Imaging of vaginal bleeding in early pregnancy

Although the first trimester begins at the first day of the last menstrual period, fertilization occurs approximately two weeks later, marking the beginning of the conceptus period of the first trimester (3-5 weeks menstrual age). Implantation of the blastocyst into the endometrium occurs during the fourth menstrual week, at which point the endometrium is referred to as the decidua.² During this time the very early chorionic sac may be visible as a small fluid-filled sac with an echogenic rim located eccentrically within the endometrium, known as the “intradecidual sign” (Figure 1).³ This can be seen as early as 4.5 weeks, and is nearly 100% specific for an intrauterine pregnancy (IUP), although it is only 60-68% sensitive.⁴ This precedes the “double decidual sign,” which consists of two concentric echogenic rings: the decidua capsularis surrounding the gestational sac, and the decidua parietalis representing the opposite wall of the endometrium, often separated by a thin collection of fluid within the endometrial cavity (Figure 2).⁵ As with the intradecidual sign, the double decidual sign is highly specific but insensitive; furthermore, a yolk sac may be visible before this sign is apparent, making it less useful in confirming an early IUP. Importantly, one should differentiate these two early signs of an IUP from a fluid collection within the endometrial canal, the “pseudo-gestational sac” (Figure 3).

The yolk sac is the first structure able to be visualized within the early gestational sac (chorionic sac), usually by the time the mean gestational sac diameter (MSD) is 8-10 mm (Figure 4).⁶ A normal yolk sac is always less than 6 mm in diameter; a yolk sac greater than 6 mm is nearly 100% specific for an abnormal pregnancy.⁷ Shortly following appearance of the yolk sac, the embryo is usually apparent at approximately 6 weeks, when the MSD is greater than 16 mm, as a small echogenic structure along one side of the yolk sac. Cardiac activity can usually be identified by the time the embryo is visible.

Formation of the amniotic sac coincides with formation of the yolk sac, but is usually not visible at this early stage secondary to its very thin membrane. By 7 weeks’ gestational age, the amniotic sac becomes visible as it fills with fluid and separates from the embryo (Figure 5). By the time the amniotic sac is visible, the embryo can be readily identified; the absence of an embryo, or “empty amnion sign,” is highly specific for a failed pregnancy (Figure 6).⁸ As the amniotic sac enlarges, it gradually obliterates the chorionic sac, with complete fusion by 12 weeks gestational age.⁹

In the absence of visualization of any of the above in the setting of a positive urine or serum β-hCG, the pregnancy should be considered a pregnancy of unknown location, or PUL.

Subchorionic, or perigestational, hemorrhage is present in approximately 20% of women presenting with a threatened abortion,¹⁵ and is the most common cause of bleeding in normal IUPs, usually presenting in the late first trimester. On US, these appear as either hyperechoic or hypoechoic, depending upon the age of the blood products (Figure 7). Most often these are not associated with any significant clinical sequelae, particularly if fetal cardiac activity is present. Large bleeds, defined as involving more than 2/3 the circumference of the gestational sac, are more likely to result in pregnancy failure (Figure 8).¹⁶ For smaller hematomas, no size thresholds have been confirmed to be prognostic,¹⁷ although this finding is a risk factor for subsequent pregnancy complications.^18,19

Visualization of a live embryo outside of the uterine cavity is 100% specific for ectopic pregnancy, but is rarely encountered in practice. More often, an adnexal tubal ring is identified. On US this consists of an echogenic ring with central fluid, separate from the ovary. The ring may or may not contain a yolk sac or embryo. The ring is typically more echogenic than the ring of a corpus luteum, with which it can potentially be confused (Figure 9).^22,23 Distinguishing between the two is vital, as the misdiagnosis of a corpus luteum as an ectopic pregnancy in the setting of PUL can have tragic consequences. Endovaginal transducer pressure on the ovary can help determine if the lesion is within or separate from the ovary. As ovarian ectopic pregnancies are exceedingly rare, demonstrating an intra-ovarian location confirms a corpus luteum and essentially excludes an ectopic mass.

Often, the ectopic may be identified only as an extra-ovarian adnexal mass, without the classic ring-like appearance, because of hemorrhage. While the presence of color flow helps to confirm an ectopic pregnancy mass, the converse is not always true. Not all ectopics are vascular, and the absence of color Doppler flow does not exclude an ectopic pregnancy. While large amounts of hemorrhage typically indicate a ruptured ectopic, occasionally a ruptured hemorrhagic cyst can present with a similar clinical and US picture.

When an ectopic pregnancy implants within the interstitial segment of the fallopian tube, it is termed an interstitial (or cornual) ectopic. These can be mistaken for IUP if not fully investigated, as they can have a normal interface with the endometrium along their inner margin. Additionally, the distinction from tubal ectopics is important, as cornual pregnancies have an increased risk of severe hemorrhage and mortality.

The interstitial location can be identified by the eccentric location high within the uterus, as well as by the presence of only a thin mantle of myometrium along the outer margin, usually less than 5 mm thick.^24,25 An additional feature that can be helpful is the “interstitial line sign,” representing a thin echogenic line extending from the endometrial canal directly to the gestational sac, representing the cornual segment of the endometrial canal or interstitial portion of the fallopian tube (Figure 10).²⁶

As with interstitial ectopic pregnancies, the risk of significant bleeding and mortality is increased with cervical ectopics relative to tubal ectopics. The gestational sac in a cervical ectopic pregnancy must be distinguished from a gestational sac passing through the cervix during an abortion in progress. In the case of a cervical ectopic, the gestational sac usually maintains its normal round or slightly ovoid shape. Additionally, the presence of perigestational blood flow on color Doppler can aid in the distinction (Figure 11⁾.^27,28 A passing gestational sac has a crenated or elongated appearance with no embryonic cardiac activity (Figure 12).²⁹

Pregnancies implanted at the cesarean section scar site frequently result in spontaneous miscarriage (44%), but are at increased risk of developing placenta previa and placenta accreta if they develop later into pregnancy, and are associated with increased risk of severe hemorrhage at delivery.³⁰ Diagnosis is easier to establish in the first trimester, when there is an empty uterine cavity, a gestational sac implanted anteriorly at the level of the cervical os or at the visible or presumed cesarean section scar site, and perigestational Doppler flow (Figure 13).

Retained products of conception (RPOC) can be found following therapeutic or spontaneous abortion, as well as post-partum. Following first-trimester abortion, there is typically normal or mildly elevated β-hCG. The presence of a retained gestational sac is not a diagnostic dilemma but is rarely encountered. The presence of blood flow within a thickened endometrium, particularly when associated with a visible mass, is highly suggestive of RPOC (Figure 14). However, the absence of Doppler flow does not necessarily exclude RPOC. Unfortunately there is no definitive endometrial thickness threshold that is entirely specific; however a thickness <10mm likely excludes the possibility of clinically significant RPOC.³¹

Arteriovenous malformations (AVMs) of the uterus can be either congenital or acquired; and can be encountered in the setting of prior therapeutic abortion, dilatation and curettage, cesarean section or invasive tumor such as endometrial carcinoma or gestational trophoblastic disease.¹⁷ AVMs can be comprised of a single arteriovenous fistula (AVF) or a complex structure of multiple vessels. US usually demonstrates a complex mass, with color Doppler revealing internal flow (Figure 15). Spectral Doppler demonstrates low-resistance arterial waveforms and pulsatile venous waveforms consistent with vascular shunting.³²

There is frequently overlap in the ultrasound appearance of AVMs and RPOC, and the distinction is not always possible. RPOC tend to be located within the endometrium, with AVMs in the myometrium; however, the presence of heterogeneous blood within the endometrial cavity can obscure the myometrial margins or mimic RPOC. Clinical history and serum β-hCG are helpful in differentiating these two entities.

Complete hydatidiform mole is the most common of these entities. On US, the classic “cluster of grapes” appearance is often not present in the first trimester and appearance is variable. Findings may include a small echogenic mass without cystic spaces or a mixed solid and cystic mass within the endometrium.³⁴ Theca lutein cysts in the ovaries result from increased β-hCG production, but are usually not present until the second trimester. Being avascular, color flow is typically not helpful in diagnosing a complete hydatidiform mole (Figure 16).³⁵

The distinction between non-invasive mole and invasive mole/choriocarcinoma is not always possible with US. In contrast to hydatidiform moles, invasive moles and choriocarcinomas demonstrate color flow on Doppler, with low-impedance waveforms (Figure 17).³⁵ Invasive moles grow deep into the myometrium, sometimes with penetration into parametrial tissues and peritoneum, but rarely metastasize. In contrast, choriocarcinoma readily metastasizes to the lungs and less frequently the pelvis,¹⁷ for which CT is useful (Figure 18). Magnetic resonance imaging may aid in evaluating persistent residual disease in the pelvis.