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Chapter 29 ■ Bioeffects and Safety of Ultrasound in Obstetrics 1067
as reported by teachers. Specific dyslexia tests showed
similar incidence rates among scanned children and controls in reading, spelling, and intelligence scores and no
discrepancy between intelligence and reading or spelling.
Therefore the original finding of dyslexia was not confirmed in subsequent randomized controlled trials.
It is considered unlikely that routine ultrasound
screening can cause dyslexia.
Non-Right-Handedness
A possible link between prenatal exposure to ultrasound
and subsequent non-right-handedness at age 8 to 9 years
in children exposed to ultrasound in utero was first
reported in 1993 from Norway.
authors, however, the difference was “only barely significant at the 5% level” and was restricted to boys.
150
According to the
152
A
second group of researchers (including Salvesen, main
author of the first study), studying a new population of
over 3000 children from Sweden, reported similar findings of a statistically significant association between
ultrasound exposure in utero and non-right-handedness
in males.
131
Evidence is insufficient to infer a direct effect
on brain structure or function, or even that non-righthandedness is an adverse effect.
Neurologic Development and
Behavioral Issues
Neurons of the cerebral neocortex in mammals, including
humans, are generated during fetal life in the brain proliferative zones and then migrate to their final destination
by following an inside-to-outside sequence. This neuronal migration occurs in the human fetal brain mainly
from 6 to 11 weeks of gestation,
weeks. It has long been thought that external factors such
as ultrasound may theoretically affect this process.
153
but continue until 32
154
In
another study, only two of 123 variables were found to
be disturbed at birth, but not at 1 year of age, in children
exposed in utero: grasp reflex and tonic neck reflex.
155
The significance was not elaborated, and some doubts
exist regarding statistical validity. In a paper previously
mentioned,
127
vision and intelligence scores were identical
among 425 exposed infants and 381 controls. A large
report found no association between routine exposure to
prenatal ultrasound and school performance (deficits in
attention, motor control, perception, vision, and
hearing).
156
In more than 4900 children age 15 to 16
years, no differences were found in school performance
between exposed and nonexposed children, except for a
lower score for exposed boys in physical education.
157
Behavioral changes may be a more sensitive marker
of subtle brain damage than obvious structural altera-
158
tions.
Such changes have been described in animals,
although often transient.
100
No changes have been
87,108
reported in humans. In particular, schizophrenia and
other psychoses have not been found to be associated
with prenatal ultrasound exposure.
159
Congenital Malformations
In humans, prenatal ultrasound has not been shown to
result in an increased incidence of congenital anomalies,
as found in animals.
Childhood Malignancies
No association has been found between ultrasound exposure in utero and the later development of leukemia
or solid tumors in children.
130,162-166
Again, although some of these studies were published
in 2007 or 2008, the populations studied were exposed
to ultrasound in utero 20 to 30 years ago, that is, with
instruments generating lower outputs and with minimal
or no information available on exposure conditions.
SAFETY GUIDELINES
It is difficult to issue precise safety recommendations
because of the multitude of ultrasound instruments, each
with a selection of transducers and used in a variety of
applications. Patient characteristics further complicate
the task.
the thermal and mechanical indices (TI, MI), using the
appropriate controls, and/or reduce the dwell time. The
1999 statement of the British Medical Ultrasound
Society (BMUS), reconfirmed in 2009, declares
The BMUS has strict recommendations for maximum
allowed exposure time (T
(Table 29-1). Interested readers are strongly encouraged
to go to the BMUS website for more detailed recommendations in obstetric and other ultrasound.
and Ziskin
between exposure duration and temperature elevation in
producing harmful bioeffects in animal fetuses. For temperatures below 43° C, the exposure time necessary for
every 1° C increase in temperature was decreased by a
factor of 4. Using a maximum “safe” exposure time of 4
minutes for a temperature elevation of 4° C, based on
these calculations, the following maximal exposure times
are allowable with no obvious risks: 4 minutes at 4° C,
16 at 3° C, 64 at 2° C and 128 at 1° C. General recommendations from major organizations follow:
1. A diagnostic ultrasound exposure that produces a
2. A diagnostic ultrasound exposure that elevates
167
An easy way to reduce exposure is to reduce
For equipment for which the safety indices are displayed
over their full range of values, the TI should always be less
than 0.5 and the MI should always be less than 0.3. When
the safety indices are not displayed, T
1° C and MI
of the same subject is to be avoided.
should be less than 0.3. Frequent exposure
max
max
59
demonstrated a logarithmic relationship
should be less than
max
), depending on the TI
maximum in situ temperature rise of no more than
1.5° C above normal physiologic levels (37° C) may
be used clinically without reservation on thermal
grounds.
170
embryonic and fetal in situ temperature above
168
169
Miller
160,161
:
1068 PART IV ■ Obstetric Sonography
TABLE 29-1. DURATION OF OBSTETRIC
ULTRASOUND AS A FUNCTION OF
THERMAL INDEX
THERMAL INDEX (TI) RECOMMENDED UPPER LIMIT
0.7 60 minutes
1 30 minutes
1.5 15 minutes
2 4 minutes
2.5 1 minute
Modified from British Medical Ultrasound Society. Guidelines for the safe use of
diagnostic ultrasound equipment. 2000, reconfirmed 2009. http://www.bmus.org/
ultras-safety/us-safety04.asp.
41° C (4° C above normal temperature) for 5
minutes or more should be considered potentially
hazardous.
170,171
In this regard, maternal
temperature elevation (e.g., from viral disease)
should be considered because body temperature of
the fetus will also be increased above normal.
3. The risk of adverse effects is increased with the
duration of exposure (dwell time).
172
50
4. Based on available information, there is no reason
to withhold scanning in B-mode for medical
indications. The risk of thermal damage secondary
to heating appears to be negligible.
5. M-mode ultrasound appears to be safe and not to
cause thermal damage.
50
170
6. Spectral Doppler ultrasound may produce high
intensities, and routine Doppler examination during
the embryonic period is rarely indicated.
173
7. Education of ultrasound operators is crucial; the
responsibility for the safe use of ultrasound devices is
shared between the users and the manufacturers, who
should ensure the accuracy of the output display.
173
8. The American Institute of Ultrasound in Medicine
(AIUM) advocates the responsible use of diagnostic
ultrasound and strongly discourages the nonmedical
use of ultrasound for “entertainment” purposes.
The use of ultrasound without a medical indication
to view the fetus, obtain a picture of the fetus, or
determine the fetal gender is inappropriate and
contrary to responsible medical practice. Ultrasound
should be used by qualified health professionals to
provide medical benefit to the patient.
29
9. Examinations should be kept as short as possible
and with as low MI and TI outputs as possible, but
without sacrificing diagnostic accuracy. Follow the
as low as reasonably achievable (ALARA)
principle.
174
CONCLUSION
Diagnostic ultrasound has been used in medicine in
general and obstetrics and gynecology in particular for
more than half a century. No confirmed biological effects
have been described in patients as a result of exposure to
diagnostic ultrasound. However, such effects have been
described in animals, often at exposure levels higher than,
but also occasionally equivalent to, those used in clinical
practice. Epidemiologic information available is from
studies performed on instruments with acoustic output
much lower than current machines. Often, exposure data
are insufficient and number of subjects too small. Furthermore, “no reported effects” does not mean “no
effects,” and such biologic effects may be identified in the
future. Prudent use of ultrasound in fetal scanning, following the ALARA principle, is therefore recommended.
Based on known mechanisms, there is no contraindication to the use of B-mode, M-mode, 3-D/4-D, and color
Doppler ultrasound, when clinically indicated. However,
special precaution is necessary when applying pulsed
Doppler ultrasound, particularly in the first trimester.
References
1. Donald I. The safety of using sonar. Dev Med Child Neurol
1974;16:90-92.
2. Hellman LM, Duffus GM, Donald I, Sunden B. Safety of diagnostic
ultrasound in obstetrics. Lancet 1970;1:1133-1134.
3. Dewhurst CJ. The safety of ultrasound. Proc R Soc Med 1971;
64:996-997.
4. Nyborg WL. Safety of ultrasound diagnosis. Science 1974;186:
1074.
5. Lele PP. Safety and potential hazards in the current applications of
ultrasound in obstetrics and gynecology. Ultrasound Med Biol
1979;5:307-320.
6. Meyer RA. Diagnostic ultrasound: hazardous or safe? Appl Radiol
1982;11:71-74.
7. Stratmeyer ME, Christman CL. Biological effects of ultrasound.
Women Health 1982;7:65-81.
8. Kremkau FW. Biological effects and possible hazards. Clin Obstet
Gynaecol 1983;10:395-405.
9. Brown BS. How safe is diagnostic ultrasonography? CMAJ
1984;131:307-311.
10. Carstensen EL, Gates AH. The effects of pulsed ultrasound on the
fetus. J Ultrasound Med 1984;3:145-147.
11. Muggah HF. The safety of diagnostic ultrasonography. CMAJ
1984;131:280, 282.
12. Andrews M, Webster M, Fleming JE, McNay MB. Ultrasound
exposure time in routine obstetric scanning. Br J Obstet Gynaecol
1987;94:843-846.
13. Wells PN. The prudent use of diagnostic ultrasound. Ultrasound
Med Biol 1987;13:391-400.
14. Desai BB, Sosolik RC, Ciaravino V, Teale JM. Effect of fetal exposure to ultrasound on B cell development in BALB/c mice. Ultrasound Med Biol 1989;15:567-573.
15. Reece EA, Assimakopoulos E, Zheng XZ, et al. The safety of obstetric ultrasonography: concern for the fetus. Obstet Gynecol 1990;
76:139-146.
16. Salvesen KA, Eik-Nes SH. Is ultrasound unsound? A review of
epidemiological studies of human exposure to ultrasound. Ultrasound Obstet Gynecol 1995;6:293-298.
17. Barnett SB, Rott HD, ter Haar GR, et al. The sensitivity of biological tissue to ultrasound. Ultrasound Med Biol 1997;23:805-812.
18. Miller MW, Brayman AA. Biological effects of ultrasound: the
perceived safety of diagnostic ultrasound within the context of
ultrasound biophysics—a personal perspective. Echocardiography
1997;14:615-628.
19. Abramowicz JS. Ultrasound in obstetrics and gynecology: is this hot
technology too hot? J Ultrasound Med 2002;21:1327-1333.
20. Kieler H, Cnattingius S, Haglund B, et al. Ultrasound and adverse
effects. Ultrasound Obstet Gynecol 2002;20:102-103.
Chapter 29 ■ Bioeffects and Safety of Ultrasound in Obstetrics 1069
21. Marinac-Dabic D, Krulewitch CJ, Moore Jr RM. The safety of
prenatal ultrasound exposure in human studies. Epidemiology
2002;13:S19-S22.
22. Bly S, van den Hof MC. Obstetric ultrasound biological effects and
safety. J Obstet Gynaecol Can 2005;27:572-580.
23. Church CC, Miller MW. Quantification of risk from fetal exposure
to diagnostic ultrasound. Prog Biophysics Mol Biol 2007;93:
331-353.
24. Duck FA. Hazards, risks and safety of diagnostic ultrasound. Med
Eng Physics 2008;30:1338-1348.
25. Safety issues in fetal ultrasound. 2007. http://fetalultrasoundsafety.
net/. Accessed August 2008.
26. Miller MW, Brayman AA, Abramowicz JS. Obstetric ultrasonography: a biophysical consideration of patient safety—the “rules” have
changed. Am J Obstetr Gynecol 1998;179:241-254.
27. Ndumbe FM, Navti O, Chilaka VN, Konje JC. Prenatal diagnosis
in the first trimester of pregnancy. Obstet Gynecol Surv 2008;63:
317-328.
28. Simonsen SE, Branch DW, Rose NC. The complexity of fetal
imaging: reconciling clinical care with patient entertainment. Obstet
Gynecol 2008;112:1351-1354.
29. American Institute of Ultrasound in Medicine. AIUM official statement: prudent use in obstetrics. 2007. http://www.aium.org/publications/statements. Accessed September 2008.
30. Wells PN. The prudent use of diagnostic ultrasound. British Institute of Radiology 1986 Presidential Address. Br J Radiol 1986;59:
1143-1151.
31. Ziskin MC. The prudent use of diagnostic ultrasound. J Ultrasound
Med 1987;6:415-416.
32. Sheiner E, Abramowicz JS. Clinical end users worldwide show poor
knowledge regarding safety issues of ultrasound during pregnancy.
J Ultrasound Med 2008;27:499-501.
Instrument Outputs
33. Duck FA, Martin K. Trends in diagnostic ultrasound exposure. Phys
Med Biol 1991;36:1423-1432.
34. Duck FA, Henderson J. Acoustic output of modern instruments: is
it increasing? In: Barnett SB, Kossoff G, editors. Safety of diagnostic
ultrasound. New York: Parthenon; 1998. p. 147.
Thermal and Other Effects
35. Chance PF, Smith DW. Hyperthermia and meningomyelocele and
anencephaly. Lancet 1978;1:769-770.
36. Edwards MJ. Congenital defects in guinea pigs: following induced
hyperthermia during gestation. Arch Pathol 1967;84:42-48.
37. Graham Jr JM, Edwards MJ, Edwards MJ. Teratogen update: gestational effects of maternal hyperthermia due to febrile illnesses and
resultant patterns of defects in humans. Teratology 1998;58:
209-221.
38. Halperin LR, Wilroy Jr RS. Maternal hyperthermia and neural-tube
defects. Lancet 1978;2:212-213.
39. Li Z, Ren A, Liu J, et al. Maternal flu or fever, medication use, and
neural tube defects: a population-based case-control study in Northern China. Birth Defects Res 2007;79:295-300.
40. Lipson AH, Edwards MJ. Maternal sauna and hyperthermia during
pregnancy and cardiovascular and other malformations in offspring.
Eur J Epidemiol 1993;9:676-678.
41. Little BB, Ghali FE, Snell LM, et al. Is hyperthermia teratogenic in
the human? Am J Perinatol 1991;8:185-189.
42. Milunsky A, Ulcickas M, Rothman KJ, et al. Maternal heat exposure
and neural tube defects. JAMA 1992;268:882-885.
43. Shaw GM, Todoroff K, Velie EM, Lammer EJ. Maternal illness,
including fever and medication use as risk factors for neural tube
defects. Teratology 1998;57:1-7.
44. Shiota K. Induction of neural tube defects and skeletal malformations in mice following brief hyperthermia in utero. Biol Neonate
1988;53:86-97.
45. Dombrowski SC, Martin RP, Huttunen MO. Association between
maternal fever and psychological/behavior outcomes: a hypothesis.
Birth Defects Res 2003;67:905-910.
46. Edwards MJ, Saunders RD, Shiota K. Effects of heat on embryos
and foetuses. Int J Hyperthermia 2003;19:295-324.
47. Layde PM, Edmonds LD, Erickson JD. Maternal fever and neural
tube defects. Teratology 1980;21:105-108.
48. Miller MW, Nyborg WL, Dewey WC, et al. Hyperthermic teratogenicity, thermal dose and diagnostic ultrasound during pregnancy:
implications of new standards on tissue heating. Int J Hyperthermia
2002;18:361-384.
49. Moretti ME, Bar-Oz B, Fried S, Koren G. Maternal hyperthermia
and the risk for neural tube defects in offspring: systematic review
and meta-analysis. Epidemiology 2005;16:216-219.
50. European Committee for Medical Ultrasound Safety (ECMUS).
Thermal teratology. Eur J Ultrasound 1999;9:281-283.
51. National Council on Radiation Protection and Measurements.
Exposure criteria for medical diagnostic ultrasound. II. Criteria
based on all known mechanisms. Report No 140. Bethesda, Md:
NCRP; 2002.
52. Acs N, Banhidy F, Puho E, Czeizel AE. Maternal influenza during
pregnancy and risk of congenital abnormalities in offspring. Birth
Defects Res 2005;73:989-996.
53. Cleves MA, Malik S, Yang S, et al. Maternal urinary tract infections
and selected cardiovascular malformations. Birth Defects Res 2008;
82:464-473.
54. Kleinebrecht J, Michaelis H, Michaelis J, Koller S. Fever in pregnancy and congenital anomalies. Lancet 1979;1:1403.
55. Miller MW, Church CC, Miller RK, Edwards MJ. Fetal thermal
dose considerations during the obstetrician’s watch: implications for
the pediatrician’s observations. Birth Defects Res C Embryo Today
2007;81:135-143.
56. Peterka M, Tvrdek M, Likovsky Z, et al. Maternal hyperthermia and
infection as one of possible causes of orofacial clefts. Acta Chir Plast
1994;36:114-118.
57. Smith DW, Clarren SK, Harvey MA. Hyperthermia as a possible
teratogenic agent. J Pediatr 1978;92:878-883.
58. Superneau DW, Wertelecki W. Similarity of effects: experimental
hyperthermia as a teratogen and maternal febrile illness associated
with oromandibular and limb defects. Am J Med Genet 1985;21:
575-580.
59. Miller MW, Ziskin MC. Biological consequences of hyperthermia.
Ultrasound Med Biol 1989;15:707-722.
60. Miller MW, Miller HE, Church CC. A new perspective on
hyperthermia-induced birth defects: The role of activation energy and
its relation to obstetric ultrasound. J Therm Biol 2005;30:400-409.
61. Brent RL. Is hyperthermia a direct or indirect teratogen? Teratology
1986;33:373-374.
62. Barnett SB. Can diagnostic ultrasound heat tissue and cause biological effects? In: Barnett SB, Kossoff G, editors. Safety of diagnostic
ultrasound. New York: Parthenon; 1998. p. 30.
63. Nyborg WL, Steele RB. Temperature elevation in a beam of ultrasound. Ultrasound Med Biol 1983;9:611-620.
64. Nyborg WL, O’Brien WD. An alternative simple formula for temperature estimate. J Ultrasound Med 1989;8:653-654.
65. Toneto AD, Lopes RA, Oliveira PT, et al. Effect of hyperthermia on
rat fetus palate epithelium. Braz Dent J 1994;5:99-103.
66. Martinez-Frias ML, Garcia Mazario MJ, Caldas CF, et al. High
maternal fever during gestation and severe congenital limb disruptions. Am J Med Genet 2001;98:201-203.
67. Tikkanen J, Heinonen OP. Maternal hyperthermia during pregnancy and cardiovascular malformations in the offspring. Eur J
Epidemiol 1991;7:628-635.
68. Horder MM, Barnett SB, Vella GJ, et al. Ultrasound-induced temperature increase in guinea-pig fetal brain in utero: third-trimester
gestation. Ultrasound Med Biol 1998;24:1501-1510.
69. Jauniaux E, Gulbis B, Burton GJ. The human first trimester gestational sac limits rather than facilitates oxygen transfer to the foetus:
a review. Placenta 2003;24(Suppl A):86-93.
70. Carbillon L, Perrot N, Uzan M, Uzan S. Doppler ultrasonography
and implantation: a critical review. Fetal Diagn Ther 2001;16:
327-332.
71. Kurjak A, Kupesic S. Doppler proof of the presence of intervillous
circulation. Ultrasound Obstet Gynecol 1996;7:463-464.
72. Jauniaux E. Intervillous circulation in the first trimester: the
phantom of the color Doppler obstetric opera. Ultrasound Obstet
Gynecol 1996;8:73-76.
73. Makikallio K, Tekay A, Jouppila P. Uteroplacental hemodynamics
during early human pregnancy: a longitudinal study. Gynecol
Obstet Invest 2004;58:49-54.
74. Wloch A, Rozmus-Warcholinska W, Czuba B, et al. Doppler study
of the embryonic heart in normal pregnant women. J Matern Fetal
Neonatal Med 2007;20:533-539.
75. Russell NE, McAuliffe FM. First-trimester fetal cardiac function.
J Ultrasound Med 2008;27:379-383.
1070 PART IV ■ Obstetric Sonography
76. Duck FA. Is it safe to use diagnostic ultrasound during the first
trimester? Ultrasound Obstet Gynecol 1999;13:385-388.
77. Smythe GE, MacRae DJ. Doppler ultrasound and fetal hazard
(letter). Lancet 1975;2:134.
78. Calvert J, Duck F, Clift S, Azaime H. Surface heating by transvaginal
transducers. Ultrasound Obstet Gynecol 2007;29:427-432.
79. Ziskin MC. Intrauterine effects of ultrasound: human epidemiology.
Teratology 1999;59:252-260.
80. O’Brien WD, Siddiqi TA. Obstetric sonography: the output display
standard and ultrasound bioeffects. In: Fleischer AC, Manning FA,
Jeanty P, Romero R, editors. Sonography in obstetrics and gynecology: principles and practice. 6th ed. New York: McGraw-Hill; 2001.
p. 29-48.
81. Bly SH, Vlahovich S, Mabee PR, Hussey RG. Computed estimates
of maximum temperature elevations in fetal tissues during transabdominal pulsed Doppler examinations. Ultrasound Med Biol
1992;18:389-397.
Mechanical Effects
82. Dalecki D, Raeman CH, Child SZ, et al. Hemolysis in vivo from
exposure to pulsed ultrasound. Ultrasound Med Biol 1997;23:
307-313.
83. Abramowicz JS. Ultrasonographic contrast media: has the time come
in obstetrics and gynecology? J Ultrasound Med 2005;24:517-531.
84. Miller MW, Brayman AA, Sherman TA, et al. Comparative sensitivity of human fetal and adult erythrocytes to hemolysis by pulsed
1 MHz ultrasound. Ultrasound Med Biol 2001;27:419-425.
85. Fatemi M, Ogburn Jr PL, Greenleaf JF. Fetal stimulation by pulsed
diagnostic ultrasound. J Ultrasound Med 2001;20:883-889.
86. Duck FA. Acoustic streaming and radiation pressure in diagnostic
applications: what are the implications? In: Barnett SB, Kossoff G,
editors. Safety of diagnostic ultrasound. New York: Parthenon;
1998. p. 87-98.
Bioeffects of Ultrasound
87. Jensh RP, Brent RL. Intrauterine effects of ultrasound: animal
studies. Teratology 1999;59:240-251.
88. Harvey EN, Loomis AL. High-frequency sound waves of small
intensity and their biological effects. Nature 1928;121:622-
624.
89. Sikov MR. Effect of ultrasound on development. Part 1. Introduction and studies in inframammalian species. Report of the Bioeffects
Committee of the American Institute of Ultrasound in Medicine.
J Ultrasound Med 1986;5:577-583.
90. Sikov MR. Effect of ultrasound on development. Part 2. Studies
in mammalian species and overview. J Ultrasound Med 1986;5:
651-661.
91. Fry FJ, Kossoff G, Eggleton RC, Dunn F. Threshold ultrasonic
dosages for structural changes in the mammalian brain. J Acoust Soc
Am 1970;48(Suppl 2):1413.
92. Frizzell LA, Carstensen EL, Davis JD. Ultrasonic absorption in liver
tissue. J Acoust Soc Am 1979;65:1309-1312.
93. Frizzell LA, Lee CS, Aschenbach PD, et al. Involvement of ultrasonically induced cavitation in the production of hind limb paralysis of
the mouse neonate. J Acoust Soc Am 1983;74:1062-1065.
94. Borrelli MJ, Frizzell LA, Dunn F. Ultrasonically induced morphological changes in the mammalian neonatal spinal cord. Ultrasound
Med Biol 1986;12:285-295.
95. Frizzell LA, Linke CA, Carstensen EL, Fridd CW. Thresholds for
focal ultrasonic lesions in rabbit kidney, liver, and testicle. IEEE
Trans Biomed Eng 1977;24:393-396.
96. Carnes KI, Hess RA, Dunn F. The effect of ultrasound exposure in
utero on the development of the fetal mouse testis: adult consequences. Ultrasound Med Biol 1995;21:1247-1257.
97. Hynynen K. The threshold for thermally significant cavitation
in dog’s thigh muscle in vivo. Ultrasound Med Biol 1991;17:
157-169.
98. Dalecki D, Raeman CH, Child SZ, Carstensen EL. Intestinal hemorrhage from exposure to pulsed ultrasound. Ultrasound Med Biol
1995;21:1067-1072.
99. Dalecki D, Child SZ, Raeman CH, et al. Ultrasonically induced
lung hemorrhage in young swine. Ultrasound Med Biol 1997;23:
777-781.
100. Tarantal AF, Hendrickx AG. Evaluation of the bioeffects of prenatal
ultrasound exposure in the cynomolgus macaque (Macaca fascicu-
laris): II. Growth and behavior during the first year. Teratology
1989;39:149-162.
101. Hande MP, Devi PU. Effect of in utero exposure to diagnostic
ultrasound on the postnatal survival and growth of mouse. Teratology 1993;48:405-411.
102. O’Brien WD. Dose-dependent effects of ultrasound on fetal weight
in mice. J Ultrasound Med 1983;2:1-8.
103. Vorhees CV, Acuff-Smith KD, Schilling MA, et al. Behavioral teratologic effects of prenatal exposure to continuous-wave ultrasound
in unanesthetized rats. Teratology 1994;50:238-249.
104. O’Brien Jr WD, Januzik SJ, Dunn F. Ultrasound biologic effects:
a suggestion of strain specificity. J Ultrasound Med 1982;1:367-
370.
105. Hande MP, Devi PU. Effect of prenatal exposure to diagnostic
ultrasound on the development of mice. Radiat Res 1992;130:
125-128.
106. Rao S, Ovchinnikov N, McRae A. Gestational stage sensitivity to
ultrasound effect on postnatal growth and development of mice.
Birth Defects Res 2006;76:602-608.
107. Borrelli MJ, Bailey KI, Dunn F. Early ultrasonic effects upon
mammalian CNS structures (chemical synapses). J Acoust Soc Am
1981;69:1514-1516.
108. Norton S, Kimler BF, Cytacki EP, Rosenthal SJ. Prenatal and postnatal consequences in the brain and behavior of rats exposed to
ultrasound in utero. J Ultrasound Med 1991;10:69-75.
109. Devi PU, Suresh R, Hande MP. Effect of fetal exposure to ultrasound
on the behavior of the adult mouse. Radiat Res 1995;141:
314-317.
110. Hande MP, Devi PU, Karanth KS. Effect of prenatal ultrasound
exposure on adult behavior in mice. Neurotoxicol Teratol 1993;15:
433-438.
111. Schneider-Kolsky ME, Ayobi Z, Lombardo P, et al. Ultrasound
exposure of the foetal chick brain: effects on learning and memory.
Int J Dev Neurosci 2009;27(7):677-683.
112. Ang ESBC, Gluncic V, Duque A, et al. Prenatal exposure to ultrasound waves impacts neuronal migration in mice. Proc NY Acad Sci
2006;103:12903-12910.
113. Abramowicz JS. Prenatal exposure to ultrasound waves: is there a
risk? Ultrasound Obstet Gynecol 2007;29:363-367.
114. Kieler H. Epidemiological studies on adverse effects of prenatal
ultrasound: which are the challenges? Prog Biophysics Mol Biol
2007;93:301-308.
115. Newman PG. Studies of ultrasound safety in humans: clinical
benefit vs. risk. In: Barnett SB, Kossoff G, editors. Safety of diagnostic ultrasound. New York: Parthenon; 1998.
116. Salvesen KA. Epidemiological prenatal ultrasound studies. Prog
Biophys Mol Biol 2007;93:295-300.
117. Ziskin MC, Petitti DB. Epidemiology of human exposure to
ultrasound: a critical review. Ultrasound Med Biol 1988;14:91-
96.
118. Edmonds PD, Abramowicz JS, Carson PL, et al. Guidelines for
Journal of Ultrasound in Medicine authors and reviewers on measurement and reporting of acoustic output and exposure. J Ultrasound
Med 2005;24:1171-1179.
119. Carvalho JS. Fetal heart scanning in the first trimester. Prenat Diagn
2004;24:1060-1067.
120. Makikallio K, Jouppila P, Rasanen J. Human fetal cardiac function
during the first trimester of pregnancy. Heart (Br Cardiac Soc)
2005;91:334-338.
121. Becker R, Wegner RD. Detailed screening for fetal anomalies and
cardiac defects at the 11-13-week scan. Ultrasound Obstet Gynecol
2006;27:613-618.
122. Vinals F, Ascenzo R, Naveas R, et al. Fetal echocardiography at
11 + 0 to 13 + 6 weeks using four-dimensional spatiotemporal image
correlation telemedicine via an Internet link: a pilot study. Ultrasound Obstet Gynecol 2008;31:633-638.
123. Ziskin MC. Survey of patients exposed to diagnostic ultrasound. In:
Reid JM, Sikov MR, editors. Interactions of ultrasound and biological tissues. Proceedings of a workshop, Battelle Seattle Research
Center, Seattle, 1971. Rockville, Md: Bureau of Radiological
Health, US Department of Health, Education and Welfare; 1973.
p. 203-206.
124. Newnham JP, Evans SF, Michael CA, et al. Effects of frequent ultrasound during pregnancy: a randomised controlled trial. Lancet
1993;342:887-891.
125. Campbell JD, Elford RW, Brant RF. Case-control study of prenatal
ultrasonography exposure in children with delayed speech. CMAJ
1993;149:1435-1440.
Chapter 29 ■ Bioeffects and Safety of Ultrasound in Obstetrics 1071
126. Kieler H, Haglund B, Waldenstrom U, Axelsson O. Routine ultrasound screening in pregnancy and the children’s subsequent growth,
vision and hearing. Br J Obstet Gynaecol 1997;104:1267-1272.
127. Stark CR, Orleans M, Haverkamp AD, Murphy J. Short- and longterm risks after exposure to diagnostic ultrasound in utero. Obstet
Gynecol 1984;63:194-200.
128. Bricker L, Neilson JP, Dowswell T. Routine ultrasound in late pregnancy (after 24 weeks’ gestation). Cochrane Database Syst Rev
(Online) 2008:CD001451.
129. Kieler H, Haglund B, Cnattingius S, et al. Does prenatal sonography
affect intellectual performance? Epidemiology 2005;16:304-310.
130. Cartwright RA, McKinney PA, Hopton PA, et al. Ultrasound examinations in pregnancy and childhood cancer. Lancet 1984;2:
999-1000.
131. Kieler H, Axelsson O, Haglund B, et al. Routine ultrasound screening in pregnancy and the children’s subsequent handedness. Early
Hum Dev 1998;50:233-245.
132. Salvesen KA. Ultrasound and left-handedness: a sinister association?
Ultrasound Obstet Gynecol 2002;19:217-221.
133. Sheiner E, Freeman J, Abramowicz JS. Acoustic output as measured
by mechanical and thermal indices during routine obstetric ultrasound examinations. J Ultrasound Med 2005;24:1665-1670.
134. Sheiner E, Shoham-Vardi I, Hussey MJ, et al. First-trimester sonography: is the fetus exposed to high levels of acoustic energy? J Clin
Ultrasound 2007;35:245-249.
135. Sheiner E, Abramowicz JS. Acoustic output as measured by thermal
and mechanical indices during fetal nuchal translucency ultrasound
examinations. Fetal Diagn Ther 2008;25:8-10.
136. Sheiner E, Shoham-Vardi I, Pombar X, et al. An increased thermal
index can be achieved when performing Doppler studies in obstetric
sonography. J Ultrasound Med 2007;26:71-76.
137. Sheiner E, Hackmon R, Shoham-Vardi I, et al. A comparison
between acoustic output indices in 2D and 3D/4D ultrasound in
obstetrics. Ultrasound Obstet Gynecol 2007;29:326-328.
138. Bellieni CV, Buonocore G, Bagnoli F, et al. Is an excessive number
of prenatal echographies a risk for fetal growth? Early Hum Dev
2005;81:689-693.
139. Newnham JP, Doherty DA, Kendall GE, et al. Effects of repeated
prenatal ultrasound examinations on childhood outcome up to 8
years of age: follow-up of a randomised controlled trial. Lancet
2004;364:2038-2044.
140. Moore Jr RM, Barrick MK, Hamilton TM. Effect of sonic radiation
on growth and development. Am J Epidemiol 1982;116:571.
141. Moore Jr RM, Diamond EL, Cavalieri RL. The relationship of birth
weight and intrauterine diagnostic ultrasound exposure. Obstet
Gynecol 1988;71:513-517.
142. Lyons EA, Dyke C, Toms M, Cheang M. In utero exposure to
diagnostic ultrasound: a 6-year follow-up. Radiology 1988;166:
687-690.
143. Newnham JP, Evans SF, Michael CA, et al. Effects of frequent ultrasound during pregnancy: a randomized controlled trial. Lancet
1993;342:887-891.
144. Saari-Kemppainen A, Karjalainen O, Ylostalo P, Heinonen OP.
Ultrasound screening and perinatal mortality: controlled trial of
systematic one-stage screening in pregnancy. The Helsinki Ultrasound Trial. Lancet 1990;336:387-391.
145. Waldenstrom U, Axelsson O, Nilsson S, et al. Effects of routine
one-stage ultrasound screening in pregnancy: a randomised controlled trial. Lancet 1988;2:585-588.
146. Salvesen KA, Vatten LJ, Bakketeig LS, Eik-Nes SH. Routine ultrasonography in utero and speech development. Ultrasound Obstet
Gynecol 1994;4:101-103.
147. Bakketeig LS, Eik-Nes SH, Jacobsen G, et al. Randomised controlled
trial of ultrasonographic screening in pregnancy. Lancet
1984;2:207-211.
148. Eik-Nes SH, Okland O, Aure JC, Ulstein M. Ultrasound screening
in pregnancy: a randomised controlled trial. Lancet 1984;1:1347.
149. Salvesen KA, Bakketeig LS, Eik-nes SH, et al. Routine ultrasonography in utero and school performance at age 8-9 years. Lancet
1992;339:85-89.
150. Salvesen KA, Vatten LJ, Eik-Nes SH, et al. Routine ultrasonography
in utero and subsequent handedness and neurological development.
BMJ Clin Res 1993;307:159-164.
151. Salvesen KA, Vatten LJ, Jacobsen G, et al. Routine ultrasonography
in utero and subsequent vision and hearing at primary school age.
Ultrasound Obstet Gynecol 1992;2:243-247.
152. Salvesen KA, Eik-Ness SH, Vatten LJ, et al. Routine ultrasound
scanning in pregnancy [authors’reply]. BMJ 1993;307:1562.
153. Sidman RL, Rakic P. Neuronal migration, with special reference
to developing human brain: a review. Brain Res 1973;62:1-
35.
154. Mole R. Possible hazards of imaging and Doppler ultrasound in
obstetrics. Birth 1986;13(Suppl):23-33.
155. Scheidt PC, Stanley F, Bryla DA. One-year follow-up of infants
exposed to ultrasound in utero. Am J Obstet Gynecol 1978;131:
743-748.
156. Salvesen K. Routine ultrasonography in utero and development in
childhood. In: Tejani N, editor. Obstetrical events and developmental sequelae. 2nd ed. Boca Raton, Fla: CRC Press; 1994.
157. Stalberg K. Prenatal ultrasound and x-ray-potentially adverse effects
on the CNS. Upsalla, Sweden: Upsalla Universitet; 2008.
158. Coyle I, Wayner MJ, Singer G. Behavioral teratogenesis: a critical
evaluation. Pharmacol Biochem Behav 1976;4:191-200.
159. Stalberg K, Haglund B, Axelsson O, et al. Prenatal ultrasound scanning and the risk of schizophrenia and other psychoses. Epidemiology 2007;18:577-582.
160. Shu XO, Potter JD, Linet MS, et al. Diagnostic x-rays and ultrasound exposure and risk of childhood acute lymphoblastic leukemia
by immunophenotype. Cancer Epidemiol Biomarkers Prev 2002;11:
177-185.
161. Naumburg E, Bellocco R, Cnattingius S, et al. Prenatal ultrasound
examinations and risk of childhood leukaemia: case-control study.
BMJ Clin Res 2000;320:282-283.
162. Kinnier Wilson LM, Waterhouse JA. Obstetric ultrasound and
childhood malignancies. Lancet 1984;2:997-999.
163. Bunin GR, Buckley JD, Boesel CP, et al. Risk factors for astrocytic
glioma and primitive neuroectodermal tumor of the brain in young
children: a report from the Children’s Cancer Group. Cancer Epidemiol Biomarkers Prev 1994;3:197-204.
164. Sorahan T, Lancashire R, Stewart A, Peck I. Pregnancy ultrasound
and childhood cancer: a second report from the Oxford Survey of
Childhood Cancers. Br J Obstet Gynaecol 1995;102:831-832.
165. Salvesen KA, Eik-Nes SH. Ultrasound during pregnancy and
birthweight, childhood malignancies and neurological development.
Ultrasound Med Biol 1999;25:1025-1031.
166. Stalberg K, Haglund B, Axelsson O, et al. Prenatal ultrasound and
the risk of childhood brain tumour and its subtypes. Br J Cancer
2008;98:1285-1287.
Safety Guidelines
167. Kossoff G, Griffiths KA, Garrett WJ, et al. Thickness of tissues
intervening between the transducer and fetus and models for fetal
exposure calculations in transvaginal sonography. Ultrasound Med
Biol 1993;19:59-65.
168. British Medical Ultrasound Society. Guidelines for the safe use
of diagnostic ultrasound equipment. 2000, reconfirmed 2009.
http://www.bmus.org/ultras-safety/us-safety03.asp. Accessed January
2010.
169. British Medical Ultrasound Society (BMUS): Guidelines for the safe
use of diagnostic ultrasound equipment. Prepared by the Safety
Group of BMUS. Ultrasound 2010;18:52-59.
170. World Federation for Ultrasound in Medicine and Biology
(WFUMB) Symposium on Safety and Standardization in Medical
Ultrasound. Issues and recommendations regarding thermal mechanisms for biological effects of ultrasound. Ultrasound Med Biol
1992;18:748.
171. Barnett SB. WFUMB Symposium on Safety of Ultrasound in Medicine. Conclusions and recommendations on thermal and nonthermal mechanisms for biological effects of ultrasound. Ultrasound
Med Biol 1998;24.
172. Canada Minister of Public Works and Government Services. Guidelines for the safe use of diagnostic ultrasound. 2001. http://www.
hc-sc.gc.ca/ewh-semt/pubs/radiation/01hecs-secs255/index-eng.
php. Accessed December 2008.
173. Abramowicz JS, Kossoff G, Marsal K, Ter Haar G. Safety statement,
2000 (reconfirmed 2003). International Society of Ultrasound in
Obstetrics and Gynecology (ISUOG). Ultrasound Obstet Gynecol
2003;21:100.
174. Barnett SB, Ter Haar GR, Ziskin MC, et al. International recommendations and guidelines for the safe use of diagnostic ultrasound
in medicine. Ultrasound Med Biol 2000;26:355-366.
CHAPTER 30
The First Trimester
Clifford S. Levi and Edward A. Lyons
Chapter Outline
MATERNAL PHYSIOLOGY AND
EMBRYOLOGY
SONOGRAPHIC APPEARANCE OF
NORMAL INTRAUTERINE
PREGNANCY
Gestational Sac
Yolk Sac
Embryo and Amnion
Embryonic Cardiac Activity
Umbilical Cord and Cord Cyst
ESTIMATION OF GESTATIONAL
AGE
Gestational Sac Size
Crown-Rump Length
Biparietal Diameter
EARLY PREGNANCY FAILURE
Sonographic Diagnosis of Embryonic
Demise
Embryonic Cardiac Activity
Gestational Sac Features
Amnion and Yolk Sac Criteria
Sonographic Predictors of Abnormal
Outcome
Embryonic Bradycardia
Mean Sac Diameter and Crown-Rump
Length
Yolk Sac Size and Shape
Low Human Chorionic Gonadotropin
Subchorionic Hemorrhage
Doppler Ultrasound Assessment
Amniotic Sac Abnormalities
Termination of Early Pregnancy
Failure
Retained Products of Conception
ECTOPIC PREGNANCY
Clinical Presentation
Sonographic Diagnosis
Specific Findings
Nonspecific Findings
Implantation Site
Heterotopic Gestation
Doppler Confirmation
The first trimester of pregnancy is a period of
rapid change that spans fertilization, formation of the
blastocyst, implantation, gastrulation, neurulation, the
embryonic period (weeks 6-10), and early fetal life.
First-trimester sonographic diagnosis traditionally
focused on evaluation of growth by serial examination
to differentiate normal from abnormal gestations. This
has changed radically since the advent of transvaginal
sonography (TVS), which affords enhanced resolution
over transabdominal sonography (TAS), with earlier
visualization of the gestational sac and its contents,
earlier identification of embryonic cardiac activity,
improved visualization of embryonic and fetal structures.
As investigators have gained experience with highresolution TAS and TVS, reliable indicators of early
pregnancy failure have been identified, making serial
examination necessary in only a minority of patients,
resulting in decreased morbidity and patient anxiety.
Despite these technologic improvements, it is important to set clinically relevant and realistic goals for firsttrimester sonographic diagnosis. Most examinations are
requested because the patient has presented with vaginal
bleeding or pain, or a palpable mass has been identified
3
and
Pregnancy of Unknown Location
Management
EVALUATION OF THE EMBRYO
Normal Embryologic Development
Mimicking Pathology
Intracranial Cystic Structures in First
Trimester
Physiologic Anterior Abdominal Wall
Herniation
Normal-Appearing Abnormal
Embryos
Anencephaly
Renal Agenesis
Discrepancy between Dates and
Embryo Size
FIRST-TRIMESTER MASSES
Ovarian Masses
Uterine Masses
CONCLUSION
on physical examination. The referring physician usually
requests the ultrasound examination to exclude a nonviable pregnancy or an ectopic pregnancy.
1
The goals of first-trimester sonography include (1)
visualization and localization of the gestational sac (intrauterine or ectopic pregnancy) and (2) early identification
of embryonic demise and other forms of nonviable gestation. It also seeks to identify those embryos that are still
alive but at increased risk for embryonic or fetal demise.
In multifetal pregnancies, first-trimester ultrasound
2
determines the number of embryos and the chorionicityamnionicity, estimates the duration or menstrual/gestational age of the pregnancy, and assists in early diagnosis
of fetal abnormalities, including identification of embryos
more likely to be abnormal, based on secondary criteria
(e.g., abnormal yolk sac).
Current trends in ultrasound late in the first trimester
focus on nuchal translucency screening combined with
maternal age and maternal serum screening to determine
the risk of chromosomal abnormalities and structural
anomalies. Associated with the increased emphasis on
late-first-trimester ultrasound and first-trimester screening, there is an opportunity to visualize fetal anomalies
1072
Chapter 30 ■ The First Trimester 1073
= +
earlier than at the time of the standard 18 to 20–week
scan. First-trimester diagnosis of specific anomalies is
discussed in the chapters covering those organ systems.
This chapter discusses basic principles in the diagnosis
of anomalies in the first trimester.
As experience with early first-trimester ultrasound
evolves, there is controversy over the use of ultrasound
parameters to diagnose early pregnancy failure or embryonic demise on a single examination.
4
Current practice
is based on the use of reliable sonographic indicators of
ectopic pregnancy and embryonic demise. The accuracy
of some sonographic signs used as indicators of the presence of a live embryo or of embryonic demise depends
on the use of modern, high-resolution ultrasound equipment and the operator’s expertise. Published values in
the literature based on data using high-frequency transducers cannot be applied to lower-resolution 5.0-MHz
transducers.
5,6
The transvaginal signs listed in this chapter
assume the use of modern equipment with a transducer
frequency of at least 7 to 8 MHz, with meticulous scanning technique. Furthermore, published values cannot
be used as “absolute” values, and allowing at least a few
millimeters leeway is critical when using these numbers.
Nyberg and Filly
4
emphasize that experienced physicians
who interpret ultrasound rarely rely on a single parameter and simultaneously consider multiple variables to
create a diagnostic impression.
Transvaginal color flow Doppler sonography became
available in the early 1990s. Some authors have suggested that color Doppler TVS provides improved diagnostic accuracy over gray-scale TVS in the identification
of early intrauterine and ectopic pregnancies and may
allow more definitive diagnoses at the initial examina-
7
However this exposes the early intrauterine preg-
tion.
nancy (IUP) to the increased power deposition of
Doppler scanning (see Chapter 29).
MATERNAL PHYSIOLOGY
AND EMBRYOLOGY
All dates presented in this chapter are in menstrual age
or gestational age, in keeping with the radiologic and
obstetric literature, rather than in embryologic age, as
used by embryologists. This can be counted as follows:
Gestational age Conceptual age 2 weeks
Early in the menstrual cycle, the pituitary secretes rising
levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which cause the growth of 4 to 12
primordial follicles into primary ovarian follicles
30-1). When a fluid-filled cavity or antrum forms in the
follicle, it is referred to as a secondary follicle. The
primary oocyte is off to one side of the follicle and surrounded by follicular cells or the cumulus oophorus.
One follicle becomes dominant, bulges on the surface of
the ovary and becomes a “mature follicle” or graafian
1
(Fig.
follicle. It continues to enlarge until ovulation, with the
remainder of the follicles becoming atretic. The developing follicles produce estrogen. The estrogen level remains
relatively low until 4 days before ovulation, when the
dominant or active follicle produces an estrogen surge,
after which an LH and prostaglandin surge results in
ovulation. Ovulation follows the LH peak within 12 to
24 hours. Actual expulsion of the oocyte from the mature
follicle is aided by several factors, including the intrafollicular pressure, possibly contraction of the smooth
muscle in the theca externa stimulated by prostaglandins, and enzymatic digestion of the follicular wall.
8
Ovulation occurs on approximately day 14 of the
menstrual cycle with expulsion of the secondary oocyte
from the surface of the ovary. In women with a menstrual cycle longer than 28 days, this ovulation occurs
later, so that the secretory phase of the menstrual cycle
remains at about 14 days. After ovulation, the follicle
collapses to form the corpus luteum, which secretes
progesterone and, to a lesser degree, estrogen. If a pregnancy does not occur, the corpus luteum involutes. In
pregnancy, involution of the corpus luteum is prevented
by human chorionic gonadotropin (hCG), which is
produced by the outer layer of cells of the gestational or
chorionic sac (syncytiotrophoblast).
Before ovulation, endometrial proliferation occurs
in response to estrogen secretion (Fig. 30-1). After ovula-
tion, the endometrium becomes thickened, soft, and
edematous under the influence of progesterone.
9
The
glandular epithelium secretes a glycogen-rich fluid. If
pregnancy occurs, continued production of progesterone
results in more marked hypertrophic changes in the
endometrial cells and glands to provide nourishment to
the blastocyst. These hypertrophic changes are referred
to as the decidual reaction and occur as a hormonal
response regardless of the site of implantation, intrauterine or ectopic.
Oocyte transport into the fimbriated end of the fallopian tube occurs at ovulation as the secondary oocyte
is expelled with the follicular fluid and is “picked up” by
the fimbria. The sweeping movement of the fimbria, the
currents produced by the action of the cilia of the
mucosal cells, and the gentle peristaltic waves from contractions of the fallopian musculature all draw the oocyte
into the tube.
10
The mechanism of sperm transport is not completely
understood. From 200 to 600 million sperm and the
ejaculate fluid are deposited in the vaginal fornix during
intercourse. Sperm must move through the cervical canal
and its mucous plug, up the endometrial cavity, and
down the fallopian tube to meet the awaiting oocyte
within the distal third or ampullary portion of the fallopian tube. Sperm were thought to move primarily
using their tails, although they travel at 2 to 3 mm per
minute, which would take about 50 minutes to travel
the 20 cm to their destination. Settlage et al.10 found
motile sperm within the ampulla between 5 and 10
1074 PART IV ■ Obstetric Sonography
FIGURE 30-1. Schematic drawing of interrelationships among the hypothalamus, pituitary gland, ovaries,
and endometrial lining. FSH, Follicle-stimulating hormone; LH, luteinizing hormone. (From Moore KL, Persaud TVN, editors.
The developing human: clinically oriented embryology. 6th ed. Philadelphia, 1998, Saunders.)
Posterior wall
of uterus
Chapter 30 ■ The First Trimester 1075
Blastocysts
Morula
Early primary
Corpus albicans
Mature corpus luteum
Endometrium
Eight-cell
stage
Secondary follicle
Growing follicle
follicle
Blood
vessels
Epithelium
Atretic (degenerating)
Atretic (degenerating) follicle
Four-cell
stage
approaching
follicle
Two-cell
stage
Follicle
maturity
Zygote
Mature
follicle
Oocyte
Connective tissue
Coagulated blood
Fertilization
Oocyte
in tube
Released oocyte
Ruptured follicle
Developing
corpus
luteum
FIGURE 30-2. Diagram of ovarian cycle, fertilization, and human development to the blastocyst stage.
(From Moore KL, Persaud TVN, editors. The developing human: clinically oriented embryology. 6th ed. Philadelphia, 1998, Saunders.)
minutes after deposition near the external cervical os. If
inert particles such as radioactive macroaggregates or
carbon particles are placed near the external os, they
too will be picked up and transported up the uterus
and down the tubes. Contractions of the inner layer of
myometrium probably create a negative pressure strong
enough to suck up particles and move them up the
endometrial canal. We have demonstrated these contractions in nonpregnant women and shown that they
increase in strength and frequency to peak at 3.5 contractions per minute at ovulation.
11
Fertilization occurs on or about day 14 as the mature
ovum and sperm unite to form the zygote in the outer
third of the fallopian tube (Fig. 30-2). Cellular division
of the zygote occurs during transit through the fallopian
tube. By the time the conceptus enters the uterus, about
day 17, it is at the 12- to 15-cell stage (morula). By day
20, the conceptus has matured to the blastocyst stage.
The blastocyst is a fluid-filled cyst lined with trophoblastic cells that contain a cluster of cells at one side called
the inner cell mass. On day 20, the blastocyst at the site
of the inner cell mass burrows through the endometrial
membrane into the hyperplastic endometrium, and
implantation begins
12
(Fig. 30-3, A).
Implantation is completed by day 23 as the endome-
trial membrane re-forms over the blastocyst (Fig. 30-3,
B). During implantation, the amniotic cavity forms in
the inner cell mass. A bilaminar embryonic disk separates
the amniotic cavity from the exocoelomic cavity. The
primary (primitive) yolk sac forms at about 23 days of
gestational age as the blastocyst cavity becomes lined by
the exocoelomic membrane and hypoblast (Fig. 30-4).
As the extraembryonic coelom forms (Fig. 30-4, A), the
primary yolk sac is pinched off and extruded, resulting
in the formation of the secondary yolk sac (Fig. 30-4,
B and C ). Standard embryology texts indicate that the
secondary yolk sac actually forms at approximately 27 to
28 days of menstrual age (MA), when the mean diameter
of the gestational sac is approximately 3 mm. It is the
secondary yolk sac, rather than the primary yolk sac, that
is visible with ultrasound. For the remainder of this
chapter, the term yolk sac is used to refer to the second-
ary yolk sac. The extraembryonic coelom becomes the
chorionic cavity.
1076 PART IV ■ Obstetric Sonography
A
B
FIGURE 30-3. Implantation of the blastocyst into endometrium. Entire conceptus is approximately 0.1 mm at this
stage. A, Partially implanted blastocyst at approximately 22 days. B, Almost completely implanted blastocyst at about 23 days. (From
Moore KL, Persaud TVN, editors. The developing human: clinically oriented embryology. 6th ed. Philadelphia, 1998, Saunders.)
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