On completion of this chapter, you should be able to:
Describe the early development of the embryo and its sonographic appearance at different gestational ages
Explain the clinical roles of first-trimester maternal serum biochemistry
Define the sonographic characteristics of the yolk sac, embryo, amnion and chorion, and gestational sac
Describe the sonographic measurements performed in the first trimester and the goals of first-trimester sonography
Discuss the use of a first-trimester fetal anatomy survey
Identify the methods of aneuploidy risk assessment used in the first trimester
First-trimester obstetric sonography is an increasingly important component of prenatal care. These examinations may diagnose conditions that require intervention, and even in “normal” intrauterine pregnancies they provide patients and clinicians with information that influences management. Information about multiple pregnancies, uterine anomalies, and pelvic masses that are readily visualized during the first trimester may be more difficult to obtain later.
Aspects of prenatal fetal screening and diagnosis are shifting from second trimester to first trimester. First-trimester aneuploidy screening protocols have higher detection rates than second-trimester tests. Genomic technology allows screening of cell-free fetal deoxyribonucleic acid (DNA) in early pregnancy. The current standard of care suggests offering aneuploidy screening during the first trimester to all obstetric patients and, where available, offering diagnostic genetic testing through chorionic villi sampling (CVS) between 11 and 13 weeks. Fetal anatomy has not been routinely assessed until the second trimester, but recent studies have demonstrated the possibility of detecting many structural anomalies earlier. In the morbidly obese gravida, assessment of fetal anatomy through transvaginal sonography in the late first trimester may be an improvement over second-trimester scanning.
Although the ability to image the first-trimester pregnancy with ultrasound may seem routine, the potential for false-positive and false-negative diagnoses for any given pathology is substantial. Extreme care should be taken when evaluating the first-trimester pregnancy sonographically.
Overview of the first trimester
A note on terminology
It is especially important to have a clear understanding of terminology when discussing embryology. Embryologists state time in conceptual age, also known as embryologic age, with conception as the first day of pregnancy. Clinicians and sonographers use gestational age, also known as menstrual age, to date the pregnancy, with the first day of the last menstrual period as the beginning of gestation. Thus the gestational age would add 2 weeks onto the conceptual age. For 12 days after conception, during the implantation process, the conceptus is called a zygote. From the time of implantation until the end of the 10th week menstrual age, the conceptus is called an embryo. After the first 10 weeks, the embryo is called a fetus.
Normal pregnancy progression
Except when specifically noted, dates in this chapter reflect menstrual age rather than embryologic age (conceptual age). The gestational age (also known as menstrual age) is calculated by adding 2 weeks (14 days) to the conceptual age. Menstrual age refers to the length of time calculated from the first day of the last menstrual period to the point at which the pregnancy is being assessed. During a 28-day menstrual cycle, a mature ovum is typically released at day 14. The ovum is swept into the distal fallopian tube via fimbriae; fertilization occurs within this region 1 to 2 days after ovulation. Meanwhile, the follicle that released the mature ovum hemorrhages and collapses to form the corpus luteum, which begins to secrete progesterone and estrogen ( Figure 49-1 ).
The fertilized conceptus that is now referred to as a zygote undergoes rapid cellular division to form the 16-cell morula. Further cell proliferation brings the morula to the blastocyst stage. The blastocyst contains trophoblastic cells and the “inner cell mass,” which forms the embryo. The trophoblastic cells begin to secrete human chorionic gonadotropin (hCG) that is absorbed within the tubes and stimulates maternal pregnancy responses.
The hCG causes the uterine endometrium to convert to decidua, a glycogen-rich mucosa that nourishes the early pregnancy. The blastocyst typically enters the uterus 4 to 5 days after fertilization. Implantation into the uterine decidua is completed within 12 days after fertilization. During implantation, proteolytic enzymes produced by the trophoblasts “eat into” decidual tissue, creating spaces for trophoblastic cell proliferation. Blood pools known as lacunae that form as maternal capillaries erode nourish the proliferating trophoblastic cells. A primitive blood exchange network between mother and conceptus is formed, and the lacunae and trophoblastic cells develop into a mature placental/maternal circulation complex that will sustain the pregnancy. By the end of the implantation process, the zygote has buried itself within one wall of the uterus. The implantation process sometimes results in light vaginal bleeding about the same time as the expected menstrual period.
When implantation is complete, the trophoblast has formed primary villi, which initially encircle the early gestational sac. Within the conceptus, the inner cell mass matures into the bilaminar embryonic disk, the future embryo, and the primary yolk sac. At approximately 23 days of menstrual age, the primary yolk sac is pinched off by the extraembryonic coelom, forming the secondary yolk sac. The secondary yolk sac is the yolk sac seen sonographically throughout the first trimester ( Figure 49-2 ). The amniotic and chorionic cavities also develop and evolve during this period of gestation.
The embryonic phase occurs from week 4 through week 10. It is during this phase that all major internal and external structures begin to develop ( Table 49-1 ). The cardiovascular system undergoes rapid development, with the initial heartbeat occurring at between 5½ and 6 weeks. The embryo’s appearance changes from a flat, disklike configuration to a C -shaped structure, and it develops a human-like appearance ( Figure 49-3 ). During this period of embryogenesis, the crown-rump length (CRL) develops rapidly, measuring 35 mm by the end of the 10th week.
|Menstrual Age||Embryonic Observations|
|Week 5||Prominent neural folds and neural groove are recognizable.|
|Day 36||Heart begins to beat.|
|Week 6||Anterior and posterior neuropores close and neural tube forms.|
|Day 41||Upper and lower limb buds are present.|
|Day 42||Crown-rump length is 4.0 mm.|
|Day 46||Paddle-shaped hand plates are present. Lens pits and optic cups have formed.|
|Day 48||Cerebral vesicles are distinct.|
|Day 50||Oral and nasal cavities are confluent.|
|Day 52||Upper lip is formed.|
|Day 54||Digital rays are distinct.|
|Day 56||Crown-rump length is 16.0 mm.|
|Week 9||Cardiac ventricular septum is closed. Truncus arteriosus divides into aorta and pulmonary trunk. Kidney collecting tubules develop.|
|Day 58||Eyelids develop.|
|Day 64||Upper limbs bend at elbows. Fingers are distinct.|
|Week 10||Glomeruli form in metanephros.|
|Day 73||Genitalia show some female characteristics but are still easily confused with male genitalia.|
|Day 80||Face has human appearance.|
|Day 82||Genitalia have male and female characteristics but still are not fully formed.|
|Day 84||Crown-rump length is 55 mm.|
|Month 7||Ossification is complete throughout vertebral column.|
|Month 8||Ossification centers appear in distal femoral epiphysis.|
The last 2 weeks of the first trimester (weeks 11 and 12) constitute the beginning of the fetal period. During the fetal period growth of the organs and structures formed during the embryonic period continues. At this stage, the fetal head is disproportionately larger than the rest of the fetus, constituting one half of the CRL ( Figure 49-4 ). As the fetus grows, body growth accelerates, and this proportionality becomes less pronounced. Fetal anatomy is fully developed in the late first trimester, and the goal of sonography at this stage includes anomaly detection.
Maternal serum analysis in early pregnancy
Maternal serum biochemistry values can be very useful in evaluation of the early pregnancy. A direct relationship exists in early pregnancy between the sonographic findings and quantitative serum hCG levels. Gestational sac size and hCG levels increase proportionately until 10 menstrual weeks, at which time the gestational sac is approximately 45 mm mean sac diameter (MSD), and an embryo should be easily detected by transabdominal or transvaginal sonography.
Quantitative hCG levels in viable intrauterine pregnancies (IUPs), nonviable IUPs, and ectopic pregnancies have considerable overlap. In general though a normal gestational sac is expected to be visible when the hCG level is greater than 3000 mIU/ml (Second International Standard) ( Table 49-2 ). The sonographer must be aware that when the hCG value is at this level and the gestational sac is not seen within the uterus, an ectopic pregnancy may be considered.
|Menstrual Weeks||hCG Levels, mIU/ml|
Ectopic pregnancies demonstrate a lower hCG level than intrauterine pregnancies, perhaps owing to limited absorption outside the uterus. The rate of rise or increase in hCG during early pregnancy may help detect ectopic pregnancies. The normal intrauterine pregnancy at less than 7 weeks demonstrates doubling of quantitative maternal serum hCG levels every 3.5 days, or an increase of 66% in hCG levels within 48 hours. If this normal rate of increase is not seen, there is a greater chance that the pregnancy is ectopic. However, some ectopic pregnancies will show a normal rate of increase, and some normal pregnancies will show a reduced rate.
Abnormal pregnancies demonstrate a low hCG level relative to gestational sac development, and it has been shown that hCG levels fall before spontaneous expulsion of nonviable gestations. Sonographers need to obtain quantitative hCG levels whenever possible before first-trimester obstetric examinations are performed, as physicians may correlate hCG levels with the gestational sac appearance. This is particularly important when vaginal bleeding or pelvic pain is present, or when an ectopic pregnancy is suspected.
At 9 to 10 weeks, hCG levels plateau and subsequently decline while gestation continues. In pregnancies where the fetus is trisomy 21, the hCG levels plateau later and fall much more slowly. Levels of hCG are increased in these pregnancies compared with normal pregnancies, and the difference increases as gestation advances. Consequently, increased hCG levels can be used as a screening marker for Down syndrome during the first and second trimesters. Increased hCG is not a strong marker and does not have sufficient sensitivity to be used by itself in screening for Down syndrome. It is combined with other independent markers to enhance detection. hCG is a component of first-trimester risk assessment and a component of triple-screen and quad-screen testing performed during the second trimester. The sensitivity of hCG for Down syndrome assessment is improved by measurement of the free beta subunit. Both total hCG and free beta hCG are used for aneuploidy screening in the United States.
Pregnancy-associated plasma protein–A (PAPP-A), also known as pappalysin-1, is an insulin-like growth factor produced by trophoblastic (placental) cells during pregnancy. It is involved in proliferative growth processes such as bone and tissue formation. Maternal serum PAPP-A increases with advancing gestation. In trisomy 21–affected pregnancies, PAPP-A levels are initially lower than in normal pregnancies, but the difference decreases with increasing gestational age. Decreased values of maternal serum PAPP-A may be a marker for Down syndrome during the first trimester but are not useful in the second trimester. Currently, PAPP-A analysis at 9 to 11 weeks of gestational age is the strongest biochemical marker for Down syndrome. PAPP-A is not sensitive enough to be used by itself, however, and is combined with hCG levels for serum biochemistry screening or with hCG and sonographic markers for combined screening. Some studies project an association between PAPP-A levels in early pregnancy and pregnancy pathology such as growth restriction, preterm labor, and preeclampsia.
Genomic techniques allow fragments of fetal DNA, cell-free fetal DNA, that originate primarily from the placenta to be found in maternal serum and analyzed from 9 weeks of gestation. The cell-free DNA screening tests have very high detection rates for trisomy 21, but false-positive and false-negative results have been reported. The positive predictive value of the tests varies depending on the prevalence of the condition and risk level of the mother. Before or after cell-free DNA screening there is substantial value in first-trimester ultrasound screening for structural fetal anomalies.
Sonographic technique and evaluation of the first trimester
First-trimester obstetric sonography has evolved rapidly with the development of transvaginal transducers, which allow the gravid uterus and adnexa to be visualized with improved resolution by allowing higher frequencies (5 to 8 MHz) and transducer placement closer to anatomic structures compared with transabdominal scanning. With transvaginal transducers, the pelvic anatomy is imaged in both sagittal and coronal/semicoronal planes. Such coronal imaging of the pelvis is unique within sonography, and the images should not be misconstrued as transverse sections ( Figure 49-5 ).
Although transvaginal sonography has gained overall acceptance within the medical community because of its improved image quality, transabdominal and transperineal sonography should not be overlooked. The transabdominal approach allows visualization of a larger field of anatomy, which is important when specific anatomic relationships are in question. For instance, the size, extent, and anatomic relationships of a large pelvic mass with surrounding structures can be determined only with transabdominal techniques. The transperineal approach may be used to visualize the cervix.
Three-dimensional sonography is also performed in the first trimester, and its clinical value during this stage of pregnancy is developing.
The value of pulsed Doppler analysis of early gestation in some situations has been reported. Pulsed Doppler should be performed in early pregnancy only when there are clear benefits.
Indications for first-trimester obstetric sonography (see Box 47-1 ) and sample protocols for these examinations are recorded in Chapter 47 . The major components of a routine first-trimester examination include the following:
The uterus and adnexa are evaluated for the presence of a gestational sac.
Sonographic measurements of the embryo and/or sac are recorded.
The presence or absence of cardiac activity is documented.
Fetal number is documented and chorionicity is assessed in multiple pregnancies.
The uterus, adnexal structures, and cul-de-sac are evaluated.
The nuchal translucency (NT) may be measured and a fetal anatomy survey is performed.
Visualization of early gestation
During the fifth week of embryonic development, the intrauterine pregnancy (IUP) can be visualized sonographically. It appears as a 1- to 2-mm sac with an echogenic ring having a sonolucent center. The anechoic center represents the chorionic cavity. The circumferential echogenic rim seen surrounding the gestational sac represents trophoblastic tissue and the associated decidual reaction. The echogenic ring around the gestational sac can be divided embryologically into several components. The portion on the myometrial or burrowing side of the conceptus is known as the decidua basalis. The villi covering the developing embryo are referred to as the decidua capsularis ( Figure 49-6 ). The interface between the decidua capsularis and the echogenic, highly vascularized decidua on the opposite wall of the endometrial cavity forms the double decidual sac sign, which has been reported to be a reliable sign of an early intrauterine gestation. The gestational sac is eccentrically placed in relation to the endometrial cavity, secondary to its implantation. Typically, a fundal location is noted ( Figure 49-7 ).
The normal sonographic features of a gestational sac include a round or oval shape; a fundal position in the uterus, or an eccentrically placed position in the middle portion of the uterus; smooth contours; and a decidual wall thickness greater than 3 mm ( Figure 49-8 ). Implantation in the lower uterine segment may be associated with placenta accreta or placenta previa.
A yolk sac should be seen when the MSD is greater than 12 mm. An embryo should be seen when the MSD is greater than 18 mm ( Box 49-1 ). Once the gestational sac is sonographically imaged, rapid growth and development occur. The gestational sac size grows at a predictable rate of 1 mm/day in early pregnancy.
Shape: round or oval
Position: fundal or middle portion of uterus; a center position relative to endometrium (double decidual sac or intradecidua finding)
Wall (trophoblastic reaction): echogenic
Internal landmarks: yolk sac typically present when gestational sac is larger than 12 mm; embryo present when gestational sac is larger than 25 mm
Often the first intragestational sac anatomy seen is the sonographic yolk sac (secondary yolk sac), which is routinely visualized at between 5 and 5½ weeks of gestation. The yolk sac is seen before the beating embryonic heart, because embryonic heart motion begins at approximately 5½ weeks. The yolk sac may be used as a landmark to image the embryo, given the connection between yolk sac and embryo.
At this point in gestation, rapid embryonic development increases gestational sac size, leading to better defined visualization of gestational structures. Between 5½ and 6 weeks of gestation, the amniotic cavity and membrane, chorionic cavity, yolk sac, and embryo should be seen.
The yolk sac is the earliest intragestational sac anatomy seen. The yolk sac is normally seen from 5 weeks of gestation. The secondary or sonographic yolk sac has essential functions in embryonic development, including (1) provision of nutrients to the developing embryo, (2) hematopoiesis, and (3) development of embryonic endoderm, which forms the primitive gut.
Initially, the yolk sac is attached to the embryo via the yolk stalk, but with amniotic cavity expansion, the yolk sac, which lies between the amniotic and chorionic membranes, detaches from the yolk stalk at approximately 8 weeks of gestation ( Figure 49-9 ).