Accurate determination of gestational age underpins good obstetric care. We assessed the performance of six existing ultrasound reference charts to determine gestational age in 1268 singleton IVF pregnancies, where “true” gestational age could be precisely calculated from date of fertilisation. All charts generated dates significantly different to IVF dates (
Accurate dating of gestational age is central to good obstetric care. It allows the clinicians to better time gestation-specific antenatal screening tests, reduces erroneous labelling of pregnancies as very preterm, preterm, and small-for-gestational-age, and decreases the risk of inappropriate induction of labour [
In the first trimester, there is a very little biologic variation in fetal size compared with later trimesters. It is therefore a good time in pregnancy to determine gestational age by ultrasound where the crown-rump length (CRL) is measured and compared to published reference charts. In contrast, dates calculated from the first day of the last menstrual period (menstrual age) may have inaccuracies arising from imprecise recollection of dates, variation in the timing of ovulation, or time to conception.
A number of CRL reference charts have been proposed and different versions are in common use (Table
Approaches used by six previous studies to generate CRL reference charts.
Robinson | Robinson/Fleming | Hadlock | Daya | Westerway (ASUM) | Verburg | |
---|---|---|---|---|---|---|
Year | 1973 | 1976 | 1992 | 1993 | 2000 | 2008 |
Probe used | TA | TA | TA | TA, TV | TA, TV | TA, TV |
Method to calculate gestation at ultrasound | LMP | LMP | LMP | IVF dates | LMP | LMP |
|
214 (80) | 334 | 452 (416) | 94 | 478 | 3760 |
Gestational ages that reference ranges were reported (weeks) | 6–14 | 6–14 | 5.7–18 | 6.1–13.3 | 5.2–14.4 | 6–15 |
Scan: type of ultrasound scanner used, technique: technique used for scanning, TA: transabdominal, TV: transvaginal, RT: real time, LMP: last menstrual period, IVF:
It should be possible to generate very accurate reference charts by using a large
We examined CRL lengths at 6–9 weeks of gestation measured in a large IVF cohort where gestational age could be calculated from date of fertilisation. We assessed the ability of six commonly used reference charts to accurately date these pregnancies. Given all these charts showed inaccuracies in their ability to date these IVF pregnancies, we developed a new reference chart based on IVF dates in a singleton cohort.
We retrospectively obtained clinical details on 1268 singleton IVF pregnancies conceived using a fresh embryo transfer cycle, had a transvaginal first trimester ultrasound done between 6 (+1d) to 9 (+0d) weeks of gestation where CRL were measured, and progressed to viability (>24 weeks of gestation). These were identified from a total cohort of 4971 first trimester ultrasound reports of IVF and naturally conceived pregnancy scans. Pregnancies that resulted from frozen embryos transfer, complicated by fetal structural anomalies, delivered before 24 weeks, or had missing data were all excluded. Of our cohort of 1268 pregnancies, 84 were scanned twice, and 2 pregnancies were scanned three times, giving a total population size of 1182. In these pregnancies with multiple scans, all data were included in the analysis as discrete values.
We restricted our analysis to those who had fresh embryo transfer since we were concerned with the need to add the time from egg pickup to freezing, together with the time from subsequent thawing to transfer might introduce inaccuracies. We determined gestational age on the day of the ultrasound (IVF dates) by nominating the day of egg pickup and fertilisation as day 14 of gestation.
We first compared IVF dates with estimated dates determined using six existing reference charts: Australian Society for Ultrasound Medicine (ASUM) [
To validate our chart, we obtained CRL measurements from an IVF twin cohort (fresh embryo transfer) at 6 (+1d) to 9 (+0d) weeks of gestation where gestational age was calculated (fertilisation age + 14 days). Taking each twin as a discrete measurement, we determined the accuracy of all six existing reference charts and The Monash Chart in estimating gestational age.
We then applied all six existing reference charts and our chart to estimate gestational age of CRL measurements obtained from 3052 consecutive first-trimester singleton ultrasound scans pregnancies at 6–9 weeks of gestation.
Ethics approval was obtained before we commenced the study (Project 05063, Monash Surgical Private Human Research Ethics Committee, Clayton, VIC, Australia). For this retrospective database study where we used de-identified data in aggregate, the ethics committee specifically approved our request not to obtain individual patient consent.
All examinations were performed at three ultrasound centres that exclusively perform women’s health ultrasounds. All ultrasounds were transvaginal, done on Advanced Technology LaboratoriesT HDI 5000 ultrasound machines by experienced sonographers. After confirmation of a live intrauterine pregnancy, the CRL was measured in the midsagittal plane by the placement of ultrasound callipers at the outer edges of the head and rump of the fetus, excluding the limbs and yolk sac. Two measurements were taken, with the average taken as the final measurement.
For comparison of data, an unpaired Student’s
To determine the relationship between true gestational age and CRL, we constructed a scattergram, plotting CRL lengths against true gestational age in our singleton IVF cohort (Figure
(a) scatterplot and (b) line of best fit (black line shows line of best fit, and blue line shows ±95% confidence interval) to describe CRL length graphed against “true” gestational age (calculated from date of conception in the IVF singleton cohort).
When we compared the six existing CRL reference charts to either IVF dates or to gestational ages derived for The Monash chart, we calculated the mean differences of the gestational ages from the six charts from either the IVF true gestational age or The Monash Chart gestational age (depending on the analysis being undertaken), and compared them with paired
We identified 1268 first trimester ultrasound scans done at 6 (+1d) to 9 (+0d) weeks of gestation where gestational age at the day of the ultrasound could be precisely determined using the IVF dates. We calculated IVF dates by noting the number of days from fertilisation until the date of the ultrasound assessment. Since day of egg pickup is day 14 of gestation by convention, an extra 14 days were added to this number in order to calculate the IVF dates.
The clinical characteristics of this IVF cohort are shown in Table
Baseline characteristics of study participants the IVF singleton cohort.
Baseline characteristics—Singleton IVF cohort |
|
---|---|
Age (years)—mean (SD) | 34.3 (4.28) |
Gestation at birth (weeks)—mean (SD) | 38.6 (2.15) |
Birthweight (grams)—mean (SD) | 3266 (603.2) |
Treatment cycle—median (range) | 2 (1–38) |
Embryos transferred—median (range) | 2 (1–3) |
SD: standard deviation.
Estimated gestational age of 1268 fetuses derived from six existing CRL reference charts compared to IVF dates.
|
Range of differences to true gestational age in days | Mean difference (95% CI) in days | Comparison with true gestational age | |
---|---|---|---|---|
ASUM | 1233* | −10.5 to 8 | 2.1 (2.0 to 2.2) |
|
Hadlock | 1268 | −9 to 8 | 1.2 (1.1 to 1.3) |
|
Daya | 1268 | −8 to 9 | −0.57 (−0.67 to −0.48) |
|
Verburg | 271* | −8 to 10 | −1.2 (−1.5 to −0.81) |
|
Old ASUM | 1263* | −9 to 8 | 0.43 (0.33 to 0.53) |
|
Robinson | 636* | −7 to 10 | 0.39 (0.21 to 0.57) |
|
A negative number denotes the number of days that estimated gestational age lagged behind true gestational age. *
We plotted CRLs against gestational age determined by IVF dating on a scattergram (Figure
The Monash Chart. CRL reference table based on true gestational age in an IVF cohort.
CRL (mm) | GA (wks, days) | GA (days) |
---|---|---|
1.0 mm | 6W1D | 42.9 |
1.5 mm | 6W1D | 43.3 |
2.0 mm | 6W2D | 43.7 |
2.5 mm | 6W2D | 44.1 |
3.0 mm | 6W3D | 44.5 |
3.5 mm | 6W3D | 45.0 |
4.0 mm | 6W3D | 45.4 |
4.5 mm | 6W4D | 45.8 |
5.0 mm | 6W4D | 46.2 |
5.5 mm | 6W5D | 46.6 |
6.0 mm | 6W5D | 47.0 |
6.5 mm | 6W5D | 47.4 |
7.0 mm | 6W6D | 47.8 |
7.5 mm | 6W6D | 48.2 |
8.0 mm | 7W0D | 48.6 |
8.5 mm | 7W0D | 49.1 |
9.0 mm | 7W0D | 49.5 |
9.5 mm | 7W1D | 49.9 |
10.0 mm | 7W1D | 50.3 |
10.5 mm | 7W2D | 50.7 |
11.0 mm | 7W2D | 51.1 |
11.5 mm | 7W3D | 51.5 |
12.0 mm | 7W3D | 51.9 |
12.5 mm | 7W3D | 52.3 |
13.0 mm | 7W4D | 52.7 |
13.5 mm | 7W4D | 53.2 |
14.0 mm | 7W5D | 53.6 |
14.5 mm | 7W5D | 54.0 |
15.0 mm | 7W5D | 54.4 |
15.5 mm | 7W6D | 54.8 |
16.0 mm | 7W6D | 55.2 |
16.5 mm | 8W0D | 55.6 |
17.0 mm | 8W0D | 56.0 |
17.5 mm | 8W0D | 56.4 |
18.0 mm | 8W1D | 56.8 |
18.5 mm | 8W1D | 57.3 |
19.0 mm | 8W2D | 57.7 |
19.5 mm | 8W2D | 58.1 |
20.0 mm | 8W2D | 58.5 |
20.5 mm | 8W3D | 58.9 |
21.0 mm | 8W3D | 59.3 |
21.5 mm | 8W4D | 59.7 |
22.0 mm | 8W4D | 60.1 |
22.5 mm | 8W5D | 60.5 |
23.0 mm | 8W5D | 60.9 |
23.5 mm | 8W5D | 61.4 |
24.0 mm | 8W6D | 61.8 |
24.5 mm | 8W6D | 62.2 |
25.0 mm | 9W0D | 62.6 |
25.5 mm | 9W0D | 63.0 |
26.0 mm | 9W0D | 63.4 |
GA: gestational age, W: weeks, and D: days.
To ensure the generation of a line of best fit to create The Monash Chart did not significantly distort prediction of gestational age, we compared estimated gestational age calculated from our chart with actual IVF dates. No difference was seen (
We next sought to validate The Monash Chart. To do this, we chose an independent IVF twin pregnancy (
The mean (SD) maternal age of the IVF twin cohort was 33 (3.9) years, mean (SD) gestation at birth was 36 (2.5) weeks’ gestation. Mean birthweight for twin 1 was 2492 (548) gms and twin 2 was 2467 (576) gms. Median (range) treatment cycle number was 3 (1–15) and the median (range) number of embryos transferred was 2 (1–3).
In this cohort of IVF twins, predicted gestational age from the six existing reference charts was significantly different from IVF dates, with mean differences ranging from −1.1 days to 2.3 days (
We next applied our chart to CRL measurements obtained from 3052 consecutive first-trimester viability ultrasounds. The purpose was to see whether The Monash Chart would pragmatically alter expected dates of delivery compared to existing charts. We found dates derived from our chart were significantly different to the existing reference charts (mean difference in estimated gestation ranged from −1.8 days to 1.8 days;
Mean differences in gestational ages derived from The Monash Chart compared to those predicted by the six existing reference charts.
|
Mean differences in days (95% CI) | Comparison with gestation determined using The Monash Chart | |
---|---|---|---|
ASUM | 2938* | 1.8 (1.7 to 1.9) |
|
Hadlock | 3052 | 0.87 (0.81 to 0.93) |
|
Daya | 3052 | −0.80 (−0.84 to −0.77) |
|
Verburg | 641* | −1.80 (−2.0 to −1.6) |
|
Old ASUM | 2997* | 0.23 (0.20 to 0.27) |
|
Robinson | 1476* | −0.16 (−0.27 to −0.05) |
|
*
Many women who have a positive pregnancy test request an ultrasound to confirm viability. Therefore, early pregnancy “viability” ultrasounds performed at 6–9 weeks’ gestation are done very often, where gestational age is derived from the CRL measurements.
We have developed a potentially highly accurate CRL reference chart to date pregnancies at the viability ultrasound. The Monash Chart is based on IVF dates. While others have proposed CRL charts based on IVF dates before, they have been based on small numbers (36–160 participants) [
In addition, we found inaccuracies in the ability of commonly used charts to estimate gestational age among IVF singleton and twin cohorts where exact dates are known. While some showed only very slight differences in the estimation of dates compared to IVF dates (e.g., 0.57 days mean difference for Daya chart) and others showed larger differences (2.1 days for ASUM chart), all were highly statistically different (Table
In order to determine precisely gestational age on the day of the ultrasound scan, we have necessarily derived our reference chart from an IVF population. While there may be some differences in final birthweight among those conceived by IVF compared to spontaneous conceptions [
In this study, we were unable to generate a reference chart that encompassed CRL reference ranges across the whole first trimester. The reason is that CRL measurements were rarely performed across 9–11 weeks of gestation among our IVF cohort. The likely reason is that being IVF pregnancies, clinicians had exact dates with which to time the late first trimester ultrasound to 12+ weeks of gestation, when nuchal translucency is best assessed. We attempted modelling a chart incorporating these late first trimester CRL lengths, but we could not be confident that the integrity and high accuracy of the 6–9 week chart we report was maintained. Also, we did not include gestations under 6 weeks given CRL at (6+1) is already just 1 mm, and it is not possible for ultrasound to accurately measure differential CRL lengths present at earlier gestations. Nevertheless, we believe our chart is still clinically useful since many spontaneous pregnancies will have the first ultrasound between 6–9 weeks of gestation.
Strengths of our study includes the fact we only used measurements obtained from high-resolution transvaginal ultrasounds of CRLs at centres that exclusively perform obstetrics and gynecological ultrasounds. Also, we utilized a large cohort, reflected by the fact that the 95% confidence intervals are very narrow (Figure
Accurate dating is important since obstetric management throughout pregnancy is strongly based on gestational age. For instance, the first trimester nuchal translucency measurements are most accurate if performed during the 12th week of gestation [
At the thresholds of viability, a matter of days can sometimes impact on clinical decisions. Many would offer conservative management if a delivered baby is judged to be around 23 weeks +3 days of gestation, but may consider actively resuscitating a baby estimated to have reached 24 weeks +2 days of gestation. Therefore, it is important to be as accurate as possible in determining gestational age.
In conclusion, we have generated The Monash Chart that we believe may be the most accurate CRL chart reference chart yet proposed to date pregnancies at 6–9 weeks’ gestation. Furthermore, our chart appears valid for both singleton and twin pregnancies.
The authors have no conflicts of interest to declare.
S. Tong is supported by a Career Development Award from The National Health and Medical Research Council of Australia (no. 490970). K. Palmer is supported by a postgraduate research scholarship from The National Health and Medical Research Council of Australia (no. 607219).