Clinical Imaging xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
Pearls and pitfalls in first-trimester obstetric sonography Fernanda S. Mazzariol ⁎, Jeffrey Roberts, Sarah K Oh, Zina Ricci, Mordecai Koenigsberg, Marjorie W. Stein Department of Radiology, Montefiore Medical Center, Albert Einstein College of Medicine
a r t i c l e
i n f o
Article history: Received 19 April 2014 Received in revised form 13 October 2014 Accepted 16 October 2014 Available online xxxx Keywords: Ultrasound Ectopic Pregnancy Bleeding Embryo
a b s t r a c t Ultrasound is the primary imaging modality used in the evaluation of first-trimester vaginal bleeding and pelvic pain. This article will summarize the ultrasound findings in normal first-trimester pregnancy, failed pregnancy, ectopic pregnancy, subchorionic hemorrhage, retained products of conception, and gestational trophoblastic disease. Mastery of the spectrum of sonographic findings in the normal and abnormal first-trimester pregnancy allows the radiologist to make accurate diagnoses and helps to appropriately guide patient management. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Vaginal bleeding and pelvic pain are common presenting complaints during first-trimester pregnancies. It is estimated that up to 15% to 20% of all pregnancies are complicated by vaginal bleeding [1]. The work-up includes serum B-HCG sampling as well as transabdominal and transvaginal sonography (TVS) to determine the gestational sac (GS) location and its shape, size, and internal contents. If present, the yolk sac(s), embryo(s), and heart rate(s) [HR(s)] are evaluated, and the presence of perigestational hemorrhage should be noted. The patient’s last menstrual period (LMP) and serum B-HCG levels are correlated with the ultrasound findings to formulate a diagnosis and guide patient management. It is incumbent on the radiologist to be familiar with the normal and abnormal ultrasound findings of first-trimester pregnancy to avoid misdiagnosis. 2. Normal and abnormal features of first-trimester intrauterine pregnancy 2.1. The Gestational Sac The GS implants in the uterine fundus at approximately day 23 of the menstrual cycle. The earliest imaging sign of an intrauterine pregnancy (IUP) seen on TVS is an eccentric, extraluminal, rounded GS located within the endometrium, termed the intradecidual sign [2,3] (Fig. 1). This sign can be observed as early as 4 ½weeks of menstrual age. The double decidual sac sign, representing the hyperechogenic peripheral
⁎ Corresponding author. Department of Radiology, Montefiore Medical Center, 111 East 210 Street, Bronx, NY 10467. Tel.: +1 718 9204396; fax: +1 718 798 7983. E-mail address: [email protected] (F.S. Mazzariol).
decidua vera and the inner decidua capsularis with intervening anechoic endometrial lumen, is seen on TVS at about 5 menstrual weeks [2] (Fig. 2).0 Teaching Points • While the intradecidual sac sign and double decidual sac signs are reassuring and useful signs prior to the appearance of the yolk sac (YS), they will not be seen in 50% of intrauterine pregnancies [3–5]. • A nonspecific intrauterine fluid collection, which is not clearly demonstrated within the decidua, has a greater than 99% chance of being an early IUP than a pseudo-GS of ectopic pregnancy because the incidence of ectopics is low (approximately 2%) and pseudo-GSs are only seen in up to 10% of ectopics [6]. Thus, a stable patient with a small nonspecific intrauterine fluid collection presenting with vaginal bleeding and/or pelvic pain should be followed with ultrasound in 2 to 3 days to help differentiate an early IUP from a pseudo-GS of ectopic pregnancy. The GS is composed of anechoic amniotic fluid and chorionic extraembryonic coelom, which may contain low-level echoes. By TVS, the YS is usually visualized within the extraembryonic coelom at approximately 5½ weeks or 8-mm mean GS diameter (MSD), and the embryo is usually seen at 6 weeks or 16 mm MSD. The embryonic heart motion is usually detected at an embryonic crown-rump length (CRL) of 5 mm [5]. More recently, the recommendation for the diagnosis of embryonic demise has been redefined as absent heart motion at a CRL of 7 mm in order to avoid false positives [7]. The amniotic cavity expands to obliterate the chorionic cavity by 14 to 16 weeks. Adverse outcomes are frequently seen with very irregular or lowlying GSs, MSD N8 mm without a YS, or MSD N 25 mm without an embryo [7]. An abnormally small GS size is a poor prognostic sign; an MSD b5 mm larger than the embryonic CRL is associated with a 94%
http://dx.doi.org/10.1016/j.clinimag.2014.10.009 0899-7071/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
2
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
Fig. 1. Intradecidual sign. Transverse view of the uterus—eccentric GS within the endometrium (arrow). Fig. 3. Anembryonic pregnancy. Transverse view of the uterus showing a 2.5-cm empty GS.
rate of first-trimester spontaneous abortion [8,9]. In a suspected case of pregnancy failure, follow-up sonography in 2 to 3days is recommended because lack of MSD or CRL growth during this interval is diagnostic. An anembryonic intrauterine pregnancy, or blighted ovum, is likely present if an embryo is absent at 16 to 24 mm MSD and is definitively diagnosed when the embryo is absent at an MSD N 25 mm on TVS [10] (Fig. 3). The GS may have an irregular, abnormal shape in a blighted ovum. Comparison with prior sonograms is also helpful in evaluating for pregnancy failure. Suspicion of pregnancy failure increases when a live embryo is not demonstrated on TVS 7–10 days after an exam demonstrating a YS or 7–13 days after an exam demonstrating an empty GS. Absence of a live embryo N11 days after seeing a YS or N 14 days after seeing an empty GS is diagnostic of pregnancy failure [10].
Normally, if an amniotic cavity is detected on TVS, an embryo with length similar to the MSD should be present. The empty amnion sign refers to visualization of an amniotic sac without a discernible embryo and is strongly associated with pregnancy failure [11] (Fig. 4). The expanded amnion sign refers to an embryo that lacks heart motion but is surrounded by visible amnion and is indicative of embryonic demise even when the CRL is less than 5 mm [8,12] (Fig. 5).
2.2. The Yolk Sac
Teaching Points • If a GS is low lying, look for a fundal fibroid, which may be displacing a normal IUP inferiorly.
A normal YS measures less than 5.6 mm internal diameter between 5 and 10 weeks and starts to regress by 11 weeks. Abnormal prognostic factors include absence of the YS in the presence of an embryo, and a large, calcified, or persistently deformed YS [8] (Fig. 6). The YS is no longer seen after the amniotic cavity expands to obliterate the chorionic cavity by 14 to 16 weeks [8,13].
Fig. 2. Double decidual sign. Long view of the uterus–hyperechogenic peripheral decidua vera (arrowhead) and inner decidua capsularis (long arrow) with intervening hypoechoic endometrial lumen (short arrow).
Fig. 4. Empty amnion sign. Empty amniotic sac (arrowhead). Mildly deformed YS (short white arrow). Note presence of echoes in the extraembryonic coelom (long white arrow). Small subchorionic hemorrhage (black arrow).
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
3
Fig. 5. Expanded amnion sign. (a) Less than 5-mm embryo (short arrow) and much larger amniotic sac (long arrow). YS (arrowhead). (b) No embryonic heart motion.
Teaching Points • A hyperechogenic, nonshadowing YS can be a normal finding and may convert to a typical appearance on follow-up scan. It should not be mistaken for a calcified YS, which is only seen with embryonic demise [13]. 2.3. Embryonic HR The embryonic HR is generally ≥120 beats per minute (bpm) in embryos larger than 5 mm. An HR b110 bpm is associated with a poorer prognosis. In embryos smaller than 5 mm, the HR can be as low as 100 bpm. However, an HR b 100 bpm is associated with an increased rate of embryonic loss, proportional to the degree of bradycardia [14,15] (Fig. 6). 2.4. B-HCG discriminatory level Obstetric sonograms should be interpreted jointly with serum BHCG assay levels. The B-HCG discriminatory level, defined as the level above which an IUP is expected to be seen on TVS, is usually quoted as 1500 to 2000 mIU/ml using the third international standard or
Fig. 6. Abnormal pregnancy that resulted in embryonic demise. (a) Large YS (arrow). (b) Low embryonic HR.
international reference preparation. However, B-HCG assay levels vary widely in early pregnancy, depending on the laboratory, and a normal IUP may not be seen on TVS even when the B-HCG is above the discriminatory level [16] (Table 1). Adherence to a set B-HCG discriminatory value may be misleading. It is important to remember that, in a normal early IUP, the B-HCG level doubles approximately every 48 h. In an ectopic or failed pregnancy, the B-HCG level rises at a slower rate, plateaus, or drops [5]. Teaching Points • Overreliance on the B-HCG discriminatory level to “assume” ectopic pregnancy in the presence of an empty endometrium can result in improper methotrexate administration to a woman with a normal early pregnancy. • A stable pregnant patient with a B-HCG above the discriminatory level and without IUP on TVS should be followed with short-term TVS and B-HCG to determine the status and site of the pregnancy.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
4
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
Table 1 β-HCG levels in weeks from LMPa Weeks from LMP
B-HCG assay level (mIU/ml)
3 4 5 6 7–8 9–12
5–50 5–426 18–7340 1080–56,500 7650–229,000 25,700–288,000
a The American Pregnancy Association (http://americanpregnancy.org/duringpregnancy/ hcglevels.html).
2.5. The Chorionic Bump The chorionic bump is a focal solid or complex protuberance from the choriodecidual region bulging into the GS (Figs. 7 and 8). Harris et al. identified this sign in 0.7% of 2178 early obstetrical sonograms and noted that 50% of these pregnancies aborted, a pregnancy failure rate four times that of the general population control group [17]. Based on the sonographic evolution of the “chorionic bump” on follow-up studies and pathologic investigation of abortuses, the chorionic bump likely represents a small subchorionic bleed [18,19]. 2.6. Subchorionic Hemorrhage Intrauterine hematomas, a common ultrasound finding associated with first-trimester bleeding, have a reported incidence between 4% and 22% [19]. Subchorionic hemorrhage is the most common type of intrauterine chorionic bleed and is thought to result from partial detachment of the trophoblast from the uterine wall with blood dissecting between the chorion and the decidual layer of endometrium [20]. When the hematoma dissects into the endometrial cavity, the patient can present with vaginal bleeding. Subchorionic bleeds are graded into small, medium, and large according to their sizes relative to GS circumference. One large retrospective review reported a rate of pregnancy loss of 7.7% for small hematomas (less than one third the circumference of the GS), 9.2% for medium hematomas (encompassing one third to one half the circumference of the GS), and 18.8% for large hematomas (encompassing at Fig. 8. The chorionic bump. (a) Complex cystic/solid appearance of the chorionic bump (white arrow) and the YS (arrowhead). (b) Another view of the same gestation showing the chorionic bump (arrow), the embryo (between calipers), and the YS (arrowhead).
least two thirds the circumference of the GS) [1]. Subchorionic hemorrhage has a worse prognosis when associated with advanced maternal age or early gestational age [19,1]. A subchorionic hemorrhage may progress into an abruption when the bleed extends behind the placenta. Subchorionic hemorrhage can be crescentic, ovoid, linear, or curvilinear, and its echogenicity is dependent on the stage of the hemorrhage. It is echo poor in the hyperacute setting, transitioning to hyperechogenic as the hematoma organizes and subsequently decreasing in echogenicity as the hematoma undergoes hemolysis and liquefaction [21] (Fig. 9). Due to its variable appearance, a first-trimester subchorionic hematoma can be confused with normal first-trimester incomplete chorioamniotic fusion, an intrauterine mass, a vanishing twin, or slow flow within perigestational veins. The latter condition may be recognized by detection of slow-moving particles on gray scale or color Doppler imaging.
Fig. 7. The chorionic bump. A solid protuberance from the choriodecidual reaction bulging into the GS (arrow).
Teaching Points • The majority of subchorionic hematomas are small, regress spontaneously, and do not result in pregnancy loss. • Larger or persistent hemorrhages tend to have worse prognoses.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
5
Fig. 10. Vanishing twin. Live gestation (long arrow) with a vanishing twin (short arrow).
fertilization, ovulation induction, presence of an intrauterine device, prior diethylstilbestrol exposure, and salpingitis isthmica nodosum [5]. Ninety-five percent of all ectopic pregnancies occur in the fallopian tubes, and 75% to 80% of these are located in the ampullary portion [5]. Less common sites of ectopic pregnancies include interstitial portion of the fallopian tube, cesarean (C)-section scar, and cervix. Ovarian and abdominal ectopic pregnancies are very rare [5]. Teaching Points • The sonographic examination should start with transabdominal technique because, occasionally, a tubal ectopic pregnancy may be located high in the pelvis, outside the field of view of the transvaginal scan.
Fig. 9. Subchorionic hemorrhage. (a) Small, hypoechoic subchorionic bleed (less than one third of circumference of GS; arrow). (b) Large subchorionic bleed with heterogeneous echogenicity (between calipers) surrounding the GS (arrow).
2.7. Pregnancy Number The vanishing twin syndrome is due to involution of one embryo of a twin or other multiple gestations. It is a common event when a multiple gestation is diagnosed early in pregnancy. The prognosis for the surviving fetus is generally excellent in the first trimester, and management is conservative. A hypoechoic subchorionic hemorrhage can mimic amniotic fluid and be mistaken for a “vanishing twin” [21] (Fig. 10).
A sonogram showing an empty uterus and an extrauterine GS with embryonic heart motion is definitive for a tubal ectopic pregnancy, but these findings are observed only in 17% to 28% of ectopic pregnancies [5,8] (Fig. 11). A very common sonographic sign of a tubal ectopic pregnancy is the tubal ring, an extraovarian cystic structure with a thickened, hyperechogenic wall of trophoblast [23–25] (Fig. 12). The tubal ring may be empty or contain an embryo or YS. It typically exhibits a “ring of fire” on color Doppler imaging, with high-velocity, low-resistance flow on spectral tracing. Useful hints to differentiate an ectopic pregnancy from a corpus luteum (CL) are eccentric position of the CL within the ovarian tissue and hyperechogenicity of the trophoblast in the tubal ring compared with the echogenicity of the CL [23,24]. However, these distinguishing features are not always obvious, and the CL may demonstrate greater peripheral echogenicity and/or a more pronounced “ring of fire” than the ectopic pregnancy [25].
Teaching Points • Reporting the number of embryos in a multiple gestation before 6 weeks may lead to over- or underestimation. Table 2 Clinical terminology for the spectrum of findings related to abortion
3. Abortion
Spontaneous abortion
Pregnancy loss without medical intervention
The clinical terminology for the spectrum of findings related to abortion is summarized on Table 2 [22].
Threatened abortion
4. Ectopic Pregnancy
Abortion in progress
Up to 20 weeks pregnant with vaginal bleeding and a closed cervix Progressive cervical dilatation with products of conception not yet expelled Open cervix with products of conception in the process of being expelled Some products of conception expelled, but some remain in the uterus Products of conception completely expelled in the presence of a closed cervix Embryonic demise in uterus with a closed cervix
Ectopic pregnancies, which account for 1.4% to 2% of all pregnancies and 4.5% of all in vitro pregnancies, are responsible for 15% of maternal deaths [8]. Risk factors include prior pelvic inflammatory disease, prior ectopic pregnancy, endometriosis, tubal surgery, infertility, in vitro
Inevitable abortion
Incomplete abortion Complete abortion Missed abortion
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
6
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
Fig. 11. Live tubal ectopic pregnancy. (a) Tubal ring containing an embryo (between calipers) of CRL 0.77, corresponding to gestation of 6 weeks and 5 days. (b) Color Doppler showing heart motion.
Fig. 12. Tubal ring. (a) Extraovarian cystic structure with a thickened wall due to the trophoblastic change (white arrow). Ovary containing a large CL (black arrow). (b) Ring of fire on color Doppler.
Teaching Points • Ovarian ectopic pregnancies are exceedingly rare, and a cystic structure within the ovary is almost always a CL. There are cases in which it is difficult to determine whether the tubal ring-like structure is a CL extending off the ovary or an adjacent ectopic. • Gentle probing with the endovaginal transducer allows the radiologist to identify the point of tenderness and may help localize the site of pathology. A complex adnexal mass that is demonstrated to separate from or slide over the ovary when transducer pressure is directed at the interface between the mass and the ovary is a strong indication of an ectopic pregnancy. However, this maneuver may not differentiate an ectopic from a CL in up to 10% of ectopics [26].
evaluated for fluid containing low-level echoes with or without hyperechogenic clot, representing hemoperitoneum. Hemoperitoneum does not necessarily imply rupture of an ectopic pregnancy, as blood may exit from the fimbriated end of an intact tube or may result from a ruptured ovarian cyst [8]. Conversely, an intact tubal ring does not exclude the presence of rupture [27].
Any complex adnexal mass distinct from the ovary in a pregnant woman without an IUP on TVS is highly suspicious for an ectopic pregnancy. A complex tubular mass may represent a hematosalpinx or hematoma in the setting of a tubal ectopic pregnancy (Fig. 13). A distinct complex cystic mass with a vascular rim may be seen within the hematosalpinx, representing the GS. In many ectopic pregnancies, however, it is not possible to detect the small ectopic sac. Moreover, we have noted that ectopic pregnancies that have been treated with methotrexate may appear as a solid mass on follow-up exam. A small amount of fluid in the cul-de-sac is usually physiologic. Fluid in Morison’s pouch is abnormal and requires careful evaluation for ectopic pregnancy. The pelvis and Morison’s pouch must be meticulously
Teaching Points • A normal pelvic sonogram, without evidence of an intrauterine pregnancy, does not exclude the possibility of an ectopic pregnancy. Uterine findings in the setting of an ectopic pregnancy include an empty uterus, a nonspecific decidual cyst, or a pseudo-GS (e.g., decidual cast) containing fluid, blood, or mobile debris (Fig. 14). The pseudosac, when present, is centrally located in the endometrial complex and surrounded by a single, often irregular decidual layer [5]. It may demonstrate acutely angulated margins along the axis of the uterine lumen. The sonographic features of an interstitial ectopic pregnancy are as follows: eccentric high location in the uterine fundus, bulge of the uterine contour, ≤5 mm of myometrial thickness between the decidual reaction and the uterine serosa, and the interstitial line sign [5,28]. The interstitial line sign is described as a thin, straight hyperechogenic line extending from the endometrial cavity to the medial aspect of the GS (Fig. 15). An interstitial ectopic pregnancy can grow larger before the
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
7
Fig. 13. Hematosalpinx. (a) Cross-sectional view of the ovary with a CL (short arrow) and adjacent hematosalpinx (long arrow). Complex fluid represents hemoperitoneum (black arrow). (b) Long view of the hematosalpinx (arrow) surrounded by hemoperitoneum (arrowheads).
patient becomes symptomatic as it is partially surrounded by myometrium. Interstitial ectopic pregnancy rupture is associated with greater morbidity and mortality due to massive hemorrhage from the dilated arcuate uterine vessels [5,28]. It is important to differentiate an interstitial pregnancy from a mildly eccentric IUP, an IUP in a septate or bicornuate uterus, or an eccentric IUP position due to a fibroid displacing the GS. In the septate uterus, a curved endometrium is seen extending to the sac [28]. An eccentric IUP will not bulge the uterine contour, will lie within the endometrial complex with ≥ 5 mm myometrial mantle, and will not demonstrate an interstitial line sign. A 3-dimensional ultrasound may be valuable in establishing the diagnosis of interstitial pregnancy. A C-section scar ectopic pregnancy is located in the anterior lower uterine segment. There is absence or paucity of myometrium between the decidual reaction and the anterior uterine serosa or the bladder wall [29] (Fig. 16). Frequently, the uterine lumen can be shown to pucker anteriorly in the region of this ectopic. Distinction should be made between a cervical ectopic and an abortion in progress. With an abortion in progress, the sac is located centrally in the canal and usually appears flattened, with an absent or nonvascular hyperechogenic rim. In the vast majority of cases, if an embryo is detected, the heart motion is absent (Fig. 17). In contrast, embryonic cardiac activity inferior to the internal os is highly suggestive of a cervical ectopic. A cervical ectopic has a surrounding hyperechogenic decidual reaction that is lacking in an abortion in progress (Fig. 18). If differentiation between a cervical ectopic and the much more frequent
Fig. 14. Pseudo-GS. (a) Tubal ectopic pregnancy with YS (long arrow) and adjacent ovary with CL (short arrow). (b) The pseudo-GS is a fluid-filled structure in the center of the endometrial cavity (arrow).
abortion in progress is not possible on the initial exam, follow-up ultrasound, sometimes within hours, may show dramatic change in appearance of abortion in progress [5,29]. A cervical ectopic pregnancy is
Fig. 15. Interstitial line sign of cornual ectopic pregnancy. On transverse view of the uterus, a thin, straight hyperechogenic line (arrow) extending from the endometrial cavity to the medial aspect of the GS.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
8
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
situated more eccentrically in the cervix, and the anterior myometrium is of normal thickness [29], a distinguishing feature from C-section scar ectopic. A cervical Nabothian cyst is nonvascular, lacks a hyperechogenic rim, and should not be confused with ectopic pregnancy. The incidence of heterotopic pregnancies is very low. However, women undergoing ovulation induction or in vitro fertilization are at increased risk, with an incidence of 1%–3% [30] (Fig. 19). Therefore, particularly in these populations, the adnexa must be carefully examined for the presence of a concomitant ectopic pregnancy. Abdominal pregnancy is exceedingly rare and usually located in the ovarian ligaments. A potential pitfall is to mistake the empty uterus for a “myoma” in the lower uterine segment, inferior to an abdominal pregnancy. In order to obviate this pitfall, careful evaluation of the sagittal midline view of the uterus must be performed to ensure that the vaginal stripe is continuous with the cervical lumen and that it leads to the GS within the uterus. 5. Retained Products of Conception In first-trimester pregnancy failure, abnormal prolonged vaginal bleeding and absent or abnormal decline of B-HCG levels raise suspicion of retained products of conception (RPOCs). RPOC is a risk factor for endometritis, and its treatment almost always includes curettage [31]. Distinction of RPOC from intrauterine clot can be difficult as both can present as an endometrial mass of variable echogenicity, complex endometrial fluid, and endometrial thickening greater than 10 mm [31]. A dynamic real-time clip of the endometrium will aid in differentiating thickened decidua and mobile blood and debris within the lumen. A study by Durfee et al. [31] found that an endometrial mass was the most sensitive (79%) and specific (89%) finding for RPOC, while another study by Kamaya et al. [32] found only a moderate positive predictive value (80%) for the diagnosis of RPOC. Atri et al. observed that increased color Doppler flow, with or without a mass, is the best sonographic predictor of RPOC, but the sensitivity of this finding is reduced [33]. Kamaya et al. [30] graded the vascularity of the endometrium relative to the myometrium on color Doppler in patients with positive RPOC. Four categories are described: type 0—no flow; type 1—minimal flow, less than that of the myometrium; type 2—moderate flow, equal to that of the myometrium; and type 3—marked flow, greater than that of the myometrium. Type 0 vascularity can be seen with intrauterine clot and RPOC. Type 1 vascularity is seen more frequently with RPOC than clot. Types 2 and 3 vascularities are only seen with RPOC (Fig. 20).
Fig. 17. Abortion in progress. Flattened GS (long arrow) without surrounding decidual reaction located centrally in the upper cervix. An embryo (short arrow) and YS (arrowhead) present.
vascularity pattern can potentially alter management, including considerations for longer course of uterotonics, more cautious dilatation and curettage, and possible embolization [34].
Teaching Points • Type 3 vascularity pattern can be confused with a uterine AVM which also demonstrates high-velocity flow. Identification of a type 3
Fig. 16. C-section scar ectopic pregnancy. Longitudinal view of the uterus. GS in the lower uterine segment, at the site of a C-section scar, with paucity of myometrium between the decidual reaction and the anterior serosa of the uterus (arrow).
Fig. 18. Live cervical ectopic pregnancy. (a) GS in the cervix with fetus (between calipers). External cervical os (short arrow) and placenta (long arrow). (b) Normal fetal heart motion.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
9
Fig. 19. Heterotopic pregnancy. (a) Longitudinal view of the uterus showing a normally situated pregnancy (long arrow) and a GS in the cervix (short arrow). (b) Eccentrically located GS in the cervix with decidual reaction (arrow) and an embryo (between calipers).
6. Gestational Trophoblastic Disease Gestational trophoblastic disease (GTD) is an uncommon cause of first-trimester bleeding. Conversely, vaginal bleeding during early pregnancy is the most common clinical presentation of patients with GTD [35]. The classic clinical signs such as hyperemesis, hypertension, and excessive uterine growth may not be present until the second trimester. In addition, these patients may demonstrate normal-range B-HCG assay levels during the first trimester [35]. TVS is often performed before GTD is clinically suspected, and the first-trimester sonographic findings are frequently nonspecific. At 9–12 weeks of menstrual age, a complete hydatiform mole may appear as a complex heterogeneous intrauterine mass with multiple tiny vesicles, termed the "snowstorm" appearance (Fig. 21), with increased vascularity and arteriovenous shunting. An embryo may be seen in a complete mole with a twin pregnancy or in a partial mole. In cases of partial hydatiform mole, an enlarged placenta with scattered “cysts” may produce a "Swiss cheese" appearance. The fetus in a partial mole has triploid aneuploidy, with symmetric intrauterine growth retardation and fetal malformations [36]. The finding of a small multicystic mass in the endometrial region may be mistakenly interpreted as a hydropically degenerating anembryonic gestation or mixture of blood/clot with RPOCs [35]. An abnormally high B-HCG level aids the diagnosis of a mole. With high B-HCG levels, enlarged ovaries demonstrating theca lutein cysts are seen in up to half of these patients [37].
Fig. 20. Retained products of conception (type 3 vascularity). (a) Longitudinal view of the uterus. Endometrial thickening and low echogenicity material in the fundus (long arrow) and hyperechoic clot in the body (short arrow). (b) Increased vascular flow on RPOC relative to myometrium on color Doppler (arrow) and low-resistance arterial flow on spectral Doppler.
7. Conclusion Sonographic evaluation of patients presenting with first-trimester vaginal bleeding and pelvic pain should begin with a thorough understanding of the normal appearance and evolution of the early gestation. The radiologist must also recognize conditions that may result in pregnancy failure and increased maternal morbidity and mortality. When imaging is not definitive, the radiologist must correlate the ultrasound findings with the clinical history and B-HCG levels to render an accurate diagnosis and guide patient management.
References [1] Bennett G, Bromley B, Lieberman E, Benacerraf. Subchorionic hemorrhage in firsttrimester pregnancies: prediction of pregnancy outcome with sonography. Radiology 1996;200:803–6. [2] Yeh HC, Goodman JD, Carr L, Rabinowitz JG. Intradecidual sign: a US criterion of early intrauterine pregnancy. Radiology 1986;161:463–7. [3] Chiang G, Levine D, Swire M, McNamara A, Mehta T. The intradecidual sign: is it reliable for diagnosis of early intrauterine pregnancy? AJR Am J Roentgenol 2004;183: 725–31. [4] Laing FC, Brown DL, Price JF, Teeger S, Wong ML. Intradecidual sign: is it effective in diagnosis of an early intrauterine pregnancy? Radiology 1997;204:655–60. [5] Levine D. Ectopic pregnancy. Radiology 2007;245:385–96.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
10
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
Fig. 21. Complete hydatiform mole. (a) Longitudinal view of retroverted uterus. Small endometrial mass containing tiny vesicles (between calipers). (b) Increased vascular flow.
[6] Doubilet P, Benson C. First, do no harm… to early pregnancies. J Ultrasound Med 2010;29:685–9. [7] Abdallah Y, Daemen A, Kirk E, Pexsters A, Naji O, Stalder C, Gould D, Ahmed S, Guha S, Syed S, Bottomley C, Timmerman D, Bourne T. Limitations of current definitions of miscarriage using mean gestational sac diameter and crown-rump length measurements: a multicenter observational study. Ultrasound Obstet Gynecol 2011;38:497–502. [8] Lyons EA, Levi CS. The first trimester. In: Rumack CM, Wilson SR, Charboneau JW, Johnson JM, editors. Diagnostic ultrasound. 3rd ed. St. Louis: Elsevier Mosby; 2005. p. 1069–125. [9] Bromley B, Harlow B, Laboda L, Benacerraf. Small sac size in the first trimester: a predictor of poor fetal outcome. Radiology 1991;178:375–7.
[10] Doubilet P, Benson C, Bourne T, Blaivas M. Diagnostic criteria for nonviable pregnancy early in the first trimester. N Engl J Med 2013;369:1443–51. [11] McKenna KM, Feldstein VA, Goldstein RB, Filly RA. The "empty amnion": a sign of early pregnancy failure. J Ultrasound Med 1995;14:117–21. [12] Yegul NT, Filly RA. The expanded amnion sign: evidence of early embryonic death. J Ultrasound Med 2009;28:1331–5. [13] Tan S, Pektas, Arslan H. Sonographic evaluation of the yolk sac. J Ultrasound Med 2012;31:87–95. [14] Arleo E, Troiano R. Outcome of early first-trimester pregnancies (b6.1 weeks) with slow embryonic heart rate. AJR 2011;197:252–5. [15] Doubilet P, Benson C. Outcome of first-trimester pregnancies with slow embryonic heart rate at 6–7 weeks gestation and normal heart rate by 8 weeks at US. Radiology 2005;236:643–6. [16] Doubilet P, Benson C. Further evidence against the reliability of the human chorionic gonadotropin discriminatory level. J Ultrasound Med 2011;30:1637–42. [17] Harris RD, Couto C, Karpovsky C, Porter MM, Ouhilal S. The chorionic bump: a firsttrimester pregnancy sonographic finding associated with a guarded prognosis. J Ultrasound Med 2006;25:757–63. [18] Tan S, Ipek A, Sivaslioglu AA, Sungu N, Sarici OU, Karaoglanoglu M. The chorionic bump: radiologic and pathologic correlation. J Clin Ultrasound 2011;39:35–7. [19] Leite J, Ross P, Rossi AC, Jeanty P. Prognosis of very large first-trimester hematomas. J Ultrasound Med 2006;25:1441–5. [20] Maso G, D’Ottavio G, De Seta F, Sartore A, Piccoli M, Mandruzzato G. First-trimester intrauterine hematoma and outcome of pregnancy. Obstet Gynecol 2005;105: 339–44. [21] Abu-Yosef MM, Bleicher JJ, Williamson RA, Wiener CP. Subchorionic hemorrhage: sonographic diagnosis and clinical significance. AJR 1987;149:737–40. [22] Griebel C, Halvorsen J, Golemon T, Day A. Management of spontaneous abortion. Am Fam Physician 2005;72:1243–50. [23] Frates MC, Visweswaran A, Laing FC. Comparison of tubal ring and corpus luteum echogenicites: a useful differentiating characteristic. J Ultrasound Med 2001;20: 27–31. [24] Stein M, Ricci Z, Novak L, Roberts J, Koenigsberg M. Sonographic comparison of the tubal ring of ectopic pregnancy with the corpus luteum. J Ultrasound Med 2004;23: 57–62. [25] Atri M. Ectopic pregnancy versus corpus luteum cyst revisited: best Doppler predictors. J Ultrasound Med 2003;22:1181–4. [26] Blaivas M, Lyon M. Reliability of adnexal mass mobility in distinguishing possible ectopic pregnancy from corpus luteum cysts. J Ultrasound Med 2005;24:599–603. [27] Frates MC, Brown DL, Doubilet PM, Hornstein MD. Tubal rupture in patients with ectopic pregnancy: diagnosis with transvaginal US. Radiology 1994;191:769–72. [28] Frates MC, Laing FC. Sonographic evaluation of ectopic pregnancy: an update. AJR 1995;165:251–9. [29] Osborn D, Williams T, Craig B. Cesarean scar pregnancy—sonographic and magnetic resonance imaging findings, complications, and treatment. J Ultrasound Med 2012; 31:1449–56. [30] Kirsch JD, Scoutt LM. Imaging of ectopic pregnancy. Appl Radiol 2010;39:10–25. [31] Durfee SM, Frates MC, Luong A, Benson CB. The sonographic and color Doppler features of retained products of conception. J Ultrasound Med 2005;24:1181–6. [32] Kamaya A, Petrovitch I, Chen B, Frederick CE, Jeffrey RB. Retained products of conception: spectrum of color Doppler findings. J Ultrasound Med 2009;28:1031–41. [33] Atri M, Rao A, Boylan C, Rasty G, Gerber D. Best predictors of grayscale ultrasound combined with color Doppler in the diagnosis of retained products of conception. J Clin Ultrasound 2011;39:122–7. [34] Jain K, Fogata M. Retained products of conception mimicking a large endometrial AVM: complete resolution following spontaneous abortion. J Clin Ultrasound 2007;35:42–7. [35] Lazarus E, Hulka C, Siewert B, Levine D. Sonographic appearance of early complete molar pregnancy. J Ultrasound Med 1999;18:589–94. [36] Fraser-Hill M, Wilson S. Gestational trophoblastic neoplasia. In: Rumack CM, Wilson SR, Charboneau JW, Johnson JM, editors. Diagnostic ultrasound. 3rd ed. St. Louis: Elsevier Mosby; 2005. p. 589–92. [37] Callen PW. Ultrasonography in obstetric and gynecology. 4th ed. Philadelphia: Saunders; 2000 848.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
Pearls and pitfalls in first-trimester obstetric sonography Fernanda S. Mazzariol ⁎, Jeffrey Roberts, Sarah K Oh, Zina Ricci, Mordecai Koenigsberg, Marjorie W. Stein Department of Radiology, Montefiore Medical Center, Albert Einstein College of Medicine
a r t i c l e
i n f o
Article history: Received 19 April 2014 Received in revised form 13 October 2014 Accepted 16 October 2014 Available online xxxx Keywords: Ultrasound Ectopic Pregnancy Bleeding Embryo
a b s t r a c t Ultrasound is the primary imaging modality used in the evaluation of first-trimester vaginal bleeding and pelvic pain. This article will summarize the ultrasound findings in normal first-trimester pregnancy, failed pregnancy, ectopic pregnancy, subchorionic hemorrhage, retained products of conception, and gestational trophoblastic disease. Mastery of the spectrum of sonographic findings in the normal and abnormal first-trimester pregnancy allows the radiologist to make accurate diagnoses and helps to appropriately guide patient management. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Vaginal bleeding and pelvic pain are common presenting complaints during first-trimester pregnancies. It is estimated that up to 15% to 20% of all pregnancies are complicated by vaginal bleeding [1]. The work-up includes serum B-HCG sampling as well as transabdominal and transvaginal sonography (TVS) to determine the gestational sac (GS) location and its shape, size, and internal contents. If present, the yolk sac(s), embryo(s), and heart rate(s) [HR(s)] are evaluated, and the presence of perigestational hemorrhage should be noted. The patient’s last menstrual period (LMP) and serum B-HCG levels are correlated with the ultrasound findings to formulate a diagnosis and guide patient management. It is incumbent on the radiologist to be familiar with the normal and abnormal ultrasound findings of first-trimester pregnancy to avoid misdiagnosis. 2. Normal and abnormal features of first-trimester intrauterine pregnancy 2.1. The Gestational Sac The GS implants in the uterine fundus at approximately day 23 of the menstrual cycle. The earliest imaging sign of an intrauterine pregnancy (IUP) seen on TVS is an eccentric, extraluminal, rounded GS located within the endometrium, termed the intradecidual sign [2,3] (Fig. 1). This sign can be observed as early as 4 ½weeks of menstrual age. The double decidual sac sign, representing the hyperechogenic peripheral
⁎ Corresponding author. Department of Radiology, Montefiore Medical Center, 111 East 210 Street, Bronx, NY 10467. Tel.: +1 718 9204396; fax: +1 718 798 7983. E-mail address: [email protected] (F.S. Mazzariol).
decidua vera and the inner decidua capsularis with intervening anechoic endometrial lumen, is seen on TVS at about 5 menstrual weeks [2] (Fig. 2).0 Teaching Points • While the intradecidual sac sign and double decidual sac signs are reassuring and useful signs prior to the appearance of the yolk sac (YS), they will not be seen in 50% of intrauterine pregnancies [3–5]. • A nonspecific intrauterine fluid collection, which is not clearly demonstrated within the decidua, has a greater than 99% chance of being an early IUP than a pseudo-GS of ectopic pregnancy because the incidence of ectopics is low (approximately 2%) and pseudo-GSs are only seen in up to 10% of ectopics [6]. Thus, a stable patient with a small nonspecific intrauterine fluid collection presenting with vaginal bleeding and/or pelvic pain should be followed with ultrasound in 2 to 3 days to help differentiate an early IUP from a pseudo-GS of ectopic pregnancy. The GS is composed of anechoic amniotic fluid and chorionic extraembryonic coelom, which may contain low-level echoes. By TVS, the YS is usually visualized within the extraembryonic coelom at approximately 5½ weeks or 8-mm mean GS diameter (MSD), and the embryo is usually seen at 6 weeks or 16 mm MSD. The embryonic heart motion is usually detected at an embryonic crown-rump length (CRL) of 5 mm [5]. More recently, the recommendation for the diagnosis of embryonic demise has been redefined as absent heart motion at a CRL of 7 mm in order to avoid false positives [7]. The amniotic cavity expands to obliterate the chorionic cavity by 14 to 16 weeks. Adverse outcomes are frequently seen with very irregular or lowlying GSs, MSD N8 mm without a YS, or MSD N 25 mm without an embryo [7]. An abnormally small GS size is a poor prognostic sign; an MSD b5 mm larger than the embryonic CRL is associated with a 94%
http://dx.doi.org/10.1016/j.clinimag.2014.10.009 0899-7071/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
2
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
Fig. 1. Intradecidual sign. Transverse view of the uterus—eccentric GS within the endometrium (arrow). Fig. 3. Anembryonic pregnancy. Transverse view of the uterus showing a 2.5-cm empty GS.
rate of first-trimester spontaneous abortion [8,9]. In a suspected case of pregnancy failure, follow-up sonography in 2 to 3days is recommended because lack of MSD or CRL growth during this interval is diagnostic. An anembryonic intrauterine pregnancy, or blighted ovum, is likely present if an embryo is absent at 16 to 24 mm MSD and is definitively diagnosed when the embryo is absent at an MSD N 25 mm on TVS [10] (Fig. 3). The GS may have an irregular, abnormal shape in a blighted ovum. Comparison with prior sonograms is also helpful in evaluating for pregnancy failure. Suspicion of pregnancy failure increases when a live embryo is not demonstrated on TVS 7–10 days after an exam demonstrating a YS or 7–13 days after an exam demonstrating an empty GS. Absence of a live embryo N11 days after seeing a YS or N 14 days after seeing an empty GS is diagnostic of pregnancy failure [10].
Normally, if an amniotic cavity is detected on TVS, an embryo with length similar to the MSD should be present. The empty amnion sign refers to visualization of an amniotic sac without a discernible embryo and is strongly associated with pregnancy failure [11] (Fig. 4). The expanded amnion sign refers to an embryo that lacks heart motion but is surrounded by visible amnion and is indicative of embryonic demise even when the CRL is less than 5 mm [8,12] (Fig. 5).
2.2. The Yolk Sac
Teaching Points • If a GS is low lying, look for a fundal fibroid, which may be displacing a normal IUP inferiorly.
A normal YS measures less than 5.6 mm internal diameter between 5 and 10 weeks and starts to regress by 11 weeks. Abnormal prognostic factors include absence of the YS in the presence of an embryo, and a large, calcified, or persistently deformed YS [8] (Fig. 6). The YS is no longer seen after the amniotic cavity expands to obliterate the chorionic cavity by 14 to 16 weeks [8,13].
Fig. 2. Double decidual sign. Long view of the uterus–hyperechogenic peripheral decidua vera (arrowhead) and inner decidua capsularis (long arrow) with intervening hypoechoic endometrial lumen (short arrow).
Fig. 4. Empty amnion sign. Empty amniotic sac (arrowhead). Mildly deformed YS (short white arrow). Note presence of echoes in the extraembryonic coelom (long white arrow). Small subchorionic hemorrhage (black arrow).
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
3
Fig. 5. Expanded amnion sign. (a) Less than 5-mm embryo (short arrow) and much larger amniotic sac (long arrow). YS (arrowhead). (b) No embryonic heart motion.
Teaching Points • A hyperechogenic, nonshadowing YS can be a normal finding and may convert to a typical appearance on follow-up scan. It should not be mistaken for a calcified YS, which is only seen with embryonic demise [13]. 2.3. Embryonic HR The embryonic HR is generally ≥120 beats per minute (bpm) in embryos larger than 5 mm. An HR b110 bpm is associated with a poorer prognosis. In embryos smaller than 5 mm, the HR can be as low as 100 bpm. However, an HR b 100 bpm is associated with an increased rate of embryonic loss, proportional to the degree of bradycardia [14,15] (Fig. 6). 2.4. B-HCG discriminatory level Obstetric sonograms should be interpreted jointly with serum BHCG assay levels. The B-HCG discriminatory level, defined as the level above which an IUP is expected to be seen on TVS, is usually quoted as 1500 to 2000 mIU/ml using the third international standard or
Fig. 6. Abnormal pregnancy that resulted in embryonic demise. (a) Large YS (arrow). (b) Low embryonic HR.
international reference preparation. However, B-HCG assay levels vary widely in early pregnancy, depending on the laboratory, and a normal IUP may not be seen on TVS even when the B-HCG is above the discriminatory level [16] (Table 1). Adherence to a set B-HCG discriminatory value may be misleading. It is important to remember that, in a normal early IUP, the B-HCG level doubles approximately every 48 h. In an ectopic or failed pregnancy, the B-HCG level rises at a slower rate, plateaus, or drops [5]. Teaching Points • Overreliance on the B-HCG discriminatory level to “assume” ectopic pregnancy in the presence of an empty endometrium can result in improper methotrexate administration to a woman with a normal early pregnancy. • A stable pregnant patient with a B-HCG above the discriminatory level and without IUP on TVS should be followed with short-term TVS and B-HCG to determine the status and site of the pregnancy.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
4
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
Table 1 β-HCG levels in weeks from LMPa Weeks from LMP
B-HCG assay level (mIU/ml)
3 4 5 6 7–8 9–12
5–50 5–426 18–7340 1080–56,500 7650–229,000 25,700–288,000
a The American Pregnancy Association (http://americanpregnancy.org/duringpregnancy/ hcglevels.html).
2.5. The Chorionic Bump The chorionic bump is a focal solid or complex protuberance from the choriodecidual region bulging into the GS (Figs. 7 and 8). Harris et al. identified this sign in 0.7% of 2178 early obstetrical sonograms and noted that 50% of these pregnancies aborted, a pregnancy failure rate four times that of the general population control group [17]. Based on the sonographic evolution of the “chorionic bump” on follow-up studies and pathologic investigation of abortuses, the chorionic bump likely represents a small subchorionic bleed [18,19]. 2.6. Subchorionic Hemorrhage Intrauterine hematomas, a common ultrasound finding associated with first-trimester bleeding, have a reported incidence between 4% and 22% [19]. Subchorionic hemorrhage is the most common type of intrauterine chorionic bleed and is thought to result from partial detachment of the trophoblast from the uterine wall with blood dissecting between the chorion and the decidual layer of endometrium [20]. When the hematoma dissects into the endometrial cavity, the patient can present with vaginal bleeding. Subchorionic bleeds are graded into small, medium, and large according to their sizes relative to GS circumference. One large retrospective review reported a rate of pregnancy loss of 7.7% for small hematomas (less than one third the circumference of the GS), 9.2% for medium hematomas (encompassing one third to one half the circumference of the GS), and 18.8% for large hematomas (encompassing at Fig. 8. The chorionic bump. (a) Complex cystic/solid appearance of the chorionic bump (white arrow) and the YS (arrowhead). (b) Another view of the same gestation showing the chorionic bump (arrow), the embryo (between calipers), and the YS (arrowhead).
least two thirds the circumference of the GS) [1]. Subchorionic hemorrhage has a worse prognosis when associated with advanced maternal age or early gestational age [19,1]. A subchorionic hemorrhage may progress into an abruption when the bleed extends behind the placenta. Subchorionic hemorrhage can be crescentic, ovoid, linear, or curvilinear, and its echogenicity is dependent on the stage of the hemorrhage. It is echo poor in the hyperacute setting, transitioning to hyperechogenic as the hematoma organizes and subsequently decreasing in echogenicity as the hematoma undergoes hemolysis and liquefaction [21] (Fig. 9). Due to its variable appearance, a first-trimester subchorionic hematoma can be confused with normal first-trimester incomplete chorioamniotic fusion, an intrauterine mass, a vanishing twin, or slow flow within perigestational veins. The latter condition may be recognized by detection of slow-moving particles on gray scale or color Doppler imaging.
Fig. 7. The chorionic bump. A solid protuberance from the choriodecidual reaction bulging into the GS (arrow).
Teaching Points • The majority of subchorionic hematomas are small, regress spontaneously, and do not result in pregnancy loss. • Larger or persistent hemorrhages tend to have worse prognoses.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
5
Fig. 10. Vanishing twin. Live gestation (long arrow) with a vanishing twin (short arrow).
fertilization, ovulation induction, presence of an intrauterine device, prior diethylstilbestrol exposure, and salpingitis isthmica nodosum [5]. Ninety-five percent of all ectopic pregnancies occur in the fallopian tubes, and 75% to 80% of these are located in the ampullary portion [5]. Less common sites of ectopic pregnancies include interstitial portion of the fallopian tube, cesarean (C)-section scar, and cervix. Ovarian and abdominal ectopic pregnancies are very rare [5]. Teaching Points • The sonographic examination should start with transabdominal technique because, occasionally, a tubal ectopic pregnancy may be located high in the pelvis, outside the field of view of the transvaginal scan.
Fig. 9. Subchorionic hemorrhage. (a) Small, hypoechoic subchorionic bleed (less than one third of circumference of GS; arrow). (b) Large subchorionic bleed with heterogeneous echogenicity (between calipers) surrounding the GS (arrow).
2.7. Pregnancy Number The vanishing twin syndrome is due to involution of one embryo of a twin or other multiple gestations. It is a common event when a multiple gestation is diagnosed early in pregnancy. The prognosis for the surviving fetus is generally excellent in the first trimester, and management is conservative. A hypoechoic subchorionic hemorrhage can mimic amniotic fluid and be mistaken for a “vanishing twin” [21] (Fig. 10).
A sonogram showing an empty uterus and an extrauterine GS with embryonic heart motion is definitive for a tubal ectopic pregnancy, but these findings are observed only in 17% to 28% of ectopic pregnancies [5,8] (Fig. 11). A very common sonographic sign of a tubal ectopic pregnancy is the tubal ring, an extraovarian cystic structure with a thickened, hyperechogenic wall of trophoblast [23–25] (Fig. 12). The tubal ring may be empty or contain an embryo or YS. It typically exhibits a “ring of fire” on color Doppler imaging, with high-velocity, low-resistance flow on spectral tracing. Useful hints to differentiate an ectopic pregnancy from a corpus luteum (CL) are eccentric position of the CL within the ovarian tissue and hyperechogenicity of the trophoblast in the tubal ring compared with the echogenicity of the CL [23,24]. However, these distinguishing features are not always obvious, and the CL may demonstrate greater peripheral echogenicity and/or a more pronounced “ring of fire” than the ectopic pregnancy [25].
Teaching Points • Reporting the number of embryos in a multiple gestation before 6 weeks may lead to over- or underestimation. Table 2 Clinical terminology for the spectrum of findings related to abortion
3. Abortion
Spontaneous abortion
Pregnancy loss without medical intervention
The clinical terminology for the spectrum of findings related to abortion is summarized on Table 2 [22].
Threatened abortion
4. Ectopic Pregnancy
Abortion in progress
Up to 20 weeks pregnant with vaginal bleeding and a closed cervix Progressive cervical dilatation with products of conception not yet expelled Open cervix with products of conception in the process of being expelled Some products of conception expelled, but some remain in the uterus Products of conception completely expelled in the presence of a closed cervix Embryonic demise in uterus with a closed cervix
Ectopic pregnancies, which account for 1.4% to 2% of all pregnancies and 4.5% of all in vitro pregnancies, are responsible for 15% of maternal deaths [8]. Risk factors include prior pelvic inflammatory disease, prior ectopic pregnancy, endometriosis, tubal surgery, infertility, in vitro
Inevitable abortion
Incomplete abortion Complete abortion Missed abortion
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
6
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
Fig. 11. Live tubal ectopic pregnancy. (a) Tubal ring containing an embryo (between calipers) of CRL 0.77, corresponding to gestation of 6 weeks and 5 days. (b) Color Doppler showing heart motion.
Fig. 12. Tubal ring. (a) Extraovarian cystic structure with a thickened wall due to the trophoblastic change (white arrow). Ovary containing a large CL (black arrow). (b) Ring of fire on color Doppler.
Teaching Points • Ovarian ectopic pregnancies are exceedingly rare, and a cystic structure within the ovary is almost always a CL. There are cases in which it is difficult to determine whether the tubal ring-like structure is a CL extending off the ovary or an adjacent ectopic. • Gentle probing with the endovaginal transducer allows the radiologist to identify the point of tenderness and may help localize the site of pathology. A complex adnexal mass that is demonstrated to separate from or slide over the ovary when transducer pressure is directed at the interface between the mass and the ovary is a strong indication of an ectopic pregnancy. However, this maneuver may not differentiate an ectopic from a CL in up to 10% of ectopics [26].
evaluated for fluid containing low-level echoes with or without hyperechogenic clot, representing hemoperitoneum. Hemoperitoneum does not necessarily imply rupture of an ectopic pregnancy, as blood may exit from the fimbriated end of an intact tube or may result from a ruptured ovarian cyst [8]. Conversely, an intact tubal ring does not exclude the presence of rupture [27].
Any complex adnexal mass distinct from the ovary in a pregnant woman without an IUP on TVS is highly suspicious for an ectopic pregnancy. A complex tubular mass may represent a hematosalpinx or hematoma in the setting of a tubal ectopic pregnancy (Fig. 13). A distinct complex cystic mass with a vascular rim may be seen within the hematosalpinx, representing the GS. In many ectopic pregnancies, however, it is not possible to detect the small ectopic sac. Moreover, we have noted that ectopic pregnancies that have been treated with methotrexate may appear as a solid mass on follow-up exam. A small amount of fluid in the cul-de-sac is usually physiologic. Fluid in Morison’s pouch is abnormal and requires careful evaluation for ectopic pregnancy. The pelvis and Morison’s pouch must be meticulously
Teaching Points • A normal pelvic sonogram, without evidence of an intrauterine pregnancy, does not exclude the possibility of an ectopic pregnancy. Uterine findings in the setting of an ectopic pregnancy include an empty uterus, a nonspecific decidual cyst, or a pseudo-GS (e.g., decidual cast) containing fluid, blood, or mobile debris (Fig. 14). The pseudosac, when present, is centrally located in the endometrial complex and surrounded by a single, often irregular decidual layer [5]. It may demonstrate acutely angulated margins along the axis of the uterine lumen. The sonographic features of an interstitial ectopic pregnancy are as follows: eccentric high location in the uterine fundus, bulge of the uterine contour, ≤5 mm of myometrial thickness between the decidual reaction and the uterine serosa, and the interstitial line sign [5,28]. The interstitial line sign is described as a thin, straight hyperechogenic line extending from the endometrial cavity to the medial aspect of the GS (Fig. 15). An interstitial ectopic pregnancy can grow larger before the
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
7
Fig. 13. Hematosalpinx. (a) Cross-sectional view of the ovary with a CL (short arrow) and adjacent hematosalpinx (long arrow). Complex fluid represents hemoperitoneum (black arrow). (b) Long view of the hematosalpinx (arrow) surrounded by hemoperitoneum (arrowheads).
patient becomes symptomatic as it is partially surrounded by myometrium. Interstitial ectopic pregnancy rupture is associated with greater morbidity and mortality due to massive hemorrhage from the dilated arcuate uterine vessels [5,28]. It is important to differentiate an interstitial pregnancy from a mildly eccentric IUP, an IUP in a septate or bicornuate uterus, or an eccentric IUP position due to a fibroid displacing the GS. In the septate uterus, a curved endometrium is seen extending to the sac [28]. An eccentric IUP will not bulge the uterine contour, will lie within the endometrial complex with ≥ 5 mm myometrial mantle, and will not demonstrate an interstitial line sign. A 3-dimensional ultrasound may be valuable in establishing the diagnosis of interstitial pregnancy. A C-section scar ectopic pregnancy is located in the anterior lower uterine segment. There is absence or paucity of myometrium between the decidual reaction and the anterior uterine serosa or the bladder wall [29] (Fig. 16). Frequently, the uterine lumen can be shown to pucker anteriorly in the region of this ectopic. Distinction should be made between a cervical ectopic and an abortion in progress. With an abortion in progress, the sac is located centrally in the canal and usually appears flattened, with an absent or nonvascular hyperechogenic rim. In the vast majority of cases, if an embryo is detected, the heart motion is absent (Fig. 17). In contrast, embryonic cardiac activity inferior to the internal os is highly suggestive of a cervical ectopic. A cervical ectopic has a surrounding hyperechogenic decidual reaction that is lacking in an abortion in progress (Fig. 18). If differentiation between a cervical ectopic and the much more frequent
Fig. 14. Pseudo-GS. (a) Tubal ectopic pregnancy with YS (long arrow) and adjacent ovary with CL (short arrow). (b) The pseudo-GS is a fluid-filled structure in the center of the endometrial cavity (arrow).
abortion in progress is not possible on the initial exam, follow-up ultrasound, sometimes within hours, may show dramatic change in appearance of abortion in progress [5,29]. A cervical ectopic pregnancy is
Fig. 15. Interstitial line sign of cornual ectopic pregnancy. On transverse view of the uterus, a thin, straight hyperechogenic line (arrow) extending from the endometrial cavity to the medial aspect of the GS.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
8
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
situated more eccentrically in the cervix, and the anterior myometrium is of normal thickness [29], a distinguishing feature from C-section scar ectopic. A cervical Nabothian cyst is nonvascular, lacks a hyperechogenic rim, and should not be confused with ectopic pregnancy. The incidence of heterotopic pregnancies is very low. However, women undergoing ovulation induction or in vitro fertilization are at increased risk, with an incidence of 1%–3% [30] (Fig. 19). Therefore, particularly in these populations, the adnexa must be carefully examined for the presence of a concomitant ectopic pregnancy. Abdominal pregnancy is exceedingly rare and usually located in the ovarian ligaments. A potential pitfall is to mistake the empty uterus for a “myoma” in the lower uterine segment, inferior to an abdominal pregnancy. In order to obviate this pitfall, careful evaluation of the sagittal midline view of the uterus must be performed to ensure that the vaginal stripe is continuous with the cervical lumen and that it leads to the GS within the uterus. 5. Retained Products of Conception In first-trimester pregnancy failure, abnormal prolonged vaginal bleeding and absent or abnormal decline of B-HCG levels raise suspicion of retained products of conception (RPOCs). RPOC is a risk factor for endometritis, and its treatment almost always includes curettage [31]. Distinction of RPOC from intrauterine clot can be difficult as both can present as an endometrial mass of variable echogenicity, complex endometrial fluid, and endometrial thickening greater than 10 mm [31]. A dynamic real-time clip of the endometrium will aid in differentiating thickened decidua and mobile blood and debris within the lumen. A study by Durfee et al. [31] found that an endometrial mass was the most sensitive (79%) and specific (89%) finding for RPOC, while another study by Kamaya et al. [32] found only a moderate positive predictive value (80%) for the diagnosis of RPOC. Atri et al. observed that increased color Doppler flow, with or without a mass, is the best sonographic predictor of RPOC, but the sensitivity of this finding is reduced [33]. Kamaya et al. [30] graded the vascularity of the endometrium relative to the myometrium on color Doppler in patients with positive RPOC. Four categories are described: type 0—no flow; type 1—minimal flow, less than that of the myometrium; type 2—moderate flow, equal to that of the myometrium; and type 3—marked flow, greater than that of the myometrium. Type 0 vascularity can be seen with intrauterine clot and RPOC. Type 1 vascularity is seen more frequently with RPOC than clot. Types 2 and 3 vascularities are only seen with RPOC (Fig. 20).
Fig. 17. Abortion in progress. Flattened GS (long arrow) without surrounding decidual reaction located centrally in the upper cervix. An embryo (short arrow) and YS (arrowhead) present.
vascularity pattern can potentially alter management, including considerations for longer course of uterotonics, more cautious dilatation and curettage, and possible embolization [34].
Teaching Points • Type 3 vascularity pattern can be confused with a uterine AVM which also demonstrates high-velocity flow. Identification of a type 3
Fig. 16. C-section scar ectopic pregnancy. Longitudinal view of the uterus. GS in the lower uterine segment, at the site of a C-section scar, with paucity of myometrium between the decidual reaction and the anterior serosa of the uterus (arrow).
Fig. 18. Live cervical ectopic pregnancy. (a) GS in the cervix with fetus (between calipers). External cervical os (short arrow) and placenta (long arrow). (b) Normal fetal heart motion.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
9
Fig. 19. Heterotopic pregnancy. (a) Longitudinal view of the uterus showing a normally situated pregnancy (long arrow) and a GS in the cervix (short arrow). (b) Eccentrically located GS in the cervix with decidual reaction (arrow) and an embryo (between calipers).
6. Gestational Trophoblastic Disease Gestational trophoblastic disease (GTD) is an uncommon cause of first-trimester bleeding. Conversely, vaginal bleeding during early pregnancy is the most common clinical presentation of patients with GTD [35]. The classic clinical signs such as hyperemesis, hypertension, and excessive uterine growth may not be present until the second trimester. In addition, these patients may demonstrate normal-range B-HCG assay levels during the first trimester [35]. TVS is often performed before GTD is clinically suspected, and the first-trimester sonographic findings are frequently nonspecific. At 9–12 weeks of menstrual age, a complete hydatiform mole may appear as a complex heterogeneous intrauterine mass with multiple tiny vesicles, termed the "snowstorm" appearance (Fig. 21), with increased vascularity and arteriovenous shunting. An embryo may be seen in a complete mole with a twin pregnancy or in a partial mole. In cases of partial hydatiform mole, an enlarged placenta with scattered “cysts” may produce a "Swiss cheese" appearance. The fetus in a partial mole has triploid aneuploidy, with symmetric intrauterine growth retardation and fetal malformations [36]. The finding of a small multicystic mass in the endometrial region may be mistakenly interpreted as a hydropically degenerating anembryonic gestation or mixture of blood/clot with RPOCs [35]. An abnormally high B-HCG level aids the diagnosis of a mole. With high B-HCG levels, enlarged ovaries demonstrating theca lutein cysts are seen in up to half of these patients [37].
Fig. 20. Retained products of conception (type 3 vascularity). (a) Longitudinal view of the uterus. Endometrial thickening and low echogenicity material in the fundus (long arrow) and hyperechoic clot in the body (short arrow). (b) Increased vascular flow on RPOC relative to myometrium on color Doppler (arrow) and low-resistance arterial flow on spectral Doppler.
7. Conclusion Sonographic evaluation of patients presenting with first-trimester vaginal bleeding and pelvic pain should begin with a thorough understanding of the normal appearance and evolution of the early gestation. The radiologist must also recognize conditions that may result in pregnancy failure and increased maternal morbidity and mortality. When imaging is not definitive, the radiologist must correlate the ultrasound findings with the clinical history and B-HCG levels to render an accurate diagnosis and guide patient management.
References [1] Bennett G, Bromley B, Lieberman E, Benacerraf. Subchorionic hemorrhage in firsttrimester pregnancies: prediction of pregnancy outcome with sonography. Radiology 1996;200:803–6. [2] Yeh HC, Goodman JD, Carr L, Rabinowitz JG. Intradecidual sign: a US criterion of early intrauterine pregnancy. Radiology 1986;161:463–7. [3] Chiang G, Levine D, Swire M, McNamara A, Mehta T. The intradecidual sign: is it reliable for diagnosis of early intrauterine pregnancy? AJR Am J Roentgenol 2004;183: 725–31. [4] Laing FC, Brown DL, Price JF, Teeger S, Wong ML. Intradecidual sign: is it effective in diagnosis of an early intrauterine pregnancy? Radiology 1997;204:655–60. [5] Levine D. Ectopic pregnancy. Radiology 2007;245:385–96.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
10
F.S. Mazzariol et al. / Clinical Imaging xxx (2014) xxx–xxx
Fig. 21. Complete hydatiform mole. (a) Longitudinal view of retroverted uterus. Small endometrial mass containing tiny vesicles (between calipers). (b) Increased vascular flow.
[6] Doubilet P, Benson C. First, do no harm… to early pregnancies. J Ultrasound Med 2010;29:685–9. [7] Abdallah Y, Daemen A, Kirk E, Pexsters A, Naji O, Stalder C, Gould D, Ahmed S, Guha S, Syed S, Bottomley C, Timmerman D, Bourne T. Limitations of current definitions of miscarriage using mean gestational sac diameter and crown-rump length measurements: a multicenter observational study. Ultrasound Obstet Gynecol 2011;38:497–502. [8] Lyons EA, Levi CS. The first trimester. In: Rumack CM, Wilson SR, Charboneau JW, Johnson JM, editors. Diagnostic ultrasound. 3rd ed. St. Louis: Elsevier Mosby; 2005. p. 1069–125. [9] Bromley B, Harlow B, Laboda L, Benacerraf. Small sac size in the first trimester: a predictor of poor fetal outcome. Radiology 1991;178:375–7.
[10] Doubilet P, Benson C, Bourne T, Blaivas M. Diagnostic criteria for nonviable pregnancy early in the first trimester. N Engl J Med 2013;369:1443–51. [11] McKenna KM, Feldstein VA, Goldstein RB, Filly RA. The "empty amnion": a sign of early pregnancy failure. J Ultrasound Med 1995;14:117–21. [12] Yegul NT, Filly RA. The expanded amnion sign: evidence of early embryonic death. J Ultrasound Med 2009;28:1331–5. [13] Tan S, Pektas, Arslan H. Sonographic evaluation of the yolk sac. J Ultrasound Med 2012;31:87–95. [14] Arleo E, Troiano R. Outcome of early first-trimester pregnancies (b6.1 weeks) with slow embryonic heart rate. AJR 2011;197:252–5. [15] Doubilet P, Benson C. Outcome of first-trimester pregnancies with slow embryonic heart rate at 6–7 weeks gestation and normal heart rate by 8 weeks at US. Radiology 2005;236:643–6. [16] Doubilet P, Benson C. Further evidence against the reliability of the human chorionic gonadotropin discriminatory level. J Ultrasound Med 2011;30:1637–42. [17] Harris RD, Couto C, Karpovsky C, Porter MM, Ouhilal S. The chorionic bump: a firsttrimester pregnancy sonographic finding associated with a guarded prognosis. J Ultrasound Med 2006;25:757–63. [18] Tan S, Ipek A, Sivaslioglu AA, Sungu N, Sarici OU, Karaoglanoglu M. The chorionic bump: radiologic and pathologic correlation. J Clin Ultrasound 2011;39:35–7. [19] Leite J, Ross P, Rossi AC, Jeanty P. Prognosis of very large first-trimester hematomas. J Ultrasound Med 2006;25:1441–5. [20] Maso G, D’Ottavio G, De Seta F, Sartore A, Piccoli M, Mandruzzato G. First-trimester intrauterine hematoma and outcome of pregnancy. Obstet Gynecol 2005;105: 339–44. [21] Abu-Yosef MM, Bleicher JJ, Williamson RA, Wiener CP. Subchorionic hemorrhage: sonographic diagnosis and clinical significance. AJR 1987;149:737–40. [22] Griebel C, Halvorsen J, Golemon T, Day A. Management of spontaneous abortion. Am Fam Physician 2005;72:1243–50. [23] Frates MC, Visweswaran A, Laing FC. Comparison of tubal ring and corpus luteum echogenicites: a useful differentiating characteristic. J Ultrasound Med 2001;20: 27–31. [24] Stein M, Ricci Z, Novak L, Roberts J, Koenigsberg M. Sonographic comparison of the tubal ring of ectopic pregnancy with the corpus luteum. J Ultrasound Med 2004;23: 57–62. [25] Atri M. Ectopic pregnancy versus corpus luteum cyst revisited: best Doppler predictors. J Ultrasound Med 2003;22:1181–4. [26] Blaivas M, Lyon M. Reliability of adnexal mass mobility in distinguishing possible ectopic pregnancy from corpus luteum cysts. J Ultrasound Med 2005;24:599–603. [27] Frates MC, Brown DL, Doubilet PM, Hornstein MD. Tubal rupture in patients with ectopic pregnancy: diagnosis with transvaginal US. Radiology 1994;191:769–72. [28] Frates MC, Laing FC. Sonographic evaluation of ectopic pregnancy: an update. AJR 1995;165:251–9. [29] Osborn D, Williams T, Craig B. Cesarean scar pregnancy—sonographic and magnetic resonance imaging findings, complications, and treatment. J Ultrasound Med 2012; 31:1449–56. [30] Kirsch JD, Scoutt LM. Imaging of ectopic pregnancy. Appl Radiol 2010;39:10–25. [31] Durfee SM, Frates MC, Luong A, Benson CB. The sonographic and color Doppler features of retained products of conception. J Ultrasound Med 2005;24:1181–6. [32] Kamaya A, Petrovitch I, Chen B, Frederick CE, Jeffrey RB. Retained products of conception: spectrum of color Doppler findings. J Ultrasound Med 2009;28:1031–41. [33] Atri M, Rao A, Boylan C, Rasty G, Gerber D. Best predictors of grayscale ultrasound combined with color Doppler in the diagnosis of retained products of conception. J Clin Ultrasound 2011;39:122–7. [34] Jain K, Fogata M. Retained products of conception mimicking a large endometrial AVM: complete resolution following spontaneous abortion. J Clin Ultrasound 2007;35:42–7. [35] Lazarus E, Hulka C, Siewert B, Levine D. Sonographic appearance of early complete molar pregnancy. J Ultrasound Med 1999;18:589–94. [36] Fraser-Hill M, Wilson S. Gestational trophoblastic neoplasia. In: Rumack CM, Wilson SR, Charboneau JW, Johnson JM, editors. Diagnostic ultrasound. 3rd ed. St. Louis: Elsevier Mosby; 2005. p. 589–92. [37] Callen PW. Ultrasonography in obstetric and gynecology. 4th ed. Philadelphia: Saunders; 2000 848.
Please cite this article as: Mazzariol FS, et al, Pearls and pitfalls in first-trimester obstetric sonography, Clin Imaging (2014), http://dx.doi.org/ 10.1016/j.clinimag.2014.10.009
