Bleeding (First Trimester)

• Approximately 25% of pregnant women will experience bleeding in the first trimester. 

• The differential diagnoses include threatened miscarriage, early pregnancy loss, ectopic pregnancy, molar pregnancy, and non-obstetric causes (polyps, ectropion, etc.). 

• Approximately 20% of women with first trimester bleeding have a subchorionic haematoma and approximately 80% of all cases of pregnancy loss occur in the first trimester 14, 15.

• Evaluation of these patients relies on thorough history and physical examination combined with ultrasound imaging (transabdominal/transvaginal). Depending on sonographic findings, other laboratory measurements may be useful (detailed below).

Useful Laboratory measurements include:

• Serum Beta HCG (ßHCG) (detectable as early as 8 days after ovulation)

• According to American College of Obstetricians and Gynecologists (ACOG) guidelines, in cases in which an intrauterine gestation cannot be identified with reasonable certainty on ultrasound, serial ßHCG measurements should be performed.

• Initially, within the first 48 hr in a viable Intrauterine Pregnancy (IUP), the level should rise by approx:

• 49% if  ßHCG <1500 mIU/ml16

• 40% if  ßHCG 1500-3000 mIU/ml16

• 33% if ßHCG >3000 mIU/ml16

• By approx 10 weeks gestational age (GA), ßHCG level plateaus or decreases after which serial USS is the preferred diagnostic tool 17.

• Discriminatory level = ßHCG above which an IUP is expected to be seen on transvaginal ultrasound18.

• The level varies depending on ultrasound scanner used, sonographer, and number of gestations

• 99% chance that intrauterine gestational sac will be seen on ultrasound with ßHCG level of 3510 mIU/ml18

• Level of 1500-3000 mIU/ml typically used18,19

• Rhesus factor

• Should be checked in any pregnant lady whose rhesus status is unknown

• Rh D immune globulin should be given within 72 hrs if abdominal trauma, ectopic pregnancy or undergoing uterine aspiration

• Also indicated within 72 hrs of early pregnancy loss5

• Progesterone

• Useful in distinguishing between viable and non-viable pregnancy in women whose USS scan is non-conclusive. Meta analysis of 26 cohort studies showed that a single progesterone level <6 ng/ml reliably excludes viable pregnancy with a negative predictive value of 99% 20.

• Low progesterone level cannot distinguish between ectopic and intrauterine pregnancy20.

• Haemoglobin

• Baseline haemoglobin (Hb) should be checked in all pregnant women presenting with bleeding7.

• Speculum examination is invasive and can be distressing for patients.

• It is performed as it may reveal a source of bleeding unrelated to pregnancy1.

• However, some studies have shown that clinical diagnosis is highly inaccurate in a STABLE patient presenting to ED with first trimester bleeding and advise that pelvic examination is not always necessary when ultrasound is readily available1,2(Level II evidence).

• If the patient is haemodynamically unstable, urgent ultrasound and Obstetrics/Gynae review is needed.

• Ultrasonography is not associated with risk and is the imaging technique of choice for the pregnant patient. Ultrasonography involves the use of sound waves and is not a form of ionising radiation. There have been no reports of documented adverse fetal effects for diagnostic ultrasonography procedures28,29.

• However, ultrasound imaging should only be performed when clinically indicated to minimise fetal exposure to risk using the ‘keeping acoustic output as low as reasonably achievable (ALARA) principle’. 

• Ultrasonography has an important role in the evaluation of Emergency Department (ED) patients presenting with early pregnancy complaints. Both TAUS and TVUS can be utilised.

• TVUS provides higher resolution and more detail than TAUS through the usage of a higher frequency transducer and the positioning of the probe closer to the cervix and uterus. Whilst acknowledging that TVUS allows for greater detail, it is not always necessary in the evaluation of ED patients with early pregnancy related complaints. Specifically, when one identifies an IUP on TAUS, the utility of subsequent TVUS is reduced as the rate of missing an ectopic pregnancy at that juncture would be low.

• TVUS is recommended if TAUS is inconclusive (Level III-2 evidence).

• The use of Point of Care Ultrasound (POCUS) in early pregnancy (by trained Emergency Physicians) is associated with a significant reduction in TVUS usage, most probably because of identification of IUP on TAUS11.

• Following the identification of an IUP on TAUS, the added diagnostic value of TVUS is low. Given the added time and cost of TVUS, selective instead of routine usage should be encouraged10.

• For a normal IUP, on TVUS clinicians should expect to see:

1. Gestational sac when the ßHCG level is 1500-3000 mIU/ml 

2. Yolk sac when gestational sac >10 mm in diameter (definitive evidence of IUP)

3. Cardiac activity should be present when the embryo exceeds 7 mm in length

• The above criteria are termed ‘discriminatory criteria’. The absence of an expected discriminatory criteria is consistent with pregnancy failure, however imaging may be performed one week later to confirm diagnosis21.

• The βHCG level at which IUP is visible on TVUS  is known as the Discriminatory Level and varies from 1500 to 3000 mUI/ml (NICE ,2012).

• Expected predictors of non-viable gestation are as follows:

• A gestational sac with a mean sac diameter of 8 mm or more without a yolk sac5.

• Gestational sac with mean sac diameter of >16 mm without an embryo (= anembryonic gestation)5.

• The most accurate way to date a pregnancy is to measure the crown-rump length. A difference of <5 mm between the mean sac diameter and the CRL carries an 80% risk of spontaneous early pregnancy loss5.

• A prospective multicentre observational trial performed by Preisler et al (2015) concluded that recently changed cut-off values of gestational sac and embryo size defining miscarriage are appropriate and not too conservative but do not take into account gestational ages22. Preisler et al confirmed that previous cut-off values for mean gestational sac diameter (MGSD) of ≥16 mm and ≥20 mm were not clinically safe and were associated with possible false positive diagnoses of miscarriage. They revised the MGSD to ≥ 25mm.

• Previous criteria using crown-rump length measurements ≥5 mm also carried considerable risk and was revised to ≥7 mm. The results from this observational trial show that the revised cut-off values recommended by the Royal College of Obstetricians and Gynaecologists (RCOG), National Institute for Health and Care Excellence (NICE), and American College of Radiology (all guidelines used to revise this pathway) for mean gestational sac diameter and crown-rump length to diagnose miscarriage are associated with 100% specificity22.

Interval scanning:

• A threatened miscarriage should be diagnosed in women who present with bleeding, but have a viable IUP identified on ultrasound7.

• The rate of early pregnancy loss is approximately 11% after a live foetus has been detected on ultrasound, therefore patients should be counselled regarding the risk despite normal ultrasound findings23.

• When intrauterine pregnancy is detected on US but viability is uncertain, repeat US should be performed24,25. Guidance on the timing between scans and expected findings on repeat scans is important to avoid misdiagnosis and the risk of terminating viable pregnancies. According to Preisler et al, the timing of the second scan relates to gestational sac size at initial scan i.e. if MGSD <12 mm, repeat scanning should be performed more than 14 days later22. This is consistent with Doubliet et al but not with the American College of Radiology which recommends repeat scanning 7-10 days without consideration for initial gestational sac size22,24,25. In these cases a normal increase in ßHCG level or progesterone level can be reassuring.

• Once a yolk sac has been visualised - if there is no embryo with a heartbeat after 11 days, the pregnancy is not viable22.

• For initially empty sacs – if a yolk sac (with no embryo) is visualised on repeat scan, the likelihood of viability is substantially increased. Accordingly, scans should be repeated in these circumstances. Preisler et al describe the possibility of initially identifying an empty sac and then visualising an embryo of CRL <7 mm with no heartbeat on repeat imaging resulting in a viable pregnancy at 11-14 weeks22.

• The requirement for repeat scans can be distressing and cause uncertainty for patients. Evidence shows that giving women information about the likely outcome can manage expectations and reduce anxiety.

• Ultrasonography, if available, is the preferred modality to verify the presence of intrauterine gestation3.

• Sonographic confirmation of an early first trimester intrauterine pregnancy (IUP) is based on the detection of an intrauterine gestational sac4. A 5 mm sonolucent gestational sac should be visible in the endometrium at the fundus by 5 weeks gestational age (GA). A normal sac in IUP consists of a central blastocyst surrounded by a double ring of echogenic chorionic villi and decidua (this distinguishes it from a pseudo gestational sac/‘intra-cavity fluid’ (as termed by Rodgers et al) associated with ectopic pregnancy)5,35. A yolk sac is visible by 6 weeks GA which confirms an IUP5. A 2-5 mm  embryo/fetal pole becomes visible by the end of the 6th week5.

• Ectopic pregnancy (EP) is defined as a gestational sac that implants anywhere other than in the endometrial cavity. It is the leading cause of maternal death in the first trimester – incidence of 5-10% of all pregnancy related deaths6.

• The most common location for an ectopic pregnancy is the fallopian tubes and is associated with high maternal morbidity and mortality if ruptured6.

• Diagnostic methods for ectopic pregnancy are serial serum ßHCGs in correlation with TVUS or TAUS. TVUS has been shown to be more sensitive in the diagnosis of early ectopic pregnancy. Ultrasound findings vary depending on location of EP.

According to the National Institute for Health and Clinical Excellence (NICE) guidelines, the following signs on TVUS indicate that there is a definite/high probability/possible ectopic pregnancy, respectively:

Go to Ectopic pregnancy (suspected) pathway for more information on this topic.

• Pregnancy of Unknown Location (PUL) is a situation in which a pregnancy test is positive but there are no signs of intrauterine or extrauterine pregnancy on transvaginal ultrasound 7, 30 .

• The differential diagnosis can include:

• undetected ectopic pregnancy

• IUP that is too early to be seen on ultrasound

• failed pregnancy

• Serial ßHCG measurements and serial ultrasound scans are recommended. 

• Women should be counselled on the warning signs of ectopic pregnancy e.g. pelvic pain, shoulder tip pain, dizziness 7 .

• In patients with PUL, 50-70% are found to have either an ectopic pregnancy or miscarriage while the remaining 30% have a normal IUP 31 . In the current literature there is no optimal strategy to predict the possible outcome in patients diagnosed with PUL and there are no published randomised controlled trials comparing different diagnostic strategies 13 . PUL management has moved away from establishing pregnancy location towards risk assessment of adverse outcomes 32 . Close monitoring of symptoms, serial quantitative ßHCG testing and ultrasonography seem to be the most practical and valuable methods of managing these patients 12,13 .

• The most feared outcome in PUL is ectopic pregnancy which, if diagnosed late, might increase mortality and morbidity.

• Evaluating the ßHCG ratio (change in ßHCG serum levels within 48 hrs) is the best diagnostic strategy in the case of ectopic pregnancy 33 .

• An increase of > 66% over 48 hrs is a good predictor of intrauterine pregnancy. 

• A decrease of >13% is a good predictor of failing PUL (92.7% sensitivity, 96.7% specificity) 33 .

• Ectopic pregnancy can rupture at any ßHCG level, therefore serial measurements should be obtained until a definitive diagnosis is made or until the level is undetectable 3 .

• Regardless of serum ßHCG levels, women with a PUL should be given written information about what to do if they experience any new or worsening symptoms (NICE 2012).

• Progesterone Level:

• Whilst serum ßHCG is the best method of predicting ectopic pregnancy, measuring progesterone may be helpful at predicting viability 33 , although the evidence is conflicting.

• According to NICE guidelines (2012), serum progesterone should not be used as an adjunct to ßHCG levels in order to diagnose either viable IUP or ectopic pregnancy in women with PUL.

• On the other hand, a metaanalysis performed by Verhaegan et.al (26 cohort studies) has shown that a single progesterone level has a good discriminative capacity to distinguish between viable and non-viable pregnancy in women presenting with early first trimester bleeding AND an  inconclusive ultrasound scan 20,36 . It cannot distinguish between ectopic and non-ectopic pregnancy, however, it may be used to identify patients at risk of ectopic pregnancy who require further evaluation 20,36 .

• Although the progesterone level can be high in both intrauterine and extrauterine pregnancies (reflecting a functionally normal corpus luteum), measuring serum progesterone in women diagnosed with PUL during the initial visit helps to evaluate the risk of early pregnancy complications. It is not recommended to routinely follow up patients with a progesterone level < 10 nmol/L 34 . If the progesterone level is <20 mmol/L, it is highly predictive of a failing pregnancy whereas a progesterone level of >60 is strongly associated with viable pregnancy 33

• Recently a multicentre trial showed that a two-step protocol using the M6 model triaged effectively the majority of women with PUL as being at low risk of EP, minimizing the need for follow up after 2 visits 36 .

• Gestational trophoblastic disease is characterised by a ‘snowstorm’ of amorphous material filling the uterus in patients presenting in the first trimester^8,9.

• If CRL or Mean Gestational sac diameter are measured on transabdominal US, repeat measurement should be obtained in >14 days before making a diagnosis (NICE 2012).