efficacy and no risk of miscarriage later in the same orally.10 Further research is required to significant difference in infection rates pregnancy in cases of early threatened determine the optimal dose and route (2–3%). The trial reported that unplanned miscarriage, and 17% of women go on to of administration. Medical management hospital admissions were significantly have further complications in pregnancy should only be performed in a unit with increased in the expectant (49%) and (such as pre-term labour or intrauterine experience in this form of management medical (18%) groups, compared with the growth restriction).7 There is insufficient Surgical evacuation is the treatment surgical group (8%). Surgical management evidence to recommend progesterone of choice for women with haemorrhage was required in 44% of the expectant administration in the setting of threatened or sepsis. A woman may choose a group and 13% of those given medication; miscarriage.8 surgical evacuation in order to avoid pain, 5% of the surgical group required a further For inevitable, incomplete and missed bleeding and prolongation of the process. surgical procedure. miscarriages, management options Medical management is contraindicated include expectant, medical and surgical in some cases, such as for a woman on Management of ectopic treatments. Depending on the method anticoagulant therapy. Complications of pregnancy chosen, follow-up will be required to surgical evacuation include anaesthetic Ninety-five per cent of ectopic ensure complete evacuation of the risks, haemorrhage, perforation, retained pregnancies are situated in the fallopian uterus. A complete miscarriage requires POC and endometritis. tube.12 Other, rarer sites include the evaluation of any ongoing bleeding, The MIST trial,11 a large, randomised cervix, ovary, other abdominal sites or in with confirmation that the cervical os is controlled trial, compared expectant, a caesarean section uterine scar. Rarely, closed, and, if necessary, a TVS to rule out medical and surgical management an ectopic pregnancy may co-exist with retained POC. Expectant management involves allowing the natural process of expulsion Table 1. Interpretation of hCG and TVS findings of uterine POC to occur without hCG/TVS in clinically stable women Interpretation/recommendation intervention. The woman must be informed regarding the expected length hCG <2000 IU/L Repeat TVS/hCG in 48–72 hours of the process, symptoms of pain and hCG >2000 IU/L and TVS with no IUP, High probability of ectopic pregnancy bleeding that she is likely to experience, complex adnexal mass and/or free fluid and how to seek emergency medical hCG >2000 IU/L and TVS with no IUP Repeat TVS/ hCG in 48–72 hours assistance. For incomplete miscarriages, and no abnormal findings 60% of women experience complete Declining or suboptimally rising hCG Indicates a non-viable pregnancy (ectopic or expulsion of products in the ensuing two levels IUP), appropriate follow-up to ensure adequate weeks and 90% by six to eight weeks.9 resolution of either diagnosis Missed miscarriages generally take longer hCG, human chorionic gonadotropin; TVS, transvaginal ultrasound; IVP, intrauterine pregnancy to expel. Ongoing review should occur at one to two weeks, and if pain and bleeding Table 2. Defintions of miscarriage have ceased, a repeat serum hCG should be performed at three weeks. If this is Miscarriage Pregnancy loss before 20 weeks’ gestation or fetal weight <400 g positive, further assessment with serial Threatened Vaginal bleeding prior to 20 weeks’ gestation hCG measurements, to ensure these fall Inevitable Passage of POC of a non-viable IUP occurring or expected to occur to negative levels, or an ultrasound scan imminently may be required to assess for retained Incomplete Some retention of POC of a non-viable IUP POC. Missed Ultrasound scans diagnosis of a non-viable IUP in the absence of vaginal If no bleeding or pain occurs within bleeding seven to 14 days of the initial consultation, repeat the ultrasound and further discuss Septic Miscarriage complicated by infection all treatment options as appropriate. Recurrent Three or more consecutive miscarriages

Medical management involves the Complete Full expulsion of POC of an IUP use of misoprostol (a prostaglandin E1 POC, products of conception; IVP, intrauterine pregnancy analogue), which has been shown to be

an intrauterine pregnancy (heterotopic treatment for ectopic pregnancy appears 4. Barnhart KT, Sammel MD, Rinaudo PF, Zhou L, pregnancy). to be similar between methotrexate, Hummel AC, Guo W. Symptomatic patients with an early viable intrauterine pregnancy: hCG curves Management options for tubal salpingotomy and salpingectomy groups.15 redefined. Obstet Gynecol 2004;104(1):50–55. ectopic pregnancy include surgery 5. Australasian Society for Ultrasound in Medicine. Management of rhesus Guidelines for the performance of first trimester (salpingectomy or salpingostomy), ultrasound. Sydney: ASUM, 2014. medical management with methotrexate, negative patients 6. Dogra V, Paspulati RM, Bhatt S. First trimester and possibly expectant management in Rh D immunoglobulin (RhIg) is indicated bleeding evaluation. Ultrsound Q 2005;21(2):69–85. 7. National Institute for Health and Clinical a limited population of carefully selected for the prevention of Rh D sensitisation Excellence. NICE Guidelines 154: Ectopic cases, although no high-level evidence in Rh D negative women. RhIg can be pregnancy and miscarriage. London: NICE, 2015. exists to recommend this approach. obtained through emergency departments 8. Wahabi HA, Fayed AA, Esmaeil SA, Al Zeidan RA. Progestogen for treating threatened miscarriage. Surgery is required for the or blood banks; 250 IU RhIg is required Cochrane Database Syst Rev 2011(12):CD005943. haemodynamically unstable patient, for a first trimester sensitising event 9. Nanda K, Lopez LM, Grimes DA, Peloggia A, those with evidence of rupture, Nanda G. Expectant care versus surgical such as miscarriage, ectopic pregnancy, treatment for miscarriage. Cochrane Database after failed medical treatment and termination of pregnancy and chorionic Syst Rev 2012;3:CD003518. if contraindications to methotrexate villous sampling. This should be given 10. Neilson JP, Gyte GM, Hickey M, Vazquez C, Dou L. Medical treatments for incomplete miscarriage therapy exist (including the possibility within 72 hours of the sensitising event, (less than 24 weeks). Cochrane Database Syst of non-compliance with follow-up). though administration of RhIg up to Rev 2010;(1):CD007223. Some patients may choose surgery over nine to 10 days later may provide some 11. Trinder J, Brocklehurst P, Porter R, Read M, Vyas S, Smith L. Management of miscarriage: Expectant, medical management. Laparsocopic protection.1 medical, or surgical? Results of randomised surgery should be performed whenever controlled trial (miscarriage treatment (MIST) trial). BMJ 2006;332(7552):1235–40. 13 Conclusion possible. A salpingectomy is usually 12. Farquar CM. Ectopic pregnancy. Lancet performed unless the contralateral tube Early pregnancy bleeding can cause great 2005;366(9485):583–91. is damaged. A salpingostomy may result anxiety and distress for a woman, her 13. Hajenius PJ, Mol F, Mol BW, Bossuyt PM, Ankum WM, van der Veen F. Interventions for 14 in a need for further treatment (4–15%) partner and family, especially where a tubal ectopic pregnancy. Cochrane Database Syst with methotrexate or a salpingectomy diagnosis of a non-viable pregnancy is Rev 2007;(1):CD000324. if follow-up hCG levels do not fall 14. Fernandez H, Capmas P, Lucot JP, et al. Fertility made. It is important that the situation is after ectopic pregnancy: The DEMETER appropriately. In women who have had dealt with both safely and sensitively and randomized trial. Hum Reprod 2013;28(5):1247–53. a salpingostomy, hCG levels should be that the woman and her family are well 15. Menon S, Colins J, Barnhart KT. Establishing a human chorionic gonadotropin cutoff to guide measured weekly until negative due supported throughout this time. Most methotrexate treatment of ectopic pregnancy: A to the potential for retained pregnancy tertiary and many regional hospitals now systematic review. Fertil Steril 2007;87(3):481–84. tissue in the affected tube. In the case of run early pregnancy assessment clinics a salpingectomy, histological confirmation that can assist GPs in the management of of a tubal pregnancy is usually all that is complications in the first trimester. required. About one-third of patients with Author Carol Breeze MBChB, FRANZCOG, Staff Specialist, ectopic pregnancy are suitable Obstetrics and Gynaecology, Cairns Hospital, for medical management with Lecturer, Obstetrics and Gynaecology, James Cook methotrexate. These women should University, Townsville, QLD. Carol.Breeze@health. qld.gov.au be haemodynamically stable, be able Competing interests: None. to comply with treatment and follow- Provenance and peer review: Commissioned, up, ideally have an hCG <5000 IU/L externally peer reviewed. (the greatest predictor of success)7, 1 5 References and an adnexal mass <3.5 cm with no 1. Queensland Clinical Guidelines. Maternity and fetal cardiac activity. Initial treatment neonatal clinical guideline. Early pregnancy loss. is with a single intramuscular dose of Brisbane: Queensland Health, 2011. 2 2. King Edward Memorial Hospital. Clinical guidelines methotrexate (50 mg/m ), with 14% of – Ectopic pregnancy. Subiaco, WA: Department of women requiring a further dose. Success Health, 2014. rates are up to 85%, which is similar to 3. UpToDate. Approach to the evaluation of early pregnancy bleeding. Alphen aan den Rijn, South 9 salpingostomy. Up to 15% of women Holland: Wolters Kluwer, 2016. Available at www. may require surgical intervention. uptodate.com/contents/image?imageKey=OBGY- N/88947&topicKey=OBGYN%2F6799&- Ongoing fertility in the two to three source=preview&rank=undefined [Accessed years following surgical or medical 4 February 2016].