Human Reproduction vol 11 no 8 pp 1771-1774, 1996
Early (34-56 days from last menstrual period)
ultrasonographic measurements in normal pregnancies
C.B.Coulam1, S.Britten and D.M.Soenksen
Genetics & IVF Institute, 3020 Javier Road, Fairfax, VA 22031,
USA
'To whom correspondence should be addressed af The Center for
Human Reproduction, 750 N. Orleans Street, Chicago, IL 60610,
USA
To assess early embryonic growth and development, 361
pregnancies were studied from 34 to 56 days from last
menstrual period. All pregnancies had a subsequent
successful outcome. Transvaginal ultrasonograpby was performed using an Acuson 128 X P/10 with a 5-7.5 MHz
probe. Gestational sac diameter, embryonic pole length
and embryonic heart rates were measured. Embryonic
heart rates were determined by M-mode. Gestational sac
diameter, embryonic pole length and embryonic heart rate
increased linearly relative to gestational age and to each
other. Regression equations comparing gestational sac diameter and embryonic pole length as well as comparing
embryonic heart rate with gestational sac diameter and
embryonic pole length were constructed. To be normal,
gestations that have (i) sac diameter of 20 mm and 30 mm
should contain at least a 2 mm and 5 mm embryo with
embryonic heart rates of at least 75 and 100 beats per min,
respectively; and (ii) embryos measuring 2 mm, 5 mm,
10 mm and 15 mm should display embryonic heart rates
of at least 75,100,120 and 130 beats per minute respectively.
Key words: early gestation/embryonic heart rate/embryonic
pole length/gestational sac diameter/transvaginal ultrasonography.
Introduction
Embryonic growth and development during the first trimester
of pregnancy have been assessed by ultrasonographic measurements of the gestationa] sac (Robinson, 1975; Nyberg et al,
1987; Daya et al., 1991; Goldstein et al, 1991), embryonic
pole (Dickey et al, 1992; Robinson and Fleming, 1975;
Goldstein, 1991; Schats et al, 1991; Tezuka et al., 1991;
Hadlock et al, 1992; Rotsztejn et al, 1993; Tadmor et al,
1994; Yapar et al, 1995) and embryonic heart rate (Hertzberg
et al, 1988; Levi et al, 1990; Schats et al, 1990; Achiron
et al., 1991; Howe et al, 1991; Merchiers et al, 1991; Tezuka
et al, 1991; Rotsztejn et al, 1993; Britton et al, 1994; Tadmor
et al, 1994; Yapar et al, 1995). We have previously reported
that embryonic cardiac activity should be present by day 37
from onset of last menstrual period (LMP) in normal pregnancies (Britton et al, 1994). Other studies have shown that
© European Society for Human Reproduction and Embryology
smaller than expected sizes (based upon LMP) of gestational
sacs and embryonic poles predict impending pregnancy loss
(Bromley et al, 1991; Nazan et al, 1991; Dickey et al.,
1992; Goldstein, 1992; Frates et al, 1993). Confusion in
interpretation of ultrasonographic findings has occurred when
the exact time of conception is not known. Because of
the uncertainty of menstrual data, evaluation of embryonic
landmarks including gestational sac size, embryonic pole length
and embryonic cardiac activity in relation to each other rather
than to menstrual age has been advocated (Goldstein, 1992).
Nomograms constructed from regression curves of ultrasonographic measurements to assess gestational growth and development have been largely derived from pregnancies >6 weeks
of gestation. Increased resolution provided by newer endovaginal ultrasonic probes allows identification of embryonic
structures earlier. To define the relationships between gestational sac size, embryonic pole length and embryonic heart
rate, 361 ultrasonographic examinations 34—56 days from
LMP during pregnancies that subsequently resulted in normal
gestations were studied.
Materials and methods
Diameter of gestational sac, length of embryonic pole and embryonic
heart rates were recorded on 361 first trimester ultrasonographic
examinations in 235 women from January 1, 1992 to August 1, 1993
All pregnancies resulted from assisted reproductive procedures, hence
the day of insemination or embryo transfer was known and used
to calculate the menstrual age of pregnancy. All ultrasonographic
examinauons were performed routinely after the second positive
pregnancy test and extended from 34 to 56 days from LMP, normalizing day 14 as the day of ovuladon. Pregnancies were included only
if it was a singleton gestation and if follow-up beyond the first
trimester revealed a normal gestauon. All ultrasonographic scans
were performed using an Acuson 128 XP/10 (Acuson Computer
Imaging, Mountain View, CA, USA) with a 5.0 MHz trans vaginal
transducer Both B-mode and simultaneous B- and M-modes were
utilized. Gestational sacs were measured in longitudinal and transverse
views and their diameters averaged. Embryonic poles were measured
in the anterior to posterior dimension. Embryonic heart rates were
calculated from frozen M-mode images with electronic calipers.
Gestational sac diameters and embryonic pole lengths were compared with gestational age. Gestational sac diameter was compared
with embryonic pole length. Embryonic heart rates were compared
with gestauon sac diameter and embryonic pole length. Regression
analysis with estimation of regression line with 95% prediction
intervals was performed using a Systat Inc computer program
(Evanston, IL, USA).
Results
Gestationa] sac diameter, embryonic pole length and embryonic
heart rate increased linearly relative to gestationa] age and to
1771
CB.Coulam, S.Britten and D.M.Soenksen
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Figure 1. Scatterogram of 361 gestational sac diameters (panel A) and embryonic pole lengths (EPL) (panel B) with gestational age
from 34 to 56 days from LMP. Panel A: gestational sac diameter in mm = 0.90 (gestational age m days from LMP) - 24.0, r = 0.73,
standard error of estimate = 4.89. Panel B: EPL in mm = 0.67 (gestational age in days from LMP) - 23.66, r = 0.87, standard error of
estimate = 2.65.
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SAC DIAMETER (mm)
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SAC DIAMETER (mm)
30
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Figure 2. Linear regression of mean and 95th percent confidence
interval of 361 gestational sac diameters and embryonic pole
lengths (EPL) from 34 to 56 days from LMP. EPL in mm =
2.17 + 0.51 (mean gestational sac diameter in mm), r = 0.79, Fit
Std Err = 2.63, FStat = 508 44.
each other as shown in Table I. Scattergrams comparing
gestational sac diameter and embryonic pole length with
gestational age are shown in Figure 1. The regression equation
for gestational sac diameter is: average gestational sac diameter
(mm) = 0.90 (gestational age in days) - 24.0. The coefficient
of correlation is 0.73. The regression equation for embryonic
pole length is: average embryonic pole length (mm) = 0.67
(gestational age in days) - 23.66. The coefficient of correlation
is 0.87.
Figure 2 compares gestational sac diameter with embryonic
pole length. The regression equation for embryonic pole length
is: embryonic pole length (mm) = 2.2 + 0.51 (gestational sac
diameter in mm) (r = 0.79, standard error 2.6, FStat = 508).
In normal pregnancies, 95% of 15 mm gestational sacs will
contain a measurable embryonic pole and 95% of 20 mm
1772
50
Figure 3. Linear regression of means and 95th percent confidence
intervals of 361 gestational sac diameters (panel A) and embryonic
pole lengths (EPL) (panel B) with embryonic heart rate (EHR)
from 34 to 56 days from LMP. Panel A: EHR in beats per mm =
81.79 -i- 2.6 (gestational sac diameter in mm), r = 0.73, Fit Std
Err = 15.98, FStat = 357.44. Panel B: EHR in beats per min =
95.72 + 4.65 (EPL in mm), r = 0.85, Fit Std Err = 12.47,
FStat = 787.49.
Ultrasonograpby in normal pregnancies
Table I Mean i standard deviation ( SD) of gestational sac diameter,
embryonic pole length and embryonic: heart rate (EHR) among 361
pregnancies from 34 to 56 days from last menstrual period I[LMP)
Day
from LMP
n
Gestational
sac (mm)
Embryonic
length (mm)
mean ± SD
EHR
(beats/mm)
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
2
8
16
9
10
9
14
23
30
23
24
29
24
18
23
17
10
13
17
11
8
8
15
8 ( 0 1)
10(4)
8(2)
9(2)
11 (3)
12(2)
13(4)
14(8)
13(4)
12(4)
15(3)
16(4)
16(5)
17(5)
18(4)
20(6)
22(5)
20(7)
21 (5)
24(5)
23(3)
29(3)
27(7)
1.6 (0.2)
1 9 (0 4)
2 1 (0 7)
2.2 (0.8)
2 6 (0 8)
2 6 (0 5)
3.2 (0 6)
3 4(12)
4 0(1 2)
3 9(1.2)
5 0(17)
5 5 (2 0)
6.22 (2 1)
6 4 (2 0)
8 2(1 8)
9 1(14)
9 5(13)
9 6(1 9)
9 9(19)
12 8 (3 8)
14 7 (2 7)
15 3 (2 0)
14 0 (2 0)
94(5)
93 (15)
99(8)
97(9)
98(6)
104(9)
107(7)
109 (13)
111 (ID
118 (12)
121 (8)
123 (9)
130 (8)
128 (15)
134(8)
148 (16)
145 (20)
144(12)
152(13)
154 (14)
158 (12)
163 (10)
166 (13)
gestation sacs will contain an embryonic pole measuring at
least 2 mm.
Embryonic heart rate has a linear relationship with gestational sac size and embryonic pole length (Figure 3). The
regression equations for embryonic heart rate (EHR) in beats
per min are:
EHR = 82 + 2.6 (gestational sac diameter in mm)
(r = 0.73, standard error = 16, FStat = 357)
EHR = 96 + 4.6 (gestational pole length in mm)
(r = 0.85, standard error = 12, FStat = 787)
To be within the 95% confidence interval of normal, embryos
measuring 2 mm should display an EHR of at least 75 beats/
min, 5 mm at least 100 beats/min, 10 mm at least 120 beats/
min and 15 mm at least 130 beats/min.
Discussion
We have previously reported that in all normal pregnancies
EHR can be detected by 37 days from LMP (Britton et al.,
1994). Because of uncertainty of exact menstrual age in women
spontaneously ovulating, we extended our previous studies on
EHR to compare EHR with gestational sac size and embryonic
pole length. During the early first trimester (days 34-56 from
LMP), gestational sac diameter, embryonic pole length and
embryonic heart rate increase linearly relative to each other.
To be normal, gestations that have a sac diameter of 15 mm
should contain a measurable embryonic pole and a diameter
of 20 mm and 30 mm should contain at least a 2 mm and 5
mm embryo with EHR of at least 75 and 100 beats per min,
respectively.
The new information provided by this study allows earlier
diagnosis of normal growth and development. Using these
definitions of normal growth and development, abnormal
growth and development can be studied earlier in pregnancy
(Coulam et al, unpublished). That these definitions can predict
impending pregnancy loss is suggested by a 94% abortion rate
(123/144) among women with small for gestational size
embryonic pole lengths (data from Figures 1 and 2) Using
sonographic measurements, a blighted ovum has been defined
as a gestational sac with a mean diameter of 20 mm without
an embryo visible (Wilson et al, 1986). Results of the current
study would provide a diagnosis of blighted ovum a week
earlier with a gestational sac with a mean diameter of 15 mm
without an embryo visible. A missed abortion has previously
been defined as an embryo of 15 mm length without cardiac
activity present (Goldstein, 1995). The diagnosis of missed
abortion can now be made 2 weeks earlier with an embryo
measuring 3 mm (Figure 3).
The effects of ultrasound on embryonic development during
the period of organogenesis are not known with certainty
although no reports document adverse effects with current
sonographic methods used in human gestation. Bioeffects of
ultrasound are related to the spatial peak time average intensity
and duration of exposure. Ultrasound during pregnancy should
be limited to 500 s at a spatial peak time intensity of less than
94 mW/cm2 (American Institute of Ultrasound Medicine,
1993). Using these techniques advances m ultrasonographic
resolution have allowed identification of embryonic structures
very early in gestation (at least by 34 days from LMP).
Previously published nomograms were constructed from
regression curves with the bulk of the data deriving from small
fetuses (embryonic pole length > 18 mm) and then extrapolated
back to embryos of 1-2 mm. It is hoped that information
obtained from improved ultrasonographic technologies which
can differentiate acceptable growth and continued development
from a pregnancy which is definitively destined for failure
can be used to enhance attempts at improving reproductive
outcome.
References
Acluron, R., Tadmor, O and Mashiach, S. (1991) Heart rate as a predictor of
first trimester spontaneous abortion after ultrasound proven viability Obstei
Gynecol, 78, 330-333
Amencan Institute of Ultrasound in Medicine (1993) Bioeffects and Safety of
Diagnostic Ultrasound, AIUM, Laurel, MD, pp 96
Bntton, S., Soenksen, D M , BusUllo, M.and Coulam, C.B (1994) Very early
(24-56 days from last menstrual period) embryonic heart rate in normal
pregnancies Hum. Reprod, 9, 2424-2426
Bromley, B , Harlow, B L , Laboda, L.A. et al (1991) Small sac size in the
first trimester A predictor of poor fetal outcome Radiology, 178, 375
Daya, S , Woods, S , Ward, S., Lappalainen, R et al (1991) Transvagmal
ultrasound scanning in early pregnancy and correlation with human chononic
gonadotropin levels. J Clin. Ultrasound, 19, 139-142
Dickey, R P , Olar, TT., Taylor, S N et al (1992) Relationship of small
gestational sac crown-rump length differences to abortion and abortus
karyotypes Obstei. Gynecol, 79, 554-559
Frates, M C , Benson, C B and Doubilet, PM (1993) Pregnancy outcome after
a first trimester sonogram demonstrating fetal cardiac activity J Ultrasound
Med., 12, 383-386
Goldstein, I , Zimmer, E Z , Tamir, A et al (1991) Evaluation of normal
gestational sac growth appearance of embryonic heartbeat and embryo
body movements using the transvagmal technique Obstet Gynecol, 77,
885-888
Goldstein, SR (1991) Embryonic ultrasonographic measurements crownrump length revisited Am J Obstet. Gynecol, 165, 497-501
1773
CB.Coulam, S-Britten and D.M-Soenksen
Goldstein, S.R. (1992) Significance of cardiac activity on endovaginal
ultrasound in very early embryos Obslet. GynecoL, 80, 670-672
Goldstein, S R. (1995) Managing abnormal early pregnancy Contemp Obstet
GynecoL, 40, 11-18
Hadlock, FP., Shah, Y.P, Kanon, D J . et al. (1992) Fetal crown rump length.
re-evaluation of relation to menstrual age (5-18 weeks) with high resolution
real time US Radiology, 182, 501-508.
Hertzberg, B S , Mahony, B.S. and Bowie, J.D. (1988) First trimester fetal
cardiac activity. Sonographic documentation of a progressive early rise in
heart rate J. Ultrasound Med., 7, 573-575
Howe, R S , Isaacson, K J , Albert, J L and Coutifaris, C.B. (1991) Embryonic
heart rate in human pregnancy. J. Ultrasound Med., 10, 367-371
Levi, C.S, Lyons, EA., Zheng, X.H et al (1990) Endovaginal USdemonstration of cardiac activity m embryos of less than 5 0 mm m crownrump length Radiology, 176, 71-74.
Merchiers, E.H , Dhont, M., DeSutter, P.A et al (1991) Predictive value of
early embryonic cardiac activity for pregnancy outcome Am. J Obstet
GynecoL, 165, 11-14
Nazan, A , Check, J.H., Epstein, R.H. et aL (1991) Relationship of small for
dates sac size to crown-rump length and spontaneous abortion in patients
with a known Hatr of ovulation. Obstet. Gynecol, 78, 369-371
Nyberg, D.A, Mack, L A., Laing, F.C et aL (1987) Distinguishing normal
from abnormal gestational sac growth in early pregnancy J. Ultrasound
Med, 6, 23-25.
Robinson, H P (1975) Gestational sac volumes as determined by sonar on the
first trimester of pregnancy Br J. Obstet GynaecoL, 82, 100-104.
Robinson, HP. and Fleming, J E.E (1975) A critical evaluation of sonar
crown rump length measurement. Br. J Obstet. GynaecoL, 82, 705-709
Rotsztejn, D., Rana, N. and Dmowski, W.P. (1993) Correlation between fetal
heart rate, crown rump length and P human chononic gonadotropin levels
during the first trimester of well-timed conceptions resulting from infertility
treatment FerhL StenL, 59, 1169-1173
Shats, R., Jansen, C A M. and Wladimiroff, J W (1990) Embryonic heart
activity appearance and development in early human pregnancy Br. J
Obstet GynecoL, 97, 989-994
Schats, R , Van Os, H C , Jansen, C.A M et al. (1991) The crown-rump
length in early human pregnancy: a reappraisal Br. J Obstet. GynecoL, 98,
460-^65.
Tadmor, O P , Achiron, R., Rabinowiz, R. et al. (1994) Predicting firsttnmester spontaneous. Ratio of mean sac diameter to crown-rump length
compared to embryonic heart rate J. Reprod. Med., 39, 459-462.
Tezuka, N , Sato, S., Kanasugi, H. and Hiroi, H (1991) Embryonic heart
rates development in early first trimester and clinical evaluation Gynecol.
Obstet Invest, 32, 210-212
Wilson, RD., Kendnck, V, Wittmann, B.K. and McGilhvray, B (1986)
Spontaneous abortion and pregnancy outcome after normal first trimester
ultrasound examination. Obstet GynecoL, 67, 352-355
Yapar, E.G., Ekici, E and Golcmen, O (1995) First trimester fetal heart rate
measurements by transvaginal ultrasound combined with pulsed Dopplen
an evaluation of 1331 cases. Eur J. Obslet. GynecoL Reprod BioL, 60,
133-137
Received on January 4, 1996; accepted on April 22, 1996
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