We report that the gestational age distribution at delivery based on ovulation timing gives the narrowest frequency distribution for observed gestation at delivery and smallest mean difference. The converse is true for LMP and CRL, with implantation date somewhere in between. When the methods of GA assignment are compared in relation to observed length of gestation, implantation and ovulation day correlate most strongly, both LMP and CRL least strongly. When all methods are compared pair-wise, the widest limits of agreement where gestational length is determined from LMP vs ultrasound CRL, and narrowest where GA assessment is by ovulation vs implantation.
To our knowledge, this type of comparison of all four possible methods of assigning gestational age has not been performed before. The results challenge the conventional wisdom, though are supported by a study on women recruited in the 1980s, in which ovulation offered a less variable way of predicting gestational length than that derived from LMP [24]. Similarly, assignment of GA using ovulation reduced intra-individual variation in hCG rise in early pregnancy compared to assignment by CRL measurement or LMP [28]. However, neither study considered using implantation date to assign GA.
It has always been assumed that first trimester ultrasound measurement of CRL is the most accurate method of assigning GA, representing an important improvement over LMP, and hence ultrasound is the method that has been recommended for dating a pregnancy worldwide. Whilst this may be true for a population of woman amongst some of whom the LMP may not be known or there may be an inaccurate recollection, it may not hold where there is a known certain LMP. Ultrasound calculation of pregnancy duration has a measurement error, due to both inaccuracies in making the measurement, and the fact that not all fetuses grow at exactly the same rate [7, 29–31].
The magnitude of this error is widely reported, consistently being shown to be around 5 days. The study Verburg showed a median gestational age of 10 weeks that has 95 % confidence limits of 9 weeks 2 days to 10 weeks 6 days (in other words, a range of 11 days for 95 % of the data) [32]. Piantelli and colleagues also found the range to be 11 days at 12 weeks [33]. The commonly used Hadlock formula gives the 95 % confidence interval of a CRL measurement as ±8 % of the predicted age (i.e., ±5.5 days at 10 weeks gestation) [10]. The most commonly used formula preset on most ultrasound equipment—states that “CRL measurement can be used to estimate maturity to within ±4.7 days with 95 % confidence” [7]. The American College of Obstetrics and Gynecology guidelines for use of LMP and ultrasound to estimate gestational age acknowledge that variability is associated with an ultrasound measurement [34]. Therefore, to avoid confusion caused by changing the LMP date, because the scan date is different, guidelines have recommended that LMP date can be kept if it is within the ultrasound’s variability, which is ±5 days for a dating scan.
Quite separately from the sources of error in making the ultrasound measurement, the Robinson and Fleming CRL charts do not account for a woman’s ovulation day [7]. As this is reported to occur later than day 14 of the menstrual cycle [13, 14], any first trimester CRL measurement, by assessing fetal size, takes account of differences in ovulation and implantation timing [20]. However, it is possible that an incorrect assumption of ovulation timing is inherent in the original construction of the CRL charts currently available and that this same assumption also underlies GA assessment based on LMP. Systematic bias has been demonstrated in several CRL conversion formulas, for example, the Hadlock formula overestimates GA by 2–3 days [11, 28]. It is plausible that using CRL to assign gestation may be less accurate than certain LMP. Conversely, of course, using CRL would almost certainly be more accurate where LMP was unknown or uncertain.
The results of this study cannot, therefore, be extrapolated to form guidance for an unselected population: the women that we recruited were all keeping accurate day-by-day menstrual records, hence giving LMP GA assessment the best chance of performing as well as possible. Where the error of using LMP to assign gestation may be in recollection by the woman, CRL, ovulation, and implantation timing are all prone to other forms of error.
Ovulation day is least prone to variability: the LH assay used in this study has been compared to ultrasound-observed ovulation and the surge was found to be on the day of ovulation in 15 % of cycles, be 1 day prior in 76 % of cycles, 2 days prior in 6 % of cycles, and more than 2 days in 3 % of cycles. Ovulation testing, hence, has a variability of ±1 day [35]. Embryonic implantation is reflected by a detectable rise in HCG in maternal urine, however, compared to current laboratory serum tests which have sensitivities of 0.01 mIU/ml, and the sensitivity of home urine tests means that hCG is not detected for up to 3–4 days after its first possible detection in urine. In addition, establishment of contact between the embryo and endometrium and time taken for excretion from maternal blood to urine mean that detection of urinary hCG is always a post-implantation event.
Though this is a relatively small cohort of women, the results are robust particularly in the context of other studies of this nature, including the seminal works by Wilcox [19] and Jukic [24] reporting on 140 women. Furthermore, the ‘standard’ CRL chart was derived from observations on only 81 women [7]. We did not censor the cases where delivery was not spontaneous, as we sought to compare gestational length by different methods in the same group of women, and hence this is unlikely to have confounded the correlation or Bland–Altman analyses of agreement. This study also only considered normal, healthy women, and extrapolation to a wider population where pre-existing conditions may affect fetal growth, greater variability may be associated with CRL measurements; we would, in particular, caution against interpreting these findings in the context of assisted conception.
In summary, widely held assumptions on GA assignment may not be robust. The implication of these findings is that the most accurate methods of assigning GA, hence predicting length of gestation, are those based on ovulation or implantation, whereas the least accurate examined in this study are those based on LMP and ultrasound CRL. Where ovulation date is known in spontaneous conception, this may, in fact, be the most accurate method of dating. More fundamentally, as the prediction of gestational length by ovulation and implantation is most strongly correlated, gestational length is probably defined by a relatively fixed time after the embryo has implanted rather than time from LMP, especially where ovulation timing diverges from what is expected in a regular cycle. Knowledge of day of ovulation in a cycle, in which conception occurs, if available, appears from this study to provide the most reliable estimate of gestational age.