The rate of increase of serum human chorionic gonadotropin in normal intrauterine pregnancy

CORRESPONDENCE The rate of increase of serum human chorionic gonadotropin in normal intrauterine pregnancy To the Editors: We read with great interest the report by Pitta way et a!. entitled "Doubling times of human chorionic gonadotropin increase in early viable intrauterine pregnancies" (AM J OBSTET GVNECOL 1985; 152:299). It is undeniable that the rate of increase of serum human chorionic gonadotropin (heG) in early pregnancy brings to the obstetrician very useful information. This is specially true in cases at risk for ectopic pregnancy, in threatened abortion, multiple pregnancy, or suspected trophoblastic disease, or simply when the last menstrual period is not reliable. The equation proposed by Pitta way et a!. to describe the rate of increase of heG fits much better with the reality of the experimental data than any of the doubling time coefficients previously published. However, for the clinician dealing with a suspected ectopic pregnancy the calculation of an expected mean increase, either from a doubling times coefficient or from a quadratic equation is not an easy task. Moreover, none of these methods gives the range that should be considered as a normal increase. We like to present here a much easier way to predict the mean increase of serum heG in early pregnancy. As reported by other investigators, we found that serum heG has a log normal distribution. Therefore mean values and standard deviations have been calculated on a logarithmic basis. Surprisingly, however, when we tried various equations to represent the increase of heG geometrical mean, we found that the

HCG

"V/al

P90

30 000

20 000

Table I. Rate of increase of serum heG concentration in early normal intrauterine pregnancy (ng/ml)* Human heG concentration (ng/mlJ

Range of the mean Daily increase P90 P30 P lO

Gestational age (wk)

3 <250 73 73 16

5-9

250-1000 210 100 48

>1000 1089 517 245

*Gestataional age is expressed as completed weeks from last menstrual period.

best curve fitting from 5 to 9 weeks from last menstrual period (LMP) was obtained by the following simple linear regression: Mean serum hCG (5 to 9 weeks) = gestational age (in days from LMP) x 517 - 17143 ng/m!.

As shown in Fig. I, that regression line fits very closely ·with the geometric means ofthe experimental data. For ease of use we suggest that the following rounded value be kept in mind: from 5 to 9 weeks from LMP the mean heG shows a daily increase of 500 ng/m!. The tenth and ninetieth percentiles of heG increase are probably more suitable parameters than the mean increase, since they can be used as arbitrary limits between normal and abnormal evolution. For instance, an increase of serum heG of <250 ng/ml/day (PIO in Fig. 1) should suggest the possibility of ectopic pregnancy or abortion. The above equation does not fit with the data obtained before day 35, and therefore other criteria should be used for the end of the cycle and the first week after the missing period. The rates of increase of serum heG in early normal intrauterine pregnancy are presented in Table I.

J.

Schwers, M.D.

e. Hubinont, M.D. 10 000 Pl0

5

J 1<1

(J2'

rw

140/

7 120/

9 127/

Wllk.

C. Thomas, M.D. E. Markowicz, M.D. Department of Obstetrics and Gynecology H 6pital E rasme Brussels University Brussels, Belgium

(nJ

Fig. 1. Serum hCG concentration in normal intrauterine pregnancy. Gestational age is expressed as completed weeks from last menstrual period. Geometric means of experimental data are represented by the open circles and the linear regression of these means by the solid line. The upper (Poo) and lower (P1O) limits of the normal range are also shown (interrupted lines). The number of samples measured in each group is indicated in parentheses.

Reply To the Editors: It was not the intent of our report to provide methods to evaluate the normalcy of early pregnancy but to de•scribe the nonlinearity of the exponential rise of serum heG in normal pregnancy before the sixth to seventh week of gestation. In another report' we have recom-

225