EARLY NORMAL AND ABNORMAL PREGNANCY
ALIN BASGUL YIGITER, PROF. M.D.
 

INTRODUCTION

Modern ultrasound technology, especially transvaginal techniques, have improved the assessment of early pregnancy development . Currently first trimester ultrasonography indications are to confirm the presence of an intrauterine pregnancy, to evaluate a suspected ectopic pregnancy, to define the cause of vaginal bleeding, to evaluate pelvic pain, to estimate gestational age, to diagnose or evaluate multiple gestations, to confirm cardiac activity, as an adjunct to chorionic villus sampling, embryo transfer, or localization and removal of an intrauterine device, to evaluate maternal pelvic masses or uterine abnormalities and to evaluate suspected hydatidiform mole . The use of diagnostic ultrasound during pregnancy is considered to be safe for both mother and fetus. Even in critical periods of development and using high-frequency transvaginal transducers, no adverse bioeffects have been demonstrated . Ultrasound provides reassurance, charts normal development, and identifies women with abnormal or high risk pregnancies . Sensitive biochemical assays and high-resolution ultrasonography now make the diagnosis of pregnancy highly sensitive and specific .

Furthermore, recent introduction of three-dimensional and four-dimensional ultrasounds combined with the transvaginal approach has produced more objective and accurate information on embryonal and early fetal development and made it possible to visualize fascinating aspects of embryonic differentiation. Three-dimensional diagnostic ultrasound techniques is changing our understanding tremendously. The opportunity to observe the volumetric morphology of the embryo from the very beginning of gestation is clearly of immense importance in understanding the events taking place in this key period of human development .

Earliest Ultrasound Detection and HCG:

Ultrasound examination was first adapted for obstetric use in the 1950's by Ian Donald and it has since become the mainstay of early pregnancy diagnosis . Using transvaginal ultrasonography, Bree and colleagues were able to discern a gestational sac, yolk sac, and fetal cardiac activity at â-hCG levels of 1025, 7200, and10,800 mIU/ml IRP , (International Reference Preparation (IRP) was developed in 1980 . The numerical value of the IRP in international units (IU) is about twice that of the second international Standard, respectively . Transvaginal sonography was introduced in the late 1980s, and it provides superior images owing to the proximity to the pelvic organs. Additionally, a transvaginal scan can be used at earlier gestations ; it gives clearer images, and can be performed instantly, as the patient needs an empty bladder. There are however some limitations; some women may feel it is an intrusion or may be concerned in case the pregnancy is harmed. Some women will refuse a transvaginal scan. Transabdominal ultrasonography is still widely used in this period of gestation for cultural and practical reasons .

The occurrence of positive qualitative evidence of pregnancy occurs shortly after implantation at about 23–28 days (menstrual). The first ultrasound evidence of pregnancy occurs at about 32–35 days . Routine ultrasonography during the first trimester is used for accurate pregnancy dating, early diagnosis of major malformations, characterization of multiple pregnancy and screening of chromosomal anomalies . Failure to understand the limitations of diagnostic ultrasound or inadequate training of physicians in this technique can result in grave complications for the patient and liability for health-care providers .

Timing of Early Pregnancy (5,16,19–21):

The traditional duration of pregnancy dates from the first day of the last menstrual period an average of 40 weeks to delivery. The beginning of this period is made up of:
Pre-ovulatory (follicular) phase of the Ovarian cycle: 13–14 days ending with ovulation of oocyte from ovary into the peritoneal (fimbriated) end of the fallopian tube. Variation typically less than 3 days, occasionally 5-7days.
Oocyte migration: The oocyte migrates into the tube, with fertilization in the tube within 24 hours, typically about day 14.
Fertilization and Zygote migration: The Zygote migrates from tube into the fundal uterus with implantation on day 22–25.
Implantation, or the process by which the embryo comes in contact, adheres, and penetrates the endometrium, is necessary prior to the diagnosis of pregnancy. First contact between the blastocyst and the endometrium occurs 6 days after fertilization. This is known as apposition. Soon after apposition, the blastocyst becomes adherent to the endometrium, and the process of implantation has begun. Trophoblastic HCG production gains access to maternal circulation and sensitive pregnancy tests turn positive, this event occurs 3–5 days prior to the first missed period.
Following implantation, a cavity or sac develops which lies inside the chorionic layer. This subchorionic layer contain the yolk sack (secondary) and the embryonic disk (early embryonic cell mass) surrounded by it's own small amniotic cavity.

First-Trimester Ultrasound: Normal Landmarks

The definition of standard developmental morphological features may open the possibility of screening for structural defects early in the first trimester of pregnancy (1).

There are key chronologic landmarks in the normal development of an embryo or fetus that can be identified by ultrasound scan, and therefore the distinction of a normal and abnormal pregnancy can be made.

4th Week

The first suspicious image of a pregnancy is the persistence proximal to the menstrual days of a decidual transformed endometrium accompanied by a vascular active corpus luteum that can be disclosed by ultrasound . A few days before the expected menses, a typical image of a hyperechogenic ring inside the uterine cavity can be identified by transvaginal ultrasound. A small gestation sac (2 to 5 mm) in the endometrium. The sac is spherical, regular in outline and eccentrically situated toward the fundus. It is implanted just below the surface of the endometrium (midline echo) and is surrounded by echogenic throphoblast. This corresponds to the gestational sac, the echogenic ring being the chorionic villi surrounding the chorionic cavity. What is first observed is the gestational sac (day 31 ± 1), and the visualization threshold is nowadaysestablished when the â-hCG values have surpassed the 1000 mUI 3-D Diagnostic ultrasound makes it possible to obtain images much earlier: on the 27th day of the cycle (13 days after fertilization). Being able to observe in the three orthogonal planes and with 3D rendering allows observation of the exact site of implantation in the endometrium.

5th Week

During the 5th week, the chorionic sac measures 7–10 mm. When this diameter reaches 9 mm, the yolk sac can always be identified as a round, fluid-filled and eccentric structure with a diameter of 3 mm. The secondary yolk sac is the first element seen in the gestational sac. It is a spherical membrane, quite echogenic and readily seen. Because it is reliably seen early, usually at 5 weeks, it is a critical landmark identifying a true gestation sac. The gestational sac can be observed with the following characteristics: an oval or round shaped with limpid boundaries, homogeneous trophoblastic rim greater than 5 mm, no internal contour irregularities. The gestational sac grows at a rate of about 1mm per day. The sac’s shape is round between the fifth and sixth week and becomes oval later on during the end of the 5th week, the embryo is first seen on high resolution scans as a thickening on the margin of the yolk sac. The embryo attains a size of 2 mm and appears sonographically as a hyper-refringent area located on the yolk sac. Pulsations can be visualized on real-time imaging, close to the wall of the yolk sac and within a 2–3 mm echogenic line corresponding to the embryo. After this time, the heart rate can be measured using simultaneous M-mode.

Measurement of the mean gestational sac diameter is an effective estimate of gestational age, used between 5 and 5.7-6 weeks. From week fifth on, different organs and structures will appear.

6th Week

The most important finding is the embryonic visualization. The embryonic pole is visible and it measures 2 to 4mm in length. Cardiac motion can be clearly seen and the mean heart rate at this gestational week is about 118 bpm. The amnion is not yet clearly seen, so the embryo and the yolk sac are apparently free floating in the chorionic cavity, although eccentrically fixed by the connecting body stalk. By High resolution vaginal scanning, embryos should be seen at Mean Sac Diameters (MSD) of 18mm, with lower resolution abdominal scanning, embryos should be seen with MSD of 25mm.

Following the visualization of the embryo, the crown-rump length should be measured. This is because later gestational sac measurements may not reflect the embryonic size (or even its presence), the embryonic CRL directly reflects embryonic growth. This measurement should be made from the cephalic pole to the rump taking care to measure the embryonic curvature.

The gestational sac grows approximately 1.15 mm per day, so that at the end of the sixth week it measures 20 mm, up from 10 mm at the beginning of this week. The embryonic growth is of 1 mm per day.

7th Week

During the 7th week, The crown-rump length measures 11 to 16 mm and the yolk sac, with a diameter of 5 mm, separates from the embryo, probably owing to the growth of the vitelline duct.

The rhombencephalon becomes as a diamond shaped cavity, enabling distinction of cephalad and caudal. The spine is seen as double echogenic parallel lines. The amniotic membrane becomes visible defining the amniotic cavity from the chorionic cavity. The umbilical cord can also be seen.

8th Week

The upper and lower limb buds are now visible in an embryo that is stil rounded in shape. The placental site can even be identified, following the umbilical cord from the abdominal wall of the embryo.

Crown-rump length is 17 to 23mm. Forebrain, midbrain, hindbrain, and skull are distinguishable. Midgut hernia is present. It is a round and well defined structure, refringent, and linked to the abdominal wall at the site of the umbilical cord insertion. Its refringency is that of the abdominal wall, its size is small, less than 7 mm, and always disappears between the 11th and 12th week. Although at this week the profile, forehead, nose and mouth are visible they will be clearly defined by the 10th week. The cranial pole is large and voluminous. The profile, face, orbits, mouth, jaw and maxilla can be identified.

The amniotic cavity expands and the umbilical cord and vitteline duct lengthens embryonic movements are detectable.

Discrete undulating body movements can be sporadically seen on real-time imaging at the end of the 8th week. In the first 8 weeks of pregnancy.

The corpus luteum is often identified as a cystic mass measuring 1 to 3 cm in diameter, although they may reach as large as 8 cm. These masses usually resolve spontaneously by the onset of the second trimester. If an adnexal mass persists into the second trimester. The two most common benign neoplasms of the ovary during pregnancy are serous cystadenoma and benign cystic teratoma. The risk of a persistent adnexal mass during pregnancy subsequently diagnosed as malignant has probably been overestimated: it is significantly less than 1%.

9th Week

Crown-rump length 23 to 32 mm. The yolk sac is in a more peripheral location. The limbs lengthen and hands and feet are seen although the fingers are not yet visible. Embryonic heart rate peaks at 170 to 180 bpm the head represents one-third of the entire body and, inside the head, the hyperechoic falx and choroid plexuses and a hypoechoic heart-shaped structure corresponding to the cerebral peduncles are visible. The physiological midgut herniation, which can be identified close to the anterior abdominal wall, will persist until the end of the 11th week. Body movements are now more frequently seen.

10th Week

The fetus occupies more than a third of the space in the gestational sac; CRL is 32–41 mm and the embryo is slightly more curved. The choroid plexuses fill the lateral ventricles completely, and are the most prominent structures in the cephalic pole.

The structural development of the heart begins on day 16 and it is finished by the 10th week. In the posterior fossa, the cisterna magna and cerebellum can be identified, though the development process of the posterior fossa will only be concluded by 16 weeks. In the trunk, the cardiac valvular apparatus can sometimes be distinguished inside the heart by the end of the 10th week, although more accurately from the 11th week onwards.
Also at the end of the 10th week, the stomach filled with a small amount of liquid, can sometimes be identified in the abdomen.

The three segments of the upper and lower limbs are clearly identified with both hands and feet in the midline.

11th Week

At 11 weeks the development of the head and neck continues. There is fusion of the parietal and capsular decidual layers, the fetus (no longer the embryo) occupies now half of the amniotic cavity. the CRL will be greater than 42 mm, reaching 76 mm at 13 weeks.

From now on, a more detailed anatomical survey can be obtained, including the cerebral and cardiovascular systems and the digestive and urinary tracts. The herniated midgut returns into the abdominal cavity. Stomach, bladder and the kidneys are visible. Fetal fingers and toes are easier to visualize.

12th Week

In week twelve the skull is fully formed. Facial and abdominal structures can be observed. Hands and feet are fully developed. It is possible to count the fingers and toes.

Abnormal ultrasound findings in early pregnancy

Fetal demise, empty gestational sac, disproportionate fetal growth with the gestational sac can be a sign of abnormal early pregnancy. Transvaginal ultrasound is useful in determining the prognosis of the pregnancy and in the differential diagnosis of early pregnancy complications.

Actually approximately 40% of early pregnancies result in miscarriage. Most of these miscarriages happen before the menstrual period is missed. Abortions (Spontaneous abortion Threatened abortion Complete abortion incomplete abortion Inevitable abortion missed abortion) can be due to unknown etiology, morphologic and chromosomal abnormalities, infection, anatomic defects, endocrine factors, immunologic factors, and maternal systemic disease. The risk of miscarriage lessens as the gestation progresses. For example while the risk of miscarriage at 5 weeks is approximately 15-30%, it is less than 5% after 9 weeks of gestation. Similarly while when CRL is less than 5 mm, the risk of pregnancy loss is around 8%, it is less than 1% when CRL is more than 10mm.

In missed abortion the fetus dies in the uterine cavity but a miscarriage has not yet occurred. Therefore No fetal heart motion can be visualized and Color or power doppler ultrasound shows the lack of blood flow in the fetus. In blighted Ovum or anembryonic pregnancy the embryo fails to develop or died at a very early stage so that we cant see it . Therefore only a gestational sac, with or without a yolk sac, is seen in the ultrasound. When the crown-rump length measures 4 to 10mm the fetal heart beat should be detectable.

Slow fetal heart rate which is less than 85bpm is associated with poor prognosis. When the gestational sac diameter is more than 12 mm, yolk sac should be visible at about 5 weeks of gestation. The scan should be repeated one week later to confirm if there is an early embryonic demise. If the gestational sac diameter is more than 20 mm, an embryo is usually visible. If not the scan should be repeated one week later to confirm the problem.
The ultrasonographic appereance of the yolk sac can also predict the pregnancy loss risk. Spontaneous abortion risk can be predicted if one of the following ultrasound findings of yolk sac is present. Absence of the yolk sac, too large (>6mm),too small (<3mm),irregular shaped or having degenerative changes (calcifications or decreased transclucency).

The presence of intrauterine hematoma carry the risk of abortion in the first trimester. The size and the location of the hematoma is important to determine the prognosis of the pregnancy. According to the localization hematomas can be retroplacental, subchorionic, marginal and supracervical. Among these, retroplacental hematomas are the most severe regarding the risk of abortion. While retroplacental or central hematomas carry the worst prognosis, supracervical hematomas carry the best prognosis in terms of abortion. Literature data shows that fundo-corporal hematomas are more likely to cause spontaneous abortion or preterm delivery than supracervical hematomas.

Fetal Sex Determination by Ultrasound at First Trimester 35,36

Prenatal gender assignment by ultrasound has a high accuracy rate at 12-14 weeks. The accuracy of sex determination increased with gestation from 70.3% at 11 weeks, to 98.7% at 12 weeks and 100% at 13 weeks. In the male fetuses, there is a significant increase in the angle of the genital tubercle from the horizontal with crown-rump length.

The genital region is examined in a midsagittal plane. The angle of the genital tubercle to a horizontal line through the lumbosacral skin surface can be measured. The fetus is usually thought to be male if the angleis > 30 degrees, and female gender if the genital tubercle is parallel or convergent (<10 degrees ) to the horizontal line. At an intermediate angle of 10–30 degrees the gender is not determined.

First Trimester Nuchal Transclucency Examination 37–39

The ultrasonographic fetal examination in the late first trimester is useful for both screening and diagnostic purposes. Between 11 and 14 weeks of gestation, that is, between 45–84 mm crown-rump length, a subcutaneous translucency behind the neck region can be disclosed in a sagittal section of the fetus. The maximum thickness between the skin and the soft tissue overlying the cervical spine can be measured, and was called nuchal translucency (NT). The term translucency is used, irrespective of whether it is septated or not and whether it is confined to the neck or envelopes the whole fetus. In fetuses with chromosomal abnormalities, cardiac defects and many genetic syndromes the NT thickness is increased.

Other benefits of the 11-13 weeks scan include: accurate dating of the pregnancy, early diagnosis of many major fetal defects, diagnosis of multiple pregnancies and early screening for severe preeclampsia.

The Fetal Medicine Foundation promoted screening for Down syndrome at 11–13+6 weeks by Nuchal Translucency or a combination of nuchal translucency and maternal serum biochemistry.

Screening by nuchal translucency can detect about 80% of affected fetuses for a false positive rate of 5%. The combination of nuchal translucency and maternal serum free â-hCG and PAPP-A improves the detection to90%. There is now evidence that the detection rate can increase to about 95% and the false positive rate can be reduced to 2.5% by also examining the nasal bone (In a high proportion of fetuses with trisomy 21 and other chromosomal abnormalities the nasal bone is hypoplastic or not visible at 11-13 weeks' gestation), facial angle (Fetuses with trisomy 21 have a flat profile because the maxilla (upper jaw) is small and set back. This produces a wide angle in a line drawn over the palate and between the maxilla and the forehead (facial angle)), ductus venosus flow(The incidence of reversed ductus venosus a-wave is related to NT and CRL as well as aneuploidy, being more common when the NT is high and the CRL is low) and tricuspid flow (If there is tricuspid regurgitation the risk is always increased. )

Early Fetal Echocardiography

Early fetal echocardiography can also be done between 11 to 14 weeks successfully. The normality of the four chamber view through a transverse section of the fetal chest: normal situs solitus; normal size and axis of the heart in relation to the chest can be evaluated.

Color Doppler also helps us to better visualize the outflow tracts and to identify normal systemic and pulmonary venous return.

Multiple pregnancy and the Chorionicity determination at the first trimester

Twin pregnancy can be diagnosed after week 6, when two gestational sacs are clearly visible, each one with its own embryo. In cases of multiple pregnancies, monochorial or bichorial, sacs and embryos can be observed. It is not acceptable to miss a diagnosis of twins by transabdominal ultrasound examination after the eight week of pregnancy.

Antenatal determination of chorionicity by ultrasound is much easier in the early first trimester. It is also accurate to perform an ultrasound scan between 10 and 14 weeks, relying on the demonstration of the lambda sign for dichorionic (with a positive predictive value of 100% for dichorionicity), or the T-sign for monochorionic twin pregnancies.

CONCLUSIONS

It is now possible to look at intrauterine events from the beginning of pregnancy, close to the time of implantation.

The high resolution, safety, and ease of performance make ultrasound the procedure of choice for routine ultrasonography in the first half of pregnancy as a standard of obstetric care (18,41). Transvaginal ultrasound has revolutionized the diagnosis and management of early pregnancy. Pregnancies can be detected earlier compared with abdominal ultrasound, patients reassured by showing normal development .

Accurate gestational age determination, sufficiently early characterization of multiple pregnancy, early diagnosis of lethal anomalies and screening of chromosomal defects are important end points to be taken into account by health authorities and to recommend routine ultrasound examination in the late first trimester of pregnancy.

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