Bleeding and pain are experienced by 20% of women during the first trimester of pregnancy. Although most pregnancies complicated by pain and bleeding tend to progress normally, these symptoms are distressing for woman, and they are also associated with an increased risk of miscarriage and ectopic pregnancy. Ultrasound is the first and often the only diagnostic modality that is used to determine location of early pregnancy and to assess its health. Ultrasound is an accurate, safe, painless and relatively inexpensive diagnostic tool, which all contributed to its widespread use in early pregnancy. Pain and bleeding in early pregnancy are sometimes caused by concomitant gynaecological, gastrointestinal, and urological problems, which could also be detected on ultrasound scan. In women with suspected intra-abdominal bleeding, ultrasound scan can be used to detect the presence of blood and provide information about the extent of bleeding.
In this chapter, we comprehensively review the use of ultrasound in the diagnosis and management of early pregnancy complications. We include information about the diagnosis of gynaecological and other pelvic abnormalities, which could cause pain or bleeding in pregnancy. We also provide a summary of the current views on the safety of ultrasound in early pregnancy.
Introduction
Pain and vaginal bleeding are experienced by about one in five women during the first trimester of pregnancy . The symptoms may vary from light painless bleeding to severe pain, accompanied by haemorrhagic shock. Clinical presentation is helpful in determining the likely cause of women’s symptoms, but, in most cases, ultrasound imaging is required to reach a conclusive diagnosis. About one-half of pregnancies complicated by bleeding will progress normally beyond the first trimester, with the remaining women suffering an early pregnancy failure . A total of 10–15% women presenting with vaginal bleeding have an ectopic pregnancy . A timely and accurate diagnosis of ectopic pregnancy is important to minimise the risk of serious adverse outcomes. It is important to remember that bleeding may also be caused by conditions that are coincidental to pregnancy, such and cervical polyps, vulval and vaginal lesions, and injury during sexual intercourse. Abdominal pain is often a late symptom in women with miscarriages and ectopic pregnancy. It may also be caused by intra-abdominal haemorrhage caused by a ruptured corpus luteum cyst or by ovarian torsion. Non-gynaecological causes of pain include acute cystitis, ureteric stones, appendicitis, and constipation. Differential diagnosis between these conditions is difficult, based on clinical symptoms alone, and some form of imaging is almost always required to reach the correct diagnosis.
The development of high-resolution transvaginal ultrasound technology in the 1980s has enabled significant progress in early pregnancy imaging. Since then, transvaginal ultrasonography has become the accepted standard for examining women with suspected complications of early pregnancy . With advances in ultrasound diagnosis, pregnancies could be identified earlier in gestation compared with transabdominal ultrasound, resulting in better diagnostic accuracy. Diagnosis of early pregnancy complications has been further enhanced by combining ultrasound findings with the results of biochemical tests such as human chorionic gonadotrophin (hCG) and progesterone. In this chapter, we aim to provide a summary of recent development in ultrasound imaging in pregnancy, with plenty of practical advice to those providing clinical care to women with suspected early pregnancy complications.
Normal early intrauterine pregnancy
When performing ultrasound scan in early pregnancy, it is important to confirm the location of pregnancy, its viability, and gestational age . Although the ultrasound diagnosis of intrauterine pregnancy is generally considered to be straightforward, criteria to diagnose an intrauterine pregnancy are conspicuously absent from the literature. This makes it hard to differentiate between a pregnancy that is normally implanted within the uterine cavity and several types of ectopic pregnancies confined to the uterus, such as interstitial, cervical, or intramural pregnancies. A normal intrauterine pregnancy should be located within the uterine cavity, which represents a virtual space lined with endometrium extending from the internal cervical orifice to tubal ostia. In addition, the trophoblast should not be invading beyond the endometrial myometrial junction .
A normal intrauterine pregnancy can be consistently visualised on ultrasound scan 3 weeks after conception (i.e. 5 weeks after last menstrual period in a woman with regular 28-day cycle) . When assessing the uterus, the probe is moved in the transverse plane from the internal orifice to the fundus in search of an intrauterine pregnancy. Longitudinal view is then used to show the location of the gestational sac beneath the endometrial surface and to confirm its intrauterine location by demonstrating a communication between the cervical canal and the uterine cavity. If a gestational sac is not immediately visible, the endometrial morphology should be assessed to search for the signs of retained products. Endometrial thickness measurements are not useful to discriminate between an early intrauterine pregnancy, incomplete miscarriage, and ectopic pregnancy . Sweeping the probe both side to side and up and down will facilitate the assessment of the cervix, caesarean section scar (if present), myometrium, and interstitial portion of the Fallopian tubes, to rule out unusual sites of ectopic pregnancy implantation.
In a normal pregnancy, the gestational sac first becomes visible on transvaginal scan at 4 weeks and 3 days of gestation ( Fig. 1 a) . The sac usually appears as a circular structure with a thick echogenic rim surrounding a clear anechoic centre, which represents early chorionic cavity. The sac is located just below the midline echo, buried into the decidualised endometrium. Myometrial cysts in women with adenomyosis may sometimes appear similar to an early gestational sac. They are typically located within the myometrium beyond the endometrial–myometrial junction, which facilitates the differential diagnosis . Accumulation of blood within the uterine cavity may also resemble an early gestational sac. This is described as a pseudosac, which is particularly common in ectopic pregnancy, and it should not be confused with an intrauterine gestation. A pseudosac appears like an elongated structure inside the cavity, surrounded by a single decidual layer. On colour Doppler examination, the pseudosac is avascular and its shape may change during the scan, whereas a normal pregnancy tends to have high peripheral blood flow and its shape is stable. The gestational sac is measured using the mean of three perpendicular diameters. In early gestation, the sac grows about 1 mm in mean diameter per day. A large, empty, slowly growing and irregular gestational sac is suggestive of pregnancy failure (this will be discussed in more detail in the miscarriage section).
The yolk sac becomes visible within the gestational sac (i.e. chorionic cavity) from 5 weeks’ gestation ( Fig. 1 b). Measurement technique is similar to that of the gestational sac, always including three perpendicular diameters from the centre of the yolk sac wall. If the yolk sac is large (>5.6 mm) or not visible when the mean gestational sac diameter reaches over 13 mm , repeat ultrasound in a week is advised, as these findings are strongly associated with early pregnancy failure.
Early embryo is typically located adjacent to the yolk sac, and it appears as a linear bright echo ( Fig. 1 c). The two structures are connected by the vitelline duct. From 7 weeks’ gestation onwards, crown (head) can be distinguished from rump (trunk) ( Fig. 1 d). Crown–rump length should be measured from a sagittal section of the embryo, with care to avoid including the yolk sac into the measurement .
Cardiac activity can be documented at around 5 weeks and 5 days’ gestation, when the embryo measures 2–5 mm in length. Background movement and maternal pulsation can sometimes be misinterpreted as embryonic cardiac activity. Heart rate should be measured using M-mode; pulsed Doppler examination produces high-energy acoustic outputs and should not be used in early first-trimester pregnancy ( Fig. 1 c) . It has been reported that heart rates below 100 beats per minute are suggestive of an abnormal pregnancy . It is important to recognise, however, that, in early normal gestations, heart rate could be below 100 beats per minute, yet increase rapidly between 6–7 weeks’ gestation. If a heartbeat is not visible in an embryo, colour Doppler may be useful to confirm a negative finding provided it is used for a short period of time with both mechanical and thermal index set to less than 1.
From 7 weeks’ gestation, the amniotic cavity becomes visible and should be measured in three dimensions. In addition, rhombencephalon and spine may be distinguished, and the umbilical cord seen. At 8 weeks’ gestation, forebrain, midbrain, hindbrain and skull are apparent, and limb buds start to grow. The amniotic cavity expands, whereas the umbilical cord and vitelline duct lengthen and a mid-gut hernia appears. Between 7–9 weeks’ gestation, amniotic and chorionic cavities are not fused, and chorionicity and amnionicity of multiple pregnancies can be confidently established.
Normal early intrauterine pregnancy
When performing ultrasound scan in early pregnancy, it is important to confirm the location of pregnancy, its viability, and gestational age . Although the ultrasound diagnosis of intrauterine pregnancy is generally considered to be straightforward, criteria to diagnose an intrauterine pregnancy are conspicuously absent from the literature. This makes it hard to differentiate between a pregnancy that is normally implanted within the uterine cavity and several types of ectopic pregnancies confined to the uterus, such as interstitial, cervical, or intramural pregnancies. A normal intrauterine pregnancy should be located within the uterine cavity, which represents a virtual space lined with endometrium extending from the internal cervical orifice to tubal ostia. In addition, the trophoblast should not be invading beyond the endometrial myometrial junction .
A normal intrauterine pregnancy can be consistently visualised on ultrasound scan 3 weeks after conception (i.e. 5 weeks after last menstrual period in a woman with regular 28-day cycle) . When assessing the uterus, the probe is moved in the transverse plane from the internal orifice to the fundus in search of an intrauterine pregnancy. Longitudinal view is then used to show the location of the gestational sac beneath the endometrial surface and to confirm its intrauterine location by demonstrating a communication between the cervical canal and the uterine cavity. If a gestational sac is not immediately visible, the endometrial morphology should be assessed to search for the signs of retained products. Endometrial thickness measurements are not useful to discriminate between an early intrauterine pregnancy, incomplete miscarriage, and ectopic pregnancy . Sweeping the probe both side to side and up and down will facilitate the assessment of the cervix, caesarean section scar (if present), myometrium, and interstitial portion of the Fallopian tubes, to rule out unusual sites of ectopic pregnancy implantation.
In a normal pregnancy, the gestational sac first becomes visible on transvaginal scan at 4 weeks and 3 days of gestation ( Fig. 1 a) . The sac usually appears as a circular structure with a thick echogenic rim surrounding a clear anechoic centre, which represents early chorionic cavity. The sac is located just below the midline echo, buried into the decidualised endometrium. Myometrial cysts in women with adenomyosis may sometimes appear similar to an early gestational sac. They are typically located within the myometrium beyond the endometrial–myometrial junction, which facilitates the differential diagnosis . Accumulation of blood within the uterine cavity may also resemble an early gestational sac. This is described as a pseudosac, which is particularly common in ectopic pregnancy, and it should not be confused with an intrauterine gestation. A pseudosac appears like an elongated structure inside the cavity, surrounded by a single decidual layer. On colour Doppler examination, the pseudosac is avascular and its shape may change during the scan, whereas a normal pregnancy tends to have high peripheral blood flow and its shape is stable. The gestational sac is measured using the mean of three perpendicular diameters. In early gestation, the sac grows about 1 mm in mean diameter per day. A large, empty, slowly growing and irregular gestational sac is suggestive of pregnancy failure (this will be discussed in more detail in the miscarriage section).
The yolk sac becomes visible within the gestational sac (i.e. chorionic cavity) from 5 weeks’ gestation ( Fig. 1 b). Measurement technique is similar to that of the gestational sac, always including three perpendicular diameters from the centre of the yolk sac wall. If the yolk sac is large (>5.6 mm) or not visible when the mean gestational sac diameter reaches over 13 mm , repeat ultrasound in a week is advised, as these findings are strongly associated with early pregnancy failure.
Early embryo is typically located adjacent to the yolk sac, and it appears as a linear bright echo ( Fig. 1 c). The two structures are connected by the vitelline duct. From 7 weeks’ gestation onwards, crown (head) can be distinguished from rump (trunk) ( Fig. 1 d). Crown–rump length should be measured from a sagittal section of the embryo, with care to avoid including the yolk sac into the measurement .
Cardiac activity can be documented at around 5 weeks and 5 days’ gestation, when the embryo measures 2–5 mm in length. Background movement and maternal pulsation can sometimes be misinterpreted as embryonic cardiac activity. Heart rate should be measured using M-mode; pulsed Doppler examination produces high-energy acoustic outputs and should not be used in early first-trimester pregnancy ( Fig. 1 c) . It has been reported that heart rates below 100 beats per minute are suggestive of an abnormal pregnancy . It is important to recognise, however, that, in early normal gestations, heart rate could be below 100 beats per minute, yet increase rapidly between 6–7 weeks’ gestation. If a heartbeat is not visible in an embryo, colour Doppler may be useful to confirm a negative finding provided it is used for a short period of time with both mechanical and thermal index set to less than 1.
From 7 weeks’ gestation, the amniotic cavity becomes visible and should be measured in three dimensions. In addition, rhombencephalon and spine may be distinguished, and the umbilical cord seen. At 8 weeks’ gestation, forebrain, midbrain, hindbrain and skull are apparent, and limb buds start to grow. The amniotic cavity expands, whereas the umbilical cord and vitelline duct lengthen and a mid-gut hernia appears. Between 7–9 weeks’ gestation, amniotic and chorionic cavities are not fused, and chorionicity and amnionicity of multiple pregnancies can be confidently established.
Multiple pregnancy
The diagnosis of multiple pregnancy in the first trimester is important, as determination of chorionicity and amnionicity is relatively simple, and women could be advised about the risk associated with different types of multiple pregnancies .
Dizygotic twins develop from two different oocytes fertilised by two different sperm, and they implant separately. As a result, each embryo has its own gestational sac (chorion), amniotic sac (amnion), and placenta. Consequently, dizygotic twins are dichorionic and diamniotic ( Fig. 2 a). Monozygotic twins arise from a single oocyte fertilised by one sperm, which then divides. The stage of development at which it divides is what determines its chorionicity and amnionicity. If it divides before implantation, it results in a dichorionic and diamniotic pregnancy. If the division occurs after implantation, a single gestational sac is formed, hence pregnancy is monochorionic. If division occurs on days 4–8 of development, the pregnancy is monochorionic and diamniotic, and if it occurs on days 9–13 of development, the pregnancy is monochorionic and monoamniotic ( Fig. 2 b).
On ultrasound, the first signs of a multiple pregnancy are the presence of more than one gestational sac at around 5 weeks’ gestation. The number of gestational sacs and yolk sacs may be variable, and it does not always correlate with the number of embryos in multiple pregnancies . It is imperative to examine the entire chorionic cavity to ensure that all embryos are seen when pregnancy progresses beyond 6 weeks’ gestation. Amnionicity should be assessed at around 7 weeks’ gestation when the amnion is seen separate to the embryo. At this stage, chorion and amnion are not fused, so that chorionicity, and amnionicity of multiple pregnancies can be easily and confidently established. After amnion and chorion are fused, the assessment of chorionicity becomes more difficult, and it relies on the assessment of thickness of dividing membrane and shape of its junction with the uterine wall (‘lambda’ or ‘T’ sign) . If the dividing membrane between two embryos or fetuses within the same gestational sac is absent, the pregnancy is classified as monochorionic and monoamniotic. In higher multiples, the same principles are applied.
Miscarriage
Miscarriage is defined as a pregnancy failure occurring before the completion of 24 weeks’ gestation, and it is the most common complication of pregnancy. The reported rate of pregnancy loss in women with a missed menstrual period and positive pregnancy test is 12–24% . The true rate of miscarriage is probably even higher considering the preclinical pregnancy losses, before a menstrual period is missed. Miscarriage can be suspected in women presenting with vaginal bleeding or abdominal pain, but ultrasound examination is usually required to diagnose early pregnancy failure. Presence of an embryonic heartbeat at the time of the initial ultrasound does not always indicate that the pregnancy will progress normally. It has been reported that as many as 12.2% may experience miscarriage after positive detection of embryonic cardiac activity in singleton pregnancies .
Early embryonic (fetal) demise
Early embryonic demise (also described as missed miscarriage or blighted ovum) refers to the early stage in the natural history of a miscarriage. On ultrasound scan, an intact gestational sac is seen within the uterine cavity, which does not contain an embryo or there is a visible embryo with no cardiac activity ( Fig. 3 a). The main difficulty when diagnosing early embryonic demise is to avoid confusing a healthy, early, normal intrauterine pregnancy with a miscarriage. As the ultrasound diagnosis of early fetal demise is based on negative findings, the risk of diagnostic errors is considerable. The risk is particularly high in women who are unsure of their dates, have irregular cycles, have conceived while taking hormonal contraception, or have had less than three menstrual periods since their last pregnancy. Uterine abnormalities, such as congenital uterine anomaly, uterine fibroids, intra-abdominal adhesions after previous caesarean sections, or other pelvic surgery affecting uterine position, increase the risk of misdiagnosis. A recent systematic review showed a lack of high-quality, prospective data on which to base guidelines for the accurate diagnosis of early embryonic demise. A wide range of cut-off points for the size of the gestational sac or embryo above which embryonic cardiac activity should be visible in a normal early intrauterine pregnancy have been proposed. Although they all include a certain margin of safety, the main cause of misdiagnosis is operator error, and this can occur irrespective of a chosen cut-off value. Recent National Institute for Health and Care Excellence guidelines suggest that fetal demise should be suspected in the absence of heartbeat when crown–rump length greater than 7 mm or gestational sac measuring greater than 25 mm without a visible embryo . National Institute for Health and Care Excellence recommend that, in all cases, the diagnosis should be confirmed at a follow-up visit 7–14 days later or by a second observer to minimise the risk of diagnostic errors.
Other morphological features have been described, which are not diagnostic of miscarriage, but they indicate that the risk of miscarriage occurring is increased. These include visualisation of an amniotic and yolk sac without a viable embryo, irregular gestational sac with a thin trophoblastic layer, early growth retardation , discrepancies between size of gestational sac and embryo , and bradycardia (heart rate below the 5th percentile or less than 85 beats per minute) .
In multiple pregnancies, a significant discrepancy in crown–rump length between twins may be associated with loss of one twin . In some cases, an empty gestational sac may be seen alongside a second one containing an embryo. This is sometimes referred to as ‘vanishing twin syndrome’ . An intrauterine subchorionic haematoma may sometimes resemble an empty gestational sac, and care has to be taken to avoid misinterpreting this finding as a ‘vanishing twin’. The presence of a clearly defined layer of trophoblast surrounding the sac and a finding of two or more corpora lutea support the diagnosis of a multiple pregnancy.
Incomplete miscarriage
Incomplete miscarriage is defined by the presence of retained products of conception without a well-defined gestation sac. Blood clots within the uterine cavity are often present in women who are bleeding, and they are sometimes difficult to differentiate from trophoblastic tissue. Retained products are usually seen as a well-defined area of hyperechoic tissue within the endometrial cavity ( Fig. 3 b) and frequently demonstrate increased vascularity on colour Doppler examination ( Fig. 3 c). Blood clots on the other hand, are ill defined and avascular. The ultrasound diagnosis of incomplete miscarriage is difficult, and no consensus exists about the best diagnostic criteria. Endometrial thickness (measured as the anterior–posterior diameter of the uterine cavity) is often used in clinical practice to aid with this diagnosis. A number of different cut-off levels have been proposed ranging from 5–25 mm . A recent prospective observational study, however, showed that none of these criteria are accurate enough to diagnose the presence of chorionic villi within the uterine cavity . Subjective assessment of the morphological characteristics of the tissue within the uterine cavity, combined with colour Doppler assessment of its vascularity, has been proposed to overcome the limitations of using cut-off measurements . No good-quality prospective studies, however, have determined the accuracy of these diagnostic criteria.
Complete miscarriage
The diagnosis of complete miscarriage is made in women in with no signs of any pregnancy tissue within the uterine cavity on ultrasound scan. This diagnosis can be made with confidence only in women who had clear evidence of intrauterine pregnancy on previous ultrasound examinations. If no scan has previously been carried out, the pregnancy should be described as a ‘pregnancy of unknown location’ and followed up with serial serum human chorionic gonadotrophin (β-hCG) measurements . A decline in serum β-hCG by 13% or more over 48 h suggests a failing pregnancy . Serum progesterone reading less than 20 nmol/l is equally accurate in predicting a failing pregnancy without the need for another blood test 2 days after the initial visit . In women taking exogenous progestogens, however, measurements of serum progesterone are not reliable. Low hCG ratio and low progesterone are used to estimate the probability of a pregnancy of unknown location resolving spontaneously. They are not test that could rule out a possibility of an ectopic pregnancy. In view of that, biochemical markers must be assessed in conjunction with clinical and ultrasound information and should not be used alone as a diagnostic tool.
Molar pregnancies
In modern clinical practice, most molar pregnancies present during the first trimester of pregnancy with clinical and ultrasound signs of early pregnancy failure. Molar pregnancies have a potential to develop into persistent trophoblastic disease (invasive hydatidiform mole, choriocarcinoma, placental site trophoblastic tumour) and their early detection on ultrasound helps to optimise the management and follow up. Ultrasound feature strongly suggestive of a complete molar pregnancy is thick, cystic tissue within the uterine cavity without a visible gestational sac. Partial hydatidiform mole is often suspected in women with intact gestational sac with cystic placental changes. The accuracy of ultrasound to diagnose molar pregnancy is difficult to assess in modern practice, as most miscarriages are managed conservatively, and histological confirmation of diagnosis is available only in a few women. The available data, however, show that ultrasound diagnosis of complete molar pregnancy is sensitive, with the reported detection rates between 80 and 95% .
The diagnosis of partial molar pregnancy is less accurate, with the detection rates between 20 and 30%. This indicates that a significant number of partial molar pregnancies may be managed non-surgically in modern practice without the diagnosis ever being made. As the risk of persistent trophoblastic disease is much lower in partial compared with complete moles (0.5% v 15%), the inability to detect partial moles on ultrasound is unlikely to have severe adverse effects on maternal health .
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