On completion of this chapter, you should be able to:
Describe viable and nonviable pregnancy with appropriate terminology
Describe sonographic features of failed pregnancy
Describe sonographic findings of retained products of conception
Explain the clinical and sonographic findings in ectopic pregnancy
Discuss the normal range for fetal cardiac rhythm
Describe the cranial abnormalities seen in the first trimester
Distinguish among normal bowel herniation, gastroschisis, and omphalocele
Explain the sonographic findings with cystic hygroma in the first trimester
Name the types of umbilical cord masses that may be seen with ultrasound
Differentiate between a hemorrhagic corpus luteum cyst and other ovarian masses
Discuss the difference between a fibroid and uterine contraction on sonography
New criteria for viability and nonviability
Historically the diagnosis of pregnancy failure has relied upon several diagnostic criteria: the absence of cardiac activity at a certain CRL, the absence of a visible embryo at a certain mean sac diameter (MSD), or the absence of an appreciable embryo by a point in time. These criteria have been recently reviewed by the Society of Radiologists in Ultrasound, whose consensus paper was published in the NEJM October 2013. The SRU found that the previous studies which determined these threshold values were based on very small patient populations, and the criteria were at risk for increased false positives. The new criteria reflect their attempt to increase the specificity to 100% and give a positive predictive value of close to 100%. The goal was to prevent erroneously diagnosing nonviability and preventing surgical or medical intervention that damages a true viable pregnancy. See the new criteria in Boxes 48-1 and 48-2.
First-trimester bleeding and sonographic appearances
Placental hematomas and subchorionic hemorrhage
The embryonic placenta, or frondosum, may become detached, resulting in the formation of a hematoma, which typically causes vaginal bleeding. Most of these hemorrhages are contiguous with a placental edge. Although no risk factors have been associated with first-trimester placental separation, it has been reported to have a 50% or greater fetal loss rate. Although the prognosis seems to depend on the size of the hematoma, no specific volumes have been correlated in the first trimester with fetal outcomes. That said, improved outcomes do seem to be consistent with smaller hematomas.
Sonographically, placental hematomas may be difficult to distinguish from subchorionic hemorrhages. Patients with placental hematomas generally do not have symptoms, bleeding, or spotting because the bleed is within the chorionic sac and has no communication with the endometrium.
The most common occurrence of bleeding in the first trimester is from subchorionic hemorrhage. These low-pressure bleeds result from the process of implantation of the fertilized ovum into the endometrial cavity and myometrial wall. The hemorrhage is found between the myometrium and the margins of the gestational sac and may or may not be associated with the placenta. This finding can help distinguish a subchorionic hemorrhage from abruptio placentae, which generally occurs in the second trimester and may present as a lucency posterior to the placenta. Clinical findings may include bleeding, spotting, or uterine cramping. If the hemorrhage becomes large enough, this can lead to spontaneous pregnancy loss (SPL).
The appearance of bleeding varies with the stage of its organization. An early bleed may appear slightly echogenic as the red blood cells actively fill the area of hemorrhage. With time, the hemorrhage becomes more anechoic and may be seen between the uterine wall and the fetal membrane ( Figure 50-1 ). Color flow Doppler will demonstrate the avascular nature of the hemorrhage. Patients may present with active vaginal bleeding, and the subchorionic bleed is easily seen by ultrasound adjacent to the gestational sac. Other patients may have no bleeding yet have a subchorionic lucency that can be seen with imaging. Patients may be symptomatic with a large subchorionic bleed, or asymptomatic with a small subchorionic bleed, perhaps only seen with transvaginal imaging.
Absent intrauterine sac
Sonography is routinely used to evaluate for the presence or absence of an intrauterine gestational sac. If the patient presents with a positive pregnancy test, the uterus appears normal but the endometrial complex shows no sign of a gestational sac; the differential diagnosis would include a very early intrauterine pregnancy, a nondeveloping pregnancy, or possible ectopic pregnancy.
Characteristics for the sonographic diagnosis of an absent intrauterine sac include an empty uterus with no evidence of an endometrial fluid collection (early gestational sac), absence of adnexal masses or free fluid, and positive beta-hCG levels. Clinical findings may be characterized by bleeding and cramping. Correlation between the serum beta-hCG level and uterine findings can be used to confirm whether the sonographic indications of a first-trimester pregnancy have been met. Recall that the gestational sac is identified sonographically at 5 weeks of gestation. The sac grows approximately 1 mm per day in the first trimester. The yolk sac should be visualized transvaginally when the gestational sac reaches 8 mm in size, and the embryo must be visualized when the mean sac diameter (MSD) measures 25 mm. The normal embryo grows at a rate of 1 mm per day. Cardiac activity is visible by 5.5 to 6.5 weeks ( Table 50-1 ). Failure to observe these developmental markers suggests a pregnancy of uncertain viability (PUV). Applying the SRU new criteria (NEJM 2013) pregnancy failure can be definitively stated when the embryo is 7 mm or greater without a heartbeat or the MSD is 25 mm but no embryo is visible.
|Viable||Pregnancy defined as viable if it can potentially result in a liveborn baby.|
|Nonviable||A pregnancy is considered nonviable if it cannot result in a liveborn baby. Ectopic pregnancies and failed intrauterine pregnancies are nonviable.|
|Intrauterine pregnancy of uncertain viability||Transvaginal ultrasonography shows an intrauterine gestational sac with no embryonic heartbeat (and no findings of definite pregnancy failure). *|
|Pregnancy of unknown location||Positive urine or serum pregnancy test and no intrauterine or ectopic pregnancy is seen on transvaginal ultrasonography.|
|Human chorionic gonadotropin (hCG)||Serum hCG concentration is measured with the use of the World Health Organization 3rd or 4th International Standard. |
A positive serum pregnancy test is defined by a serum hCG concentration above a positivity threshold (5 mIU/ml).
|Pelvic ultrasonography †||Transvaginal assessment of the uterus and adnexa and transabdominal evaluation for free intraperitoneal fluid and a mass high in the pelvis; oversight provided by an appropriately trained physician; scans performed by providers and interpreted by physicians, all of whom meet at least minimum training or certification standards for ultrasonography, including transvaginal ultrasonography; and scanning equipment permitting adequate visualization of structures early in the first trimester.|
* In a woman with a positive urine or serum pregnancy test, an intrauterine fluid collection with rounded edges containing no yolk sac or embryo is most likely a gestational sac; it is certain to be a gestational sac if it contains a yolk sac or embryo.
† Transabdominal imaging without transvaginal scanning may be sufficient for diagnosing early pregnancy failure when an embryo whose crown-rump length is 15 mm or more has no visible cardiac activity.
In the case of pregnancy loss (complete abortion), serial hCG levels demonstrate successive decline. Caution should be taken when a positive pregnancy test and an empty uterus are seen, given the possibility that an early normal intrauterine pregnancy between 3 and 5 weeks of gestation may be present. Consequently, serial hCG levels should always be obtained and followed for appropriate rise or decline.
If the endometrium is abnormally thick or irregularly echogenic, the differential diagnosis includes intrauterine blood, retained products of conception after an incomplete spontaneous abortion, a decidual reaction associated with an ectopic pregnancy, or decidual changes resulting from an early but not yet visible intrauterine pregnancy. Incomplete spontaneous abortion may show several sonographic findings, ranging from an intact gestational sac with a nonviable embryo to a collapsed gestational sac that is grossly misshapen ( Figure 50-2 ). Women who are clinically undergoing a spontaneous abortion or who have had an elective termination often require follow-up sonography to determine whether retained products of conception are present. Sonographic signs of retained products may be subtle; a thickened endometrium greater than 8 mm and increased vascularization of the endometrial complex with color Doppler are strongly predictive. The presence of visible embryonic parts, a gestational sac, or an embryonic disk is obvious evidence of retained products of conception ( Figure 50-3 ). It sometimes can be difficult to distinguish retained products of conception from blood clots. Quantitative hCG levels, which do not decline normally, a thickened endometrium, and increased vascular flow will provide discriminating evidence for retained products. Patients most often present with persistent bleeding following spontaneous pregnancy loss, dilation and curettage, or after being prescribed misoprostol for uterine evacuation.
Gestational sac without an embryo or yolk sac
A gestational sac without an embryo or yolk sac on sonography may represent one of three conditions: (1) a normal early intrauterine pregnancy of less than 5 weeks, (2) an abnormal intrauterine pregnancy, or (3) a pseudogestational sac in a patient with an ectopic pregnancy.
Criteria for abnormal sac
The gestational sac should be imaged consistently by both transabdominal and transvaginal sonography when its mean diameter is 5 mm, which corresponds to a gestational age of 4 to 5 weeks. Transvaginal sonography may demonstrate the sac as early as 4 weeks, when it measures 2 to 3 mm. At this early size the “sac” can only be described as an intrauterine fluid collection. This cannot be definitively called a gestational sac until there is further growth and a yolk sac can be identified. Calculating the gestational sac at this early stage provides a baseline for monitoring appropriate interval growth. Caution should be used in evaluating these early stages of pregnancy to allow for the possibility that the patient may have inaccurate dates for her last menstrual period. Sequential scanning can document appropriate interval growth of 1 mm per day. Lack of appropriate growth indicates an abnormally growing gestational sac or a pregnancy of unknown viability.
In their opinion paper, “Predicting Pregnancy Failure in Empty Gestational Sacs,” Drs. Nyberg and Filly discuss the importance of establishing threshold levels and discriminatory levels for the diagnosis of SPL. A threshold level tells us when we “might” be able to discern early pregnancy structures. For instance, we might be able to visualize a living embryo at 5.5 weeks. The discriminatory level tells us when we should be able to visualize an embryonic structure. Several studies have confirmed that an embryo can be expected to be seen at 6.4 weeks, if it is not then follow-up ultrasound is recommended and this would be termed pregnancy of uncertain viability. Note that the new SRU criteria have changed the terminology we employ in these descriptions.
Regarding gestational sac values, a gestational sac may be seen as early as 4.3 weeks, the threshold level, and must be seen by 5.2 weeks, the discriminatory level. Given the new pregnancy failure criteria absence of a gestational sac at this stage would also be termed pregnancy of uncertain viability and follow up ultrasound would be ordered.
Transvaginal sonography is the ideal method to examine the early gestational sac. When the sac measures 8 mm or greater, a definitive yolk sac should be demonstrated. The yolk sac can be expected to grow 0.1 mm per 1 mm of MSD growth up to 15 mm. When the gestational sac measures 25 mm, an embryo with cardiac activity must be seen. Follow-up examination in 7 to 10 days is recommended if the findings are indeterminate.
Anembryonic pregnancy (blighted ovum)
By definition, anembryonic pregnancy, or blighted ovum, is a gestational sac in which the embryo fails to develop or stops developing at such an early stage that it is imperceptible by ultrasound ( Table 50-2 ; also see Table 50-1 ). The trophoblastic tissue may continue to proliferate despite the failed embryonic growth, the gestational sac will continue to grow, and hCG levels may continue to rise, although not at the expected rate. The typical sonographic appearance of anembryonic pregnancy is a large, empty gestational sac that does not demonstrate a yolk sac, an amnion, or an embryo ( Figure 50-4 ). The MSD increases by 1.13 mm/day in a normal gestation, but the growth rate of an abnormal sac is only 0.70 mm/day. Therefore abnormal sac growth can be diagnosed when the MSD fails to increase by 0.6 mm/day. In subsequent repeat studies, the sonographer evaluates growth size of the sac, presence of the yolk sac, development of an embryo, and presence or absence of cardiac activity. Box 50-1 outlines several sonographic intrauterine findings associated with abnormal pregnancies. The SRU criteria for failed pregnancy in the presence of an empty sac is an MSD of 25 mm without an embryo.
|Findings Diagnostic of Pregnancy Failure||Findings Suspicious for, but Not Diagnostic of, Pregnancy Failure †|
|Crown-rump length of ≥7 mm and no heartbeat||Crown-rump length of <7 mm and no heartbeat|
|Mean sac diameter of ≥25 mm and no embryo||Mean sac diameter of 16–24 mm and no embryo|
|Absence of embryo with heartbeat ≥2 wk after a scan that showed a gestational sac without a yolk sac||Absence of embryo with heartbeat 7–13 days after a scan that showed a gestational sac without a yolk sac|
|Absence of embryo with heartbeat ≥11 days after a scan that showed a gestational sac with a yolk sac||Absence of embryo with heartbeat 7–10 days after a scan that showed a gestational sac with a yolk sac |
Absence of embryo ≥6 wk after last menstrual period
Empty amnion (amnion seen adjacent to yolk sac, with no visible embryo)
Enlarged yolk sac (>7 mm)
Small gestational sac in relation to the size of the embryo (<5 mm difference between mean sac diameter and crown-rump length)
* Criteria are from the Society of Radiologists in Ultrasound Multispecialty Consensus Conference on Early First Trimester Diagnosis of Miscarriage and Exclusion of a Viable Intrauterine Pregnancy, October 2012.
Absence of cardiac motion in embryos 5 mm or larger
Absence of cardiac motion after 6.5 menstrual weeks
Yolk sac and amnion
Large yolk sac or amnion without a visible embryo
Calcified yolk sac
Large gestational sac
>18 mm lacking a viable embryo
>8 mm lacking a visible yolk sac
Irregular or misshapen
Cornual, low, or hour-glassing through cervical os
Absent double decidual sac finding
Thin trophoblastic reaction <2 mm
Intratrophoblastic venous flow
Gestational sac growth of <0.6 mm/day
Absent embryonic growth
Human chorionic gonadotropin (hcg) correlation
Discrepancy in sac size with hCG levels
From Nyberg DA, Laing FC: In Nyberg DA, Hill LM, Bohm-Velez M, et al, editors: Transvaginal ultrasound, St Louis, 1992, Mosby.
Gestational trophoblastic disease
Gestational trophoblastic disease is a proliferative disease of the trophoblast that occurs after an abnormal conception. It represents a spectrum of disease from a relatively benign form called hydatidiform (partial, complete, or coexistent) mole to a more malignant form called an invasive mole, or choriocarcinoma. The clinical hallmark of gestational trophoblastic disease is vaginal bleeding in the first or early second trimester. Serum levels of beta-hCG are dramatically elevated and are often greater than 100,000 IU/ml. The patient may also experience symptoms of hyperemesis gravidarum or preeclampsia. Maternal serum alpha-fetoprotein levels will be notably low in pregnancies complicated by a complete hydatidiform mole.
In the United States gestational trophoblastic disease affects approximately 1 out of every 1000 pregnancies. Associations with women younger than age 20 and older than age 40 with molar pregnancy have been reported. Molar pregnancies are divided into two categories: partial and complete. A partial mole is karyotypically abnormal, usually triploid, and commonly occurs when a normal egg is fertilized by two sperm. Fetal parts may develop concurrently with abnormal trophoblastic tissue. In contrast, genetic studies indicate that a complete hydatidiform mole has a normal diploid karyotype of 46XX, which is usually entirely derived from the father. Complete moles occur when an egg without a nucleus is fertilized by one normal sperm. Trophoblastic tissue proliferates, but no fetal parts ever develop.
The sonographic appearance of molar pregnancy varies with gestational age. The characteristic “snowstorm” appearance of a hydatidiform mole, which includes a moderately echogenic soft tissue mass filling the uterine cavity that is marked with small cystic spaces representing hydropic chorionic villi, may not be apparent initially, but will present with advancing time ( Figure 50-5 ). The appearance of first-trimester molar pregnancy may simulate a missed abortion, incomplete abortion, blighted ovum, or hydropic degeneration of the placenta associated with missed abortion ( Figure 50-6 ).
On transvaginal sonography, the abnormal appearing choriodecidual or trophoblastic reaction consists of a distorted sac shape with a thin, weakly echogenic or irregular choriodecidual reaction and absence of a double decidual sac when the MSD exceeds 10 mm. There is usually no sign of a viable embryo, and the early developing placenta exhibits multiple abnormal trophoblastic changes. The sonographic examination may reveal a uterus that is larger in size than dates and filled with a heterogeneous complex pattern (“cluster of grapes”) along with bilateral adnexal fullness that may represent ovarian enlargement of theca lutein cysts. The trophoblastic reaction may also be seen as a small echogenic mass filling the uterine cavity without the characteristic vesicles. Typically, remarkable increased blood flow is seen with color Doppler, and spectral Doppler shows low-resistive waveforms with high diastolic flow.
The primary treatment of molar pregnancy is uterine curettage followed by serial monitoring of serum hCG levels and possibly methotrexate administration. Serum hCG level falls toward normal within 10 to 12 weeks after evacuation. The reported incidence of residual disease after curettage is approximately 20%. The use of sonography for direct visualization of the uterine content to ensure complete evacuation during the curettage procedure has been shown to substantially reduce the incidence of residual gestational trophoblastic disease.
A partial mole on sonography has an identifiable placenta, although the placental tissue is grossly enlarged and engorged with cystic spaces, which represent the hydropic villi. An embryo or embryonic tissue may also be identified, but often the embryo is abnormal and is aborted in the first trimester. In later stages of pregnancy (greater than 12 weeks), careful analysis should be performed to look for structural defects, as triploid fetuses usually exist with a partial mole. This includes trisomies 13, 18, and 21.
Bilateral thecalutein cysts have been reported in as many as half of molar pregnancies. Enlarged ovaries may rupture or torse, causing extreme pain for the patient. Thecalutein cysts are well demonstrated on sonography as enlarged ovaries with multiple cystic areas throughout.
Malignant forms of trophoblastic disease include invasive mole and choriocarcinoma. An invasive hydatidiform mole occurs when the hydropic villi of a partial or complete mole invade the uterine myometrium and may further penetrate the uterine wall. This may occur along with the molar pregnancy or may progress after evacuation of the molar tissue has occurred. If this occurs postoperatively, it is referred to as persistent trophoblastic disease. Clinically, the patient presents with continued heavy bleeding and highly elevated hCG levels. The sonographic appearance shows an enlarged uterus with multiple focal areas of grapelike clusters throughout.
Choriocarcinoma is a malignant form of trophoblastic disease that occurs in 2% to 3% of molar pregnancies. This tumor is fast-growing and commonly metastasizes to the lungs, liver, and brain. Clinical symptoms include vaginal bleeding, in addition to dyspnea, abdominal pain, and neurologic symptoms, depending on where the metastasis has spread.