Excerpt from Embryonic Demise

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Background

The embryonic phase of development is complete by the end of the 10th menstrual or gestational week (this corresponds to 10 wk following the onset of the last normal menstrual period). During this critical period of development, a single fertilized cell undergoes dramatic transformation as the cell mass evolves into major organs and a recognizable human form. Because of the complex sequence of events that occurs during this short time period, it is not unusual for complications to develop. Currently, transvaginal ultrasound is the imaging examination of choice to evaluate the rapidly evolving intrauterine events that occur following implantation of the gestational sac and the development of a visible embryo. Although a variety of terms are used to describe early pregnancy failure, in the presence of clear-cut sonographic evidence that a nonliving embryo is present, the term embryonic demise should apply.

Pathophysiology

Some causes of first trimester demise are well understood; however, in most instances, the etiology is unknown (Moore, 1998). In general, significant embryologic malformations that result in demise can be the result of genetic or chromosomal, environmental, or combined factors. Chromosome abnormalities are the leading known cause of pregnancy loss. An estimated 6-7% of zygotes have chromosome aberrations (Moore, 1998), and more than 95% of chromosomally abnormal concepti die in utero. Although the precise incidence is unknown, cytogenic abnormalities are reported in 20% of concepti in women who undergo in vitro fertilization (Bateman, 1992) and in 70% of women with spontaneous abortion (Ohno, 1991). In addition, many chromosome aberrations increase with advancing maternal age (Hook, 1981). This is particularly true for Down syndrome (trisomy 21) but is also evident with other less common trisomies.

Pathologic examination of chromosomally abnormal concepti confirms trisomy in approximately 50% of cases.

The timing of exposure to environmental causes or teratogens is crucial to the outcome of pregnancy. Early exposure, typically before 5 weeks gestational age (GA), has an all-or-none result such that the embryo will either die or be unaffected (Moore, 1998). Not surprisingly, exposure during the period of organ formation (5-10 wk) usually affects organ development and results in either demise or severe congenital abnormalities. Environmental causes include immunologic factors, drugs, infectious agents, alcohol, smoking, environmental chemicals, and radiation.

Once implantation has occurred, another cause of early pregnancy failure relates to an inability of the corpus luteum to adequately support the conceptus (Blumenfeld, 1992). This condition, which tends to occur with maternal obesity and/or advancing maternal age, can be treated successfully during the embryonic phase of development by administrating human choriogonadotropin (hCG).

A developmental uterine anomaly such as a uterine septum or acquired uterine anomalies such as submucosal, large, or degenerating leiomyomas also can increase the incidence of embryonic demise.

Frequency

United States

Overall, an estimated 75% of pregnancies fail to result in a living offspring. Of course, most of these failures occur before implantation of the gestational sac. In these chemical or preclinical pregnancies, the only proof of pregnancy is a transiently positive pregnancy test and possibly a history of an atypical menstrual cycle. According to some investigators (Wilcox, 1988; Bateman, 1992), the incidence of loss following implantation ranges from 20-31%.

• Studies confirm that during embryonic development, the rate of pregnancy failure is inversely related to GA and that with onset of fetal development (beginning at 11 wk GA), demise becomes relatively unusual. Using vaginal ultrasound, one study (Goldstein, 1994) showed that if a gestational sac was visible, the embryonic loss rate was 11.5%; with a yolk sac it was 8.5%; with an embryo less than 5 mm in length, it was 7.2%; and with an embryonic length of 6-10 mm, it was 3.3%. In contrast, loss during the fetal phase of development was 2%.

Clinical Details

During the first trimester of pregnancy, approximately 25% of women experience mild vaginal bleeding and/or cramping. Pelvic examination usually reveals a closed and normal appearing cervix. This clinical presentation characterizes a threatened abortion. Analysis of women with these findings reveals that 50% of the pregnancies will fail, and 50% will have a normal outcome. If the cervix is dilated, the pregnancy will certainly fail, although based on clinical examination, it is not usually possible to determine whether there are retained products of conception. Some women with embryonic demise will be asymptomatic, and in these patients the diagnosis may be suggested based on subnormal uterine growth, inability to auscultate fetal cardiac activity, or failure of the hCG level to increase at the expected rate.

Preferred Examination

In most instances the clinical pelvic examination cannot determine the cause for the patient's symptoms. Thus, the patient should be referred for a real-time pelvic ultrasound examination. If clinical dating suggests a GA of 8 weeks or older, some sonographers begin the ultrasound study using a transabdominal approach. This is because in a normal pregnancy, when using a transabdominal approach, cardiac activity should be visible by 8 weeks GA. However, an increasing number of sonographers begin the ultrasound examination with a transvaginal approach. This is because a higher transducer frequency is used, which in a normal pregnancy can detect cardiac activity approximately 2 weeks earlier or by 6 weeks GA. Furthermore, in comparison to a transabdominal approach, vaginal transducers provide superior resolution with respect to examining the appearance and contents of the gestational sac as well as the ovaries and adnexa.

Limitations of Techniques

Transabdominal probes are limited because they typically use 3.5-5 MHz transducers compared to transvaginal probes, which use 5-10 MHz transducers. Even if a 5-MHz transducer is used for a transabdominal and transvaginal scan, the transabdominal images of an early intrauterine pregnancy (IUP) would be inferior to those obtained by the transvaginal probe. This is because the transvaginal probe is physically closer to the object being scanned, and the transvaginal ultrasound beam does not traverse the abdominal wall. This results in fewer near-field artifactual echoes. These comparative effects are most pronounced when scanning obese patients.

A limitation of the transvaginal approach is if a large pelvic mass is present that precludes visualizing the intrauterine contents. Most often, large or strategically placed calcified uterine fibroids cause this problem. Under these circumstances, an abdominal approach should be used in an effort to image the uterus and its contents.

Another limitation is if the ultrasound study is performed prior to the time a yolk sac can be detected. Using a vaginal approach, this structure should be observed by 5.5 weeks GA. If a small saclike structure b is imaged but it does not contain a yolk sac, it is often not possible to determine if the intrauterine finding is the result of an early IUP or a pseudosac associated with an ectopic pregnancy. In these instances, careful evaluation of the adnexa may be helpful to detect an ectopic pregnancy. Occasionally, serial ultrasound and/or hCG determinations may be required to determine the etiology for the intrauterine sac.

A final but important admonition (that relates to all ultrasound examinations) is to recognize the technical adequacy of the study, to know the limitation(s) of the equipment, and, importantly, to determine the experience of the person who performs and interprets the examination.

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